Two retrievals from a single cue: A bottleneck persists across episodic and semantic memory.

PubMed

Orscheschek, Franziska; Strobach, Tilo; Schubert, Torsten; Rickard, Timothy

2018-05-01

There is evidence in the literature that two retrievals from long-term memory cannot occur in parallel. To date, however, that work has explored only the case of two retrievals from newly acquired episodic memory. These studies demonstrated a retrieval bottleneck even after dual-retrieval practice. That retrieval bottleneck may be a global property of long-term memory retrieval, or it may apply only to the case of two retrievals from episodic memory. In the current experiments, we explored whether that apparent dual-retrieval bottleneck applies to the case of one retrieval from episodic memory and one retrieval from highly overlearned semantic memory. Across three experiments, subjects learned to retrieve a left or right keypress response form a set of 14 unique word cues (e.g., black-right keypress). In addition, they learned a verbal response which involved retrieving the antonym of the presented cue (e.g., black-"white"). In the dual-retrieval condition, subjects had to retrieve both the keypress response and the antonym word. The results suggest that the retrieval bottleneck is superordinate to specific long-term memory systems and holds across different memory components. In addition, the results support the assumption of a cue-level response chunking account of learned retrieval parallelism.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

PubMed

Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

2016-01-05

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

PubMed Central

Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.

2016-01-01

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

Natural history of Ashkenazi intelligence.

PubMed

Cochran, Gregory; Hardy, Jason; Harpending, Henry

2006-09-01

This paper elaborates the hypothesis that the unique demography and sociology of Ashkenazim in medieval Europe selected for intelligence. Ashkenazi literacy, economic specialization, and closure to inward gene flow led to a social environment in which there was high fitness payoff to intelligence, specifically verbal and mathematical intelligence but not spatial ability. As with any regime of strong directional selection on a quantitative trait, genetic variants that were otherwise fitness reducing rose in frequency. In particular we propose that the well-known clusters of Ashkenazi genetic diseases, the sphingolipid cluster and the DNA repair cluster in particular, increase intelligence in heterozygotes. Other Ashkenazi disorders are known to increase intelligence. Although these disorders have been attributed to a bottleneck in Ashkenazi history and consequent genetic drift, there is no evidence of any bottleneck. Gene frequencies at a large number of autosomal loci show that if there was a bottleneck then subsequent gene flow from Europeans must have been very large, obliterating the effects of any bottleneck. The clustering of the disorders in only a few pathways and the presence at elevated frequency of more than one deleterious allele at many of them could not have been produced by drift. Instead these are signatures of strong and recent natural selection.

Dual-Task Interference When A Response is Not Required

NASA Technical Reports Server (NTRS)

VanSelst, Mark; Johnston, James C.; Shafto, Michael (Technical Monitor)

2002-01-01

When subjects are required to respond to two stimuli presented in rapid succession, responses to the second stimulus are delayed. Such dual-task interference has been attributed to a fundamental processing bottleneck preventing simultaneous processing on both tasks. Two experiments show dual-task interference even when the first task does not require a response. The observed interference is caused by a bottleneck in central cognitive processing, rather than in response initiation or execution.

Nucleotide Diversity and Selection Signature in the Domesticated Silkworm, Bombyx mori, and Wild Silkworm, Bombyx mandarina

PubMed Central

Guo, Yi; Shen, Yi-Hong; Sun, Wei; Kishino, Hirohisa; Xiang, Zhong-Huai; Zhang, Ze

2011-01-01

To investigate the patterns of nucleotide diversity in domesticated silkworm, Bombyx mori L. (Lepidoptera: Bombycidae) and its wild relative, Chinese wild silkworm, Bombyx mandarina Moore, we sequenced nine nuclear genes. Neutrality test and coalescent simulation for these genes were performed to look at bottleneck intensity and selection signature; linkage disequilibrium (LD) within and between loci was employed to investigate allele association. As a result, B. mori lost 33–49% of nucleotide diversity relative to wild silkworm, which is similar to the loss levels found in major cultivated crops. Diversity of B. mori is significantly lower than that of B. mandarina measured as πtotal (0.01166 vs. 0.1741) or θW(0.01124 vs. 0.02206). Bottleneck intensity of domesticated silkworm is 1.5 (in terms of k = Nb/d, Nb-bottleneck population size; d-bottleneck duration) with different durations. Gene DefA showed signature of artificial selection by all analysis methods and might experience strong artificial selection in B. mori during domestication. For nine loci, both curves of LD decay rapidly within 200 bp and drop slowly when distance is > 200 bp, although that of B. mori decays slower than B. mandarina at loci investigated. However, LD could not be estimated at DefA in B. mori and at ER in both silkworms. Elevated LD observed in B. mori may be indicator of selection and demographic events. PMID:22239062

Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection.

PubMed

Chang, Hsiao-Han; Hartl, Daniel L

2015-02-01

Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could influence the patterns of genetic diversity and the power of existing population genetic tools to identify sites under positive selection. We therefore simulated the site-frequency spectrum of a beneficial mutant allele through time under the malaria life cycle. We investigated the power of current population genetic methods to detect positive selection based on the site-frequency spectrum as well as temporal changes in allele frequency. We found that a within-host selective advantage is difficult to detect using these methods. Although a between-host transmission advantage could be detected, the power is decreased when compared with the classical Wright-Fisher (WF) population model. Using an adjusted null site-frequency spectrum that takes the malaria life cycle into account, the power of tests based on the site-frequency spectrum to detect positive selection is greatly improved. Our study demonstrates the importance of considering the life cycle in genetic analysis, especially in parasites with complex life cycles.

Mutational Effects and Population Dynamics During Viral Adaptation Challenge Current Models

PubMed Central

Miller, Craig R.; Joyce, Paul; Wichman, Holly A.

2011-01-01

Adaptation in haploid organisms has been extensively modeled but little tested. Using a microvirid bacteriophage (ID11), we conducted serial passage adaptations at two bottleneck sizes (104 and 106), followed by fitness assays and whole-genome sequencing of 631 individual isolates. Extensive genetic variation was observed including 22 beneficial, several nearly neutral, and several deleterious mutations. In the three large bottleneck lines, up to eight different haplotypes were observed in samples of 23 genomes from the final time point. The small bottleneck lines were less diverse. The small bottleneck lines appeared to operate near the transition between isolated selective sweeps and conditions of complex dynamics (e.g., clonal interference). The large bottleneck lines exhibited extensive interference and less stochasticity, with multiple beneficial mutations establishing on a variety of backgrounds. Several leapfrog events occurred. The distribution of first-step adaptive mutations differed significantly from the distribution of second-steps, and a surprisingly large number of second-step beneficial mutations were observed on a highly fit first-step background. Furthermore, few first-step mutations appeared as second-steps and second-steps had substantially smaller selection coefficients. Collectively, the results indicate that the fitness landscape falls between the extremes of smooth and fully uncorrelated, violating the assumptions of many current mutational landscape models. PMID:21041559

Bottlenecks of Motion Processing during a Visual Glance: The Leaky Flask Model

PubMed Central

Öğmen, Haluk; Ekiz, Onur; Huynh, Duong; Bedell, Harold E.; Tripathy, Srimant P.

2013-01-01

Where do the bottlenecks for information and attention lie when our visual system processes incoming stimuli? The human visual system encodes the incoming stimulus and transfers its contents into three major memory systems with increasing time scales, viz., sensory (or iconic) memory, visual short-term memory (VSTM), and long-term memory (LTM). It is commonly believed that the major bottleneck of information processing resides in VSTM. In contrast to this view, we show major bottlenecks for motion processing prior to VSTM. In the first experiment, we examined bottlenecks at the stimulus encoding stage through a partial-report technique by delivering the cue immediately at the end of the stimulus presentation. In the second experiment, we varied the cue delay to investigate sensory memory and VSTM. Performance decayed exponentially as a function of cue delay and we used the time-constant of the exponential-decay to demarcate sensory memory from VSTM. We then decomposed performance in terms of quality and quantity measures to analyze bottlenecks along these dimensions. In terms of the quality of information, two thirds to three quarters of the motion-processing bottleneck occurs in stimulus encoding rather than memory stages. In terms of the quantity of information, the motion-processing bottleneck is distributed, with the stimulus-encoding stage accounting for one third of the bottleneck. The bottleneck for the stimulus-encoding stage is dominated by the selection compared to the filtering function of attention. We also found that the filtering function of attention is operating mainly at the sensory memory stage in a specific manner, i.e., influencing only quantity and sparing quality. These results provide a novel and more complete understanding of information processing and storage bottlenecks for motion processing. PMID:24391806

Bottlenecks of motion processing during a visual glance: the leaky flask model.

PubMed

Öğmen, Haluk; Ekiz, Onur; Huynh, Duong; Bedell, Harold E; Tripathy, Srimant P

2013-01-01

Where do the bottlenecks for information and attention lie when our visual system processes incoming stimuli? The human visual system encodes the incoming stimulus and transfers its contents into three major memory systems with increasing time scales, viz., sensory (or iconic) memory, visual short-term memory (VSTM), and long-term memory (LTM). It is commonly believed that the major bottleneck of information processing resides in VSTM. In contrast to this view, we show major bottlenecks for motion processing prior to VSTM. In the first experiment, we examined bottlenecks at the stimulus encoding stage through a partial-report technique by delivering the cue immediately at the end of the stimulus presentation. In the second experiment, we varied the cue delay to investigate sensory memory and VSTM. Performance decayed exponentially as a function of cue delay and we used the time-constant of the exponential-decay to demarcate sensory memory from VSTM. We then decomposed performance in terms of quality and quantity measures to analyze bottlenecks along these dimensions. In terms of the quality of information, two thirds to three quarters of the motion-processing bottleneck occurs in stimulus encoding rather than memory stages. In terms of the quantity of information, the motion-processing bottleneck is distributed, with the stimulus-encoding stage accounting for one third of the bottleneck. The bottleneck for the stimulus-encoding stage is dominated by the selection compared to the filtering function of attention. We also found that the filtering function of attention is operating mainly at the sensory memory stage in a specific manner, i.e., influencing only quantity and sparing quality. These results provide a novel and more complete understanding of information processing and storage bottlenecks for motion processing.

Civil Preparedness and Post-Attack U.S. Economic Recovery. A State-of-the-Art Assessment and Selected Annotated Bibliography.

DTIC Science & Technology

1979-10-01

Although bottlenecks have been discussed thus far in an indus- trial or microeconomic sense, national bottlenecks are possible too, with...Texas Division of Disaster Emergency Services, 1978. JThis workbook provides a detailed format for a multi-meeting workshop to enable local (city/council

Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus.

PubMed

Moncla, Louise H; Zhong, Gongxun; Nelson, Chase W; Dinis, Jorge M; Mutschler, James; Hughes, Austin L; Watanabe, Tokiko; Kawaoka, Yoshihiro; Friedrich, Thomas C

2016-02-10

Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a "loose" bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses. Copyright © 2016 Elsevier Inc. All rights reserved.

Duplication and population dynamics shape historic patterns of selection and genetic variation at the major histocompatibility complex in rodents

PubMed Central

Winternitz, Jamie C; Wares, John P

2013-01-01

Genetic variation at the major histocompatibility complex (MHC) is vitally important for wildlife populations to respond to pathogen threats. As natural populations can fluctuate greatly in size, a key issue concerns how population cycles and bottlenecks that could reduce genetic diversity will influence MHC genes. Using 454 sequencing, we characterized genetic diversity at the DRB Class II locus in montane voles (Microtus montanus), a North American rodent that regularly undergoes high-amplitude fluctuations in population size. We tested for evidence of historic balancing selection, recombination, and gene duplication to identify mechanisms maintaining allelic diversity. Counter to our expectations, we found strong evidence of purifying selection acting on the DRB locus in montane voles. We speculate that the interplay between population fluctuations and gene duplication might be responsible for the weak evidence of historic balancing selection and strong evidence of purifying selection detected. To further explore this idea, we conducted a phylogenetically controlled comparative analysis across 16 rodent species with varying demographic histories and MHC duplication events (based on the maximum number of alleles detected per individual). On the basis of phylogenetic generalized linear model-averaging, we found evidence that the estimated number of duplicated loci was positively related to allelic diversity and, surprisingly, to the strength of purifying selection at the DRB locus. Our analyses also revealed that species that had undergone population bottlenecks had lower allelic richness than stable species. This study highlights the need to consider demographic history and genetic structure alongside patterns of natural selection to understand resulting patterns of genetic variation at the MHC. PMID:23789067

Mutations in Global Regulators Lead to Metabolic Selection during Adaptation to Complex Environments

PubMed Central

Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.; Ansong, Charles; Deatherage Kaiser, Brooke L.; Valovska, Marie-Thérèse; Ristic, Nikola; Yeh, Ping T.; Prakash, Vittal P.; Leiser, Owen P.; Nakhleh, Luay; Gibbons, Henry S.; Kreuzer, Helen W.; Shamoo, Yousif

2014-01-01

Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes if many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased genetic and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that subtle modulations of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order metabolic selection that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism, and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation. PMID:25501822

Variation in Susceptibility to Wheat dwarf virus among Wild and Domesticated Wheat

PubMed Central

Nygren, Jim; Shad, Nadeem; Kvarnheden, Anders; Westerbergh, Anna

2015-01-01

We investigated the variation in plant response in host-pathogen interactions between wild (Aegilops spp., Triticum spp.) and domesticated wheat (Triticum spp.) and Wheat dwarf virus (WDV). The distribution of WDV and its wild host species overlaps in Western Asia in the Fertile Crescent, suggesting a coevolutionary relationship. Bread wheat originates from a natural hybridization between wild emmer wheat (carrying the A and B genomes) and the wild D genome donor Aegilops tauschii, followed by polyploidization and domestication. We studied whether the strong selection during these evolutionary processes, leading to genetic bottlenecks, may have resulted in a loss of resistance in domesticated wheat. In addition, we investigated whether putative fluctuations in intensity of selection imposed on the host-pathogen interactions have resulted in a variation in susceptibility to WDV. To test our hypotheses we evaluated eighteen wild and domesticated wheat taxa, directly or indirectly involved in wheat evolution, for traits associated with WDV disease such as leaf chlorosis, different growth traits and WDV content. The plants were exposed to viruliferous leafhoppers (Psammotettix alienus) in a greenhouse trial and evaluated at two time points. We found three different plant response patterns: i) continuous reduction in growth over time, ii) weak response at an early stage of plant development but a much stronger response at a later stage, and iii) remission of symptoms over time. Variation in susceptibility may be explained by differences in the intensity of natural selection, shaping the coevolutionary interaction between WDV and the wild relatives. However, genetic bottlenecks during wheat evolution have not had a strong impact on WDV resistance. Further, this study indicates that the variation in susceptibility may be associated with the genome type and that the ancestor Ae. tauschii may be useful as genetic resource for the improvement of WDV resistance in wheat. PMID:25837893

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus

PubMed Central

Tully, Damien C.; Ogilvie, Colin B.; Batorsky, Rebecca E.; Bean, David J.; Power, Karen A.; Ghebremichael, Musie; Bedard, Hunter E.; Gladden, Adrianne D.; Seese, Aaron M.; Amero, Molly A.; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B.; Tinsley, Jake; Lennon, Niall J.; Henn, Matthew R.; Brumme, Zabrina L.; Norris, Philip J.; Rosenberg, Eric S.; Mayer, Kenneth H.; Jessen, Heiko; Kosakovsky Pond, Sergei L.; Walker, Bruce D.; Altfeld, Marcus; Carlson, Jonathan M.; Allen, Todd M.

2016-01-01

Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic “signatures” within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission. PMID:27163788

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

PubMed

Tully, Damien C; Ogilvie, Colin B; Batorsky, Rebecca E; Bean, David J; Power, Karen A; Ghebremichael, Musie; Bedard, Hunter E; Gladden, Adrianne D; Seese, Aaron M; Amero, Molly A; Lane, Kimberly; McGrath, Graham; Bazner, Suzane B; Tinsley, Jake; Lennon, Niall J; Henn, Matthew R; Brumme, Zabrina L; Norris, Philip J; Rosenberg, Eric S; Mayer, Kenneth H; Jessen, Heiko; Kosakovsky Pond, Sergei L; Walker, Bruce D; Altfeld, Marcus; Carlson, Jonathan M; Allen, Todd M

2016-05-01

Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

Lessons from acute HIV infection.

PubMed

Robb, Merlin L; Ananworanich, Jintanat

2016-11-01

Understanding the characteristics of transmission during acute HIV infection (AHI) may inform targets for vaccine-induced immune interdiction. Individuals treated in AHI with a small HIV reservoir size may be ideal candidates for therapeutic HIV vaccines aiming for HIV remission (i.e. viremic control after treatment interruption). The AHI period is brief and peak viremia predicts a viral set point that occurs 4-5 weeks following infection. Robust HIV-specific CD8 T-cell responses lower viral set points. Phylogenetic analyses of founder viruses demonstrated unique bottleneck selections and specific genetic signatures to optimize for high-fitness variants and successful transmission events. HIV clades, route of transmission and the presence of minor variants may affect vaccine protection. Antiretroviral treatment in AHI results in smaller HIV reservoir size, better CD4 T-cell recovery and fewer virus escapes. The knowledge of untreated and treated AHI informs the development of vaccines, in that preventive vaccines will require broad coverage for multiple clades and antigenic variants associated with unique bottleneck selections. Vaccines that help the host to control viremia could minimize onward transmission. Therapeutic HIV vaccines aimed at HIV remission should be studied in early-treated individuals who have few or no viral escape mutants and a more preserved immune system.

Changes in variation at the MHC class II DQA locus during the final demise of the woolly mammoth

NASA Astrophysics Data System (ADS)

Pečnerová, Patrícia; Díez-Del-Molino, David; Vartanyan, Sergey; Dalén, Love

2016-05-01

According to the nearly-neutral theory of evolution, the relative strengths of selection and drift shift in favour of drift at small population sizes. Numerous studies have analysed the effect of bottlenecks and small population sizes on genetic diversity in the MHC, which plays a central role in pathogen recognition and immune defense and is thus considered a model example for the study of adaptive evolution. However, to understand changes in genetic diversity at loci under selection, it is necessary to compare the genetic diversity of a population before and after the bottleneck. In this study, we analyse three fragments of the MHC DQA gene in woolly mammoth samples radiocarbon dated to before and after a well-documented bottleneck that took place about ten thousand years ago. Our results indicate a decrease in observed heterozygosity and number of alleles, suggesting that genetic drift had an impact on the variation on MHC. Based on coalescent simulations, we found no evidence of balancing selection maintaining MHC diversity during the Holocene. However, strong trans-species polymorphism among mammoths and elephants points to historical effects of balancing selection on the woolly mammoth lineage.

Dual-task interference with equal task emphasis: graded capacity sharing or central postponement?

NASA Technical Reports Server (NTRS)

Ruthruff, Eric; Pashler, Harold E.; Hazeltine, Eliot

2003-01-01

Most studies using the psychological refractory period (PRP) design suggest that dual-task performance is limited by a central bottleneck. Because subjects are usually told to emphasize Task 1, however, the bottleneck might reflect a strategic choice rather than a structural limitation. To evaluate the possibility that central operations can proceed in parallel, albeit with capacity limitations, we conducted two dual-task experiments with equal task emphasis. In both experiments, subjects tended to either group responses together or respond to one task well before the other. In addition, stimulus-response compatibility effects were roughly constant across stimulus onset asynchronies (SOAs). At the short SOA, compatibility effects also carried over onto response times for the other task. This pattern of results is difficult to reconcile with the possibility that subjects share capacity roughly equally between simultaneous central operations. However, this pattern is consistent with the existence of a structural central bottleneck.

Historical connectivity, contemporary isolation and local adaptation in a widespread but discontinuously distributed species endemic to Taiwan, Rhododendron oldhamii (Ericaceae)

PubMed Central

Hsieh, Y-C; Chung, J-D; Wang, C-N; Chang, C-T; Chen, C-Y; Hwang, S-Y

2013-01-01

Elucidation of the evolutionary processes that constrain or facilitate adaptive divergence is a central goal in evolutionary biology, especially in non-model organisms. We tested whether changes in dynamics of gene flow (historical vs contemporary) caused population isolation and examined local adaptation in response to environmental selective forces in fragmented Rhododendron oldhamii populations. Variation in 26 expressed sequence tag-simple sequence repeat loci from 18 populations in Taiwan was investigated by examining patterns of genetic diversity, inbreeding, geographic structure, recent bottlenecks, and historical and contemporary gene flow. Selection associated with environmental variables was also examined. Bayesian clustering analysis revealed four regional population groups of north, central, south and southeast with significant genetic differentiation. Historical bottlenecks beginning 9168–13,092 years ago and ending 1584–3504 years ago were revealed by estimates using approximate Bayesian computation for all four regional samples analyzed. Recent migration within and across geographic regions was limited. However, major dispersal sources were found within geographic regions. Altitudinal clines of allelic frequencies of environmentally associated positively selected outliers were found, indicating adaptive divergence. Our results point to a transition from historical population connectivity toward contemporary population isolation and divergence on a regional scale. Spatial and temporal dispersal differences may have resulted in regional population divergence and local adaptation associated with environmental variables, which may have played roles as selective forces at a regional scale. PMID:23591517

Electron-Phonon Coupling and Resonant Relaxation from 1D and 1P States in PbS Quantum Dots.

PubMed

Kennehan, Eric R; Doucette, Grayson S; Marshall, Ashley R; Grieco, Christopher; Munson, Kyle T; Beard, Matthew C; Asbury, John B

2018-05-31

Observations of the hot-phonon bottleneck, which is predicted to slow the rate of hot carrier cooling in quantum confined nanocrystals, have been limited to date for reasons that are not fully understood. We used time-resolved infrared spectroscopy to directly measure higher energy intraband transitions in PbS colloidal quantum dots. Direct measurements of these intraband transitions permitted detailed analysis of the electronic overlap of the quantum confined states that may influence their relaxation processes. In smaller PbS nanocrystals, where the hot-phonon bottleneck is expected to be most pronounced, we found that relaxation of parity selection rules combined with stronger electron-phonon coupling led to greater spectral overlap of transitions among the quantum confined states. This created pathways for fast energy transfer and relaxation that may bypass the predicted hot-phonon bottleneck. In contrast, larger, but still quantum confined nanocrystals did not exhibit such relaxation of the parity selection rules and possessed narrower intraband states. These observations were consistent with slower relaxation dynamics that have been measured in larger quantum confined systems. These findings indicated that, at small radii, electron-phonon interactions overcome the advantageous increase in energetic separation of the electronic states for PbS quantum dots. Selection of appropriately sized quantum dots, which minimize spectral broadening due to electron-phonon interactions while maximizing electronic state separation, is necessary to observe the hot-phonon bottleneck. Such optimization may provide a framework for achieving efficient hot carrier collection and multiple exciton generation.

Genetic bottlenecks during systemic movement of Cucumber mosaic virus vary in different host plants

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

Ali, Akhtar; Roossinck, Marilyn J., E-mail: mroossinck@noble.or

2010-09-01

Genetic bottlenecks are stochastic events that narrow variation in a population. We compared bottlenecks during the systemic infection of Cucumber mosaic virus (CMV) in four host plants. We mechanically inoculated an artificial population of twelve CMV mutants to young leaves of tomato, pepper, Nicotiana benthamiana, and squash. The inoculated leaves and primary and secondary systemically infected leaves were sampled at 2, 10, and 15 days post-inoculation. All twelve mutants were detected in all of the inoculated leaves. The number of mutants recovered from the systemically infected leaves of all host species was reduced significantly, indicating bottlenecks in systemic movement. Themore » recovery frequencies of a few of the mutants were significantly different in each host probably due to host-specific selective forces. These results have implications for the differences in virus population variation that is seen in different host plants.« less

Impact of the HIV-1 genetic background and HIV-1 population size on the evolution of raltegravir resistance.

PubMed

Fun, Axel; Leitner, Thomas; Vandekerckhove, Linos; Däumer, Martin; Thielen, Alexander; Buchholz, Bernd; Hoepelman, Andy I M; Gisolf, Elizabeth H; Schipper, Pauline J; Wensing, Annemarie M J; Nijhuis, Monique

2018-01-05

Emergence of resistance against integrase inhibitor raltegravir in human immunodeficiency virus type 1 (HIV-1) patients is generally associated with selection of one of three signature mutations: Y143C/R, Q148K/H/R or N155H, representing three distinct resistance pathways. The mechanisms that drive selection of a specific pathway are still poorly understood. We investigated the impact of the HIV-1 genetic background and population dynamics on the emergence of raltegravir resistance. Using deep sequencing we analyzed the integrase coding sequence (CDS) in longitudinal samples from five patients who initiated raltegravir plus optimized background therapy at viral loads > 5000 copies/ml. To investigate the role of the HIV-1 genetic background we created recombinant viruses containing the viral integrase coding region from pre-raltegravir samples from two patients in whom raltegravir resistance developed through different pathways. The in vitro selections performed with these recombinant viruses were designed to mimic natural population bottlenecks. Deep sequencing analysis of the viral integrase CDS revealed that the virological response to raltegravir containing therapy inversely correlated with the relative amount of unique sequence variants that emerged suggesting diversifying selection during drug pressure. In 4/5 patients multiple signature mutations representing different resistance pathways were observed. Interestingly, the resistant population can consist of a single resistant variant that completely dominates the population but also of multiple variants from different resistance pathways that coexist in the viral population. We also found evidence for increased diversification after stronger bottlenecks. In vitro selections with low viral titers, mimicking population bottlenecks, revealed that both recombinant viruses and HXB2 reference virus were able to select mutations from different resistance pathways, although typically only one resistance pathway emerged in each individual culture. The generation of a specific raltegravir resistant variant is not predisposed in the genetic background of the viral integrase CDS. Typically, in the early phases of therapy failure the sequence space is explored and multiple resistance pathways emerge and then compete for dominance which frequently results in a switch of the dominant population over time towards the fittest variant or even multiple variants of similar fitness that can coexist in the viral population.

Mutations in global regulators lead to metabolic selection during adaptation to complex environments

DOE PAGES

Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.; ...

2014-12-11

Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased geneticmore » and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation.« less

Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: support for a variable-size bottleneck

PubMed Central

Li, Mingkun; Rothwell, Rebecca; Vermaat, Martijn; Wachsmuth, Manja; Schröder, Roland; Laros, Jeroen F.J.; van Oven, Mannis; de Bakker, Paul I.W.; Bovenberg, Jasper A.; van Duijn, Cornelia M.; van Ommen, Gert-Jan B.; Slagboom, P. Eline; Swertz, Morris A.; Wijmenga, Cisca; Kayser, Manfred; Boomsma, Dorret I.; Zöllner, Sebastian; de Knijff, Peter; Stoneking, Mark

2016-01-01

Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies. PMID:26916109

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses.

PubMed

Joseph, Sarah B; Swanstrom, Ronald; Kashuba, Angela D M; Cohen, Myron S

2015-07-01

HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. Studies of these HIV-1 variants provide critical information about the transmission bottlenecks and the selective pressures acting on the virus in the transmission fluid and in the recipient tissues. These studies reveal that T/F virus phenotypes are shaped by stochastic and selective forces that restrict transmission and may be targets for prevention strategies. In this Review, we highlight how studies of T/F viruses contribute to a better understanding of the biology of HIV-1 transmission and discuss how these findings affect HIV-1 prevention strategies.

EFFECTIVENESS OF SELECTION IN REDUCING THE GENETIC LOAD IN POPULATIONS OF PEROMYSCUS POLIONOTUS DURING GENERATIONS OF INBREEDING.

PubMed

Lacy, Robert C; Ballou, Jonathan D

1998-06-01

It has been hypothesized that natural selection reduces the "genetic load" of deleterious alleles from populations that inbreed during bottlenecks, thereby ameliorating impacts of future inbreeding. We tested the efficiency with which natural selection purges deleterious alleles from three subspecies of Peromyscus polionotus during 10 generations of laboratory inbreeding by monitoring pairing success, litter size, viability, and growth in 3604 litters produced from 3058 pairs. In P. p. subgriseus, there was no reduction across generations in inbreeding depression in any of the fitness components. Strongly deleterious recessive alleles may have been removed previously during episodes of local inbreeding in the wild, and the residual genetic load in this population was not further reduced by selection in the lab. In P. p. rhoadsi, four of seven fitness components did show a reduction of the genetic load with continued inbreeding. The average reduction in the genetic load was as expected if inbreeding depression in this population is caused by highly deleterious recessive alleles that are efficiently removed by selection. For P. p. leucocephalus a population that experiences periodic bottlenecks in the wild, the effect of further inbreeding in the laboratory was to exacerbate rather than reduce the genetic load. Recessive deleterious alleles may have been removed from this population during repeated bottlenecks in the wild; the population may be close to a threshold level of heterozygosity below which fitness declines rapidly. Thus, the effects of selection on inbreeding depression varied substantially among populations, perhaps due to different histories of inbreeding and selection. © 1998 The Society for the Study of Evolution.

Potential performance bottleneck in Linux TCP

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

Wu, Wenji; Crawford, Matt; /Fermilab

2006-12-01

TCP is the most widely used transport protocol on the Internet today. Over the years, especially recently, due to requirements of high bandwidth transmission, various approaches have been proposed to improve TCP performance. The Linux 2.6 kernel is now preemptible. It can be interrupted mid-task, making the system more responsive and interactive. However, we have noticed that Linux kernel preemption can interact badly with the performance of the networking subsystem. In this paper we investigate the performance bottleneck in Linux TCP. We systematically describe the trip of a TCP packet from its ingress into a Linux network end system tomore » its final delivery to the application; we study the performance bottleneck in Linux TCP through mathematical modeling and practical experiments; finally we propose and test one possible solution to resolve this performance bottleneck in Linux TCP.« less

Distinguishing Positive Selection From Neutral Evolution: Boosting the Performance of Summary Statistics

PubMed Central

Lin, Kao; Li, Haipeng; Schlötterer, Christian; Futschik, Andreas

2011-01-01

Summary statistics are widely used in population genetics, but they suffer from the drawback that no simple sufficient summary statistic exists, which captures all information required to distinguish different evolutionary hypotheses. Here, we apply boosting, a recent statistical method that combines simple classification rules to maximize their joint predictive performance. We show that our implementation of boosting has a high power to detect selective sweeps. Demographic events, such as bottlenecks, do not result in a large excess of false positives. A comparison to other neutrality tests shows that our boosting implementation performs well compared to other neutrality tests. Furthermore, we evaluated the relative contribution of different summary statistics to the identification of selection and found that for recent sweeps integrated haplotype homozygosity is very informative whereas older sweeps are better detected by Tajima's π. Overall, Watterson's θ was found to contribute the most information for distinguishing between bottlenecks and selection. PMID:21041556

Bottlenecks in HIV-1 transmission: insights from the study of founder viruses

PubMed Central

Joseph, Sarah B.; Swanstrom, Ronald; Kashuba, Angela D. M.; Cohen, Myron S.

2016-01-01

HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. Studies of these HIV-1 variants provide critical information about the transmission bottlenecks and the selective pressures acting on the virus in the transmission fluid and in the recipient tissues. These studies reveal that T/F virus phenotypes are shaped by stochastic and selective forces that restrict transmission and may be targets for prevention strategies. In this Review, we highlight how studies of T/F viruses contribute to a better understanding of the biology of HIV-1 transmission and discuss how these findings affect HIV-1 prevention strategies. PMID:26052661

Adaptive potential of northernmost tree populations to climate change, with emphasis on Scots pine (Pinus sylvestris L.).

PubMed

Savolainen, Outi; Kujala, Sonja T; Sokol, Catherina; Pyhäjärvi, Tanja; Avia, Komlan; Knürr, Timo; Kärkkäinen, Katri; Hicks, Sheila

2011-01-01

The adaptive potential of the northernmost Pinus sylvestris L. (and other northern tree) populations is considered by examining first the current patterns of quantitative genetic adaptive traits, which show high population differentiation and clines. We then consider the postglacial history of the populations using both paleobiological and genetic data. The current patterns of diversity at nuclear genes suggest that the traces of admixture are mostly visible in mitochondrial DNA variation patterns. There is little evidence of increased diversity due to admixture between an eastern and western colonization lineage, but no signal of reduced diversity (due to sequential bottlenecks) either. Quantitative trait variation in the north is not associated with the colonizing lineages. The current clines arose rapidly and may be based on standing genetic variation. The initial phenotypic response of Scots pine in the north is predicted to be increased survival and growth. The genetic responses are examined based on quantitative genetic predictions of sustained selection response and compared with earlier simulation results that have aimed at more ecological realism. The phenotypic responses of increased growth and survival reduce the opportunity for selection and delay the evolutionary responses. The lengthening of the thermal growing period also causes selection on the critical photoperiod in the different populations. Future studies should aim at including multiple ecological and genetic factors in evaluating potential responses.

Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

PubMed Central

McElroy, Kerensa; Gaudieri, Silvana; Pham, Son T.; Chopra, Abha; Cameron, Barbara; Maher, Lisa; Dore, Gregory J.; White, Peter A.; Lloyd, Andrew R.

2011-01-01

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection. PMID:21912520

The impact of selection, gene flow and demographic history on heterogeneous genomic divergence: three-spine sticklebacks in divergent environments.

PubMed

Ferchaud, Anne-Laure; Hansen, Michael M

2016-01-01

Heterogeneous genomic divergence between populations may reflect selection, but should also be seen in conjunction with gene flow and drift, particularly population bottlenecks. Marine and freshwater three-spine stickleback (Gasterosteus aculeatus) populations often exhibit different lateral armour plate morphs. Moreover, strikingly parallel genomic footprints across different marine-freshwater population pairs are interpreted as parallel evolution and gene reuse. Nevertheless, in some geographic regions like the North Sea and Baltic Sea, different patterns are observed. Freshwater populations in coastal regions are often dominated by marine morphs, suggesting that gene flow overwhelms selection, and genomic parallelism may also be less pronounced. We used RAD sequencing for analysing 28 888 SNPs in two marine and seven freshwater populations in Denmark, Europe. Freshwater populations represented a variety of environments: river populations accessible to gene flow from marine sticklebacks and large and small isolated lakes with and without fish predators. Sticklebacks in an accessible river environment showed minimal morphological and genomewide divergence from marine populations, supporting the hypothesis of gene flow overriding selection. Allele frequency spectra suggested bottlenecks in all freshwater populations, and particularly two small lake populations. However, genomic footprints ascribed to selection could nevertheless be identified. No genomic regions were consistent freshwater-marine outliers, and parallelism was much lower than in other comparable studies. Two genomic regions previously described to be under divergent selection in freshwater and marine populations were outliers between different freshwater populations. We ascribe these patterns to stronger environmental heterogeneity among freshwater populations in our study as compared to most other studies, although the demographic history involving bottlenecks should also be considered in the interpretation of results. © 2015 John Wiley & Sons Ltd.

Toll-like receptor variation in the bottlenecked population of the Seychelles warbler: computer simulations see the 'ghost of selection past' and quantify the 'drift debt'.

PubMed

Gilroy, D L; Phillips, K P; Richardson, D S; van Oosterhout, C

2017-07-01

Balancing selection can maintain immunogenetic variation within host populations, but detecting its signal in a postbottlenecked population is challenging due to the potentially overriding effects of drift. Toll-like receptor genes (TLRs) play a fundamental role in vertebrate immune defence and are predicted to be under balancing selection. We previously characterized variation at TLR loci in the Seychelles warbler (Acrocephalus sechellensis), an endemic passerine that has undergone a historical bottleneck. Five of seven TLR loci were polymorphic, which is in sharp contrast to the low genomewide variation observed. However, standard population genetic statistical methods failed to detect a contemporary signature of selection at any TLR locus. We examined whether the observed TLR polymorphism could be explained by neutral evolution, simulating the population's demography in the software DIYABC. This showed that the posterior distributions of mutation rates had to be unrealistically high to explain the observed genetic variation. We then conducted simulations with an agent-based model using typical values for the mutation rate, which indicated that weak balancing selection has acted on the three TLR genes. The model was able to detect evidence of past selection elevating TLR polymorphism in the prebottleneck populations, but was unable to discern any effects of balancing selection in the contemporary population. Our results show drift is the overriding evolutionary force that has shaped TLR variation in the contemporary Seychelles warbler population, and the observed TLR polymorphisms might be merely the 'ghost of selection past'. Forecast models predict immunogenetic variation in this species will continue to be eroded in the absence of contemporary balancing selection. Such 'drift debt' occurs when a gene pool has not yet reached its new equilibrium level of polymorphism, and this loss could be an important threat to many recently bottlenecked populations. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Improving traffic flow at a 2-to-1 lane reduction with wirelessly connected, adaptive cruise control vehicles

NASA Astrophysics Data System (ADS)

Davis, L. C.

2016-06-01

Wirelessly connected vehicles that exchange information about traffic conditions can reduce delays caused by congestion. At a 2-to-1 lane reduction, the improvement in flow past a bottleneck due to traffic with a random mixture of 40% connected vehicles is found to be 52%. Control is based on connected-vehicle-reported velocities near the bottleneck. In response to indications of congestion the connected vehicles, which are also adaptive cruise control vehicles, reduce their speed in slowdown regions. Early lane changes of manually driven vehicles from the terminated lane to the continuous lane are induced by the slowing connected vehicles. Self-organized congestion at the bottleneck is thus delayed or eliminated, depending upon the incoming flow magnitude. For the large majority of vehicles, travel times past the bottleneck are substantially reduced. Control is responsible for delaying the onset of congestion as the incoming flow increases. Adaptive cruise control increases the flow out of the congested state at the bottleneck. The nature of the congested state, when it occurs, appears to be similar under a variety of conditions. Typically 80-100 vehicles are approximately equally distributed between the lanes in the 500 m region prior to the end of the terminated lane. Without the adaptive cruise control capability, connected vehicles can delay the onset of congestion but do not increase the asymptotic flow past the bottleneck. Calculations are done using the Kerner-Klenov three-phase theory, stochastic discrete-time model for manual vehicles. The dynamics of the connected vehicles is given by a conventional adaptive cruise control algorithm plus commanded deceleration. Because time in the model for manual vehicles is discrete (one-second intervals), it is assumed that the acceleration of any vehicle immediately in front of a connected vehicle is constant during the time interval, thereby preserving the computational simplicity and speed of a discrete-time model.

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

Saxer, Gerda; Krepps, Michael D.; Merkley, Eric D.

Adaptation to ecologically complex environments can provide insights into the evolutionary dynamics and functional constraints encountered by organisms during natural selection. Unlike adaptation to a single limiting resource, adaptation to a new environment with abundant and varied resources can be difficult to achieve by small incremental changes since many mutations are required to achieve even modest gains in fitness. Since changing complex environments are quite common in nature, we investigated how such an epistatic bottleneck can be avoided to allow rapid adaptation. We show that adaptive mutations arise repeatedly in independently evolved populations in the context of greatly increased geneticmore » and phenotypic diversity. We go on to show that weak selection requiring substantial metabolic reprogramming can be readily achieved by mutations in the global response regulator arcA and the stress response regulator rpoS. We identified 46 unique single-nucleotide variants of arcA and 18 mutations in rpoS, nine of which resulted in stop codons or large deletions, suggesting that a subtle modulation of ArcA function and knockouts of rpoS are largely responsible for the metabolic shifts leading to adaptation. These mutations allow a higher order “metabolic selection” that eliminates epistatic bottlenecks, which could occur when many changes would be required. Proteomic and carbohydrate analysis of adapting E. coli populations revealed an up-regulation of enzymes associated with the TCA cycle and amino acid metabolism and an increase in the secretion of putrescine. The overall effect of adaptation across populations is to redirect and efficiently utilize uptake and catabolism of abundant amino acids. Concomitantly, there is a pronounced spread of more ecologically limited strains that results from specialization through metabolic erosion. Remarkably, the global regulators arcA and rpoS can provide a “one-step” mechanism of adaptation to a novel environment, which highlights the importance of global resource management as a powerful strategy to adaptation.« less

Task choice and semantic interference in picture naming.

PubMed

Piai, Vitória; Roelofs, Ardi; Schriefers, Herbert

2015-05-01

Evidence from dual-task performance indicates that speakers prefer not to select simultaneous responses in picture naming and another unrelated task, suggesting a response selection bottleneck in naming. In particular, when participants respond to tones with a manual response and name pictures with superimposed semantically related or unrelated distractor words, semantic interference in naming tends to be constant across stimulus onset asynchronies (SOAs) between the tone stimulus and the picture-word stimulus. In the present study, we examine whether semantic interference in picture naming depends on SOA in case of a task choice (naming the picture vs reading the word of a picture-word stimulus) based on tones. This situation requires concurrent processing of the tone stimulus and the picture-word stimulus, but not a manual response to the tones. On each trial, participants either named a picture or read aloud a word depending on the pitch of a tone, which was presented simultaneously with picture-word onset or 350 ms or 1000 ms before picture-word onset. Semantic interference was present with tone pre-exposure, but absent when tone and picture-word stimulus were presented simultaneously. Against the background of the available studies, these results support an account according to which speakers tend to avoid concurrent response selection, but can engage in other types of concurrent processing, such as task choices. Copyright © 2015 Elsevier B.V. All rights reserved.

Bottom-up implementation of disease-management programmes: results of a multisite comparison.

PubMed

Lemmens, K M M; Nieboer, A P; Rutten-Van Mölken, M P M H; van Schayck, C P; Spreeuwenberg, C; Asin, J D; Huijsman, R

2011-01-01

To evaluate the implementation of three regional disease-management programmes on chronic obstructive pulmonary disease (COPD) based on bottlenecks experienced in professional practice. The authors performed a multisite comparison of three Dutch regional disease-management programmes combining patient-related, professional-directed and organisational interventions. Process (Assessing Chronic Illness Care survey) and outcome (disease specific quality of life (clinical COPD questionnaire (CCQ); chronic respiratory questionnaire (CRQ)), Medical Research Council dyspnoea and patients' experiences) data were collected for 370 COPD patients and their care providers. Bottlenecks in region A were mostly related to patient involvement, in region B to organisational issues and in region C to both. Selected interventions related to identified bottlenecks were implemented in all programmes, except for patient-related interventions in programme A. Within programmes, significant improvements were found on dyspnoea and patients' experiences with practice nurses. Outcomes on quality of life differed between programmes: programme A did not show any significant improvements; programme B did show any significant improvements on CCQ total (p<0.001), functional (p=0.011) and symptom (p<0.001), CRQ fatigue (p<0.001) and emotional scales (p<0.001); in programme C, CCQ symptom (p<0.001) improved significantly, whereas CCQ mental score (p<0.001) deteriorated significantly. Regression analyses showed that programmes with better implementation of selected interventions resulted in relatively larger improvements in quality of life (CCQ). Bottom-up implementation of COPD disease-management programmes is a feasible approach, which in multiple settings leads to significant improvements in outcomes of care. Programmes with a better fit between implemented interventions and bottlenecks showed more positive changes in outcomes.

High-throughput crystal-optimization strategies in the South Paris Yeast Structural Genomics Project: one size fits all?

PubMed

Leulliot, Nicolas; Trésaugues, Lionel; Bremang, Michael; Sorel, Isabelle; Ulryck, Nathalie; Graille, Marc; Aboulfath, Ilham; Poupon, Anne; Liger, Dominique; Quevillon-Cheruel, Sophie; Janin, Joël; van Tilbeurgh, Herman

2005-06-01

Crystallization has long been regarded as one of the major bottlenecks in high-throughput structural determination by X-ray crystallography. Structural genomics projects have addressed this issue by using robots to set up automated crystal screens using nanodrop technology. This has moved the bottleneck from obtaining the first crystal hit to obtaining diffraction-quality crystals, as crystal optimization is a notoriously slow process that is difficult to automatize. This article describes the high-throughput optimization strategies used in the Yeast Structural Genomics project, with selected successful examples.

Health-system strengthening and tuberculosis control.

PubMed

Atun, Rifat; Weil, Diana E C; Eang, Mao Tan; Mwakyusa, David

2010-06-19

Weak health systems are hindering global efforts for tuberculosis care and control, but little evidence is available on effective interventions to address system bottlenecks. This report examines published evidence, programme reviews, and case studies to identify innovations in system design and tuberculosis control to resolve these bottlenecks. We outline system bottlenecks in relation to governance, financing, supply chain management, human resources, health-information systems, and service delivery; and adverse effects from rapid introduction of suboptimum system designs. This report also documents innovative solutions for disease control and system design. Solutions pursued in individual countries are specific to the nature of the tuberculosis epidemic, the underlying national health system, and the contributors engaged: no one size fits all. Findings from countries, including Bangladesh, Cambodia, India, Tanzania, Thailand, and Vietnam, suggest that advances in disease control and system strengthening are complementary. Tuberculosis care and control are essential elements of health systems, and simultaneous efforts to innovate systems and disease response are mutually reinforcing. Highly varied and context-specific responses to tuberculosis show that solutions need to be documented and compared to develop evidence-based policies and practice. Copyright 2010 Elsevier Ltd. All rights reserved.

Cultural Hitchhiking in the Matrilineal Whales.

PubMed

Whitehead, Hal; Vachon, Felicia; Frasier, Timothy R

2017-05-01

Five species of whale with matrilineal social systems (daughters remain with mothers) have remarkably low levels of mitochondrial DNA diversity. Non-heritable matriline-level demography could reduce genetic diversity but the required conditions are not consistent with the natural histories of the matrilineal whales. The diversity of nuclear microsatellites is little reduced in the matrilineal whales arguing against bottlenecks. Selective sweeps of the mitochondrial genome are feasible causes but it is not clear why these only occurred in the matrilineal species. Cultural hitchhiking (cultural selection reducing diversity at neutral genetic loci transmitted in parallel to the culture) is supported in sperm whales which possess suitable matrilineal socio-cultural groups (coda clans). Killer whales are delineated into ecotypes which likely originated culturally. Culture, bottlenecks and selection, as well as their interactions, operating between- or within-ecotypes, may have reduced their mitochondrial diversity. The societies, cultures and genetics of false killer and two pilot whale species are insufficiently known to assess drivers of low mitochondrial diversity.

Time-Sampled Population Sequencing Reveals the Interplay of Selection and Genetic Drift in Experimental Evolution of Potato Virus Y

PubMed Central

2017-01-01

ABSTRACT RNA viruses are one of the fastest-evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection, and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant-pathogenic virus, we performed evolution experiments with Potato virus Y (PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly generated variations in the evolving viral lineages. A time-sampled approach allowed us to (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less-susceptible host (efficient in the accumulation of salicylic acid). IMPORTANCE High diversity of within-host populations of RNA viruses is an important aspect of their biology, since they represent a reservoir of genetic variants, which can enable quick adaptation of viruses to a changing environment. This study focuses on an important plant virus, Potato virus Y, and describes, at high resolution, temporal changes in the structure of viral populations within different potato genotypes. A novel and easy-to-implement computational approach was established to cluster single nucleotide polymorphisms into viral haplotypes from very short sequencing reads. During the experiment, a shift in the frequency of selected viral haplotypes was observed after a narrow genetic bottleneck, indicating an important role of the genetic drift in the evolution of the virus. On the other hand, a possible case of diversifying selection of the virus was observed in less susceptible host genotypes. PMID:28592544

Acoustic-optical phonon up-conversion and hot-phonon bottleneck in lead-halide perovskites

PubMed Central

Yang, Jianfeng; Wen, Xiaoming; Xia, Hongze; Sheng, Rui; Ma, Qingshan; Kim, Jincheol; Tapping, Patrick; Harada, Takaaki; Kee, Tak W.; Huang, Fuzhi; Cheng, Yi-Bing; Green, Martin; Ho-Baillie, Anita; Huang, Shujuan; Shrestha, Santosh; Patterson, Robert; Conibeer, Gavin

2017-01-01

The hot-phonon bottleneck effect in lead-halide perovskites (APbX3) prolongs the cooling period of hot charge carriers, an effect that could be used in the next-generation photovoltaics devices. Using ultrafast optical characterization and first-principle calculations, four kinds of lead-halide perovskites (A=FA+/MA+/Cs+, X=I−/Br−) are compared in this study to reveal the carrier-phonon dynamics within. Here we show a stronger phonon bottleneck effect in hybrid perovskites than in their inorganic counterparts. Compared with the caesium-based system, a 10 times slower carrier-phonon relaxation rate is observed in FAPbI3. The up-conversion of low-energy phonons is proposed to be responsible for the bottleneck effect. The presence of organic cations introduces overlapping phonon branches and facilitates the up-transition of low-energy modes. The blocking of phonon propagation associated with an ultralow thermal conductivity of the material also increases the overall up-conversion efficiency. This result also suggests a new and general method for achieving long-lived hot carriers in materials. PMID:28106061

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population ▿ †

PubMed Central

Russell, Elizabeth S.; Kwiek, Jesse J.; Keys, Jessica; Barton, Kirston; Mwapasa, Victor; Montefiori, David C.; Meshnick, Steven R.; Swanstrom, Ronald

2011-01-01

Subtype C human immunodeficiency virus type 1 (HIV-1C) continues to cause the majority of new cases of mother-to-child transmission (MTCT), and yet there are limited data on HIV-1C transmission. We amplified env from plasma RNA for 19 HIV-1C MTCT pairs, 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP). There was a strong genetic bottleneck between all mother-infant pairs, with a majority of transmission events involving the transmission of a single virus. env genes of viruses transmitted to infants IP, but not IU, encoded Env proteins that were shorter and had fewer putative N-linked glycosylation sites in the V1-V5 region than matched maternal sequences. Viruses pseudotyped with env clones representative of each maternal and infant population were tested for neutralization sensitivity. The 50% inhibitory concentration of autologous serum was similar against both transmitted (infant) and nontransmitted (maternal) viruses in a paired analysis. Mother and infant Env proteins were also similar in sensitivity to soluble CD4, to a panel of monoclonal antibodies, and to heterologous HIV-1C sera. In addition, there was no difference in the breadth or potency of neutralizing antibodies between sera from 50 nontransmitting and 23 IU and 23 IP transmitting HIV-1C-infected women against four Env proteins from heterologous viruses. Thus, while a strong genetic bottleneck was detected during MCTC, with viruses of shorter and fewer glycosylation sites in env present in IP transmission, our data do not support this bottleneck being driven by selective resistance to antibodies. PMID:21593171

Response terminated displays unload selective attention

PubMed Central

Roper, Zachary J. J.; Vecera, Shaun P.

2013-01-01

Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional “spill-over” to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional “spill-over” by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented. PMID:24399983

Response terminated displays unload selective attention.

PubMed

Roper, Zachary J J; Vecera, Shaun P

2013-01-01

Perceptual load theory successfully replaced the early vs. late selection debate by appealing to adaptive control over the efficiency of selective attention. Early selection is observed unless perceptual load (p-Load) is sufficiently low to grant attentional "spill-over" to task-irrelevant stimuli. Many studies exploring load theory have used limited display durations that perhaps impose artificial limits on encoding processes. We extended the exposure duration in a classic p-Load task to alleviate temporal encoding demands that may otherwise tax mnemonic consolidation processes. If the load effect arises from perceptual demands alone, then freeing-up available mnemonic resources by extending the exposure duration should have little effect. The results of Experiment 1 falsify this prediction. We observed a reliable flanker effect under high p-Load, response-terminated displays. Next, we orthogonally manipulated exposure duration and task-relevance. Counter-intuitively, we found that the likelihood of observing the flanker effect under high p-Load resides with the duration of the task-relevant array, not the flanker itself. We propose that stimulus and encoding demands interact to produce the load effect. Our account clarifies how task parameters differentially impinge upon cognitive processes to produce attentional "spill-over" by appealing to visual short-term memory as an additional processing bottleneck when stimuli are briefly presented.

Amodal processing in human prefrontal cortex.

PubMed

Tamber-Rosenau, Benjamin J; Dux, Paul E; Tombu, Michael N; Asplund, Christopher L; Marois, René

2013-07-10

Information enters the cortex via modality-specific sensory regions, whereas actions are produced by modality-specific motor regions. Intervening central stages of information processing map sensation to behavior. Humans perform this central processing in a flexible, abstract manner such that sensory information in any modality can lead to response via any motor system. Cognitive theories account for such flexible behavior by positing amodal central information processing (e.g., "central executive," Baddeley and Hitch, 1974; "supervisory attentional system," Norman and Shallice, 1986; "response selection bottleneck," Pashler, 1994). However, the extent to which brain regions embodying central mechanisms of information processing are amodal remains unclear. Here we apply multivariate pattern analysis to functional magnetic resonance imaging (fMRI) data to compare response selection, a cognitive process widely believed to recruit an amodal central resource across sensory and motor modalities. We show that most frontal and parietal cortical areas known to activate across a wide variety of tasks code modality, casting doubt on the notion that these regions embody a central processor devoid of modality representation. Importantly, regions of anterior insula and dorsolateral prefrontal cortex consistently failed to code modality across four experiments. However, these areas code at least one other task dimension, process (instantiated as response selection vs response execution), ensuring that failure to find coding of modality is not driven by insensitivity of multivariate pattern analysis in these regions. We conclude that abstract encoding of information modality is primarily a property of subregions of the prefrontal cortex.

More insight into the interplay of response selection and visual attention in dual-tasks: masked visual search and response selection are performed in parallel.

PubMed

Reimer, Christina B; Schubert, Torsten

2017-09-15

Both response selection and visual attention are limited in capacity. According to the central bottleneck model, the response selection processes of two tasks in a dual-task situation are performed sequentially. In conjunction search, visual attention is required to select the items and to bind their features (e.g., color and form), which results in a serial search process. Search time increases as items are added to the search display (i.e., set size effect). When the search display is masked, visual attention deployment is restricted to a brief period of time and target detection decreases as a function of set size. Here, we investigated whether response selection and visual attention (i.e., feature binding) rely on a common or on distinct capacity limitations. In four dual-task experiments, participants completed an auditory Task 1 and a conjunction search Task 2 that were presented with an experimentally modulated temporal interval between them (Stimulus Onset Asynchrony, SOA). In Experiment 1, Task 1 was a two-choice discrimination task and the conjunction search display was not masked. In Experiment 2, the response selection difficulty in Task 1 was increased to a four-choice discrimination and the search task was the same as in Experiment 1. We applied the locus-of-slack method in both experiments to analyze conjunction search time, that is, we compared the set size effects across SOAs. Similar set size effects across SOAs (i.e., additive effects of SOA and set size) would indicate sequential processing of response selection and visual attention. However, a significantly smaller set size effect at short SOA compared to long SOA (i.e., underadditive interaction of SOA and set size) would indicate parallel processing of response selection and visual attention. In both experiments, we found underadditive interactions of SOA and set size. In Experiments 3 and 4, the conjunction search display in Task 2 was masked. Task 1 was the same as in Experiments 1 and 2, respectively. In both experiments, the d' analysis revealed that response selection did not affect target detection. Overall, Experiments 1-4 indicated that neither the response selection difficulty in the auditory Task 1 (i.e., two-choice vs. four-choice) nor the type of presentation of the search display in Task 2 (i.e., not masked vs. masked) impaired parallel processing of response selection and conjunction search. We concluded that in general, response selection and visual attention (i.e., feature binding) rely on distinct capacity limitations.

Genetic consequences of selection cutting on sugar maple (Acer saccharum Marshall).

PubMed

Graignic, Noémie; Tremblay, Francine; Bergeron, Yves

2016-07-01

Selection cutting is a treatment that emulates tree-by-tree replacement for forests with uneven-age structures. It creates small openings in large areas and often generates a more homogenous forest structure (fewer large leaving trees and defective trees) that differs from old-growth forest. In this study, we evaluated whether this type of harvesting has an impact on genetic diversity of sugar maple (Acer saccharum Marshall). Genetic diversity among seedlings, saplings, and mature trees was compared between selection cut and old-growth forest stands in Québec, Canada. We found higher observed heterozygosity and a lower inbreeding coefficient in mature trees than in younger regeneration cohorts of both forest types. We detected a recent bottleneck in all stands undergoing selection cutting. Other genetic indices of diversity (allelic richness, observed and expected heterozygosity, and rare alleles) were similar between forest types. We concluded that the effect of selection cutting on the genetic diversity of sugar maple was recent and no evidence of genetic erosion was detectable in Québec stands after one harvest. However, the cumulative effect of recurring applications of selection cutting in bottlenecked stands could lead to fixation of deleterious alleles, and this highlights the need for adopting better forest management practices.

Investigation of the bottleneck leading to the domestication of maize

PubMed Central

Eyre-Walker, Adam; Gaut, Rebecca L.; Hilton, Holly; Feldman, Dawn L.; Gaut, Brandon S.

1998-01-01

Maize (Zea mays ssp. mays) is genetically diverse, yet it is also morphologically distinct from its wild relatives. These two observations are somewhat contradictory: the first observation is consistent with a large historical population size for maize, but the latter observation is consistent with strong, diversity-limiting selection during maize domestication. In this study, we sampled sequence diversity, coupled with simulations of the coalescent process, to study the dynamics of a population bottleneck during the domestication of maize. To do this, we determined the DNA sequence of a 1,400-bp region of the Adh1 locus from 19 individuals representing maize, its presumed progenitor (Z. mays ssp. parviglumis), and a more distant relative (Zea luxurians). The sequence data were used to guide coalescent simulations of population bottlenecks associated with domestication. Our study confirms high genetic diversity in maize—maize contains 75% of the variation found in its progenitor and is more diverse than its wild relative, Z. luxurians—but it also suggests that sequence diversity in maize can be explained by a bottleneck of short duration and very small size. For example, the breadth of genetic diversity in maize is consistent with a founding population of only 20 individuals when the domestication event is 10 generations in length. PMID:9539756

Impact of historical founder effects and a recent bottleneck on MHC variability in Commander Arctic foxes (Vulpes lagopus)

PubMed Central

Ploshnitsa, Anna I; Goltsman, Mikhail E; Macdonald, David W; Kennedy, Lorna J; Sommer, Simone

2012-01-01

Populations of Arctic foxes (Vulpes lagopus) have been isolated on two of the Commander Islands (Bering and Mednyi) from the circumpolar distributed mainland population since the Pleistocene. In 1970–1980, an epizootic outbreak of mange caused a severe population decline on Mednyi Island. Genes of the major histocompatibility complex (MHC) play a primary role in infectious disease resistance. The main objectives of our study were to compare contemporary variation of MHC class II in mainland and island Arctic foxes, and to document the effects of the isolation and the recent bottleneck on MHC polymorphism by analyzing samples from historical and contemporary Arctic foxes. In 184 individuals, we found 25 unique MHC class II DRB and DQB alleles, and identified evidence of balancing selection maintaining allelic lineages over time at both loci. Twenty different MHC alleles were observed in mainland foxes and eight in Bering Island foxes. The historical Mednyi population contained five alleles and all contemporary individuals were monomorphic at both DRB and DQB. Our data indicate that despite positive and diversifying selection leading to elevated rates of amino acid replacement in functionally important antigen-binding sites, below a certain population size, balancing selection may not be strong enough to maintain genetic diversity in functionally important genes. This may have important fitness consequences and might explain the high pathogen susceptibility in some island populations. This is the first study that compares MHC diversity before and after a bottleneck in a wild canid population using DNA from museum samples. PMID:22408734

Staphylococcus aureus infection dynamics.

PubMed

Pollitt, Eric J G; Szkuta, Piotr T; Burns, Nicola; Foster, Simon J

2018-06-01

Staphylococcus aureus is a human commensal that can also cause systemic infections. This transition requires evasion of the immune response and the ability to exploit different niches within the host. However, the disease mechanisms and the dominant immune mediators against infection are poorly understood. Previously it has been shown that the infecting S. aureus population goes through a population bottleneck, from which very few bacteria escape to establish the abscesses that are characteristic of many infections. Here we examine the host factors underlying the population bottleneck and subsequent clonal expansion in S. aureus infection models, to identify underpinning principles of infection. The bottleneck is a common feature between models and is independent of S. aureus strain. Interestingly, the high doses of S. aureus required for the widely used "survival" model results in a reduced population bottleneck, suggesting that host defences have been simply overloaded. This brings into question the applicability of the survival model. Depletion of immune mediators revealed key breakpoints and the dynamics of systemic infection. Loss of macrophages, including the liver Kupffer cells, led to increased sensitivity to infection as expected but also loss of the population bottleneck and the spread to other organs still occurred. Conversely, neutrophil depletion led to greater susceptibility to disease but with a concomitant maintenance of the bottleneck and lack of systemic spread. We also used a novel microscopy approach to examine abscess architecture and distribution within organs. From these observations we developed a conceptual model for S. aureus disease from initial infection to mature abscess. This work highlights the need to understand the complexities of the infectious process to be able to assign functions for host and bacterial components, and why S. aureus disease requires a seemingly high infectious dose and how interventions such as a vaccine may be more rationally developed.

Squeezing through the Now-or-Never bottleneck: Reconnecting language processing, acquisition, change, and structure.

PubMed

Chater, Nick; Christiansen, Morten H

2016-01-01

If human language must be squeezed through a narrow cognitive bottleneck, what are the implications for language processing, acquisition, change, and structure? In our target article, we suggested that the implications are far-reaching and form the basis of an integrated account of many apparently unconnected aspects of language and language processing, as well as suggesting revision of many existing theoretical accounts. With some exceptions, commentators were generally supportive both of the existence of the bottleneck and its potential implications. Many commentators suggested additional theoretical and linguistic nuances and extensions, links with prior work, and relevant computational and neuroscientific considerations; some argued for related but distinct viewpoints; a few, though, felt traditional perspectives were being abandoned too readily. Our response attempts to build on the many suggestions raised by the commentators and to engage constructively with challenges to our approach.

A single origin and moderate bottleneck during domestication of soybean (Glycine max): implications from microsatellites and nucleotide sequences

PubMed Central

Guo, Juan; Wang, Yunsheng; Song, Chi; Zhou, Jianfeng; Qiu, Lijuan; Huang, Hongwen; Wang, Ying

2010-01-01

Background and Aims It is essential to illuminate the evolutionary history of crop domestication in order to understand further the origin and development of modern cultivation and agronomy; however, despite being one of the most important crops, the domestication origin and bottleneck of soybean (Glycine max) are poorly understood. In the present study, microsatellites and nucleotide sequences were employed to elucidate the domestication genetics of soybean. Methods The genomes of 79 landrace soybeans (endemic cultivated soybeans) and 231 wild soybeans (G. soja) that represented the species-wide distribution of wild soybean in East Asia were scanned with 56 microsatellites to identify the genetic structure and domestication origin of soybean. To understand better the domestication bottleneck, four nucleotide sequences were selected to simulate the domestication bottleneck. Key Results Model-based analysis revealed that most of the landrace genotypes were assigned to the inferred wild soybean cluster of south China, South Korea and Japan. Phylogeny for wild and landrace soybeans showed that all landrace soybeans formed a single cluster supporting a monophyletic origin of all the cultivars. The populations of the nearest branches which were basal to the cultivar lineage were wild soybeans from south China. The coalescent simulation detected a bottleneck severity of K′ = 2 during soybean domestication, which could be explained by a foundation population of 6000 individuals if domestication duration lasted 3000 years. Conclusions As a result of integrating geographic distribution with microsatellite genotype assignment and phylogeny between landrace and wild soybeans, a single origin of soybean in south China is proposed. The coalescent simulation revealed a moderate genetic bottleneck with an effective wild soybean population used for domestication estimated to be ≈2 % of the total number of ancestral wild soybeans. Wild soybeans in Asia, especially in south China contain tremendous genetic resources for cultivar improvement. PMID:20566681

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

A first packet processing subdomain cluster model based on SDN

NASA Astrophysics Data System (ADS)

Chen, Mingyong; Wu, Weimin

2017-08-01

For the current controller cluster packet processing performance bottlenecks and controller downtime problems. An SDN controller is proposed to allocate the priority of each device in the SDN (Software Defined Network) network, and the domain contains several network devices and Controller, the controller is responsible for managing the network equipment within the domain, the switch performs data delivery based on the load of the controller, processing network equipment data. The experimental results show that the model can effectively solve the risk of single point failure of the controller, and can solve the performance bottleneck of the first packet processing.

Antenatal corticosteroids for management of preterm birth: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background Preterm birth complications are the leading cause of deaths for children under five years. Antenatal corticosteroids (ACS) are effective at reducing mortality and serious morbidity amongst infants born at <34 weeks gestation. WHO guidelines strongly recommend use of ACS for women at risk of imminent preterm birth where gestational age, imminent preterm birth, and risk of maternal infection can be assessed, and appropriate maternal/newborn care provided. However, coverage remains low in high-burden countries for reasons not previously systematically investigated. Methods The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for ACS. Results Eleven out of twelve countries provided data in response to the ACS questionnaire. Health system building blocks most frequently reported as having significant or very major bottlenecks were health information systems (11 countries), essential medical products and technologies (9 out of 11 countries) and health service delivery (9 out of 11 countries). Bottlenecks included absence of coverage data, poor gestational age metrics, lack of national essential medicines listing, discrepancies between prescribing authority and provider cadres managing care, delays due to referral, and lack of supervision, mentoring and quality improvement systems. Conclusions Analysis centred on health system building blocks in which 9 or more countries (>75%) reported very major or significant bottlenecks. Health information systems should include improved gestational age assessment and track ACS coverage, use and outcomes. Better health service delivery requires clarified policy assigning roles by level of care and cadre of provider, dependent on capability to assess gestational age and risk of preterm birth, and the implementation of guidelines with adequate supervision, mentoring and quality improvement systems, including audit and feedback. National essential medicines lists should include dexamethasone for antenatal use, and dexamethasone should be integrated into supply logistics. PMID:26390927

Heterosexual Transmission of Subtype C HIV-1 Selects Consensus-Like Variants without Increased Replicative Capacity or Interferon-α Resistance

PubMed Central

Fenton-May, Angharad E.; Dilernia, Dario A.; Kilembe, William; Allen, Susan A.; Borrow, Persephone; Hunter, Eric

2015-01-01

Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-α (IFN-α) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-α resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential. PMID:26378795

Research on Production Scheduling System with Bottleneck Based on Multi-agent

NASA Astrophysics Data System (ADS)

Zhenqiang, Bao; Weiye, Wang; Peng, Wang; Pan, Quanke

Aimed at the imbalance problem of resource capacity in Production Scheduling System, this paper uses Production Scheduling System based on multi-agent which has been constructed, and combines the dynamic and autonomous of Agent; the bottleneck problem in the scheduling is solved dynamically. Firstly, this paper uses Bottleneck Resource Agent to find out the bottleneck resource in the production line, analyses the inherent mechanism of bottleneck, and describes the production scheduling process based on bottleneck resource. Bottleneck Decomposition Agent harmonizes the relationship of job's arrival time and transfer time in Bottleneck Resource Agent and Non-Bottleneck Resource Agents, therefore, the dynamic scheduling problem is simplified as the single machine scheduling of each resource which takes part in the scheduling. Finally, the dynamic real-time scheduling problem is effectively solved in Production Scheduling System.

