Epigenetically-inherited centromere and neocentromere DNA replicates earliest in S-phase.

PubMed

Koren, Amnon; Tsai, Hung-Ji; Tirosh, Itay; Burrack, Laura S; Barkai, Naama; Berman, Judith

2010-08-19

Eukaryotic centromeres are maintained at specific chromosomal sites over many generations. In the budding yeast Saccharomyces cerevisiae, centromeres are genetic elements defined by a DNA sequence that is both necessary and sufficient for function; whereas, in most other eukaryotes, centromeres are maintained by poorly characterized epigenetic mechanisms in which DNA has a less definitive role. Here we use the pathogenic yeast Candida albicans as a model organism to study the DNA replication properties of centromeric DNA. By determining the genome-wide replication timing program of the C. albicans genome, we discovered that each centromere is associated with a replication origin that is the first to fire on its respective chromosome. Importantly, epigenetic formation of new ectopic centromeres (neocentromeres) was accompanied by shifts in replication timing, such that a neocentromere became the first to replicate and became associated with origin recognition complex (ORC) components. Furthermore, changing the level of the centromere-specific histone H3 isoform led to a concomitant change in levels of ORC association with centromere regions, further supporting the idea that centromere proteins determine origin activity. Finally, analysis of centromere-associated DNA revealed a replication-dependent sequence pattern characteristic of constitutively active replication origins. This strand-biased pattern is conserved, together with centromere position, among related strains and species, in a manner independent of primary DNA sequence. Thus, inheritance of centromere position is correlated with a constitutively active origin of replication that fires at a distinct early time. We suggest a model in which the distinct timing of DNA replication serves as an epigenetic mechanism for the inheritance of centromere position.

Replication domains are self-interacting structural chromatin units of human chromosomes

NASA Astrophysics Data System (ADS)

Arneodo, Alain

2011-03-01

In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. In silico analysis of nucleotide compositional skew has predicted the existence, in the germline, of replication N-domains bordered by putative replication origins and where the skew decreases rather linearly as the signature of a progressive inversion of the average fork polarity. Here, from the demonstration that the average fork polarity can be directly extracted from the derivative of replication timing profiles, we develop a wavelet-based pattern recognition methodology to delineate replication U-domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines as covering a significant portion (40-50%) of the human genome where the replication timing data actually displays some plasticity between cell lines. The early replication initiation zones at U-domains borders are found to be hypersensitive to DNase I cleavage, to be associated with transcriptional activity and to present a significant enrichment in insular-binding proteins CTCF, the hallmark of an open chromatin structure. A comparative analysis of genome-wide chromatin interaction (HiC) data shows that replication-U domains correspond to self-interacting structural high order chromatin units of megabase characteristic size. Taken together, these findings provide evidence that the epigenetic compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the threedimensional chromosome architecture during development or in specific diseases. The observed cell specific conservation of the replication timing between the human and mouse genomes strongly suggests that this chromosome organization into self-interacting structural and functional units is a general feature of mammalian organisms.

Preventing alcohol and drug exposed births in Washington state: intervention findings from three parent-child assistance program sites.

PubMed

Grant, Therese M; Ernst, Cara C; Streissguth, Ann; Stark, Kenneth

2005-01-01

Home visitation interventions show promise for helping at-risk mothers, yet few programs have been developed and evaluated specifically for alcohol and drug-abusing pregnant women. This study examines outcomes among 216 women enrolled in the Washington State Parent-Child Assistance Program, a three-year intervention program for women who abuse alcohol and drugs during an index pregnancy. Pretest-posttest comparison was made across three sites: the original demonstration (1991-1995), and the Seattle and Tacoma replications (1996-2003). In the original demonstration, the client group performed significantly better than controls. Compared to the original demonstration, outcomes at replication sites were maintained (for regular use of contraception and use of reliable method; and number of subsequent deliveries), or improved (for alcohol/drug treatment completed; alcohol/ drug abstinence; subsequent delivery unexposed to alcohol/drugs). Improved outcomes at replication sites are not attributable to enrolling lower-risk women. Public policies and programs initiated over the study period may have had a positive effect on outcomes. Study findings suggest that this community-based intervention model is effective over time and across venues.