Linkage Disequilibrium Under Recurrent Bottlenecks

PubMed Central

Schaper, E.; Eriksson, A.; Rafajlovic, M.; Sagitov, S.; Mehlig, B.

2012-01-01

To model deviations from selectively neutral genetic variation caused by different forms of selection, it is necessary to first understand patterns of neutral variation. Best understood is neutral genetic variation at a single locus. But, as is well known, additional insights can be gained by investigating multiple loci. The resulting patterns reflect the degree of association (linkage) between loci and provide information about the underlying multilocus gene genealogies. The statistical properties of two-locus gene genealogies have been intensively studied for populations of constant size, as well as for simple demographic histories such as exponential population growth and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright–Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci in samples of two chromosomes. This covariance reflects the degree of association and thus linkage disequilibrium between these loci. We find, first, that an effective population-size approximation describes the numerically observed association between two loci provided that recombination occurs either much faster or much more slowly than the population-size fluctuations. Second, when recombination occurs frequently between but rarely within bottlenecks, we observe that the association of gene histories becomes independent of physical distance over a certain range of distances. Third, we show that in this case, a commonly used measure of linkage disequilibrium, σd2 (closely related to r^2), fails to capture the long-range association between two loci. The reason is that constituent terms, each reflecting the long-range association, cancel. Fourth, we analyze a limiting case in which the long-range association can be described in terms of a Xi coalescent allowing for simultaneous multiple mergers of ancestral lines. PMID:22048021

Considering the Influence of Nonadaptive Evolution on Primate Color Vision.

PubMed

Jacobs, Rachel L; Bradley, Brenda J

2016-01-01

Color vision in primates is variable across species, and it represents a rare trait in which the genetic mechanisms underlying phenotypic variation are fairly well-understood. Research on primate color vision has largely focused on adaptive explanations for observed variation, but it remains unclear why some species have trichromatic or polymorphic color vision while others are red-green color blind. Lemurs, in particular, are highly variable. While some species are polymorphic, many closely-related species are strictly dichromatic. We provide the first characterization of color vision in a wild population of red-bellied lemurs (Eulemur rubriventer, Ranomafana National Park, Madagascar) with a sample size (87 individuals; NX chromosomes = 134) large enough to detect even rare variants (0.95 probability of detection at ≥ 3% frequency). By sequencing exon 5 of the X-linked opsin gene we identified opsin spectral sensitivity based on known diagnostic sites and found this population to be dichromatic and monomorphic for a long wavelength allele. Apparent fixation of this long allele is in contrast to previously published accounts of Eulemur species, which exhibit either polymorphic color vision or only the medium wavelength opsin. This unexpected result may represent loss of color vision variation, which could occur through selective processes and/or genetic drift (e.g., genetic bottleneck). To indirectly assess the latter scenario, we genotyped 55 adult red-bellied lemurs at seven variable microsatellite loci and used heterozygosity excess and M-ratio tests to assess if this population may have experienced a recent genetic bottleneck. Results of heterozygosity excess but not M-ratio tests suggest a bottleneck might have occurred in this red-bellied lemur population. Therefore, while selection may also play a role, the unique color vision observed in this population might have been influenced by a recent genetic bottleneck. These results emphasize the need to consider adaptive and nonadaptive mechanisms of color vision evolution in primates.

Considering the Influence of Nonadaptive Evolution on Primate Color Vision

PubMed Central

Jacobs, Rachel L.; Bradley, Brenda J.

2016-01-01

Color vision in primates is variable across species, and it represents a rare trait in which the genetic mechanisms underlying phenotypic variation are fairly well-understood. Research on primate color vision has largely focused on adaptive explanations for observed variation, but it remains unclear why some species have trichromatic or polymorphic color vision while others are red-green color blind. Lemurs, in particular, are highly variable. While some species are polymorphic, many closely-related species are strictly dichromatic. We provide the first characterization of color vision in a wild population of red-bellied lemurs (Eulemur rubriventer, Ranomafana National Park, Madagascar) with a sample size (87 individuals; NX chromosomes = 134) large enough to detect even rare variants (0.95 probability of detection at ≥ 3% frequency). By sequencing exon 5 of the X-linked opsin gene we identified opsin spectral sensitivity based on known diagnostic sites and found this population to be dichromatic and monomorphic for a long wavelength allele. Apparent fixation of this long allele is in contrast to previously published accounts of Eulemur species, which exhibit either polymorphic color vision or only the medium wavelength opsin. This unexpected result may represent loss of color vision variation, which could occur through selective processes and/or genetic drift (e.g., genetic bottleneck). To indirectly assess the latter scenario, we genotyped 55 adult red-bellied lemurs at seven variable microsatellite loci and used heterozygosity excess and M-ratio tests to assess if this population may have experienced a recent genetic bottleneck. Results of heterozygosity excess but not M-ratio tests suggest a bottleneck might have occurred in this red-bellied lemur population. Therefore, while selection may also play a role, the unique color vision observed in this population might have been influenced by a recent genetic bottleneck. These results emphasize the need to consider adaptive and nonadaptive mechanisms of color vision evolution in primates. PMID:26959829

The Deterministic Information Bottleneck

NASA Astrophysics Data System (ADS)

Strouse, D. J.; Schwab, David

2015-03-01

A fundamental and ubiquitous task that all organisms face is prediction of the future based on past sensory experience. Since an individual's memory resources are limited and costly, however, there is a tradeoff between memory cost and predictive payoff. The information bottleneck (IB) method (Tishby, Pereira, & Bialek 2000) formulates this tradeoff as a mathematical optimization problem using an information theoretic cost function. IB encourages storing as few bits of past sensory input as possible while selectively preserving the bits that are most predictive of the future. Here we introduce an alternative formulation of the IB method, which we call the deterministic information bottleneck (DIB). First, we argue for an alternative cost function, which better represents the biologically-motivated goal of minimizing required memory resources. Then, we show that this seemingly minor change has the dramatic effect of converting the optimal memory encoder from stochastic to deterministic. Next, we propose an iterative algorithm for solving the DIB problem. Additionally, we compare the IB and DIB methods on a variety of synthetic datasets, and examine the performance of retinal ganglion cell populations relative to the optimal encoding strategy for each problem.

Impacts of moving bottlenecks on traffic flow

NASA Astrophysics Data System (ADS)

Ou, Hui; Tang, Tie-Qiao

2018-06-01

Bottleneck (especially the moving bottleneck) widely exists in the urban traffic system. However, little effort has been made to study the impacts of the moving bottleneck on traffic flow (especially the evolution and propagation of traffic flow). In this article, we introduce the speed of a moving bottleneck into a traffic flow model, then propose an extended macro traffic flow with a moving bottleneck, and finally use the proposed model to study the effects of a moving bottleneck on the evolution and propagation of traffic flow under uniform flow and a small perturbation. The numerical results indicate that the moving bottleneck has prominent influences on the evolution of traffic flow under the two typical traffic situations and that the impacts are dependent on the initial density.

Transmission bottlenecks and RNAi collectively influence tick-borne flavivirus evolution.

PubMed

Grubaugh, Nathan D; Rückert, Claudia; Armstrong, Philip M; Bransfield, Angela; Anderson, John F; Ebel, Gregory D; Brackney, Doug E

2016-07-01

Arthropod-borne RNA viruses exist within hosts as heterogeneous populations of viral variants and, as a result, possess great genetic plasticity. Understanding the micro-evolutionary forces shaping these viruses can provide insights into how they emerge, adapt, and persist in new and changing ecological niches. While considerable attention has been directed toward studying the population dynamics of mosquito-borne viruses, little is known about tick-borne virus populations. Therefore, using a mouse and Ixodes scapularis tick transmission model, we examined Powassan virus (POWV; Flaviviridae, Flavivirus ) populations in and between both the vertebrate host and arthropod vector. We found that genetic bottlenecks, RNAi-mediated diversification, and selective constraints collectively influence POWV evolution. Together, our data provide a mechanistic explanation for the slow, long-term evolutionary trends of POWV, and suggest that all arthropod-borne viruses encounter similar selective pressures at the molecular level (i.e. RNAi), yet evolve much differently due to their unique rates and modes of transmission.

Selection on hemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses

PubMed Central

Wilker, Peter R.; Dinis, Jorge M.; Starrett, Gabriel; Imai, Masaki; Hatta, Masato; Nelson, Chase W.; O’Connor, David H.; Hughes, Austin L.; Neumann, Gabriele; Kawaoka, Yoshihiro; Friedrich, Thomas C.

2013-01-01

The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts, but the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that although within-host genetic diversity in hemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, where infection is established by only 1–2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck. PMID:24149915

Lagrangian-averaged model for magnetohydrodynamic turbulence and the absence of bottlenecks.

PubMed

Pietarila Graham, Jonathan; Mininni, Pablo D; Pouquet, Annick

2009-07-01

We demonstrate that, for the case of quasiequipartition between the velocity and the magnetic field, the Lagrangian-averaged magnetohydrodynamics (LAMHD) alpha model reproduces well both the large-scale and the small-scale properties of turbulent flows; in particular, it displays no increased (superfilter) bottleneck effect with its ensuing enhanced energy spectrum at the onset of the subfilter scales. This is in contrast to the case of the neutral fluid in which the Lagrangian-averaged Navier-Stokes alpha model is somewhat limited in its applications because of the formation of spatial regions with no internal degrees of freedom and subsequent contamination of superfilter-scale spectral properties. We argue that, as the Lorentz force breaks the conservation of circulation and enables spectrally nonlocal energy transfer (associated with Alfvén waves), it is responsible for the absence of a viscous bottleneck in magnetohydrodynamics (MHD), as compared to the fluid case. As LAMHD preserves Alfvén waves and the circulation properties of MHD, there is also no (superfilter) bottleneck found in LAMHD, making this method capable of large reductions in required numerical degrees of freedom; specifically, we find a reduction factor of approximately 200 when compared to a direct numerical simulation on a large grid of 1536;{3} points at the same Reynolds number.

Bottlenecks, concerns and needs in malaria operational research: the perspectives of key stakeholders in Nigeria.

PubMed

Onyiah, Pamela; Adamu, Al-Mukhtar Y; Afolabi, Rotimi F; Ajumobi, Olufemi; Ughasoro, Maduka D; Odeyinka, Oluwaseun; Nguku, Patrick; Ajayi, IkeOluwapo O

2018-05-04

We conducted a study to determine stakeholders' perspective of the bottlenecks, concerns and needs to malaria operational research (MOR) agenda setting in Nigeria. Eighty-five (37.9%) stakeholders identified lack of positive behavioural change as the major bottleneck to MOR across the malaria thematic areas comprising of malaria prevention 58.8% (50), case management 34.8% (39), advocacy communication and social mobilisation 4.7% (4) while procurement and supply chain management (PSM) and programme management experts had the least response of 1.2% (1) each. Other bottlenecks were inadequate capacity to implement (13.8%, n = 31), inadequate funds (11.6%, n = 26), poor supply management (9.4%, n = 21), administrative bureaucracy (5.8%, n = 13), inadequacy of experts (1.3%, n = 3) and poor policy implementation (4.9%, n = 11). Of the 31 stakeholders who opined lack of capacity to execute malaria operational research; 17 (54.8%), 10 (32.3%), 3 (9.7%) and 1 (3.2%) were experts in case management, malaria prevention, surveillance, monitoring and evaluation and PSM respectively. Improvement in community enlightenment and awareness strategies; and active involvement of health care workers public and private sectors were identified solutions to lack of positive behavioural change.

Contrasting epidemic histories reveal pathogen-mediated balancing selection on class II MHC diversity in a wild songbird.

PubMed

Hawley, Dana M; Fleischer, Robert C

2012-01-01

The extent to which pathogens maintain the extraordinary polymorphism at vertebrate Major Histocompatibility Complex (MHC) genes via balancing selection has intrigued evolutionary biologists for over half a century, but direct tests remain challenging. Here we examine whether a well-characterized epidemic of Mycoplasmal conjunctivitis resulted in balancing selection on class II MHC in a wild songbird host, the house finch (Carpodacus mexicanus). First, we confirmed the potential for pathogen-mediated balancing selection by experimentally demonstrating that house finches with intermediate to high multi-locus MHC diversity are more resistant to challenge with Mycoplasma gallisepticum. Second, we documented sequence and diversity-based signatures of pathogen-mediated balancing selection at class II MHC in exposed host populations that were absent in unexposed, control populations across an equivalent time period. Multi-locus MHC diversity significantly increased in exposed host populations following the epidemic despite initial compromised diversity levels from a recent introduction bottleneck in the exposed host range. We did not observe equivalent changes in allelic diversity or heterozygosity across eight neutral microsatellite loci, suggesting that the observations reflect selection rather than neutral demographic processes. Our results indicate that a virulent pathogen can exert sufficient balancing selection on class II MHC to rescue compromised levels of genetic variation for host resistance in a recently bottlenecked population. These results provide evidence for Haldane's long-standing hypothesis that pathogens directly contribute to the maintenance of the tremendous levels of genetic variation detected in natural populations of vertebrates.

Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

PubMed Central

2013-01-01

Background Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly respond to selection pressures, such as those imposed by the immunological host response and antiviral therapy. We have applied deep sequencing to characterize influenza intra-host variation in a transmission chain consisting of three cases due to oseltamivir-sensitive viruses, and one derived oseltamivir-resistant case. Methods Following detection of the A(H1N1)pdm09 infections, we deep-sequenced the complete NA gene from two of the oseltamivir-sensitive virus-infected cases, and all eight gene segments of the viruses causing the remaining two cases. Results No evidence for the resistance-causing mutation (resulting in NA H275Y substitution) was observed in the oseltamivir-sensitive cases. Furthermore, deep sequencing revealed a subpopulation of oseltamivir-sensitive viruses in the case carrying resistant viruses. We detected higher levels of intra-host variation in the case carrying oseltamivir-resistant viruses than in those infected with oseltamivir-sensitive viruses. Conclusions Oseltamivir-resistance was only detected after prophylaxis with oseltamivir, suggesting that the mutation was selected for as a result of antiviral intervention. The persisting oseltamivir-sensitive virus population in the case carrying resistant viruses suggests either that a small proportion survive the treatment, or that the oseltamivir-sensitive virus rapidly re-establishes itself in the virus population after the bottleneck. Moreover, the increased intra-host variation in the oseltamivir-resistant case is consistent with the hypothesis that the population diversity of a RNA virus can increase rapidly following a population bottleneck. PMID:23587185

Mother-to-Child HIV Transmission Bottleneck Selects for Consensus Virus with Lower Gag-Protease-Driven Replication Capacity

PubMed Central

Naidoo, Vanessa L.; Mann, Jaclyn K.; Noble, Christie; Adland, Emily; Carlson, Jonathan M.; Thomas, Jake; Brumme, Chanson J.; Thobakgale-Tshabalala, Christina F.; Brumme, Zabrina L.; Goulder, Philip J. R.

2017-01-01

ABSTRACT In the large majority of cases, HIV infection is established by a single variant, and understanding the characteristics of successfully transmitted variants is relevant to prevention strategies. Few studies have investigated the viral determinants of mother-to-child transmission. To determine the impact of Gag-protease-driven viral replication capacity on mother-to-child transmission, the replication capacities of 148 recombinant viruses encoding plasma-derived Gag-protease from 53 nontransmitter mothers, 48 transmitter mothers, and 47 infected infants were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. All study participants were infected with HIV-1 subtype C. There was no significant difference in replication capacities between the nontransmitter (n = 53) and transmitter (n = 44) mothers (P = 0.48). Infant-derived Gag-protease NL4-3 recombinant viruses (n = 41) were found to have a significantly lower Gag-protease-driven replication capacity than that of viruses derived from the mothers (P < 0.0001 by a paired t test). High percent similarities to consensus subtype C Gag, p17, p24, and protease sequences were also found in the infants (n = 28) in comparison to their mothers (P = 0.07, P = 0.002, P = 0.03, and P = 0.02, respectively, as determined by a paired t test). These data suggest that of the viral quasispecies found in mothers, the HIV mother-to-child transmission bottleneck favors the transmission of consensus-like viruses with lower viral replication capacities. IMPORTANCE Understanding the characteristics of successfully transmitted HIV variants has important implications for preventative interventions. Little is known about the viral determinants of HIV mother-to-child transmission (MTCT). We addressed the role of viral replication capacity driven by Gag, a major structural protein that is a significant determinant of overall viral replicative ability and an important target of the host immune response, in the MTCT bottleneck. This study advances our understanding of the genetic bottleneck in MTCT by revealing that viruses transmitted to infants have a lower replicative ability as well as a higher similarity to the population consensus (in this case HIV subtype C) than those of their mothers. Furthermore, the observation that “consensus-like” virus sequences correspond to lower in vitro replication abilities yet appear to be preferentially transmitted suggests that viral characteristics favoring transmission are decoupled from those that enhance replicative capacity. PMID:28637761

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy.

PubMed

Findlay, John M; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S; MacGregor, Thomas P; Church, David; Maynard, Nicholas D; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A; Wang, Lai-Mun; Sharma, Ricky A; Middleton, Mark; Tomlinson, Ian

2016-04-05

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful.

Room-Temperature Coherent Optical Phonon in 2D Electronic Spectra of CH 3NH 3PbI 3 Perovskite as a Possible Cooling Bottleneck

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

Monahan, Daniele M.; Guo, Liang; Lin, Jia

2017-06-29

A hot phonon bottleneck may be responsible for slow hot carrier cooling in methylammonium lead iodide hybrid perovskite, creating the potential for more efficient hot carrier photovoltaics. In room-temperature 2D electronic spectra near the band edge, we observe in this paper amplitude oscillations due to a remarkably long lived 0.9 THz coherent phonon population at room temperature. This phonon (or set of phonons) is assigned to angular distortions of the Pb–I lattice, not coupled to cation rotations. The strong coupling between the electronic transition and the 0.9 THz mode(s), together with relative isolation from other phonon modes, makes it likelymore » to cause a phonon bottleneck. Finally, the pump frequency resolution of the 2D spectra also enables independent observation of photoinduced absorptions and bleaches independently and confirms that features due to band gap renormalization are longer-lived than in transient absorption spectra.« less

Mental rotation impairs attention shifting and short-term memory encoding: neurophysiological evidence against the response-selection bottleneck model of dual-task performance.

PubMed

Pannebakker, Merel M; Jolicœur, Pierre; van Dam, Wessel O; Band, Guido P H; Ridderinkhof, K Richard; Hommel, Bernhard

2011-09-01

Dual tasks and their associated delays have often been used to examine the boundaries of processing in the brain. We used the dual-task procedure and recorded event-related potentials (ERPs) to investigate how mental rotation of a first stimulus (S1) influences the shifting of visual-spatial attention to a second stimulus (S2). Visual-spatial attention was monitored by using the N2pc component of the ERP. In addition, we examined the sustained posterior contralateral negativity (SPCN) believed to index the retention of information in visual short-term memory. We found modulations of both the N2pc and the SPCN, suggesting that engaging mechanisms of mental rotation impairs the deployment of visual-spatial attention and delays the passage of a representation of S2 into visual short-term memory. Both results suggest interactions between mental rotation and visual-spatial attention in capacity-limited processing mechanisms indicating that response selection is not pivotal in dual-task delays and all three processes are likely to share a common resource like executive control. Copyright © 2011 Elsevier Ltd. All rights reserved.

Increased genetic variation and evolutionary potential drive the success of an invasive grass.

PubMed

Lavergne, Sébastien; Molofsky, Jane

2007-03-06

Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species. Here, we focus on the invasive wetland grass Phalaris arundinacea L. and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions. Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes. This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range. Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range. The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity. Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential. Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future. More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination.

The Mouse-colored Tyrannulet (Phaeomyias murina) is a species complex that includes the Cocos Flycatcher (Nesotriccus ridgwayi), an island form that underwent a population bottleneck.

PubMed

Zucker, Marc R; Harvey, Michael G; Oswald, Jessica A; Cuervo, Andrés; Derryberry, Elizabeth; Brumfield, Robb T

2016-08-01

Simultaneous examination of evolutionary history in island forms and closely related mainland relatives can provide reciprocal insight into the evolution of island and mainland faunas. The Cocos Flycatcher (Nesotriccus ridgwayi) is a small tyrant flycatcher (Tyrannidae) endemic to Cocos Island, an oceanic island in the eastern Pacific Ocean. We first established its close relationship to the mainland species Mouse-colored Tyrannulet (Phaeomyias murina) using a phylogeny from genome-wide ultraconserved elements and exons. We then used mitochondrial DNA to explore the relationships between Nesotriccus and Phaeomyias populations from across its distribution in Central and South America. We found that Nesotriccus is nested within the Phaeomyias evolutionary tree, and that Phaeomyias represents a complex of at least four evolutionarily distinct species that differ in plumage, voice, and habitat association. Nesotriccus underwent a population bottleneck subsequent to its divergence from Central American and northern South American Phaeomyias populations in the middle Pleistocene. The 46 UCE loci containing alleles that are fixed between the two species are widely distributed across the genome, which suggests that selective or neutral processes responsible for divergence have occurred genome-wide. Overall, our simultaneous examination of Phaeomyias and Nesotriccus revealed divergent levels of genetic diversity and evolutionary histories between island and mainland forms. Copyright © 2016 Elsevier Inc. All rights reserved.

The PRP Effect Following Callosotomy: Residual Interference Despite Uncoupling of Lateralized Response Codes

NASA Technical Reports Server (NTRS)

Ivry, Richard B.; Franz, Elizabeth A.; Kingstone, Alan; Johnston, James C.; Null, Cynthia H. (Technical Monitor)

1995-01-01

A callosotomy patient was tested in two dual-task experiments requiring successive speeded responses to lateralized stimuli. In accord with the recent findings of Pashler, O'Brien, Luck, Hillyard, Mangun, and Gazzaniga (in press), the patient showed a robust psychological refractory period effect (PRP) responses on Task 2 were inversely related to the stimulus-onset asynchrony (SOA). However, three aspects of our data indicated that the processing limitations for the patient were different than those observed with control subjects. First, the split-brain patient did not show an increase in reaction time when the two tasks required responses from a common output system (i.e., both manual responses) in comparison to when different output systems were used (i.e., manual-vocal). Second, inconsistent stimulus-response mappings for the two tasks greatly inflated response latencies for the control subjects, but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with SOA for only the patient, suggesting a later bottleneck in processing following callosotomy than was observed for the control subjects. It is proposed that sectioning the corpus callosum eliminates interference resulting from competing stimulus response codes. Nonetheless, dual-task interference persists for the split-brain subject because a subcortical gate constrains when selected responses can be implemented.

Artificial selection for a secondary sexual character in males of Drosophila silvestris from Hawaii

PubMed Central

Carson, Hampton L.; Teramoto, Linden T.

1984-01-01

Drosophila silvestris is endemic to the rain forests of Hawaii Island. In populations from the northeast side, the male foreleg tibia bears about 100 long cilia; these are used as a brush to stimulate the female during courtship. Cyclical family selection for high and low cilia number was carried out on progeny of lines started from single wild isofemales collected at a single site. Significant response in both directions was obtained; in the third generation the lines differed by a mean of 25 cilia. Despite much effort to save them, both lines died out without further advance; the low cilia number line died after five and the high cilia number line died after nine generations. The data are compatible with the view that the cilia character is polygenic and is maintained in nature by a stabilizing sexual selection that also favors a polygenic heterozygous state. Although selection in these experiments resulted in dysgenesis, such a result is not inevitable. Disorganization and reorganization of such a genetic system following a population bottleneck might be important as a predisposing condition for the emergence of a specifically novel and possibly isolating mode of courtship. PMID:16593479

Neural Network-Based Sensor Validation for Turboshaft Engines

NASA Technical Reports Server (NTRS)

Moller, James C.; Litt, Jonathan S.; Guo, Ten-Huei

1998-01-01

Sensor failure detection, isolation, and accommodation using a neural network approach is described. An auto-associative neural network is configured to perform dimensionality reduction on the sensor measurement vector and provide estimated sensor values. The sensor validation scheme is applied in a simulation of the T700 turboshaft engine in closed loop operation. Performance is evaluated based on the ability to detect faults correctly and maintain stable and responsive engine operation. The set of sensor outputs used for engine control forms the network input vector. Analytical redundancy is verified by training networks of successively smaller bottleneck layer sizes. Training data generation and strategy are discussed. The engine maintained stable behavior in the presence of sensor hard failures. With proper selection of fault determination thresholds, stability was maintained in the presence of sensor soft failures.

Gene Flow Among Different Teosinte Taxa and Into the Domesticated Maize Gene Pool

USDA-ARS?s Scientific Manuscript database

Maize (Zea mays ssp. mays) was domesticated from one wild species ancestor, the Balsas teosinte (Zea mays ssp. parviglumis) about 9000 years ago. Higher levels of gene diversity are found in teosinte taxa compared to maize following domestication and selection bottlenecks. Diversity in maize can b...

Transmission Bottleneck Size Estimation from Pathogen Deep-Sequencing Data, with an Application to Human Influenza A Virus.

PubMed

Sobel Leonard, Ashley; Weissman, Daniel B; Greenbaum, Benjamin; Ghedin, Elodie; Koelle, Katia

2017-07-15

The bottleneck governing infectious disease transmission describes the size of the pathogen population transferred from the donor to the recipient host. Accurate quantification of the bottleneck size is particularly important for rapidly evolving pathogens such as influenza virus, as narrow bottlenecks reduce the amount of transferred viral genetic diversity and, thus, may decrease the rate of viral adaptation. Previous studies have estimated bottleneck sizes governing viral transmission by using statistical analyses of variants identified in pathogen sequencing data. These analyses, however, did not account for variant calling thresholds and stochastic viral replication dynamics within recipient hosts. Because these factors can skew bottleneck size estimates, we introduce a new method for inferring bottleneck sizes that accounts for these factors. Through the use of a simulated data set, we first show that our method, based on beta-binomial sampling, accurately recovers transmission bottleneck sizes, whereas other methods fail to do so. We then apply our method to a data set of influenza A virus (IAV) infections for which viral deep-sequencing data from transmission pairs are available. We find that the IAV transmission bottleneck size estimates in this study are highly variable across transmission pairs, while the mean bottleneck size of 196 virions is consistent with a previous estimate for this data set. Furthermore, regression analysis shows a positive association between estimated bottleneck size and donor infection severity, as measured by temperature. These results support findings from experimental transmission studies showing that bottleneck sizes across transmission events can be variable and influenced in part by epidemiological factors. IMPORTANCE The transmission bottleneck size describes the size of the pathogen population transferred from the donor to the recipient host and may affect the rate of pathogen adaptation within host populations. Recent advances in sequencing technology have enabled bottleneck size estimation from pathogen genetic data, although there is not yet a consistency in the statistical methods used. Here, we introduce a new approach to infer the bottleneck size that accounts for variant identification protocols and noise during pathogen replication. We show that failing to account for these factors leads to an underestimation of bottleneck sizes. We apply this method to an existing data set of human influenza virus infections, showing that transmission is governed by a loose, but highly variable, transmission bottleneck whose size is positively associated with the severity of infection of the donor. Beyond advancing our understanding of influenza virus transmission, we hope that this work will provide a standardized statistical approach for bottleneck size estimation for viral pathogens. Copyright © 2017 Sobel Leonard et al.

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

PubMed Central

Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

2018-01-01

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

Vanishing dual-task interference after practice: has the bottleneck been eliminated or is it merely latent?

NASA Technical Reports Server (NTRS)

Ruthruff, Eric; Johnston, James C.; Van Selst, Mark; Whitsell, Shelly; Remington, Roger

2003-01-01

Practice can, in some cases, largely eliminate measured dual-task interference. Does this absence of interference indicate the absence of a processing bottleneck (defined as an inability to carry out certain stages in parallel)? The authors show that a bottleneck need not produce any observable interference, provided that there is no temporal overlap in the demand for bottleneck stages on the 2 tasks. Such a "latent" bottleneck is especially likely after practice, when central stages are short. The authors provide new evidence that a latent bottleneck occurred for a participant who produced no interference in M. Van Selst, E. Ruthruff, and J. C. Johnston (1999). These findings demonstrate that the absence of dual-task interference does not necessarily indicate the absence of a processing bottleneck.

Separability of stimulus parameter encoding by on-off directionally selective rabbit retinal ganglion cells

PubMed Central

Nowak, Przemyslaw; Dobbins, Allan C.; Gawne, Timothy J.; Grzywacz, Norberto M.

2011-01-01

The ganglion cell output of the retina constitutes a bottleneck in sensory processing in that ganglion cells must encode multiple stimulus parameters in their responses. Here we investigate encoding strategies of On-Off directionally selective retinal ganglion cells (On-Off DS RGCs) in rabbits, a class of cells dedicated to representing motion. The exquisite axial discrimination of these cells to preferred vs. null direction motion is well documented: it is invariant with respect to speed, contrast, spatial configuration, spatial frequency, and motion extent. However, these cells have broad direction tuning curves and their responses also vary as a function of other parameters such as speed and contrast. In this study, we examined whether the variation in responses across multiple stimulus parameters is systematic, that is the same for all cells, and separable, such that the response to a stimulus is a product of the effects of each stimulus parameter alone. We extracellularly recorded single On-Off DS RGCs in a superfused eyecup preparation while stimulating them with moving bars. We found that spike count responses of these cells scaled as independent functions of direction, speed, and luminance. Moreover, the speed and luminance functions were common across the whole sample of cells. Based on these findings, we developed a model that accurately predicted responses of On-Off DS RGCs as products of separable functions of direction, speed, and luminance (r = 0.98; P < 0.0001). Such a multiplicatively separable encoding strategy may simplify the decoding of these cells' outputs by the higher visual centers. PMID:21325684

Elevated Proportions of Deleterious Genetic Variation in Domestic Animals and Plants

PubMed Central

Rubin, Carl-Johan; Carneiro, Miguel; Axelsson, Erik; Andersson, Leif

2018-01-01

Abstract A fraction of genetic variants segregating in any population are deleterious, which negatively impacts individual fitness. The domestication of animals and plants is associated with population bottlenecks and artificial selection, which are predicted to increase the proportion of deleterious variants. However, the extent to which this is a general feature of domestic species is unclear. Here, we examine the effects of domestication on the prevalence of deleterious variation using pooled whole-genome resequencing data from five domestic animal species (dog, pig, rabbit, chicken, and silkworm) and two domestic plant species (rice and soybean) compared with their wild ancestors. We find significantly reduced genetic variation and increased proportion of nonsynonymous amino acid changes in all but one of the domestic species. These differences are observable across a range of allele frequencies, both common and rare. We find proportionally more single nucleotide polymorphisms in highly conserved elements in domestic species and a tendency for domestic species to harbor a higher proportion of changes classified as damaging. Our findings most likely reflect an increased incidence of deleterious variants in domestic species, which is most likely attributable to population bottlenecks that lead to a reduction in the efficacy of selection. An exception to this pattern is displayed by European domestic pigs, which do not show traces of a strong population bottleneck and probably continued to exchange genes with wild boar populations after domestication. The results presented here indicate that an elevated proportion of deleterious variants is a common, but not ubiquitous, feature of domestic species. PMID:29325102

A Qualitative Study of Bottlenecks and Causes of Fractions for Dedicated Incomes of Health Centers and Solutions for their Reduction.

PubMed

Tabrizi, Jafar Sadegh; Alidoost, Saeide; Mashhadi Abdolahi, Hossein

2016-09-01

Primary health care is one of effective approaches for improving public health. Providing optimal cares requires supplication of various resources such as financial resources. "Fractions of incomes" in health centers is one of the remarkable problems for the domain of financial resources management in Iran. This study was aimed to identify bottlenecks and causes of fractions for incomes in health centers and solutions for their reduction. The current study was conducted in a qualitative phenomenology method in East Azerbaijan province of Iran in 2014. Data collection method was focus group discussion and semi-structured interview. Purposive sampling was used for selecting participants. Focus group discussions and interviews were conducted based on pre-prepared guidance and continued till data saturation. Validity of guidance was approved by qualitative studies experts. Data were analyzed using content analysis method. Based on the opinions of participants, two and six themes were respectively extracted for bottlenecks of fractions and causes and solutions for their reduction. Themes for bottlenecks of fractions included cash (monetary) and non-cash (non-monetary) fractions and themes for causes and solutions included causes and solutions for fractions per capita, insurance deductions, fractions related to sending documents, registration fractions, discounts fractions, and incomplete deposit of cash incomes. All cash and non-cash incomes of health centers are subject to fractions. The causes of fractions are related to the whole process of converting services to incomes and insurance requirements. Identified solutions and interventions also focus on these areas.

Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck.

PubMed

Wilson, Ian J; Carling, Phillipa J; Alston, Charlotte L; Floros, Vasileios I; Pyle, Angela; Hudson, Gavin; Sallevelt, Suzanne C E H; Lamperti, Costanza; Carelli, Valerio; Bindoff, Laurence A; Samuels, David C; Wonnapinij, Passorn; Zeviani, Massimo; Taylor, Robert W; Smeets, Hubert J M; Horvath, Rita; Chinnery, Patrick F

2016-03-01

With a combined carrier frequency of 1:200, heteroplasmic mitochondrial DNA (mtDNA) mutations cause human disease in ∼1:5000 of the population. Rapid shifts in the level of heteroplasmy seen within a single generation contribute to the wide range in the severity of clinical phenotypes seen in families transmitting mtDNA disease, consistent with a genetic bottleneck during transmission. Although preliminary evidence from human pedigrees points towards a random drift process underlying the shifting heteroplasmy, some reports describe differences in segregation pattern between different mtDNA mutations. However, based on limited observations and with no direct comparisons, it is not clear whether these observations simply reflect pedigree ascertainment and publication bias. To address this issue, we studied 577 mother-child pairs transmitting the m.11778G>A, m.3460G>A, m.8344A>G, m.8993T>G/C and m.3243A>G mtDNA mutations. Our analysis controlled for inter-assay differences, inter-laboratory variation and ascertainment bias. We found no evidence of selection during transmission but show that different mtDNA mutations segregate at different rates in human pedigrees. m.8993T>G/C segregated significantly faster than m.11778G>A, m.8344A>G and m.3243A>G, consistent with a tighter mtDNA genetic bottleneck in m.8993T>G/C pedigrees. Our observations support the existence of different genetic bottlenecks primarily determined by the underlying mtDNA mutation, explaining the different inheritance patterns observed in human pedigrees transmitting pathogenic mtDNA mutations. © The Author 2016. Published by Oxford University Press.

A Qualitative Study of Bottlenecks and Causes of Fractions for Dedicated Incomes of Health Centers and Solutions for their Reduction

PubMed Central

Tabrizi, Jafar Sadegh; Alidoost, Saeide; Abdolahi, Hossein Mashhadi

2016-01-01

Background: Primary health care is one of effective approaches for improving public health. Providing optimal cares requires supplication of various resources such as financial resources. “Fractions of incomes” in health centers is one of the remarkable problems for the domain of financial resources management in Iran. This study was aimed to identify bottlenecks and causes of fractions for incomes in health centers and solutions for their reduction. Methods: The current study was conducted in a qualitative phenomenology method in East Azerbaijan province of Iran in 2014. Data collection method was focus group discussion and semi-structured interview. Purposive sampling was used for selecting participants. Focus group discussions and interviews were conducted based on pre-prepared guidance and continued till data saturation. Validity of guidance was approved by qualitative studies experts. Data were analyzed using content analysis method. Results: Based on the opinions of participants, two and six themes were respectively extracted for bottlenecks of fractions and causes and solutions for their reduction. Themes for bottlenecks of fractions included cash (monetary) and non-cash (non-monetary) fractions and themes for causes and solutions included causes and solutions for fractions per capita, insurance deductions, fractions related to sending documents, registration fractions, discounts fractions, and incomplete deposit of cash incomes. Conclusion: All cash and non-cash incomes of health centers are subject to fractions. The causes of fractions are related to the whole process of converting services to incomes and insurance requirements. Identified solutions and interventions also focus on these areas. PMID:27157155

Use of in vivo Expression Technology for the Identification of Putative Host Adaptation Factors of the Lyme Disease Spirochete.

PubMed

Casselli, Timothy; Bankhead, Troy

2015-01-01

The causative agent of Lyme disease, Borrelia burgdorferi, is an obligate parasite that requires either a tick vector or a mammalian host for survival. Identification of the bacterial genes that are specifically expressed during infection of the mammalian host could provide targets for novel therapeutics and vaccines. In vivo expression technology (IVET) is a reporter-based promoter trap system that utilizes selectable markers to identify promoters of bacterial host-specific genes. Using previously characterized genes for in vivo and in vitro selection, this study utilized an IVET system that allows for selection of B. burgdorferi sequences that act as active promoters only during murine infection. This promoter trap system was able to successfully distinguish active promoter sequences both in vivo and in vitro from control sequences and a library of cloned B. burgdorferi genomic fragments. However, a bottleneck effect during the experimental mouse infection limited the utility for genome-wide promoter screening. Overall, IVET was demonstrated as a tool for the identification of in vivo-induced promoter elements of B. burgdorferi, and the observed infection bottleneck apparent using a polyclonal infection pool provides insight into the dynamics of experimental infection with B. burgdorferi. © 2015 S. Karger AG, Basel.

Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

NASA Astrophysics Data System (ADS)

Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

2015-01-01

The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1.

PubMed

Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

2015-01-28

The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr(6.63) forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr(6.63) to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr356(6.63) allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R.

Bottlenecks drive temporal and spatial genetic changes in alpine caddisfly metapopulations.

PubMed

Shama, Lisa N S; Kubow, Karen B; Jokela, Jukka; Robinson, Christopher T

2011-09-27

Extinction and re-colonisation of local populations is common in ephemeral habitats such as temporary streams. In most cases, such population turnover leads to reduced genetic diversity within populations and increased genetic differentiation among populations due to stochastic founder events, genetic drift, and bottlenecks associated with re-colonisation. Here, we examined the spatio-temporal genetic structure of 8 alpine caddisfly populations inhabiting permanent and temporary streams from four valleys in two regions of the Swiss Alps in years before and after a major stream drying event, the European heat wave in summer 2003. We found that population turnover after 2003 led to a loss of allelic richness and gene diversity but not to significant changes in observed heterozygosity. Within all valleys, permanent and temporary streams in any given year were not differentiated, suggesting considerable gene flow and admixture between streams with differing hydroperiods. Large changes in allele frequencies after 2003 resulted in a substantial increase in genetic differentiation among valleys within one to two years (1-2 generations) driven primarily by drift and immigration. Signatures of genetic bottlenecks were detected in all 8 populations after 2003 using the M-ratio method, but in no populations when using a heterozygosity excess method, indicating differential sensitivity of bottleneck detection methods. We conclude that genetic differentiation among A. uncatus populations changed markedly both temporally and spatially in response to the extreme climate event in 2003. Our results highlight the magnitude of temporal population genetic changes in response to extreme events. More specifically, our results show that extreme events can cause rapid genetic divergence in metapopulations. Further studies are needed to determine if recovery from this perturbation through gradual mixing of diverged populations by migration and gene flow leads to the pre-climate event state, or whether the observed changes represent a new genetic equilibrium.

Target-responsive DNA/RNA nanomaterials for microRNA sensing and inhibition: the jack-of-all-trades in cancer nanotheranostics?

PubMed

Conde, João; Edelman, Elazer R; Artzi, Natalie

2015-01-01

microRNAs (miRNAs) show high potential for cancer treatment, however one of the most significant bottlenecks in enabling miRNA effect is the need for an efficient vehicle capable of selective targeting to tumor cells without disrupting normal cells. Even more challenging is the ability to detect and silence multiple targets simultaneously with high sensitivity while precluding resistance to the therapeutic agents. Focusing on the pervasive role of miRNAs, herein we review the multiple nanomaterial-based systems that encapsulate DNA/RNA for miRNA sensing and inhibition in cancer therapy. Understanding the potential of miRNA detection and silencing while overcoming existing limitations will be critical to the optimization and clinical utilization of this technology. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of historical bottleneck effects and genetic consequences of re-introduction in a critically endangered island passerine.

PubMed

Bristol, Rachel M; Tucker, Rachel; Dawson, Deborah A; Horsburgh, Gavin; Prys-Jones, Robert P; Frantz, Alain C; Krupa, Andy; Shah, Nirmal J; Burke, Terry; Groombridge, Jim J

2013-09-01

Re-introduction is an important tool for recovering endangered species; however, the magnitude of genetic consequences for re-introduced populations remains largely unknown, in particular the relative impacts of historical population bottlenecks compared to those induced by conservation management. We characterize 14 microsatellite loci developed for the Seychelles paradise flycatcher and use them to quantify temporal and spatial measures of genetic variation across a 134-year time frame encompassing a historical bottleneck that reduced the species to ~28 individuals in the 1960s, through the initial stages of recovery and across a second contemporary conservation-introduction-induced bottleneck. We then evaluate the relative impacts of the two bottlenecks, and finally apply our findings to inform broader re-introduction strategy. We find a temporal trend of significant decrease in standard measures of genetic diversity across the historical bottleneck, but only a nonsignificant downward trend in number of alleles across the contemporary bottleneck. However, accounting for the different timescales of the two bottlenecks (~40 historical generations versus <1 contemporary generation), the loss of genetic diversity per generation is greater across the contemporary bottleneck. Historically, the flycatcher population was genetically structured; however, extinction on four of five islands has resulted in a homogeneous contemporary population. We conclude that severe historical bottlenecks can leave a large footprint in terms of sheer quantity of genetic diversity lost. However, severely depleted genetic diversity does not render a species immune to further genetic erosion upon re-introduction. In some cases, the loss of genetic diversity per generation can, initially at least, be greater across re-introduction-induced bottlenecks. © 2013 John Wiley & Sons Ltd.

Urban park characteristics, genetic variation, and historical demography of white-footed mouse (Peromyscus leucopus) populations in New York City

PubMed Central

Nagy, Christopher

2014-01-01

Severe fragmentation is a typical fate of native remnant habitats in cities, and urban wildlife with limited dispersal ability are predicted to lose genetic variation in isolated urban patches. However, little information exists on the characteristics of urban green spaces required to conserve genetic variation. In this study, we examine whether isolation in New York City (NYC) parks results in genetic bottlenecks in white-footed mice (Peromyscus leucopus), and test the hypotheses that park size and time since isolation are associated with genetic variability using nonlinear regression and information-theoretic model selection. White-footed mice have previously been documented to exhibit male-biased dispersal, which may create disparities in genetic variation between males and females in urban parks. We use genotypes of 18 neutral microsatellite data and four different statistical tests to assess this prediction. Given that sex-biased dispersal may create disparities between population genetic patterns inferred from bi- vs. uni-parentally inherited markers, we also sequenced a 324 bp segment of the mitochondrial D-loop for independent inferences of historical demography in urban P. leucopus. We report that isolation in urban parks does not necessarily result in genetic bottlenecks; only three out of 14 populations in NYC parks exhibited a signature of a recent bottleneck at 18 neutral microsatellite loci. Mouse populations in larger urban parks, or parks that have been isolated for shorter periods of time, also do not generally contain greater genetic variation than populations in smaller parks. These results suggest that even small networks of green spaces may be sufficient to maintain the evolutionary potential of native species with certain characteristics. We also found that isolation in urban parks results in weak to nonexistent sex-biased dispersal in a species known to exhibit male-biased dispersal in less fragmented environments. In contrast to nuclear loci, mitochondrial D-loop haplotypes exhibited a mutational pattern of demographic expansion after a recent bottleneck or selective sweep. Estimates of the timing of this expansion suggest that it occurred concurrent with urbanization of NYC over the last few dozens to hundreds of years. Given the general non-neutrality of mtDNA in many systems and evidence of selection on related coding sequences in urban P. leucopus, we argue that the P. leucopus mitochondrial genome experienced recent negative selection against haplotypes not favored in isolated urban parks. In general, rapid adaptive evolution driven by urbanization, global climate change, and other human-caused factors is underappreciated by evolutionary biologists, but many more cases will likely be documented in the near future. PMID:24688884

Increased genetic variation and evolutionary potential drive the success of an invasive grass

PubMed Central

Lavergne, Sébastien; Molofsky, Jane

2007-01-01

Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species. Here, we focus on the invasive wetland grass Phalaris arundinacea L. and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions. Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes. This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range. Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range. The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity. Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential. Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future. More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination. PMID:17360447

Identification and Validation of Ifit1 as an Important Innate Immune Bottleneck

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

McDermott, Jason E.; Vartanian, Keri B.; Mitchell, Hugh D.

The innate immune system plays important roles in a number of disparate processes. Foremost, innate immunity is a first responder to invasion by pathogens and triggers early defensive responses and recruits the adaptive immune system. The innate immune system also responds to endogenous damage signals that arise from tissue injury. Recently it has been found that innate immunity plays an important role in neuroprotection against ischemic stroke through the activation of the primary innate immune receptors, Toll-like receptors (TLRs). Using several large-scale transcriptomic data sets from mouse and mouse macrophage studies we identified targets predicted to be important in controllingmore » innate immune processes initiated by TLR activation. Targets were identified as genes with high betweenness centrality, so-called bottlenecks, in networks inferred from statistical associations between gene expression patterns. A small set of putative bottlenecks were identified in each of the data sets investigated including interferon-stimulated genes (Ifit1, Ifi47, Tgtp and Oasl2) as well as genes uncharacterized in immune responses (Axud1 and Ppp1r15a). We further validated one of these targets, Ifit1, in mouse macrophages by showing that silencing it suppresses induction of predicted downstream genes by lipopolysaccharide (LPS)-mediated TLR4 activation through an unknown direct or indirect mechanism. Our study demonstrates the utility of network analysis for identification of interesting targets related to innate immune function, and highlights that Ifit1 can exert a positive regulatory effect on downstream genes.« less

Genetic diversity and fitness in black-footed ferrets before and during a bottleneck.

PubMed

Wisely, S M; Buskirk, S W; Fleming, M A; McDonald, D B; Ostrander, E A

2002-01-01

The black-footed ferret (Mustela nigripes) is an endangered North American carnivore that underwent a well-documented population bottleneck in the mid-1980s. To better understand the effects of a bottleneck on a free-ranging carnivore population, we used 24 microsatellite loci to compare genetic diversity before versus during the bottleneck, and compare the last wild population to two historical populations. We also compared genetic diversity in black-footed ferrets to that of two sibling species, the steppe polecat (Mustela eversmanni) and the European polecat (Mustela putorius). Black-footed ferrets during the bottleneck had less genetic diversity than steppe polecats. The three black-footed ferret populations were well differentiated (F(ST) = 0.57 +/- 0.15; mean +/- SE). We attributed the decrease in genetic diversity in black-footed ferrets to localized extinction of these genetically distinct subpopulations and to the bottleneck in the surviving subpopulation. Although genetic diversity decreased, female fecundity and juvenile survival were not affected by the population bottleneck.

Narrow Bottlenecks Affect Pea Seedborne Mosaic Virus Populations during Vertical Seed Transmission but not during Leaf Colonization

PubMed Central

Johansen, Elisabeth Ida; Simon, Vincent; Jacquemond, Mireille; Senoussi, Rachid

2014-01-01

The effective size of populations (Ne) determines whether selection or genetic drift is the predominant force shaping their genetic structure and evolution. Populations having high Ne adapt faster, as selection acts more intensely, than populations having low Ne, where random effects of genetic drift dominate. Estimating Ne for various steps of plant virus life cycle has been the focus of several studies in the last decade, but no estimates are available for the vertical transmission of plant viruses, although virus seed transmission is economically significant in at least 18% of plant viruses in at least one plant species. Here we study the co-dynamics of two variants of Pea seedborne mosaic virus (PSbMV) colonizing leaves of pea plants (Pisum sativum L.) during the whole flowering period, and their subsequent transmission to plant progeny through seeds. Whereas classical estimators of Ne could be used for leaf infection at the systemic level, as virus variants were equally competitive, dedicated stochastic models were needed to estimate Ne during vertical transmission. Very little genetic drift was observed during the infection of apical leaves, with Ne values ranging from 59 to 216. In contrast, a very drastic genetic drift was observed during vertical transmission, with an average number of infectious virus particles contributing to the infection of a seedling from an infected mother plant close to one. A simple model of vertical transmission, assuming a cumulative action of virus infectious particles and a virus density threshold required for vertical transmission to occur fitted the experimental data very satisfactorily. This study reveals that vertically-transmitted viruses endure bottlenecks as narrow as those imposed by horizontal transmission. These bottlenecks are likely to slow down virus adaptation and could decrease virus fitness and virulence. PMID:24415934

Design of a model to predict surge capacity bottlenecks for burn mass casualties at a large academic medical center.

PubMed

Abir, Mahshid; Davis, Matthew M; Sankar, Pratap; Wong, Andrew C; Wang, Stewart C

2013-02-01

To design and test a model to predict surge capacity bottlenecks at a large academic medical center in response to a mass-casualty incident (MCI) involving multiple burn victims. Using the simulation software ProModel, a model of patient flow and anticipated resource use, according to principles of disaster management, was developed based upon historical data from the University Hospital of the University of Michigan Health System. Model inputs included: (a) age and weight distribution for casualties, and distribution of size and depth of burns; (b) rate of arrival of casualties to the hospital, and triage to ward or critical care settings; (c) eligibility for early discharge of non-MCI inpatients at time of MCI; (d) baseline occupancy of intensive care unit (ICU), surgical step-down, and ward; (e) staff availability-number of physicians, nurses, and respiratory therapists, and the expected ratio of each group to patients; (f) floor and operating room resources-anticipating the need for mechanical ventilators, burn care and surgical resources, blood products, and intravenous fluids; (g) average hospital length of stay and mortality rate for patients with inhalation injury and different size burns; and (h) average number of times that different size burns undergo surgery. Key model outputs include time to bottleneck for each limiting resource and average waiting time to hospital bed availability. Given base-case model assumptions (including 100 mass casualties with an inter-arrival rate to the hospital of one patient every three minutes), hospital utilization is constrained within the first 120 minutes to 21 casualties, due to the limited number of beds. The first bottleneck is attributable to exhausting critical care beds, followed by floor beds. Given this limitation in number of patients, the temporal order of the ensuing bottlenecks is as follows: Lactated Ringer's solution (4 h), silver sulfadiazine/Silvadene (6 h), albumin (48 h), thrombin topical (72 h), type AB packed red blood cells (76 h), silver dressing/Acticoat (100 h), bismuth tribromophenate/Xeroform (102 h), and gauze bandage rolls/Kerlix (168 h). The following items do not precipitate a bottleneck: ventilators, topical epinephrine, staplers, foams, antimicrobial non-adherent dressing/Telfa types A, B, or O blood. Nurse, respiratory therapist, and physician staffing does not induce bottlenecks. This model, and similar models for non-burn-related MCIs, can serve as a real-time estimation and management tool for hospital capacity in the setting of MCIs, and can inform supply decision support for disaster management.

Host-Pathogen Checkpoints and Population Bottlenecks in Persistent and Intracellular Uropathogenic E. coli Bladder Infection

PubMed Central

Hannan, Thomas J.; Totsika, Makrina; Mansfield, Kylie J.; Moore, Kate H.; Schembri, Mark A.; Hultgren, Scott J.

2013-01-01

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multi-drug resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic E. coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the Quiescent Intracellular Reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection: QIR, ASB, or chronic cystitis, is determined within the first 24 hours of infection and constitutes a putative host-pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies. PMID:22404313

Traffic behavior at freeway bottlenecks.

DOT National Transportation Integrated Search

2014-09-01

This study examines traffic behavior in the vicinity of a freeway bottleneck, revisiting commonly held : assumptions and uncovering systematic biases that likely have distorted empirical studies of bottleneck : formation, capacity drop, and the funda...

Damage to white matter bottlenecks contributes to language impairments after left hemispheric stroke.

PubMed

Griffis, Joseph C; Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

2017-01-01

Damage to the white matter underlying the left posterior temporal lobe leads to deficits in multiple language functions. The posterior temporal white matter may correspond to a bottleneck where both dorsal and ventral language pathways are vulnerable to simultaneous damage. Damage to a second putative white matter bottleneck in the left deep prefrontal white matter involving projections associated with ventral language pathways and thalamo-cortical projections has recently been proposed as a source of semantic deficits after stroke. Here, we first used white matter atlases to identify the previously described white matter bottlenecks in the posterior temporal and deep prefrontal white matter. We then assessed the effects of damage to each region on measures of verbal fluency, picture naming, and auditory semantic decision-making in 43 chronic left hemispheric stroke patients. Damage to the posterior temporal bottleneck predicted deficits on all tasks, while damage to the anterior bottleneck only significantly predicted deficits in verbal fluency. Importantly, the effects of damage to the bottleneck regions were not attributable to lesion volume, lesion loads on the tracts traversing the bottlenecks, or damage to nearby cortical language areas. Multivariate lesion-symptom mapping revealed additional lesion predictors of deficits. Post-hoc fiber tracking of the peak white matter lesion predictors using a publicly available tractography atlas revealed evidence consistent with the results of the bottleneck analyses. Together, our results provide support for the proposal that spatially specific white matter damage affecting bottleneck regions, particularly in the posterior temporal lobe, contributes to chronic language deficits after left hemispheric stroke. This may reflect the simultaneous disruption of signaling in dorsal and ventral language processing streams.

Investigation of the performance of fermentation processes using a mathematical model including effects of metabolic bottleneck and toxic product on cells.

PubMed

Sriyudthsak, Kansuporn; Shiraishi, Fumihide

2010-11-01

A number of recent research studies have focused on theoretical and experimental investigation of a bottleneck in a metabolic reaction network. However, there is no study on how the bottleneck affects the performance of a fermentation process when a product is highly toxic and remarkably influences the growth and death of cells. The present work therefore studies the effect of bottleneck on product concentrations under different product toxicity conditions. A generalized bottleneck model in a fed-batch fermentation is constructed including both the bottleneck and the product influences on cell growth and death. The simulation result reveals that when the toxic product strongly influences the cell growth and death, the final product concentration is hardly changed even if the bottleneck is removed, whereas it is markedly changed by the degree of product toxicity. The performance of an ethanol fermentation process is also discussed as a case example to validate this result. In conclusion, when the product is highly toxic, one cannot expect a significant increase in the final product concentration even if removing the bottleneck; rather, it may be more effective to somehow protect the cells so that they can continuously produce the product. Copyright © 2010 Elsevier Inc. All rights reserved.

Museum samples reveal rapid evolution by wild honey bees exposed to a novel parasite

PubMed Central

Mikheyev, Alexander S.; Tin, Mandy M. Y.; Arora, Jatin; Seeley, Thomas D.

2015-01-01

Understanding genetic changes caused by novel pathogens and parasites can reveal mechanisms of adaptation and genetic robustness. Using whole-genome sequencing of museum and modern specimens, we describe the genomic changes in a wild population of honey bees in North America following the introduction of the ectoparasitic mite, Varroa destructor. Even though colony density in the study population is the same today as in the past, a major loss of haplotypic diversity occurred, indicative of a drastic mitochondrial bottleneck, caused by massive colony mortality. In contrast, nuclear genetic diversity did not change, though hundreds of genes show signs of selection. The genetic diversity within each bee colony, particularly as a consequence of polyandry by queens, may enable preservation of genetic diversity even during population bottlenecks. These findings suggest that genetically diverse honey bee populations can recover from introduced diseases by evolving rapid tolerance, while maintaining much of the standing genetic variation. PMID:26246313

Museum samples reveal rapid evolution by wild honey bees exposed to a novel parasite.

PubMed

Mikheyev, Alexander S; Tin, Mandy M Y; Arora, Jatin; Seeley, Thomas D

2015-08-06

Understanding genetic changes caused by novel pathogens and parasites can reveal mechanisms of adaptation and genetic robustness. Using whole-genome sequencing of museum and modern specimens, we describe the genomic changes in a wild population of honey bees in North America following the introduction of the ectoparasitic mite, Varroa destructor. Even though colony density in the study population is the same today as in the past, a major loss of haplotypic diversity occurred, indicative of a drastic mitochondrial bottleneck, caused by massive colony mortality. In contrast, nuclear genetic diversity did not change, though hundreds of genes show signs of selection. The genetic diversity within each bee colony, particularly as a consequence of polyandry by queens, may enable preservation of genetic diversity even during population bottlenecks. These findings suggest that genetically diverse honey bee populations can recover from introduced diseases by evolving rapid tolerance, while maintaining much of the standing genetic variation.

Keeping mtDNA in Shape between Generations

PubMed Central

Stewart, James B.; Larsson, Nils-Göran

2014-01-01

Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing. PMID:25299061

Genome-culture coevolution promotes rapid divergence of killer whale ecotypes.

PubMed

Foote, Andrew D; Vijay, Nagarjun; Ávila-Arcos, María C; Baird, Robin W; Durban, John W; Fumagalli, Matteo; Gibbs, Richard A; Hanson, M Bradley; Korneliussen, Thorfinn S; Martin, Michael D; Robertson, Kelly M; Sousa, Vitor C; Vieira, Filipe G; Vinař, Tomáš; Wade, Paul; Worley, Kim C; Excoffier, Laurent; Morin, Phillip A; Gilbert, M Thomas P; Wolf, Jochen B W

2016-05-31

Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.

Genome-culture coevolution promotes rapid divergence of killer whale ecotypes

PubMed Central

Foote, Andrew D.; Vijay, Nagarjun; Ávila-Arcos, María C.; Baird, Robin W.; Durban, John W.; Fumagalli, Matteo; Gibbs, Richard A.; Hanson, M. Bradley; Korneliussen, Thorfinn S.; Martin, Michael D.; Robertson, Kelly M.; Sousa, Vitor C.; Vieira, Filipe G.; Vinař, Tomáš; Wade, Paul; Worley, Kim C.; Excoffier, Laurent; Morin, Phillip A.; Gilbert, M. Thomas P.; Wolf, Jochen B.W.

2016-01-01

Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level. PMID:27243207

MRM for the verification of cancer biomarker proteins: recent applications to human plasma and serum.

PubMed

Chambers, Andrew G; Percy, Andrew J; Simon, Romain; Borchers, Christoph H

2014-04-01

Accurate cancer biomarkers are needed for early detection, disease classification, prediction of therapeutic response and monitoring treatment. While there appears to be no shortage of candidate biomarker proteins, a major bottleneck in the biomarker pipeline continues to be their verification by enzyme linked immunosorbent assays. Multiple reaction monitoring (MRM), also known as selected reaction monitoring, is a targeted mass spectrometry approach to protein quantitation and is emerging to bridge the gap between biomarker discovery and clinical validation. Highly multiplexed MRM assays are readily configured and enable simultaneous verification of large numbers of candidates facilitating the development of biomarker panels which can increase specificity. This review focuses on recent applications of MRM to the analysis of plasma and serum from cancer patients for biomarker verification. The current status of this approach is discussed along with future directions for targeted mass spectrometry in clinical biomarker validation.

Testing founder effect speciation: Divergence population genetics of the Spoonbills Platalea regia and Pl. minor (Threskiornithidae, Aves)

USGS Publications Warehouse

Yeung, Carol K.L.; Tsai, Pi-Wen; Chesser, R. Terry; Lin, Rong-Chien; Yao, Cheng-Te; Tian, Xiu-Hua; Li, Shou-Hsien

2011-01-01

Although founder effect speciation has been a popular theoretical model for the speciation of geographically isolated taxa, its empirical importance has remained difficult to evaluate due to the intractability of past demography, which in a founder effect speciation scenario would involve a speciational bottleneck in the emergent species and the complete cessation of gene flow following divergence. Using regression-weighted approximate Bayesian computation, we tested the validity of these two fundamental conditions of founder effect speciation in a pair of sister species with disjunct distributions: the royal spoonbill Platalea regia in Australasia and the black-faced spoonbill Pl. minor in eastern Asia. When compared with genetic polymorphism observed at 20 nuclear loci in the two species, simulations showed that the founder effect speciation model had an extremely low posterior probability (1.55 × 10-8) of producing the extant genetic pattern. In contrast, speciation models that allowed for postdivergence gene flow were much more probable (posterior probabilities were 0.37 and 0.50 for the bottleneck with gene flow and the gene flow models, respectively) and postdivergence gene flow persisted for a considerable period of time (more than 80% of the divergence history in both models) following initial divergence (median = 197,000 generations, 95% credible interval [CI]: 50,000-478,000, for the bottleneck with gene flow model; and 186,000 generations, 95% CI: 45,000-477,000, for the gene flow model). Furthermore, the estimated population size reduction in Pl. regia to 7,000 individuals (median, 95% CI: 487-12,000, according to the bottleneck with gene flow model) was unlikely to have been severe enough to be considered a bottleneck. Therefore, these results do not support founder effect speciation in Pl. regia but indicate instead that the divergence between Pl. regia and Pl. minor was probably driven by selection despite continuous gene flow. In this light, we discuss the potential importance of evolutionarily labile traits with significant fitness consequences, such as migratory behavior and habitat preference, in facilitating divergence of the spoonbills.

Task analysis of intersection driving scenarios : information processing bottlenecks

DOT National Transportation Integrated Search

2006-08-01

The purpose of this report is to identify the information processing bottlenecks that drivers face in specific intersection driving scenarios. These bottlenecks represent situations in which drivers may become 'overloaded' by driving demands, which c...

High-throughput profiling and analysis of plant responses over time to abiotic stress

USDA-ARS?s Scientific Manuscript database

Energy sorghum (Sorghum bicolor (L.) Moench) is a rapidly growing, high-biomass, annual crop prized for abiotic stress tolerance. Measuring genotype-by-environment (G x E) interactions remains a progress bottleneck. High throughput phenotyping within controlled environments has been proposed as a po...

Residues remote from the binding pocket control the antagonist selectivity towards the corticotropin-releasing factor receptor-1

PubMed Central

Sun, Xianqiang; Cheng, Jianxin; Wang, Xu; Tang, Yun; Ågren, Hans; Tu, Yaoquan

2015-01-01

The corticotropin releasing factors receptor-1 and receptor-2 (CRF1R and CRF2R) are therapeutic targets for treating neurological diseases. Antagonists targeting CRF1R have been developed for the potential treatment of anxiety disorders and alcohol addiction. It has been found that antagonists targeting CRF1R always show high selectivity, although CRF1R and CRF2R share a very high rate of sequence identity. This has inspired us to study the origin of the selectivity of the antagonists. We have therefore built a homology model for CRF2R and carried out unbiased molecular dynamics and well-tempered metadynamics simulations for systems with the antagonist CP-376395 in CRF1R or CRF2R to address this issue. We found that the side chain of Tyr6.63 forms a hydrogen bond with the residue remote from the binding pocket, which allows Tyr6.63 to adopt different conformations in the two receptors and results in the presence or absence of a bottleneck controlling the antagonist binding to or dissociation from the receptors. The rotameric switch of the side chain of Tyr3566.63 allows the breaking down of the bottleneck and is a perquisite for the dissociation of CP-376395 from CRF1R. PMID:25628267

High variance in reproductive success generates a false signature of a genetic bottleneck in populations of constant size: a simulation study

PubMed Central

2013-01-01

Background Demographic bottlenecks can severely reduce the genetic variation of a population or a species. Establishing whether low genetic variation is caused by a bottleneck or a constantly low effective number of individuals is important to understand a species’ ecology and evolution, and it has implications for conservation management. Recent studies have evaluated the power of several statistical methods developed to identify bottlenecks. However, the false positive rate, i.e. the rate with which a bottleneck signal is misidentified in demographically stable populations, has received little attention. We analyse this type of error (type I) in forward computer simulations of stable populations having greater than Poisson variance in reproductive success (i.e., variance in family sizes). The assumption of Poisson variance underlies bottleneck tests, yet it is commonly violated in species with high fecundity. Results With large variance in reproductive success (Vk ≥ 40, corresponding to a ratio between effective and census size smaller than 0.1), tests based on allele frequencies, allelic sizes, and DNA sequence polymorphisms (heterozygosity excess, M-ratio, and Tajima’s D test) tend to show erroneous signals of a bottleneck. Similarly, strong evidence of population decline is erroneously detected when ancestral and current population sizes are estimated with the model based method MSVAR. Conclusions Our results suggest caution when interpreting the results of bottleneck tests in species showing high variance in reproductive success. Particularly in species with high fecundity, computer simulations are recommended to confirm the occurrence of a population bottleneck. PMID:24131797

Kangaroo mother care: a multi-country analysis of health system bottlenecks and potential solutions.

PubMed

Vesel, Linda; Bergh, Anne-Marie; Kerber, Kate J; Valsangkar, Bina; Mazia, Goldy; Moxon, Sarah G; Blencowe, Hannah; Darmstadt, Gary L; de Graft Johnson, Joseph; Dickson, Kim E; Ruiz Peláez, Juan; von Xylander, Severin; Lawn, Joy E

2015-01-01

Preterm birth is now the leading cause of under-five child deaths worldwide with one million direct deaths plus approximately another million where preterm is a risk factor for neonatal deaths due to other causes. There is strong evidence that kangaroo mother care (KMC) reduces mortality among babies with birth weight <2000 g (mostly preterm). KMC involves continuous skin-to-skin contact, breastfeeding support, and promotion of early hospital discharge with follow-up. The World Health Organization has endorsed KMC for stabilised newborns in health facilities in both high-income and low-resource settings. The objectives of this paper are to: (1) use a 12-country analysis to explore health system bottlenecks affecting the scale-up of KMC; (2) propose solutions to the most significant bottlenecks; and (3) outline priority actions for scale-up. The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale-up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for KMC. Marked differences were found in the perceived severity of health system bottlenecks between Asian and African countries, with the former reporting more significant or very major bottlenecks for KMC with respect to all the health system building blocks. Community ownership and health financing bottlenecks were significant or very major bottlenecks for KMC in both low and high mortality contexts, particularly in South Asia. Significant bottlenecks were also reported for leadership and governance and health workforce building blocks. There are at least a dozen countries worldwide with national KMC programmes, and we identify three pathways to scale: (1) champion-led; (2) project-initiated; and (3) health systems designed. The combination of all three pathways may lead to more rapid scale-up. KMC has the potential to save lives, and change the face of facility-based newborn care, whilst empowering women to care for their preterm newborns.

Kangaroo mother care: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background Preterm birth is now the leading cause of under-five child deaths worldwide with one million direct deaths plus approximately another million where preterm is a risk factor for neonatal deaths due to other causes. There is strong evidence that kangaroo mother care (KMC) reduces mortality among babies with birth weight <2000 g (mostly preterm). KMC involves continuous skin-to-skin contact, breastfeeding support, and promotion of early hospital discharge with follow-up. The World Health Organization has endorsed KMC for stabilised newborns in health facilities in both high-income and low-resource settings. The objectives of this paper are to: (1) use a 12-country analysis to explore health system bottlenecks affecting the scale-up of KMC; (2) propose solutions to the most significant bottlenecks; and (3) outline priority actions for scale-up. Methods The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale-up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for KMC. Results Marked differences were found in the perceived severity of health system bottlenecks between Asian and African countries, with the former reporting more significant or very major bottlenecks for KMC with respect to all the health system building blocks. Community ownership and health financing bottlenecks were significant or very major bottlenecks for KMC in both low and high mortality contexts, particularly in South Asia. Significant bottlenecks were also reported for leadership and governance and health workforce building blocks. Conclusions There are at least a dozen countries worldwide with national KMC programmes, and we identify three pathways to scale: (1) champion-led; (2) project-initiated; and (3) health systems designed. The combination of all three pathways may lead to more rapid scale-up. KMC has the potential to save lives, and change the face of facility-based newborn care, whilst empowering women to care for their preterm newborns. PMID:26391115

Quality care during labour and birth: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background Good outcomes during pregnancy and childbirth are related to availability, utilisation and effective implementation of essential interventions for labour and childbirth. The majority of the estimated 289,000 maternal deaths, 2.8 million neonatal deaths and 2.6 million stillbirths every year could be prevented by improving access to and scaling up quality care during labour and birth. Methods The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops engaged technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks", factors that hinder the scale up, of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for skilled birth attendance and basic and comprehensive emergency obstetric care. Results Across 12 countries the most critical bottlenecks identified by workshop participants for skilled birth attendance were health financing (10 out of 12 countries) and health workforce (9 out of 12 countries). Health service delivery bottlenecks were found to be the most critical for both basic and comprehensive emergency obstetric care (9 out of 12 countries); health financing was identified as having critical bottlenecks for comprehensive emergency obstetric care (9 out of 12 countries). Solutions to address health financing bottlenecks included strengthening national financing mechanisms and removing financial barriers to care seeking. For addressing health workforce bottlenecks, improved human resource planning is needed, including task shifting and improving training quality. For health service delivery, proposed solutions included improving quality of care and establishing public private partnerships. Conclusions Progress towards the 2030 targets for ending preventable maternal and newborn deaths is dependent on improving quality of care during birth and the immediate postnatal period. Strengthening national health systems to improve maternal and newborn health, as a cornerstone of universal health coverage, will only be possible by addressing specific health system bottlenecks during labour and birth, including those within health workforce, health financing and health service delivery. PMID:26390886

Blended learning in chemistry laboratory courses: Enhancing learning outcomes and aligning student needs with available resources

NASA Astrophysics Data System (ADS)

Burchett, Shayna Brianne

Freshman science courses are intended to prepare students for the rigor and expectations of subsequent college science. While secondary education aims to prepare students for the college curriculum, many incoming freshman lack the sense of responsibility for their own learning that is essential for success in a college-level course. The freshman general-chemistry laboratory course at Missouri University of Science and Technology (Missouri S&T) was identified as a bottleneck course with a demand beyond accommodation capacity. To address the bottleneck and develop a sense of learner responsibility, a decision was made to investigate laboratory course delivery strategies. As a result of the investigation into delivery strategies, a blended freshman general-chemistry laboratory course was designed and implemented at Missouri S&T, which increased student access to the bottleneck course and improved learner engagement while meeting American Chemical Society (ACS) guidelines. The implementation of the Missouri S&T project and its continued evolution at other institutions have a great potential to provide insight on the impact of blended teaching on learner success. This dissertation describes research and design of a blended laboratory course that economically improves capacity while intentionally focusing pedagogy to support learner success, meet industry expectations, and maintain ACS certification. To evaluate success, the project documented and analyzed student performance during the development of the transformation to a blended freshman chemistry laboratory course at Missouri S&T. The findings support the efficacy of the blended teaching model and offer a structure upon which future courses may build.

The ancient tropical rainforest tree Symphonia globulifera L. f. (Clusiaceae) was not restricted to postulated Pleistocene refugia in Atlantic Equatorial Africa.

PubMed

Budde, K B; González-Martínez, S C; Hardy, O J; Heuertz, M

2013-07-01

Understanding the history of forests and their species' demographic responses to past disturbances is important for predicting impacts of future environmental changes. Tropical rainforests of the Guineo-Congolian region in Central Africa are believed to have survived the Pleistocene glacial periods in a few major refugia, essentially centred on mountainous regions close to the Atlantic Ocean. We tested this hypothesis by investigating the phylogeographic structure of a widespread, ancient rainforest tree species, Symphonia globulifera L. f. (Clusiaceae), using plastid DNA sequences (chloroplast DNA [cpDNA], psbA-trnH intergenic spacer) and nuclear microsatellites (simple sequence repeats, SSRs). SSRs identified four gene pools located in Benin, West Cameroon, South Cameroon and Gabon, and São Tomé. This structure was also apparent at cpDNA. Approximate Bayesian Computation detected recent bottlenecks approximately dated to the last glacial maximum in Benin, West Cameroon and São Tomé, and an older bottleneck in South Cameroon and Gabon, suggesting a genetic effect of Pleistocene cycles of forest contraction. CpDNA haplotype distribution indicated wide-ranging long-term persistence of S. globulifera both inside and outside of postulated forest refugia. Pollen flow was four times greater than that of seed in South Cameroon and Gabon, which probably enabled rapid population recovery after bottlenecks. Furthermore, our study suggested ecotypic differentiation-coastal or swamp vs terra firme-in S. globulifera. Comparison with other tree phylogeographic studies in Central Africa highlighted the relevance of species-specific responses to environmental change in forest trees.

The ancient tropical rainforest tree Symphonia globulifera L. f. (Clusiaceae) was not restricted to postulated Pleistocene refugia in Atlantic Equatorial Africa

PubMed Central

Budde, K B; González-Martínez, S C; Hardy, O J; Heuertz, M

2013-01-01

Understanding the history of forests and their species' demographic responses to past disturbances is important for predicting impacts of future environmental changes. Tropical rainforests of the Guineo-Congolian region in Central Africa are believed to have survived the Pleistocene glacial periods in a few major refugia, essentially centred on mountainous regions close to the Atlantic Ocean. We tested this hypothesis by investigating the phylogeographic structure of a widespread, ancient rainforest tree species, Symphonia globulifera L. f. (Clusiaceae), using plastid DNA sequences (chloroplast DNA [cpDNA], psbA-trnH intergenic spacer) and nuclear microsatellites (simple sequence repeats, SSRs). SSRs identified four gene pools located in Benin, West Cameroon, South Cameroon and Gabon, and São Tomé. This structure was also apparent at cpDNA. Approximate Bayesian Computation detected recent bottlenecks approximately dated to the last glacial maximum in Benin, West Cameroon and São Tomé, and an older bottleneck in South Cameroon and Gabon, suggesting a genetic effect of Pleistocene cycles of forest contraction. CpDNA haplotype distribution indicated wide-ranging long-term persistence of S. globulifera both inside and outside of postulated forest refugia. Pollen flow was four times greater than that of seed in South Cameroon and Gabon, which probably enabled rapid population recovery after bottlenecks. Furthermore, our study suggested ecotypic differentiation—coastal or swamp vs terra firme—in S. globulifera. Comparison with other tree phylogeographic studies in Central Africa highlighted the relevance of species-specific responses to environmental change in forest trees. PMID:23572126

Addressing an I/O Bottleneck in a Web-Based CERES QC Tool

NASA Astrophysics Data System (ADS)

Heckert, E.; Sun-Mack, S.; Chen, Y.; Chu, C.; Smith, R. A.

2016-12-01

In this poster, we explore the technologies we have used to overcome the problem of transmitting and analyzing large datasets in our web-based CERES Quality Control tool and consider four technologies to potentially adopt for future performance improvements. The CERES team uses this tool to validate pixel-level data from Terra, Aqua, SNPP, MSG, MTSAT, and many geostationary GOES satellites, as well as to develop cloud retrieval algorithms. The tool includes a histogram feature that allows the user to aggregate data from many different timestamps and different scenes globally or locally selected by the user by drawing bounding boxes. In order to provide a better user experience, the tool passes a large amount of data to the user's browser. The browser then processes the data in order to present it to users in various formats, for example as a histogram. In addition to using multiple servers to subset data and pass a smaller set of data to the browser, the tool also makes use of a compression technology, Gzip, to reduce the size of the data. However, sometimes the application in the browser is still slow when dealing with these large sets of data due to the delay in the browser receiving the server's response. To address this I/O bottleneck, we will investigate four alternatives and present the results in this poster: 1) sending uncompressed data, 2) ESRI's Limited Error Raster Compression (LERC), 3) Gzip, and 4) WebSocket protocol. These approaches are compared to each other and to the uncompressed control to determine the optimal solution.

"Bottleneck study" : transportation infrastructure and traffic management analysis of cross border bottlenecks.

DOT National Transportation Integrated Search

2004-11-01

The motivation behind the Transportation Infrastructure and Traffic Management Analysis of : Cross Border Bottlenecks study was generated by the U.S.-Mexico Border Partnership Action : Plan (Action item #2 of the 22-Point Smart Border Action Plan: De...

Ultrafast gigantic photo-response in charge-ordered organic salt (EDO-TTF)2PF6 on 10-fs time scales

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

Itatani, J.; Rini, M.; Cavalleri, A.

2008-08-01

The initial dynamics of photo-induced phase transition in charge-ordered organic salt (EDO-TTF){sub 2}PF{sub 6} was investigated using 10-fs near-infrared laser pulses. We observed sub-20-fs gigantic photo-responses (|{Delta}R/R|>100%) due to intra-molecular vibration and a clear signature of a structural bottleneck ({approx}50 fs) for the first time.

Avoiding Local Optima with Interactive Evolutionary Robotics

DTIC Science & Technology

2012-07-09

the top of a flight of stairs selects for climbing ; suspending the robot and the target object above the ground and creating rungs between the two will...REPORT Avoiding Local Optimawith Interactive Evolutionary Robotics 14. ABSTRACT 16. SECURITY CLASSIFICATION OF: The main bottleneck in evolutionary... robotics has traditionally been the time required to evolve robot controllers. However with the continued acceleration in computational resources, the

The colours of humanity: the evolution of pigmentation in the human lineage.

PubMed

Jablonski, Nina G; Chaplin, George

2017-07-05

Humans are a colourful species of primate, with human skin, hair and eye coloration having been influenced by a great variety of evolutionary forces throughout prehistory. Functionally naked skin has been the physical interface between the physical environment and the human body for most of the history of the genus Homo , and hence skin coloration has been under intense natural selection. From an original condition of protective, dark, eumelanin-enriched coloration in early tropical-dwelling Homo and Homo sapiens , loss of melanin pigmentation occurred under natural selection as Homo sapiens dispersed into non-tropical latitudes of Africa and Eurasia. Genes responsible for skin, hair and eye coloration appear to have been affected significantly by population bottlenecks in the course of Homo sapiens dispersals. Because specific skin colour phenotypes can be created by different combinations of skin colour-associated genetic markers, loss of genetic variability due to genetic drift appears to have had negligible effects on the highly redundant genetic 'palette' for the skin colour. This does not appear to have been the case for hair and eye coloration, however, and these traits appear to have been more strongly influenced by genetic drift and, possibly, sexual selection.This article is part of the themed issue 'Animal coloration: production, perception, function and application'. © 2017 The Author(s).

"Bottleneck study" : transportation infrastructure and traffic management analysis of cross border bottlenecks. [Executive summary].

DOT National Transportation Integrated Search

2004-11-01

The motivation behind the Transportation Infrastructure and Traffic Management Analysis of : Cross Border Bottlenecks study was generated by the U.S.-Mexico Border Partnership Action : Plan (Action item #2 of the 22-Point Smart Border Action Plan: De...

Bottleneck Effect on Evolutionary Rate in the Nearly Neutral Mutation Model

PubMed Central

Araki, H.; Tachida, H.

1997-01-01

Variances of evolutionary rates among lineages in some proteins are larger than those expected from simple Poisson processes. This phenomenon is called overdispersion of the molecular clock. If population size N is constant, the overdispersion is observed only in a limited range of 2Nσ under the nearly neutral mutation model, where σ represents the standard deviation of selection coefficients of new mutants. In this paper, we investigated effects of changing population size on the evolutionary rate by computer simulations assuming the nearly neutral mutation model. The size was changed cyclically between two numbers, N(1) and N(2) (N(1) > N(2)), in the simulations. The overdispersion is observed if 2N(2)σ is less than two and the state of reduced size (bottleneck state) continues for more than ~0.1/u generations, where u is the mutation rate. The overdispersion results mainly because the average fitnesses of only a portion of populations go down when the population size is reduced and only in these populations subsequent advantageous substitutions occur after the population size becomes large. Since the fitness reduction after the bottleneck is stochastic, acceleration of the evolutionary rate does not necessarily occur uniformly among loci. From these results, we argue that the nearly neutral mutation model is a candidate mechanism to explain the overdispersed molecular clock. PMID:9335622

Estimating Bottleneck Bandwidth using TCP

NASA Technical Reports Server (NTRS)

Allman, Mark

1998-01-01

Various issues associated with estimating bottleneck bandwidth using TCP are presented in viewgraph form. Specific topics include: 1) Why TCP is wanted to estimate the bottleneck bandwidth; 2) Setting ssthresh to an appropriate value to reduce loss; 3) Possible packet-pair solutions; and 4) Preliminary results: ACTS and the Internet.

Bottleneck Concepts in Psychology: Exploratory First Steps

ERIC Educational Resources Information Center

Gurung, Regan A. R.; Landrum, R. Eric

2013-01-01

The authors take an initial step in identifying potential bottleneck concepts in psychology, that is, concepts that are deceptively difficult, perhaps due to student overconfidence. In order to first identify bottleneck concepts, faculty (n = 65) rated the difficulty of 91 psychological concepts from across the discipline. Students (n = 35) rated…

The Impact of Population Bottlenecks on Microbial Adaptation

NASA Astrophysics Data System (ADS)

LeClair, Joshua S.; Wahl, Lindi M.

2018-07-01

Population bottlenecks—sudden, severe reductions in population size—are ubiquitous in nature. Because of their critical implications for conservation genetics, the effects of population bottlenecks on the loss of genetic diversity have been well studied. Bottlenecks also have important implications for adaptation, however, and these effects have been addressed more recently, typically in microbial populations. In this short review, we survey both experimental and theoretical work describing the impact of population bottlenecks on microbial adaptation. Focusing on theoretical contributions, we highlight emerging insights and conclude with several open questions of interest in the field.

Bottlenecks and Waiting Points in Nucleosynthesis in X-ray bursts and Novae

NASA Astrophysics Data System (ADS)

Smith, Michael S.; Sunayama, Tomomi; Hix, W. Raphael; Lingerfelt, Eric J.; Nesaraja, Caroline D.

2010-08-01

To better understand the energy generation and element synthesis occurring in novae and X-ray bursts, we give quantitative definitions to the concepts of ``bottlenecks'' and ``waiting points'' in the thermonuclear reaction flow. We use these criteria to search for bottlenecks and waiting points in post-processing element synthesis explosion simulations. We have incorporated these into the Computational Infrastructure for Nuclear Astrophysics, a suite of nuclear astrophysics codes available online at nucastrodata.org, so that anyone may perform custom searches for bottlenecks and waiting points.

Bottlenecks and Waiting Points in Nucleosynthesis in X-ray bursts and Novae

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

Smith, Michael S.; Hix, W. Raphael; Nesaraja, Caroline D.

2010-08-12

To better understand the energy generation and element synthesis occurring in novae and X-ray bursts, we give quantitative definitions to the concepts of ''bottlenecks'' and ''waiting points'' in the thermonuclear reaction flow. We use these criteria to search for bottlenecks and waiting points in post-processing element synthesis explosion simulations. We have incorporated these into the Computational Infrastructure for Nuclear Astrophysics, a suite of nuclear astrophysics codes available online at nucastrodata.org, so that anyone may perform custom searches for bottlenecks and waiting points.

Reconstruction of the astaxanthin biosynthesis pathway in rice endosperm reveals a metabolic bottleneck at the level of endogenous β-carotene hydroxylase activity.

PubMed

Bai, Chao; Berman, Judit; Farre, Gemma; Capell, Teresa; Sandmann, Gerhard; Christou, Paul; Zhu, Changfu

2017-02-01

Astaxanthin is a high-value ketocarotenoid rarely found in plants. It is derived from β-carotene by the 3-hydroxylation and 4-ketolation of both ionone end groups, in reactions catalyzed by β-carotene hydroxylase and β-carotene ketolase, respectively. We investigated the feasibility of introducing an extended carotenoid biosynthesis pathway into rice endosperm to achieve the production of astaxanthin. This allowed us to identify potential metabolic bottlenecks that have thus far prevented the accumulation of this valuable compound in storage tissues such as cereal grains. Rice endosperm does not usually accumulate carotenoids because phytoene synthase, the enzyme responsible for the first committed step in the pathway, is not present in this tissue. We therefore expressed maize phytoene synthase 1 (ZmPSY1), Pantoea ananatis phytoene desaturase (PaCRTI) and a synthetic Chlamydomonas reinhardtii β-carotene ketolase (sCrBKT) in transgenic rice plants under the control of endosperm-specific promoters. The resulting grains predominantly accumulated the diketocarotenoids canthaxanthin, adonirubin and astaxanthin as well as low levels of monoketocarotenoids. The predominance of canthaxanthin and adonirubin indicated the presence of a hydroxylation bottleneck in the ketocarotenoid pathway. This final rate-limiting step must therefore be overcome to maximize the accumulation of astaxanthin, the end product of the pathway.

Mapping the yeast host cell response to recombinant membrane protein production: relieving the biological bottlenecks.

PubMed

Ashe, Mark P; Bill, Roslyn M

2011-06-01

Understanding the structures and functions of membrane proteins is an active area of research within bioscience. Membrane proteins are key players in essential cellular processes such as the uptake of nutrients, the export of waste products, and the way in which cells communicate with their environment. It is therefore not surprising that membrane proteins are targeted by over half of all prescription drugs. Since most membrane proteins are not abundant in their native membranes, it is necessary to produce them in recombinant host cells to enable further structural and functional studies. Unfortunately, achieving the required yields of functional recombinant membrane proteins is still a bottleneck in contemporary bioscience. This has highlighted the need for defined and rational optimization strategies based upon experimental observation rather than relying on trial and error. We have published a transcriptome and subsequent genetic analysis that has identified genes implicated in high-yielding yeast cells. These results have highlighted a role for alterations to a cell's protein synthetic capacity in the production of high yields of recombinant membrane protein: paradoxically, reduced protein synthesis favors higher yields. These results highlight a potential bottleneck at the protein folding or translocation stage of protein production. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Purine biosynthesis is the bottleneck in trimethoprim-treated Bacillus subtilis.

PubMed

Stepanek, Jennifer Janina; Schäkermann, Sina; Wenzel, Michaela; Prochnow, Pascal; Bandow, Julia Elisabeth

2016-10-01

Trimethoprim is a folate biosynthesis inhibitor. Tetrahydrofolates are essential for the transfer of C 1 units in several biochemical pathways including purine, thymine, methionine, and glycine biosynthesis. This study addressed the effects of folate biosynthesis inhibition on bacterial physiology. Two complementary proteomic approaches were employed to analyze the response of Bacillus subtilis to trimethoprim. Acute changes in protein synthesis rates were monitored by radioactive pulse labeling of newly synthesized proteins and subsequent 2DE analysis. Changes in protein levels were detected using gel-free quantitative MS. Proteins involved in purine and histidine biosynthesis, the σ B -dependent general stress response, and sporulation were upregulated. Most prominently, the PurR-regulon required for de novo purine biosynthesis was derepressed indicating purine depletion. The general stress response was activated energy dependently and in a subpopulation of treated cultures an early onset of sporulation was observed, most likely triggered by low guanosine triphosphate levels. Supplementation of adenosine triphosphate, adenosine, and guanosine to the medium substantially decreased antibacterial activity, showing that purine depletion becomes the bottleneck in trimethoprim-treated B. subtilis. The frequently prescribed antibiotic trimethoprim causes purine depletion in B. subtilis, which can be complemented by supplementing purines to the medium. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Health Monitoring and Evaluation of Long-Span Bridges Based on Sensing and Data Analysis: A Survey

PubMed Central

Zhou, Jianting; Li, Xiaogang; Xia, Runchuan; Yang, Jun; Zhang, Hong

2017-01-01

Aimed at the health monitoring and evaluation of bridges based on sensing technology, the monitoring contents of different structural types of long-span bridges were defined. Then, the definition, classification, selection principle, and installation requirements of the sensors were summarized. The concept was proposed that new adaptable long-life sensors could be developed by new theories and new effects. The principle and methods to select controlled sections and optimize the layout design of measuring points were illustrated. The functional requirements were elaborated on about the acquisition, transmission, processing, and management of sensing information. Some advanced concepts about the method of bridge safety evaluation were demonstrated and technology bottlenecks in the current safety evaluation were also put forward. Ultimately, combined with engineering practices, an application was carried out. The results showed that new, intelligent, and reliable sensor technology would be one of the main future development directions in the long-span bridge health monitoring and evaluation field. Also, it was imperative to optimize the design of the health monitoring system and realize its standardization. Moreover, it is a heavy responsibility to explore new thoughts and new concepts regarding practical bridge safety and evaluation technology. PMID:28300785

Theory of Constraints: What Can We Learn to Support the Nursing Workforce?

PubMed

Pawlak, Roberta

2016-11-01

Demand for nurses is influenced by many factors. Labor statistics and health services literature reveal current and predicted supply gaps in meeting this demand. One strategy in response can be drawn from manufacturing industries. This column suggests the application of the Theory of Constraints in efforts to relieve bottlenecks in producing and retaining nurse labor.

How Strategic Is the Central Bottleneck: Can It Be Overcome by Trying Harder?

ERIC Educational Resources Information Center

Ruthruff, Eric; Johnston, James C.; Remington, Roger W.

2009-01-01

Recent dual-task studies suggest that a bottleneck prevents central mental operations from working on more than one task at a time, especially at relatively low practice levels. It remains highly controversial, however, whether this bottleneck is structural (inherent to human cognitive architecture) or merely a strategic choice. If the strategic…

Anatomy of a bottleneck: diagnosing factors limiting population growth in the Puerto Rican Parrot

Treesearch

S.R. Beissinger; Jr Wunderle; J.M. Meyers; B.E. Saether; S. Engen

2008-01-01

The relative importance of genetic, demographic, environmental, and catastrophic processes that maintain population bottlenecks has received little consideration. We evaluate the role of these factors in maintaining the Puerto Rican Parrot (Amazona vittata) in a prolonged bottleneck from 1973 through 2000 despite intensive conservation efforts. We first conduct a risk...

GrigoraSNPs: Optimized Analysis of SNPs for DNA Forensics.

PubMed

Ricke, Darrell O; Shcherbina, Anna; Michaleas, Adam; Fremont-Smith, Philip

2018-04-16

High-throughput sequencing (HTS) of single nucleotide polymorphisms (SNPs) enables additional DNA forensic capabilities not attainable using traditional STR panels. However, the inclusion of sets of loci selected for mixture analysis, extended kinship, phenotype, biogeographic ancestry prediction, etc., can result in large panel sizes that are difficult to analyze in a rapid fashion. GrigoraSNP was developed to address the allele-calling bottleneck that was encountered when analyzing SNP panels with more than 5000 loci using HTS. GrigoraSNPs uses a MapReduce parallel data processing on multiple computational threads plus a novel locus-identification hashing strategy leveraging target sequence tags. This tool optimizes the SNP calling module of the DNA analysis pipeline with runtimes that scale linearly with the number of HTS reads. Results are compared with SNP analysis pipelines implemented with SAMtools and GATK. GrigoraSNPs removes a computational bottleneck for processing forensic samples with large HTS SNP panels. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Slow cooling and highly efficient extraction of hot carriers in colloidal perovskite nanocrystals.

PubMed

Li, Mingjie; Bhaumik, Saikat; Goh, Teck Wee; Kumar, Muduli Subas; Yantara, Natalia; Grätzel, Michael; Mhaisalkar, Subodh; Mathews, Nripan; Sum, Tze Chien

2017-02-08

Hot-carrier solar cells can overcome the Schottky-Queisser limit by harvesting excess energy from hot carriers. Inorganic semiconductor nanocrystals are considered prime candidates. However, hot-carrier harvesting is compromised by competitive relaxation pathways (for example, intraband Auger process and defects) that overwhelm their phonon bottlenecks. Here we show colloidal halide perovskite nanocrystals transcend these limitations and exhibit around two orders slower hot-carrier cooling times and around four times larger hot-carrier temperatures than their bulk-film counterparts. Under low pump excitation, hot-carrier cooling mediated by a phonon bottleneck is surprisingly slower in smaller nanocrystals (contrasting with conventional nanocrystals). At high pump fluence, Auger heating dominates hot-carrier cooling, which is slower in larger nanocrystals (hitherto unobserved in conventional nanocrystals). Importantly, we demonstrate efficient room temperature hot-electrons extraction (up to ∼83%) by an energy-selective electron acceptor layer within 1 ps from surface-treated perovskite NCs thin films. These insights enable fresh approaches for extremely thin absorber and concentrator-type hot-carrier solar cells.

Engineering oilseeds for sustainable production of industrial and nutritional feedstocks: solving bottlenecks in fatty acid flux.

PubMed

Cahoon, Edgar B; Shockey, Jay M; Dietrich, Charles R; Gidda, Satinder K; Mullen, Robert T; Dyer, John M

2007-06-01

Oilseeds provide a unique platform for the production of high-value fatty acids that can replace non-sustainable petroleum and oceanic sources of specialty chemicals and aquaculture feed. However, recent efforts to engineer the seeds of crop and model plant species to produce new types of fatty acids, including hydroxy and conjugated fatty acids for industrial uses and long-chain omega-3 polyunsaturated fatty acids for farmed fish feed, have met with only modest success. The collective results from these studies point to metabolic 'bottlenecks' in the engineered plant seeds that substantially limit the efficient or selective flux of unusual fatty acids between different substrate pools and ultimately into storage triacylglycerol. Evidence is emerging that diacylglycerol acyltransferase 2, which catalyzes the final step in triacylglycerol assembly, is an important contributor to the synthesis of unusual fatty acid-containing oils, and is likely to be a key target for future oilseed metabolic engineering efforts.

Time-Lapse Analysis of Human Embryonic Stem Cells Reveals Multiple Bottlenecks Restricting Colony Formation and Their Relief upon Culture Adaptation

PubMed Central

Barbaric, Ivana; Biga, Veronica; Gokhale, Paul J.; Jones, Mark; Stavish, Dylan; Glen, Adam; Coca, Daniel; Andrews, Peter W.

2014-01-01

Summary Using time-lapse imaging, we have identified a series of bottlenecks that restrict growth of early-passage human embryonic stem cells (hESCs) and that are relieved by karyotypically abnormal variants that are selected by prolonged culture. Only a minority of karyotypically normal cells divided after plating, and these were mainly cells in the later stages of cell cycle at the time of plating. Furthermore, the daughter cells showed a continued pattern of cell death after division, so that few formed long-term proliferating colonies. These colony-forming cells showed distinct patterns of cell movement. Increasing cell density enhanced cell movement facilitating cell:cell contact, which resulted in increased proportion of dividing cells and improved survival postplating of normal hESCs. In contrast, most of the karyotypically abnormal cells reentered the cell cycle on plating and gave rise to healthy progeny, without the need for cell:cell contacts and independent of their motility patterns. PMID:25068128

A Real-time Breakdown Prediction Method for Urban Expressway On-ramp Bottlenecks

NASA Astrophysics Data System (ADS)

Ye, Yingjun; Qin, Guoyang; Sun, Jian; Liu, Qiyuan

2018-01-01

Breakdown occurrence on expressway is considered to relate with various factors. Therefore, to investigate the association between breakdowns and these factors, a Bayesian network (BN) model is adopted in this paper. Based on the breakdown events identified at 10 urban expressways on-ramp in Shanghai, China, 23 parameters before breakdowns are extracted, including dynamic environment conditions aggregated with 5-minutes and static geometry features. Different time periods data are used to predict breakdown. Results indicate that the models using 5-10 min data prior to breakdown performs the best prediction, with the prediction accuracies higher than 73%. Moreover, one unified model for all bottlenecks is also built and shows reasonably good prediction performance with the classification accuracy of breakdowns about 75%, at best. Additionally, to simplify the model parameter input, the random forests (RF) model is adopted to identify the key variables. Modeling with the selected 7 parameters, the refined BN model can predict breakdown with adequate accuracy.

The genetic rescue of two bottlenecked South Island robin populations using translocations of inbred donors.

PubMed

Heber, S; Varsani, A; Kuhn, S; Girg, A; Kempenaers, B; Briskie, J

2013-02-07

Populations forced through bottlenecks typically lose genetic variation and exhibit inbreeding depression. 'Genetic rescue' techniques that introduce individuals from outbred populations can be highly effective in reversing the deleterious effects of inbreeding, but have limited application for the majority of endangered species, which survive only in a few bottlenecked populations. We tested the effectiveness of using highly inbred populations as donors to rescue two isolated and bottlenecked populations of the South Island robin (Petroica australis). Reciprocal translocations significantly increased heterozygosity and allelic diversity. Increased genetic diversity was accompanied by increased juvenile survival and recruitment, sperm quality, and immunocompetence of hybrid individuals (crosses between the two populations) compared with inbred control individuals (crosses within each population). Our results confirm that the implementation of 'genetic rescue' using bottlenecked populations as donors provides a way of preserving endangered species and restoring their viability when outbred donor populations no longer exist.

Patterns of genetic diversity and candidate genes for ecological divergence in a homoploid hybrid sunflower, Helianthus anomalus

PubMed Central

SAPIR, YUVAL; MOODY, MICHAEL L.; BROUILLETTE, LARRY C.; DONOVAN, LISA A.; RIESEBERG, LOREN H.

2008-01-01

Natural hybridization accompanied by a shift in niche preference by hybrid genotypes can lead to hybrid speciation. Natural selection may cause the fixation of advantageous alleles in the ecologically diverged hybrids, and the loci experiencing selection should exhibit a reduction in allelic diversity relative to neutral loci. Here, we analyzed patterns of genetic diversity at 59 microsatellite loci associated with expressed sequence tags (ESTs) in a homoploid hybrid sunflower species, Helianthus anomalus. We used two indices, ln RV and ln RH, to compare variation and heterozygosity (respectively) at each locus between the hybrid species and its two parental species, H. annuus and H. petiolaris. Mean values of ln RV and ln RH were significantly lower than zero, which implies that H. anomalus experienced a population bottleneck during its recent evolutionary history. After correcting for the apparent bottleneck, we found six loci with a significant reduction in variation or with heterozygosity in the hybrid species, compared to one or both of the parental species. These loci should be viewed as a ranked list of candidate loci, pending further sequencing and functional analyses. Sequence data were generated for two of the candidate loci, but population genetics tests failed to detect deviations from neutral evolution at either locus. Nonetheless, a greater than eight-fold excess of nonsynonymous substitutions was found near a putative N-myristoylation motif at the second locus (HT998), and likelihood-based models indicated that the protein has been under selection in H. anomalus in the past and, perhaps, in one or both parental species. Finally, our data suggest that selective sweeps may have united populations of H. anomalus isolated by a mountain range, indicating that even low gene-flow species may be held together by the spread of advantageous alleles. PMID:17944850

Seismic Window Selection and Misfit Measurements for Global Adjoint Tomography

NASA Astrophysics Data System (ADS)

Lei, W.; Bozdag, E.; Lefebvre, M.; Podhorszki, N.; Smith, J. A.; Tromp, J.

2013-12-01

Global Adjoint Tomography requires fast parallel processing of large datasets. After obtaing the preprocessed observed and synthetic seismograms, we use the open source software packages FLEXWIN (Maggi et al. 2007) to select time windows and MEASURE_ADJ to make measurements. These measurements define adjoint sources for data assimilation. Previous versions of these tools work on a pair of SAC files---observed and synthetic seismic data for the same component and station, and loop over all seismic records associated with one earthquake. Given the large number of stations and earthquakes, the frequent read and write operations create severe I/O bottlenecks on modern computing platforms. We present new versions of these tools utilizing a new seismic data format, namely the Adaptive Seismic Data Format(ASDF). This new format shows superior scalability for applications on high-performance computers and accommodates various types of data, including earthquake, industry and seismic interferometry datasets. ASDF also provides user-friendly APIs, which can be easily integrated into the adjoint tomography workflow and combined with other data processing tools. In addition to solving the I/O bottleneck, we are making several improvements to these tools. For example, FLEXWIN is tuned to select windows for different types of earthquakes. To capture their distinct features, we categorize earthquakes by their depths and frequency bands. Moreover, instead of only picking phases between the first P arrival and the surface-wave arrivals, our aim is to select and assimilate many other later prominent phases in adjoint tomography. For example, in the body-wave band (17 s - 60 s), we include SKS, sSKS and their multiple, while in the surface-wave band (60 s - 120 s) we incorporate major-arc surface waves.

Genetic depletion at adaptive but not neutral loci in an endangered bird species.

PubMed

Hartmann, Stefanie A; Schaefer, H Martin; Segelbacher, Gernot

2014-12-01

Many endangered species suffer from the loss of genetic diversity, but some populations may be able to thrive even if genetically depleted. To investigate the underlying genetic processes of population bottlenecks, we apply an innovative approach for assessing genetic diversity in the last known population of the endangered Pale-headed Brushfinch (Atlapetes pallidiceps) in Ecuador. First, we measure genetic diversity at eleven neutral microsatellite loci and adaptive SNP variation in five Toll-like receptor (TLR) immune system genes. Bottleneck tests confirm genetic drift as the main force shaping genetic diversity in this species and indicate a 99 % reduction in population size dating back several hundred years. Second, we compare contemporary microsatellite diversity with historic museum samples of A. pallidiceps, finding no change in genetic diversity. Third, we compare genetic diversity in the Pale-headed Brushfinch with two co-occurring-related brushfinch species (Atlapetes latinuchus, Buarremon torquatus), finding a reduction of up to 91% diversity in the immune system genes but not in microsatellites. High TLR diversity is linked to decreased survival probabilities in A. pallidiceps. Low TLR diversity is thus probably an adaptation to the specific selection regime within its currently very restricted distribution (approximately 200 ha), but could severely restrict the adaptive potential of the species in the long run. Our study illustrates the importance of investigating both neutral and adaptive markers to assess the effect of population bottlenecks and for recommending specific management plans in endangered species. © 2014 John Wiley & Sons Ltd.

Study on traffic characteristics for a typical expressway on-ramp bottleneck considering various merging behaviors

NASA Astrophysics Data System (ADS)

Sun, Jie; Li, Zhipeng; Sun, Jian

2015-12-01

Recurring bottlenecks at freeway/expressway are considered as the main cause of traffic congestion in urban traffic system while on-ramp bottlenecks are the most significant sites that may result in congestion. In this paper, the traffic bottleneck characteristics for a simple and typical expressway on-ramp are investigated by the means of simulation modeling under the open boundary condition. In simulations, the running behaviors of each vehicle are described by a car-following model with a calibrated optimal velocity function, and lane changing actions at the merging section are modeled by a novel set of rules. We numerically derive the traffic volume of on-ramp bottleneck under different upstream arrival rates of mainline and ramp flows. It is found that the vehicles from the ramp strongly affect the pass of mainline vehicles and the merging ratio changes with the increasing of ramp vehicle, when the arrival rate of mainline flow is greater than a critical value. In addition, we clarify the dependence of the merging ratio of on-ramp bottleneck on the probability of lane changing and the length of the merging section, and some corresponding intelligent control strategies are proposed in actual traffic application.

Lake Ontario: Food web dynamics in a changing ecosystem (1970-2000)

USGS Publications Warehouse

Mills, E.L.; Casselman, J.M.; Dermott, R.; Fitzsimons, J.D.; Gal, G.; Holeck, K. T.; Hoyle, J.A.; Johannsson, O.E.; Lantry, B.F.; Makarewicz, J.C.; Millard, E.S.; Munawar, I.F.; Munawar, M.; O'Gorman, R.; Owens, R.W.; Rudstam, L. G.; Schaner, T.; Stewart, T.J.

2003-01-01

We examined stressors that have led to profound ecological changes in the Lake Ontario ecosystem and its fish community since 1970. The most notable changes have been reductions in phosphorus loading, invasion by Dreissena spp., fisheries management through stocking of exotic salmonids and control of sea lamprey (Petromyzon marinus), and fish harvest by anglers and double-crested cormorants (Phalacrocorax auritus). The response to these stressors has led to (i) declines in both algal photosynthesis and epilimnetic zooplankton production, (ii) decreases in alewife (Alosa pseudoharengus) abundance, (iii) declines in native Diporeia and lake whitefish (Coregonus clupeaformis), (iv) behavioral shifts in alewife spatial distribution benefitting native lake trout (Salvelinus namaycush), threespine stickleback (Gasterosteus aculeatus), and emerald shiner (Notropis atherinoides) populations, (v) dramatic increases in water clarity, (vi) predation impacts by cormorants on select fish species, and (vii) lake trout recruitment bottlenecks associated with alewife-induced thiamine deficiency. We expect stressor responses associated with anthropogenic forces like exotic species invasions and global climate warming to continue to impact the Lake Ontario ecosystem in the future and recommend continuous long-term ecological studies to enhance scientific understanding and management of this important resource.

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture.

PubMed

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong; Kim, Sunghoon; She, Ji; Cang, Chunlei; Ren, Dejian; Jiang, Youxing

2017-07-27

TMEM175 is a lysosomal K + channel that is important for maintaining the membrane potential and pH stability in lysosomes. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K + channels and lacks the TVGYG selectivity filter motif found in these channels. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completely different fold from that of canonical K + channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K + channel family.

FPGA-based prototype storage system with phase change memory

NASA Astrophysics Data System (ADS)

Li, Gezi; Chen, Xiaogang; Chen, Bomy; Li, Shunfen; Zhou, Mi; Han, Wenbing; Song, Zhitang

2016-10-01

With the ever-increasing amount of data being stored via social media, mobile telephony base stations, and network devices etc. the database systems face severe bandwidth bottlenecks when moving vast amounts of data from storage to the processing nodes. At the same time, Storage Class Memory (SCM) technologies such as Phase Change Memory (PCM) with unique features like fast read access, high density, non-volatility, byte-addressability, positive response to increasing temperature, superior scalability, and zero standby leakage have changed the landscape of modern computing and storage systems. In such a scenario, we present a storage system called FLEET which can off-load partial or whole SQL queries to the storage engine from CPU. FLEET uses an FPGA rather than conventional CPUs to implement the off-load engine due to its highly parallel nature. We have implemented an initial prototype of FLEET with PCM-based storage. The results demonstrate that significant performance and CPU utilization gains can be achieved by pushing selected query processing components inside in PCM-based storage.

A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera.

PubMed

Wallberg, Andreas; Han, Fan; Wellhagen, Gustaf; Dahle, Bjørn; Kawata, Masakado; Haddad, Nizar; Simões, Zilá Luz Paulino; Allsopp, Mike H; Kandemir, Irfan; De la Rúa, Pilar; Pirk, Christian W; Webster, Matthew T

2014-10-01

The honeybee Apis mellifera has major ecological and economic importance. We analyze patterns of genetic variation at 8.3 million SNPs, identified by sequencing 140 honeybee genomes from a worldwide sample of 14 populations at a combined total depth of 634×. These data provide insight into the evolutionary history and genetic basis of local adaptation in this species. We find evidence that population sizes have fluctuated greatly, mirroring historical fluctuations in climate, although contemporary populations have high genetic diversity, indicating the absence of domestication bottlenecks. Levels of genetic variation are strongly shaped by natural selection and are highly correlated with patterns of gene expression and DNA methylation. We identify genomic signatures of local adaptation, which are enriched in genes expressed in workers and in immune system- and sperm motility-related genes that might underlie geographic variation in reproduction, dispersal and disease resistance. This study provides a framework for future investigations into responses to pathogens and climate change in honeybees.

Task-set inertia and memory-consolidation bottleneck in dual tasks.

PubMed

Koch, Iring; Rumiati, Raffaella I

2006-11-01

Three dual-task experiments examined the influence of processing a briefly presented visual object for deferred verbal report on performance in an unrelated auditory-manual reaction time (RT) task. RT was increased at short stimulus-onset asynchronies (SOAs) relative to long SOAs, showing that memory consolidation processes can produce a functional processing bottleneck in dual-task performance. In addition, the experiments manipulated the spatial compatibility of the orientation of the visual object and the side of the speeded manual response. This cross-task compatibility produced relative RT benefits only when the instruction for the visual task emphasized overlap at the level of response codes across the task sets (Experiment 1). However, once the effective task set was in place, it continued to produce cross-task compatibility effects even in single-task situations ("ignore" trials in Experiment 2) and when instructions for the visual task did not explicitly require spatial coding of object orientation (Experiment 3). Taken together, the data suggest a considerable degree of task-set inertia in dual-task performance, which is also reinforced by finding costs of switching task sequences (e.g., AC --> BC vs. BC --> BC) in Experiment 3.

A heuristic model on the role of plasticity in adaptive evolution: plasticity increases adaptation, population viability and genetic variation.

PubMed

Gomez-Mestre, Ivan; Jovani, Roger

2013-11-22

An ongoing new synthesis in evolutionary theory is expanding our view of the sources of heritable variation beyond point mutations of fixed phenotypic effects to include environmentally sensitive changes in gene regulation. This expansion of the paradigm is necessary given ample evidence for a heritable ability to alter gene expression in response to environmental cues. In consequence, single genotypes are often capable of adaptively expressing different phenotypes in different environments, i.e. are adaptively plastic. We present an individual-based heuristic model to compare the adaptive dynamics of populations composed of plastic or non-plastic genotypes under a wide range of scenarios where we modify environmental variation, mutation rate and costs of plasticity. The model shows that adaptive plasticity contributes to the maintenance of genetic variation within populations, reduces bottlenecks when facing rapid environmental changes and confers an overall faster rate of adaptation. In fluctuating environments, plasticity is favoured by selection and maintained in the population. However, if the environment stabilizes and costs of plasticity are high, plasticity is reduced by selection, leading to genetic assimilation, which could result in species diversification. More broadly, our model shows that adaptive plasticity is a common consequence of selection under environmental heterogeneity, and hence a potentially common phenomenon in nature. Thus, taking adaptive plasticity into account substantially extends our view of adaptive evolution.

Genetic variability and evolutionary dynamics of viruses of the family Closteroviridae

PubMed Central

Rubio, Luis; Guerri, José; Moreno, Pedro

2013-01-01

RNA viruses have a great potential for genetic variation, rapid evolution and adaptation. Characterization of the genetic variation of viral populations provides relevant information on the processes involved in virus evolution and epidemiology and it is crucial for designing reliable diagnostic tools and developing efficient and durable disease control strategies. Here we performed an updated analysis of sequences available in Genbank and reviewed present knowledge on the genetic variability and evolutionary processes of viruses of the family Closteroviridae. Several factors have shaped the genetic structure and diversity of closteroviruses. (I) A strong negative selection seems to be responsible for the high genetic stability in space and time for some viruses. (2) Long distance migration, probably by human transport of infected propagative plant material, have caused that genetically similar virus isolates are found in distant geographical regions. (3) Recombination between divergent sequence variants have generated new genotypes and plays an important role for the evolution of some viruses of the family Closteroviridae. (4) Interaction between virus strains or between different viruses in mixed infections may alter accumulation of certain strains. (5) Host change or virus transmission by insect vectors induced changes in the viral population structure due to positive selection of sequence variants with higher fitness for host-virus or vector-virus interaction (adaptation) or by genetic drift due to random selection of sequence variants during the population bottleneck associated to the transmission process. PMID:23805130

A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans

PubMed Central

Koch, Evan; Novembre, John

2017-01-01

When mutations have small effects on fitness, population size plays an important role in determining the amount and nature of deleterious genetic variation. The extent to which recent population size changes have impacted deleterious variation in humans has been a question of considerable interest and debate. An emerging consensus is that the Out-of-Africa bottleneck and subsequent growth events have been too short to cause meaningful differences in genetic load between populations; though changes in the number and average frequencies of deleterious variants have taken place. To provide more support for this view and to offer additional insight into the divergent evolution of deleterious variation across populations, we numerically solve time-inhomogeneous diffusion equations and study the temporal dynamics of the frequency spectra in models of population size change for modern humans. We observe how the response to demographic change differs by the strength of selection, and we then assess whether similar patterns are observed in exome sequence data from 33,370 and 5203 individuals of non-Finnish European and West African ancestry, respectively. Our theoretical results highlight how even simple summaries of the frequency spectrum can have complex responses to demographic change. These results support the finding that some apparent discrepancies between previous results have been driven by the behaviors of the precise summaries of deleterious variation. Further, our empirical results make clear the difficulty of inferring slight differences in frequency spectra using recent next-generation sequence data. PMID:28159863

The Case for a Gaian Bottleneck: The Biology of Habitability.

PubMed

Chopra, Aditya; Lineweaver, Charles H

2016-01-01

The prerequisites and ingredients for life seem to be abundantly available in the Universe. However, the Universe does not seem to be teeming with life. The most common explanation for this is a low probability for the emergence of life (an emergence bottleneck), notionally due to the intricacies of the molecular recipe. Here, we present an alternative Gaian bottleneck explanation: If life emerges on a planet, it only rarely evolves quickly enough to regulate greenhouse gases and albedo, thereby maintaining surface temperatures compatible with liquid water and habitability. Such a Gaian bottleneck suggests that (i) extinction is the cosmic default for most life that has ever emerged on the surfaces of wet rocky planets in the Universe and (ii) rocky planets need to be inhabited to remain habitable. In the Gaian bottleneck model, the maintenance of planetary habitability is a property more associated with an unusually rapid evolution of biological regulation of surface volatiles than with the luminosity and distance to the host star.

Attention in a Bayesian Framework

PubMed Central

Whiteley, Louise; Sahani, Maneesh

2012-01-01

The behavioral phenomena of sensory attention are thought to reflect the allocation of a limited processing resource, but there is little consensus on the nature of the resource or why it should be limited. Here we argue that a fundamental bottleneck emerges naturally within Bayesian models of perception, and use this observation to frame a new computational account of the need for, and action of, attention – unifying diverse attentional phenomena in a way that goes beyond previous inferential, probabilistic and Bayesian models. Attentional effects are most evident in cluttered environments, and include both selective phenomena, where attention is invoked by cues that point to particular stimuli, and integrative phenomena, where attention is invoked dynamically by endogenous processing. However, most previous Bayesian accounts of attention have focused on describing relatively simple experimental settings, where cues shape expectations about a small number of upcoming stimuli and thus convey “prior” information about clearly defined objects. While operationally consistent with the experiments it seeks to describe, this view of attention as prior seems to miss many essential elements of both its selective and integrative roles, and thus cannot be easily extended to complex environments. We suggest that the resource bottleneck stems from the computational intractability of exact perceptual inference in complex settings, and that attention reflects an evolved mechanism for approximate inference which can be shaped to refine the local accuracy of perception. We show that this approach extends the simple picture of attention as prior, so as to provide a unified and computationally driven account of both selective and integrative attentional phenomena. PMID:22712010

An analysis of the influence of deep neural network (DNN) topology in bottleneck feature based language recognition.

PubMed

Lozano-Diez, Alicia; Zazo, Ruben; Toledano, Doroteo T; Gonzalez-Rodriguez, Joaquin

2017-01-01

Language recognition systems based on bottleneck features have recently become the state-of-the-art in this research field, showing its success in the last Language Recognition Evaluation (LRE 2015) organized by NIST (U.S. National Institute of Standards and Technology). This type of system is based on a deep neural network (DNN) trained to discriminate between phonetic units, i.e. trained for the task of automatic speech recognition (ASR). This DNN aims to compress information in one of its layers, known as bottleneck (BN) layer, which is used to obtain a new frame representation of the audio signal. This representation has been proven to be useful for the task of language identification (LID). Thus, bottleneck features are used as input to the language recognition system, instead of a classical parameterization of the signal based on cepstral feature vectors such as MFCCs (Mel Frequency Cepstral Coefficients). Despite the success of this approach in language recognition, there is a lack of studies analyzing in a systematic way how the topology of the DNN influences the performance of bottleneck feature-based language recognition systems. In this work, we try to fill-in this gap, analyzing language recognition results with different topologies for the DNN used to extract the bottleneck features, comparing them and against a reference system based on a more classical cepstral representation of the input signal with a total variability model. This way, we obtain useful knowledge about how the DNN configuration influences bottleneck feature-based language recognition systems performance.

Post-Domestication Selection in the Maize Starch Pathway

PubMed Central

Fan, Longjiang; Bao, Jiandong; Wang, Yu; Yao, Jianqiang; Gui, Yijie; Hu, Weiming; Zhu, Jinqing; Zeng, Mengqian; Li, Yu; Xu, Yunbi

2009-01-01

Modern crops have usually experienced domestication selection and subsequent genetic improvement (post-domestication selection). Chinese waxy maize, which originated from non-glutinous domesticated maize (Zea mays ssp. mays), provides a unique model for investigating the post-domestication selection of maize. In this study, the genetic diversity of six key genes in the starch pathway was investigated in a glutinous population that included 55 Chinese waxy accessions, and a selective bottleneck that resulted in apparent reductions in diversity in Chinese waxy maize was observed. Significant positive selection in waxy (wx) but not amylose extender1 (ae1) was detected in the glutinous population, in complete contrast to the findings in non-glutinous maize, which indicated a shift in the selection target from ae1 to wx during the improvement of Chinese waxy maize. Our results suggest that an agronomic trait can be quickly improved into a target trait with changes in the selection target among genes in a crop pathway. PMID:19859548

The genomics of selection in dogs and the parallel evolution between dogs and humans.

PubMed

Wang, Guo-dong; Zhai, Weiwei; Yang, He-chuan; Fan, Ruo-xi; Cao, Xue; Zhong, Li; Wang, Lu; Liu, Fei; Wu, Hong; Cheng, Lu-guang; Poyarkov, Andrei D; Poyarkov, Nikolai A; Tang, Shu-sheng; Zhao, Wen-ming; Gao, Yun; Lv, Xue-mei; Irwin, David M; Savolainen, Peter; Wu, Chung-I; Zhang, Ya-ping

2013-01-01

The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.

Invasions and extinctions through the looking glass of evolutionary ecology

PubMed Central

2017-01-01

Invasive and endangered species reflect opposite ends of a spectrum of ecological success, yet they experience many similar eco-evolutionary challenges including demographic bottlenecks, hybridization and novel environments. Despite these similarities, important differences exist. Demographic bottlenecks are more transient in invasive species, which (i) maintains ecologically relevant genetic variation, (ii) reduces mutation load, and (iii) increases the efficiency of natural selection relative to genetic drift. Endangered species are less likely to benefit from admixture, which offsets mutation load but also reduces fitness when populations are locally adapted. Invading species generally experience more benign environments with fewer natural enemies, which increases fitness directly and also indirectly by masking inbreeding depression. Adaptive phenotypic plasticity can maintain fitness in novel environments but is more likely to evolve in invasive species encountering variable habitats and to be compromised by demographic factors in endangered species. Placed in an eco-evolutionary context, these differences affect the breadth of the ecological niche, which arises as an emergent property of antagonistic selection and genetic constraints. Comparative studies of invasions and extinctions that apply an eco-evolutionary perspective could provide new insights into the environmental and genetic basis of ecological success in novel environments and improve efforts to preserve global biodiversity. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920376

Working Memory Influences Processing Speed and Reading Fluency in ADHD

PubMed Central

Jacobson, Lisa A.; Ryan, Matthew; Martin, Rebecca B.; Ewen, Joshua; Mostofsky, Stewart H.; Denckla, Martha B.; Mahone, E. Mark

2012-01-01

Processing speed deficits affect reading efficiency, even among individuals who recognize and decode words accurately. Children with ADHD who decode words accurately can still have inefficient reading fluency, leading to a bottleneck in other cognitive processes. This “slowing” in ADHD is associated with deficits in fundamental components of executive function underlying processing speed, including response selection. The purpose of the present study was to deconstruct processing speed in order to determine which components of executive control best explain the “processing” speed deficits related to reading fluency in ADHD. Participants (41 ADHD, 21 controls), ages 9-14, screened for language disorders, word reading deficits, and psychiatric disorders, were administered measures of copying speed, processing speed, reading fluency, working memory, reaction time, inhibition, and auditory attention span. Compared to controls, children with ADHD showed reduced oral and silent reading fluency, and reduced processing speed—driven primarily by deficits on WISC-IV Coding. In contrast, groups did not differ on copying speed. After controlling for copying speed, sex, severity of ADHD-related symptomatology, and GAI, slowed “processing” speed (i.e., Coding) was significantly associated with verbal span and measures of working memory, but not with measures of response control/inhibition, lexical retrieval speed, reaction time, or intra-subject variability. Further, “processing” speed (i.e., Coding, residualized for copying speed) and working memory were significant predictors of oral reading fluency. Abnormalities in working memory and response selection (which are frontally-mediated and enter into the output side of processing speed) may play an important role in deficits in reading fluency in ADHD, potentially more than posteriorally-mediated problems with orienting of attention or perceiving the stimulus. PMID:21287422

Working memory influences processing speed and reading fluency in ADHD.

PubMed

Jacobson, Lisa A; Ryan, Matthew; Martin, Rebecca B; Ewen, Joshua; Mostofsky, Stewart H; Denckla, Martha B; Mahone, E Mark

2011-01-01

Processing-speed deficits affect reading efficiency, even among individuals who recognize and decode words accurately. Children with ADHD who decode words accurately can still have inefficient reading fluency, leading to a bottleneck in other cognitive processes. This "slowing" in ADHD is associated with deficits in fundamental components of executive function underlying processing speed, including response selection. The purpose of the present study was to deconstruct processing speed in order to determine which components of executive control best explain the "processing" speed deficits related to reading fluency in ADHD. Participants (41 ADHD, 21 controls), ages 9-14 years, screened for language disorders, word reading deficits, and psychiatric disorders, were administered measures of copying speed, processing speed, reading fluency, working memory, reaction time, inhibition, and auditory attention span. Compared to controls, children with ADHD showed reduced oral and silent reading fluency and reduced processing speed-driven primarily by deficits on WISC-IV Coding. In contrast, groups did not differ on copying speed. After controlling for copying speed, sex, severity of ADHD-related symptomatology, and GAI, slowed "processing" speed (i.e., Coding) was significantly associated with verbal span and measures of working memory but not with measures of response control/inhibition, lexical retrieval speed, reaction time, or intrasubject variability. Further, "processing" speed (i.e., Coding, residualized for copying speed) and working memory were significant predictors of oral reading fluency. Abnormalities in working memory and response selection (which are frontally mediated and enter into the output side of processing speed) may play an important role in deficits in reading fluency in ADHD, potentially more than posteriorally mediated problems with orienting of attention or perceiving the stimulus.

Basic newborn care and neonatal resuscitation: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background An estimated two-thirds of the world's 2.7 million newborn deaths could be prevented with quality care at birth and during the postnatal period. Basic Newborn Care (BNC) is part of the solution and includes hygienic birth and newborn care practices including cord care, thermal care, and early and exclusive breastfeeding. Timely provision of resuscitation if needed is also critical to newborn survival. This paper describes health system barriers to BNC and neonatal resuscitation and proposes solutions to scale up evidence-based strategies. Methods The maternal and newborn bottleneck analysis tool was applied by 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops engaged technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" that hinder the scale up of maternal-newborn intervention packages. We used quantitative and qualitative methods to analyse the bottleneck data, combined with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for BNC and neonatal resuscitation. Results Eleven of the 12 countries provided grading data. Overall, bottlenecks were graded more severely for resuscitation. The most severely graded bottlenecks for BNC were health workforce (8 of 11 countries), health financing (9 out of 11) and service delivery (7 out of 9); and for neonatal resuscitation, workforce (9 out of 10), essential commodities (9 out of 10) and service delivery (8 out of 10). Country teams from Africa graded bottlenecks overall more severely. Improving workforce performance, availability of essential commodities, and well-integrated health service delivery were the key solutions proposed. Conclusions BNC was perceived to have the least health system challenges among the seven maternal and newborn intervention packages assessed. Although neonatal resuscitation bottlenecks were graded more severe than for BNC, similarities particularly in the workforce and service delivery building blocks highlight the inextricable link between the two interventions and the need to equip birth attendants with requisite skills and commodities to assess and care for every newborn. Solutions highlighted by country teams include ensuring more investment to improve workforce performance and distribution, especially numbers of skilled birth attendants, incentives for placement in challenging settings, and skills-based training particularly for neonatal resuscitation. PMID:26391000

Probabilistic physical characteristics of phase transitions at highway bottlenecks: incommensurability of three-phase and two-phase traffic-flow theories.

PubMed

Kerner, Boris S; Klenov, Sergey L; Schreckenberg, Michael

2014-05-01

Physical features of induced phase transitions in a metastable free flow at an on-ramp bottleneck in three-phase and two-phase cellular automaton (CA) traffic-flow models have been revealed. It turns out that at given flow rates at the bottleneck, to induce a moving jam (F → J transition) in the metastable free flow through the application of a time-limited on-ramp inflow impulse, in both two-phase and three-phase CA models the same critical amplitude of the impulse is required. If a smaller impulse than this critical one is applied, neither F → J transition nor other phase transitions can occur in the two-phase CA model. We have found that in contrast with the two-phase CA model, in the three-phase CA model, if the same smaller impulse is applied, then a phase transition from free flow to synchronized flow (F → S transition) can be induced at the bottleneck. This explains why rather than the F → J transition, in the three-phase theory traffic breakdown at a highway bottleneck is governed by an F → S transition, as observed in real measured traffic data. None of two-phase traffic-flow theories incorporates an F → S transition in a metastable free flow at the bottleneck that is the main feature of the three-phase theory. On the one hand, this shows the incommensurability of three-phase and two-phase traffic-flow theories. On the other hand, this clarifies why none of the two-phase traffic-flow theories can explain the set of fundamental empirical features of traffic breakdown at highway bottlenecks.

Budget process bottlenecks for immunization financing in the Democratic Republic of the Congo (DRC).

PubMed

Le Gargasson, Jean-Bernard; Mibulumukini, Benoît; Gessner, Bradford D; Colombini, Anaïs

2014-02-19

In Democratic Republic of the Congo (DRC), the availability of domestic resources for the immunization program is limited and relies mostly on external donor support. DRC has introduced a series of reforms to move the country toward performance-based management and program budgets. The objectives of the study were to: (i) describe the budget process norm, (ii) analyze the budget process in practice and associated bottlenecks at each of its phases, and (iii) collect suggestions made by the actors involved to improve the situation. Quantitative and qualitative data were collected through: a review of published and gray literature, and individual interviews. Bottlenecks in the budget process and disbursement of funds for immunization are one of the causes of limited domestic resources for the program. Critical bottlenecks include: excessive use of off-budget procedures; limited human resources and capacity; lack of motivation; interference from ministries with the standard budget process; dependency toward the development partner's disbursements schedule; and lack of budget implementation tracking. Results show that the health sector's mobilization rate was 59% in 2011. For the credit line specific to immunization program activities, the mobilization rate for the national Expanded Program for Immunization (EPI) was 26% in 2011 and 43% for vaccines (2010). The main bottleneck for the EPI budget line (2011) and vaccine budget line (2011) occurs at the authorization phase. Budget process bottlenecks identified in the analysis lead to a low mobilization rate for the immunization program. The bottlenecks identified show that a poor flow of funds causes an insufficient percentage of already allocated resources to reach various health system levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

Concordance of nuclear and mitochondrial DNA markers in detecting a founder event in Lake Clark sockeye salmon

USGS Publications Warehouse

Ramstad, Kristina M.; Woody, Carol Ann; Habicht, Chris; Sage, G. Kevin; Seeb, James E.; Allendorf, Fred W.

2007-01-01

Genetic bottleneck effects can reduce genetic variation, persistence probability, and evolutionary potential of populations. Previous microsatellite analysis suggested a bottleneck associated with a common founding of sock-eye salmon Oncorhynchus nerka populations of Lake Clark, Alaska, about 100 to 400 generations ago. The common foundingevent occurred after the last glacial recession and resulted in reduced allelic diversity and strong divergence of Lake Clarksockeye salmon relative to neighboring Six Mile Lake and LakeIliamna populations. Here we used two additional genetic marker types (allozymes and mtDNA) to examine these patterns further. Allozyme and mtDNA results were congruent with the microsatellite data in suggesting a common founder event in LakeClark sockeye salmon and confirmed the divergence of Lake Clarkpopulations from neighboring Six Mile Lake and Lake Iliamna populations. The use of multiple marker types provided better understanding of the bottleneck in Lake Clark. For example, the Sucker Bay Lake population had an exceptionally severe reduction in allelic diversity at microsatellite loci, but not at mtDNA. This suggests that the reduced microsatellite variation in Sucker Bay Lake fish is due to consistently smaller effective population size than other Lake Clark populations, rather than a more acute or additional bottleneck since founding. Caution is urged in using reduced heterozygosity as a measure of genetic bottleneck effects because stochastic variance among loci resulted in an overall increase in allozyme heterozygosity within bottlenecked Lake Clark populations. However, heterozygosity excess, which assesses heterozygosity relative to allelic variation, detected genetic bottleneck effects in both allozyme and microsatellite loci. 

Brown world forests: increased ungulate browsing keeps temperate trees in recruitment bottlenecks in resource hotspots.

PubMed

Churski, Marcin; Bubnicki, Jakub W; Jędrzejewska, Bogumiła; Kuijper, Dries P J; Cromsigt, Joris P G M

2017-04-01

Plant biomass consumers (mammalian herbivory and fire) are increasingly seen as major drivers of ecosystem structure and function but the prevailing paradigm in temperate forest ecology is still that their dynamics are mainly bottom-up resource-controlled. Using conceptual advances from savanna ecology, particularly the demographic bottleneck model, we present a novel view on temperate forest dynamics that integrates consumer and resource control. We used a fully factorial experiment, with varying levels of ungulate herbivory and resource (light) availability, to investigate how these factors shape recruitment of five temperate tree species. We ran simulations to project how inter- and intraspecific differences in height increment under the different experimental scenarios influence long-term recruitment of tree species. Strong herbivore-driven demographic bottlenecks occurred in our temperate forest system, and bottlenecks were as strong under resource-rich as under resource-poor conditions. Increased browsing by herbivores in resource-rich patches strongly counteracted the increased escape strength of saplings in these patches. This finding is a crucial extension of the demographic bottleneck model which assumes that increased resource availability allows plants to more easily escape consumer-driven bottlenecks. Our study demonstrates that a more dynamic understanding of consumer-resource interactions is necessary, where consumers and plants both respond to resource availability. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Of cuts and cracks: data analytics on constrained graphs for early prediction of failure in cementitious materials

NASA Astrophysics Data System (ADS)

Kahagalage, Sanath; Tordesillas, Antoinette; Nitka, Michał; Tejchman, Jacek

2017-06-01

Using data from discrete element simulations, we develop a data analytics approach using network flow theory to study force transmission and failure in a `dog-bone' concrete specimen submitted to uniaxial tension. With this approach, we establish the extent to which the bottlenecks, i.e., a subset of contacts that impedes flow and are prone to becoming overloaded, can predict the location of the ultimate macro-crack. At the heart of this analysis is a capacity function that quantifies, in relative terms, the maximum force that can be transmitted through the different contacts or edges in the network. Here we set this function to be solely governed by the size of the contact area between the deformable spherical grains. During all the initial stages of the loading history, when no bonds are broken, we find the bottlenecks coincide consistently with, and therefore predict, the location of the crack that later forms in the failure regime after peak force. When bonds do start to break, they are spread throughout the specimen: in, near, and far from, the bottlenecks. In one stage leading up to peak force, bonds collectively break in the lower portion of the specimen, momentarily shifting the bottlenecks to this location. Just before and around peak force, however, the bottlenecks return to their original location and remain there until the macro-crack emerges right along the bottlenecks.

Self-organized phenomena of pedestrian counterflow through a wide bottleneck in a channel

NASA Astrophysics Data System (ADS)

Dong, Li-Yun; Lan, Dong-Kai; Li, Xiang

2016-09-01

The pedestrian counterflow through a bottleneck in a channel shows a variety of flow patterns due to self-organization. In order to reveal the underlying mechanism, a cellular automaton model was proposed by incorporating the floor field and the view field which reflects the global information of the studied area and local interactions with others. The presented model can well reproduce typical collective behaviors, such as lane formation. Numerical simulations were performed in the case of a wide bottleneck and typical flow patterns at different density ranges were identified as rarefied flow, laminar flow, interrupted bidirectional flow, oscillatory flow, intermittent flow, and choked flow. The effects of several parameters, such as the size of view field and the width of opening, on the bottleneck flow are also analyzed in detail. The view field plays a vital role in reproducing self-organized phenomena of pedestrian. Numerical results showed that the presented model can capture key characteristics of bottleneck flows. Project supported by the National Basic Research Program of China (Grant No. 2012CB725404) and the National Natural Science Foundation of China (Grant Nos. 11172164 and 11572184).

Epigenetic Potential as a Mechanism of Phenotypic Plasticity in Vertebrate Range Expansions.

PubMed

Kilvitis, Holly J; Hanson, Haley; Schrey, Aaron W; Martin, Lynn B

2017-08-01

During range expansions, organisms are often exposed to multiple pressures, including novel enemies (i.e., predators, competitors and/or parasites) and unfamiliar or limited resources. Additionally, small propagule sizes at range edges can result in genetic founder effects and bottlenecks, which can affect phenotypic diversity and thus selection. Despite these obstacles, individuals in expanding populations often thrive at the periphery of a range, and this success may be mediated by phenotypic plasticity. Increasing evidence suggests that epigenetic mechanisms may underlie such plasticity because they allow for more rapid phenotypic responses to novel environments than are possible via the accumulation of genetic variation. Here, we review how molecular epigenetic mechanisms could facilitate plasticity in range-expanding organisms, emphasizing the roles of DNA methylation and other epigenetic marks in the physiological regulatory networks that drive whole-organism performance. We focus on the hypothalamic-pituitary-adrenal (HPA) axis, arguing that epigenetically-mediated plasticity in the regulation of glucocorticoids in particular might strongly impact range expansions. We hypothesize that novel environments release and/or select for epigenetic potential in HPA variation and hence organismal performance and ultimately fitness. © 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.