Laying a Solid Foundation: Strategies for Effective Program Replication

ERIC Educational Resources Information Center

Summerville, Geri

2009-01-01

The replication of proven social programs is a cost-effective and efficient way to achieve large-scale, positive social change. Yet there has been little guidance available about how to approach program replication and limited development of systems--at local, state or federal levels--to support replication efforts. "Laying a Solid Foundation:…

Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

PubMed

Miller, Ted R; Hendrie, Delia

2015-12-01

The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale.

Evaluating effects of developmental education for college students using a regression discontinuity design.

PubMed

Moss, Brian G; Yeaton, William H

2013-10-01

Annually, American colleges and universities provide developmental education (DE) to millions of underprepared students; however, evaluation estimates of DE benefits have been mixed. Using a prototypic exemplar of DE, our primary objective was to investigate the utility of a replicative evaluative framework for assessing program effectiveness. Within the context of the regression discontinuity (RD) design, this research examined the effectiveness of a DE program for five, sequential cohorts of first-time college students. Discontinuity estimates were generated for individual terms and cumulatively, across terms. Participants were 3,589 first-time community college students. DE program effects were measured by contrasting both college-level English grades and a dichotomous measure of pass/fail, for DE and non-DE students. Parametric and nonparametric estimates of overall effect were positive for continuous and dichotomous measures of achievement (grade and pass/fail). The variability of program effects over time was determined by tracking results within individual terms and cumulatively, across terms. Applying this replication strategy, DE's overall impact was modest (an effect size of approximately .20) but quite consistent, based on parametric and nonparametric estimation approaches. A meta-analysis of five RD results yielded virtually the same estimate as the overall, parametric findings. Subset analysis, though tentative, suggested that males benefited more than females, while academic gains were comparable for different ethnicities. The cumulative, within-study comparison, replication approach offers considerable potential for the evaluation of new and existing policies, particularly when effects are relatively small, as is often the case in applied settings.

Replication landscape of the human genome

PubMed Central

Petryk, Nataliya; Kahli, Malik; d'Aubenton-Carafa, Yves; Jaszczyszyn, Yan; Shen, Yimin; Silvain, Maud; Thermes, Claude; Chen, Chun-Long; Hyrien, Olivier

2016-01-01

Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains' (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs. PMID:26751768

Managing schedule and financial risk in a faster, better, cheaper development

NASA Technical Reports Server (NTRS)

Boyd, R. W.

2000-01-01

The X2000 Program is a technology development program that will provide next generation avionics for missions to deep space. The goal of the X2000 Program is to develop revolutionary flight and ground systems which can be replicated by missions at a low cost, affording timely new science and mission opportunities to investigators and institutions.

One Year Program to Train Developers in Public Education Systems. Final Report.

ERIC Educational Resources Information Center

New York Univ., NY. Inst. of Afro-American Affairs.

The purpose of this program to train developers in public education systems was to construct and test a viable model that would fulfill its training goals in one year and which could also be replicated under similar conditions by comparable institutions. The model involved a part-time program which provided theoretical and experiential training…

Development and pilot study findings of the Delta Garden Study

USDA-ARS?s Scientific Manuscript database

The purpose of this study was to explore how school–based gardening programs can affect health and related behaviors and to assess how such programs can be sustainable over time and replicated to more settings. Across the world, there has been a recent revitalization and reinvention of gardening eff...

The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription▿

PubMed Central

Dutta, Chaitali; Patel, Prasanta K.; Rosebrock, Adam; Oliva, Anna; Leatherwood, Janet; Rhind, Nicholas

2008-01-01

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes. PMID:18662996

Different nucleosomal architectures at early and late replicating origins in Saccharomyces cerevisiae.

PubMed

Soriano, Ignacio; Morafraile, Esther C; Vázquez, Enrique; Antequera, Francisco; Segurado, Mónica

2014-09-13

Eukaryotic genomes are replicated during S phase according to a temporal program. Several determinants control the timing of origin firing, including the chromatin environment and epigenetic modifications. However, how chromatin structure influences the timing of the activation of specific origins is still poorly understood. By performing high-resolution analysis of genome-wide nucleosome positioning we have identified different chromatin architectures at early and late replication origins. These different patterns are already established in G1 and are tightly correlated with the organization of adjacent transcription units. Moreover, specific early and late nucleosomal patterns are fixed robustly, even in rpd3 mutants in which histone acetylation and origin timing have been significantly altered. Nevertheless, higher histone acetylation levels correlate with the local modulation of chromatin structure, leading to increased origin accessibility. In addition, we conducted parallel analyses of replication and nucleosome dynamics that revealed that chromatin structure at origins is modulated during origin activation. Our results show that early and late replication origins present distinctive nucleosomal configurations, which are preferentially associated to different genomic regions. Our data also reveal that origin structure is dynamic and can be locally modulated by histone deacetylation, as well as by origin activation. These data offer novel insight into the contribution of chromatin structure to origin selection and firing in budding yeast.