Slow cooling and highly efficient extraction of hot carriers in colloidal perovskite nanocrystals

PubMed Central

Li, Mingjie; Bhaumik, Saikat; Goh, Teck Wee; Kumar, Muduli Subas; Yantara, Natalia; Grätzel, Michael; Mhaisalkar, Subodh; Mathews, Nripan; Sum, Tze Chien

2017-01-01

Hot-carrier solar cells can overcome the Shockley-Queisser limit by harvesting excess energy from hot carriers. Inorganic semiconductor nanocrystals are considered prime candidates. However, hot-carrier harvesting is compromised by competitive relaxation pathways (for example, intraband Auger process and defects) that overwhelm their phonon bottlenecks. Here we show colloidal halide perovskite nanocrystals transcend these limitations and exhibit around two orders slower hot-carrier cooling times and around four times larger hot-carrier temperatures than their bulk-film counterparts. Under low pump excitation, hot-carrier cooling mediated by a phonon bottleneck is surprisingly slower in smaller nanocrystals (contrasting with conventional nanocrystals). At high pump fluence, Auger heating dominates hot-carrier cooling, which is slower in larger nanocrystals (hitherto unobserved in conventional nanocrystals). Importantly, we demonstrate efficient room temperature hot-electrons extraction (up to ∼83%) by an energy-selective electron acceptor layer within 1 ps from surface-treated perovskite NCs thin films. These insights enable fresh approaches for extremely thin absorber and concentrator-type hot-carrier solar cells. PMID:28176882

The Role of Host and Microbial Factors in the Pathogenesis of Pneumococcal Bacteraemia Arising from a Single Bacterial Cell Bottleneck

PubMed Central

Furi, Leonardo; Braccini, Tiziana; Manso, Ana Sousa; Pammolli, Andrea; Wang, Bo; Vivi, Antonio; Tassini, Maria; van Rooijen, Nico; Pozzi, Gianni; Ricci, Susanna; Andrew, Peter W.; Koedel, Uwe; Moxon, E. Richard; Oggioni, Marco R.

2014-01-01

The pathogenesis of bacteraemia after challenge with one million pneumococci of three isogenic variants was investigated. Sequential analyses of blood samples indicated that most episodes of bacteraemia were monoclonal events providing compelling evidence for a single bacterial cell bottleneck at the origin of invasive disease. With respect to host determinants, results identified novel properties of splenic macrophages and a role for neutrophils in early clearance of pneumococci. Concerning microbial factors, whole genome sequencing provided genetic evidence for the clonal origin of the bacteraemia and identified SNPs in distinct sub-units of F0/F1 ATPase in the majority of the ex vivo isolates. When compared to parental organisms of the inoculum, ex-vivo pneumococci with mutant alleles of the F0/F1 ATPase had acquired the capacity to grow at low pH at the cost of the capacity to grow at high pH. Although founded by a single cell, the genotypes of pneumococci in septicaemic mice indicate strong selective pressure for fitness, emphasising the within-host complexity of the pathogenesis of invasive disease. PMID:24651834

Kin-selected cooperation without lifetime monogamy: human insights and animal implications.

PubMed

Kramer, Karen L; Russell, Andrew F

2014-11-01

Recent phylogenetic analyses suggest that monogamy precedes the evolution of cooperative breeding involving non-breeding helpers. The rationale: only through monogamy can helper-recipient relatedness coefficients match those of parent-offspring. Given that humans are cooperative breeders, these studies imply a monogamy bottleneck during hominin evolution. However, evidence from multiple sources is not compelling. In reconciliation, we propose that selection against cooperative breeding under alternative mating patterns will be mitigated by: (i) kin discrimination, (ii) reduced birth-intervals, and (iii) constraints on independent breeding, particularly for premature and post-fertile individuals. We suggest that such alternatives require consideration to derive a complete picture of the selection pressures acting on the evolution of cooperative breeding in humans and other animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of a high-throughput microscale cell disruption platform for Pichia pastoris in rapid bioprocess design.

PubMed

Bláha, Benjamin A F; Morris, Stephen A; Ogonah, Olotu W; Maucourant, Sophie; Crescente, Vincenzo; Rosenberg, William; Mukhopadhyay, Tarit K

2018-01-01

The time and cost benefits of miniaturized fermentation platforms can only be gained by employing complementary techniques facilitating high-throughput at small sample volumes. Microbial cell disruption is a major bottleneck in experimental throughput and is often restricted to large processing volumes. Moreover, for rigid yeast species, such as Pichia pastoris, no effective high-throughput disruption methods exist. The development of an automated, miniaturized, high-throughput, noncontact, scalable platform based on adaptive focused acoustics (AFA) to disrupt P. pastoris and recover intracellular heterologous protein is described. Augmented modes of AFA were established by investigating vessel designs and a novel enzymatic pretreatment step. Three different modes of AFA were studied and compared to the performance high-pressure homogenization. For each of these modes of cell disruption, response models were developed to account for five different performance criteria. Using multiple responses not only demonstrated that different operating parameters are required for different response optima, with highest product purity requiring suboptimal values for other criteria, but also allowed for AFA-based methods to mimic large-scale homogenization processes. These results demonstrate that AFA-mediated cell disruption can be used for a wide range of applications including buffer development, strain selection, fermentation process development, and whole bioprocess integration. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:130-140, 2018. © 2017 American Institute of Chemical Engineers.

On the Inefficiency of Equilibria in Linear Bottleneck Congestion Games

NASA Astrophysics Data System (ADS)

de Keijzer, Bart; Schäfer, Guido; Telelis, Orestis A.

We study the inefficiency of equilibrium outcomes in bottleneck congestion games. These games model situations in which strategic players compete for a limited number of facilities. Each player allocates his weight to a (feasible) subset of the facilities with the goal to minimize the maximum (weight-dependent) latency that he experiences on any of these facilities. We derive upper and (asymptotically) matching lower bounds on the (strong) price of anarchy of linear bottleneck congestion games for a natural load balancing social cost objective (i.e., minimize the maximum latency of a facility). We restrict our studies to linear latency functions. Linear bottleneck congestion games still constitute a rich class of games and generalize, for example, load balancing games with identical or uniformly related machines with or without restricted assignments.

Infrastructure and Private Sector Investment in Pakistan

DTIC Science & Technology

1997-03-01

manner in which the expansion in various types of infrastructural facilities interact with private sector investment, and whether there is a long run...passive role in the country’s development. That is public facilities have largely expanded in response to the needs created by private sector investment...tangible needs created by private sector expansion it has, no doubt, been very effective in alleviating real bottlenecks. (JEL F21, 053).

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

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

Lee, Changkeun; Guo, Jiangtao; Zeng, Weizhong

TMEM175 is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability in lysosomes1. It contains two homologous copies of a six-transmembrane-helix (6-TM) domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels2, 3, 4. The prokaryotic TMEM175 channel, which is present in a subset of bacteria and archaea, contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 channel from Chamaesiphon minutus, CmTMEM175, the architecture of which represents a completelymore » different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family.« less

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design.

PubMed

Keppel Hesselink, Jan M; Kopsky, David J; Stahl, Stephen M

2017-01-01

Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.

Exploring for Martian Life

NASA Technical Reports Server (NTRS)

Farmer, Jack D.; Chang, Sherwood (Technical Monitor)

1997-01-01

Terrestrial life appears to have arisen very quickly during late accretion, sometime between approximately 3.5 and 4.2 Ga. During this same time, liquid water appears to have been abundant at the surface of Mars and it is quite plausable that life originated there as well. We now believe that the last common ancestor of terrestrial life was a sulfur-metabolizing microbe that lived at high temperatures. Rooting of the RNA tree in thermophily probably reflects high temperature "bottle-necking" of the biosphere by giant impacts during late accretion, sometime after life had originated. If high temperature bottle-necking is a general property of early biosphere development, Martian life may have also developed in close association with hydrothermal systems. Several independent lines of evidence suggest that hydrothermal processes have played an important role during the geological history of Mars. Because hydrothermal deposits on Earth are known to capture and retain abundant microbial fossil information, they are considered prime targets in the search for an ancient Martian biosphere. An important step in planning for future landed missions to Mars is the selection of priority targets for high resolution orbital mapping. Geotectonic terranes on Mars that provide a present focus for ongoing site selection studies include channels located along the margins of impact crater melt sheets, or on the slopes of ancient Martian volcanoes, chaotic and fretted terranes where shallow subsurface heat sources are thought to have interacted with ground ice, and the floors of calderas and rifted basins. Orbital missions in 1996, 1998 and 2001 will provide opportunities for high resolution geological mapping at key sites in such terranes, as a basis for selecting targets for future landed missions for exopaleontology.

Modeling cooperative driving behavior in freeway merges.

DOT National Transportation Integrated Search

2011-11-01

Merging locations are major sources of freeway bottlenecks and are therefore important for freeway operations analysis. Microscopic simulation tools have been successfully used to analyze merging bottlenecks and to design optimum geometric configurat...

Cloud Technology May Widen Genomic Bottleneck - TCGA

Cancer.gov

Computational biologist Dr. Ilya Shmulevich suggests that renting cloud computing power might widen the bottleneck for analyzing genomic data. Learn more about his experience with the Cloud in this TCGA in Action Case Study.

Effect of a Phonon Bottleneck on Exciton and Spin Generation in Self-Assembled In1 -xGaxAs Quantum Dots

NASA Astrophysics Data System (ADS)

Huang, Y. Q.; Buyanova, I. A.; Yang, X. J.; Murayama, A.; Chen, W. M.

2018-04-01

We provide direct experimental evidence for the effect of a phonon bottleneck on exciton and spin generation in self-assembled In0.5Ga0.5As quantum dots (QDs). With the aid of tunable laser spectroscopy, we resolve and identify efficient exciton generation channels in the QDs mediated by longitudinal-optical (LO) phonons from an otherwise inhomogeneously broadened QD emission background that suffers from the phonon bottleneck effect in exciton generation. Spin-generation efficiency is found to be enhanced under the LO-assisted excitation condition due to suppressed spin relaxation accompanying accelerated exciton generation. These findings underline the importance of fine-tuning QD energy levels that will benefit potential spin-optoelectronic applications of QDs by reducing spin loss due to the phonon bottleneck.

Interference of two codirectional exclusion processes in the presence of a static bottleneck: A biologically motivated model

NASA Astrophysics Data System (ADS)

Mishra, Bhavya; Chowdhury, Debashish

2017-06-01

We develop a two-species exclusion process with a distinct pair of entry and exit sites for each species of rigid rods. The relatively slower forward stepping of the rods in an extended bottleneck region, located in between the two entry sites, controls the extent of interference of the codirectional flow of the two species of rods. The relative positions of the sites of entry of the two species of rods with respect to the location of the bottleneck are motivated by a biological phenomenon. However, the primary focus of the study here is to explore the effects of the interference of the flow of the two species of rods on their spatiotemporal organization and the regulations of this interference by the extended bottleneck. By a combination of mean-field theory and computer simulation, we calculate the flux of both species of rods and their density profiles as well as the composite phase diagrams of the system. If the bottleneck is sufficiently stringent, then some of the phases become practically unrealizable, although not ruled out on the basis of any fundamental physical principle. Moreover, the extent of suppression of flow of the downstream entrants by the flow of the upstream entrants can also be regulated by the strength of the bottleneck. We speculate on the possible implications of the results in the context of the biological phenomenon that motivated the formulation of the theoretical model.

Demography or selection on linked cultural traits or genes? Investigating the driver of low mtDNA diversity in the sperm whale using complementary mitochondrial and nuclear genome analyses.

PubMed

Morin, Phillip A; Foote, Andrew D; Baker, Charles Scott; Hancock-Hanser, Brittany L; Kaschner, Kristin; Mate, Bruce R; Mesnick, Sarah L; Pease, Victoria L; Rosel, Patricia E; Alexander, Alana

2018-06-01

Mitochondrial DNA has been heavily utilized in phylogeography studies for several decades. However, underlying patterns of demography and phylogeography may be misrepresented due to coalescence stochasticity, selection, variation in mutation rates and cultural hitchhiking (linkage of genetic variation to culturally-transmitted traits affecting fitness). Cultural hitchhiking has been suggested as an explanation for low genetic diversity in species with strong social structures, counteracting even high mobility, abundance and limited barriers to dispersal. One such species is the sperm whale, which shows very limited phylogeographic structure and low mtDNA diversity despite a worldwide distribution and large population. Here, we use analyses of 175 globally distributed mitogenomes and three nuclear genomes to evaluate hypotheses of a population bottleneck/expansion vs. a selective sweep due to cultural hitchhiking or selection on mtDNA as the mechanism contributing to low worldwide mitochondrial diversity in sperm whales. In contrast to mtDNA control region (CR) data, mitogenome haplotypes are largely ocean-specific, with only one of 80 shared between the Atlantic and Pacific. Demographic analyses of nuclear genomes suggest low mtDNA diversity is consistent with a global reduction in population size that ended approximately 125,000 years ago, correlated with the Eemian interglacial. Phylogeographic analysis suggests that extant sperm whales descend from maternal lineages endemic to the Pacific during the period of reduced abundance and have subsequently colonized the Atlantic several times. Results highlight the apparent impact of past climate change, and suggest selection and hitchhiking are not the sole processes responsible for low mtDNA diversity in this highly social species. © 2018 John Wiley & Sons Ltd.

Enhanced nonlinearity interval mapping scheme for high-performance simulation-optimization of watershed-scale BMP placement

NASA Astrophysics Data System (ADS)

Zou, Rui; Riverson, John; Liu, Yong; Murphy, Ryan; Sim, Youn

2015-03-01

Integrated continuous simulation-optimization models can be effective predictors of a process-based responses for cost-benefit optimization of best management practices (BMPs) selection and placement. However, practical application of simulation-optimization model is computationally prohibitive for large-scale systems. This study proposes an enhanced Nonlinearity Interval Mapping Scheme (NIMS) to solve large-scale watershed simulation-optimization problems several orders of magnitude faster than other commonly used algorithms. An efficient interval response coefficient (IRC) derivation method was incorporated into the NIMS framework to overcome a computational bottleneck. The proposed algorithm was evaluated using a case study watershed in the Los Angeles County Flood Control District. Using a continuous simulation watershed/stream-transport model, Loading Simulation Program in C++ (LSPC), three nested in-stream compliance points (CP)—each with multiple Total Maximum Daily Loads (TMDL) targets—were selected to derive optimal treatment levels for each of the 28 subwatersheds, so that the TMDL targets at all the CP were met with the lowest possible BMP implementation cost. Genetic Algorithm (GA) and NIMS were both applied and compared. The results showed that the NIMS took 11 iterations (about 11 min) to complete with the resulting optimal solution having a total cost of 67.2 million, while each of the multiple GA executions took 21-38 days to reach near optimal solutions. The best solution obtained among all the GA executions compared had a minimized cost of 67.7 million—marginally higher, but approximately equal to that of the NIMS solution. The results highlight the utility for decision making in large-scale watershed simulation-optimization formulations.

Similar genomic proportions of copy number variation within gray wolves and modern dog breeds inferred from whole genome sequencing.

PubMed

Serres-Armero, Aitor; Povolotskaya, Inna S; Quilez, Javier; Ramirez, Oscar; Santpere, Gabriel; Kuderna, Lukas F K; Hernandez-Rodriguez, Jessica; Fernandez-Callejo, Marcos; Gomez-Sanchez, Daniel; Freedman, Adam H; Fan, Zhenxin; Novembre, John; Navarro, Arcadi; Boyko, Adam; Wayne, Robert; Vilà, Carles; Lorente-Galdos, Belen; Marques-Bonet, Tomas

2017-12-19

Whole genome re-sequencing data from dogs and wolves are now commonly used to study how natural and artificial selection have shaped the patterns of genetic diversity. Single nucleotide polymorphisms, microsatellites and variants in mitochondrial DNA have been interrogated for links to specific phenotypes or signals of domestication. However, copy number variation (CNV), despite its increasingly recognized importance as a contributor to phenotypic diversity, has not been extensively explored in canids. Here, we develop a new accurate probabilistic framework to create fine-scale genomic maps of segmental duplications (SDs), compare patterns of CNV across groups and investigate their role in the evolution of the domestic dog by using information from 34 canine genomes. Our analyses show that duplicated regions are enriched in genes and hence likely possess functional importance. We identify 86 loci with large CNV differences between dogs and wolves, enriched in genes responsible for sensory perception, immune response, metabolic processes, etc. In striking contrast to the observed loss of nucleotide diversity in domestic dogs following the population bottlenecks that occurred during domestication and breed creation, we find a similar proportion of CNV loci in dogs and wolves, suggesting that other dynamics are acting to particularly select for CNVs with potentially functional impacts. This work is the first comparison of genome wide CNV patterns in domestic and wild canids using whole-genome sequencing data and our findings contribute to study the impact of novel kinds of genetic changes on the evolution of the domestic dog.

Reduced MHC and neutral variation in the Galápagos hawk, an island endemic

PubMed Central

2011-01-01

Background Genes at the major histocompatibility complex (MHC) are known for high levels of polymorphism maintained by balancing selection. In small or bottlenecked populations, however, genetic drift may be strong enough to overwhelm the effect of balancing selection, resulting in reduced MHC variability. In this study we investigated MHC evolution in two recently diverged bird species: the endemic Galápagos hawk (Buteo galapagoensis), which occurs in small, isolated island populations, and its widespread mainland relative, the Swainson's hawk (B. swainsoni). Results We amplified at least two MHC class II B gene copies in each species. We recovered only three different sequences from 32 Galápagos hawks, while we amplified 20 unique sequences in 20 Swainson's hawks. Most of the sequences clustered into two groups in a phylogenetic network, with one group likely representing pseudogenes or nonclassical loci. Neutral genetic diversity at 17 microsatellite loci was also reduced in the Galápagos hawk compared to the Swainson's hawk. Conclusions The corresponding loss in neutral diversity suggests that the reduced variability present at Galápagos hawk MHC class II B genes compared to the Swainson's hawk is primarily due to a founder event followed by ongoing genetic drift in small populations. However, purifying selection could also explain the low number of MHC alleles present. This lack of variation at genes involved in the adaptive immune response could be cause for concern should novel diseases reach the archipelago. PMID:21612651

MHC class II diversity of koala (Phascolarctos cinereus) populations across their range

PubMed Central

Lau, Q; Jaratlerdsiri, W; Griffith, J E; Gongora, J; Higgins, D P

2014-01-01

Major histocompatibility complex class II (MHCII) genes code for proteins that bind and present antigenic peptides and trigger the adaptive immune response. We present a broad geographical study of MHCII DA β1 (DAB) and DB β1 (DBB) variants of the koala (Phascolarctos cinereus; n=191) from 12 populations across eastern Australia, with a total of 13 DAB and 7 DBB variants found. We identified greater MHCII variation and, possibly, additional gene copies in koala populations in the north (Queensland and New South Wales) relative to the south (Victoria), confirmed by STRUCTURE analyses and genetic differentiation using analysis of molecular variance. The higher MHCII diversity in the north relative to south could potentially be attributed to (i) significant founder effect in Victorian populations linked to historical translocation of bottlenecked koala populations and (ii) increased pathogen-driven balancing selection and/or local genetic drift in the north. Low MHCII genetic diversity in koalas from the south could reduce their potential response to disease, although the three DAB variants found in the south had substantial sequence divergence between variants. This study assessing MHCII diversity in the koala with historical translocations in some populations contributes to understanding the effects of population translocations on functional genetic diversity. PMID:24690756

Unveiling CO2 heterogeneous freezing plumes during champagne cork popping.

PubMed

Liger-Belair, Gérard; Cordier, Daniel; Honvault, Jacques; Cilindre, Clara

2017-09-14

Cork popping from clear transparent bottles of champagne stored at different temperatures (namely, 6, 12, and 20 °C) was filmed through high-speed video imaging in the visible light spectrum. During the cork popping process, a plume mainly composed of gaseous CO 2 with traces of water vapour freely expands out of the bottleneck through ambient air. Most interestingly, for the bottles stored at 20 °C, the characteristic grey-white cloud of fog classically observed above the bottlenecks of champagne stored at lower temperatures simply disappeared. It is replaced by a more evanescent plume, surprisingly blue, starting from the bottleneck. We suggest that heterogeneous freezing of CO 2 occurs on ice water clusters homogeneously nucleated in the bottlenecks, depending on the saturation ratio experienced by gas-phase CO 2 after adiabatic expansion (indeed highly bottle temperature dependent). Moreover, and as observed for the bottles stored at 20 °C, we show that the freezing of only a small portion of all the available CO 2 is able to pump the energy released through adiabatic expansion, thus completely inhibiting the condensation of water vapour found in air packages adjacent to the gas volume gushing out of the bottleneck.

About the Role of the Bottleneck/Cork Interface on Oxygen Transfer.

PubMed

Lagorce-Tachon, Aurélie; Karbowiak, Thomas; Paulin, Christian; Simon, Jean-Marc; Gougeon, Régis D; Bellat, Jean-Pierre

2016-09-07

The transfer of oxygen through a corked bottleneck was investigated using a manometric technique. First, the effect of cork compression on oxygen transfer was evaluated without considering the glass/cork interface. No significant effect of cork compression (at 23% strain, corresponding to the compression level of cork in a bottleneck for still wines) was noticeable on the effective diffusion coefficient of oxygen. The mean value of the effective diffusion coefficient is equal to 10(-8) m(2) s(-1), with a statistical distribution ranging from 10(-10) to 10(-7) m(2) s(-1), which is of the same order of magnitude as for the non-compressed cork. Then, oxygen transfer through cork compressed in a glass bottleneck was determined to assess the effect of the glass/cork interface. In the particular case of a gradient-imposed diffusion of oxygen through our model corked bottleneck system (dry cork without surface treatment; 200 and ∼0 hPa of oxygen on both sides of the sample), the mean effective diffusion coefficient is of 5 × 10(-7) m(2) s(-1), thus revealing the possible importance of the role of the glass/stopper interface in the oxygen transfer.

Anatomy of a bottleneck: diagnosing factors limiting population growth in the Puerto Rican parrot

USGS Publications Warehouse

Beissenger, S.R.; Wunderle, J.M.; Meyers, J.M.; Saether, B.-E.; Engen, S.

2008-01-01

The relative importance of genetic, demographic, environmental, and catastrophic processes that maintain population bottlenecks has received little consideration. We evaluate the role of these factors in maintaining the Puerto Rican Parrot (Amazona vittata) in a prolonged bottleneck from 1973 through 2000 despite intensive conservation efforts. We first conduct a risk analysis, then examine evidence for the importance of specific processes maintaining the bottleneck using the multiple competing hypotheses approach, and finally integrate these results through a sensitivity analysis of a demographic model using life-stage simulation analysis (LSA) to determine the relative importance of genetic, demographic, environmental, and catastrophic processes on population growth. Annual population growth has been slow and variable (1.0 6 5.2 parrots per year, or an average k?1.05 6 0.19) from 16 parrots (1973) to a high of 40-42 birds (1997-1998). A risk analysis based on population prediction intervals (PPI) indicates great risk and large uncertainty, with a range of 22?83 birds in the 90% PPI only five years into the future. Four primary factors (reduced hatching success due to inbreeding, failure of adults to nest, nest failure due to nongenetic causes, and reduced survival of adults and juveniles) were responsible for maintaining the bottleneck. Egghatchability rates were low (70.6% per egg and 76.8% per pair), and hatchability increased after mate changes, suggesting inbreeding effects. Only an average of 34% of the population nested annually, which was well below the percentage of adults that should have reached an age of first breeding (41-56%). This chronic failure to nest appears to have been caused primarily by environmental and/or behavioral factors, and not by nest-site scarcity or a skewed sex ratio. Nest failure rates from nongenetic causes (i.e., predation, parasitism, and wet cavities) were low (29%) due to active management (protecting nests and fostering captive young into wild nests), diminishing the importance of nest failure as a limiting factor. Annual survival has been periodically reduced by catastrophes (hurricanes), which have greatly constrained population growth, but survival rates were high under non-catastrophic conditions. Although the importance of factors maintaining the Puerto Rican Parrot bottleneck varied throughout the 30-year period of study, we determined their long-term influence using LSA simulations to correlate variation in demographic rates with variation in population growth (k). The bottleneck appears to have been maintained primarily by periodic catastrophes (hurricanes) that reduced adult survival, and secondarily by environmental and/or behavioral factors that resulted in a failure of many adults to nest. The influence of inbreeding through reduced hatching success played a much less significant role, even when additional effects of inbreeding on the production and mortality of young were incorporated into the LSA. Management actions needed to speed recovery include (1) continued nest guarding to minimize the effects of nest failure due to nongenetic causes; (2) creating a second population at another location on the island --a process that was recently initiated--to reduce the chance that hurricane strikes will cause extinction; and (3) determining the causes of the low percentage of breeders in the population and ameliorating them, which would have a large impact on population growth.

Intermodal freight capacity box : intermodal freight bottleneck measures

DOT National Transportation Integrated Search

2000-09-01

The Bureau of Transportation Statistics in partnership with the U.S. Department of Transportation's Office of Intermodalism and the Federal Highway Administration sponsored the development of an Intermodal Bottleneck Evaluation Tool (IBET) to provide...

Identification, genealogical structure and population genetics of S-alleles in Malus sieversii, the wild ancestor of domesticated apple.

PubMed

Ma, X; Cai, Z; Liu, W; Ge, S; Tang, L

2017-09-01

The self-incompatibility (SI) gene that is specifically expressed in pistils encodes the SI-associated ribonuclease (S-RNase), functioning as the female-specificity determinant of a gametophytic SI system. Despite extensive surveys in Malus domestica, the S-alleles have not been fully investigated for Malus sieversii, the primary wild ancestor of the domesticated apple. Here we screened the M. sieversii S-alleles via PCR amplification and sequencing, and identified 14 distinct alleles in this species. By contrast, nearly 40 are present in its close wild relative, Malus sylvestris. We further sequenced 8 nuclear genes to provide a neutral reference, and investigated the evolution of S-alleles via genealogical and population genetic analyses. Both shared ancestral polymorphism and an excess of non-synonymous substitution were detected in the S-RNases of the tribe Maleae in Rosaceae, indicating the action of long-term balancing selection. Approximate Bayesian Computations based on the reference neutral loci revealed a severe bottleneck in four of the six studied M. sieversii populations, suggesting that the low number of S-alleles found in this species is mainly the result of diversity loss due to a drastic population contraction. Such a bottleneck may lead to ambiguous footprints of ongoing balancing selection detected at the S-locus. This study not only elucidates the constituents and number of S-alleles in M. sieversii but also illustrates the potential utility of S-allele number shifts in demographic inference for self-incompatible plant species.

Advances and bottlenecks in microbial hydrogen production.

PubMed

Stephen, Alan J; Archer, Sophie A; Orozco, Rafael L; Macaskie, Lynne E

2017-09-01

Biological production of hydrogen is poised to become a significant player in the future energy mix. This review highlights recent advances and bottlenecks in various approaches to biohydrogen processes, often in concert with management of organic wastes or waste CO 2 . Some key bottlenecks are highlighted in terms of the overall energy balance of the process and highlighting the need for economic and environmental life cycle analyses with regard also to socio-economic and geographical issues. © 2017 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Selective separation of americium from europium using 2,9-bis(triazine)-1,10-phenanthrolines in ionic liquids: a new twist on an old story

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

Williams, Neil J.; Dehaudt, Jeremy; Bryantsev, Vyacheslav S.

Bis-triazine phenanthrolines have shown great promise for f-block metal separations, attributable to their highly preorganized structure, nitrogen donors, and more enhanced covalent bonding with actinides over lanthanides. However, their limited solubility in traditional solvents remains a technological bottleneck. Here in this paper we report our recent work using a simple 2,9-bis(triazine)-1,10-phenanthroline (Me-BTPhen) dissolved in an ionic liquid (IL), demonstrating the efficacy of IL extraction systems for the selective separation of americium from europium, achieving separation factors in excess of 7500 and selectively removing up to 99% of the americium. Characterization of the coordination environment was performed using a combination ofmore » X-ray absorption fine structure spectroscopy (XAFS) and density functional theory (DFT) calculations.« less

Selective separation of americium from europium using 2,9-bis(triazine)-1,10-phenanthrolines in ionic liquids: a new twist on an old story

DOE PAGES

Williams, Neil J.; Dehaudt, Jeremy; Bryantsev, Vyacheslav S.; ...

2017-02-10

Bis-triazine phenanthrolines have shown great promise for f-block metal separations, attributable to their highly preorganized structure, nitrogen donors, and more enhanced covalent bonding with actinides over lanthanides. However, their limited solubility in traditional solvents remains a technological bottleneck. Here in this paper we report our recent work using a simple 2,9-bis(triazine)-1,10-phenanthroline (Me-BTPhen) dissolved in an ionic liquid (IL), demonstrating the efficacy of IL extraction systems for the selective separation of americium from europium, achieving separation factors in excess of 7500 and selectively removing up to 99% of the americium. Characterization of the coordination environment was performed using a combination ofmore » X-ray absorption fine structure spectroscopy (XAFS) and density functional theory (DFT) calculations.« less

Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways.

PubMed

Karbalaei, Reza; Allahyari, Marzieh; Rezaei-Tavirani, Mostafa; Asadzadeh-Aghdaei, Hamid; Zali, Mohammad Reza

2018-01-01

Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on. Therefore, systems biology approach can help to discover their relationship. DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. An R package used to define best centrality method. Finally, based on degree and Betweenness, hubs and bottleneck nodes were defined. Common genes between NAFLD and Alzheimer`s disease were 190 genes that used construct a network with STRING database. The resulting network contained 182 nodes and 2591 edges and comprises from four clusters. Enrichment of these clusters separately lead to carbohydrate metabolism, long chain fatty acid and regulation of JAK-STAT and IL-17 signaling pathways, respectively. Also seven genes selected as hub-bottleneck include: IL6, AKT1, TP53, TNF, JUN, VEGFA and PPARG. Enrichment of these proteins and their first neighbors in network by OMIM database lead to diabetes and obesity as ancestors of NAFLD and AD. Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

Analysis of viral (zucchini yellow mosaic virus) genetic diversity during systemic movement through a Cucurbita pepo vine

PubMed Central

Holmes, E.C.; Stephenson, A.G.

2014-01-01

Determining the extent and structure of intra-host genetic diversity and the magnitude and impact of population bottlenecks is central to understanding the mechanisms of viral evolution. To determine the nature of viral evolution following systemic movement through a plant, we performed deep sequencing of 23 leaves that grew sequentially along a single Cucurbita pepo vine that was infected with zucchini yellow mosaic virus (ZYMV), and on a leaf that grew in on a side branch. Strikingly, of 112 genetic (i.e. sub-consensus) variants observed in the data set as a whole, only 22 were found in multiple leaves. Similarly, only three of the 13 variants present in the inoculating population were found in the subsequent leaves on the vine. Hence, it appears that systemic movement is characterized by sequential population bottlenecks, although not sufficient to reduce the population to a single virion as multiple variants were consistently transmitted between leaves. In addition, the number of variants within a leaf increases as a function of distance from the inoculated (source) leaf, suggesting that the circulating sap may serve as a continual source of virus. Notably, multiple mutational variants were observed in the cylindrical Inclusion (CI) protein (known to be involved in both cell-to-cell and systemic movement of the virus) that were present in multiple (19/24) leaf samples. These mutations resulted in a conformational change, suggesting that they might confer a selective advantage in systemic movement within the vine. Overall, these data reveal that bottlenecks occur during systemic movement, that variants circulate in the phloem sap throughout the infection process, and that important conformational changes in CI protein may arise during individual infections. PMID:25107623

Identifying, anticipating, and mitigating freight bottlenecks on Alabama interstates.

DOT National Transportation Integrated Search

2011-07-31

"This project established a framework for the creation and maintenance of a statewide strategy for identifying, : anticipating, and mitigating freight bottlenecks on interstate highways in the state of Alabama. It used : methodology developed by Camb...

A recent bottleneck of Y chromosome diversity coincides with a global change in culture

PubMed Central

Saag, Lauri; Vicente, Mário; Sayres, Melissa A. Wilson; Järve, Mari; Talas, Ulvi Gerst; Rootsi, Siiri; Ilumäe, Anne-Mai; Mägi, Reedik; Mitt, Mario; Pagani, Luca; Puurand, Tarmo; Faltyskova, Zuzana; Clemente, Florian; Cardona, Alexia; Metspalu, Ene; Sahakyan, Hovhannes; Yunusbayev, Bayazit; Hudjashov, Georgi; DeGiorgio, Michael; Loogväli, Eva-Liis; Eichstaedt, Christina; Eelmets, Mikk; Chaubey, Gyaneshwer; Tambets, Kristiina; Litvinov, Sergei; Mormina, Maru; Xue, Yali; Ayub, Qasim; Zoraqi, Grigor; Korneliussen, Thorfinn Sand; Akhatova, Farida; Lachance, Joseph; Tishkoff, Sarah; Momynaliev, Kuvat; Ricaut, François-Xavier; Kusuma, Pradiptajati; Razafindrazaka, Harilanto; Pierron, Denis; Cox, Murray P.; Sultana, Gazi Nurun Nahar; Willerslev, Rane; Muller, Craig; Westaway, Michael; Lambert, David; Skaro, Vedrana; Kovačevic´, Lejla; Turdikulova, Shahlo; Dalimova, Dilbar; Khusainova, Rita; Trofimova, Natalya; Akhmetova, Vita; Khidiyatova, Irina; Lichman, Daria V.; Isakova, Jainagul; Pocheshkhova, Elvira; Sabitov, Zhaxylyk; Barashkov, Nikolay A.; Nymadawa, Pagbajabyn; Mihailov, Evelin; Seng, Joseph Wee Tien; Evseeva, Irina; Migliano, Andrea Bamberg; Abdullah, Syafiq; Andriadze, George; Primorac, Dragan; Atramentova, Lubov; Utevska, Olga; Yepiskoposyan, Levon; Marjanovic´, Damir; Kushniarevich, Alena; Behar, Doron M.; Gilissen, Christian; Vissers, Lisenka; Veltman, Joris A.; Balanovska, Elena; Derenko, Miroslava; Malyarchuk, Boris; Metspalu, Andres; Fedorova, Sardana; Eriksson, Anders; Manica, Andrea; Mendez, Fernando L.; Karafet, Tatiana M.; Veeramah, Krishna R.; Bradman, Neil; Hammer, Michael F.; Osipova, Ludmila P.; Balanovsky, Oleg; Khusnutdinova, Elza K.; Johnsen, Knut; Remm, Maido; Thomas, Mark G.; Tyler-Smith, Chris; Underhill, Peter A.; Willerslev, Eske; Nielsen, Rasmus; Metspalu, Mait; Villems, Richard

2015-01-01

It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50–100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192–307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47–52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males. PMID:25770088

Assay optimization: a statistical design of experiments approach.

PubMed

Altekar, Maneesha; Homon, Carol A; Kashem, Mohammed A; Mason, Steven W; Nelson, Richard M; Patnaude, Lori A; Yingling, Jeffrey; Taylor, Paul B

2007-03-01

With the transition from manual to robotic HTS in the last several years, assay optimization has become a significant bottleneck. Recent advances in robotic liquid handling have made it feasible to reduce assay optimization timelines with the application of statistically designed experiments. When implemented, they can efficiently optimize assays by rapidly identifying significant factors, complex interactions, and nonlinear responses. This article focuses on the use of statistically designed experiments in assay optimization.

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

NASA Astrophysics Data System (ADS)

Guo, Li; Tan, Guangguo; Liu, Ping; Li, Huijie; Tang, Lulu; Huang, Lan; Ren, Qian

2015-10-01

High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

The franchise bottleneck

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

Fairman, J.F.

Franchise terms can shape the structure and direction for much of the electricity industry`s future. The electricity distribution franchise can become a wide-mouth jar quenching the large retail customers` thirst for low-cost, reliable energy - or a bottleneck for captive customers.

Unclogging America's arteries : prescriptions for healthier highways

DOT National Transportation Integrated Search

1999-11-01

This first-of-its-kind study examines a significant cause of traffic congestion - America's worst bottlenecks - from three perspectives. First, it examines how much worse the gridlock will become at each of the 18 worst bottlenecks in the United Stat...

Saving Time, Saving Money: The Economics of Unclogging America's Worst Bottlenecks

DOT National Transportation Integrated Search

2000-01-01

A 1999 study by the American Highway Users Alliance entitled "Unclogging America's Arteries: Prescriptions for Healthier Highways" identified the 166 worst bottlenecks in the country and evaluated the benefits of removing them. By assigning monetary ...

Overcoming gaps and bottlenecks to advance precision agriculture

USDA-ARS?s Scientific Manuscript database

Maintaining a clear understanding of the technology gaps, knowledge needs, and training bottlenecks is required for improving adoption of precision agriculture. As an industry, precision agriculture embraces tools, methods, and practices that are constantly changing, requiring industry, education, a...

Inpatient care of small and sick newborns: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background Preterm birth is the leading cause of child death worldwide. Small and sick newborns require timely, high-quality inpatient care to survive. This includes provision of warmth, feeding support, safe oxygen therapy and effective phototherapy with prevention and treatment of infections. Inpatient care for newborns requires dedicated ward space, staffed by health workers with specialist training and skills. Many of the estimated 2.8 million newborns that die every year do not have access to such specialised care. Methods The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" (or factors that hinder the scale up) of maternal-newborn intervention packages. For this paper, we used quantitative and qualitative methods to analyse the bottleneck data, and combined these with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for inpatient care of small and sick newborns. Results Inpatient care of small and sick newborns is an intervention package highlighted by all country workshop participants as having critical health system challenges. Health system building blocks with the highest graded (significant or major) bottlenecks were health workforce (10 out of 12 countries) and health financing (10 out of 12 countries), followed by community ownership and partnership (9 out of 12 countries). Priority actions based on solution themes for these bottlenecks are discussed. Conclusions Whilst major bottlenecks to the scale-up of quality inpatient newborn care are present, effective solutions exist. For all countries included, there is a critical need for a neonatal nursing cadre. Small and sick newborns require increased, sustained funding with specific insurance schemes to cover inpatient care and avoid catastrophic out-of-pocket payments. Core competencies, by level of care, should be defined for monitoring of newborn inpatient care, as with emergency obstetric care. Rather than fatalism that small and sick newborns will die, community interventions need to create demand for accessible, high-quality, family-centred inpatient care, including kangaroo mother care, so that every newborn can survive and thrive. PMID:26391335

Addressing the medicinal chemistry bottleneck: a lean approach to centralized purification.

PubMed

Weller, Harold N; Nirschl, David S; Paulson, James L; Hoffman, Steven L; Bullock, William H

2012-09-10

The use of standardized lean manufacturing principles to improve drug discovery productivity is often thought to be at odds with fostering innovation. This manuscript describes how selective implementation of a lean optimized process, in this case centralized purification for medicinal chemistry, can improve operational productivity and increase scientist time available for innovation. A description of the centralized purification process is provided along with both operational and impact (productivity) metrics, which indicate lower cost, higher output, and presumably more free time for innovation as a result of the process changes described.

Lexical Access and Dual-Task Performance: Determining the Locus of the Bottleneck

NASA Technical Reports Server (NTRS)

Allen, Phil

2004-01-01

During the two years of funding for NASA Grant "NCC21325, Lexical access and dual-task performance: Determining the locus of the bottleneck," we completed three experiments involving the psychological refractory period (PRP) and word frequency.

Management of Knowledge Representation Standards Activities

NASA Technical Reports Server (NTRS)

Patil, Ramesh S. (Principal Investigator)

1993-01-01

This report describes the efforts undertaken over the last two years to identify the issues underlying the current difficulties in sharing and reuse, and a community wide initiative to overcome them. First, we discuss four bottlenecks to sharing and reuse, present a vision of a future in which these bottlenecks have been ameliorated, and describe the efforts of the initiative's four working groups to address these bottlenecks. We then address the supporting technology and infrastructure that is critical to enabling the vision of the future. Finally, we consider topics of longer-range interest by reviewing some of the research issues raised by our vision.

Reduced genetic variation and the success of an invasive species.

PubMed

Tsutsui, N D; Suarez, A V; Holway, D A; Case, T J

2000-05-23

Despite the severe ecological and economic damage caused by introduced species, factors that allow invaders to become successful often remain elusive. Of invasive taxa, ants are among the most widespread and harmful. Highly invasive ants are often unicolonial, forming supercolonies in which workers and queens mix freely among physically separate nests. By reducing costs associated with territoriality, unicolonial species can attain high worker densities, allowing them to achieve interspecific dominance. Here we examine the behavior and population genetics of the invasive Argentine ant (Linepithema humile) in its native and introduced ranges, and we provide a mechanism to explain its success as an invader. Using microsatellite markers, we show that a population bottleneck has reduced the genetic diversity of introduced populations. This loss is associated with reduced intraspecific aggression among spatially separate nests, and leads to the formation of interspecifically dominant supercolonies. In contrast, native populations are more genetically variable and exhibit pronounced intraspecific aggression. Although reductions in genetic diversity are generally considered detrimental, these findings provide an example of how a genetic bottleneck can lead to widespread ecological success. In addition, these results provide insights into the origin and evolution of unicoloniality, which is often considered a challenge to kin selection theory.

Nutritional Attributes, Substitutability, Scalability, and Environmental Intensity of an Illustrative Subset of Current and Future Protein Sources for Aquaculture Feeds: Joint Consideration of Potential Synergies and Trade-offs.

PubMed

Pelletier, Nathan; Klinger, Dane H; Sims, Neil A; Yoshioka, Janice-Renee; Kittinger, John N

2018-05-15

Aquaculture is anticipated to play an increasingly important role in global food security because it may represent one of the best opportunities to increase the availability of healthy animal protein in the context of resource and environmental constraints. However, the growth and sustainability of the aquaculture industry faces important bottlenecks with respect to feed resources, which may be derived from diverse sources. Here, using a small but representative subset of potential aquafeed inputs (which we selected to highlight a range of relevant attributes), we review a core suite of considerations that need to be accommodated in concert in order to overcome key bottlenecks to the continued development and expansion of the aquaculture industry. Specifically, we evaluate the nutritional attributes, substitutability, scalability, and resource and environmental intensity of each input. On this basis, we illustrate a range of potential synergies and trade-offs within and across attributes that are characteristic of ingredient types. We posit that the recognition and management of such synergies and trade-offs is imperative to satisfying the multi-objective decision-making associated with sustainable increases in future aquaculture production.

Species mtDNA genetic diversity explained by infrapopulation size in a host-symbiont system.

PubMed

Doña, Jorge; Moreno-García, Marina; Criscione, Charles D; Serrano, David; Jovani, Roger

2015-12-01

Understanding what shapes variation in genetic diversity among species remains a major challenge in evolutionary ecology, and it has been seldom studied in parasites and other host-symbiont systems. Here, we studied mtDNA variation in a host-symbiont non-model system: 418 individual feather mites from 17 feather mite species living on 17 different passerine bird species. We explored how a surrogate of census size, the median infrapopulation size (i.e., the median number of individual parasites per infected host individual), explains mtDNA genetic diversity. Feather mite species genetic diversity was positively correlated with mean infrapopulation size, explaining 34% of the variation. As expected from the biology of feather mites, we found bottleneck signatures for most of the species studied but, in particular, three species presented extremely low mtDNA diversity values given their infrapopulation size. Their star-like haplotype networks (in contrast with more reticulated networks for the other species) suggested that their low genetic diversity was the consequence of severe bottlenecks or selective sweeps. Our study shows for the first time that mtDNA diversity can be explained by infrapopulation sizes, and suggests that departures from this relationship could be informative of underlying ecological and evolutionary processes.

An initial assessment of freight bottlenecks on highways.

DOT National Transportation Integrated Search

2005-10-01

This white paper is an initial effort to identify and quantify, on a national basis, highway bottlenecks that delay trucks and increase costs to businesses and consumers. The paper is the first to look specifically at the impacts and costs of highway...

Microscopic theory of traffic-flow instability governing traffic breakdown at highway bottlenecks: Growing wave of increase in speed in synchronized flow.

PubMed

Kerner, Boris S

2015-12-01

We have revealed a growing local speed wave of increase in speed that can randomly occur in synchronized flow (S) at a highway bottleneck. The development of such a traffic flow instability leads to free flow (F) at the bottleneck; therefore, we call this instability an S→F instability. Whereas the S→F instability leads to a local increase in speed (growing acceleration wave), in contrast, the classical traffic flow instability introduced in the 1950s-1960s and incorporated later in a huge number of traffic flow models leads to a growing wave of a local decrease in speed (growing deceleration wave). We have found that the S→F instability can occur only if there is a finite time delay in driver overacceleration. The initial speed disturbance of increase in speed (called "speed peak") that initiates the S→F instability occurs usually at the downstream front of synchronized flow at the bottleneck. There can be many speed peaks with random amplitudes that occur randomly over time. It has been found that the S→F instability exhibits a nucleation nature: Only when a speed peak amplitude is large enough can the S→F instability occur; in contrast, speed peaks of smaller amplitudes cause dissolving speed waves of a local increase in speed (dissolving acceleration waves) in synchronized flow. We have found that the S→F instability governs traffic breakdown-a phase transition from free flow to synchronized flow (F→S transition) at the bottleneck: The nucleation nature of the S→F instability explains the metastability of free flow with respect to an F→S transition at the bottleneck.

Microscopic theory of traffic-flow instability governing traffic breakdown at highway bottlenecks: Growing wave of increase in speed in synchronized flow

NASA Astrophysics Data System (ADS)

Kerner, Boris S.

2015-12-01

We have revealed a growing local speed wave of increase in speed that can randomly occur in synchronized flow (S) at a highway bottleneck. The development of such a traffic flow instability leads to free flow (F) at the bottleneck; therefore, we call this instability an S →F instability. Whereas the S →F instability leads to a local increase in speed (growing acceleration wave), in contrast, the classical traffic flow instability introduced in the 1950s-1960s and incorporated later in a huge number of traffic flow models leads to a growing wave of a local decrease in speed (growing deceleration wave). We have found that the S →F instability can occur only if there is a finite time delay in driver overacceleration. The initial speed disturbance of increase in speed (called "speed peak") that initiates the S →F instability occurs usually at the downstream front of synchronized flow at the bottleneck. There can be many speed peaks with random amplitudes that occur randomly over time. It has been found that the S →F instability exhibits a nucleation nature: Only when a speed peak amplitude is large enough can the S →F instability occur; in contrast, speed peaks of smaller amplitudes cause dissolving speed waves of a local increase in speed (dissolving acceleration waves) in synchronized flow. We have found that the S →F instability governs traffic breakdown—a phase transition from free flow to synchronized flow (F →S transition) at the bottleneck: The nucleation nature of the S →F instability explains the metastability of free flow with respect to an F →S transition at the bottleneck.

Tetracycline Selective Pressure and Homologous Recombination Shape the Evolution of Chlamydia suis: A Recently Identified Zoonotic Pathogen.

PubMed

Joseph, Sandeep J; Marti, Hanna; Didelot, Xavier; Read, Timothy D; Dean, Deborah

2016-09-02

Species closely related to the human pathogen Chlamydia trachomatis (Ct) have recently been found to cause zoonotic infections, posing a public health threat especially in the case of tetracycline resistant Chlamydia suis (Cs) strains. These strains acquired a tet(C)-containing cassette via horizontal gene transfer (HGT). Genomes of 11 Cs strains from various tissues were sequenced to reconstruct evolutionary pathway(s) for tet(C) HGT. Cs had the highest recombination rate of Chlamydia species studied to date. Admixture occurred among Cs strains and with Chlamydia muridarum but not with Ct Although in vitro tet(C) cassette exchange with Ct has been documented, in vivo evidence may require examining human samples from Ct and Cs co-infected sites. Molecular-clock dating indicated that ancestral clades of resistant Cs strains predated the 1947 discovery of tetracycline, which was subsequently used in animal feed. The cassette likely spread throughout Cs strains by homologous recombination after acquisition from an external source, and our analysis suggests Betaproteobacteria as the origin. Selective pressure from tetracycline may be responsible for recent bottlenecks in Cs populations. Since tetracycline is an important antibiotic for treating Ct, zoonotic infections at mutual sites of infection indicate the possibility for cassette transfer and major public health repercussions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Molecular evolution of the Bovini tribe (Bovidae, Bovinae): Is there evidence of rapid evolution or reduced selective constraint in Domestic cattle?

PubMed Central

MacEachern, Sean; McEwan, John; McCulloch, Alan; Mather, Andrew; Savin, Keith; Goddard, Mike

2009-01-01

Background If mutation within the coding region of the genome is largely not adaptive, the ratio of nonsynonymous (dN) to synonymous substitutions (dS) per site (dN/dS) should be approximately equal among closely related species. Furthermore, dN/dS in divergence between species should be equivalent to dN/dS in polymorphisms. This hypothesis is of particular interest in closely related members of the Bovini tribe, because domestication has promoted rapid phenotypic divergence through strong artificial selection of some species while others remain undomesticated. We examined a number of genes that may be involved in milk production in Domestic cattle and a number of their wild relatives for evidence that domestication had affected molecular evolution. Elevated rates of dN/dS were further queried to determine if they were the result of positive selection, low effective population size (Ne) or reduced selective constraint. Results We have found that the domestication process has contributed to higher dN/dS ratios in cattle, especially in the lineages leading to the Domestic cow (Bos taurus) and Mithan (Bos frontalis) and within some breeds of Domestic cow. However, the high rates of dN/dS polymorphism within B. taurus when compared to species divergence suggest that positive selection has not elevated evolutionary rates in these genes. Likewise, the low rate of dN/dS in Bison, which has undergone a recent population bottleneck, indicates a reduction in population size alone is not responsible for these observations. Conclusion The effect of selection depends on effective population size and the selection coefficient (Nes). Typically under domestication both selection pressure for traits important in fitness in the wild and Ne are reduced. Therefore, reduced selective constraint could be responsible for the observed elevated evolutionary ratios in domesticated species, especially in B. taurus and B. frontalis, which have the highest dN/dS in the Bovini. This may have important implications for tests of selection such as the McDonald-Kreitman test. Surprisingly we have also detected a significant difference in the supposed neutral substitution rate between synonymous and noncoding sites in the Bovine genome, with a 30% higher rate of substitution at synonymous sites. This is due, at least in part, to an excess of the highly mutable CpG dinucleotides at synonymous sites, which will have implications for time of divergence estimates from molecular data. PMID:19393048

Genetic and life-history consequences of extreme climate events

PubMed Central

Mangel, Marc; Jesensek, Dusan; Garza, John Carlos; Crivelli, Alain J.

2017-01-01

Climate change is predicted to increase the frequency and intensity of extreme climate events. Tests on empirical data of theory-based predictions on the consequences of extreme climate events are thus necessary to understand the adaptive potential of species and the overarching risks associated with all aspects of climate change. We tested predictions on the genetic and life-history consequences of extreme climate events in two populations of marble trout Salmo marmoratus that have experienced severe demographic bottlenecks due to flash floods. We combined long-term field and genotyping data with pedigree reconstruction in a theory-based framework. Our results show that after flash floods, reproduction occurred at a younger age in one population. In both populations, we found the highest reproductive variance in the first cohort born after the floods due to a combination of fewer parents and higher early survival of offspring. A small number of parents allowed for demographic recovery after the floods, but the genetic bottleneck further reduced genetic diversity in both populations. Our results also elucidate some of the mechanisms responsible for a greater prevalence of faster life histories after the extreme event. PMID:28148745

Low Dose X-Ray Speckle Visibility Spectroscopy Reveals Nanoscale Dynamics in Radiation Sensitive Ionic Liquids

NASA Astrophysics Data System (ADS)

Verwohlt, Jan; Reiser, Mario; Randolph, Lisa; Matic, Aleksandar; Medina, Luis Aguilera; Madsen, Anders; Sprung, Michael; Zozulya, Alexey; Gutt, Christian

2018-04-01

X-ray radiation damage provides a serious bottleneck for investigating microsecond to second dynamics on nanometer length scales employing x-ray photon correlation spectroscopy. This limitation hinders the investigation of real time dynamics in most soft matter and biological materials which can tolerate only x-ray doses of kGy and below. Here, we show that this bottleneck can be overcome by low dose x-ray speckle visibility spectroscopy. Employing x-ray doses of 22-438 kGy and analyzing the sparse speckle pattern of count rates as low as 6.7 ×10-3 per pixel, we follow the slow nanoscale dynamics of an ionic liquid (IL) at the glass transition. At the prepeak of nanoscale order in the IL, we observe complex dynamics upon approaching the glass transition temperature TG with a freezing in of the alpha relaxation and a multitude of millisecond local relaxations existing well below TG . We identify this fast relaxation as being responsible for the increasing development of nanoscale order observed in ILs at temperatures below TG .

Dynamic bottleneck elimination in mattress manufacturing line using theory of constraints.

PubMed

Gundogar, Emin; Sari, Murat; Kokcam, Abdullah H

2016-01-01

There is a tough competition in the furniture sector like other sectors. Along with the varying product range, production system should also be renewed on a regular basis and the production costs should be kept under control. In this study, spring mattress manufacturing line of a furniture manufacturing company is analyzed. The company wants to increase its production output with new investments. The objective is to find the bottlenecks in production line in order to balance the semi-finished material flow. These bottlenecks are investigated and several different scenarios are tested to improve the current manufacturing system. The problem with a main theme based on the elimination of the bottleneck is solved using Goldratt and Cox's theory of constraints with a simulation based heuristic method. Near optimal alternatives are determined by system models built in Arena 13.5 simulation software. Results show that approximately 46 % capacity enhancements with 2 buffer stocks have increased average production by 88.8 %.

Using barcoded Zika virus to assess virus population structure in vitro and in Aedes aegypti mosquitoes.

PubMed

Weger-Lucarelli, James; Garcia, Selene M; Rückert, Claudia; Byas, Alex; O'Connor, Shelby L; Aliota, Matthew T; Friedrich, Thomas C; O'Connor, David H; Ebel, Gregory D

2018-06-20

Arboviruses such as Zika virus (ZIKV, Flaviviridae; Flavivirus) must replicate in both mammalian and insect hosts possessing strong immune defenses. Accordingly, transmission between and replication within hosts involves genetic bottlenecks, during which viral population size and genetic diversity may be significantly reduced. To help quantify these bottlenecks and their effects, we constructed 4 "barcoded" ZIKV populations that theoretically contain thousands of barcodes each. After identifying the most diverse barcoded virus, we passaged this virus 3 times in 2 mammalian and mosquito cell lines and characterized the population using deep sequencing of the barcoded region of the genome. C6/36 maintain higher barcode diversity, even after 3 passages, than Vero. Additionally, field-caught mosquitoes exposed to the virus to assess bottlenecks in a natural host. A progressive reduction in barcode diversity occurred throughout systemic infection of these mosquitoes. Differences in bottlenecks during systemic spread were observed between different populations of Aedes aegypti. Copyright © 2018. Published by Elsevier Inc.

A recent bottleneck of Y chromosome diversity coincides with a global change in culture.

PubMed

Karmin, Monika; Saag, Lauri; Vicente, Mário; Wilson Sayres, Melissa A; Järve, Mari; Talas, Ulvi Gerst; Rootsi, Siiri; Ilumäe, Anne-Mai; Mägi, Reedik; Mitt, Mario; Pagani, Luca; Puurand, Tarmo; Faltyskova, Zuzana; Clemente, Florian; Cardona, Alexia; Metspalu, Ene; Sahakyan, Hovhannes; Yunusbayev, Bayazit; Hudjashov, Georgi; DeGiorgio, Michael; Loogväli, Eva-Liis; Eichstaedt, Christina; Eelmets, Mikk; Chaubey, Gyaneshwer; Tambets, Kristiina; Litvinov, Sergei; Mormina, Maru; Xue, Yali; Ayub, Qasim; Zoraqi, Grigor; Korneliussen, Thorfinn Sand; Akhatova, Farida; Lachance, Joseph; Tishkoff, Sarah; Momynaliev, Kuvat; Ricaut, François-Xavier; Kusuma, Pradiptajati; Razafindrazaka, Harilanto; Pierron, Denis; Cox, Murray P; Sultana, Gazi Nurun Nahar; Willerslev, Rane; Muller, Craig; Westaway, Michael; Lambert, David; Skaro, Vedrana; Kovačevic, Lejla; Turdikulova, Shahlo; Dalimova, Dilbar; Khusainova, Rita; Trofimova, Natalya; Akhmetova, Vita; Khidiyatova, Irina; Lichman, Daria V; Isakova, Jainagul; Pocheshkhova, Elvira; Sabitov, Zhaxylyk; Barashkov, Nikolay A; Nymadawa, Pagbajabyn; Mihailov, Evelin; Seng, Joseph Wee Tien; Evseeva, Irina; Migliano, Andrea Bamberg; Abdullah, Syafiq; Andriadze, George; Primorac, Dragan; Atramentova, Lubov; Utevska, Olga; Yepiskoposyan, Levon; Marjanovic, Damir; Kushniarevich, Alena; Behar, Doron M; Gilissen, Christian; Vissers, Lisenka; Veltman, Joris A; Balanovska, Elena; Derenko, Miroslava; Malyarchuk, Boris; Metspalu, Andres; Fedorova, Sardana; Eriksson, Anders; Manica, Andrea; Mendez, Fernando L; Karafet, Tatiana M; Veeramah, Krishna R; Bradman, Neil; Hammer, Michael F; Osipova, Ludmila P; Balanovsky, Oleg; Khusnutdinova, Elza K; Johnsen, Knut; Remm, Maido; Thomas, Mark G; Tyler-Smith, Chris; Underhill, Peter A; Willerslev, Eske; Nielsen, Rasmus; Metspalu, Mait; Villems, Richard; Kivisild, Toomas

2015-04-01

It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males. © 2015 Karmin et al.; Published by Cold Spring Harbor Laboratory Press.

Recycling policies and programmes for PET drink bottles in Mexico.

PubMed

Schwanse, Elvira

2011-09-01

Transition and emerging economies confront a steadily increasing generation of municipal solid waste in the form of disposable packaging. The following article reports the situation of soft drink bottles made of polyethylene terephthalate (PET) in Mexico. Since 2002 schemes following the European Green Dot principle have been partly implemented to place responsibility on the producer, mainly soft drink bottlers. Private stakeholders are responsible for national recovery activities. Meanwhile Government presence to promote recovery is absent. Of post-consumer PET 75% is exported, and the newly created bottle-to-bottle (BTB) PET industry is confronted with bottlenecks in their post-consumer PET supply.

Novel Digital Features Discriminate Between Drought Resistant and Drought Sensitive Rice Under Controlled and Field Conditions.

PubMed

Duan, Lingfeng; Han, Jiwan; Guo, Zilong; Tu, Haifu; Yang, Peng; Zhang, Dong; Fan, Yuan; Chen, Guoxing; Xiong, Lizhong; Dai, Mingqiu; Williams, Kevin; Corke, Fiona; Doonan, John H; Yang, Wanneng

2018-01-01

Dynamic quantification of drought response is a key issue both for variety selection and for functional genetic study of rice drought resistance. Traditional assessment of drought resistance traits, such as stay-green and leaf-rolling, has utilized manual measurements, that are often subjective, error-prone, poorly quantified and time consuming. To relieve this phenotyping bottleneck, we demonstrate a feasible, robust and non-destructive method that dynamically quantifies response to drought, under both controlled and field conditions. Firstly, RGB images of individual rice plants at different growth points were analyzed to derive 4 features that were influenced by imposition of drought. These include a feature related to the ability to stay green, which we termed greenness plant area ratio (GPAR) and 3 shape descriptors [total plant area/bounding rectangle area ratio (TBR), perimeter area ratio (PAR) and total plant area/convex hull area ratio (TCR)]. Experiments showed that these 4 features were capable of discriminating reliably between drought resistant and drought sensitive accessions, and dynamically quantifying the drought response under controlled conditions across time (at either daily or half hourly time intervals). We compared the 3 shape descriptors and concluded that PAR was more robust and sensitive to leaf-rolling than the other shape descriptors. In addition, PAR and GPAR proved to be effective in quantification of drought response in the field. Moreover, the values obtained in field experiments using the collection of rice varieties were correlated with those derived from pot-based experiments. The general applicability of the algorithms is demonstrated by their ability to probe archival Miscanthus data previously collected on an independent platform. In conclusion, this image-based technology is robust providing a platform-independent tool for quantifying drought response that should be of general utility for breeding and functional genomics in future.

Reducing the Analytical Bottleneck for Domain Scientists: Lessons from a Climate Data Visualization Case Study

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

Dasgupta, Aritra; Poco, Jorge; Bertini, Enrico

2016-01-01

The gap between large-scale data production rate and the rate of generation of data-driven scientific insights has led to an analytical bottleneck in scientific domains like climate, biology, etc. This is primarily due to the lack of innovative analytical tools that can help scientists efficiently analyze and explore alternative hypotheses about the data, and communicate their findings effectively to a broad audience. In this paper, by reflecting on a set of successful collaborative research efforts between with a group of climate scientists and visualization researchers, we introspect how interactive visualization can help reduce the analytical bottleneck for domain scientists.

Haplotype structure in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers

PubMed Central

Im, Kate M.; Kirchhoff, Tomas; Wang, Xianshu; Green, Todd; Chow, Clement Y.; Vijai, Joseph; Korn, Joshua; Gaudet, Mia M.; Fredericksen, Zachary; Pankratz, V. Shane; Guiducci, Candace; Crenshaw, Andrew; McGuffog, Lesley; Kartsonaki, Christiana; Morrison, Jonathan; Healey, Sue; Sinilnikova, Olga M.; Mai, Phuong L.; Greene, Mark H.; Piedmonte, Marion; Rubinstein, Wendy S.; Hogervorst, Frans B.; Rookus, Matti A.; Collée, J. Margriet; Hoogerbrugge, Nicoline; van Asperen, Christi J.; Meijers-Heijboer, Hanne E. J.; Van Roozendaal, Cees E.; Caldes, Trinidad; Perez-Segura, Pedro; Jakubowska, Anna; Lubinski, Jan; Huzarski, Tomasz; Blecharz, Paweł; Nevanlinna, Heli; Aittomäki, Kristiina; Lazaro, Conxi; Blanco, Ignacio; Barkardottir, Rosa B.; Montagna, Marco; D'Andrea, Emma; Devilee, Peter; Olopade, Olufunmilayo I.; Neuhausen, Susan L.; Peissel, Bernard; Bonanni, Bernardo; Peterlongo, Paolo; Singer, Christian F.; Rennert, Gad; Lejbkowicz, Flavio; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Toland, Amanda Ewart; Caligo, Maria Adelaide; Beattie, Mary S.; Chan, Salina; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Phelan, Catherine; Narod, Steven; John, Esther M.; Hopper, John L.; Buys, Saundra S.; Daly, Mary B.; Southey, Melissa C.; Terry, Mary-Beth; Tung, Nadine; Hansen, Thomas v. O.; Osorio, Ana; Benitez, Javier; Durán, Mercedes; Weitzel, Jeffrey N.; Garber, Judy; Hamann, Ute; Peock, Susan; Cook, Margaret; Oliver, Clare T.; Frost, Debra; Platte, Radka; Evans, D. Gareth; Eeles, Ros; Izatt, Louise; Paterson, Joan; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Porteous, Mary; Walker, Lisa; Rogers, Mark T.; Side, Lucy E.; Godwin, Andrew K.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Laitman, Yael; Meindl, Alfons; Deissler, Helmut; Varon-Mateeva, Raymonda; Preisler-Adams, Sabine; Kast, Karin; Venat-Bouvet, Laurence; Stoppa-Lyonnet, Dominique; Chenevix-Trench, Georgia; Easton, Douglas F.; Klein, Robert J.; Daly, Mark J.; Friedman, Eitan; Dean, Michael; Clark, Andrew G.; Altshuler, David M.; Antoniou, Antonis C.; Couch, Fergus J.; Offit, Kenneth; Gold, Bert

2011-01-01

Abstract Three founder mutations in BRCA1 and BRCA2 contribute to the risk of hereditary breast and ovarian cancer in Ashkenazi Jews (AJ). They are observed at increased frequency in the AJ compared to other BRCA mutations in Caucasian non-Jews (CNJ). Several authors have proposed that elevated allele frequencies in the surrounding genomic regions reflect adaptive or balancing selection. Such proposals predict long-range linkage dis-equilibrium (LD) resulting from a selective sweep, although genetic drift in a founder population may also act to create long-distance LD. To date, few studies have used the tools of statistical genomics to examine the likelihood of long-range LD at a deleterious locus in a population that faced a genetic bottleneck. We studied the genotypes of hundreds of women from a large international consortium of BRCA1 and BRCA2 mutation carriers and found that AJ women exhibited long-range haplotypes compared to CNJ women. More than 50% of the AJ chromosomes with the BRCA1 185delAG mutation share an identical 2.1 Mb haplotype and nearly 16% of AJ chromosomes carrying the BRCA2 6174delT mutation share a 1.4 Mb haplotype. Simulations based on the best inference of Ashkenazi population demography indicate that long-range haplotypes are expected in the context of a genome-wide survey. Our results are consistent with the hypothesis that a local bottleneck effect from population size constriction events could by chance have resulted in the large haplotype blocks observed at high frequency in the BRCA1 and BRCA2 regions of Ashkenazi Jews. PMID:21597964

Ultrathin and Ion-Selective Janus Membranes for High-Performance Osmotic Energy Conversion.

PubMed

Zhang, Zhen; Sui, Xin; Li, Pei; Xie, Ganhua; Kong, Xiang-Yu; Xiao, Kai; Gao, Longcheng; Wen, Liping; Jiang, Lei

2017-07-05

The osmotic energy existing in fluids is recognized as a promising "blue" energy source that can help solve the global issues of energy shortage and environmental pollution. Recently, nanofluidic channels have shown great potential for capturing this worldwide energy because of their novel transport properties contributed by nanoconfinement. However, with respect to membrane-scale porous systems, high resistance and undesirable ion selectivity remain bottlenecks, impeding their applications. The development of thinner, low-resistance membranes, meanwhile promoting their ion selectivity, is a necessity. Here, we engineered ultrathin and ion-selective Janus membranes prepared via the phase separation of two block copolymers, which enable osmotic energy conversion with power densities of approximately 2.04 W/m 2 by mixing natural seawater and river water. Both experiments and continuum simulation help us to understand the mechanism for how membrane thickness and channel structure dominate the ion transport process and overall device performance, which can serve as a general guiding principle for the future design of nanochannel membranes for high-energy concentration cells.

Mule deer and pronghorn migration in western Wyoming

USGS Publications Warehouse

Sawyer, H.; Lindzey, F.; McWhirter, D.

2005-01-01

Migratory mule deer (Odocoileus hemionus) and pronghorn (Antilocapra americana) populations rely on seasonal ranges to meet their annual nutritional and energetic requirements. Because seasonal ranges often occur great distances apart and across a mix of vegetation types and land ownership, maintaining migration corridors to and from these ranges can be difficult, especially if managers do not have detailed information on mule deer and pronghorn seasonal movements. We captured, radiomarked, and monitored mule deer (n = 171) and pronghorn (n = 34) in western Wyoming to document seasonal distribution patterns and migration routes. Mule deer and pronghorn migrated 20-158 km and 116-258 km, respectively, between seasonal ranges. These distances represented the longest recorded migrations for either species. We identified a number of bottlenecks along the migration routes of mule deer and pronghorn, but the most critical appeared to be the 1.6-km-wide Trapper's Point bottleneck, which was used by both mule deer and pronghorn during their spring and autumn migrations. Housing developments and roadways apparently have reduced the effective width of this bottleneck to <0.8 km. We estimate 2,500-3,500 mule deer and 1,500-2,000 pronghorn move through the bottleneck twice a year during spring and autumn migrations. Identification and protection of migration corridors and bottlenecks will be necessary to maintain mule deer and pronghorn populations throughout their range.

Bottlenecks in the implementation of essential screening tests in antenatal care: Syphilis, HIV, and anemia testing in rural Tanzania and Uganda.

PubMed

Baker, Ulrika; Okuga, Monica; Waiswa, Peter; Manzi, Fatuma; Peterson, Stefan; Hanson, Claudia

2015-06-01

To identify and compare implementation bottlenecks for effective coverage of screening for syphilis, HIV, and anemia in antenatal care in rural Tanzania and Uganda; and explore the underlying determinants and perceived solutions to overcome these bottlenecks. In this multiple case study, we analyzed data collected as part of the Expanded Quality Management Using Information Power (EQUIP) project between November 2011 and April 2014. Indicators from household interviews (n=4415 mothers) and health facility surveys (n=122) were linked to estimate coverage in stages of implementation between which bottlenecks can be identified. Key informant interviews (n=15) were conducted to explore underlying determinants and analyzed using a framework approach. Large differences in implementation were found within and between countries. Availability and effective coverage was significantly lower for all tests in Uganda compared with Tanzania. Syphilis screening had the lowest availability and effective coverage in both countries. The main implementation bottleneck was poor availability of tests and equipment. Key informant interviews validated these findings and perceived solutions included the need for improved procurement at the central level. Our findings reinforce essential screening as a missed opportunity, caused by a lack of integration of funding and support for comprehensive antenatal care programs. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

A liquid chromatography method for determination of selected amino acids, coenzymes, growth regulators, and vitamins from Cicer arietinum (L.) and Solanum lycopersicum (L.).

PubMed

Meher, Hari Charan; Gajbhiye, Vijay T; Singh, Ghanendra

2012-01-01

A bottleneck in crosstalk and QC research has been the quantification of diverse chemotypes in small amounts of tissue. An LC-UV method for estimating 28 selected metabolites of the regulatory network underlying growth, development, maintenance, vital functions, defense reactions, and food quality is reported. The method was based on binary gradient resolutions of the analytes in an RP C18 column. The mobile phase comprised solvent A [water+0.1% trifluoroacetic acid (TFA)] and B (acetonitrile + 0.085% TFA at a flow rate of 1 ml/min. Twenty-three metabolites (selected amino acids, coenzymes, growth regulators, phenolic antioxidant, and water-soluble vitamins) were detected at 254 nm, and four fat-soluble vitamins at 280 nm. Jasmonic acid was quantified at 210 nm. The RSDs of peak area and retention time for each metabolite were <5.8%. The calibration graphs were linear with R2 values ranging from 0.98 to 0.99. The LODs (microg/mL) were about 0.01-1.0 for 23 metabolites quantified at 254 nm, 0.1-0.2 for fat-soluble vitamins, and 0.1 for jasmonic acid. The recoveries ranged from 80 to 105%, with RSDs of 2.8 to 11.2%. The method has been satisfactorily applied for determination of 28 metabolites from Cicer arietinum (L.) and Solanum lycopersicum (L.). It could be an alternative and competitive method of choice that can cheaply and easily perform routine analysis for food quality and targeted metabolomics of chickpea and tomato in response to stressors.

Viewer Perspective Affects Central Bottleneck Requirements in Spatial Translation Tasks

ERIC Educational Resources Information Center

Franz, Elizabeth A.; Sebastian, Alexandra; Hust, Christina; Norris, Tom

2008-01-01

A psychological refractory period (PRP) approach and the locus of slack logic were applied to examine the novel question of whether spatial translation processes can begin before the central bottleneck when effector or noneffector stimuli are processed from an egocentric (viewer-centered) perspective. In single tasks, trials requiring spatial…

Machine Learning. Part 1. A Historical and Methodological Analysis.

DTIC Science & Technology

1983-05-31

Machine learning has always been an integral part of artificial intelligence, and its methodology has evolved in concert with the major concerns of the field. In response to the difficulties of encoding ever-increasing volumes of knowledge in modern Al systems, many researchers have recently turned their attention to machine learning as a means to overcome the knowledge acquisition bottleneck. Part 1 of this paper presents a taxonomic analysis of machine learning organized primarily by learning strategies and secondarily by

Rational adaptation under task and processing constraints: implications for testing theories of cognition and action.

PubMed

Howes, Andrew; Lewis, Richard L; Vera, Alonso

2009-10-01

The authors assume that individuals adapt rationally to a utility function given constraints imposed by their cognitive architecture and the local task environment. This assumption underlies a new approach to modeling and understanding cognition-cognitively bounded rational analysis-that sharpens the predictive acuity of general, integrated theories of cognition and action. Such theories provide the necessary computational means to explain the flexible nature of human behavior but in doing so introduce extreme degrees of freedom in accounting for data. The new approach narrows the space of predicted behaviors through analysis of the payoff achieved by alternative strategies, rather than through fitting strategies and theoretical parameters to data. It extends and complements established approaches, including computational cognitive architectures, rational analysis, optimal motor control, bounded rationality, and signal detection theory. The authors illustrate the approach with a reanalysis of an existing account of psychological refractory period (PRP) dual-task performance and the development and analysis of a new theory of ordered dual-task responses. These analyses yield several novel results, including a new understanding of the role of strategic variation in existing accounts of PRP and the first predictive, quantitative account showing how the details of ordered dual-task phenomena emerge from the rational control of a cognitive system subject to the combined constraints of internal variance, motor interference, and a response selection bottleneck.

Ancient and Contemporary DNA Reveal a Pre-Human Decline but No Population Bottleneck Associated with Recent Human Persecution in the Kea (Nestor notabilis)

PubMed Central

Dussex, Nicolas; Rawlence, Nicolas J.; Robertson, Bruce C.

2015-01-01

The impact of population bottlenecks is an important factor to consider when assessing species survival. Population declines can considerably limit the evolutionary potential of species and make them more susceptible to stochastic events. New Zealand has a well documented history of decline of endemic avifauna related to human colonization. Here, we investigate the genetic effects of a recent population decline in the endangered kea (Nestor notabilis). Kea have undergone a long-lasting persecution between the late 1800s to 1970s where an estimated 150,000 kea were culled under a governmental bounty scheme. Kea now number 1,000–5,000 individuals in the wild and it is likely that the recent population decline may have reduced the genetic diversity of the species. Comparison of contemporary (n = 410), historical (n = 15) and fossil samples (n = 4) showed a loss of mitochondrial diversity since the end of the last glaciation (Otiran Glacial) but no loss of overall genetic diversity associated with the cull. Microsatellite data indicated a recent bottleneck for only one population and a range-wide decline in Ne dating back some 300 – 6,000 years ago, a period predating European arrival in NZ. These results suggest that despite a recent human persecution, kea might have experienced a large population decline before stabilizing in numbers prior to human settlement of New Zealand in response to Holocene changes in habitat distribution. Our study therefore highlights the need to understand the respective effects of climate change and human activities on endangered species dynamics when proposing conservation guidelines. PMID:25719752

Who has the D? How clear decision roles enhance organizational performance.

PubMed

Rogers, Paul; Blenko, Marcia

2006-01-01

Decisions are the coin of the realm in business. But even in highly respected companies, decisions can get stuck inside the organization like loose change. As a result, the entire decision-making process can stall, usually at one of four bottlenecks: global versus local, center versus business unit, function versus function, and inside versus outside partners. Decision-making bottlenecks can occur whenever there is ambiguity or tension over who gets to decide what. For example, do marketers or product developers get to decide the features of a new product? Should a major capital investment depend on the approval of the business unit that will own it, or should headquarters make the final call? Which decisions can be delegated to an outsourcing partner, and which must be made internally? Bain consultants Paul Rogers and Marcia Blenko use an approach called RAPID (recommend, agree, perform, input, and decide) to help companies unclog their decision-making bottlenecks by explicitly defining roles and responsibilities. For example, British American Tobacco struck a new balance between global and local decision making to take advantage of the company's scale while maintaining its agility in local markets. At Wyeth Pharmaceuticals, a growth opportunity revealed the need to push more decisions down to the business units. And at the UK department-store chain John Lewis, buyers and sales staff clarified their decision roles in order to implement a new strategy for selling its salt and pepper mills. When revamping its decision-making process, a company must take some practical steps: Align decision roles with the most important sources of value, make sure that decisions are made by the right people at the right levels of the organization, and let the people who will live with the new process help design it.

Sample treatments prior to capillary electrophoresis-mass spectrometry.

PubMed

Hernández-Borges, Javier; Borges-Miquel, Teresa M; Rodríguez-Delgado, Miguel Angel; Cifuentes, Alejandro

2007-06-15

Sample preparation is a crucial part of chemical analysis and in most cases can become the bottleneck of the whole analytical process. Its adequacy is a key factor in determining the success of the analysis and, therefore, careful selection and optimization of the parameters controlling sample treatment should be carried out. This work revises the different strategies that have been developed for sample preparation prior to capillary electrophoresis-mass spectrometry (CE-MS). Namely the present work presents an exhaustive and critical revision of the different samples treatments used together with on-line CE-MS including works published from January 2000 to July 2006.

Data-driven battery product development: Turn battery performance into a competitive advantage.

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

Sholklapper, Tal

Poor battery performance is a primary source of user dissatisfaction across a broad range of applications, and is a key bottleneck hindering the growth of mobile technology, wearables, electric vehicles, and grid energy storage. Engineering battery systems is difficult, requiring extensive testing for vendor selection, BMS programming, and application-specific lifetime testing. This work also generates huge quantities of data. This presentation will explain how to leverage this data to help ship quality products faster using fewer resources while ensuring safety and reliability in the field, ultimately turning battery performance into a competitive advantage.

Candidate loci involved in domestication and improvement detected by a published 90K wheat SNP array

PubMed Central

Gao, Lifeng; Zhao, Guangyao; Huang, Dawei; Jia, Jizeng

2017-01-01

Selection is one of the most important forces in crop evolution. Common wheat is a major world food crop and a typical allopolyploid with a huge and complex genome. We applied four approaches to detect loci selected in wheat during domestication and improvement. A total of 7,984 candidate loci were detected, accounting for 23.3% of all 34,317 SNPs analysed, a much higher proportion than estimated in previous reports. We constructed a first generation wheat selection map which revealed the following new insights on genome-wide selection: (1) diversifying selection acted by increasing, decreasing or not affecting gene frequencies; (2) the number of loci under selection during domestication was much higher than that during improvement; (3) the contribution to wheat improvement by the D sub-genome was relatively small due to the bottleneck of hexaploidisation and diversity can be expanded by using synthetic wheat and introgression lines; and (4) clustered selection regions occur throughout the wheat genome, including the centromere regions. This study will not only help future wheat breeding and evolutionary studies, but will also accelerate study of other crops, especially polyploids. PMID:28327671

76 FR 2748 - Competition in the Railroad Industry

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-14

...) (Bottleneck II), aff'd sub nom. MidAmerican Energy Co. v. STB, 169 F.3d 1099 (8th Cir. 1999). The Board also... segment-by-segment basis--can reasonably be applied in today's transportation world. In particular, we... through rates, and whether the reasoning in Great Northern Railway encompasses ``bottleneck'' situations...

Widening the Knowledge Acquisition Bottleneck for Constraint-Based Tutors

ERIC Educational Resources Information Center

Suraweera, Pramuditha; Mitrovic, Antonija; Martin, Brent

2010-01-01

Intelligent Tutoring Systems (ITS) are effective tools for education. However, developing them is a labour-intensive and time-consuming process. A major share of the effort is devoted to acquiring the domain knowledge that underlies the system's intelligence. The goal of this research is to reduce this knowledge acquisition bottleneck and better…

What's Feeling Got to Do with It? Decoding Emotional Bottlenecks in the History Classroom

ERIC Educational Resources Information Center

Middendorf, Joan; Mickute, Jolanta; Saunders, Tara; Najar, José; Clark-Huckstep, Andrew E.; Pace, David

2015-01-01

The understandings and preconceptions students bring into the history classroom can interfere with student learning. Analyses of student and professor interviews in light of emotional bottlenecks revealed two different, though related, student preconceptions: procedural preconceptions about history as a field of study and pre-existing worldviews…

The nocturnal bottleneck and the evolution of activity patterns in mammals.

PubMed

Gerkema, Menno P; Davies, Wayne I L; Foster, Russell G; Menaker, Michael; Hut, Roelof A

2013-08-22

In 1942, Walls described the concept of a 'nocturnal bottleneck' in placental mammals, where these species could survive only by avoiding daytime activity during times in which dinosaurs were the dominant taxon. Walls based this concept of a longer episode of nocturnality in early eutherian mammals by comparing the visual systems of reptiles, birds and all three extant taxa of the mammalian lineage, namely the monotremes, marsupials (now included in the metatherians) and placentals (included in the eutherians). This review describes the status of what has become known as the nocturnal bottleneck hypothesis, giving an overview of the chronobiological patterns of activity. We review the ecological plausibility that the activity patterns of (early) eutherian mammals were restricted to the night, based on arguments relating to endothermia, energy balance, foraging and predation, taking into account recent palaeontological information. We also assess genes, relating to light detection (visual and non-visual systems) and the photolyase DNA protection system that were lost in the eutherian mammalian lineage. Our conclusion presently is that arguments in favour of the nocturnal bottleneck hypothesis in eutherians prevail.

Origin of the correlations between exit times in pedestrian flows through a bottleneck

NASA Astrophysics Data System (ADS)

Nicolas, Alexandre; Touloupas, Ioannis

2018-01-01

Robust statistical features have emerged from the microscopic analysis of dense pedestrian flows through a bottleneck, notably with respect to the time gaps between successive passages. We pinpoint the mechanisms at the origin of these features thanks to simple models that we develop and analyse quantitatively. We disprove the idea that anticorrelations between successive time gaps (i.e. an alternation between shorter ones and longer ones) are a hallmark of a zipper-like intercalation of pedestrian lines and show that they simply result from the possibility that pedestrians from distinct ‘lines’ or directions cross the bottleneck within a short time interval. A second feature concerns the bursts of escapes, i.e. egresses that come in fast succession. Despite the ubiquity of exponential distributions of burst sizes, entailed by a Poisson process, we argue that anomalous (power-law) statistics arise if the bottleneck is nearly congested, albeit only in a tiny portion of parameter space. The generality of the proposed mechanisms implies that similar statistical features should also be observed for other types of particulate flows.

Percolation transition in dynamical traffic network with evolving critical bottlenecks.

PubMed

Li, Daqing; Fu, Bowen; Wang, Yunpeng; Lu, Guangquan; Berezin, Yehiel; Stanley, H Eugene; Havlin, Shlomo

2015-01-20

A critical phenomenon is an intrinsic feature of traffic dynamics, during which transition between isolated local flows and global flows occurs. However, very little attention has been given to the question of how the local flows in the roads are organized collectively into a global city flow. Here we characterize this organization process of traffic as "traffic percolation," where the giant cluster of local flows disintegrates when the second largest cluster reaches its maximum. We find in real-time data of city road traffic that global traffic is dynamically composed of clusters of local flows, which are connected by bottleneck links. This organization evolves during a day with different bottleneck links appearing in different hours, but similar in the same hours in different days. A small improvement of critical bottleneck roads is found to benefit significantly the global traffic, providing a method to improve city traffic with low cost. Our results may provide insights on the relation between traffic dynamics and percolation, which can be useful for efficient transportation, epidemic control, and emergency evacuation.

Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism

PubMed Central

Johnston, Iain G; Burgstaller, Joerg P; Havlicek, Vitezslav; Kolbe, Thomas; Rülicke, Thomas; Brem, Gottfried; Poulton, Jo; Jones, Nick S

2015-01-01

Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck. DOI: http://dx.doi.org/10.7554/eLife.07464.001 PMID:26035426

The Effect of an Extreme and Prolonged Population Bottleneck on Patterns of Deleterious Variation: Insights from the Greenlandic Inuit.

PubMed

Pedersen, Casper-Emil T; Lohmueller, Kirk E; Grarup, Niels; Bjerregaard, Peter; Hansen, Torben; Siegismund, Hans R; Moltke, Ida; Albrechtsen, Anders

2017-02-01

The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit we show that the Inuit have undergone a severe ∼20,000-year-long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population tested to date, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inuit show, at most, a slight increase in load compared to European, East Asian, and African populations. Specifically, we observe <4% increase in the number of derived deleterious alleles in the Inuit. In contrast, proxies for genetic load under a recessive model suggest that the Inuit have a significantly higher load (20% increase or more) compared to other less bottlenecked human populations. Forward simulations under realistic models of demography support our empirical findings, showing up to a 6% increase in the genetic load for the Inuit population across all models of dominance. Further, the Inuit population carries fewer deleterious variants than other human populations, but those that are present tend to be at higher frequency than in other populations. Overall, our results show how recent demographic history has affected patterns of deleterious variants in human populations. Copyright © 2017 by the Genetics Society of America.

Genetics of the Shimokita macaque population suggest an ancient bottleneck.

PubMed

Kawamoto, Yoshi; Tomari, Ken-ichiro; Kawai, Shizuka; Kawamoto, Sakie

2008-01-01

The macaque population of the Shimokita Peninsula represents the northernmost distribution of this species and is isolated from other populations in the Tohoku region of Japan. A previous protein-based study revealed a high level of genetic variability in this population and considerable differentiation from other populations. In order to reassess the genetic features of the Shimokita macaques, we examined 11 autosomal microsatellite loci and three Y chromosomal microsatellite loci. We observed considerable differentiation from other Japanese populations of macaques, but in contrast to the previous results, we observed significantly lower genetic variability in this population. There was a weak indication of a population bottleneck, suggesting a decay over time from an excess of heterozygotes that might be expected in the initial stages of a bottleneck. This may indicate that an ancient bottleneck occurred during the warm period after the last glacial period rather than a recent bottleneck due to hunting in modern times. The frequencies of private alleles were exceptionally high in the Shimokita population, suggesting that the difference in variability as determined in various studies was due to accidental sampling of marker loci with low power to resolve genetic variations in the protein-based studies. The assessments of interpopulation differentiation as determined using autosomal and Y chromosomal markers were highly correlated, and using both types of markers the Shimokita population was found to be the most differentiated of the study populations, probably due to infrequent gene flow with surrounding populations.

Bottlenecks to coral recovery in the Seychelles

NASA Astrophysics Data System (ADS)

Chong-Seng, K. M.; Graham, N. A. J.; Pratchett, M. S.

2014-06-01

Processes that affect recovery of coral assemblages require investigation because coral reefs are experiencing a diverse array of more frequent disturbances. Potential bottlenecks to coral recovery include limited larval supply, low rates of settlement, and high mortality of new recruits or juvenile corals. We investigated spatial variation in local abundance of scleractinian corals in the Seychelles at three distinct life history stages (recruits, juveniles, and adults) on reefs with differing benthic conditions. Following widespread coral loss due to the 1998 bleaching event, some reefs are recovering (i.e., relatively high scleractinian coral cover: `coral-dominated'), some reefs have low cover of living macrobenthos and unconsolidated rubble substrates (`rubble-dominated'), and some reefs have high cover of macroalgae (`macroalgal-dominated'). Rates of coral recruitment to artificial settlement tiles were similar across all reef conditions, suggesting that larval supply does not explain differential coral recovery across the three reef types. However, acroporid recruits were absent on macroalgal-dominated reefs (0.0 ± 0.0 recruits tile-1) in comparison to coral-dominated reefs (5.2 ± 1.6 recruits tile-1). Juvenile coral colony density was significantly lower on macroalgal-dominated reefs (2.4 ± 1.1 colonies m-2), compared to coral-dominated reefs (16.8 ± 2.4 m-2) and rubble-dominated reefs (33.1 ± 7.3 m-2), suggesting that macroalgal-dominated reefs have either a bottleneck to successful settlement on the natural substrates or a high post-settlement mortality bottleneck. Rubble-dominated reefs had very low cover of adult corals (10.0 ± 1.7 %) compared to coral-dominated reefs (33.4 ± 3.6 %) despite no statistical difference in their juvenile coral densities. A bottleneck caused by low juvenile colony survivorship on unconsolidated rubble-dominated reefs is possible, or alternatively, recruitment to rubble-dominated reefs has only recently begun. This study identified bottlenecks to recovery of coral assemblages that varied depending on post-disturbance habitat condition.

Scaling up quality care for mothers and newborns around the time of birth: an overview of methods and analyses of intervention-specific bottlenecks and solutions.

PubMed

Dickson, Kim E; Kinney, Mary V; Moxon, Sarah G; Ashton, Joanne; Zaka, Nabila; Simen-Kapeu, Aline; Sharma, Gaurav; Kerber, Kate J; Daelmans, Bernadette; Gülmezoglu, A; Mathai, Matthews; Nyange, Christabel; Baye, Martina; Lawn, Joy E

2015-01-01

The Every Newborn Action Plan (ENAP) and Ending Preventable Maternal Mortality targets cannot be achieved without high quality, equitable coverage of interventions at and around the time of birth. This paper provides an overview of the methodology and findings of a nine paper series of in-depth analyses which focus on the specific challenges to scaling up high-impact interventions and improving quality of care for mothers and newborns around the time of birth, including babies born small and sick. The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the ENAP process. Country workshops engaged technical experts to complete a tool designed to synthesise "bottlenecks" hindering the scale up of maternal-newborn intervention packages across seven health system building blocks. We used quantitative and qualitative methods and literature review to analyse the data and present priority actions relevant to different health system building blocks for skilled birth attendance, emergency obstetric care, antenatal corticosteroids (ACS), basic newborn care, kangaroo mother care (KMC), treatment of neonatal infections and inpatient care of small and sick newborns. The 12 countries included in our analysis account for the majority of global maternal (48%) and newborn (58%) deaths and stillbirths (57%). Our findings confirm previously published results that the interventions with the most perceived bottlenecks are facility-based where rapid emergency care is needed, notably inpatient care of small and sick newborns, ACS, treatment of neonatal infections and KMC. Health systems building blocks with the highest rated bottlenecks varied for different interventions. Attention needs to be paid to the context specific bottlenecks for each intervention to scale up quality care. Crosscutting findings on health information gaps inform two final papers on a roadmap for improvement of coverage data for newborns and indicate the need for leadership for effective audit systems. Achieving the Sustainable Development Goal targets for ending preventable mortality and provision of universal health coverage will require large-scale approaches to improving quality of care. These analyses inform the development of systematic, targeted approaches to strengthening of health systems, with a focus on overcoming specific bottlenecks for the highest impact interventions.

Scaling up quality care for mothers and newborns around the time of birth: an overview of methods and analyses of intervention-specific bottlenecks and solutions

PubMed Central

2015-01-01

Background The Every Newborn Action Plan (ENAP) and Ending Preventable Maternal Mortality targets cannot be achieved without high quality, equitable coverage of interventions at and around the time of birth. This paper provides an overview of the methodology and findings of a nine paper series of in-depth analyses which focus on the specific challenges to scaling up high-impact interventions and improving quality of care for mothers and newborns around the time of birth, including babies born small and sick. Methods The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the ENAP process. Country workshops engaged technical experts to complete a tool designed to synthesise "bottlenecks" hindering the scale up of maternal-newborn intervention packages across seven health system building blocks. We used quantitative and qualitative methods and literature review to analyse the data and present priority actions relevant to different health system building blocks for skilled birth attendance, emergency obstetric care, antenatal corticosteroids (ACS), basic newborn care, kangaroo mother care (KMC), treatment of neonatal infections and inpatient care of small and sick newborns. Results The 12 countries included in our analysis account for the majority of global maternal (48%) and newborn (58%) deaths and stillbirths (57%). Our findings confirm previously published results that the interventions with the most perceived bottlenecks are facility-based where rapid emergency care is needed, notably inpatient care of small and sick newborns, ACS, treatment of neonatal infections and KMC. Health systems building blocks with the highest rated bottlenecks varied for different interventions. Attention needs to be paid to the context specific bottlenecks for each intervention to scale up quality care. Crosscutting findings on health information gaps inform two final papers on a roadmap for improvement of coverage data for newborns and indicate the need for leadership for effective audit systems. Conclusions Achieving the Sustainable Development Goal targets for ending preventable mortality and provision of universal health coverage will require large-scale approaches to improving quality of care. These analyses inform the development of systematic, targeted approaches to strengthening of health systems, with a focus on overcoming specific bottlenecks for the highest impact interventions. PMID:26390820

Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons

PubMed Central

Arun-Chinnappa, Kiruba S.; McCurdy, David W.

2016-01-01

Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic-symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal–enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal–enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc-finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID:27252730

Fluctuating Selection in the Moran

PubMed Central

Dean, Antony M.; Lehman, Clarence; Yi, Xiao

2017-01-01

Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model, we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large, and the variance in selection is big. Lowering the frequency of fluctuations makes selection more directional, and so heterozygosity declines. We also show that fluctuating selection raises dn/ds ratios for polymorphism, not only by sweeping selected alleles into the population, but also by purging the neutral variants of selected alleles as they undergo repeated bottlenecks. Our analysis shows that randomly fluctuating selection increases the rate of evolution by increasing the probability of fixation. The impact is especially noticeable when the selection is strong and mutation is weak. Simulations show the increase in the rate of evolution declines as the rate of new mutations entering the population increases, an effect attributable to clonal interference. Intriguingly, fluctuating selection increases the dn/ds ratios for divergence more than for polymorphism, a pattern commonly seen in comparative genomics. Our model, which extends the classical neutral model of molecular evolution by incorporating random fluctuations in selection, accommodates a wide variety of observations, both neutral and selected, with economy. PMID:28108586

Independent Bottlenecks Characterize Colonization of Systemic Compartments and Gut Lymphoid Tissue by Salmonella

PubMed Central

Lim, Chee Han; Voedisch, Sabrina; Wahl, Benjamin; Rouf, Syed Fazle; Geffers, Robert

2014-01-01

Vaccination represents an important instrument to control typhoid fever in humans and protects mice from lethal infection with mouse pathogenic serovars of Salmonella species. Mixed infections with tagged Salmonella can be used in combination with probabilistic models to describe the dynamics of the infection process. Here we used mixed oral infections with tagged Salmonella strains to identify bottlenecks in the infection process in naïve and vaccinated mice. We established a next generation sequencing based method to characterize the composition of tagged Salmonella strains which offers a fast and reliable method to characterise the composition of genome-tagged Salmonella strains. We show that initial colonization of Salmonella was distinguished by a non-Darwinian selection of few bacteria setting up the infection independently in gut associated lymphoid tissue and systemic compartments. Colonization of Peyer's patches fuels the sustained spread of bacteria into mesenteric lymph nodes via dendritic cells. In contrast, infection of liver and spleen originated from an independent pool of bacteria. Vaccination only moderately reduced invasion of Peyer's patches but potently uncoupled bacterial populations present in different systemic compartments. Our data indicate that vaccination differentially skews the capacity of Salmonella to colonize systemic and gut immune compartments and provide a framework for the further dissection of infection dynamics. PMID:25079958

Molecular evolution and emergence of avian gammacoronaviruses.

PubMed

Jackwood, Mark W; Hall, David; Handel, Andreas

2012-08-01

Coronaviruses, which are single stranded, positive sense RNA viruses, are responsible for a wide variety of existing and emerging diseases in humans and other animals. The gammacoronaviruses primarily infect avian hosts. Within this genus of coronaviruses, the avian coronavirus infectious bronchitis virus (IBV) causes a highly infectious upper-respiratory tract disease in commercial poultry. IBV shows rapid evolution in chickens, frequently producing new antigenic types, which adds to the multiple serotypes of the virus that do not cross protect. Rapid evolution in IBV is facilitated by strong selection, large population sizes and high genetic diversity within hosts, and transmission bottlenecks between hosts. Genetic diversity within a host arises primarily by mutation, which includes substitutions, insertions and deletions. Mutations are caused both by the high error rate, and limited proof reading capability, of the viral RNA-dependent RNA-polymerase, and by recombination. Recombination also generates new haplotype diversity by recombining existing variants. Rapid evolution of avian coronavirus IBV makes this virus extremely difficult to diagnose and control, but also makes it an excellent model system to study viral genetic diversity and the mechanisms behind the emergence of coronaviruses in their natural host. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic Signatures of Demographic Changes in an Avian Top Predator during the Last Century: Bottlenecks and Expansions of the Eurasian Eagle Owl in the Iberian Peninsula

PubMed Central

Graciá, Eva; Ortego, Joaquín; Godoy, José Antonio; Pérez-García, Juan Manuel; Blanco, Guillermo; del Mar Delgado, María; Penteriani, Vincenzo; Almodóvar, Irene; Botella, Francisco; Sánchez-Zapata, José Antonio

2015-01-01

The study of the demographic history of species can help to understand the negative impact of recent population declines in organisms of conservation concern. Here, we use neutral molecular markers to explore the genetic consequences of the recent population decline and posterior recovery of the Eurasian eagle owl (Bubo bubo) in the Iberian Peninsula. During the last century, the species was the object of extermination programs, suffering direct persecution by hunters until the 70’s. Moreover, during the last decades the eagle owl was severely impacted by increased mortality due to electrocution and the decline of its main prey species, the European rabbit (Oryctolagus cuniculus). In recent times, the decrease of direct persecution and the implementation of some conservation schemes have allowed the species’ demographic recovery. Yet, it remains unknown to which extent the past population decline and the later expansion have influenced the current species’ pattern of genetic diversity. We used eight microsatellite markers to genotype 235 eagle owls from ten Spanish subpopulations and analyse the presence of genetic signatures attributable to the recent population fluctuations experienced by the species. We found moderate levels of differentiation among the studied subpopulations and Bayesian analyses revealed the existence of three genetic clusters that grouped subpopulations from central, south-western and south-eastern Spain. The observed genetic structure could have resulted from recent human-induced population fragmentation, a patchy distribution of prey populations and/or the philopatric behaviour and habitat selection of the species. We detected an old population bottleneck, which occurred approximately 10,000 years ago, and significant signatures of recent demographic expansions. However, we did not find genetic signatures for a recent bottleneck, which may indicate that population declines were not severe enough to leave detectable signals on the species genetic makeup or that such signals have been eroded by the rapid demographic recovery experienced by the species in recent years. PMID:26230922

The Paradox of the Diffusion of Innovations Research: Creating More Communication Bottlenecks Than Breaking Them.

ERIC Educational Resources Information Center

Melkote, Srinivas R.; Babbili, Anantha S.

The paradox of the diffusion of innovations research is that in its efforts to find ways and means of breaking the communication constraint in Third World countries, it has generated many bottlenecks that cumulatively constitute the major constraint: lack of an efficient system for delivering adequate and reliable information, knowledge, and…

Saccadic Eye Movements Impose a Natural Bottleneck on Visual Short-Term Memory

ERIC Educational Resources Information Center

Ohl, Sven; Rolfs, Martin

2017-01-01

Visual short-term memory (VSTM) is a crucial repository of information when events unfold rapidly before our eyes, yet it maintains only a fraction of the sensory information encoded by the visual system. Here, we tested the hypothesis that saccadic eye movements provide a natural bottleneck for the transition of fragile content in sensory memory…

Fair and efficient network congestion control based on minority game

NASA Astrophysics Data System (ADS)

Wang, Zuxi; Wang, Wen; Hu, Hanping; Deng, Zhaozhang

2011-12-01

Low link utility, RTT unfairness and unfairness of Multi-Bottleneck network are the existing problems in the present network congestion control algorithms at large. Through the analogy of network congestion control with the "El Farol Bar" problem, we establish a congestion control model based on minority game(MG), and then present a novel network congestion control algorithm based on the model. The result of simulations indicates that the proposed algorithm can make the achievements of link utility closing to 100%, zero packet lose rate, and small of queue size. Besides, the RTT unfairness and the unfairness of Multi-Bottleneck network can be solved, to achieve the max-min fairness in Multi-Bottleneck network, while efficiently weaken the "ping-pong" oscillation caused by the overall synchronization.

Emerging from the bottleneck: Benefits of the comparative approach to modern neuroscience

PubMed Central

Brenowitz, Eliot A.; Zakon, Harold H.

2015-01-01

Neuroscience historically exploited a wide diversity of animal taxa. Recently, however, research focused increasingly on a few model species. This trend accelerated with the genetic revolution, as genomic sequences and genetic tools became available for a few species, which formed a bottleneck. This coalescence on a small set of model species comes with several costs often not considered, especially in the current drive to use mice explicitly as models for human diseases. Comparative studies of strategically chosen non-model species can complement model species research and yield more rigorous studies. As genetic sequences and tools become available for many more species, we are poised to emerge from the bottleneck and once again exploit the rich biological diversity offered by comparative studies. PMID:25800324

Cultural hitchhiking and competition between patrilineal kin groups explain the post-Neolithic Y-chromosome bottleneck.

PubMed

Zeng, Tian Chen; Aw, Alan J; Feldman, Marcus W

2018-05-25

In human populations, changes in genetic variation are driven not only by genetic processes, but can also arise from cultural or social changes. An abrupt population bottleneck specific to human males has been inferred across several Old World (Africa, Europe, Asia) populations 5000-7000 BP. Here, bringing together anthropological theory, recent population genomic studies and mathematical models, we propose a sociocultural hypothesis, involving the formation of patrilineal kin groups and intergroup competition among these groups. Our analysis shows that this sociocultural hypothesis can explain the inference of a population bottleneck. We also show that our hypothesis is consistent with current findings from the archaeogenetics of Old World Eurasia, and is important for conceptions of cultural and social evolution in prehistory.

ovoD Co-selection: A Method for Enriching CRISPR/Cas9-Edited Alleles in Drosophila.

PubMed

Ewen-Campen, Ben; Perrimon, Norbert

2018-06-22

Screening for successful CRISPR/Cas9 editing events remains a time consuming technical bottleneck in the field of Drosophila genome editing. This step can be particularly laborious for events that do not cause a visible phenotype, or those which occur at relatively low frequency. A promising strategy to enrich for desired CRISPR events is to co-select for an independent CRISPR event that produces an easily detectable phenotype. Here, we describe a simple negative co-selection strategy involving CRISPR-editing of a dominant female sterile allele, ovo D1 In this system (" ovo D co-selection"), the only functional germ cells in injected females are those that have been edited at the ovo D1 locus, and thus all offspring of these flies have undergone editing of at least one locus. We demonstrate that ovo D co-selection can be used to enrich for knock-out mutagenesis via nonhomologous end-joining (NHEJ), and for knock-in alleles via homology-directed repair (HDR). Altogether, our results demonstrate that ovoD co-selection reduces the amount of screening necessary to isolate desired CRISPR events in Drosophila. Copyright © 2018, G3: Genes, Genomes, Genetics.

Directed evolution of stereoselective enzymes based on genetic selection as opposed to screening systems.

PubMed

Acevedo-Rocha, Carlos G; Agudo, Ruben; Reetz, Manfred T

2014-12-10

Directed evolution of stereoselective enzymes provides a means to generate useful biocatalysts for asymmetric transformations in organic chemistry and biotechnology. Almost all of the numerous examples reported in the literature utilize high-throughput screening systems based on suitable analytical techniques. Since the screening step is the bottleneck of the overall procedure, researchers have considered the use of genetic selection systems as an alternative to screening. In principle, selection would be the most elegant and efficient approach because it is based on growth advantage of host cells harboring stereoselective mutants, but devising such selection systems is very challenging. They must be designed so that the host organism profits from the presence of an enantioselective variant. Progress in this intriguing research area is summarized in this review, which also includes some examples of display systems designed for enantioselectivity as assayed by fluorescence-activated cell sorting (FACS). Although the combination of display systems and FACS is a powerful approach, we also envision innovative ideas combining metabolic engineering and genetic selection systems with protein directed evolution for the development of highly selective and efficient biocatalysts. Copyright © 2014 Elsevier B.V. All rights reserved.

Utilization of lean management principles in the ambulatory clinic setting.

PubMed

Casey, Jessica T; Brinton, Thomas S; Gonzalez, Chris M

2009-03-01

The principles of 'lean management' have permeated many sectors of today's business world, secondary to the success of the Toyota Production System. This management method enables workers to eliminate mistakes, reduce delays, lower costs, and improve the overall quality of the product or service they deliver. These lean management principles can be applied to health care. Their implementation within the ambulatory care setting is predicated on the continuous identification and elimination of waste within the process. The key concepts of flow time, inventory and throughput are utilized to improve the flow of patients through the clinic, and to identify points that slow this process -- so-called bottlenecks. Nonessential activities are shifted away from bottlenecks (i.e. the physician), and extra work capacity is generated from existing resources, rather than being added. The additional work capacity facilitates a more efficient response to variability, which in turn results in cost savings, more time for the physician to interact with patients, and faster completion of patient visits. Finally, application of the lean management principle of 'just-in-time' management can eliminate excess clinic inventory, better synchronize office supply with patient demand, and reduce costs.

Population genetic signatures of a climate change driven marine range extension.

PubMed

Ramos, Jorge E; Pecl, Gretta T; Moltschaniwskyj, Natalie A; Semmens, Jayson M; Souza, Carla A; Strugnell, Jan M

2018-06-22

Shifts in species distribution, or 'range shifts', are one of the most commonly documented responses to ocean warming, with important consequences for the function and structure of ecosystems, and for socio-economic activities. Understanding the genetic signatures of range shifts can help build our knowledge of the capacity of species to establish and persist in colonised areas. Here, seven microsatellite loci were used to examine the population connectivity, genetic structure and diversity of Octopus tetricus, which has extended its distribution several hundred kilometres polewards associated with the southwards extension of the warm East Australian Current along south-eastern Australia. The historical distribution and the range extension zones had significant genetic differences but levels of genetic diversity were comparable. The population in the range extension zone was sub-structured, contained relatively high levels of self-recruitment and was sourced by migrants from along the entire geographic distribution. Genetic bottlenecks and changes in population size were detected throughout the range extension axis. Persistent gene flow from throughout the historical zone and moderate genetic diversity may buffer the genetic bottlenecks and favour the range extension of O. tetricus. These characteristics may aid adaptation, establishment, and long-term persistence of the population in the range extension zone.

Public-private relationships in biobanking: a still underestimated key component of open innovation.

PubMed

Hofman, Paul; Bréchot, Christian; Zatloukal, Kurt; Dagher, Georges; Clément, Bruno

2014-01-01

Access to human bioresources is essential to the understanding of human diseases and to the discovery of new biomarkers aimed at improving the diagnosis, prognosis, and the predictive response of patients to treatments. The use of biospecimens is strictly controlled by ethical assessment, which complies with the laws of the country. These laws regulate the partnerships between the biobanks and industrial actors. However, private-public partnerships (PPP) can be limiting for several reasons, which can hamper the discovery of new biological tests and new active molecules targeted to human diseases. The bottlenecks and roadblocks in establishing these partnerships include: poor organization of the biobank in setting up PPP, evaluation of the cost of human samples, the absence of experience on the public side in setting up contracts with industry, and the fact that public and private partners may not share the same objectives. However, it is critical, in particular for academic biobanks, to establish strong PPP to accelerate translational research for the benefits of patients, and to allow the sustainability of the biobank. The purpose of this review is to discuss the main bottlenecks and roadblocks that can hamper the establishment of PPP based on solid and trusting relationships.

A boost and bounce theory of temporal attention.

PubMed

Olivers, Christian N L; Meeter, Martijn

2008-10-01

What is the time course of visual attention? Attentional blink studies have found that the 2nd of 2 targets is often missed when presented within about 500 ms from the 1st target, resulting in theories about relatively long-lasting capacity limitations or bottlenecks. Earlier studies, however, reported quite the opposite finding: Attention is transiently enhanced, rather than reduced, for several hundreds of milliseconds after a relevant event. The authors present a general theory, as well as a working computational model, that integrate these findings. There is no central role for capacity limitations or bottlenecks. Central is a rapidly responding gating system (or attentional filter) that seeks to enhance relevant and suppress irrelevant information. When items sufficiently match the target description, they elicit transient excitatory feedback activity (a "boost" function), meant to provide access to working memory. However, in the attentional blink task, the distractor after the target is accidentally boosted, resulting in subsequent strong inhibitory feedback response (a "bounce"), which, in effect, closes the gate to working memory. The theory explains many findings that are problematic for limited-capacity accounts, including a new experiment showing that the attentional blink can be postponed.

Genetic and life-history consequences of extreme climate events.

PubMed

Vincenzi, Simone; Mangel, Marc; Jesensek, Dusan; Garza, John Carlos; Crivelli, Alain J

2017-02-08

Climate change is predicted to increase the frequency and intensity of extreme climate events. Tests on empirical data of theory-based predictions on the consequences of extreme climate events are thus necessary to understand the adaptive potential of species and the overarching risks associated with all aspects of climate change. We tested predictions on the genetic and life-history consequences of extreme climate events in two populations of marble trout Salmo marmoratus that have experienced severe demographic bottlenecks due to flash floods. We combined long-term field and genotyping data with pedigree reconstruction in a theory-based framework. Our results show that after flash floods, reproduction occurred at a younger age in one population. In both populations, we found the highest reproductive variance in the first cohort born after the floods due to a combination of fewer parents and higher early survival of offspring. A small number of parents allowed for demographic recovery after the floods, but the genetic bottleneck further reduced genetic diversity in both populations. Our results also elucidate some of the mechanisms responsible for a greater prevalence of faster life histories after the extreme event. © 2017 The Author(s).

Recurrent Reverse Evolution Maintains Polymorphism after Strong Bottlenecks in Commensal Gut Bacteria

PubMed Central

Ramiro, Ricardo S.; Barroso-Batista, João; Güleresi, Daniela; Lourenço, Marta; Gordo, Isabel

2017-01-01

Abstract The evolution of new strains within the gut ecosystem is poorly understood. We used a natural but controlled system to follow the emergence of intraspecies diversity of commensal Escherichia coli, during three rounds of adaptation to the mouse gut (∼1,300 generations). We previously showed that, in the first round, a strongly beneficial phenotype (loss-of-function for galactitol consumption; gat-negative) spread to >90% frequency in all colonized mice. Here, we show that this loss-of-function is repeatedly reversed when a gat-negative clone colonizes new mice. The regain of function occurs via compensatory mutation and reversion, the latter leaving no trace of past adaptation. We further show that loss-of-function adaptive mutants reevolve, after colonization with an evolved gat-positive clone. Thus, even under strong bottlenecks a regime of strong-mutation-strong-selection dominates adaptation. Coupling experiments and modeling, we establish that reverse evolution recurrently generates two coexisting phenotypes within the microbiota that can or not consume galactitol (gat-positive and gat-negative, respectively). Although the abundance of the dominant strain, the gat-negative, depends on the microbiota composition, gat-positive abundance is independent of the microbiota composition and can be precisely manipulated by supplementing the diet with galactitol. These results show that a specific diet is able to change the abundance of specific strains. Importantly, we find polymorphism for these phenotypes in indigenous Enterobacteria of mice and man. Our results demonstrate that natural selection can greatly overwhelm genetic drift at structuring the strain diversity of gut commensals and that competition for limiting resources may be a key mechanism for maintaining polymorphism in the gut. PMID:28961745

An invasive social insect overcomes genetic load at the sex locus.

PubMed

Gloag, Rosalyn; Ding, Guiling; Christie, Joshua R; Buchmann, Gabriele; Beekman, Madeleine; Oldroyd, Benjamin P

2016-11-07

Some invasive hymenopteran social insects found new populations with very few reproductive individuals. This is despite the high cost of founder effects for such insects, which generally require heterozygosity at a single locus-the complementary sex determiner, csd-to develop as females. Individuals that are homozygous at csd develop as either infertile or subfertile diploid males or not at all. Furthermore, diploid males replace the female workers that are essential for colony function. Here we document how the Asian honey bee (Apis cerana) overcame the diploid male problem during its invasion of Australia. Natural selection prevented the loss of rare csd alleles due to genetic drift and corrected the skew in allele frequencies caused by founder effects to restore high average heterozygosity. Thus, balancing selection can alleviate the genetic load at csd imposed by severe bottlenecks, and so facilitate invasiveness.

High-throughput selection for cellulase catalysts using chemical complementation.

PubMed

Peralta-Yahya, Pamela; Carter, Brian T; Lin, Hening; Tao, Haiyan; Cornish, Virginia W

2008-12-24

Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases, however, is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Because of the large number of enzyme variants that selections can now test as compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity.

A High-throughput Selection for Cellulase Catalysts Using Chemical Complementation

PubMed Central

Peralta-Yahya, Pamela; Carter, Brian T.; Lin, Hening; Tao, Haiyan; Cornish, Virginia W.

2010-01-01

Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases however is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Due to the large number of enzyme variants selections can test compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity. PMID:19053460

Population bottlenecks, genetic diversity and breeding ability of the three-spined stickleback (Gasterosteus aculeatus) from three polluted English Rivers.

PubMed

Santos, Eduarda M; Hamilton, Patrick B; Coe, Tobias S; Ball, Jonathan S; Cook, Alastair C; Katsiadaki, Ioanna; Tyler, Charles R

2013-10-15

Pollution is a significant environmental pressure on fish populations in both freshwater and marine environments. Populations subjected to chronic exposure to pollutants can experience impacts ranging from altered reproductive capacity to changes in population genetic structure. Few studies, however, have examined the reproductive vigor of individuals within populations inhabiting environments characterized by chronic pollution. In this study we undertook an analysis of populations of three-spined sticklebacks (Gasterosteus aculeatus) from polluted sites, to determine levels of genetic diversity, assess for evidence of historic population genetic bottlenecks and determine the reproductive competitiveness of males from these locations. The sites chosen included locations in the River Aire, the River Tees and the River Birket, English rivers that have been impacted by pollution from industrial and/or domestic effluents for over 100 years. Male reproductive competitiveness was determined via competitive breeding experiments with males and females derived from a clean water site, employing DNA microsatellites to determine parentage outcome. Populations of stickleback collected from the three historically polluted sites showed evidence of recent population bottlenecks, although only the River Aire population showed low genetic diversity. In contrast, fish collected from two relatively unpolluted sites within the River Gowy and Houghton Springs showed weak, or no evidence of such bottlenecks. Nevertheless, males derived from polluted sites were able to reproduce successfully in competition with males derived from clean water exposures, indicating that these bottlenecks have not resulted in any substantial loss of reproductive fitness in males. Copyright © 2013 Elsevier B.V. All rights reserved.

Learning to Achieve Perfect Timesharing: Architectural Implications of Hazeltine, Teague, and Ivry (2002)

ERIC Educational Resources Information Center

Anderson, John R.; Taatgen, Niels A.; Byrne, Michael D.

2005-01-01

E. Hazeltine, D. Teague, and R. B. Ivry have presented data that have been interpreted as evidence against a central bottleneck. This article describes simulations of their Experiments 1 and 4 in the ACT-R cognitive architecture, which does possess a central bottleneck in production execution. The simulation model is capable of accounting for the…

Dana-Farber Cancer Institute: Discovery of Resistance Mechanisms | Office of Cancer Genomics

Cancer.gov

Resistance to targeted therapy is emerging as a bottleneck to achieving durable drug responses in cancer. The goal of the CTD2 Center at Dana Farber Cancer Institute is to identify mechanisms of resistance for both existing therapeutics as well as for emerging targets even prior to the identification of lead compounds. They aim to use this information to inform combinatorial treatments. In representative examples they have found that YAP1 leads to resistance after KRAS targeting and that PRKACA mediates resistance to HER2 therapy.

The Importance of Biopsy in the Era of Molecular Medicine.

PubMed

Ziv, Etay; Durack, Jeremy C; Solomon, Stephen B

Recent advances in the molecular characterization of cancers have triggered interest in developing a new taxonomy of disease in oncology with the goal of using the molecular profile of a patient's tumor to predict response to treatment. Image-guided needle biopsy is central to this "precision medicine" effort. In this review, we first discuss the current role of biopsy in relation to clinical examples of molecular medicine. We then outline important bottlenecks to the advancement of precision medicine and highlight the potential role of image-guided biopsy to address these challenges.

Efficient Constant-Time Complexity Algorithm for Stochastic Simulation of Large Reaction Networks.

PubMed

Thanh, Vo Hong; Zunino, Roberto; Priami, Corrado

2017-01-01

Exact stochastic simulation is an indispensable tool for a quantitative study of biochemical reaction networks. The simulation realizes the time evolution of the model by randomly choosing a reaction to fire and update the system state according to a probability that is proportional to the reaction propensity. Two computationally expensive tasks in simulating large biochemical networks are the selection of next reaction firings and the update of reaction propensities due to state changes. We present in this work a new exact algorithm to optimize both of these simulation bottlenecks. Our algorithm employs the composition-rejection on the propensity bounds of reactions to select the next reaction firing. The selection of next reaction firings is independent of the number reactions while the update of propensities is skipped and performed only when necessary. It therefore provides a favorable scaling for the computational complexity in simulating large reaction networks. We benchmark our new algorithm with the state of the art algorithms available in literature to demonstrate its applicability and efficiency.

Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

PubMed Central

Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Wei-Jun; Smith, Richard D.

2012-01-01

Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides including posttranslational modifications (PTMs), as well as advances in MS instrumentation which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed. PMID:22577010

Homogeneity of Powassan virus populations in naturally infected Ixodes scapularis

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

Brackney, Doug E.; Brown, Ivy K.; Nofchissey, Robert A.

2010-07-05

Powassan virus (POWV, Flaviviridae: Flavivirus) is the sole North American member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. The underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. Therefore, intra- and interhost genetic diversity was analyzed to determine if POWV exists as a quasispecies in nature and quantify selective pressures within and between hosts. In contrast to previous reports for West Nile virus (WNV), significant intrahost genetic diversity was not observed. However, pN (0.238) and d{sub N}/d{sub S} ratios (0.092) for interhost diversitymore » were similar to those of WNV. Combined, these data suggest that purifying selection and/or population bottlenecks constrain quasispecies diversity within ticks. These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks.« less

Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

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

Shi, Tujin; Su, Dian; Liu, Tao

2012-04-01

Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, whichmore » have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.« less

Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes.

PubMed

Frantz, Laurent A F; Schraiber, Joshua G; Madsen, Ole; Megens, Hendrik-Jan; Cagan, Alex; Bosse, Mirte; Paudel, Yogesh; Crooijmans, Richard P M A; Larson, Greger; Groenen, Martien A M

2015-10-01

Traditionally, the process of domestication is assumed to be initiated by humans, involve few individuals and rely on reproductive isolation between wild and domestic forms. We analyzed pig domestication using over 100 genome sequences and tested whether pig domestication followed a traditional linear model or a more complex, reticulate model. We found that the assumptions of traditional models, such as reproductive isolation and strong domestication bottlenecks, are incompatible with the genetic data. In addition, our results show that, despite gene flow, the genomes of domestic pigs have strong signatures of selection at loci that affect behavior and morphology. We argue that recurrent selection for domestic traits likely counteracted the homogenizing effect of gene flow from wild boars and created 'islands of domestication' in the genome. Our results have major ramifications for the understanding of animal domestication and suggest that future studies should employ models that do not assume reproductive isolation.

Homogeneity of Powassan virus populations in naturally infected Ixodes scapularis.

PubMed

Brackney, Doug E; Brown, Ivy K; Nofchissey, Robert A; Fitzpatrick, Kelly A; Ebel, Gregory D

2010-07-05

Powassan virus (POWV, Flaviviridae: Flavivirus) is the sole North American member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. The underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. Therefore, intra- and interhost genetic diversity was analyzed to determine if POWV exists as a quasispecies in nature and quantify selective pressures within and between hosts. In contrast to previous reports for West Nile virus (WNV), significant intrahost genetic diversity was not observed. However, pN (0.238) and d(N)/d(S) ratios (0.092) for interhost diversity were similar to those of WNV. Combined, these data suggest that purifying selection and/or population bottlenecks constrain quasispecies diversity within ticks. These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks. Copyright 2010 Elsevier Inc. All rights reserved.

HOMOGENEITY OF POWASSAN VIRUS POPULATIONS IN NATURALLY INFECTED IXODES SCAPULARIS

PubMed Central

Brackney, Doug E.; Brown, Ivy K.; Nofchissey, Robert A.; Fitzpatrick, Kelly A.; Ebel, Gregory D.

2010-01-01

Powassan virus (POWV, Flaviviridae: Flavivirus) is the sole North American member of the tick-borne encephalitis complex and consists of two distinct lineages that are maintained in ecologically discrete enzootic transmission cycles. The underlying genetic mechanisms that lead to niche partitioning in arboviruses are poorly understood. Therefore, intra- and interhost genetic diversity was analyzed to determine if POWV exists as a quasispecies in nature and quantify selective pressures within and between hosts. In contrast to previous reports for West Nile virus (WNV), significant intrahost genetic diversity was not observed. However, pN (0.238) and dN/dS ratios (0.092) for interhost diversity were similar to those of WNV. Combined, these data suggest that purifying selection and/or population bottlenecks constrain quasispecies diversity within ticks. These same selective and stochastic mechanisms appear to drive minor sequence changes between ticks. Moreover, Powassan virus populations seem not to be structured as quasispecies in naturally infected adult deer ticks. PMID:20434750

An Orthogonal and pH-Tunable Sensor-Selector for Muconic Acid Biosynthesis in Yeast.

PubMed

Snoek, Tim; Romero-Suarez, David; Zhang, Jie; Ambri, Francesca; Skjoedt, Mette L; Sudarsan, Suresh; Jensen, Michael K; Keasling, Jay D

2018-04-20

Microbes offer enormous potential for production of industrially relevant chemicals and therapeutics, yet the rapid identification of high-producing microbes from large genetic libraries is a major bottleneck in modern cell factory development. Here, we develop and apply a synthetic selection system in Saccharomyces cerevisiae that couples the concentration of muconic acid, a plastic precursor, to cell fitness by using the prokaryotic transcriptional regulator BenM driving an antibiotic resistance gene. We show that the sensor-selector does not affect production nor fitness, and find that tuning pH of the cultivation medium limits the rise of nonproducing cheaters. We apply the sensor-selector to selectively enrich for best-producing variants out of a large library of muconic acid production strains, and identify an isolate that produces more than 2 g/L muconic acid in a bioreactor. We expect that this sensor-selector can aid the development of other synthetic selection systems based on allosteric transcription factors.

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

High-throughput platform assay technology for the discovery of pre-microrna-selective small molecule probes.

PubMed

Lorenz, Daniel A; Song, James M; Garner, Amanda L

2015-01-21

MicroRNAs (miRNA) play critical roles in human development and disease. As such, the targeting of miRNAs is considered attractive as a novel therapeutic strategy. A major bottleneck toward this goal, however, has been the identification of small molecule probes that are specific for select RNAs and methods that will facilitate such discovery efforts. Using pre-microRNAs as proof-of-concept, herein we report a conceptually new and innovative approach for assaying RNA-small molecule interactions. Through this platform assay technology, which we term catalytic enzyme-linked click chemistry assay or cat-ELCCA, we have designed a method that can be implemented in high throughput, is virtually free of false readouts, and is general for all nucleic acids. Through cat-ELCCA, we envision the discovery of selective small molecule ligands for disease-relevant miRNAs to promote the field of RNA-targeted drug discovery and further our understanding of the role of miRNAs in cellular biology.

Evaluating the performance of selection scans to detect selective sweeps in domestic dogs

PubMed Central

Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R.; Messer, Philipp W.

2015-01-01

Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analyzed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used, and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. PMID:26589239

Evaluating the performance of selection scans to detect selective sweeps in domestic dogs.

PubMed

Schlamp, Florencia; van der Made, Julian; Stambler, Rebecca; Chesebrough, Lewis; Boyko, Adam R; Messer, Philipp W

2016-01-01

Selective breeding of dogs has resulted in repeated artificial selection on breed-specific morphological phenotypes. A number of quantitative trait loci associated with these phenotypes have been identified in genetic mapping studies. We analysed the population genomic signatures observed around the causal mutations for 12 of these loci in 25 dog breeds, for which we genotyped 25 individuals in each breed. By measuring the population frequencies of the causal mutations in each breed, we identified those breeds in which specific mutations most likely experienced positive selection. These instances were then used as positive controls for assessing the performance of popular statistics to detect selection from population genomic data. We found that artificial selection during dog domestication has left characteristic signatures in the haplotype and nucleotide polymorphism patterns around selected loci that can be detected in the genotype data from a single population sample. However, the sensitivity and accuracy at which such signatures were detected varied widely between loci, the particular statistic used and the choice of analysis parameters. We observed examples of both hard and soft selective sweeps and detected strong selective events that removed genetic diversity almost entirely over regions >10 Mbp. Our study demonstrates the power and limitations of selection scans in populations with high levels of linkage disequilibrium due to severe founder effects and recent population bottlenecks. © 2015 John Wiley & Sons Ltd.

High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal

PubMed Central

Aguilar, Andres; Roemer, Gary; Debenham, Sally; Binns, Matthew; Garcelon, David; Wayne, Robert K.

2004-01-01

The San Nicolas Island fox (Urocyon littoralis dickeyi) is genetically the most monomorphic sexually reproducing animal population yet reported and has no variation in hypervariable genetic markers. Such low levels of variation imply lower resistance to pathogens, reduced fitness, and problems in distinguishing kin from non-kin. In vertebrates, the MHC contains genes that influence disease resistance and kin recognition and may be under intense balancing selection in some populations. Hence, genetic variation at the MHC might persist despite the extreme monomorphism shown by neutral markers. We examine variation of five loci within the MHC of San Nicolas Island foxes and find remarkably high levels of variation. Further, we show by simulation that genetic monomorphism at neutral loci and high MHC variation could arise only through an extreme population bottleneck of <10 individuals, ≈10–20 generations ago, accompanied by unprecedented selection coefficients of >0.5 on MHC loci. These results support the importance of balancing selection as a mechanism to maintain variation in natural populations and expose the difficulty of using neutral markers as surrogates for variation in fitness-related loci. PMID:14990802

Four disruptive strategies for removing drug discovery bottlenecks.

PubMed

Ekins, Sean; Waller, Chris L; Bradley, Mary P; Clark, Alex M; Williams, Antony J

2013-03-01

Drug discovery is shifting focus from industry to outside partners and, in the process, creating new bottlenecks. Technologies like high throughput screening (HTS) have moved to a larger number of academic and institutional laboratories in the USA, with little coordination or consideration of the outputs and creating a translational gap. Although there have been collaborative public-private partnerships in Europe to share pharmaceutical data, the USA has seemingly lagged behind and this may hold it back. Sharing precompetitive data and models may accelerate discovery across the board, while finding the best collaborators, mining social media and mobile approaches to open drug discovery should be evaluated in our efforts to remove drug discovery bottlenecks. We describe four strategies to rectify the current unsustainable situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Natural language processing and the Now-or-Never bottleneck.

PubMed

Gómez-Rodríguez, Carlos

2016-01-01

Researchers, motivated by the need to improve the efficiency of natural language processing tools to handle web-scale data, have recently arrived at models that remarkably match the expected features of human language processing under the Now-or-Never bottleneck framework. This provides additional support for said framework and highlights the research potential in the interaction between applied computational linguistics and cognitive science.

Treatment of neonatal infections: a multi-country analysis of health system bottlenecks and potential solutions.

PubMed

Simen-Kapeu, Aline; Seale, Anna C; Wall, Steve; Nyange, Christabel; Qazi, Shamim A; Moxon, Sarah G; Young, Mark; Liu, Grace; Darmstadt, Gary L; Dickson, Kim E; Lawn, Joy E

2015-01-01

Around one-third of the world's 2.8 million neonatal deaths are caused by infections. Most of these deaths are preventable, but occur due to delays in care-seeking, and access to effective antibiotic treatment with supportive care. Understanding variation in health system bottlenecks to scale-up of case management of neonatal infections and identifying solutions is essential to reduce mortality, and also morbidity. A standardised bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the development of the Every Newborn Action Plan. Country workshops involved technical experts to complete a survey tool, to grade health system "bottlenecks" hindering scale up of maternal-newborn intervention packages. Quantitative and qualitative methods were used to analyse the data, combined with literature review, to present priority bottlenecks and synthesise actions to improve case management of newborn infections. For neonatal infections, the health system building blocks most frequently graded as major or significant bottlenecks, irrespective of mortality context and geographical region, were health workforce (11 out of 12 countries), and community ownership and partnership (11 out of 12 countries). Lack of data to inform decision making, and limited funding to increase access to quality neonatal care were also major challenges. Rapid recognition of possible serious bacterial infection and access to care is essential. Inpatient hospital care remains the first line of treatment for neonatal infections. In situations where referral is not possible, the use of simplified antibiotic regimens for outpatient management for non-critically ill young infants has recently been reported in large clinical trials; WHO is developing a guideline to treat this group of young infants. Improving quality of care through more investment in the health workforce at all levels of care is critical, in addition to ensuring development and dissemination of national guidelines. Improved information systems are needed to track coverage and adequately manage drug supply logistics for improved health outcomes. It is important to increase community ownership and partnership, for example through involvement of community groups.

Treatment of neonatal infections: a multi-country analysis of health system bottlenecks and potential solutions

PubMed Central

2015-01-01

Background Around one-third of the world's 2.8 million neonatal deaths are caused by infections. Most of these deaths are preventable, but occur due to delays in care-seeking, and access to effective antibiotic treatment with supportive care. Understanding variation in health system bottlenecks to scale-up of case management of neonatal infections and identifying solutions is essential to reduce mortality, and also morbidity. Methods A standardised bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the development of the Every Newborn Action Plan. Country workshops involved technical experts to complete a survey tool, to grade health system "bottlenecks" hindering scale up of maternal-newborn intervention packages. Quantitative and qualitative methods were used to analyse the data, combined with literature review, to present priority bottlenecks and synthesise actions to improve case management of newborn infections. Results For neonatal infections, the health system building blocks most frequently graded as major or significant bottlenecks, irrespective of mortality context and geographical region, were health workforce (11 out of 12 countries), and community ownership and partnership (11 out of 12 countries). Lack of data to inform decision making, and limited funding to increase access to quality neonatal care were also major challenges. Conclusions Rapid recognition of possible serious bacterial infection and access to care is essential. Inpatient hospital care remains the first line of treatment for neonatal infections. In situations where referral is not possible, the use of simplified antibiotic regimens for outpatient management for non-critically ill young infants has recently been reported in large clinical trials; WHO is developing a guideline to treat this group of young infants. Improving quality of care through more investment in the health workforce at all levels of care is critical, in addition to ensuring development and dissemination of national guidelines. Improved information systems are needed to track coverage and adequately manage drug supply logistics for improved health outcomes. It is important to increase community ownership and partnership, for example through involvement of community groups. PMID:26391217

Fluctuating Selection in the Moran.

PubMed

Dean, Antony M; Lehman, Clarence; Yi, Xiao

2017-03-01

Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model, we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large, and the variance in selection is big. Lowering the frequency of fluctuations makes selection more directional, and so heterozygosity declines. We also show that fluctuating selection raises d n / d s ratios for polymorphism, not only by sweeping selected alleles into the population, but also by purging the neutral variants of selected alleles as they undergo repeated bottlenecks. Our analysis shows that randomly fluctuating selection increases the rate of evolution by increasing the probability of fixation. The impact is especially noticeable when the selection is strong and mutation is weak. Simulations show the increase in the rate of evolution declines as the rate of new mutations entering the population increases, an effect attributable to clonal interference. Intriguingly, fluctuating selection increases the d n / d s ratios for divergence more than for polymorphism, a pattern commonly seen in comparative genomics. Our model, which extends the classical neutral model of molecular evolution by incorporating random fluctuations in selection, accommodates a wide variety of observations, both neutral and selected, with economy. Copyright © 2017 by the Genetics Society of America.

Modular Engineering of l-Tyrosine Production in Escherichia coli

PubMed Central

Juminaga, Darmawi; Baidoo, Edward E. K.; Redding-Johanson, Alyssa M.; Batth, Tanveer S.; Burd, Helcio; Mukhopadhyay, Aindrila; Petzold, Christopher J.

2012-01-01

Efficient biosynthesis of l-tyrosine from glucose is necessary to make biological production economically viable. To this end, we designed and constructed a modular biosynthetic pathway for l-tyrosine production in E. coli MG1655 by encoding the enzymes for converting erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP) to l-tyrosine on two plasmids. Rational engineering to improve l-tyrosine production and to identify pathway bottlenecks was directed by targeted proteomics and metabolite profiling. The bottlenecks in the pathway were relieved by modifications in plasmid copy numbers, promoter strength, gene codon usage, and the placement of genes in operons. One major bottleneck was due to the bifunctional activities of quinate/shikimate dehydrogenase (YdiB), which caused accumulation of the intermediates dehydroquinate (DHQ) and dehydroshikimate (DHS) and the side product quinate; this bottleneck was relieved by replacing YdiB with its paralog AroE, resulting in the production of over 700 mg/liter of shikimate. Another bottleneck in shikimate production, due to low expression of the dehydroquinate synthase (AroB), was alleviated by optimizing the first 15 codons of the gene. Shikimate conversion to l-tyrosine was improved by replacing the shikimate kinase AroK with its isozyme, AroL, which effectively consumed all intermediates formed in the first half of the pathway. Guided by the protein and metabolite measurements, the best producer, consisting of two medium-copy-number, dual-operon plasmids, was optimized to produce >2 g/liter l-tyrosine at 80% of the theoretical yield. This work demonstrates the utility of targeted proteomics and metabolite profiling in pathway construction and optimization, which should be applicable to other metabolic pathways. PMID:22020510

A Wide Range of 3243A>G/tRNALeu(UUR) (MELAS) Mutation Loads May Segregate in Offspring through the Female Germline Bottleneck

PubMed Central

Pallotti, Francesco; Binelli, Giorgio; Fabbri, Raffaella; Valentino, Maria L.; Vicenti, Rossella; Macciocca, Maria; Cevoli, Sabina; Baruzzi, Agostino; DiMauro, Salvatore; Carelli, Valerio

2014-01-01

Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size. PMID:24805791

Consequences of a demographic bottleneck on genetic structure and variation in the Scandinavian brown bear.