Where are they now? Cash and Counseling successes and challenges over time

PubMed Central

Simon-Rusinowitz, Lori; Schwartz, Abby J.; Loughlin, Dawn; Sciegaj, Mark; Mahoney, Kevin J.; Donkoh, Yaw

2014-01-01

The positive results of the Cash & Counseling Demonstration and Evaluation (CCDE) led to the funding of a replication project that included 12 more states in 2008. Since then, the political and economic environments have changed. The authors sought to investigate how well the three original and 12 replication CCDE programs are coping with current challenges, and how their experiences may inform the growth and sustainability of emerging participant-directed programs. Semistructured telephone interviews were conducted with the 15 Cash & Counseling state program administrators. Key topics addressed included: successful aspects of state programs, biggest challenges for each program, and information program administrators would like to learn from state colleagues. Themes related to budget issues (e.g., staff shortages and program funding cuts) and non-budget related issues (e.g., understanding of program operations) emerged from the interviews. State program administrators also discussed program successes. To promote the sustainability and growth of participant-directed programs, existing participant-directed programs should be tied to national policy trends as well as review whether or not the programs address participant-directed principles. The development of new participant-directed programs should be based on other states’ experiences as discussed in this paper. PMID:25750590

Physician training protocol within the WEB Intrasaccular Therapy (WEB-IT) study.

PubMed

Arthur, Adam; Hoit, Daniel; Coon, Alexander; Delgado Almandoz, Josser E; Elijovich, Lucas; Cekirge, Saruhan; Fiorella, David

2018-05-01

The WEB Intra-saccular Therapy (WEB-IT) trial is an investigational device exemption study to demonstrate the safety and effectiveness of the WEB device for the treatment of wide-neck bifurcation aneurysms. The neurovascular replicator (Vascular Simulations, Stony Brook, New York, USA) creates a physical environment that replicates patient-specific neurovascular anatomy and hemodynamic physiology, and allows devices to be implanted under fluoroscopic guidance. To report the results of a unique neurovascular replicator-based training program, which was incorporated into the WEB-IT study to optimize technical performance and patient safety. US investigators participated in a new training program that incorporated full surgical rehearsals on a neurovascular replicator. No roll-in cases were permitted within the trial. Custom replicas of patient-specific neurovascular anatomy were created for the initial cases treated at each center, as well as for cases expected to be challenging. On-site surgical rehearsals were performed before these procedures. A total of 48 participating investigators at 25 US centers trained using the replicator. Sessions included centralized introductory training, on-site training, and patient-specific full surgical rehearsal. Fluoroscopy and procedure times in the WEB-IT study were not significantly different from those seen in two European trials where participating physicians had significant WEB procedure experience before study initiation. A new program of neurovascular-replicator-based physician training was employed within the WEB-IT study. This represents a new methodology for education and training that may be an effective means to optimize technical success and patient safety during the introduction of a new technology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

CLB5-dependent activation of late replication origins in S. cerevisiae.

PubMed

Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L

1998-08-01

Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.

Activation of human herpesvirus replication by apoptosis.

PubMed

Prasad, Alka; Remick, Jill; Zeichner, Steven L

2013-10-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

Activation of Human Herpesvirus Replication by Apoptosis

PubMed Central

Prasad, Alka; Remick, Jill

2013-01-01

A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance. PMID:23885073

Predicting Treatment Time with the Lidcombe Program: Replication and Meta-Analysis

ERIC Educational Resources Information Center

Kingston, Mary; Huber, Anna; Onslow, Mark; Jones, Mark; Packman, Ann

2003-01-01

Background: The benefits of treating stuttering close to onset have become obvious in recent years, and the Lidcombe Program has emerged as an effective and safe treatment method for children in their preschool years. The benefits of implementing the programme with young children, however, need to be weighed against the knowledge that many…

The Spatiotemporal Program of Replication in the Genome of Lachancea kluyveri

PubMed Central

Agier, Nicolas; Romano, Orso Maria; Touzain, Fabrice; Cosentino Lagomarsino, Marco; Fischer, Gilles