PubMed

Xenikoudakis, G; Ersmark, E; Tison, J-L; Waits, L; Kindberg, J; Swenson, J E; Dalén, L

2015-07-01

The Scandinavian brown bear went through a major decline in population size approximately 100 years ago, due to intense hunting. After being protected, the population subsequently recovered and today numbers in the thousands. The genetic diversity in the contemporary population has been investigated in considerable detail, and it has been shown that the population consists of several subpopulations that display relatively high levels of genetic variation. However, previous studies have been unable to resolve the degree to which the demographic bottleneck impacted the contemporary genetic structure and diversity. In this study, we used mitochondrial and microsatellite DNA markers from pre- and postbottleneck Scandinavian brown bear samples to investigate the effect of the bottleneck. Simulation and multivariate analysis suggested the same genetic structure for the historical and modern samples, which are clustered into three subpopulations in southern, central and northern Scandinavia. However, the southern subpopulation appears to have gone through a marked change in allele frequencies. When comparing the mitochondrial DNA diversity in the whole population, we found a major decline in haplotype numbers across the bottleneck. However, the loss of autosomal genetic diversity was less pronounced, although a significant decline in allelic richness was observed in the southern subpopulation. Approximate Bayesian computations provided clear support for a decline in effective population size during the bottleneck, in both the southern and northern subpopulations. These results have implications for the future management of the Scandinavian brown bear because they indicate a recent loss in genetic diversity and also that the current genetic structure may have been caused by historical ecological processes rather than recent anthropogenic persecution. © 2015 John Wiley & Sons Ltd.

Emerging from the bottleneck: benefits of the comparative approach to modern neuroscience.

PubMed

Brenowitz, Eliot A; Zakon, Harold H

2015-05-01

Neuroscience has historically exploited a wide diversity of animal taxa. Recently, however, research has focused increasingly on a few model species. This trend has accelerated with the genetic revolution, as genomic sequences and genetic tools became available for a few species, which formed a bottleneck. This coalescence on a small set of model species comes with several costs that are often not considered, especially in the current drive to use mice explicitly as models for human diseases. Comparative studies of strategically chosen non-model species can complement model species research and yield more rigorous studies. As genetic sequences and tools become available for many more species, we are poised to emerge from the bottleneck and once again exploit the rich biological diversity offered by comparative studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automatic choroid cells segmentation and counting in fluorescence microscopic image

NASA Astrophysics Data System (ADS)

Fei, Jianjun; Zhu, Weifang; Shi, Fei; Xiang, Dehui; Lin, Xiao; Yang, Lei; Chen, Xinjian

2016-03-01

In this paper, we proposed a method to automatically segment and count the rhesus choroid-retinal vascular endothelial cells (RF/6A) in fluorescence microscopic images which is based on shape classification, bottleneck detection and accelerated Dijkstra algorithm. The proposed method includes four main steps. First, a thresholding filter and morphological operations are applied to reduce the noise. Second, a shape classifier is used to decide whether a connected component is needed to be segmented. In this step, the AdaBoost classifier is applied with a set of shape features. Third, the bottleneck positions are found based on the contours of the connected components. Finally, the cells segmentation and counting are completed based on the accelerated Dijkstra algorithm with the gradient information between the bottleneck positions. The results show the feasibility and efficiency of the proposed method.

[Application of ecosystem service value in land use change research: Bottlenecks and prospects].

PubMed

Zhang, Zhou; Wu, Ci-Fang; Tan, Rong

2013-02-01

In recent years, the application of ecosystem service value in land use change research is a hot topic in many famous international journals. However, policy makers are seldom taking into account the achievements of the related studies in practice. This paper summarized the three main bottlenecks in applying ecosystem service value in land management practices, i. e., the difficulty in measuring the service values, the complexity of driving factors, and the bias of evaluation criteria. Some solutions on the bottlenecks were provided, and the future research directions in China were prospected. It was suggested that in the studies of land use change based on ecosystem service value, it would be more appropriate to adopt comparative analysis method in small scale case studies, especially focusing on the natural ecological resources and the excessive loss of their values.

Exploiting Artificial Intelligence for Analysis and Data Selection on-board the Puerto Rico CubeSat

NASA Astrophysics Data System (ADS)

Bergman, J. E. S.; Bruhn, F.; Funk, P.; Isham, B.; Rincón-Charris, A. A.; Capo-Lugo, P.; Åhlén, L.

2015-10-01

CubeSat missions are constrained by the limited resources provided by the platform. Many payload providers have learned to cope with the low mass and power but the poor telemetry allocation remains a bottleneck. In the end, it is the data delivered to ground which determines the value of the mission. However, transmitting more data does not necessarily guarantee high value, since the value also depends on the data quality. By exploiting fast on-board computing and efficient artificial intelligence (AI) algorithms for analysis and data selection one could optimize the usage of the telemetry link and so increase the value of the mission. In a pilot project, we attempt to do this on the Puerto Rico CubeSat, where science objectives include the acquisition of space weather data to aid better understanding of the Sun to Earth connection.

A Binary Segmentation Approach for Boxing Ribosome Particles in Cryo EM Micrographs

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

Adiga, Umesh P.S.; Malladi, Ravi; Baxter, William

Three-dimensional reconstruction of ribosome particles from electron micrographs requires selection of many single-particle images. Roughly 100,000 particles are required to achieve approximately 10 angstrom resolution. Manual selection of particles, by visual observation of the micrographs on a computer screen, is recognized as a bottleneck in automated single particle reconstruction. This paper describes an efficient approach for automated boxing of ribosome particles in micrographs. Use of a fast, anisotropic non-linear reaction-diffusion method to pre-process micrographs and rank-leveling to enhance the contrast between particles and the background, followed by binary and morphological segmentation constitute the core of this technique. Modifying the shapemore » of the particles to facilitate segmentation of individual particles within clusters and boxing the isolated particles is successfully attempted. Tests on a limited number of micrographs have shown that over 80 percent success is achieved in automatic particle picking.« less

Airport security inspection process model and optimization based on GSPN

NASA Astrophysics Data System (ADS)

Mao, Shuainan

2018-04-01

Aiming at the efficiency of airport security inspection process, Generalized Stochastic Petri Net is used to establish the security inspection process model. The model is used to analyze the bottleneck problem of airport security inspection process. The solution to the bottleneck is given, which can significantly improve the efficiency and reduce the waiting time by adding the place for people to remove their clothes and the X-ray detector.

Health systems and noncommunicable diseases in the Asia-Pacific region: a review of the published literature.

PubMed

Mannava, Priya; Abdullah, Asnawi; James, Chris; Dodd, Rebecca; Annear, Peter Leslie

2015-03-01

Addressing the growing burden of noncommunicable diseases (NCDs) in countries of the Asia-Pacific region requires well-functioning health systems. In low- and middle-income countries (LMICs), however, health systems are generally characterized by inadequate financial and human resources, unsuitable service delivery models, and weak information systems. The aims of this review were to identify (a) health systems interventions being implemented to deliver NCD programs and services and their outcomes and (b) the health systems bottlenecks impeding access to or delivery of these programs and services in LMICs of the Asia-Pacific region. A search of 4 databases for literature published between 1990 and 2010 retrieved 36 relevant studies. For each study, information on basic characteristics, type of health systems bottleneck/intervention, and outcome was extracted, and methodological quality appraised. Health systems interventions and bottlenecks were classified as per the World Health Organization health systems building blocks framework. The review identified interventions and bottlenecks in the building blocks of service delivery, health workforce, financing, health information systems, and medical products, vaccines, and technologies. Studies, however, were heterogeneous in methodologies used, and the overall quality was generally low. There are several gaps in the evidence base around NCDs in the Asia-Pacific region that require further investigation. © 2013 APJPH.

Genetics Show Current Decline and Pleistocene Expansion in Northern Spotted Owls

USGS Publications Warehouse

Funk, W. Chris; Forsman, Eric D.; Mullins, Thomas D.; Haig, Susan M.

2008-01-01

The northern spotted owl (Strix occidentalis caurina) is one of the most controversial threatened subspecies ever listed under the U.S. Endangered Species Act. Because of concern for persistence of the subspecies, logging on Federal lands in the U.S. Pacific Northwest was dramatically reduced under the Northwest Forest Plan in 1994. Despite protection of its remaining forest habitat, recent field studies show continued demographic declines of northern spotted owls. One potential threat to northern spotted owls that has not yet been shown is loss of genetic variation from population bottlenecks that can increase inbreeding depression and decrease adaptive potential. Here, we show recent genetic bottlenecks in northern spotted owls using a large genetic dataset (352 individuals from across the subspecies' range and 11 microsatellite loci). The signature of bottlenecks was strongest in Washington State, in agreement with field data. Interestingly, we also found a genetic signature of Pleistocene expansion in the same study areas where recent bottlenecks were shown. Our results provide independent evidence that northern spotted owls have recently declined, and suggest that loss of genetic variation is an emerging threat to the subspecies' persistence. Reduced effective population size (Ne), shown here in addition to field evidence for demographic decline, highlights the increasing vulnerability of this bird to extinction.

Rules for biocatalyst and reaction engineering to implement effective, NAD(P)H-dependent, whole cell bioreductions

PubMed Central

Kratzer, Regina; Woodley, John M.; Nidetzky, Bernd

2016-01-01

Access to chiral alcohols of high optical purity is today frequently provided by the enzymatic reduction of precursor ketones. However, bioreductions are complicated by the need for reducing equivalents in the form of NAD(P)H. The high price and molecular weight of NAD(P)H necessitate in situ recycling of catalytic quantities, which is mostly accomplished by enzymatic oxidation of a cheap co-substrate. The coupled oxidoreduction can be either performed by free enzymes in solution or by whole cells. Reductase selection, the decision between cell-free and whole cell reduction system, coenzyme recycling mode and reaction conditions represent design options that strongly affect bioreduction efficiency. In this paper, each option was critically scrutinized and decision rules formulated based on well-described literature examples. The development chain was visualized as a decision-tree that can be used to identify the most promising route towards the production of a specific chiral alcohol. General methods, applications and bottlenecks in the set-up are presented and key experiments required to “test” for decision-making attributes are defined. The reduction of o-chloroacetophenone to (S)-1-(2-chlorophenyl)ethanol was used as one example to demonstrate all the development steps. Detailed analysis of reported large scale bioreductions identified product isolation as a major bottleneck in process design. PMID:26343336

Population bottleneck triggering millennial-scale morphospace shifts in endemic thermal-spring melanopsids.

PubMed

Neubauer, Thomas A; Harzhauser, Mathias; Georgopoulou, Elisavet; Wrozyna, Claudia

2014-11-15

For more than hundred years the thermal spring-fed Lake Pețea near Oradea, Romania, was studied for its highly endemic subfossil and recent fauna and flora. One point of focus was the species lineage of the melanopsid gastropod Microcolpia parreyssii , which exhibited a tremendous diversity of shapes during the earlier Holocene. As a consequence many new species, subspecies, and variety-names have been introduced over time, trying to categorize this overwhelming variability. In contrast to the varied subfossil assemblage, only a single phenotype is present today. We critically review the apparent "speciation event" implied by the taxonomy, based on the presently available information and new data from morphometric analyses of shell outlines and oxygen and carbon isotope data. This synthesis shows that one turning point in morphological evolution coincides with high accumulation of peaty deposits during a short time interval of maximally a few thousand years. The formation of a small, highly eutrophic swamp with increased input of organic matter marginalized the melanopsids and reduced population size. The presented data make natural selection as the dominating force unlikely but rather indicates genetic drift following a bottleneck effect induced by the environmental changes. This claim contrasts the "obvious trend" and shows that great morphological variability has to be carefully and objectively evaluated in order to allow sound interpretations of the underlying mechanisms.

Reproductive Resilience to Food Shortage in a Small Heterothermic Primate

PubMed Central

Perret, Martine; Henry, Pierre-Yves

2012-01-01

The massive energetic costs entailed by reproduction in most mammalian females may increase the vulnerability of reproductive success to food shortage. Unexpected events of unfavorable climatic conditions are expected to rise in frequency and intensity as climate changes. The extent to which physiological flexibility allows organisms to maintain reproductive output constant despite energetic bottlenecks has been poorly investigated. In mammals, reproductive resilience is predicted to be maximal during early stages of reproduction, due to the moderate energetic costs of ovulation and gestation relative to lactation. We experimentally tested the consequences of chronic-moderate and short-acute food shortages on the reproductive output of a small seasonally breeding primate, the grey mouse lemur (Microcebus murinus) under thermo-neutral conditions. These two food treatments were respectively designed to simulate the energetic constraints imposed by a lean year (40% caloric restriction over eight months) or by a sudden, severe climatic event occurring shortly before reproduction (80% caloric restriction over a month). Grey mouse lemurs evolved under the harsh, unpredictable climate of the dry forest of Madagascar and should thus display great potential for physiological adjustments to energetic bottlenecks. We assessed the resilience of the early stages of reproduction (mating success, fertility, and gestation) to these contrasted food treatments, and on the later stages (lactation and offspring growth) in response to the chronic food shortage only. Food deprived mouse lemurs managed to maintain constant most reproductive parameters, including oestrus timing, estrogenization level at oestrus, mating success, litter size, and litter mass as well as their overall number of surviving offspring at weaning. However, offspring growth was delayed in food restricted mothers. These results suggest that heterothermic, fattening-prone mammals display important reproductive resilience to energetic bottlenecks. More generally, species living in variable and unpredictable habitats may have evolved a flexible reproductive physiology that helps buffer environmental fluctuations. PMID:22848507

Reproductive resilience to food shortage in a small heterothermic primate.

PubMed

Canale, Cindy I; Huchard, Elise; Perret, Martine; Henry, Pierre-Yves

2012-01-01

The massive energetic costs entailed by reproduction in most mammalian females may increase the vulnerability of reproductive success to food shortage. Unexpected events of unfavorable climatic conditions are expected to rise in frequency and intensity as climate changes. The extent to which physiological flexibility allows organisms to maintain reproductive output constant despite energetic bottlenecks has been poorly investigated. In mammals, reproductive resilience is predicted to be maximal during early stages of reproduction, due to the moderate energetic costs of ovulation and gestation relative to lactation. We experimentally tested the consequences of chronic-moderate and short-acute food shortages on the reproductive output of a small seasonally breeding primate, the grey mouse lemur (Microcebus murinus) under thermo-neutral conditions. These two food treatments were respectively designed to simulate the energetic constraints imposed by a lean year (40% caloric restriction over eight months) or by a sudden, severe climatic event occurring shortly before reproduction (80% caloric restriction over a month). Grey mouse lemurs evolved under the harsh, unpredictable climate of the dry forest of Madagascar and should thus display great potential for physiological adjustments to energetic bottlenecks. We assessed the resilience of the early stages of reproduction (mating success, fertility, and gestation) to these contrasted food treatments, and on the later stages (lactation and offspring growth) in response to the chronic food shortage only. Food deprived mouse lemurs managed to maintain constant most reproductive parameters, including oestrus timing, estrogenization level at oestrus, mating success, litter size, and litter mass as well as their overall number of surviving offspring at weaning. However, offspring growth was delayed in food restricted mothers. These results suggest that heterothermic, fattening-prone mammals display important reproductive resilience to energetic bottlenecks. More generally, species living in variable and unpredictable habitats may have evolved a flexible reproductive physiology that helps buffer environmental fluctuations.

Bottlenecks and multiple introductions: Population genetics of the vector of avian malaria in Hawaii

USGS Publications Warehouse

Fonseca, Dina M.; LaPointe, Dennis A.; Fleischer, Robert C.

2000-01-01

Avian malaria has had a profound impact on the demographics and behaviour of Hawaiian forest birds since its vector, Culex quinquefasciatusthe southern house mosquito, was first introduced to Hawaii around 1830. In order to understand the dynamics of the disease in Hawaii and gain insights into the evolution of vector-mediated parasite–host interactions in general we studied the population genetics of Cx. quinquefasciatus in the Hawaiian Islands. We used both microsatellite and mitochondrial loci. Not surprisingly we found that mosquitoes in Midway, a small island in the Western group, are quite distinct from the populations in the main Hawaiian Islands. However, we also found that in general mosquito populations are relatively isolated even among the main islands, in particular between Hawaii (the Big Island) and the remaining Hawaiian Islands. We found evidence of bottlenecks among populations within the Big Island and an excess of alleles in Maui, the site of the original introduction. The mitochondrial diversity was typically low but higher than expected. The current distribution of mitochondrial haplotypes combined with the microsatellite information lead us to conclude that there have been several introductions and to speculate on some processes that may be responsible for the current population genetics of vectors of avian malaria in Hawaii.

Research on laser marking speed optimization by using genetic algorithm.

PubMed

Wang, Dongyun; Yu, Qiwei; Zhang, Yu

2015-01-01

Laser Marking Machine is the most common coding equipment on product packaging lines. However, the speed of laser marking has become a bottleneck of production. In order to remove this bottleneck, a new method based on a genetic algorithm is designed. On the basis of this algorithm, a controller was designed and simulations and experiments were performed. The results show that using this algorithm could effectively improve laser marking efficiency by 25%.

Linguistics, cognitive psychology, and the Now-or-Never bottleneck.

PubMed

Endress, Ansgar D; Katzir, Roni

2016-01-01

Christiansen & Chater (C&C)'s key premise is that "if linguistic information is not processed rapidly, that information is lost for good" (sect. 1, para. 1). From this "Now-or-Never bottleneck" (NNB), C&C derive "wide-reaching and fundamental implications for language processing, acquisition and change as well as for the structure of language itself" (sect. 2, para. 10). We question both the premise and the consequentiality of its purported implications.

Topographic Steering of Enhanced Ice Flow at the Bottleneck Between East and West Antarctica

NASA Astrophysics Data System (ADS)

Winter, Kate; Ross, Neil; Ferraccioli, Fausto; Jordan, Tom A.; Corr, Hugh F. J.; Forsberg, René; Matsuoka, Kenichi; Olesen, Arne V.; Casal, Tania G.

2018-05-01

Hypothesized drawdown of the East Antarctic Ice Sheet through the "bottleneck" zone between East and West Antarctica would have significant impacts for a large proportion of the Antarctic Ice Sheet. Earth observation satellite orbits and a sparseness of radio echo sounding data have restricted investigations of basal boundary controls on ice flow in this region until now. New airborne radio echo sounding surveys reveal complex topography of high relief beneath the southernmost Weddell/Ross ice divide, with three subglacial troughs connecting interior Antarctica to the Foundation and Patuxent Ice Streams and Siple Coast ice streams. These troughs route enhanced ice flow through the interior of Antarctica but limit potential drawdown of the East Antarctic Ice Sheet through the bottleneck zone. In a thinning or retreating scenario, these topographically controlled corridors of enhanced flow could however drive ice divide migration and increase mass discharge from interior West Antarctica to the Southern Ocean.

Zero-temperature quantum annealing bottlenecks in the spin-glass phase.

PubMed

Knysh, Sergey

2016-08-05

A promising approach to solving hard binary optimization problems is quantum adiabatic annealing in a transverse magnetic field. An instantaneous ground state-initially a symmetric superposition of all possible assignments of N qubits-is closely tracked as it becomes more and more localized near the global minimum of the classical energy. Regions where the energy gap to excited states is small (for instance at the phase transition) are the algorithm's bottlenecks. Here I show how for large problems the complexity becomes dominated by O(log N) bottlenecks inside the spin-glass phase, where the gap scales as a stretched exponential. For smaller N, only the gap at the critical point is relevant, where it scales polynomially, as long as the phase transition is second order. This phenomenon is demonstrated rigorously for the two-pattern Gaussian Hopfield model. Qualitative comparison with the Sherrington-Kirkpatrick model leads to similar conclusions.

Nonbolometric bottleneck in electron-phonon relaxation in ultrathin WSi films

NASA Astrophysics Data System (ADS)

Sidorova, Mariia V.; Kozorezov, A. G.; Semenov, A. V.; Korneeva, Yu. P.; Mikhailov, M. Yu.; Devizenko, A. Yu.; Korneev, A. A.; Chulkova, G. M.; Goltsman, G. N.

2018-05-01

We developed the model of the internal phonon bottleneck to describe the energy exchange between the acoustically soft ultrathin metal film and acoustically rigid substrate. Discriminating phonons in the film into two groups, escaping and nonescaping, we show that electrons and nonescaping phonons may form a unified subsystem, which is cooled down only due to interactions with escaping phonons, either due to direct phonon conversion or indirect sequential interaction with an electronic system. Using an amplitude-modulated absorption of the sub-THz radiation technique, we studied electron-phonon relaxation in ultrathin disordered films of tungsten silicide. We found an experimental proof of the internal phonon bottleneck. The experiment and simulation based on the proposed model agree well, resulting in τe -ph˜14 0 -19 0 ps at TC=3.4 K , supporting the results of earlier measurements by independent techniques.

Chirality specific and spatially uniform synthesis of single-walled carbon nanotubes from a sputtered Co-W bimetallic catalyst

NASA Astrophysics Data System (ADS)

An, Hua; Kumamoto, Akihito; Takezaki, Hiroki; Ohyama, Shinnosuke; Qian, Yang; Inoue, Taiki; Ikuhara, Yuichi; Chiashi, Shohei; Xiang, Rong; Maruyama, Shigeo

2016-07-01

Synthesis of single-walled carbon nanotubes (SWNTs) with well-defined atomic arrangements has been widely recognized in the past few decades as the biggest challenge in the SWNT community, and has become a bottleneck for the application of SWNTs in nano-electronics. Here, we report a selective synthesis of (12, 6) SWNTs with an enrichment of 50%-70% by chemical vapor deposition (CVD) using sputtered Co-W as a catalyst. This is achieved under much milder reduction and growth conditions than those in the previous report using transition-metal molecule clusters as catalyst precursors (Nature, 2014, 510, 522). Meanwhile, in-plane transmission electron microscopy unambiguously identified an intermediate structure of Co6W6C, which is strongly associated with selective growth. However, most of the W atoms disappear after a 5 min CVD growth, which implies that anchoring W may be important in this puzzling Co-W system.Synthesis of single-walled carbon nanotubes (SWNTs) with well-defined atomic arrangements has been widely recognized in the past few decades as the biggest challenge in the SWNT community, and has become a bottleneck for the application of SWNTs in nano-electronics. Here, we report a selective synthesis of (12, 6) SWNTs with an enrichment of 50%-70% by chemical vapor deposition (CVD) using sputtered Co-W as a catalyst. This is achieved under much milder reduction and growth conditions than those in the previous report using transition-metal molecule clusters as catalyst precursors (Nature, 2014, 510, 522). Meanwhile, in-plane transmission electron microscopy unambiguously identified an intermediate structure of Co6W6C, which is strongly associated with selective growth. However, most of the W atoms disappear after a 5 min CVD growth, which implies that anchoring W may be important in this puzzling Co-W system. Electronic supplementary information (ESI) available: Raman spectroscopy (G-band) of SWNTs grown from Co and Co-W catalyst; Kataura plot for chirality assignment; Raman spectra (RBM region) of SWNTs grown from low temperature reduced monometallic Co; relative intensities of the 197 cm-1 peak with respect to the total sum intensity; TEM image of Co-W catalyst reduced at six different temperatures (600, 650, 700, 750, 800, and 850 °C) TEM images of SWNTs grown from Co monometallic catalyst. See DOI: 10.1039/c6nr02749k

The footwear factory's assembly sector: opposing organizational structure and quality from the ergonomic work analysis.

PubMed

Silva, Kláudia M M N; Coelho, Bernardo G P; Junior, Josemir V S; Faria, Luiz F M; Dutra, Ludmila; Alvarenga, Marília; Roggini, Renan; Echternach, Eliza Helena de Oliveira

2012-01-01

Data from 2006 indicated that Brazilian footwear leather industry was composed of approximately 9,488 formally registered establishments, considering the leather industry, footwear and leather goods. It was responsible for 211,582 people employed. However, in spite of having many employees, this kind of organization found several problems when analyzed from the ergonomics view. With this premise, then, in order to identify bottlenecks and other engineering problems that could cause discomfort and motivation lack among workers, leading directly to the loss of the product quality, the assembly sector of women's shoes factory was characterized.

Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations.

PubMed

Tamborero, David; Rubio-Perez, Carlota; Deu-Pons, Jordi; Schroeder, Michael P; Vivancos, Ana; Rovira, Ana; Tusquets, Ignasi; Albanell, Joan; Rodon, Jordi; Tabernero, Josep; de Torres, Carmen; Dienstmann, Rodrigo; Gonzalez-Perez, Abel; Lopez-Bigas, Nuria

2018-03-28

While tumor genome sequencing has become widely available in clinical and research settings, the interpretation of tumor somatic variants remains an important bottleneck. Here we present the Cancer Genome Interpreter, a versatile platform that automates the interpretation of newly sequenced cancer genomes, annotating the potential of alterations detected in tumors to act as drivers and their possible effect on treatment response. The results are organized in different levels of evidence according to current knowledge, which we envision can support a broad range of oncology use cases. The resource is publicly available at http://www.cancergenomeinterpreter.org .

Principles of cell-free genetic circuit assembly.

PubMed

Noireaux, Vincent; Bar-Ziv, Roy; Libchaber, Albert

2003-10-28

Cell-free genetic circuit elements were constructed in a transcription-translation extract. We engineered transcriptional activation and repression cascades, in which the protein product of each stage is the input required to drive or block the following stage. Although we can find regions of linear response for single stages, cascading to subsequent stages requires working in nonlinear regimes. Substantial time delays and dramatic decreases in output production are incurred with each additional stage because of a bottleneck at the translation machinery. Faster turnover of RNA message can relieve competition between genes and stabilize output against variations in input and parameters.

Prehistoric genomes reveal the genetic foundation and cost of horse domestication.

PubMed

Schubert, Mikkel; Jónsson, Hákon; Chang, Dan; Der Sarkissian, Clio; Ermini, Luca; Ginolhac, Aurélien; Albrechtsen, Anders; Dupanloup, Isabelle; Foucal, Adrien; Petersen, Bent; Fumagalli, Matteo; Raghavan, Maanasa; Seguin-Orlando, Andaine; Korneliussen, Thorfinn S; Velazquez, Amhed M V; Stenderup, Jesper; Hoover, Cindi A; Rubin, Carl-Johan; Alfarhan, Ahmed H; Alquraishi, Saleh A; Al-Rasheid, Khaled A S; MacHugh, David E; Kalbfleisch, Ted; MacLeod, James N; Rubin, Edward M; Sicheritz-Ponten, Thomas; Andersson, Leif; Hofreiter, Michael; Marques-Bonet, Tomas; Gilbert, M Thomas P; Nielsen, Rasmus; Excoffier, Laurent; Willerslev, Eske; Shapiro, Beth; Orlando, Ludovic

2014-12-30

The domestication of the horse ∼ 5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the "cost of domestication" hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place.

A Catalog of Regulatory Sequences for Trait Gene for the Genome Editing of Wheat.

PubMed

Makai, Szabolcs; Tamás, László; Juhász, Angéla

2016-01-01

Wheat has been cultivated for 10000 years and ever since the origin of hexaploid wheat it has been exempt from natural selection. Instead, it was under the constant selective pressure of human agriculture from harvest to sowing during every year, producing a vast array of varieties. Wheat has been adopted globally, accumulating variation for genes involved in yield traits, environmental adaptation and resistance. However, one small but important part of the wheat genome has hardly changed: the regulatory regions of both the x- and y-type high molecular weight glutenin subunit (HMW-GS) genes, which are alone responsible for approximately 12% of the grain protein content. The phylogeny of the HMW-GS regulatory regions of the Triticeae demonstrates that a genetic bottleneck may have led to its decreased diversity during domestication and the subsequent cultivation. It has also highlighted the fact that the wild relatives of wheat may offer an unexploited genetic resource for the regulatory region of these genes. Significant research efforts have been made in the public sector and by international agencies, using wild crosses to exploit the available genetic variation, and as a result synthetic hexaploids are now being utilized by a number of breeding companies. However, a newly emerging tool of genome editing provides significantly improved efficiency in exploiting the natural variation in HMW-GS genes and incorporating this into elite cultivars and breeding lines. Recent advancement in the understanding of the regulation of these genes underlines the needs for an overview of the regulatory elements for genome editing purposes.

Prehistoric genomes reveal the genetic foundation and cost of horse domestication

PubMed Central

Jónsson, Hákon; Chang, Dan; Der Sarkissian, Clio; Ermini, Luca; Ginolhac, Aurélien; Albrechtsen, Anders; Dupanloup, Isabelle; Foucal, Adrien; Petersen, Bent; Fumagalli, Matteo; Raghavan, Maanasa; Seguin-Orlando, Andaine; Velazquez, Amhed M. V.; Stenderup, Jesper; Hoover, Cindi A.; Rubin, Carl-Johan; Alfarhan, Ahmed H.; Alquraishi, Saleh A.; Al-Rasheid, Khaled A. S.; Kalbfleisch, Ted; MacLeod, James N.; Rubin, Edward M.; Andersson, Leif; Hofreiter, Michael; Marques-Bonet, Tomas; Gilbert, M. Thomas P.; Nielsen, Rasmus; Excoffier, Laurent; Willerslev, Eske; Shapiro, Beth; Orlando, Ludovic

2014-01-01

The domestication of the horse ∼5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski’s horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the “cost of domestication” hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place. PMID:25512547

How cognitive heuristics can explain social interactions in spatial movement.

PubMed

Seitz, Michael J; Bode, Nikolai W F; Köster, Gerta

2016-08-01

The movement of pedestrian crowds is a paradigmatic example of collective motion. The precise nature of individual-level behaviours underlying crowd movements has been subject to a lively debate. Here, we propose that pedestrians follow simple heuristics rooted in cognitive psychology, such as 'stop if another step would lead to a collision' or 'follow the person in front'. In other words, our paradigm explicitly models individual-level behaviour as a series of discrete decisions. We show that our cognitive heuristics produce realistic emergent crowd phenomena, such as lane formation and queuing behaviour. Based on our results, we suggest that pedestrians follow different cognitive heuristics that are selected depending on the context. This differs from the widely used approach of capturing changes in behaviour via model parameters and leads to testable hypotheses on changes in crowd behaviour for different motivation levels. For example, we expect that rushed individuals more often evade to the side and thus display distinct emergent queue formations in front of a bottleneck. Our heuristics can be ranked according to the cognitive effort that is required to follow them. Therefore, our model establishes a direct link between behavioural responses and cognitive effort and thus facilitates a novel perspective on collective behaviour. © 2016 The Author(s).

How cognitive heuristics can explain social interactions in spatial movement

PubMed Central

Köster, Gerta

2016-01-01

The movement of pedestrian crowds is a paradigmatic example of collective motion. The precise nature of individual-level behaviours underlying crowd movements has been subject to a lively debate. Here, we propose that pedestrians follow simple heuristics rooted in cognitive psychology, such as ‘stop if another step would lead to a collision’ or ‘follow the person in front’. In other words, our paradigm explicitly models individual-level behaviour as a series of discrete decisions. We show that our cognitive heuristics produce realistic emergent crowd phenomena, such as lane formation and queuing behaviour. Based on our results, we suggest that pedestrians follow different cognitive heuristics that are selected depending on the context. This differs from the widely used approach of capturing changes in behaviour via model parameters and leads to testable hypotheses on changes in crowd behaviour for different motivation levels. For example, we expect that rushed individuals more often evade to the side and thus display distinct emergent queue formations in front of a bottleneck. Our heuristics can be ranked according to the cognitive effort that is required to follow them. Therefore, our model establishes a direct link between behavioural responses and cognitive effort and thus facilitates a novel perspective on collective behaviour. PMID:27581483

Massive gene acquisitions in Mycobacterium indicus pranii provide a perspective on mycobacterial evolution

PubMed Central

Saini, Vikram; Raghuvanshi, Saurabh; Khurana, Jitendra P.; Ahmed, Niyaz; Hasnain, Seyed E.; Tyagi, Akhilesh K.; Tyagi, Anil K.

2012-01-01

Understanding the evolutionary and genomic mechanisms responsible for turning the soil-derived saprophytic mycobacteria into lethal intracellular pathogens is a critical step towards the development of strategies for the control of mycobacterial diseases. In this context, Mycobacterium indicus pranii (MIP) is of specific interest because of its unique immunological and evolutionary significance. Evolutionarily, it is the progenitor of opportunistic pathogens belonging to M. avium complex and is endowed with features that place it between saprophytic and pathogenic species. Herein, we have sequenced the complete MIP genome to understand its unique life style, basis of immunomodulation and habitat diversification in mycobacteria. As a case of massive gene acquisitions, 50.5% of MIP open reading frames (ORFs) are laterally acquired. We show, for the first time for Mycobacterium, that MIP genome has mosaic architecture. These gene acquisitions have led to the enrichment of selected gene families critical to MIP physiology. Comparative genomic analysis indicates a higher antigenic potential of MIP imparting it a unique ability for immunomodulation. Besides, it also suggests an important role of genomic fluidity in habitat diversification within mycobacteria and provides a unique view of evolutionary divergence and putative bottlenecks that might have eventually led to intracellular survival and pathogenic attributes in mycobacteria. PMID:22965120

Finding stable cellulase and xylanase: evaluation of the synergistic effect of pH and temperature.

PubMed

Farinas, Cristiane S; Loyo, Marcel Moitas; Baraldo, Anderson; Tardioli, Paulo W; Neto, Victor Bertucci; Couri, Sonia

2010-12-31

Ethanol from lignocellulosic biomass has been recognized as one of the most promising alternatives for the production of renewable and sustainable energy. However, one of the major bottlenecks holding back its commercialization is the high costs of the enzymes needed for biomass conversion. In this work, we studied the enzymes produced from a selected strain of Aspergillus niger under solid state fermentation. The cellulase and xylanase enzymatic cocktail was characterized in terms of pH and temperature by using response surface methodology. Thermostability and kinetic parameters were also determined. The statistical analysis of pH and temperature effects on enzymatic activity showed a synergistic interaction of these two variables, thus enabling to find a pH and temperature range in which the enzymes have a higher activity. The results obtained allowed the construction of mathematical models used to predict endoglucanase, β-glucosidase and xylanase activities under different pH and temperature conditions. Optimum temperature values for all three enzymes were found to be in the range between 35°C and 60°C, and the optimum pH range was found between 4 and 5.5. The methodology employed here was very effective in estimating enzyme behavior under different process conditions. Copyright © 2010 Elsevier B.V. All rights reserved.

Exact Markov chains versus diffusion theory for haploid random mating.

PubMed

Tyvand, Peder A; Thorvaldsen, Steinar

2010-05-01

Exact discrete Markov chains are applied to the Wright-Fisher model and the Moran model of haploid random mating. Selection and mutations are neglected. At each discrete value of time t there is a given number n of diploid monoecious organisms. The evolution of the population distribution is given in diffusion variables, to compare the two models of random mating with their common diffusion limit. Only the Moran model converges uniformly to the diffusion limit near the boundary. The Wright-Fisher model allows the population size to change with the generations. Diffusion theory tends to under-predict the loss of genetic information when a population enters a bottleneck. 2010 Elsevier Inc. All rights reserved.

HRSSA - Efficient hybrid stochastic simulation for spatially homogeneous biochemical reaction networks

NASA Astrophysics Data System (ADS)

Marchetti, Luca; Priami, Corrado; Thanh, Vo Hong

2016-07-01

This paper introduces HRSSA (Hybrid Rejection-based Stochastic Simulation Algorithm), a new efficient hybrid stochastic simulation algorithm for spatially homogeneous biochemical reaction networks. HRSSA is built on top of RSSA, an exact stochastic simulation algorithm which relies on propensity bounds to select next reaction firings and to reduce the average number of reaction propensity updates needed during the simulation. HRSSA exploits the computational advantage of propensity bounds to manage time-varying transition propensities and to apply dynamic partitioning of reactions, which constitute the two most significant bottlenecks of hybrid simulation. A comprehensive set of simulation benchmarks is provided for evaluating performance and accuracy of HRSSA against other state of the art algorithms.

Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans.

PubMed

Keinan, Alon; Mullikin, James C; Patterson, Nick; Reich, David

2007-10-01

Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians.

Non-invasive optical modulation of local vascular permeability

NASA Astrophysics Data System (ADS)

Choi, Myunghwan; Choi, Chulhee

2011-03-01

For a systemically administered drug to act, it first needs to cross the vascular wall. This step represents a bottleneck for drug development, especially in the brain or retina, where tight junctions between endothelial cells form physiological barriers. Here, we demonstrate that femtosecond pulsed laser irradiation focused on the blood vessel wall induces transient permeabilization of plasma. Nonlinear absorption of the pulsed laser enabled the noninvasive modulation of vascular permeability with high spatial selectivity in three dimensions. By combining this method with systemic injection, we could locally deliver molecular probes in various tissues, such as brain cortex, meninges, ear, striated muscle, and bone. We suggest this method as a novel delivery tool for molecular probes or drugs.

Human resources and access to maternal health care.

PubMed

ten Hoope-Bender, P; Liljestrand, J; MacDonagh, S

2006-09-01

The lack of human resources is one of the main bottlenecks to achieving the Millennium Development Goals on maternal and child health. A coherent national policy, recognized across government, needs to be in place to overcome this especially in countries severely affected by HIV/AIDS. Such a policy should cover selection of pre-service students, the qualifications of trainers and training sites, supportive supervision, career path development, a package of carefully thought-out incentives for the retention of staff, strategies for interaction with communities, and an agreed-upon health staff HIV/AIDS policy. Without such coherent human resource planning, a large number of countries will fail to reduce maternal and newborn mortality.

Evaluating the roles of directed breeding and gene flow in animal domestication

PubMed Central

Marshall, Fiona B.; Dobney, Keith; Denham, Tim; Capriles, José M.

2014-01-01

For the last 150 y scholars have focused upon the roles of intentional breeding and genetic isolation as fundamental to understanding the process of animal domestication. This analysis of ethnoarchaeological, archaeological, and genetic data suggests that long-term gene flow between wild and domestic stocks was much more common than previously assumed, and that selective breeding of females was largely absent during the early phases of animal domestication. These findings challenge assumptions about severe genetic bottlenecks during domestication, expectations regarding monophyletic origins, and interpretations of multiple domestications. The findings also raise new questions regarding ways in which behavioral and phenotypic domestication traits were developed and maintained. PMID:24753599

Facial recognition using multisensor images based on localized kernel eigen spaces.

PubMed

Gundimada, Satyanadh; Asari, Vijayan K

2009-06-01

A feature selection technique along with an information fusion procedure for improving the recognition accuracy of a visual and thermal image-based facial recognition system is presented in this paper. A novel modular kernel eigenspaces approach is developed and implemented on the phase congruency feature maps extracted from the visual and thermal images individually. Smaller sub-regions from a predefined neighborhood within the phase congruency images of the training samples are merged to obtain a large set of features. These features are then projected into higher dimensional spaces using kernel methods. The proposed localized nonlinear feature selection procedure helps to overcome the bottlenecks of illumination variations, partial occlusions, expression variations and variations due to temperature changes that affect the visual and thermal face recognition techniques. AR and Equinox databases are used for experimentation and evaluation of the proposed technique. The proposed feature selection procedure has greatly improved the recognition accuracy for both the visual and thermal images when compared to conventional techniques. Also, a decision level fusion methodology is presented which along with the feature selection procedure has outperformed various other face recognition techniques in terms of recognition accuracy.

Research on Laser Marking Speed Optimization by Using Genetic Algorithm

PubMed Central

Wang, Dongyun; Yu, Qiwei; Zhang, Yu

2015-01-01

Laser Marking Machine is the most common coding equipment on product packaging lines. However, the speed of laser marking has become a bottleneck of production. In order to remove this bottleneck, a new method based on a genetic algorithm is designed. On the basis of this algorithm, a controller was designed and simulations and experiments were performed. The results show that using this algorithm could effectively improve laser marking efficiency by 25%. PMID:25955831

Architecture studies and system demonstrations for optical parallel processor for AI and NI

NASA Astrophysics Data System (ADS)

Lee, Sing H.

1988-03-01

In solving deterministic AI problems the data search for matching the arguments of a PROLOG expression causes serious bottleneck when implemented sequentially by electronic systems. To overcome this bottleneck we have developed the concepts for an optical expert system based on matrix-algebraic formulation, which will be suitable for parallel optical implementation. The optical AI system based on matrix-algebraic formation will offer distinct advantages for parallel search, adult learning, etc.

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps

PubMed Central

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J.; Hunt, Sarah; Deloukas, Panos; Bentley, David R.; Morton, Newton E.

2004-01-01

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences. PMID:15604137

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.

PubMed

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J; Hunt, Sarah; Deloukas, Panos; Bentley, David R; Morton, Newton E

2004-12-28

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences.

Bottleneck effects on the bidirectional crowd dynamics

NASA Astrophysics Data System (ADS)

Yang, Xiao-Xia; Dong, Hai-Rong; Yao, Xiu-Ming; Sun, Xu-Bin

2016-12-01

The bottleneck effect on bidirectional crowd dynamics is of great theoretical and practical significance, especially for the designing of corridors in public places, such as subway stations or airports. Based on the famous social force model, this paper investigates the bottleneck effects on the free flow dynamics and breakdown phenomenon under different scenarios, in which different corridor shapes and inflow ratios are considered simultaneously. Numerical simulation finds an interesting self-organization phenomenon in the bidirectional flow, a typical characteristic of such a phenomenon is called lane formation, and the existence of which is independent of the corridor’s shape and inflow rate. However, the pattern of the lane formed by pedestrian flow is related to the corridor’s shape, and the free flow efficiency has close relationship with the inflow rate. Specifically, breakdown phenomenon occurs when inflows from both sides of the corridor are large enough, which mostly originates from the bottleneck and then gradually spreads to the other regions. Simulation results further indicate that the leaving efficiency becomes low as breakdown occurs, and the degree of congestion is proportional to the magnitude of inflow. The findings presented in this paper match well with some of our daily observations, hence it is possible to use them to provide us with theoretical suggestions in design of infrastructures. Project supported jointly by the National Natural Science Foundation of China (Grant Nos. 61322307 and 2016YJS023).

Process-based Assignment-Setting Change for Support of Overcoming Bottlenecks in Learning by Problem-Posing in Arithmetic Word Problems

NASA Astrophysics Data System (ADS)

Supianto, A. A.; Hayashi, Y.; Hirashima, T.

2017-02-01

Problem-posing is well known as an effective activity to learn problem-solving methods. Monsakun is an interactive problem-posing learning environment to facilitate arithmetic word problems learning for one operation of addition and subtraction. The characteristic of Monsakun is problem-posing as sentence-integration that lets learners make a problem of three sentences. Monsakun provides learners with five or six sentences including dummies, which are designed through careful considerations by an expert teacher as a meaningful distraction to the learners in order to learn the structure of arithmetic word problems. The results of the practical use of Monsakun in elementary schools show that many learners have difficulties in arranging the proper answer at the high level of assignments. The analysis of the problem-posing process of such learners found that their misconception of arithmetic word problems causes impasses in their thinking and mislead them to use dummies. This study proposes a method of changing assignments as a support for overcoming bottlenecks of thinking. In Monsakun, the bottlenecks are often detected as a frequently repeated use of a specific dummy. If such dummy can be detected, it is the key factor to support learners to overcome their difficulty. This paper discusses how to detect the bottlenecks and to realize such support in learning by problem-posing.

Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae

PubMed Central

2011-01-01

Background The expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations to high-level expression of active viral surface glycoproteins in yeast are not well understood. To identify possible bottlenecks we performed a detailed study on overexpression of recombinant mumps hemagglutinin-neuraminidase (MuHN) and measles hemagglutinin (MeH) in yeast Saccharomyces cerevisiae, combining the analysis of recombinant proteins with a proteomic approach. Results Overexpressed recombinant MuHN and MeH proteins were present in large aggregates, were inactive and totally insoluble under native conditions. Moreover, the majority of recombinant protein was found in immature form of non-glycosylated precursors. Fractionation of yeast lysates revealed that the core of viral surface protein aggregates consists of MuHN or MeH disulfide-linked multimers involving eukaryotic translation elongation factor 1A (eEF1A) and is closely associated with small heat shock proteins (sHsps) that can be removed only under denaturing conditions. Complexes of large Hsps seem to be bound to aggregate core peripherally as they can be easily removed at high salt concentrations. Proteomic analysis revealed that the accumulation of unglycosylated viral protein precursors results in specific cytosolic unfolded protein response (UPR-Cyto) in yeast cells, characterized by different action and regulation of small Hsps versus large chaperones of Hsp70, Hsp90 and Hsp110 families. In contrast to most environmental stresses, in the response to synthesis of recombinant MuHN and MeH, only the large Hsps were upregulated whereas sHsps were not. Interestingly, the amount of eEF1A was also increased during this stress response. Conclusions Inefficient translocation of MuHN and MeH precursors through ER membrane is a bottleneck for high-level expression in yeast. Overexpression of these recombinant proteins induces the UPR's cytosolic counterpart, the UPR-Cyto, which represent a subset of proteins involved in the heat-shock response. The involvement of eEF1A may explain the mechanism by which only large chaperones, but not small Hsps are upregulated during this stress response. Our study highlights important differences between viral surface protein expression in yeast and mammalian cells at the first stage of secretory pathway. PMID:21595909

Reducing bottlenecks: professionals’ and adolescents’ experiences with transitional care delivery

PubMed Central

2014-01-01

Background The purpose of this study was to describe the interventions implemented in a quality improvement programme to improve transitional care and evaluate its effectiveness in reducing bottlenecks as perceived by professionals and improving chronically ill adolescents’ experiences with care delivery. Methods This longitudinal study was undertaken with adolescents and professionals who participated in the Dutch ‘On Your Own Feet Ahead!’ quality improvement programme. This programme followed the Breakthrough Series improvement and implementation strategy. A total of 102/128 (79.7%) professionals from 21 hospital teams filled out a questionnaire at the start of the programme (T0), and 79/123 (64.2%; five respondents had changed jobs) professionals completed the same questionnaire 1 year later (T1). Seventy-two (58.5%) professionals from 21 teams returned questionnaires at both time points. Of 389 and 430 participating adolescents, 36% and 41% returned questionnaires at T0 and T1, respectively. We used descriptive statistics and two-tailed, paired t-tests to investigate improvements in bottlenecks in transitional care (perceived by professionals) and care delivery (perceived by adolescents). Results Professionals observed improvement in all bottlenecks at T1 (vs. T0; p < 0.05), especially in the organisation of care, such as the presence of a joint mission between paediatric and adult care, coordination of care, and availability of more resources for joint care services. Within a 1-year period, the transition programme improved some aspects of patients’ experiences with care delivery, such as the provision of opportunities for adolescents to visit the clinic alone (p < 0.001) and to decide who should be present during consultations (p < 0.05). Conclusions This study demonstrated that transitional care interventions may improve the organisation and coordination of transitional care and better prepare adolescents for the transition to adult care within a 1-year period. By setting specific goals based on experiences with bottlenecks, the breakthrough approach helped to improve transitional care delivery for adolescents with chronic conditions. PMID:24485282

Hydroetching of high surface area ceramics using moist supercritical fluids

DOEpatents

Fryxell, Glen; Zemanian, Thomas S.

2004-11-02

Aerogels having a high density of hydroxyl groups and a more uniform pore size with fewer bottlenecks are described. The aerogel is exposed to a mixture of a supercritical fluid and water, whereupon the aerogel forms a high density of hydroxyl groups. The process also relaxes the aerogel into a more open uniform internal structure, in a process referred to as hydroetching. The hydroetching process removes bottlenecks from the aerogels, and forms the hydrogels into more standard pore sizes while preserving their high surface area.

Brain mechanisms of recovery from pure alexia: A single case study with multiple longitudinal scans.

PubMed

Cohen, Laurent; Dehaene, Stanislas; McCormick, Samantha; Durant, Szonya; Zanker, Johannes M

2016-10-01

Pure alexia is an acquired reading disorder, typically due to a left occipito-temporal lesion affecting the Visual Word Form Area (VWFA). It is unclear whether the VWFA acts as a unique bottleneck for reading, or whether alternative routes are available for recovery. Here, we address this issue through the single-case longitudinal study of a neuroscientist who experienced pure alexia and participated in 17 behavioral, 9 anatomical, and 9 fMRI assessment sessions over a period of two years. The origin of the impairment was assigned to a small left fusiform lesion, accompanied by a loss of VWFA responsivity and by the degeneracy of the associated white matter pathways. fMRI experiments allowed us to image longitudinally the visual perception of words, as compared to other classes of stimuli, as well as the mechanisms of letter-by-letter reading. The progressive improvement of reading was not associated with the re-emergence of a new area selective to words, but with increasing responses in spared occipital cortex posterior to the lesion and in contralateral right occipital cortex. Those regions showed a non-specific increase of activations over time and an increase in functional correlation with distant language areas. Those results confirm the existence of an alternative occipital route for reading, bypassing the VWFA, but they also point to its key limitation: the patient remained a slow letter-by-letter reader, thus supporting the critical importance of the VWFA for the efficient parallel recognition of written words. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibitory masking controls the threshold sensitivity of retinal ganglion cells

PubMed Central

Pan, Feng; Toychiev, Abduqodir; Zhang, Yi; Atlasz, Tamas; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Völgyi, Béla; Akopian, Abram

2016-01-01

Key points Retinal ganglion cells (RGCs) in dark‐adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance.Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways.The masking inhibition is subserved by GABAC receptors, probably on bipolar cell axon terminals.The GABAergic masking inhibition appears independent of dopaminergic circuitry that has been shown also to affect RGC sensitivity.The results indicate a novel mechanism whereby inhibition controls the sensitivity of different cohorts of RGCs. This can limit and thereby ensure that appropriate signals are carried centrally in scotopic conditions when sensitivity rather than acuity is crucial. Abstract The responses of rod photoreceptors, which subserve dim light vision, are carried through the retina by three independent pathways. These pathways carry signals with largely different sensitivities. Retinal ganglion cells (RGCs), the output neurons of the retina, show a wide range of sensitivities in the same dark‐adapted conditions, suggesting a divergence of the rod pathways. However, this organization is not supported by the known synaptic morphology of the retina. Here, we tested an alternative idea that the rod pathways converge onto single RGCs, but inhibitory circuits selectively mask signals so that one pathway predominates. Indeed, we found that application of GABA receptor blockers increased the sensitivity of most RGCs by unmasking rod signals, which were suppressed. Our results indicate that inhibition controls the threshold responses of RGCs under dim ambient light. This mechanism can ensure that appropriate signals cross the bottleneck of the optic nerve in changing stimulus conditions. PMID:27350405

Automating X-ray Fluorescence Analysis for Rapid Astrobiology Surveys.

PubMed

Thompson, David R; Flannery, David T; Lanka, Ravi; Allwood, Abigail C; Bue, Brian D; Clark, Benton C; Elam, W Timothy; Estlin, Tara A; Hodyss, Robert P; Hurowitz, Joel A; Liu, Yang; Wade, Lawrence A

2015-11-01

A new generation of planetary rover instruments, such as PIXL (Planetary Instrument for X-ray Lithochemistry) and SHERLOC (Scanning Habitable Environments with Raman Luminescence for Organics and Chemicals) selected for the Mars 2020 mission rover payload, aim to map mineralogical and elemental composition in situ at microscopic scales. These instruments will produce large spectral cubes with thousands of channels acquired over thousands of spatial locations, a large potential science yield limited mainly by the time required to acquire a measurement after placement. A secondary bottleneck also faces mission planners after downlink; analysts must interpret the complex data products quickly to inform tactical planning for the next command cycle. This study demonstrates operational approaches to overcome these bottlenecks by specialized early-stage science data processing. Onboard, simple real-time systems can perform a basic compositional assessment, recognizing specific features of interest and optimizing sensor integration time to characterize anomalies. On the ground, statistically motivated visualization can make raw uncalibrated data products more interpretable for tactical decision making. Techniques such as manifold dimensionality reduction can help operators comprehend large databases at a glance, identifying trends and anomalies in data. These onboard and ground-side analyses can complement a quantitative interpretation. We evaluate system performance for the case study of PIXL, an X-ray fluorescence spectrometer. Experiments on three representative samples demonstrate improved methods for onboard and ground-side automation and illustrate new astrobiological science capabilities unavailable in previous planetary instruments. Dimensionality reduction-Planetary science-Visualization.

Genetic variability and founder effect in the pitcher plant Sarracenia purpurea (Sarraceniaceae) in populations introduced into Switzerland: from inbreeding to invasion.

PubMed

Parisod, Christian; Trippi, Charlotte; Galland, Nicole

2005-01-01

The long-lived and mainly outcrossing species Sarracenia purpurea has been introduced into Switzerland and become invasive. This creates the opportunity to study reactions to founder effect and how a species can circumvent deleterious effects of bottlenecks such as reduced genetic diversity, inbreeding and extinction through mutational meltdown, to emerge as a highly invasive plant. A population genetic survey by random amplified polymorphism DNA markers (RAPD) together with historical insights and a field pollination experiment were carried out. At the regional scale, S. purpurea shows low structure (thetast=0.072) due to a recent founder event and important subsequent growth. Nevertheless, multivariate statistical analyses reveal that, because of a bottleneck that shifted allele frequencies, most of the variability is independent among populations. In one population (Tenasses) the species has become invasive and genetic analysis reveals restricted gene flow and family structure (thetast=0.287). Although inbreeding appears to be high (Fis >0.410 from a Bayesian estimation), a field pollination experiment failed to detect significant inbreeding depression upon F1 seed number and seed weight fitness-traits. Furthermore, crosses between unrelated individuals produced F1 seeds with significantly reduced fitness, thus showing local outbreeding depression. The results suggest that, under restricted gene flow among families, the species may not only have rapidly purged deleterious alleles, but also have undergone some form of selection for inbreeding due to co-adaptation between loci.

Improving the delivery of global tobacco control.

PubMed

Bitton, Asaf; Green, Carol; Colbert, James

2011-01-01

Tobacco control must remain a critical global health priority given the growing burden of tobacco-induced disease in the developing world. Insights from the emerging field of global health delivery suggest that tobacco control could be improved through a systematic, granular analysis of the processes through which it is promoted, implemented, and combated. Using this framework, a critical bottleneck to the delivery of proven health promotion emerges in the role that the tobacco industry plays in promoting tobacco use and blocking effective tobacco-control policies. This "corporate bottleneck" can also be understood as a root cause of massive disease and suffering upon vulnerable populations worldwide, for the goal of maximizing corporate profit. Naming, understanding, and responding to this corporate bottleneck is crucial to the success of tobacco-control policies. Three case studies of tobacco-control policy--South Africa, the Framework Convention on Tobacco Control, and Uruguay--are presented to explore and understand the implications of this analysis. © 2011 Mount Sinai School of Medicine.

Understanding of empty container movement: A study on a bottleneck at an off-dock depot

NASA Astrophysics Data System (ADS)

Zain, Rosmaizura Mohd; Rahman, Mohd Nizam Ab; Nopiah, Zulkifli Mohd; Saibani, Nizaroyani

2014-09-01

Port not only function as connections between marine and land transportation but also as core business areas. In a port terminal, available space is limited, but the influx of container is growing. The off-dock depot is one of the key supply chain players that hold empty containers in the inventory. Therefore, this paper aims to identify the main factors of bottlenecks or congestion that hinder the rapid movement of empty containers from the off-dock depot to the customers. Thirty interviews were conducted with individuals who are key players in the container supply chain. The data were analyzed using Atlas.ti software and the analytic hierarchy process to rank the priority factors of bottlenecks. Findings show that several pertinent factors act as barriers to the key players in the container movement in the day-to-day operations. In future studies, strategies to overcome fragmentation in the container supply chain and logistics must be determined.

STEPS: lean thinking, theory of constraints and identifying bottlenecks in an emergency department.

PubMed

Ryan, A; Hunter, K; Cunningham, K; Williams, J; O'Shea, H; Rooney, P; Hickey, F

2013-04-01

This study aimed to identify the bottlenecks in patients' journeys through an emergency department (ED). For each stage of the patient journey, the average times were compared between two groups divided according to the four hour time frame and disproportionate delays were identified using a significance test These bottlenecks were evaluated with reference to a lean thinking value-stream map and the five focusing steps of the theory of constraints. A total of 434 (72.5%) ED patients were tracked over one week. Logistic regression showed that patients who had radiological tests, blood tests or who were admitted were 4.4, 4.1 and 7.7 times more likely, respectively, to stay over four hours in the ED than those who didn't The stages that were significantly delayed were the time spent waiting for radiology (p = 0.001), waiting for the in-patient team (p = 0.004), waiting for a bed (p < 0.001) and ED doctor turnaround time (p < 0.001).

Are all intertidal wetlands naturally created equal? Bottlenecks, thresholds and knowledge gaps to mangrove and saltmarsh ecosystems

USGS Publications Warehouse

Friess, Daniel A.; Krauss, Ken W.; Horstman, Erik M.; Balke, Thorsten; Bouma, Tjeerd J.; Galli, Demis; Webb, Edward L.

2011-01-01

Intertidal wetlands such as saltmarshes and mangroves provide numerous important ecological functions, though they are in rapid and global decline. To better conserve and restore these wetland ecosystems, we need an understanding of the fundamental natural bottlenecks and thresholds to their establishment and long-term ecological maintenance. Despite inhabiting similar intertidal positions, the biological traits of these systems differ markedly in structure, phenology, life history, phylogeny and dispersal, suggesting large differences in biophysical interactions. By providing the first systematic comparison between saltmarshes and mangroves, we unravel how the interplay between species-specific life-history traits, biophysical interactions and biogeomorphological feedback processes determine where, when and what wetland can establish, the thresholds to long-term ecosystem stability, and constraints to genetic connectivity between intertidal wetland populations at the landscape level. To understand these process interactions, research into the constraints to wetland development, and biological adaptations to overcome these critical bottlenecks and thresholds requires a truly interdisciplinary approach.

Impact of memory bottleneck on the performance of graphics processing units

NASA Astrophysics Data System (ADS)

Son, Dong Oh; Choi, Hong Jun; Kim, Jong Myon; Kim, Cheol Hong

2015-12-01

Recent graphics processing units (GPUs) can process general-purpose applications as well as graphics applications with the help of various user-friendly application programming interfaces (APIs) supported by GPU vendors. Unfortunately, utilizing the hardware resource in the GPU efficiently is a challenging problem, since the GPU architecture is totally different to the traditional CPU architecture. To solve this problem, many studies have focused on the techniques for improving the system performance using GPUs. In this work, we analyze the GPU performance varying GPU parameters such as the number of cores and clock frequency. According to our simulations, the GPU performance can be improved by 125.8% and 16.2% on average as the number of cores and clock frequency increase, respectively. However, the performance is saturated when memory bottleneck problems incur due to huge data requests to the memory. The performance of GPUs can be improved as the memory bottleneck is reduced by changing GPU parameters dynamically.

Helical bottleneck effect in 3D homogeneous isotropic turbulence

NASA Astrophysics Data System (ADS)

Stepanov, Rodion; Golbraikh, Ephim; Frick, Peter; Shestakov, Alexander

2018-02-01

We present the results of modelling the development of homogeneous and isotropic turbulence with a large-scale source of energy and a source of helicity distributed over scales. We use the shell model for numerical simulation of the turbulence at high Reynolds number. The results show that the helicity injection leads to a significant change in the behavior of the energy and helicity spectra in scales larger and smaller than the energy injection scale. We suggest the phenomenology for direct turbulent cascades with the helicity effect, which reduces the efficiency of the spectral energy transfer. Therefore the energy is accumulated and redistributed so that non-linear interactions will be sufficient to provide a constant energy flux. It can be interpreted as the ‘helical bottleneck effect’ which, depending on the parameters of the injection helicity, reminds one of the well-known bottleneck effect at the end of inertial range. Simulations which included the infrared part of the spectrum show that the inverse cascade hardly develops under distributed helicity forcing.

A novel cell autolysis system for cost-competitive downstream processing.

PubMed

Hajnal, Ivan; Chen, Xiangbin; Chen, Guo-Qiang

2016-11-01

The industrial production of low value-added biological products poses significant challenges due to cost pressures. In recent years, it has been argued that synthetic biology approaches will lead to breakthroughs that eliminate price bottlenecks for the production of a wide range of biological products including bioplastics and biofuels. One significant bottleneck lies in the necessity to break the tough cell walls of microbes in order to release intracellular products. We here report the implementation of the first synthetic biology standard part based on the lambda phage SRRz genes and a synthetic ribosome binding site (RBS) that works in Escherichia coli and Halomonas campaniensis, which enables the producer strains to induce lysis after the addition of small amounts (1-5 %) of solvents or to spontaneously lyse during the stresses of downstream processing, and thus has the potential to eliminate the mechanical cell disruption step as both an efficiency bottleneck and a significant capex barrier when implementing downstream bioprocesses.

The Suite for Embedded Applications and Kernels

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

2016-05-10

Many applications of high performance embedded computing are limited by performance or power bottlenecks. We havedesigned SEAK, a new benchmark suite, (a) to capture these bottlenecks in a way that encourages creative solutions to these bottlenecks? and (b) to facilitate rigorous, objective, end-user evaluation for their solutions. To avoid biasing solutions toward existing algorithms, SEAK benchmarks use a mission-centric (abstracted from a particular algorithm) andgoal-oriented (functional) specification. To encourage solutions that are any combination of software or hardware, we use an end-user blackbox evaluation that can capture tradeoffs between performance, power, accuracy, size, and weight. The tradeoffs are especially informativemore » for procurement decisions. We call our benchmarks future proof because each mission-centric interface and evaluation remains useful despite shifting algorithmic preferences. It is challenging to create both concise and precise goal-oriented specifications for mission-centric problems. This paper describes the SEAK benchmark suite and presents an evaluation of sample solutions that highlights power and performance tradeoffs.« less

Physics of automated driving in framework of three-phase traffic theory.

PubMed

Kerner, Boris S

2018-04-01

We have revealed physical features of automated driving in the framework of the three-phase traffic theory for which there is no fixed time headway to the preceding vehicle. A comparison with the classical model approach to automated driving for which an automated driving vehicle tries to reach a fixed (desired or "optimal") time headway to the preceding vehicle has been made. It turns out that automated driving in the framework of the three-phase traffic theory can exhibit the following advantages in comparison with the classical model of automated driving: (i) The absence of string instability. (ii) Considerably smaller speed disturbances at road bottlenecks. (iii) Automated driving vehicles based on the three-phase theory can decrease the probability of traffic breakdown at the bottleneck in mixed traffic flow consisting of human driving and automated driving vehicles; on the contrary, even a single automated driving vehicle based on the classical approach can provoke traffic breakdown at the bottleneck in mixed traffic flow.

Physics of automated driving in framework of three-phase traffic theory

NASA Astrophysics Data System (ADS)

Kerner, Boris S.

2018-04-01

We have revealed physical features of automated driving in the framework of the three-phase traffic theory for which there is no fixed time headway to the preceding vehicle. A comparison with the classical model approach to automated driving for which an automated driving vehicle tries to reach a fixed (desired or "optimal") time headway to the preceding vehicle has been made. It turns out that automated driving in the framework of the three-phase traffic theory can exhibit the following advantages in comparison with the classical model of automated driving: (i) The absence of string instability. (ii) Considerably smaller speed disturbances at road bottlenecks. (iii) Automated driving vehicles based on the three-phase theory can decrease the probability of traffic breakdown at the bottleneck in mixed traffic flow consisting of human driving and automated driving vehicles; on the contrary, even a single automated driving vehicle based on the classical approach can provoke traffic breakdown at the bottleneck in mixed traffic flow.

Bayesian inference of a historical bottleneck in a heavily exploited marine mammal.

PubMed

Hoffman, J I; Grant, S M; Forcada, J; Phillips, C D

2011-10-01

Emerging Bayesian analytical approaches offer increasingly sophisticated means of reconstructing historical population dynamics from genetic data, but have been little applied to scenarios involving demographic bottlenecks. Consequently, we analysed a large mitochondrial and microsatellite dataset from the Antarctic fur seal Arctocephalus gazella, a species subjected to one of the most extreme examples of uncontrolled exploitation in history when it was reduced to the brink of extinction by the sealing industry during the late eighteenth and nineteenth centuries. Classical bottleneck tests, which exploit the fact that rare alleles are rapidly lost during demographic reduction, yielded ambiguous results. In contrast, a strong signal of recent demographic decline was detected using both Bayesian skyline plots and Approximate Bayesian Computation, the latter also allowing derivation of posterior parameter estimates that were remarkably consistent with historical observations. This was achieved using only contemporary samples, further emphasizing the potential of Bayesian approaches to address important problems in conservation and evolutionary biology. © 2011 Blackwell Publishing Ltd.

Deep Learning for Population Genetic Inference.

PubMed

Sheehan, Sara; Song, Yun S

2016-03-01

Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme.

Deep Learning for Population Genetic Inference

PubMed Central

Sheehan, Sara; Song, Yun S.

2016-01-01

Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme. PMID:27018908

Population genomics of the inbred Scandinavian wolf.

PubMed

Hagenblad, Jenny; Olsson, Maria; Parker, Heidi G; Ostrander, Elaine A; Ellegren, Hans

2009-04-01

The Scandinavian wolf population represents one of the genetically most well-characterized examples of a severely bottlenecked natural population (with only two founders), and of how the addition of new genetic material (one immigrant) can at least temporarily provide a 'genetic rescue'. However, inbreeding depression has been observed in this population and in the absence of additional immigrants, its long-term viability is questioned. To study the effects of inbreeding and selection on genomic diversity, we performed a genomic scan with approximately 250 microsatellite markers distributed across all autosomes and the X chromosome. We found linkage disequilibrium (LD) that extended up to distances of 50 Mb, exceeding that of most outbreeding species studied thus far. LD was particularly pronounced on the X chromosome. Overall levels of observed genomic heterozygosity did not deviate significantly from simulations based on known population history, giving no support for a general selection for heterozygotes. However, we found evidence supporting balancing selection at a number of loci and also evidence suggesting directional selection at other loci. For markers on chromosome 23, the signal of selection was particularly strong, indicating that purifying selection against deleterious alleles may have occurred even in this very small population. These data suggest that population genomics allows the exploration of the effects of neutral and non-neutral evolution on a finer scale than what has previously been possible.

What cost mitochondria? The maintenance of functional mitochondrial DNA within and across generations

PubMed Central

Aanen, Duur K.; Spelbrink, Johannes N.; Beekman, Madeleine

2014-01-01

The peculiar biology of mitochondrial DNA (mtDNA) potentially has detrimental consequences for organismal health and lifespan. Typically, eukaryotic cells contain multiple mitochondria, each with multiple mtDNA genomes. The high copy number of mtDNA implies that selection on mtDNA functionality is relaxed. Furthermore, because mtDNA replication is not strictly regulated, within-cell selection may favour mtDNA variants with a replication advantage, but a deleterious effect on cell fitness. The opportunities for selfish mtDNA mutations to spread are restricted by various organism-level adaptations, such as uniparental transmission, germline mtDNA bottlenecks, germline selection and, during somatic growth, regular alternation between fusion and fission of mitochondria. These mechanisms are all hypothesized to maintain functional mtDNA. However, the strength of selection for maintenance of functional mtDNA progressively declines with age, resulting in age-related diseases. Furthermore, organismal adaptations that most probably evolved to restrict the opportunities for selfish mtDNA create secondary problems. Owing to predominantly maternal mtDNA transmission, recombination among mtDNA from different individuals is highly restricted or absent, reducing the scope for repair. Moreover, maternal inheritance precludes selection against mtDNA variants with male-specific effects. We finish by discussing the consequences of life-history differences among taxa with respect to mtDNA evolution and make a case for the use of microorganisms to experimentally manipulate levels of selection. PMID:24864309

Population history, gene flow, and bottlenecks in island populations of a secondary seed disperser, the southern grey shrike (Lanius meridionalis koenigi)

PubMed Central

Padilla, David P; Spurgin, Lewis G; Fairfield, Eleanor A; Illera, Juan Carlos; Richardson, David S

2015-01-01

Studying the population history and demography of organisms with important ecological roles can aid understanding of evolutionary processes at the community level and inform conservation. We screened genetic variation (mtDNA and microsatellite) across the populations of the southern grey shrike (Lanius meridionalis koenigi) in the Canary Islands, where it is an endemic subspecies and an important secondary seed disperser. We show that the Canarian subspecies is polyphyletic with L. meridionalis elegans from North Africa and that shrikes have colonized the Canary Islands from North Africa multiple times. Substantial differences in genetic diversity exist across islands, which are most likely the product of a combination of historical colonization events and recent bottlenecks. The Eastern Canary Islands had the highest overall levels of genetic diversity and have probably been most recently and/or frequently colonized from Africa. Recent or ongoing bottlenecks were detected in three of the islands and are consistent with anecdotal evidence of population declines due to human disturbance. These findings are troubling given the shrike's key ecological role in the Canary Islands, and further research is needed to understand the community-level consequences of declines in shrike populations. Finally, we found moderate genetic differentiation among populations, which largely reflected the shrike's bottleneck history; however, a significant pattern of isolation-by-distance indicated that some gene flow occurs between islands. This study is a useful first step toward understanding how secondary seed dispersal operates over broad spatial scales. PMID:25628862

Aging and Attentional Control

PubMed Central

Tsang, Pamela S.

2013-01-01

The research examines the structural bottleneck account and the resource account of the substantial dual-task deficits among older adults. Procedures from two common dual-task methodologies--the psychological refractory period and the relative-priority manipulation--were used to encourage maximization of the joint performance. Performance and time-sharing strategies from subjects between the ages of 20 and 70 were examined. Age-related declines in time-sharing efficiency and in the precision of the executive control process were observed. The age-related effect was larger when two manual responses were required than when one manual and one vocal response were required but no evidence for obligatory sequential processing was found. Except for the most demanding conditions, comparable practice effects were observed between the younger and older subjects, suggesting considerable cognitive plasticity in the older subjects. Implications for the two attentional accounts were discussed. PMID:23281799

MO detector (MOD): a dual-function optical modulator-detector for on-chip communication

NASA Astrophysics Data System (ADS)

Sun, Shuai; Zhang, Ruoyu; Peng, Jiaxin; Narayana, Vikram K.; Dalir, Hamed; El-Ghazawi, Tarek; Sorger, Volker J.

2018-04-01

Physical challenges at the device and interconnect level limit both network and computing energy efficiency. While photonics is being considered to address interconnect bottlenecks, optical routing is still limited by electronic circuitry, requiring substantial overhead for optical-electrical-optical conversion. Here we show a novel design of an integrated broadband photonic-plasmonic hybrid device termed MODetector featuring dual light modulation and detection function to act as an optical transceiver in the photonic network-on-chip. With over 10 dB extinction ratio and 0.8 dB insertion loss at the modulation state, this MODetector provides 0.7 W/A responsivity in the detection state with 36 ps response time. This multi-functional device: (i) eliminates OEO conversion, (ii) reduces optical losses from photodetectors when not needed, and (iii) enables cognitive routing strategies for network-on-chips.

Identification of Direct Protein Targets of Small Molecules

PubMed Central

2010-01-01

Small-molecule target identification is a vital and daunting task for the chemical biology community as well as for researchers interested in applying the power of chemical genetics to impact biology and medicine. To overcome this “target ID” bottleneck, new technologies are being developed that analyze protein–drug interactions, such as drug affinity responsive target stability (DARTS), which aims to discover the direct binding targets (and off targets) of small molecules on a proteome scale without requiring chemical modification of the compound. Here, we review the DARTS method, discuss why it works, and provide new perspectives for future development in this area. PMID:21077692

Cancer stem cells in solid tumors: is 'evading apoptosis' a hallmark of cancer?

PubMed

Enderling, Heiko; Hahnfeldt, Philip

2011-08-01

Conventional wisdom has long held that once a cancer cell has developed it will inevitably progress to clinical disease. Updating this paradigm, it has more recently become apparent that the tumor interacts with its microenvironment and that some environmental bottlenecks, such as the angiogenic switch, must be overcome for the tumor to progress. In parallel, attraction has been drawn to the concept that there is a minority population of cells - the cancer stem cells - bestowed with the exclusive ability to self-renew and regenerate the tumor. With therapeutic targeting issues at stake, much attention has shifted to the identification of cancer stem cells, the thinking being that the remaining non-stem population, already fated to die, will play a negligible role in tumor development. In fact, the newly appreciated importance of intercellular interactions in cancer development also extends in a unique and unexpected way to interactions between the stem and non-stem compartments of the tumor. Here we discuss recent findings drawn from a hybrid mathematical-cellular automaton model that simulates growth of a heterogeneous solid tumor comprised of cancer stem cells and non-stem cancer cells. The model shows how the introduction of cell fate heterogeneity paradoxically influences the tumor growth dynamic in response to apoptosis, to reveal yet another bottleneck to tumor progression potentially exploitable for disease control. Copyright © 2011 Elsevier Ltd. All rights reserved.

Conservation genetics of extremely isolated urban populations of the northern dusky salamander (Desmognathus fuscus) in New York City

PubMed Central

Zak, Yana; Pehek, Ellen

2013-01-01

Urbanization is a major cause of amphibian decline. Stream-dwelling plethodontid salamanders are particularly susceptible to urbanization due to declining water quality and hydrological changes, but few studies have examined these taxa in cities. The northern dusky salamander (Desmognathus fuscus) was once common in the New York City metropolitan area, but has substantially declined throughout the region in recent decades. We used five tetranucleotide microsatellite loci to examine population differentiation, genetic variation, and bottlenecks among five remnant urban populations of dusky salamanders in NYC. These genetic measures provide information on isolation, prevalence of inbreeding, long-term prospects for population persistence, and potential for evolutionary responses to future environmental change. All populations were genetically differentiated from each other, and the most isolated populations in Manhattan have maintained very little genetic variation (i.e. <20% heterozygosity). A majority of the populations also exhibited evidence of genetic bottlenecks. These findings contrast with published estimates of high genetic variation within and lack of structure between populations of other desmognathine salamanders sampled over similar or larger spatial scales. Declines in genetic variation likely resulted from population extirpations and the degradation of stream and terrestrial paths for dispersal in NYC. Loss of genetic variability in populations isolated by human development may be an underappreciated cause and/or consequence of the decline of this species in urbanized areas of the northeast USA. PMID:23646283

Proteolytic crosstalk in multi-protease networks

NASA Astrophysics Data System (ADS)

Ogle, Curtis T.; Mather, William H.

2016-04-01

Processive proteases, such as ClpXP in E. coli, are conserved enzyme assemblies that can recognize and rapidly degrade proteins. These proteases are used for a number of purposes, including degrading mistranslated proteins and controlling cellular stress response. However, proteolytic machinery within the cell is limited in capacity and can lead to a bottleneck in protein degradation, whereby many proteins compete (‘queue’) for proteolytic resources. Previous work has demonstrated that such queueing can lead to pronounced statistical relationships between different protein counts when proteins compete for a single common protease. However, real cells contain many different proteases, e.g. ClpXP, ClpAP, and Lon in E. coli, and it is not clear how competition between proteins for multiple classes of protease would influence the dynamics of cellular networks. In the present work, we theoretically demonstrate that a multi-protease proteolytic bottleneck can substantially couple the dynamics for both simple and complex (oscillatory) networks, even between substrates with substantially different affinities for protease. For these networks, queueing often leads to strong positive correlations between protein counts, and these correlations are strongest near the queueing theoretic point of balance. Furthermore, we find that the qualitative behavior of these networks depends on the relative size of the absolute affinity of substrate to protease compared to the cross affinity of substrate to protease, leading in certain regimes to priority queue statistics.

Delayed pull-in transitions in overdamped MEMS devices

NASA Astrophysics Data System (ADS)

Gomez, Michael; Moulton, Derek E.; Vella, Dominic

2018-01-01

We consider the dynamics of overdamped MEMS devices undergoing the pull-in instability. Numerous previous experiments and numerical simulations have shown a significant increase in the pull-in time under DC voltages close to the pull-in voltage. Here the transient dynamics slow down as the device passes through a meta-stable or bottleneck phase, but this slowing down is not well understood quantitatively. Using a lumped parallel-plate model, we perform a detailed analysis of the pull-in dynamics in this regime. We show that the bottleneck phenomenon is a type of critical slowing down arising from the pull-in transition. This allows us to show that the pull-in time obeys an inverse square-root scaling law as the transition is approached; moreover we determine an analytical expression for this pull-in time. We then compare our prediction to a wide range of pull-in time data reported in the literature, showing that the observed slowing down is well captured by our scaling law, which appears to be generic for overdamped pull-in under DC loads. This realization provides a useful design rule with which to tune dynamic response in applications, including state-of-the-art accelerometers and pressure sensors that use pull-in time as a sensing mechanism. We also propose a method to estimate the pull-in voltage based only on data of the pull-in times.

HRSSA – Efficient hybrid stochastic simulation for spatially homogeneous biochemical reaction networks

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

Marchetti, Luca, E-mail: marchetti@cosbi.eu; Priami, Corrado, E-mail: priami@cosbi.eu; University of Trento, Department of Mathematics

This paper introduces HRSSA (Hybrid Rejection-based Stochastic Simulation Algorithm), a new efficient hybrid stochastic simulation algorithm for spatially homogeneous biochemical reaction networks. HRSSA is built on top of RSSA, an exact stochastic simulation algorithm which relies on propensity bounds to select next reaction firings and to reduce the average number of reaction propensity updates needed during the simulation. HRSSA exploits the computational advantage of propensity bounds to manage time-varying transition propensities and to apply dynamic partitioning of reactions, which constitute the two most significant bottlenecks of hybrid simulation. A comprehensive set of simulation benchmarks is provided for evaluating performance andmore » accuracy of HRSSA against other state of the art algorithms.« less

Favoring the unfavored: Selective electrochemical nitrogen fixation using a reticular chemistry approach

PubMed Central

Lee, Hiang Kwee; Koh, Charlynn Sher Lin; Lee, Yih Hong; Liu, Chong; Phang, In Yee; Han, Xuemei; Tsung, Chia-Kuang; Ling, Xing Yi

2018-01-01

Electrochemical nitrogen-to-ammonia fixation is emerging as a sustainable strategy to tackle the hydrogen- and energy-intensive operations by Haber-Bosch process for ammonia production. However, current electrochemical nitrogen reduction reaction (NRR) progress is impeded by overwhelming competition from the hydrogen evolution reaction (HER) across all traditional NRR catalysts and the requirement for elevated temperature/pressure. We achieve both excellent NRR selectivity (~90%) and a significant boost to Faradic efficiency by 10 percentage points even at ambient operations by coating a superhydrophobic metal-organic framework (MOF) layer over the NRR electrocatalyst. Our reticular chemistry approach exploits MOF’s water-repelling and molecular-concentrating effects to overcome HER-imposed bottlenecks, uncovering the unprecedented electrochemical features of NRR critical for future theoretical studies. By favoring the originally unfavored NRR, we envisage our electrocatalytic design as a starting point for high-performance nitrogen-to-ammonia electroconversion directly from water vapor–abundant air to address increasing global demand of ammonia in (bio)chemical and energy industries. PMID:29536047

Stochastic processes constrain the within and between host evolution of influenza virus.

PubMed

McCrone, John T; Woods, Robert J; Martin, Emily T; Malosh, Ryan E; Monto, Arnold S; Lauring, Adam S

2018-05-03

The evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define influenza virus dynamics in human hosts through sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected from individuals in a prospective community-based cohort, they are broadly representative of natural infections with seasonal viruses. Consistent with a neutral model of evolution, sequence data from 49 serially sampled individuals illustrated the dynamic turnover of synonymous and nonsynonymous single nucleotide variants and provided little evidence for positive selection of antigenic variants. We also identified 43 genetically-validated transmission pairs in this cohort. Maximum likelihood optimization of multiple transmission models estimated an effective transmission bottleneck of 1-2 genomes. Our data suggest that positive selection is inefficient at the level of the individual host and that stochastic processes dominate the host-level evolution of influenza viruses. © 2018, McCrone et al.

Spatial filter with volume gratings for high-peak-power multistage laser amplifiers

NASA Astrophysics Data System (ADS)

Tan, Yi-zhou; Yang, Yi-sheng; Zheng, Guang-wei; Shen, Ben-jian; Pan, Heng-yue; Liu, Li

2010-08-01

The regular spatial filters comprised of lens and pinhole are essential component in high power laser systems, such as lasers for inertial confinement fusion, nonlinear optical technology and directed-energy weapon. On the other hand the pinhole is treated as a bottleneck of high power laser due to harmful plasma created by the focusing beam. In this paper we present a spatial filter based on angular selectivity of Bragg diffraction grating to avoid the harmful focusing effect in the traditional pinhole filter. A spatial filter consisted of volume phase gratings in two-pass amplifier cavity were reported. Two-dimensional filter was proposed by using single Pi-phase-shifted Bragg grating, numerical simulation results shown that its angular spectrum bandwidth can be less than 160urad. The angular selectivity of photo-thermorefractive glass and RUGATE film filters, construction stability, thermal stability and the effects of misalignments of gratings on the diffraction efficiencies under high-pulse-energy laser operating condition are discussed.

Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development.

PubMed

Wiehe, Kevin; Bradley, Todd; Meyerhoff, R Ryan; Hart, Connor; Williams, Wilton B; Easterhoff, David; Faison, William J; Kepler, Thomas B; Saunders, Kevin O; Alam, S Munir; Bonsignori, Mattia; Haynes, Barton F

2018-06-13

HIV-1 broadly neutralizing antibodies (bnAbs) require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations for optimal neutralization potency. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. One bottleneck for induction of bnAbs is the evolution of viral envelopes (Envs) that can select bnAb B cell receptors (BCR) with improbable mutations. Here we define the probability of bnAb mutations and demonstrate the functional significance of key improbable mutations in three bnAb B cell lineages. We show that bnAbs are enriched for improbable mutations, which implies that their elicitation will be critical for successful vaccine induction of potent bnAb B cell lineages. We discuss a mutation-guided vaccine strategy for identification of Envs that can select B cells with BCRs that have key improbable mutations required for bnAb development. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

Estimating time since infection in early homogeneous HIV-1 samples using a poisson model

PubMed Central

2010-01-01

Background The occurrence of a genetic bottleneck in HIV sexual or mother-to-infant transmission has been well documented. This results in a majority of new infections being homogeneous, i.e., initiated by a single genetic strain. Early after infection, prior to the onset of the host immune response, the viral population grows exponentially. In this simple setting, an approach for estimating evolutionary and demographic parameters based on comparison of diversity measures is a feasible alternative to the existing Bayesian methods (e.g., BEAST), which are instead based on the simulation of genealogies. Results We have devised a web tool that analyzes genetic diversity in acutely infected HIV-1 patients by comparing it to a model of neutral growth. More specifically, we consider a homogeneous infection (i.e., initiated by a unique genetic strain) prior to the onset of host-induced selection, where we can assume a random accumulation of mutations. Previously, we have shown that such a model successfully describes about 80% of sexual HIV-1 transmissions provided the samples are drawn early enough in the infection. Violation of the model is an indicator of either heterogeneous infections or the initiation of selection. Conclusions When the underlying assumptions of our model (homogeneous infection prior to selection and fast exponential growth) are met, we are under a very particular scenario for which we can use a forward approach (instead of backwards in time as provided by coalescent methods). This allows for more computationally efficient methods to derive the time since the most recent common ancestor. Furthermore, the tool performs statistical tests on the Hamming distance frequency distribution, and outputs summary statistics (mean of the best fitting Poisson distribution, goodness of fit p-value, etc). The tool runs within minutes and can readily accommodate the tens of thousands of sequences generated through new ultradeep pyrosequencing technologies. The tool is available on the LANL website. PMID:20973976

Iterative algorithm-guided design of massive strain libraries, applied to itaconic acid production in yeast.

PubMed

Young, Eric M; Zhao, Zheng; Gielesen, Bianca E M; Wu, Liang; Benjamin Gordon, D; Roubos, Johannes A; Voigt, Christopher A

2018-05-09

Metabolic engineering requires multiple rounds of strain construction to evaluate alternative pathways and enzyme concentrations. Optimizing multigene pathways stepwise or by randomly selecting enzymes and expression levels is inefficient. Here, we apply methods from design of experiments (DOE) to guide the construction of strain libraries from which the maximum information can be extracted without sampling every possible combination. We use Saccharomyces cerevisiae as a host for a novel six-gene pathway to itaconic acid, selected by comparing alternative shunt pathways that bypass the mitochondrial TCA cycle. The pathway is distinctive for the use of acetylating acetaldehyde dehydrogenase to increase cytosolic acetyl-CoA pools, a bacterial enzyme to synthesize citrate in the cytosol, and an itaconic acid exporter. Precise control over the expression of each gene is enabled by a set of promoter-terminator pairs that span a 174-fold range. Two large combinatorial libraries (160 variants, 2.4Mb and 32 variants, 0.6Mb) are designed where the expression levels are selected by statistical methods (I-optimal response surface methodology, full factorial, or Plackett-Burman) with the intent of extracting different types of guiding information after the screen. This is applied to the design of a third library (24 variants, 0.5Mb) intended to alleviate a bottleneck in cis-aconitate decarboxylase (CAD) expression. The top strain produces 815mg/l itaconic acid, a 4-fold improvement over the initial strain achieved by iteratively balancing pathway expression. Including a methylated product in the total, the strain produces 1.3g/l combined itaconic acids. Further, a regression analysis of the libraries reveals the optimal expression level of CAD as well as pairwise interdependencies between genes that result in increased titer and purity of itaconic acid. This work demonstrates adapting algorithmic design strategies to guide automated yeast strain construction and learn information after each iteration. Copyright © 2018. Published by Elsevier Inc.

Curvature and bottlenecks control molecular transport in inverse bicontinuous cubic phases

NASA Astrophysics Data System (ADS)

Assenza, Salvatore; Mezzenga, Raffaele

2018-02-01

We perform a simulation study of the diffusion of small solutes in the confined domains imposed by inverse bicontinuous cubic phases for the primitive, diamond, and gyroid symmetries common to many lipid/water mesophase systems employed in experiments. For large diffusing domains, the long-time diffusion coefficient shows universal features when the size of the confining domain is renormalized by the Gaussian curvature of the triply periodic minimal surface. When bottlenecks are widely present, they become the most relevant factor for transport, regardless of the connectivity of the cubic phase.

RAMA: A file system for massively parallel computers

NASA Technical Reports Server (NTRS)

Miller, Ethan L.; Katz, Randy H.

1993-01-01

This paper describes a file system design for massively parallel computers which makes very efficient use of a few disks per processor. This overcomes the traditional I/O bottleneck of massively parallel machines by storing the data on disks within the high-speed interconnection network. In addition, the file system, called RAMA, requires little inter-node synchronization, removing another common bottleneck in parallel processor file systems. Support for a large tertiary storage system can easily be integrated in lo the file system; in fact, RAMA runs most efficiently when tertiary storage is used.

Breaking CFD Bottlenecks in Gas-Turbine Flow-Path Design

NASA Technical Reports Server (NTRS)

Davis, Roger L.; Dannenhoffer, John F., III; Clark, John P.

2010-01-01

New ideas are forthcoming to break existing bottlenecks in using CFD during design. CAD-based automated grid generation. Multi-disciplinary use of embedded, overset grids to eliminate complex gridding problems. Use of time-averaged detached-eddy simulations as norm instead of "steady" RANS to include effects of self-excited unsteadiness. Combined GPU/Core parallel computing to provide over an order of magnitude increase in performance/price ratio. Gas-turbine applications are shown here but these ideas can be used for other Air Force, Navy, and NASA applications.

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

PubMed Central

Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

2014-01-01

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

Spin bottleneck in resonant tunneling through double quantum dots with different Zeeman splittings.

PubMed

Huang, S M; Tokura, Y; Akimoto, H; Kono, K; Lin, J J; Tarucha, S; Ono, K

2010-04-02

We investigated the electron transport property of the InGaAs/GaAs double quantum dots, the electron g factors of which are different from each other. We found that in a magnetic field, the resonant tunneling is suppressed even if one of the Zeeman sublevels is aligned. This is because the other misaligned Zeeman sublevels limit the total current. A finite broadening of the misaligned sublevel partially relieves this bottleneck effect, and the maximum current is reached when interdot detuning is half the Zeeman energy difference.

Potential of Genomic Selection in Mass Selection Breeding of an Allogamous Crop: An Empirical Study to Increase Yield of Common Buckwheat.

PubMed

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2018-01-01

To evaluate the potential of genomic selection (GS), a selection experiment with GS and phenotypic selection (PS) was performed in an allogamous crop, common buckwheat ( Fagopyrum esculentum Moench). To indirectly select for seed yield per unit area, which cannot be measured on a single-plant basis, a selection index was constructed from seven agro-morphological traits measurable on a single plant basis. Over 3 years, we performed two GS and one PS cycles per year for improvement in the selection index. In GS, a prediction model was updated every year on the basis of genotypes of 14,598-50,000 markers and phenotypes. Plants grown from seeds derived from a series of generations of GS and PS populations were evaluated for the traits in the selection index and other yield-related traits. GS resulted in a 20.9% increase and PS in a 15.0% increase in the selection index in comparison with the initial population. Although the level of linkage disequilibrium in the breeding population was low, the target trait was improved with GS. Traits with higher weights in the selection index were improved more than those with lower weights, especially when prediction accuracy was high. No trait changed in an unintended direction in either GS or PS. The accuracy of genomic prediction models built in the first cycle decreased in the later cycles because the genetic bottleneck through the selection cycles changed linkage disequilibrium patterns in the breeding population. The present study emphasizes the importance of updating models in GS and demonstrates the potential of GS in mass selection of allogamous crop species, and provided a pilot example of successful application of GS to plant breeding.

Potential of Genomic Selection in Mass Selection Breeding of an Allogamous Crop: An Empirical Study to Increase Yield of Common Buckwheat

PubMed Central

Yabe, Shiori; Hara, Takashi; Ueno, Mariko; Enoki, Hiroyuki; Kimura, Tatsuro; Nishimura, Satoru; Yasui, Yasuo; Ohsawa, Ryo; Iwata, Hiroyoshi

2018-01-01

To evaluate the potential of genomic selection (GS), a selection experiment with GS and phenotypic selection (PS) was performed in an allogamous crop, common buckwheat (Fagopyrum esculentum Moench). To indirectly select for seed yield per unit area, which cannot be measured on a single-plant basis, a selection index was constructed from seven agro-morphological traits measurable on a single plant basis. Over 3 years, we performed two GS and one PS cycles per year for improvement in the selection index. In GS, a prediction model was updated every year on the basis of genotypes of 14,598–50,000 markers and phenotypes. Plants grown from seeds derived from a series of generations of GS and PS populations were evaluated for the traits in the selection index and other yield-related traits. GS resulted in a 20.9% increase and PS in a 15.0% increase in the selection index in comparison with the initial population. Although the level of linkage disequilibrium in the breeding population was low, the target trait was improved with GS. Traits with higher weights in the selection index were improved more than those with lower weights, especially when prediction accuracy was high. No trait changed in an unintended direction in either GS or PS. The accuracy of genomic prediction models built in the first cycle decreased in the later cycles because the genetic bottleneck through the selection cycles changed linkage disequilibrium patterns in the breeding population. The present study emphasizes the importance of updating models in GS and demonstrates the potential of GS in mass selection of allogamous crop species, and provided a pilot example of successful application of GS to plant breeding. PMID:29619035

Insect photoreceptor adaptations to night vision

PubMed Central

Honkanen, Anna; Salmela, Iikka; Weckström, Matti

2017-01-01

Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals. This article is part of the themed issue ‘Vision in dim light’. PMID:28193821

Designing Financial Instruments for Rapid Flood Response Using Remote Sensed and Archival Hazard and Exposure Information

NASA Astrophysics Data System (ADS)

Lall, U.; Allaire, M.; Ceccato, P.; Haraguchi, M.; Cian, F.; Bavandi, A.

2017-12-01

Catastrophic floods can pose a significant challenge for response and recovery. A key bottleneck in the speed of response is the availability of funds to a country or regions finance ministry to mobilize resources. Parametric instruments, where the release of funs is tied to the exceedance of a specified index or threshold, rather than to loss verification are well suited for this purpose. However, designing and appropriate index, that is not subject to manipulation and accurately reflects the need is a challenge, especially in developing countries which have short hydroclimatic and loss records, and where rapid land use change has led to significant changes in exposure and hydrology over time. The use of long records of rainfall from climate re-analyses, flooded area and land use from remote sensing to design and benchmark a parametric index considering the uncertainty and representativeness of potential loss is explored with applications to Bangladesh and Thailand. Prospects for broader applicability and limitations are discussed.

The specificity of learned parallelism in dual-memory retrieval.

PubMed

Strobach, Tilo; Schubert, Torsten; Pashler, Harold; Rickard, Timothy

2014-05-01

Retrieval of two responses from one visually presented cue occurs sequentially at the outset of dual-retrieval practice. Exclusively for subjects who adopt a mode of grouping (i.e., synchronizing) their response execution, however, reaction times after dual-retrieval practice indicate a shift to learned retrieval parallelism (e.g., Nino & Rickard, in Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 373-388, 2003). In the present study, we investigated how this learned parallelism is achieved and why it appears to occur only for subjects who group their responses. Two main accounts were considered: a task-level versus a cue-level account. The task-level account assumes that learned retrieval parallelism occurs at the level of the task as a whole and is not limited to practiced cues. Grouping response execution may thus promote a general shift to parallel retrieval following practice. The cue-level account states that learned retrieval parallelism is specific to practiced cues. This type of parallelism may result from cue-specific response chunking that occurs uniquely as a consequence of grouped response execution. The results of two experiments favored the second account and were best interpreted in terms of a structural bottleneck model.

Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification.

PubMed

Sobel Leonard, Ashley; McClain, Micah T; Smith, Gavin J D; Wentworth, David E; Halpin, Rebecca A; Lin, Xudong; Ransier, Amy; Stockwell, Timothy B; Das, Suman R; Gilbert, Anthony S; Lambkin-Williams, Robert; Ginsburg, Geoffrey S; Woods, Christopher W; Koelle, Katia

2016-12-15

Knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. Here, we analyze a unique viral data set of next-generation sequencing (NGS) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. Nasal wash samples collected from 7 of these subjects were successfully deep sequenced. From these, we characterized changes in the subjects' viral populations during infection and identified differences between the virus in these samples and the viral stock used to inoculate the subjects. We first calculated pairwise genetic distances between the subjects' nasal wash samples, the viral stock, and the influenza virus A/Wisconsin/67/2005 (H3N2) reference strain used to generate the stock virus. These distances revealed that considerable viral evolution occurred at various points in the human challenge study. Further quantitative analyses indicated that (i) the viral stock contained genetic variants that originated and likely were selected for during the passaging process, (ii) direct intranasal inoculation with the viral stock resulted in a selective bottleneck that reduced nonsynonymous genetic diversity in the viral hemagglutinin and nucleoprotein, and (iii) intrahost viral evolution continued over the course of infection. These intrahost evolutionary dynamics were dominated by purifying selection. Our findings indicate that rapid viral evolution can occur during acute influenza infection in otherwise healthy human hosts when the founding population size of the virus is large, as is the case with direct intranasal inoculation. Influenza viruses circulating among humans are known to rapidly evolve over time. However, little is known about how influenza virus evolves across single transmission events and over the course of a single infection. To address these issues, we analyze influenza virus sequences from a human challenge experiment that initiated infection with a cell- and egg-passaged viral stock, which appeared to have adapted during its preparation. We find that the subjects' viral populations differ genetically from the viral stock, with subjects' viral populations having lower representation of the amino-acid-changing variants that arose during viral preparation. We also find that most of the viral evolution occurring over single infections is characterized by further decreases in the frequencies of these amino-acid-changing variants and that only limited intrahost genetic diversification through new mutations is apparent. Our findings indicate that influenza virus populations can undergo rapid genetic changes during acute human infections. Copyright © 2016 Sobel Leonard et al.

Identification of the chemical constituents of Chinese medicine Yi-Xin-Shu capsule by molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation.

PubMed

Wang, Hong-ping; Chen, Chang; Liu, Yan; Yang, Hong-Jun; Wu, Hong-Wei; Xiao, Hong-Bin

2015-11-01

The incomplete identification of the chemical components of traditional Chinese medicinal formula has been one of the bottlenecks in the modernization of traditional Chinese medicine. Tandem mass spectrometry has been widely used for the identification of chemical substances. Current automatic tandem mass spectrometry acquisition, where precursor ions were selected according to their signal intensity, encounters a drawback in chemical substances identification when samples contain many overlapping signals. Compounds in minor or trace amounts could not be identified because most tandem mass spectrometry information was lost. Herein, a molecular feature orientated precursor ion selection and tandem mass spectrometry structure elucidation method for complex Chinese medicine chemical constituent analysis was developed. The precursor ions were selected according to their two-dimensional characteristics of retention times and mass-to-charge ratio ranges from herbal compounds, so that all precursor ions from herbal compounds were included and more minor chemical constituents in Chinese medicine were identified. Compared to the conventional automatic tandem mass spectrometry setups, the approach is novel and can overcome the drawback for chemical substances identification. As an example, 276 compounds from the Chinese Medicine of Yi-Xin-Shu capsule were identified. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mini-review: Strategies for Variation and Evolution of Bacterial Antigens

PubMed Central

Foley, Janet

2015-01-01

Across the eubacteria, antigenic variation has emerged as a strategy to evade host immunity. However, phenotypic variation in some of these antigens also allows the bacteria to exploit variable host niches as well. The specific mechanisms are not shared-derived characters although there is considerable convergent evolution and numerous commonalities reflecting considerations of natural selection and biochemical restraints. Unlike in viruses, mechanisms of antigenic variation in most bacteria involve larger DNA movement such as gene conversion or DNA rearrangement, although some antigens vary due to point mutations or modified transcriptional regulation. The convergent evolution that promotes antigenic variation integrates various evolutionary forces: these include mutations underlying variant production; drift which could remove alleles especially early in infection or during life history phases in arthropod vectors (when the bacterial population size goes through a bottleneck); selection not only for any particular variant but also for the mechanism for the production of variants (i.e., selection for mutability); and overcoming negative selection against variant production. This review highlights the complexities of drivers of antigenic variation, in particular extending evaluation beyond the commonly cited theory of immune evasion. A deeper understanding of the diversity of purpose and mechanisms of antigenic variation in bacteria will contribute to greater insight into bacterial pathogenesis, ecology and coevolution with hosts. PMID:26288700

Traditional healers, faith healers and medical practitioners: the contribution of medical pluralism to bottlenecks along the cascade of care for HIV/AIDS in Eastern and Southern Africa

PubMed Central

Bukenya, Dominic; Darong, Gabriel; Wamoyi, Joyce; McLean, Estelle; Skovdal, Morten; Ddaaki, William; Ondeng’e, Kenneth; Bonnington, Oliver; Seeley, Janet; Hosegood, Victoria; Wringe, Alison

2017-01-01

Objectives There are concerns that medical pluralism may delay patients’ progression through the HIV cascade-of-care. However, the pathways of impact through which medical pluralism influence the care of people living with HIV (PLHIV) in African settings remain unclear. We sought to establish the manifestation of medical pluralism among PLHIV, and explore mechanisms through which medical pluralism contributes bottlenecks along the HIV care cascade. Methods We conducted a multicountry exploratory qualitative study in seven health and demographic surveillance sites in six eastern and southern African countries: Uganda, Kenya, Tanzania, Malawi, Zimbabwe and South Africa. We interviewed 258 PLHIV at different stages of the HIV cascade-of-care, 48 family members of deceased PLHIV and 53 HIV healthcare workers. Interviews were conducted using shared standardised topic guides, and data managed through NVIVO 8/10/11. We conducted a thematic analysis of healthcare pathways and bottlenecks related to medical pluralism. Results Medical pluralism, manifesting across traditional, faith-based and biomedical health-worlds, contributed to the care cascade bottlenecks for PLHIV through three pathways of impact. First, access to HIV treatment was delayed through the nature of health-related beliefs, knowledge and patient journeys. Second, HIV treatment was interrupted by availability of alternative options, perceived failed treatment and exploitation of PLHIV by opportunistic traders and healers. Lastly, the mixing of biomedical healthcare providers and treatment with traditional and faith-based options fuelled tensions driven by fear of drug-to-drug interactions and mistrust between providers operating in different health-worlds. Conclusion Medical pluralism contributes to delays and interruptions of care along the HIV cascade, and mistrust between health providers. Region-wide interventions and policies are urgently needed in sub-Saharan Africa to minimise potential harm and consequences of medical pluralism for PLHIV. The role of sociocultural beliefs in mediating bottlenecks necessitate adoption of culture-sensitive approaches intervention designs and policy reforms appropriate to the context of sub-Saharan Africa. PMID:28736393

Traditional healers, faith healers and medical practitioners: the contribution of medical pluralism to bottlenecks along the cascade of care for HIV/AIDS in Eastern and Southern Africa.

PubMed

Moshabela, Mosa; Bukenya, Dominic; Darong, Gabriel; Wamoyi, Joyce; McLean, Estelle; Skovdal, Morten; Ddaaki, William; Ondeng'e, Kenneth; Bonnington, Oliver; Seeley, Janet; Hosegood, Victoria; Wringe, Alison

2017-07-01

There are concerns that medical pluralism may delay patients' progression through the HIV cascade-of-care. However, the pathways of impact through which medical pluralism influence the care of people living with HIV (PLHIV) in African settings remain unclear. We sought to establish the manifestation of medical pluralism among PLHIV, and explore mechanisms through which medical pluralism contributes bottlenecks along the HIV care cascade. We conducted a multicountry exploratory qualitative study in seven health and demographic surveillance sites in six eastern and southern African countries: Uganda, Kenya, Tanzania, Malawi, Zimbabwe and South Africa. We interviewed 258 PLHIV at different stages of the HIV cascade-of-care, 48 family members of deceased PLHIV and 53 HIV healthcare workers. Interviews were conducted using shared standardised topic guides, and data managed through NVIVO 8/10/11. We conducted a thematic analysis of healthcare pathways and bottlenecks related to medical pluralism. Medical pluralism, manifesting across traditional, faith-based and biomedical health-worlds, contributed to the care cascade bottlenecks for PLHIV through three pathways of impact. First, access to HIV treatment was delayed through the nature of health-related beliefs, knowledge and patient journeys. Second, HIV treatment was interrupted by availability of alternative options, perceived failed treatment and exploitation of PLHIV by opportunistic traders and healers. Lastly, the mixing of biomedical healthcare providers and treatment with traditional and faith-based options fuelled tensions driven by fear of drug-to-drug interactions and mistrust between providers operating in different health-worlds. Medical pluralism contributes to delays and interruptions of care along the HIV cascade, and mistrust between health providers. Region-wide interventions and policies are urgently needed in sub-Saharan Africa to minimise potential harm and consequences of medical pluralism for PLHIV. The role of sociocultural beliefs in mediating bottlenecks necessitate adoption of culture-sensitive approaches intervention designs and policy reforms appropriate to the context of sub-Saharan Africa. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Historical and Contemporary DNA Indicate Fisher Decline and Isolation Occurred Prior to the European Settlement of California

PubMed Central

Tucker, Jody M.; Schwartz, Michael K.; Truex, Richard L.; Pilgrim, Kristine L.; Allendorf, Fred W.

2012-01-01

Establishing if species contractions were the result of natural phenomena or human induced landscape changes is essential for managing natural populations. Fishers (Martes pennanti) in California occur in two geographically and genetically isolated populations in the northwestern mountains and southern Sierra Nevada. Their isolation is hypothesized to have resulted from a decline in abundance and distribution associated with European settlement in the 1800s. However, there is little evidence to establish that fisher occupied the area between the two extant populations at that time. We analyzed 10 microsatellite loci from 275 contemporary and 21 historical fisher samples (1880–1920) to evaluate the demographic history of fisher in California. We did not find any evidence of a recent (post-European) bottleneck in the northwestern population. In the southern Sierra Nevada, genetic subdivision within the population strongly influenced bottleneck tests. After accounting for genetic subdivision, we found a bottleneck signal only in the northern and central portions of the southern Sierra Nevada, indicating that the southernmost tip of these mountains may have acted as a refugium for fisher during the anthropogenic changes of the late 19th and early 20th centuries. Using a coalescent-based Bayesian analysis, we detected a 90% decline in effective population size and dated the time of decline to over a thousand years ago. We hypothesize that fisher distribution in California contracted to the two current population areas pre-European settlement, and that portions of the southern Sierra Nevada subsequently experienced another more recent bottleneck post-European settlement. PMID:23300783

Stochastic Modeling of Sediment Connectivity for Reconstructing Sand Fluxes and Origins in the Unmonitored Se Kong, Se San, and Sre Pok Tributaries of the Mekong River

NASA Astrophysics Data System (ADS)

Schmitt, R. J. P.; Bizzi, S.; Castelletti, A. F.; Kondolf, G. M.

2018-01-01

Sediment supply to rivers, subsequent fluvial transport, and the resulting sediment connectivity on network scales are often sparsely monitored and subject to major uncertainty. We propose to approach that uncertainty by adopting a stochastic method for modeling network sediment connectivity, which we present for the Se Kong, Se San, and Sre Pok (3S) tributaries of the Mekong. We quantify how unknown properties of sand sources translate into uncertainty regarding network connectivity by running the CASCADE (CAtchment Sediment Connectivity And DElivery) modeling framework in a Monte Carlo approach for 7,500 random realizations. Only a small ensemble of realizations reproduces downstream observations of sand transport. This ensemble presents an inverse stochastic approximation of the magnitude and variability of transport capacity, sediment flux, and grain size distribution of the sediment transported in the network (i.e., upscaling point observations to the entire network). The approximated magnitude of sand delivered from each tributary to the Mekong is controlled by reaches of low transport capacity ("bottlenecks"). These bottlenecks limit the ability to predict transport in the upper parts of the catchment through inverse stochastic approximation, a limitation that could be addressed by targeted monitoring upstream of identified bottlenecks. Nonetheless, bottlenecks also allow a clear partitioning of natural sand deliveries from the 3S to the Mekong, with the Se Kong delivering less (1.9 Mt/yr) and coarser (median grain size: 0.4 mm) sand than the Se San (5.3 Mt/yr, 0.22 mm) and Sre Pok (11 Mt/yr, 0.19 mm).

Repeated cis-regulatory tuning of a metabolic bottleneck gene during evolution.

PubMed

Kuang, Meihua Christina; Kominek, Jacek; Alexander, William G; Cheng, Jan-Fang; Wrobel, Russell L; Hittinger, Chris Todd

2018-05-21

Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.

Identifying Loci Under Selection Against Gene Flow in Isolation-with-Migration Models

PubMed Central

Sousa, Vitor C.; Carneiro, Miguel; Ferrand, Nuno; Hey, Jody

2013-01-01

When divergence occurs in the presence of gene flow, there can arise an interesting dynamic in which selection against gene flow, at sites associated with population-specific adaptations or genetic incompatibilities, can cause net gene flow to vary across the genome. Loci linked to sites under selection may experience reduced gene flow and may experience genetic bottlenecks by the action of nearby selective sweeps. Data from histories such as these may be poorly fitted by conventional neutral model approaches to demographic inference, which treat all loci as equally subject to forces of genetic drift and gene flow. To allow for demographic inference in the face of such histories, as well as the identification of loci affected by selection, we developed an isolation-with-migration model that explicitly provides for variation among genomic regions in migration rates and/or rates of genetic drift. The method allows for loci to fall into any of multiple groups, each characterized by a different set of parameters, thus relaxing the assumption that all loci share the same demography. By grouping loci, the method can be applied to data with multiple loci and still have tractable dimensionality and statistical power. We studied the performance of the method using simulated data, and we applied the method to study the divergence of two subspecies of European rabbits (Oryctolagus cuniculus). PMID:23457232

Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

PubMed

Eckert, Andrew J; Wegrzyn, Jill L; Pande, Barnaly; Jermstad, Kathleen D; Lee, Jennifer M; Liechty, John D; Tearse, Brandon R; Krutovsky, Konstantin V; Neale, David B

2009-09-01

Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular diversity in forest tree genomes. Here, we report an analysis of diversity and divergence for a set of 121 cold-hardiness candidate genes in coastal Douglas fir (Pseudotsuga menziesii var. menziesii). Application of several different tests for neutrality, including those that incorporated demographic models, revealed signatures of selection consistent with selective sweeps at three to eight loci, depending upon the severity of a bottleneck event and the method used to detect selection. Given the high levels of recombination, these candidate genes are likely to be closely linked to the target of selection if not the genes themselves. Putative homologs in Arabidopsis act primarily to stabilize the plasma membrane and protect against denaturation of proteins at freezing temperatures. These results indicate that surveys of nucleotide diversity and divergence, when framed within the context of further association mapping experiments, will come full circle with respect to their utility in the dissection of complex phenotypic traits into their genetic components.

Antibiotic Combinations That Enable One-Step, Targeted Mutagenesis of Chromosomal Genes.

PubMed

Lee, Wonsik; Do, Truc; Zhang, Ge; Kahne, Daniel; Meredith, Timothy C; Walker, Suzanne

2018-06-08

Targeted modification of bacterial chromosomes is necessary to understand new drug targets, investigate virulence factors, elucidate cell physiology, and validate results of -omics-based approaches. For some bacteria, reverse genetics remains a major bottleneck to progress in research. Here, we describe a compound-centric strategy that combines new negative selection markers with known positive selection markers to achieve simple, efficient one-step genome engineering of bacterial chromosomes. The method was inspired by the observation that certain nonessential metabolic pathways contain essential late steps, suggesting that antibiotics targeting a late step can be used to select for the absence of genes that control flux into the pathway. Guided by this hypothesis, we have identified antibiotic/counterselectable markers to accelerate reverse engineering of two increasingly antibiotic-resistant pathogens, Staphylococcus aureus and Acinetobacter baumannii. For S. aureus, we used wall teichoic acid biosynthesis inhibitors to select for the absence of tarO and for A. baumannii, we used colistin to select for the absence of lpxC. We have obtained desired gene deletions, gene fusions, and promoter swaps in a single plating step with perfect efficiency. Our method can also be adapted to generate markerless deletions of genes using FLP recombinase. The tools described here will accelerate research on two important pathogens, and the concept we outline can be readily adapted to any organism for which a suitable target pathway can be identified.

Assessment of quality and relevance of curricula development in health training institutions: a case study of Kenya.

PubMed

Mumbo, Hazel M; Kinaro, Joyce W

2015-08-13

The World Health Organization lists Kenya among African countries experiencing health workforce crisis catalysed through immigration, underproduction, inconsistent quality of production and unequal distribution. Strengthening health training institutions to increase production of high-quality health workers is acknowledged as a measure to mitigate the crisis.IntraHealth International's USAID-funded FUNZOKenya Project (2012-2017) undertook an assessment to identify the bottlenecks to increasing the number and quality of pre-service graduates in Kenya. The assessment, a cross-sectional descriptive study, collected data through structured respondent interviews among faculty, students in health training institutions, key informants and desk review. The assessment purposively selected 14 institutions from 18 institutions identified for initial collaboration with the project towards strengthening health workforce training. The statistical package for social sciences (SPSS) application helped analyse quantitative data and quotes used to illustrate perceptions on the quality of curricula.The findings revealed major gaps in quality and adequacy of curricula in the training institutions. A national standard framework to guide curricula review process is lacking. Further, curricula did not adequately prepare students for clinical placement, as most failed to directly respond to national health needs. The study recommended reviews of curricula to ensure their responsiveness to emerging issues in the health sector, the formation of curriculum committees to review curricula, development of official curricula review standards and an integrated mechanism to disseminate policies and guidelines.

SNPHunter: a bioinformatic software for single nucleotide polymorphism data acquisition and management.

PubMed

Wang, Lin; Liu, Simin; Niu, Tianhua; Xu, Xin

2005-03-18

Single nucleotide polymorphisms (SNPs) provide an important tool in pinpointing susceptibility genes for complex diseases and in unveiling human molecular evolution. Selection and retrieval of an optimal SNP set from publicly available databases have emerged as the foremost bottlenecks in designing large-scale linkage disequilibrium studies, particularly in case-control settings. We describe the architectural structure and implementations of a novel software program, SNPHunter, which allows for both ad hoc-mode and batch-mode SNP search, automatic SNP filtering, and retrieval of SNP data, including physical position, function class, flanking sequences at user-defined lengths, and heterozygosity from NCBI dbSNP. The SNP data extracted from dbSNP via SNPHunter can be exported and saved in plain text format for further down-stream analyses. As an illustration, we applied SNPHunter for selecting SNPs for 10 major candidate genes for type 2 diabetes, including CAPN10, FABP4, IL6, NOS3, PPARG, TNF, UCP2, CRP, ESR1, and AR. SNPHunter constitutes an efficient and user-friendly tool for SNP screening, selection, and acquisition. The executable and user's manual are available at http://www.hsph.harvard.edu/ppg/software.htm

A Step-by-Step Framework on Discrete Events Simulation in Emergency Department; A Systematic Review.

PubMed

Dehghani, Mahsa; Moftian, Nazila; Rezaei-Hachesu, Peyman; Samad-Soltani, Taha

2017-04-01

To systematically review the current literature of simulation in healthcare including the structured steps in the emergency healthcare sector by proposing a framework for simulation in the emergency department. For the purpose of collecting the data, PubMed and ACM databases were used between the years 2003 and 2013. The inclusion criteria were to select English-written articles available in full text with the closest objectives from among a total of 54 articles retrieved from the databases. Subsequently, 11 articles were selected for further analysis. The studies focused on the reduction of waiting time and patient stay, optimization of resources allocation, creation of crisis and maximum demand scenarios, identification of overcrowding bottlenecks, investigation of the impact of other systems on the existing system, and improvement of the system operations and functions. Subsequently, 10 simulation steps were derived from the relevant studies after an expert's evaluation. The 10-steps approach proposed on the basis of the selected studies provides simulation and planning specialists with a structured method for both analyzing problems and choosing best-case scenarios. Moreover, following this framework systematically enables the development of design processes as well as software implementation of simulation problems.

Mitogenomics data reveal effective population size, historical bottlenecks, and the effects of hunting on New Zealand fur seals (Arctocephalus forsteri).

PubMed

Emami-Khoyi, Arsalan; Paterson, Adrian M; Hartley, David A; Boren, Laura J; Cruickshank, Robert H; Ross, James G; Murphy, Elaine C; Else, Terry-Ann

2018-05-01

The New Zealand fur seal (Arctocephalus forsteri) passed through a population bottleneck due to commercial sealing during the eighteenth to nineteenth centuries. To facilitate future management options, we reconstructed the demographic history of New Zealand fur seals in a Bayesian framework using maternally inherited, mitochondrial DNA sequences. Mitogenomic data suggested two separate clades (most recent common ancestor 5000 years ago) of New Zealand fur seals that survived large-scale human harvest. Mitochondrial haplotype diversity was high, with 45 singletons identified from 46 individuals although mean nucleotide diversity was low (0.012 ± 0.0061). Variation was not constrained geographically. Analyses of mitogenomes support the hypothesis for a population bottleneck approximately 35 generations ago, which coincides with the peak of commercial sealing. Mitogenomic data are consistent with a pre-human effective population size of approximately 30,000 that first declined to around 10,000 (due to the impact of Polynesian colonization, particularly in the first 100 years of their arrival into New Zealand), and then to 100-200 breeding individuals during peak of commercial sealing.

Flagella-Driven Flows Circumvent Diffusive Bottlenecks that Inhibit Metabolite Exchange

NASA Astrophysics Data System (ADS)

Short, Martin; Solari, Cristian; Ganguly, Sujoy; Kessler, John; Goldstein, Raymond; Powers, Thomas

2006-03-01

The evolution of single cells to large and multicellular organisms requires matching the organisms' needs to the rate of exchange of metabolites with the environment. This logistic problem can be a severe constraint on development. For organisms with a body plan that approximates a spherical shell, such as colonies of the volvocine green algae, the required current of metabolites grows quadratically with colony radius whereas the rate at which diffusion can exchange metabolites grows only linearly with radius. Hence, there is a bottleneck radius beyond which the diffusive current cannot keep up with metabolic demands. Using Volvox carteri as a model organism, we examine experimentally and theoretically the role that advection of fluid by surface-mounted flagella plays in enhancing nutrient uptake. We show that fluid flow driven by the coordinated beating of flagella produces a convective boundary layer in the concentration of a diffusing solute which in turn renders the metabolite exchange rate quadratic in the colony radius. This enhanced transport circumvents the diffusive bottleneck, allowing increase in size and thus evolutionary transitions to multicellularity in the Volvocales.

Genetic structure and conservation of Mountain Lions in the South-Brazilian Atlantic Rain Forest.

PubMed

Castilho, Camila S; Marins-Sá, Luiz G; Benedet, Rodrigo C; Freitas, Thales R O

2012-01-01

The Brazilian Atlantic Rain Forest, one of the most endangered ecosystems worldwide, is also among the most important hotspots as regards biodiversity. Through intensive logging, the initial area has been reduced to around 12% of its original size. In this study we investigated the genetic variability and structure of the mountain lion, Puma concolor. Using 18 microsatellite loci we analyzed evidence of allele dropout, null alleles and stuttering, calculated the number of allele/locus, PIC, observed and expected heterozygosity, linkage disequilibrium, Hardy-Weinberg equilibrium, F(IS), effective population size and genetic structure (MICROCHECKER, CERVUS, GENEPOP, FSTAT, ARLEQUIN, ONESAMP, LDNe, PCAGEN, GENECLASS software), we also determine whether there was evidence of a bottleneck (HYBRIDLAB, BOTTLENECK software) that might influence the future viability of the population in south Brazil. 106 alleles were identified, with the number of alleles/locus ranging from 2 to 11. Mean observed heterozygosity, mean number of alleles and polymorphism information content were 0.609, 5.89, and 0.6255, respectively. This population presented evidence of a recent bottleneck and loss of genetic variation. Persistent regional poaching constitutes an increasing in the extinction risk.

The nocturnal bottleneck and the evolution of activity patterns in mammals

PubMed Central

Gerkema, Menno P.; Davies, Wayne I. L.; Foster, Russell G.; Menaker, Michael; Hut, Roelof A.

2013-01-01

In 1942, Walls described the concept of a ‘nocturnal bottleneck’ in placental mammals, where these species could survive only by avoiding daytime activity during times in which dinosaurs were the dominant taxon. Walls based this concept of a longer episode of nocturnality in early eutherian mammals by comparing the visual systems of reptiles, birds and all three extant taxa of the mammalian lineage, namely the monotremes, marsupials (now included in the metatherians) and placentals (included in the eutherians). This review describes the status of what has become known as the nocturnal bottleneck hypothesis, giving an overview of the chronobiological patterns of activity. We review the ecological plausibility that the activity patterns of (early) eutherian mammals were restricted to the night, based on arguments relating to endothermia, energy balance, foraging and predation, taking into account recent palaeontological information. We also assess genes, relating to light detection (visual and non-visual systems) and the photolyase DNA protection system that were lost in the eutherian mammalian lineage. Our conclusion presently is that arguments in favour of the nocturnal bottleneck hypothesis in eutherians prevail. PMID:23825205

Traffic dynamics around weaving section influenced by accident: Cellular automata approach

NASA Astrophysics Data System (ADS)

Kong, Lin-Peng; Li, Xin-Gang; Lam, William H. K.

2015-07-01

The weaving section, as a typical bottleneck, is one source of vehicle conflicts and an accident-prone area. Traffic accident will block lanes and the road capacity will be reduced. Several models have been established to study the dynamics around traffic bottlenecks. However, little attention has been paid to study the complex traffic dynamics influenced by the combined effects of bottleneck and accident. This paper presents a cellular automaton model to characterize accident-induced traffic behavior around the weaving section. Some effective control measures are proposed and verified for traffic management under accident condition. The total flux as a function of inflow rates, the phase diagrams, the spatial-temporal diagrams, and the density and velocity profiles are presented to analyze the impact of accident. It was shown that the proposed control measures for weaving traffic can improve the capacity of weaving section under both normal and accident conditions; the accidents occurring on median lane in the weaving section are more inclined to cause traffic jam and reduce road capacity; the capacity of weaving section will be greatly reduced when the accident happens downstream the weaving section.

Performances of multiprocessor multidisk architectures for continuous media storage

NASA Astrophysics Data System (ADS)

Gennart, Benoit A.; Messerli, Vincent; Hersch, Roger D.

1996-03-01

Multimedia interfaces increase the need for large image databases, capable of storing and reading streams of data with strict synchronicity and isochronicity requirements. In order to fulfill these requirements, we consider a parallel image server architecture which relies on arrays of intelligent disk nodes, each disk node being composed of one processor and one or more disks. This contribution analyzes through bottleneck performance evaluation and simulation the behavior of two multi-processor multi-disk architectures: a point-to-point architecture and a shared-bus architecture similar to current multiprocessor workstation architectures. We compare the two architectures on the basis of two multimedia algorithms: the compute-bound frame resizing by resampling and the data-bound disk-to-client stream transfer. The results suggest that the shared bus is a potential bottleneck despite its very high hardware throughput (400Mbytes/s) and that an architecture with addressable local memories located closely to their respective processors could partially remove this bottleneck. The point- to-point architecture is scalable and able to sustain high throughputs for simultaneous compute- bound and data-bound operations.

Molecular Determinants and Bottlenecks in the Dissociation Dynamics of Biotin-Streptavidin.

PubMed

Tiwary, Pratyush

2017-12-07

Biotin-streptavidin is a very popular system used to gain insight into protein-ligand interactions. In its tetrameric form, it is well-known for its exceptionally high kinetic stability, being one of the strongest known noncovalent interactions in nature, and it is heavily used across the biotechnological industry. In this work, we gain understanding of the molecular determinants and bottlenecks in the dissociation of the dimeric biotin-streptavidin system in wild type and with a point mutation. Using recently proposed enhanced sampling methods with full atomistic resolution, we reproduce the experimentally reported effect of the mutation on the dissociation rate. We also answer a longstanding question regarding cause/effect in the coupled events of bond stretching and bond hydration during dissociation and establish that in this system, it is the bond stretching and not hydration which forms the bottleneck in the early parts of the dissociation process. We believe these calculations represent a step forward in the use of atomistic simulations to study pharmacokinetics. An improved understanding of biotin-streptavidin dissociation dynamics should also have direct benefits in biotechnological and nanobiotechnological applications.

Manufacturing Enhancement through Reduction of Cycle Time using Different Lean Techniques

NASA Astrophysics Data System (ADS)

Suganthini Rekha, R.; Periyasamy, P.; Nallusamy, S.

2017-08-01

In recent manufacturing system the most important parameters in production line are work in process, TAKT time and line balancing. In this article lean tools and techniques were implemented to reduce the cycle time. The aim is to enhance the productivity of the water pump pipe by identifying the bottleneck stations and non value added activities. From the initial time study the bottleneck processes were identified and then necessary expanding processes were also identified for the bottleneck process. Subsequently the improvement actions have been established and implemented using different lean tools like value stream mapping, 5S and line balancing. The current state value stream mapping was developed to describe the existing status and to identify various problem areas. 5S was used to implement the steps to reduce the process cycle time and unnecessary movements of man and material. The improvement activities were implemented with required suggested and the future state value stream mapping was developed. From the results it was concluded that the total cycle time was reduced about 290.41 seconds and the customer demand has been increased about 760 units.

MASCAL: RFID Tracking of Patients, Staff and Equipment to Enhance Hospital Response to Mass Casualty Events

PubMed Central

Fry, Emory A.; Lenert, Leslie A.

2005-01-01

Most medical facilities practice managing the large numbers of seriously injured patients expected during catastrophic events. As the demands on the healthcare team increase, however, the challenges faced by managers escalate, workflow bottlenecks develop and system capacity decreases. This paper describes MASCAL, an integrated software–hardware system designed to enhance management of resources at a hospital during a mass casualty situation. MASCAL uses active 802.11b asset tags to track patients, equipment and staff during the response to a disaster. The system integrates tag position information with data from personnel databases, medical information systems, registration applications and the US Navy’s TACMEDCS triage application in a custom visual disaster management environment. MASCAL includes interfaces for a hospital command center, local area managers (emergency room, operating suites, radiology, etc.) and registration personnel. MASCAL is an operational system undergoing functional evaluation at the Naval Medical Center, San Diego, CA. PMID:16779042

Selection bias at the heterosexual HIV-1 transmission bottleneck

PubMed Central

Carlson, Jonathan M.; Schaefer, Malinda; Monaco, Daniela C.; Batorsky, Rebecca; Claiborne, Daniel T.; Prince, Jessica; Deymier, Martin J.; Ende, Zachary S.; Klatt, Nichole R.; DeZiel, Charles E.; Lin, Tien-Ho; Peng, Jian; Seese, Aaron M.; Shapiro, Roger; Frater, John; Ndung’u, Thumbi; Tang, Jianming; Goepfert, Paul; Gilmour, Jill; Price, Matt A.; Kilembe, William; Heckerman, David; Goulder, Philip J.R.; Allen, Todd M.; Allen, Susan; Hunter, Eric

2014-01-01

SUMMARY Introduction Heterosexual HIV-1 transmission is an inefficient process with rates reported at <1% per unprotected sexual exposure. When transmission occurs, systemic infection is typically established by a single genetic variant, taken from the swarm of genetically distinct viruses circulating in the donor. Whether that founder virus represents a chance event or was systematically favored is unclear. Our work has tested a central hypothesis that founder virus selection is biased toward certain genetic characteristics. Rationale If HIV-1 transmission involves selection for viruses with certain favorable characteristics, then such advantages should emerge as statistical biases when viewed across many viral loci in many transmitting partners. We therefore identified 137 Zambian heterosexual transmission pairs, for whom plasma samples were available for both the donor and recipient partner soon after transmission, and compared the viral sequences obtained from each partner to identify features that predicted whether the majority amino acid observed at any particular position in the donor was transmitted. We focused attention on two features: viral genetic characteristics that correlate with viral fitness, and clinical factors that influence transmission. Statistical modeling indicates that the former will be favored for transmission, while the latter will nullify this relative advantage. Results We observed a highly significant selection bias that favors the transmission of amino acids associated with increased fitness. These features included the frequency of the amino acid in the study cohort, the relative advantage of the amino acid with respect to the stability of the protein, and features related to immune escape and compensation. This selection bias was reduced in couples with high risk of transmission. In particular, significantly less selection bias was observed in women and in men with genital inflammation, compared to healthy men, suggesting a more permissive environment in the female than male genital tract. Consistent with this observation, viruses transmitted to women were characterized by lower predicted fitness than those in men. The presence of amino acids favored during transmission predicted which individual virus within a donor was transmitted to their partner, while chronically infected individuals with viral populations characterized by a predominance of these amino acids were more likely to transmit to their partners. Conclusion These data highlight the clear selection biases that benefit fitter viruses during transmission in the context of a stochastic process. That such biases exist, and are tempered by certain risk factors, suggests that transmission is frequently characterized by many abortive transmission events in which some target cells are nonproductively infected. Moreover, for efficient transmission, some changes that favored survival in the transmitting partner are frequently discarded, resulting in overall slower evolution of HIV-1 in the population. Paradoxically, by increasing the selection bias at the transmission bottleneck, reduction of susceptibility may increase the expected fitness of breakthrough viruses that establish infection and may therefore worsen the prognosis for the newly infected partner. Conversely, preventative or therapeutic approaches that weaken the virus may reduce overall transmission rates via a mechanism that is independent from the quantity of circulating virus, and may therefore provide long-term benefits even upon breakthrough infection. PMID:25013080

Genetic Variability and Founder Effect in the Pitcher Plant Sarracenia purpurea (Sarraceniaceae) in Populations Introduced into Switzerland: from Inbreeding to Invasion

PubMed Central

PARISOD, CHRISTIAN; TRIPPI, CHARLOTTE; GALLAND, NICOLE

2004-01-01

• Background and Aims The long-lived and mainly outcrossing species Sarracenia purpurea has been introduced into Switzerland and become invasive. This creates the opportunity to study reactions to founder effect and how a species can circumvent deleterious effects of bottlenecks such as reduced genetic diversity, inbreeding and extinction through mutational meltdown, to emerge as a highly invasive plant. • Methods A population genetic survey by random amplified polymorphism DNA markers (RAPD) together with historical insights and a field pollination experiment were carried out. • Key Results At the regional scale, S. purpurea shows low structure (θst = 0·072) due to a recent founder event and important subsequent growth. Nevertheless, multivariate statistical analyses reveal that, because of a bottleneck that shifted allele frequencies, most of the variability is independent among populations. In one population (Tenasses) the species has become invasive and genetic analysis reveals restricted gene flow and family structure (θst = 0·287). Although inbreeding appears to be high (Fis > 0·410 from a Bayesian estimation), a field pollination experiment failed to detect significant inbreeding depression upon F1 seed number and seed weight fitness-traits. Furthermore, crosses between unrelated individuals produced F1 seeds with significantly reduced fitness, thus showing local outbreeding depression. • Conclusions The results suggest that, under restricted gene flow among families, the species may not only have rapidly purged deleterious alleles, but also have undergone some form of selection for inbreeding due to co-adaptation between loci. PMID:15546932

The origin of chow chows in the light of the East Asian breeds.

PubMed

Yang, Hechuan; Wang, Guodong; Wang, Meng; Ma, Yaping; Yin, Tingting; Fan, Ruoxi; Wu, Hong; Zhong, Li; Irwin, David M; Zhai, Weiwei; Zhang, Yaping

2017-02-16

East Asian dog breeds are one of the most ancient groups of dogs that radiated after the domestication of the dog and represent the most basal lineages of dog evolution. Among these, the Chow Chow is an ancient breed that embodies very distinct morphological and physiological features, such as sturdy build, dense coat, and blue/purple tongue. Using a Restricted site Associated DNA (RAD) sequencing approach, we sequenced the genomes of nine Chow Chows from China. Combined with a dataset of 37 canid whole genome sequencing (WGS) from several published works, we found that the Chow Chow is one of the most basal lineages, which originated together with other East Asian breeds, such as the Shar-Pei and Akita. Demographic analysis found that Chow Chows originated from the Chinese indigenous dog about 8300 years ago. The bottleneck leading to Chow Chows was not strong and genetic migration between Chow Chows and other populations is low. Two classes of genes show strong evidence of positive selection along the Chow Chow lineage, namely genes related to metabolism and digestion as well as muscle/heart development and differentiation. Dog breeds from East Asia, including the Chow Chow, originated from Chinese indigenous dogs very early in time. The genetic bottleneck leading to Chow Chows and migrations with other populations are found to be quite mild. Our current study represents an early endeavor to characterize the origin of East Asian dog breeds and establishes an important reference point for understanding the origin of ancient breeds in Asia.

Implementing controlled-unitary operations over the butterfly network

NASA Astrophysics Data System (ADS)

Soeda, Akihito; Kinjo, Yoshiyuki; Turner, Peter S.; Murao, Mio

2014-12-01

We introduce a multiparty quantum computation task over a network in a situation where the capacities of both the quantum and classical communication channels of the network are limited and a bottleneck occurs. Using a resource setting introduced by Hayashi [1], we present an efficient protocol for performing controlled-unitary operations between two input nodes and two output nodes over the butterfly network, one of the most fundamental networks exhibiting the bottleneck problem. This result opens the possibility of developing a theory of quantum network coding for multiparty quantum computation, whereas the conventional network coding only treats multiparty quantum communication.

Implementing controlled-unitary operations over the butterfly network

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

Soeda, Akihito; Kinjo, Yoshiyuki; Turner, Peter S.

2014-12-04

We introduce a multiparty quantum computation task over a network in a situation where the capacities of both the quantum and classical communication channels of the network are limited and a bottleneck occurs. Using a resource setting introduced by Hayashi [1], we present an efficient protocol for performing controlled-unitary operations between two input nodes and two output nodes over the butterfly network, one of the most fundamental networks exhibiting the bottleneck problem. This result opens the possibility of developing a theory of quantum network coding for multiparty quantum computation, whereas the conventional network coding only treats multiparty quantum communication.

Evaluation of Swift Start TCP in Long-Delay Environment

NASA Technical Reports Server (NTRS)

Lawas-Grodek, Frances J.; Tran, Diepchi T.

2004-01-01

This report presents the test results of the Swift Start algorithm in single-flow and multiple-flow testbeds under the effects of high propagation delays, various slow bottlenecks, and small queue sizes. Although this algorithm estimates capacity and implements packet pacing, the findings were that in a heavily congested link, the Swift Start algorithm will not be applicable. The reason is that the bottleneck estimation is falsely influenced by timeouts induced by retransmissions and the expiration of delayed acknowledgment (ACK) timers, thus causing the modified Swift Start code to fall back to regular transmission control protocol (TCP).

Limited genomic consequences of mixed mating in the recently derived sister species pair, Collinsia concolor and Collinsia parryi.

PubMed

Salcedo, A; Kalisz, S; Wright, S I

2014-07-01

Highly selfing species often show reduced effective population sizes and reduced selection efficacy. Whether mixed mating species, which produce both self and outcross progeny, show similar patterns of diversity and selection remains less clear. Examination of patterns of molecular evolution and levels of diversity in species with mixed mating systems can be particularly useful for investigating the relative importance of linked selection and demographic effects on diversity and the efficacy of selection, as the effects of linked selection should be minimal in mixed mating populations, although severe bottlenecks tied to founder events could still be frequent. To begin to address this gap, we assembled and analysed the transcriptomes of individuals from a recently diverged mixed mating sister species pair in the self-compatible genus, Collinsia. The de novo assembly of 52 and 37 Mbp C. concolor and C. parryi transcriptomes resulted in ~40 000 and ~55 000 contigs, respectively, both with an average contig size ~945. We observed a high ratio of shared polymorphisms to fixed differences in the species pair and minimal differences between species in the ratio of synonymous to replacement substitutions or codon usage bias implying comparable effective population sizes throughout species divergence. Our results suggest that differences in effective population size and selection efficacy in mixed mating taxa shortly after their divergence may be minimal and are likely influenced by fluctuating mating systems and population sizes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

A Survey on Distributed Mobile Database and Data Mining

NASA Astrophysics Data System (ADS)

Goel, Ajay Mohan; Mangla, Neeraj; Patel, R. B.

2010-11-01

The anticipated increase in popular use of the Internet has created more opportunity in information dissemination, Ecommerce, and multimedia communication. It has also created more challenges in organizing information and facilitating its efficient retrieval. In response to this, new techniques have evolved which facilitate the creation of such applications. Certainly the most promising among the new paradigms is the use of mobile agents. In this paper, mobile agent and distributed database technologies are applied in the banking system. Many approaches have been proposed to schedule data items for broadcasting in a mobile environment. In this paper, an efficient strategy for accessing multiple data items in mobile environments and the bottleneck of current banking will be proposed.

Bomb blast imaging: bringing order to chaos.

PubMed

Dick, E A; Ballard, M; Alwan-Walker, H; Kashef, E; Batrick, N; Hettiaratchy, S; Moran, C G

2018-06-01

Blast injuries are complex, severe, and outside of our everyday clinical practice, but every radiologist needs to understand them. By their nature, bomb blasts are unpredictable and affect multiple victims, yet require an immediate, coordinated, and whole-hearted response from all members of the clinical team, including all radiology staff. This article will help you gain the requisite expertise in blast imaging including recognising primary, secondary, and tertiary blast injuries. It will also help you understand the fundamental role that imaging plays during mass casualty attacks and how to avoid radiology becoming a bottleneck to the forward flow of severely injured patients as they are triaged and treated. Copyright © 2018. Published by Elsevier Ltd.

Image-guided positioning and tracking.

PubMed

Ruan, Dan; Kupelian, Patrick; Low, Daniel A

2011-01-01

Radiation therapy aims at maximizing tumor control while minimizing normal tissue complication. The introduction of stereotactic treatment explores the volume effect and achieves dose escalation to tumor target with small margins. The use of ablative irradiation dose and sharp dose gradients requires accurate tumor definition and alignment between patient and treatment geometry. Patient geometry variation during treatment may significantly compromise the conformality of delivered dose and must be managed properly. Setup error and interfraction/intrafraction motion are incorporated in the target definition process by expanding the clinical target volume to planning target volume, whereas the alignment between patient and treatment geometry is obtained with an adaptive control process, by taking immediate actions in response to closely monitored patient geometry. This article focuses on the monitoring and adaptive response aspect of the problem. The term "image" in "image guidance" will be used in a most general sense, to be inclusive of some important point-based monitoring systems that can be considered as degenerate cases of imaging. Image-guided motion adaptive control, as a comprehensive system, involves a hierarchy of decisions, each of which balances simplicity versus flexibility and accuracy versus robustness. Patient specifics and machine specifics at the treatment facility also need to be incorporated into the decision-making process. Identifying operation bottlenecks from a system perspective and making informed compromises are crucial in the proper selection of image-guidance modality, the motion management mechanism, and the respective operation modes. Not intended as an exhaustive exposition, this article focuses on discussing the major issues and development principles for image-guided motion management systems. We hope these information and methodologies will facilitate conscientious practitioners to adopt image-guided motion management systems accounting for patient and institute specifics and to embrace advances in knowledge and new technologies subsequent to the publication of this article.

Strengthening district health service management and delivery through internal contracting: lessons from pilot projects in Cambodia.

PubMed

Khim, Keovathanak; Annear, Peter Leslie

2013-11-01

Following a decade of piloting different models of contracting, in mid-2009 the Cambodian Ministry of Health began to test a form of 'internal contracting' for health care delivery in selected health districts (including hospitals and health centers) contracted by the provincial health department as Special Operating Agencies (SOAs) and provided with greater management autonomy. This study assesses the internal contracting approach as a means for improving the management of district health services and strengthening service delivery. While the study may contribute to the emerging field now known as performance-based financing, the lessons deal more broadly with the impact of management reform and increased autonomy in contrast to traditional public sector line-management and budgeting. Carried out during 2011, the study was based on: (i) a review of the literature and of operational documents; (ii) primary data from semi-structured key informant interviews with 20 health officials in two provinces involved in four SOA pilot districts; and (iii) routine data from the 2011 SOA performance monitoring report. Five prerequisites were identified for effective contract management and improved service delivery: a clear understanding of roles and responsibilities by the contracting parties; implementation of clear rules and procedures; effective management of performance; effective monitoring of the contract; and adequate and timely provision of resources. Both the level and allocation of incentives and management bottlenecks at various levels continue to impede implementation. We conclude that, in contracted arrangements like these, the clear separation of contracting functions (purchasing, commissioning, monitoring and regulating), management autonomy where responsibilities are genuinely devolved and accepted, and the provision of resources adequate to meet contract demands are necessary conditions for success. Copyright © 2013 Elsevier Ltd. All rights reserved.

A selective sweep of >8 Mb on chromosome 26 in the Boxer genome.

PubMed

Quilez, Javier; Short, Andrea D; Martínez, Verónica; Kennedy, Lorna J; Ollier, William; Sanchez, Armand; Altet, Laura; Francino, Olga

2011-07-01

Modern dog breeds display traits that are either breed-specific or shared by a few breeds as a result of genetic bottlenecks during the breed creation process and artificial selection for breed standards. Selective sweeps in the genome result from strong selection and can be detected as a reduction or elimination of polymorphism in a given region of the genome. Extended regions of homozygosity, indicative of selective sweeps, were identified in a genome-wide scan dataset of 25 Boxers from the United Kingdom genotyped at ~20,000 single-nucleotide polymorphisms (SNPs). These regions were further examined in a second dataset of Boxers collected from a different geographical location and genotyped using higher density SNP arrays (~170,000 SNPs). A selective sweep previously associated with canine brachycephaly was detected on chromosome 1. A novel selective sweep of over 8 Mb was observed on chromosome 26 in Boxer and for a shorter region in English and French bulldogs. It was absent in 171 samples from eight other dog breeds and 7 Iberian wolf samples. A region of extended increased heterozygosity on chromosome 9 overlapped with a previously reported copy number variant (CNV) which was polymorphic in multiple dog breeds. A selective sweep of more than 8 Mb on chromosome 26 was identified in the Boxer genome. This sweep is likely caused by strong artificial selection for a trait of interest and could have inadvertently led to undesired health implications for this breed. Furthermore, we provide supporting evidence for two previously described regions: a selective sweep on chromosome 1 associated with canine brachycephaly and a CNV on chromosome 9 polymorphic in multiple dog breeds.

Genetic and phenotypic divergence in an island bird: isolation by distance, by colonization or by adaptation?

PubMed

Spurgin, Lewis G; Illera, Juan Carlos; Jorgensen, Tove H; Dawson, Deborah A; Richardson, David S

2014-03-01

Discerning the relative roles of adaptive and nonadaptive processes in generating differences among populations and species, as well as how these processes interact, is a fundamental aim in biology. Both genetic and phenotypic divergence across populations can be the product of limited dispersal and gradual genetic drift across populations (isolation by distance), of colonization history and founder effects (isolation by colonization) or of adaptation to different environments preventing migration between populations (isolation by adaptation). Here, we attempt to differentiate between these processes using island populations of Berthelot's pipit (Anthus berthelotii), a passerine bird endemic to three Atlantic archipelagos. Using microsatellite markers and approximate Bayesian computation, we reveal that the northward colonization of this species ca. 8500 years ago resulted in genetic bottlenecks in the colonized archipelagos. We then show that high levels of genetic structure exist across archipelagos and that these are consistent with a pattern of isolation by colonization, but not with isolation by distance or adaptation. Finally, we show that substantial morphological divergence also exists and that this is strongly concordant with patterns of genetic structure and bottleneck history, but not with environmental differences or geographic distance. Overall, our data suggest that founder effects are responsible for both genetic and phenotypic changes across archipelagos. Our findings provide a rare example of how founder effects can persist over evolutionary timescales and suggest that they may play an important role in the early stages of speciation. © 2014 John Wiley & Sons Ltd.

Neuroadaptive technology enables implicit cursor control based on medial prefrontal cortex activity.

PubMed

Zander, Thorsten O; Krol, Laurens R; Birbaumer, Niels P; Gramann, Klaus

2016-12-27

The effectiveness of today's human-machine interaction is limited by a communication bottleneck as operators are required to translate high-level concepts into a machine-mandated sequence of instructions. In contrast, we demonstrate effective, goal-oriented control of a computer system without any form of explicit communication from the human operator. Instead, the system generated the necessary input itself, based on real-time analysis of brain activity. Specific brain responses were evoked by violating the operators' expectations to varying degrees. The evoked brain activity demonstrated detectable differences reflecting congruency with or deviations from the operators' expectations. Real-time analysis of this activity was used to build a user model of those expectations, thus representing the optimal (expected) state as perceived by the operator. Based on this model, which was continuously updated, the computer automatically adapted itself to the expectations of its operator. Further analyses showed this evoked activity to originate from the medial prefrontal cortex and to exhibit a linear correspondence to the degree of expectation violation. These findings extend our understanding of human predictive coding and provide evidence that the information used to generate the user model is task-specific and reflects goal congruency. This paper demonstrates a form of interaction without any explicit input by the operator, enabling computer systems to become neuroadaptive, that is, to automatically adapt to specific aspects of their operator's mindset. Neuroadaptive technology significantly widens the communication bottleneck and has the potential to fundamentally change the way we interact with technology.

Deadly competition and life-saving predation: the potential for alternative stable states in a stage-structured predator–prey system

PubMed Central

Rombado, Bianca R.; Rudolf, Volker H. W.

2016-01-01

Predators often undergo complete ontogenetic diet shifts, engaging in resource competition with species that become their prey during later developmental stages. Theory posits that this mix of stage-specific competition and predation, termed life-history intraguild predation (LHIGP), can lead to alternative stable states. In one state, prey exclude predators through competition (i.e. juvenile competitive bottleneck), while in the alternative, adult predators control prey density to limit competition and foster coexistence. Nevertheless, the interactions leading to these states have not been demonstrated in an empirical LHIGP system. To address this gap, we manipulated densities of cannibalistic adult cyclopoid copepods (Mesocyclops edax) and their cladoceran prey (Daphnia pulex) in a response-surface design and measured the maturation and survival of juvenile copepods (nauplii). We found that Daphnia reduced and even precluded both nauplii maturation and survival through depletion of a shared food resource. As predicted, adult copepods enhanced nauplii maturation and survival through Daphnia consumption, yet this positive effect was dependent on the relative abundance of Daphnia as well as the absolute density of adult copepods. Adult copepods reduced nauplii survival through cannibalism at low Daphnia densities and at the highest copepod density. This work demonstrates that predation can relax a strong juvenile competitive bottleneck in freshwater zooplankton, though cannibalism can reduce predator recruitment. Thus, our results highlight a key role for cannibalism in LHIGP dynamics and provide evidence for the interactions that drive alternative stable states in such systems. PMID:27581881

LBMR: Load-Balanced Multipath Routing for Wireless Data-Intensive Transmission in Real-Time Medical Monitoring.

PubMed

Tseng, Chinyang Henry

2016-05-31

In wireless networks, low-power Zigbee is an excellent network solution for wireless medical monitoring systems. Medical monitoring generally involves transmission of a large amount of data and easily causes bottleneck problems. Although Zigbee's AODV mesh routing provides extensible multi-hop data transmission to extend network coverage, it originally does not, and needs to support some form of load balancing mechanism to avoid bottlenecks. To guarantee a more reliable multi-hop data transmission for life-critical medical applications, we have developed a multipath solution, called Load-Balanced Multipath Routing (LBMR) to replace Zigbee's routing mechanism. LBMR consists of three main parts: Layer Routing Construction (LRC), a Load Estimation Algorithm (LEA), and a Route Maintenance (RM) mechanism. LRC assigns nodes into different layers based on the node's distance to the medical data gateway. Nodes can have multiple next-hops delivering medical data toward the gateway. All neighboring layer-nodes exchange flow information containing current load, which is the used by the LEA to estimate future load of next-hops to the gateway. With LBMR, nodes can choose the neighbors with the least load as the next-hops and thus can achieve load balancing and avoid bottlenecks. Furthermore, RM can detect route failures in real-time and perform route redirection to ensure routing robustness. Since LRC and LEA prevent bottlenecks while RM ensures routing fault tolerance, LBMR provides a highly reliable routing service for medical monitoring. To evaluate these accomplishments, we compare LBMR with Zigbee's AODV and another multipath protocol, AOMDV. The simulation results demonstrate LBMR achieves better load balancing, less unreachable nodes, and better packet delivery ratio than either AODV or AOMDV.

LBMR: Load-Balanced Multipath Routing for Wireless Data-Intensive Transmission in Real-Time Medical Monitoring

PubMed Central

Tseng, Chinyang Henry

2016-01-01

In wireless networks, low-power Zigbee is an excellent network solution for wireless medical monitoring systems. Medical monitoring generally involves transmission of a large amount of data and easily causes bottleneck problems. Although Zigbee’s AODV mesh routing provides extensible multi-hop data transmission to extend network coverage, it originally does not, and needs to support some form of load balancing mechanism to avoid bottlenecks. To guarantee a more reliable multi-hop data transmission for life-critical medical applications, we have developed a multipath solution, called Load-Balanced Multipath Routing (LBMR) to replace Zigbee’s routing mechanism. LBMR consists of three main parts: Layer Routing Construction (LRC), a Load Estimation Algorithm (LEA), and a Route Maintenance (RM) mechanism. LRC assigns nodes into different layers based on the node’s distance to the medical data gateway. Nodes can have multiple next-hops delivering medical data toward the gateway. All neighboring layer-nodes exchange flow information containing current load, which is the used by the LEA to estimate future load of next-hops to the gateway. With LBMR, nodes can choose the neighbors with the least load as the next-hops and thus can achieve load balancing and avoid bottlenecks. Furthermore, RM can detect route failures in real-time and perform route redirection to ensure routing robustness. Since LRC and LEA prevent bottlenecks while RM ensures routing fault tolerance, LBMR provides a highly reliable routing service for medical monitoring. To evaluate these accomplishments, we compare LBMR with Zigbee’s AODV and another multipath protocol, AOMDV. The simulation results demonstrate LBMR achieves better load balancing, less unreachable nodes, and better packet delivery ratio than either AODV or AOMDV. PMID:27258297

Identification of bottlenecks in the accumulation of cyclic fatty acids in camelina seed oil

DOE PAGES

Yu, Xiao-Hong; Cahoon, Rebecca E.; Horn, Patrick J.; ...

2017-09-20

Modified fatty acids (mFA) have diverse uses, e.g., cyclopropane fatty acids (CPA) are feedstocks for producing coatings, lubricants, plastics, and cosmetics. The expression of mFA-producing enzymes in crop and model plants generally results in lower levels of mFA accumulation than in their natural-occurring source plants. In order to further our understanding of metabolic bottlenecks that limit mFA accumulation, we generated transgenic Camelina sativa lines co-expressing Escherichia coli cyclopropane synthase (EcCPS) and Sterculia foetida lysophosphatidic acid acyltransferase (SfLPAT). In contrast to transgenic CPA-accumulating Arabidopsis, CPA accumulation in camelina caused only minor changes in seed weight, germination rate, oil accumulation, and seedlingmore » development. CPA accumulated to much higher levels in membrane than storage lipids, comprising more than 60% of total fatty acid in both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) versus 26% in diacylglycerol (DAG) and 12% in triacylglycerol (TAG) indicating bottlenecks in the transfer of CPA from PC to DAG and from DAG to TAG. Upon coexpression of SfLPAT with EcCPS, di-CPA-PC increased by ~50% relative to lines expressing EcCPS alone with the di-CPA-PC primarily observed in the embryonic axis and mono-CPA-PC primarily in cotyledon tissue. EcCPS-SfLPAT lines revealed a redistribution of CPA from the sn-1 to sn-2 positions within PC and PE that was associated with a doubling of CPA accumulation in both DAG and TAG. Finally, the identification of metabolic bottlenecks in acyl transfer between site of synthesis (phospholipids) and deposition in storage oils (TAGs) lays the foundation for the optimizing CPA accumulation through directed engineering of oil synthesis in target crops.« less

Molecular Population Genetics of the Northern Elephant Seal Mirounga angustirostris.

PubMed

Abadía-Cardoso, Alicia; Freimer, Nelson B; Deiner, Kristy; Garza, John Carlos

2017-09-01

The northern elephant seal, Mirounga angustirostris, was heavily hunted and declared extinct in the 19th century. However, a colony remained on remote Guadalupe Island, Mexico and the species has since repopulated most of its historical distribution. Here, we present a comprehensive evaluation of genetic variation in the species. First, we assess the effect of the demographic bottleneck on microsatellite variability and compare it with that found in other pinnipeds, demonstrating levels of variation similar to that in species that continue to be threatened with extinction. Next, we use sequence data from these markers to demonstrate that some of the limited polymorphism predates the bottleneck. However, most contemporary variation appears to have arisen recently and persisted due to exponential growth. We also describe how we use the range in allele size of microsatellites to estimate ancestral effective population size before the bottleneck, demonstrating a large reduction in effective size. We then employ a classical method for bacteria to estimate the microsatellite mutation rate in the species, deriving an estimate that is extremely similar to that estimated for a similar set of loci in humans, indicating consistency of microsatellite mutation rates in mammals. Finally, we find slight significant structure between some geographically separated colonies, although its biological significance is unclear. This work demonstrates that genetic analysis can be useful for evaluating the population biology of the northern elephant seal, in spite of the bottleneck that removed most genetic variation from the species. Published by Oxford University Press on behalf of The American Genetic Association 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Identification of bottlenecks in the accumulation of cyclic fatty acids in camelina seed oil

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

Yu, Xiao-Hong; Cahoon, Rebecca E.; Horn, Patrick J.

Modified fatty acids (mFA) have diverse uses, e.g., cyclopropane fatty acids (CPA) are feedstocks for producing coatings, lubricants, plastics, and cosmetics. The expression of mFA-producing enzymes in crop and model plants generally results in lower levels of mFA accumulation than in their natural-occurring source plants. In order to further our understanding of metabolic bottlenecks that limit mFA accumulation, we generated transgenic Camelina sativa lines co-expressing Escherichia coli cyclopropane synthase (EcCPS) and Sterculia foetida lysophosphatidic acid acyltransferase (SfLPAT). In contrast to transgenic CPA-accumulating Arabidopsis, CPA accumulation in camelina caused only minor changes in seed weight, germination rate, oil accumulation, and seedlingmore » development. CPA accumulated to much higher levels in membrane than storage lipids, comprising more than 60% of total fatty acid in both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) versus 26% in diacylglycerol (DAG) and 12% in triacylglycerol (TAG) indicating bottlenecks in the transfer of CPA from PC to DAG and from DAG to TAG. Upon coexpression of SfLPAT with EcCPS, di-CPA-PC increased by ~50% relative to lines expressing EcCPS alone with the di-CPA-PC primarily observed in the embryonic axis and mono-CPA-PC primarily in cotyledon tissue. EcCPS-SfLPAT lines revealed a redistribution of CPA from the sn-1 to sn-2 positions within PC and PE that was associated with a doubling of CPA accumulation in both DAG and TAG. Finally, the identification of metabolic bottlenecks in acyl transfer between site of synthesis (phospholipids) and deposition in storage oils (TAGs) lays the foundation for the optimizing CPA accumulation through directed engineering of oil synthesis in target crops.« less

Bottleneck analysis and strategic planning using Tanahashi model for childhood diarrhea management in Gujarat, Western India.

PubMed

Rupani, Mihir Prafulbhai; Gaonkar, Narayan T; Bhatt, Gneyaa S

2016-10-01

In spite of continued efforts, India is still lagging behind in achieving its MDG goals. The objectives of this study were to identify stake-holders who have a role to play in childhood diarrhea management, to identify gaps in childhood diarrhea management and to propose strategic options for relieving these gaps. Bottleneck analysis exercise was carried out based on the Tanahashi model in six High Priority Districts (HPDs) of Gujarat in period between July-November 2013. The major bottlenecks identified for Childhood Diarrhea management were poor demand generation, unsafe drinking water, poor access to improved sanitation facility and lack of equitable distribution and replenishment mechanisms for Oral Rehydration Solution (ORS) packets and Zinc tablets till the front-line worker level. The main strategic options that were suggested for relieving these bottlenecks were Zinc-ORS roll out in scale-up districts, develop Information Education Communication/Behaviour Change Communication (IEC/BCC) plan for childhood diarrhea management at state/district level, use of Drug Logistics Information Management System (DLIMS) software for supply chain management of Zinc-ORS, strengthening of chlorination activity at household level, monitoring implementation of Nirmal Bharat Abhiyaan (NBA) for constructing improved sanitation facilities at household level and to develop an IEC/BCC plan for hygiene promotion and usage of sanitary latrines. Use of Zinc tablets need to be intensified through an effective scale-up. Adequate demand generation activity is needed. There is need to address safe drinking water and improved sanitation measures at household levels. Multi-sectoral engagements and ownership of Zinc-ORS program is the need of the hour. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contemporary evolution during invasion: evidence for differentiation, natural selection, and local adaptation.

PubMed

Colautti, Robert I; Lau, Jennifer A

2015-05-01

Biological invasions are 'natural' experiments that can improve our understanding of contemporary evolution. We evaluate evidence for population differentiation, natural selection and adaptive evolution of invading plants and animals at two nested spatial scales: (i) among introduced populations (ii) between native and introduced genotypes. Evolution during invasion is frequently inferred, but rarely confirmed as adaptive. In common garden studies, quantitative trait differentiation is only marginally lower (~3.5%) among introduced relative to native populations, despite genetic bottlenecks and shorter timescales (i.e. millennia vs. decades). However, differentiation between genotypes from the native vs. introduced range is less clear and confounded by nonrandom geographic sampling; simulations suggest this causes a high false-positive discovery rate (>50%) in geographically structured populations. Selection differentials (¦s¦) are stronger in introduced than in native species, although selection gradients (¦β¦) are not, consistent with introduced species experiencing weaker genetic constraints. This could facilitate rapid adaptation, but evidence is limited. For example, rapid phenotypic evolution often manifests as geographical clines, but simulations demonstrate that nonadaptive trait clines can evolve frequently during colonization (~two-thirds of simulations). Additionally, QST-FST studies may often misrepresent the strength and form of natural selection acting during invasion. Instead, classic approaches in evolutionary ecology (e.g. selection analysis, reciprocal transplant, artificial selection) are necessary to determine the frequency of adaptive evolution during invasion and its influence on establishment, spread and impact of invasive species. These studies are rare but crucial for managing biological invasions in the context of global change. © 2015 John Wiley & Sons Ltd.

Bayesian Analysis for Inference of an Emerging Epidemic: Citrus Canker in Urban Landscapes

PubMed Central

Neri, Franco M.; Cook, Alex R.; Gibson, Gavin J.; Gottwald, Tim R.; Gilligan, Christopher A.

2014-01-01

Outbreaks of infectious diseases require a rapid response from policy makers. The choice of an adequate level of response relies upon available knowledge of the spatial and temporal parameters governing pathogen spread, affecting, amongst others, the predicted severity of the epidemic. Yet, when a new pathogen is introduced into an alien environment, such information is often lacking or of no use, and epidemiological parameters must be estimated from the first observations of the epidemic. This poses a challenge to epidemiologists: how quickly can the parameters of an emerging disease be estimated? How soon can the future progress of the epidemic be reliably predicted? We investigate these issues using a unique, spatially and temporally resolved dataset for the invasion of a plant disease, Asiatic citrus canker in urban Miami. We use epidemiological models, Bayesian Markov-chain Monte Carlo, and advanced spatial statistical methods to analyse rates and extent of spread of the disease. A rich and complex epidemic behaviour is revealed. The spatial scale of spread is approximately constant over time and can be estimated rapidly with great precision (although the evidence for long-range transmission is inconclusive). In contrast, the rate of infection is characterised by strong monthly fluctuations that we associate with extreme weather events. Uninformed predictions from the early stages of the epidemic, assuming complete ignorance of the future environmental drivers, fail because of the unpredictable variability of the infection rate. Conversely, predictions improve dramatically if we assume prior knowledge of either the main environmental trend, or the main environmental events. A contrast emerges between the high detail attained by modelling in the spatiotemporal description of the epidemic and the bottleneck imposed on epidemic prediction by the limits of meteorological predictability. We argue that identifying such bottlenecks will be a fundamental step in future modelling of weather-driven epidemics. PMID:24762851

Car accidents induced by a bottleneck

NASA Astrophysics Data System (ADS)

Marzoug, Rachid; Echab, Hicham; Ez-Zahraouy, Hamid

2017-12-01

Based on the Nagel-Schreckenberg model (NS) we study the probability of car accidents to occur (Pac) at the entrance of the merging part of two roads (i.e. junction). The simulation results show that the existence of non-cooperative drivers plays a chief role, where it increases the risk of collisions in the intermediate and high densities. Moreover, the impact of speed limit in the bottleneck (Vb) on the probability Pac is also studied. This impact depends strongly on the density, where, the increasing of Vb enhances Pac in the low densities. Meanwhile, it increases the road safety in the high densities. The phase diagram of the system is also constructed.

A model of airport security work flow based on petri net

NASA Astrophysics Data System (ADS)

Dong, Xinming

2017-09-01

Extremely long lines at airports in the United States have been sharply criticized. In order to find out the bottleneck in the existing security system and put forward reasonable improvement plans and proposal, the Petri net model and the Markov Chain are introduced in this paper. This paper uses data collected by transportation Security Agency (TSA), assuming the data can represent the average level of all airports in the Unites States, to analysis the performance of security check system. By calculating the busy probabilities and the utilization probabilities, the bottleneck is found. Moreover, recommendation is given based on the parameters’ modification in Petri net model.

Low worldwide genetic diversity in the killer whale (Orcinus orca): implications for demographic history.

PubMed Central

Hoelzel, A Rus; Natoli, Ada; Dahlheim, Marilyn E; Olavarria, Carlos; Baird, Robin W; Black, Nancy A

2002-01-01

A low level of genetic variation in mammalian populations where the census population size is relatively large has been attributed to various factors, such as a naturally small effective population size, historical bottlenecks and social behaviour. The killer whale (Orcinus orca) is an abundant, highly social species with reduced genetic variation. We find no consistent geographical pattern of global diversity and no mtDNA variation within some regional populations. The regional lack of variation is likely to be due to the strict matrilineal expansion of local populations. The worldwide pattern and paucity of diversity may indicate a historical bottleneck as an additional factor. PMID:12137576

Replantation surgery in Quebec: The bottlenecks to rapid care

PubMed Central

Borsuk, Daniel E; Zadeh, Teanoosh; Lee, Chen; Moore, Karl; Tan, Grace

2006-01-01

INTRODUCTION Time delays resulting in prolonged ischemia have a significant impact on the successful reattachment of amputated body parts. No studies have addressed the issues surrounding delays from the time of the accident to the start of replantation surgery. The present paper identifies the bottlenecks that prolong the time before patients are able to gain access to a replant team. METHODS A total of 50 patients underwent microsurgical replantation, because of traumatic amputation, at a university-based hospital from 1996 to 2003. The charts were analyzed to ascertain individual time intervals from the onset of injury until the beginning of replant surgery. RESULTS The average length of time for patients who came directly to the replant centre was 3 h 40 min before surgery began. In contrast, for those referred from outlying hospitals, the elapsed time was 6 h 21 min. CONCLUSIONS Two major bottlenecks were found. First, for patients who were referred from other health centres, delays were due to a lack of information as to where patients could receive appropriate replant surgery. Second, delays at the replant centre were primarily due to insufficient physical and human resources in the operating room. PMID:19554107

Resistance of virus to extinction on bottleneck passages: study of a decaying and fluctuating pattern of fitness loss

NASA Technical Reports Server (NTRS)

Lazaro, Ester; Escarmis, Cristina; Perez-Mercader, Juan; Manrubia, Susanna C.; Domingo, Esteban

2003-01-01

RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.

Genetic structure and conservation of Mountain Lions in the South-Brazilian Atlantic Rain Forest

PubMed Central

Castilho, Camila S.; Marins-Sá, Luiz G.; Benedet, Rodrigo C.; Freitas, Thales R.O.

2012-01-01

The Brazilian Atlantic Rain Forest, one of the most endangered ecosystems worldwide, is also among the most important hotspots as regards biodiversity. Through intensive logging, the initial area has been reduced to around 12% of its original size. In this study we investigated the genetic variability and structure of the mountain lion, Puma concolor. Using 18 microsatellite loci we analyzed evidence of allele dropout, null alleles and stuttering, calculated the number of allele/locus, PIC, observed and expected heterozygosity, linkage disequilibrium, Hardy-Weinberg equilibrium, FIS, effective population size and genetic structure (MICROCHECKER, CERVUS, GENEPOP, FSTAT, ARLEQUIN, ONESAMP, LDNe, PCAGEN, GENECLASS software), we also determine whether there was evidence of a bottleneck (HYBRIDLAB, BOTTLENECK software) that might influence the future viability of the population in south Brazil. 106 alleles were identified, with the number of alleles/locus ranging from 2 to 11. Mean observed heterozygosity, mean number of alleles and polymorphism information content were 0.609, 5.89, and 0.6255, respectively. This population presented evidence of a recent bottleneck and loss of genetic variation. Persistent regional poaching constitutes an increasing in the extinction risk. PMID:22481876

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

PubMed Central

Alter, S. Elizabeth; Newsome, Seth D.; Palumbi, Stephen R.

2012-01-01

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size. PMID:22590499

Decoupled systems on trial: Eliminating bottlenecks to improve aquaponic processes.

PubMed

Monsees, Hendrik; Kloas, Werner; Wuertz, Sven

2017-01-01

In classical aquaponics (coupled aquaponic systems, 1-loop systems) the production of fish in recirculating aquaculture systems (RAS) and plants in hydroponics are combined in a single loop, entailing systemic compromises on the optimal production parameters (e.g. pH). Recently presented decoupled aquaponics (2-loop systems) have been awarded for eliminating major bottlenecks. In a pilot study, production in an innovative decoupled aquaponic system was compared with a coupled system and, as a control, a conventional RAS, assessing growth parameters of fish (FCR, SGR) and plants over an experimental period of 5 months. Soluble nutrients (NO3--N, NO2--N, NH4+-N, PO43-, K+, Ca2+, Mg2+, SO42-, Cl2- and Fe2+), elemental composition of plants, fish and sludge (N, P, K, Ca, Mg, Na, C), abiotic factors (temperature, pH, oxygen, and conductivity), fertilizer and water consumption were determined. Fruit yield was 36% higher in decoupled aquaponics and pH and fertilizer management was more effective, whereas fish production was comparable in both systems. The results of this pilot study clearly illustrate the main advantages of decoupled, two-loop aquaponics and demonstrate how bottlenecks commonly encountered in coupled aquaponics can be managed to promote application in aquaculture.

Engineering of protein folding and secretion-strategies to overcome bottlenecks for efficient production of recombinant proteins.

PubMed

Delic, Marizela; Göngrich, Rebecca; Mattanovich, Diethard; Gasser, Brigitte

2014-07-20

Recombinant protein production has developed into a huge market with enormous positive implications for human health and for the future direction of a biobased economy. Limitations in the economic and technical feasibility of production processes are often related to bottlenecks of in vivo protein folding. Based on cell biological knowledge, some major bottlenecks have been overcome by the overexpression of molecular chaperones and other folding related proteins, or by the deletion of deleterious pathways that may lead to misfolding, mistargeting, or degradation. While important success could be achieved by this strategy, the list of reported unsuccessful cases is disappointingly long and obviously dependent on the recombinant protein to be produced. Singular engineering of protein folding steps may not lead to desired results if the pathway suffers from several limitations. In particular, the connection between folding quality control and proteolytic degradation needs further attention. Based on recent understanding that multiple steps in the folding and secretion pathways limit productivity, synergistic combinations of the cell engineering approaches mentioned earlier need to be explored. In addition, systems biology-based whole cell analysis that also takes energy and redox metabolism into consideration will broaden the knowledge base for future rational engineering strategies.

Mosquito bottlenecks alter viral mutant swarm in a tissue and time-dependent manner with contraction and expansion of variant positions and diversity.

PubMed

Patterson, Edward I; Khanipov, Kamil; Rojas, Mark M; Kautz, Tiffany F; Rockx-Brouwer, Dedeke; Golovko, Georgiy; Albayrak, Levent; Fofanov, Yuriy; Forrester, Naomi L

2018-01-01

Viral diversity is theorized to play a significant role during virus infections, particularly for arthropod-borne viruses (arboviruses) that must infect both vertebrate and invertebrate hosts. To determine how viral diversity influences mosquito infection and dissemination Culex taeniopus mosquitoes were infected with the Venezuelan equine encephalitis virus endemic strain 68U201. Bodies and legs/wings of the mosquitoes were collected individually and subjected to multi-parallel sequencing. Virus sequence diversity was calculated for each tissue. Greater diversity was seen in mosquitoes with successful dissemination versus those with no dissemination. Diversity across time revealed that bottlenecks influence diversity following dissemination to the legs/wings, but levels of diversity are restored by Day 12 post-dissemination. Specific minority variants were repeatedly identified across the mosquito cohort, some in nearly every tissue and time point, suggesting that certain variants are important in mosquito infection and dissemination. This study demonstrates that the interaction between the mosquito and the virus results in changes in diversity and the mutational spectrum and may be essential for successful transition of the bottlenecks associated with arbovirus infection.

Uniparental Inheritance Promotes Adaptive Evolution in Cytoplasmic Genomes

PubMed Central

Christie, Joshua R.; Beekman, Madeleine

2017-01-01

Eukaryotes carry numerous asexual cytoplasmic genomes (mitochondria and plastids). Lacking recombination, asexual genomes should theoretically suffer from impaired adaptive evolution. Yet, empirical evidence indicates that cytoplasmic genomes experience higher levels of adaptive evolution than predicted by theory. In this study, we use a computational model to show that the unique biology of cytoplasmic genomes—specifically their organization into host cells and their uniparental (maternal) inheritance—enable them to undergo effective adaptive evolution. Uniparental inheritance of cytoplasmic genomes decreases competition between different beneficial substitutions (clonal interference), promoting the accumulation of beneficial substitutions. Uniparental inheritance also facilitates selection against deleterious cytoplasmic substitutions, slowing Muller’s ratchet. In addition, uniparental inheritance generally reduces genetic hitchhiking of deleterious substitutions during selective sweeps. Overall, uniparental inheritance promotes adaptive evolution by increasing the level of beneficial substitutions relative to deleterious substitutions. When we assume that cytoplasmic genome inheritance is biparental, decreasing the number of genomes transmitted during gametogenesis (bottleneck) aids adaptive evolution. Nevertheless, adaptive evolution is always more efficient when inheritance is uniparental. Our findings explain empirical observations that cytoplasmic genomes—despite their asexual mode of reproduction—can readily undergo adaptive evolution. PMID:28025277

On the Overdispersed Molecular Clock

PubMed Central

Takahata, Naoyuki

1987-01-01

Rates of molecular evolution at some loci are more irregular than described by simple Poisson processes. Three situations under which molecular evolution would not follow simple Poisson processes are reevaluated from the viewpoint of the neutrality hypothesis: (i) concomitant or multiple substitutions in a gene, (ii) fluctuating substitution rates in time caused by coupled effects of deleterious mutations and bottlenecks, and (iii) changes in the degree of selective constraints against a gene (neutral space) caused by successive substitutions. The common underlying assumption that these causes are lineage nonspecific excludes the case where mutation rates themselves change systematically among lineages or taxonomic groups, and severely limits the extent of variation in the number of substitutions among lineages. Even under this stringent condition, however, the third hypothesis, the fluctuating neutral space model, can generate fairly large variation. This is described by a time-dependent renewal process, which does not exhibit any episodic nature of molecular evolution. It is argued that the observed elevated variances in the number of nucleotide or amino acid substitutions do not immediately call for positive Darwinian selection in molecular evolution. PMID:3596230

DEApp: an interactive web interface for differential expression analysis of next generation sequence data.

PubMed

Li, Yan; Andrade, Jorge

2017-01-01

A growing trend in the biomedical community is the use of Next Generation Sequencing (NGS) technologies in genomics research. The complexity of downstream differential expression (DE) analysis is however still challenging, as it requires sufficient computer programing and command-line knowledge. Furthermore, researchers often need to evaluate and visualize interactively the effect of using differential statistical and error models, assess the impact of selecting different parameters and cutoffs, and finally explore the overlapping consensus of cross-validated results obtained with different methods. This represents a bottleneck that slows down or impedes the adoption of NGS technologies in many labs. We developed DEApp, an interactive and dynamic web application for differential expression analysis of count based NGS data. This application enables models selection, parameter tuning, cross validation and visualization of results in a user-friendly interface. DEApp enables labs with no access to full time bioinformaticians to exploit the advantages of NGS applications in biomedical research. This application is freely available at https://yanli.shinyapps.io/DEAppand https://gallery.shinyapps.io/DEApp.

A genetically optimized kinetic model for ethanol electro-oxidation on Pt-based binary catalysts used in direct ethanol fuel cells

NASA Astrophysics Data System (ADS)

Sánchez-Monreal, Juan; García-Salaberri, Pablo A.; Vera, Marcos

2017-09-01

A one-dimensional model is proposed for the anode of a liquid-feed direct ethanol fuel cell. The complex kinetics of the ethanol electro-oxidation reaction is described using a multi-step reaction mechanism that considers free and adsorbed intermediate species on Pt-based binary catalysts. The adsorbed species are modeled using coverage factors to account for the blockage of the active reaction sites on the catalyst surface. The reaction rates are described by Butler-Volmer equations that are coupled to a one-dimensional mass transport model, which incorporates the effect of ethanol and acetaldehyde crossover. The proposed kinetic model circumvents the acetaldehyde bottleneck effect observed in previous studies by incorporating CH3CHOHads among the adsorbed intermediates. A multi-objetive genetic algorithm is used to determine the reaction constants using anode polarization and product selectivity data obtained from the literature. By adjusting the reaction constants using the methodology developed here, different catalyst layers could be modeled and their selectivities could be successfully reproduced.

The legacy of domestication: accumulation of deleterious mutations in the dog genome.

PubMed

Cruz, Fernando; Vilà, Carles; Webster, Matthew T

2008-11-01

Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The d(N)/d(S) ratio (omega) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill-Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.

Independent Molecular Basis of Convergent Highland Adaptation in Maize

PubMed Central

Takuno, Shohei; Ralph, Peter; Swarts, Kelly; Elshire, Rob J.; Glaubitz, Jeffrey C.; Buckler, Edward S.; Hufford, Matthew B.; Ross-Ibarra, Jeffrey

2015-01-01

Convergent evolution is the independent evolution of similar traits in different species or lineages of the same species; this often is a result of adaptation to similar environments, a process referred to as convergent adaptation. We investigate here the molecular basis of convergent adaptation in maize to highland climates in Mesoamerica and South America, using genome-wide SNP data. Taking advantage of archaeological data on the arrival of maize to the highlands, we infer demographic models for both populations, identifying evidence of a strong bottleneck and rapid expansion in South America. We use these models to then identify loci showing an excess of differentiation as a means of identifying putative targets of natural selection and compare our results to expectations from recently developed theory on convergent adaptation. Consistent with predictions across a wide parameter space, we see limited evidence for convergent evolution at the nucleotide level in spite of strong similarities in overall phenotypes. Instead, we show that selection appears to have predominantly acted on standing genetic variation and that introgression from wild teosinte populations appears to have played a role in highland adaptation in Mexican maize. PMID:26078279

Sequence polymorphism in an insect RNA virus field population: A snapshot from a single point in space and time reveals stochastic differences among and within individual hosts

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

Stenger, Drake C., E-mail: drake.stenger@ars.usda.

Population structure of Homalodisca coagulata Virus-1 (HoCV-1) among and within field-collected insects sampled from a single point in space and time was examined. Polymorphism in complete consensus sequences among single-insect isolates was dominated by synonymous substitutions. The mutant spectrum of the C2 helicase region within each single-insect isolate was unique and dominated by nonsynonymous singletons. Bootstrapping was used to correct the within-isolate nonsynonymous:synonymous arithmetic ratio (N:S) for RT-PCR error, yielding an N:S value ~one log-unit greater than that of consensus sequences. Probability of all possible single-base substitutions for the C2 region predicted N:S values within 95% confidence limits of themore » corrected within-isolate N:S when the only constraint imposed was viral polymerase error bias for transitions over transversions. These results indicate that bottlenecks coupled with strong negative/purifying selection drive consensus sequences toward neutral sequence space, and that most polymorphism within single-insect isolates is composed of newly-minted mutations sampled prior to selection. -- Highlights: •Sampling protocol minimized differential selection/history among isolates. •Polymorphism among consensus sequences dominated by negative/purifying selection. •Within-isolate N:S ratio corrected for RT-PCR error by bootstrapping. •Within-isolate mutant spectrum dominated by new mutations yet to undergo selection.« less

Fabrication and Optimization of Stable, Optically Transparent, and Reusable pH-Responsive Silk Membranes

PubMed Central

Toytziaridis, Andreas; Dicko, Cedric

2016-01-01

The fabrication of silk-based membranes that are stable, optically transparent and reusable is yet to be achieved. To address this bottleneck we have developed a method to produce transparent chromogenic silk patches that are optically responsive to pH. The patches were produced by blending regenerated silk fibroin (RSF), Laponite RD (nano clay) and the organic dyes neutral red and Thionine acetate. The Laponite RD played a central role in the patch mechanical integrity and prevention of dye leaching. The process was optimized using a factorial design to maximize the patch response to pH by UV absorbance and fluorescence emission. New patches of the optimized protocol, made from solutions containing 125 μM neutral red or 250 μM of Thionine and 15 mg/mL silk, were further tested for operational stability over several cycles of pH altering. Stability, performance, and reusability were achieved over the tested cycles. The approach could be extended to other reporting molecules or enzymes able to bind to Laponite. PMID:27854303

Insect photoreceptor adaptations to night vision.

PubMed

Honkanen, Anna; Immonen, Esa-Ville; Salmela, Iikka; Heimonen, Kyösti; Weckström, Matti

2017-04-05

Night vision is ultimately about extracting information from a noisy visual input. Several species of nocturnal insects exhibit complex visually guided behaviour in conditions where most animals are practically blind. The compound eyes of nocturnal insects produce strong responses to single photons and process them into meaningful neural signals, which are amplified by specialized neuroanatomical structures. While a lot is known about the light responses and the anatomical structures that promote pooling of responses to increase sensitivity, there is still a dearth of knowledge on the physiology of night vision. Retinal photoreceptors form the first bottleneck for the transfer of visual information. In this review, we cover the basics of what is known about physiological adaptations of insect photoreceptors for low-light vision. We will also discuss major enigmas of some of the functional properties of nocturnal photoreceptors, and describe recent advances in methodologies that may help to solve them and broaden the field of insect vision research to new model animals.This article is part of the themed issue 'Vision in dim light'. © 2017 The Author(s).

Age-associated metabolic dysregulation in bone marrow-derived macrophages stimulated with lipopolysaccharide

NASA Astrophysics Data System (ADS)

Fei, Fan; Lee, Keith M.; McCarry, Brian E.; Bowdish, Dawn M. E.

2016-03-01

Macrophages are major contributors to age-associated inflammation. Metabolic processes such as oxidative phosphorylation, glycolysis and the urea cycle regulate inflammatory responses by macrophages. Metabolic profiles changes with age; therefore, we hypothesized that dysregulation of metabolic processes could contribute to macrophage hyporesponsiveness to LPS. We examined the intracellular metabolome of bone marrow-derived macrophages from young (6-8 wk) and old (18-22 mo) mice following lipopolysaccharide (LPS) stimulation and tolerance. We discovered known and novel metabolites that were associated with the LPS response of macrophages from young mice, which were not inducible in macrophages from old mice. Macrophages from old mice were largely non-responsive towards LPS stimulation, and we did not observe a shift from oxidative phosphorylation to glycolysis. The critical regulatory metabolites succinate, γ-aminobutyric acid, arginine, ornithine and adenosine were increased in LPS-stimulated macrophages from young mice, but not macrophages from old mice. A shift between glycolysis and oxidative phosphorylation was not observed during LPS tolerance in macrophages from either young or old mice. Metabolic bottlenecks may be one of the mechanisms that contribute to the dysregulation of LPS responses with age.

Quick Vegas: Improving Performance of TCP Vegas for High Bandwidth-Delay Product Networks

NASA Astrophysics Data System (ADS)

Chan, Yi-Cheng; Lin, Chia-Liang; Ho, Cheng-Yuan

An important issue in designing a TCP congestion control algorithm is that it should allow the protocol to quickly adjust the end-to-end communication rate to the bandwidth on the bottleneck link. However, the TCP congestion control may function poorly in high bandwidth-delay product networks because of its slow response with large congestion windows. In this paper, we propose an enhanced version of TCP Vegas called Quick Vegas, in which we present an efficient congestion window control algorithm for a TCP source. Our algorithm improves the slow-start and congestion avoidance techniques of original Vegas. Simulation results show that Quick Vegas significantly improves the performance of connections as well as remaining fair when the bandwidth-delay product increases.

Quantum Speedup for Active Learning Agents

NASA Astrophysics Data System (ADS)

Paparo, Giuseppe Davide; Dunjko, Vedran; Makmal, Adi; Martin-Delgado, Miguel Angel; Briegel, Hans J.

2014-07-01

Can quantum mechanics help us build intelligent learning agents? A defining signature of intelligent behavior is the capacity to learn from experience. However, a major bottleneck for agents to learn in real-life situations is the size and complexity of the corresponding task environment. Even in a moderately realistic environment, it may simply take too long to rationally respond to a given situation. If the environment is impatient, allowing only a certain time for a response, an agent may then be unable to cope with the situation and to learn at all. Here, we show that quantum physics can help and provide a quadratic speedup for active learning as a genuine problem of artificial intelligence. This result will be particularly relevant for applications involving complex task environments.

Studies on bacterial inclusion bodies.

PubMed

de Groot, Natalia S; Espargaró, Alba; Morell, Montserrat; Ventura, Salvador

2008-08-01

The field of protein misfolding and aggregation has become an extremely active area of research in recent years. Of particular interest is the deposition of polypeptides into inclusion bodies inside bacterial cells. One reason for this interest is that protein aggregation constitutes a major bottleneck in protein production and restricts the spectrum of protein-based drugs available for commercialization. Additionally, prokaryotic cells could provide a simple yet powerful system for studying the formation and prevention of toxic aggregates, such as those responsible for a number of degenerative diseases. Here, we review recent work that has challenged our understanding of the structure and physiology of inclusion bodies and provided us with a new view of intracellular protein deposition, which has important implications in microbiology, biomedicine and biotechnology.

Proteomic researches for lignocellulose-degrading enzymes: A mini-review.

PubMed

Guo, Hongliang; Wang, Xiao-Dong; Lee, Duu-Jong

2018-05-31

Protective action of lignin/hemicellulose networks and crystalline structures of embedded cellulose render lignocellulose material resistant to external enzymatic attack. To eliminate this bottleneck, research has been conducted in which advanced proteomic techniques are applied to identify effective commercial hydrolytic enzymes. This mini-review summarizes researches on lignocellulose-degrading enzymes, the mechanisms of the responses of various lignocellulose-degrading strains and microbial communities to various carbon sources and various biomass substrates, post-translational modifications of lignocellulose-degrading enzymes, new lignocellulose-degrading strains, new lignocellulose-degrading enzymes and a new method of secretome analysis. The challenges in the practical use of enzymatic hydrolysis process to realize lignocellulose biorefineries are discussed, along with the prospects for the same. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficient multi-site two-photon functional imaging of neuronal circuits.

PubMed

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R

2016-12-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms.

Efficient multi-site two-photon functional imaging of neuronal circuits

PubMed Central

Castanares, Michael Lawrence; Gautam, Vini; Drury, Jack; Bachor, Hans; Daria, Vincent R.

2016-01-01

Two-photon imaging using high-speed multi-channel detectors is a promising approach for optical recording of cellular membrane dynamics at multiple sites. A main bottleneck of this technique is the limited number of photons captured within a short exposure time (~1ms). Here, we implement temporal gating to improve the two-photon fluorescence yield from holographically projected multiple foci whilst maintaining a biologically safe incident average power. We observed up to 6x improvement in the signal-to-noise ratio (SNR) in Fluorescein and cultured hippocampal neurons showing evoked calcium transients. With improved SNR, we could pave the way to achieving multi-site optical recording of fluorogenic probes with response times in the order of ~1ms. PMID:28018745

Climate adaption and post-fire restoration of a foundational perennial in cold desert: Insights from intraspecific variation in response to weather

USGS Publications Warehouse

Brabec, Martha M.; Germino, Matthew; Richardson, Bryce A.

2017-01-01

1.The loss of foundational but fire-intolerant perennials such as sagebrush due to increases in fire size and frequency in semiarid regions has motivated efforts to restore them, often with mixed or even no success. Seeds of sagebrush Artemisia tridentata and related species must be moved considerable distances from seed source to planting sites, but such transfers have not been guided by an understanding of local climate adaptation. Initial seedling establishment and its response to weather are a key demographic bottleneck that likely varies among subspecies and populations of sagebrush. 2.We assessed differences in survival, growth, and physiological responses of sagebrush to weather among eleven seed sources that varied in subspecies, cytotype, and climates-of-origin over 18 months following outplanting. Diploid or polyploid populations of mountain, Wyoming, and basin big sagebrush (A.tridentata ssp. vaseyana, A.tridentata ssp. wyomingensis, and A.tridentata ssp. tridentata, respectively) were planted onto five burned sites that normally support A.t.wyomingensis with some A.t.tridentata. 3.A.t.wyomingensis had the most growth and survival, and tetraploid populations had greater survival and height than diploids. Seasonal timing of mortality varied among the subspecies/cytotypes and was more closely related to minimum temperatures than water deficit. 4.Temperatures required to induce ice formation were up to 6°C more negative in 4n-A.t.tridentata and A.t.wyomingensis than other subspecies/cytotypes, indicating greater freezing avoidance. In contrast, freezing resistance of photosynthesis varied only 1°C among subspecies/cytotypes, being greatest in A.t.wyomingensis and least in the subspecies normally considered most cold-adapted,A.t.vaseyana. A large spectrum of reliance on freezing-avoidance vs. freezing-tolerance was observed and corresponded to differences in post-fire survivorship among subspecies/cytotypes. Differences in water deficit responses among subspecies/cytotypes were not as strong and did not relate to survival patterns. 5.Synthesis and applications. Low temperature responses are a key axis defining climate adaptation in young sagebrush seedlings and vary more with cytotype than with subspecies, which contrasts with the traditional emphases on (i) water limitations to explain establishment in these deserts, and (ii) subspecies in selecting restoration seedings. These important and novel insights on climate adaptation are critical for seed selection and parameterizing seed transfer zones, and were made possible by incorporating weather data with survival statistics. The survival/weather statistics used here could be applied to any restoration planting or seeding to help elucidate factors contributing to success and enable adaptive management.

Ancient mitochondrial DNA analysis reveals complexity of indigenous North American turkey domestication

PubMed Central

Speller, Camilla F.; Kemp, Brian M.; Wyatt, Scott D.; Monroe, Cara; Lipe, William D.; Arndt, Ursula M.; Yang, Dongya Y.

2010-01-01

Although the cultural and nutritive importance of the turkey (Meleagris gallopavo) to precontact Native Americans and contemporary people worldwide is clear, little is known about the domestication of this bird compared to other domesticates. Mitochondrial DNA analysis of 149 turkey bones and 29 coprolites from 38 archaeological sites (200 BC–AD 1800) reveals a unique domesticated breed in the precontact Southwestern United States. Phylogeographic analyses indicate that this domestic breed originated from outside the region, but rules out the South Mexican domestic turkey (Meleagris gallopavo gallopavo) as a progenitor. A strong genetic bottleneck within the Southwest turkeys also reflects intensive human selection and breeding. This study points to at least two occurrences of turkey domestication in precontact North America and illuminates the intensity and sophistication of New World animal breeding practices. PMID:20133614

[Study on the automatic parameters identification of water pipe network model].

PubMed

Jia, Hai-Feng; Zhao, Qi-Feng

2010-01-01

Based on the problems analysis on development and application of water pipe network model, the model parameters automatic identification is regarded as a kernel bottleneck of model's application in water supply enterprise. The methodology of water pipe network model parameters automatic identification based on GIS and SCADA database is proposed. Then the kernel algorithm of model parameters automatic identification is studied, RSA (Regionalized Sensitivity Analysis) is used for automatic recognition of sensitive parameters, and MCS (Monte-Carlo Sampling) is used for automatic identification of parameters, the detail technical route based on RSA and MCS is presented. The module of water pipe network model parameters automatic identification is developed. At last, selected a typical water pipe network as a case, the case study on water pipe network model parameters automatic identification is conducted and the satisfied results are achieved.

Understanding RNA modifications: the promises and technological bottlenecks of the ‘epitranscriptome’

PubMed Central

Kapoor, Utkarsh

2017-01-01

The discovery of mechanisms that alter genetic information via RNA editing or introducing covalent RNA modifications points towards a complexity in gene expression that challenges long-standing concepts. Understanding the biology of RNA modifications represents one of the next frontiers in molecular biology. To this date, over 130 different RNA modifications have been identified, and improved mass spectrometry approaches are still adding to this list. However, only recently has it been possible to map selected RNA modifications at single-nucleotide resolution, which has created a number of exciting hypotheses about the biological function of RNA modifications, culminating in the proposition of the ‘epitranscriptome’. Here, we review some of the technological advances in this rapidly developing field, identify the conceptual challenges and discuss approaches that are needed to rigorously test the biological function of specific RNA modifications. PMID:28566301

A tool for selective inline quantification of co-eluting proteins in chromatography using spectral analysis and partial least squares regression.

PubMed

Brestrich, Nina; Briskot, Till; Osberghaus, Anna; Hubbuch, Jürgen

2014-07-01

Selective quantification of co-eluting proteins in chromatography is usually performed by offline analytics. This is time-consuming and can lead to late detection of irregularities in chromatography processes. To overcome this analytical bottleneck, a methodology for selective protein quantification in multicomponent mixtures by means of spectral data and partial least squares regression was presented in two previous studies. In this paper, a powerful integration of software and chromatography hardware will be introduced that enables the applicability of this methodology for a selective inline quantification of co-eluting proteins in chromatography. A specific setup consisting of a conventional liquid chromatography system, a diode array detector, and a software interface to Matlab® was developed. The established tool for selective inline quantification was successfully applied for a peak deconvolution of a co-eluting ternary protein mixture consisting of lysozyme, ribonuclease A, and cytochrome c on SP Sepharose FF. Compared to common offline analytics based on collected fractions, no loss of information regarding the retention volumes and peak flanks was observed. A comparison between the mass balances of both analytical methods showed, that the inline quantification tool can be applied for a rapid determination of pool yields. Finally, the achieved inline peak deconvolution was successfully applied to make product purity-based real-time pooling decisions. This makes the established tool for selective inline quantification a valuable approach for inline monitoring and control of chromatographic purification steps and just in time reaction on process irregularities. © 2014 Wiley Periodicals, Inc.

Low Major Histocompatibility Complex Class II Variation in the Endangered Indo-Pacific Humpback Dolphin (Sousa chinensis): Inferences About the Role of Balancing Selection.

PubMed

Zhang, Xiyang; Lin, Wenzhi; Zhou, Ruilian; Gui, Duan; Yu, Xinjian; Wu, Yuping

2016-03-01

It has been widely reported that the major histocompatibility complex (MHC) is under balancing selection due to its immune function across terrestrial and aquatic mammals. The comprehensive studies at MHC and other neutral loci could give us a synthetic evaluation about the major force determining genetic diversity of species. Previously, a low level of genetic diversity has been reported among the Indo-Pacific humpback dolphin (Sousa chinensis) in the Pearl River Estuary (PRE) using both mitochondrial marker and microsatellite loci. Here, the expression and sequence polymorphism of 2 MHC class II genes (DQB and DRB) in 32 S. chinensis from PRE collected between 2003 and 2011 were investigated. High ratios of non-synonymous to synonymous substitution rates, codon-based selection analysis, and trans-species polymorphism (TSP) support the hypothesis that balancing selection acted on S. chinensis MHC sequences. However, only 2 haplotypes were detected at either DQB or DRB loci. Moreover, the lack of deviation from the Hardy-Weinberg expectation at DRB locus combined with the relatively low heterozygosity at both DQB locus and microsatellite loci suggested that balancing selection might not be sufficient, which further suggested that genetic drift associated with historical bottlenecks was not mitigated by balancing selection in terms of the loss of MHC and neutral variation in S. chinensis. The combined results highlighted the importance of maintaining the genetic diversity of the endangered S. chinensis. © The American Genetic Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Photocatalytic Conversion of CO2 to CO by a Copper(II) Quaterpyridine Complex.

PubMed

Guo, Zhenguo; Yu, Fei; Yang, Ying; Leung, Chi-Fai; Ng, Siu-Mui; Ko, Chi-Chiu; Cometto, Claudio; Lau, Tai-Chu; Robert, Marc

2017-10-23

The invention of efficient systems for the photocatalytic reduction of CO 2 comprising earth-abundant metal catalysts is a promising approach for the production of solar fuels. One bottleneck is to design highly selective and robust molecular complexes that are able to transform the CO 2 gas. The Cu II quaterpyridine complex [Cu(qpy)] 2+ (1) is found to be a highly efficient and selective catalyst for visible-light driven CO 2 reduction in CH 3 CN using [Ru(bpy) 3 ] 2+ (bpy: bipyridine) as photosensitizer and BIH/TEOA (1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole/triethanolamine) as sacrificial reductant. The photocatalytic reaction is greatly enhanced by the presence of H 2 O (1-4 % v/v), and a turnover number of >12 400 for CO production can be achieved with 97 % selectivity, which is among the highest of molecular 3d CO 2 reduction catalysts. Results from Hg poisoning and dynamic light scattering experiments suggest that this photocatalyst is homogenous. To the best of our knowledge, 1 is the first example of molecular Cu-based catalyst for the photoreduction of CO 2 . © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses.

PubMed

Furuse, Yuki; Matsuzaki, Yoko; Nishimura, Hidekazu; Oshitani, Hitoshi

2016-11-26

Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1) multiple lineages have been circulating globally; (2) there have been weak and infrequent selective bottlenecks; (3) the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4) there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics.

Analyses of Evolutionary Characteristics of the Hemagglutinin-Esterase Gene of Influenza C Virus during a Period of 68 Years Reveals Evolutionary Patterns Different from Influenza A and B Viruses

PubMed Central

Furuse, Yuki; Matsuzaki, Yoko; Nishimura, Hidekazu; Oshitani, Hitoshi

2016-01-01

Infections with the influenza C virus causing respiratory symptoms are common, particularly among children. Since isolation and detection of the virus are rarely performed, compared with influenza A and B viruses, the small number of available sequences of the virus makes it difficult to analyze its evolutionary dynamics. Recently, we reported the full genome sequence of 102 strains of the virus. Here, we exploited the data to elucidate the evolutionary characteristics and phylodynamics of the virus compared with influenza A and B viruses. Along with our data, we obtained public sequence data of the hemagglutinin-esterase gene of the virus; the dataset consists of 218 unique sequences of the virus collected from 14 countries between 1947 and 2014. Informatics analyses revealed that (1) multiple lineages have been circulating globally; (2) there have been weak and infrequent selective bottlenecks; (3) the evolutionary rate is low because of weak positive selection and a low capability to induce mutations; and (4) there is no significant positive selection although a few mutations affecting its antigenicity have been induced. The unique evolutionary dynamics of the influenza C virus must be shaped by multiple factors, including virological, immunological, and epidemiological characteristics. PMID:27898037

Contrasting patterns of nonneutral evolution in proteins encoded in nuclear and mitochondrial genomes.

PubMed Central

Weinreich, D M; Rand, D M

2000-01-01

We report that patterns of nonneutral DNA sequence evolution among published nuclear and mitochondrially encoded protein-coding loci differ significantly in animals. Whereas an apparent excess of amino acid polymorphism is seen in most (25/31) mitochondrial genes, this pattern is seen in fewer than half (15/36) of the nuclear data sets. This differentiation is even greater among data sets with significant departures from neutrality (14/15 vs. 1/6). Using forward simulations, we examined patterns of nonneutral evolution using parameters chosen to mimic the differences between mitochondrial and nuclear genetics (we varied recombination rate, population size, mutation rate, selective dominance, and intensity of germ line bottleneck). Patterns of evolution were correlated only with effective population size and strength of selection, and no single genetic factor explains the empirical contrast in patterns. We further report that in Arabidopsis thaliana, a highly self-fertilizing plant with effectively low recombination, five of six published nuclear data sets also exhibit an excess of amino acid polymorphism. We suggest that the contrast between nuclear and mitochondrial nonneutrality in animals stems from differences in rates of recombination in conjunction with a distribution of selective effects. If the majority of mutations segregating in populations are deleterious, high linkage may hinder the spread of the occasional beneficial mutation. PMID:10978302

Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

PubMed Central

Petersen, Jessica L.; Mickelson, James R.; Cothran, E. Gus; Andersson, Lisa S.; Axelsson, Jeanette; Bailey, Ernie; Bannasch, Danika; Binns, Matthew M.; Borges, Alexandre S.; Brama, Pieter; da Câmara Machado, Artur; Distl, Ottmar; Felicetti, Michela; Fox-Clipsham, Laura; Graves, Kathryn T.; Guérin, Gérard; Haase, Bianca; Hasegawa, Telhisa; Hemmann, Karin; Hill, Emmeline W.; Leeb, Tosso; Lindgren, Gabriella; Lohi, Hannes; Lopes, Maria Susana; McGivney, Beatrice A.; Mikko, Sofia; Orr, Nicholas; Penedo, M. Cecilia T; Piercy, Richard J.; Raekallio, Marja; Rieder, Stefan; Røed, Knut H.; Silvestrelli, Maurizio; Swinburne, June; Tozaki, Teruaki; Vaudin, Mark; M. Wade, Claire; McCue, Molly E.

2013-01-01

Horses were domesticated from the Eurasian steppes 5,000–6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection. PMID:23383025

A Step-by-Step Framework on Discrete Events Simulation in Emergency Department; A Systematic Review

PubMed Central

Dehghani, Mahsa; Moftian, Nazila; Rezaei-Hachesu, Peyman; Samad-Soltani, Taha

2017-01-01

Objective: To systematically review the current literature of simulation in healthcare including the structured steps in the emergency healthcare sector by proposing a framework for simulation in the emergency department. Methods: For the purpose of collecting the data, PubMed and ACM databases were used between the years 2003 and 2013. The inclusion criteria were to select English-written articles available in full text with the closest objectives from among a total of 54 articles retrieved from the databases. Subsequently, 11 articles were selected for further analysis. Results: The studies focused on the reduction of waiting time and patient stay, optimization of resources allocation, creation of crisis and maximum demand scenarios, identification of overcrowding bottlenecks, investigation of the impact of other systems on the existing system, and improvement of the system operations and functions. Subsequently, 10 simulation steps were derived from the relevant studies after an expert’s evaluation. Conclusion: The 10-steps approach proposed on the basis of the selected studies provides simulation and planning specialists with a structured method for both analyzing problems and choosing best-case scenarios. Moreover, following this framework systematically enables the development of design processes as well as software implementation of simulation problems. PMID:28507994

Rapid high-throughput cloning and stable expression of antibodies in HEK293 cells.

PubMed

Spidel, Jared L; Vaessen, Benjamin; Chan, Yin Yin; Grasso, Luigi; Kline, J Bradford

2016-12-01

Single-cell based amplification of immunoglobulin variable regions is a rapid and powerful technique for cloning antigen-specific monoclonal antibodies (mAbs) for purposes ranging from general laboratory reagents to therapeutic drugs. From the initial screening process involving small quantities of hundreds or thousands of mAbs through in vitro characterization and subsequent in vivo experiments requiring large quantities of only a few, having a robust system for generating mAbs from cloning through stable cell line generation is essential. A protocol was developed to decrease the time, cost, and effort required by traditional cloning and expression methods by eliminating bottlenecks in these processes. Removing the clonal selection steps from the cloning process using a highly efficient ligation-independent protocol and from the stable cell line process by utilizing bicistronic plasmids to generate stable semi-clonal cell pools facilitated an increased throughput of the entire process from plasmid assembly through transient transfections and selection of stable semi-clonal cell pools. Furthermore, the time required by a single individual to clone, express, and select stable cell pools in a high-throughput format was reduced from 4 to 6months to only 4 to 6weeks. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparative population genomics of latitudinal variation in Drosophila simulans and Drosophila melanogaster

PubMed Central

MACHADO, HEATHER E.; BERGLAND, ALAN O.; O’BRIEN, KATHERINE R.; BEHRMAN, EMILY L.; SCHMIDT, PAUL S.; PETROV, DMITRI A.

2016-01-01

Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. Here, we examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of Drosophila simulans and Drosophila melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple time points over 2 years. Consistent with phenotypic studies, we find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, we find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and we find evidence for a stronger contribution of migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in stability of clinal variation between the two species, we also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. PMID:26523848

Boronate affinity-based surface molecularly imprinted polymers using glucose as fragment template for excellent recognition of glucosides.

PubMed

Peng, Mijun; Xiang, Haiyan; Hu, Xin; Shi, Shuyun; Chen, Xiaoqing

2016-11-25

Rapid and efficient extraction of bioactive glycosides from complex natural origins poses a difficult challenge, and then is often inherent bottleneck for their highly utilization. Herein, we propose a strategy to fabricate boronate affinity based surface molecularly imprinted polymers (MIPs) for excellent recognition of glucosides. d-glucose was used as fragment template. Boronic acid, dynamic covalent binding with d-glucose under different pH conditions, was selected as functional monomer to improve specificity. Fe 3 O 4 solid core for surface imprinting using tetraethyl orthosilicate (TEOS) as crosslinker could control imprinted shell thickness for favorable adsorption capacity and satisfactory mass transfer rate, improve hydrophilicity, separate easily by a magnet. Model adsorption studies showed that the resulting MIPs show specific recognition of glucosides. The equilibrium data fitted well to Langmuir equation and the adsorption process could be described by pseudo-second order model. Furthermore, the MIPs were successfully applied for selective extraction of three flavonoid glucosides (daidzin, glycitin, and genistin) from soybean. Results indicated that selective extraction of glucosides from complex aqueous media based on the prepared MIPs is simple, rapid, efficient and specific. Moreover, this method opens up a universal route for imprinting saccharide with cis-diol group for glycosides recognition. Copyright © 2016 Elsevier B.V. All rights reserved.