2013-01-01

We generated a genome-wide replication profile in the genome of Lachancea kluyveri and assessed the relationship between replication and base composition. This species diverged from Saccharomyces cerevisiae before the ancestral whole genome duplication. The genome comprises eight chromosomes among which a chromosomal arm of 1 Mb has a G + C-content much higher than the rest of the genome. We identified 252 active replication origins in L. kluyveri and found considerable divergence in origin location with S. cerevisiae and with Lachancea waltii. Although some global features of S. cerevisiae replication are conserved: Centromeres replicate early, whereas telomeres replicate late, we found that replication origins both in L. kluyveri and L. waltii do not behave as evolutionary fragile sites. In L. kluyveri, replication timing along chromosomes alternates between regions of early and late activating origins, except for the 1 Mb GC-rich chromosomal arm. This chromosomal arm contains an origin consensus motif different from other chromosomes and is replicated early during S-phase. We showed that precocious replication results from the specific absence of late firing origins in this chromosomal arm. In addition, we found a correlation between GC-content and distance from replication origins as well as a lack of replication-associated compositional skew between leading and lagging strands specifically in this GC-rich chromosomal arm. These findings suggest that the unusual base composition in the genome of L. kluyveri could be linked to replication. PMID:23355306

A dynamic programming approach for the alignment of signal peaks in multiple gas chromatography-mass spectrometry experiments.

PubMed

Robinson, Mark D; De Souza, David P; Keen, Woon Wai; Saunders, Eleanor C; McConville, Malcolm J; Speed, Terence P; Likić, Vladimir A

2007-10-29

Gas chromatography-mass spectrometry (GC-MS) is a robust platform for the profiling of certain classes of small molecules in biological samples. When multiple samples are profiled, including replicates of the same sample and/or different sample states, one needs to account for retention time drifts between experiments. This can be achieved either by the alignment of chromatographic profiles prior to peak detection, or by matching signal peaks after they have been extracted from chromatogram data matrices. Automated retention time correction is particularly important in non-targeted profiling studies. A new approach for matching signal peaks based on dynamic programming is presented. The proposed approach relies on both peak retention times and mass spectra. The alignment of more than two peak lists involves three steps: (1) all possible pairs of peak lists are aligned, and similarity of each pair of peak lists is estimated; (2) the guide tree is built based on the similarity between the peak lists; (3) peak lists are progressively aligned starting with the two most similar peak lists, following the guide tree until all peak lists are exhausted. When two or more experiments are performed on different sample states and each consisting of multiple replicates, peak lists within each set of replicate experiments are aligned first (within-state alignment), and subsequently the resulting alignments are aligned themselves (between-state alignment). When more than two sets of replicate experiments are present, the between-state alignment also employs the guide tree. We demonstrate the usefulness of this approach on GC-MS metabolic profiling experiments acquired on wild-type and mutant Leishmania mexicana parasites. We propose a progressive method to match signal peaks across multiple GC-MS experiments based on dynamic programming. A sensitive peak similarity function is proposed to balance peak retention time and peak mass spectra similarities. This approach can produce the optimal alignment between an arbitrary number of peak lists, and models explicitly within-state and between-state peak alignment. The accuracy of the proposed method was close to the accuracy of manually-curated peak matching, which required tens of man-hours for the analyzed data sets. The proposed approach may offer significant advantages for processing of high-throughput metabolomics data, especially when large numbers of experimental replicates and multiple sample states are analyzed.

Electronic Ecosystem.

ERIC Educational Resources Information Center

Travis, John

1991-01-01

A discipline in which scientists seek to simulate and synthesize lifelike behaviors within computers, chemical mixtures, and other media is discussed. A computer program with self-replicating digital "organisms" that evolve as they compete for computer time and memory is described. (KR)

Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication

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

Haruta, Mayumi; Shimada, Midori, E-mail: midorism@med.nagoya-cu.ac.jp; Nishiyama, Atsuya

The mammalian maintenance methyltransferase DNMT1 [DNA (cytosine-5-)-methyltransferase 1] mediates the inheritance of the DNA methylation pattern during replication. Previous studies have shown that depletion of DNMT1 causes a severe growth defect and apoptosis in differentiated cells. However, the detailed mechanisms behind this phenomenon remain poorly understood. Here we show that conditional ablation of Dnmt1 in murine embryonic fibroblasts (MEFs) resulted in an aberrant DNA replication program showing an accumulation of late-S phase replication and causing severely defective growth. Furthermore, we found that the catalytic activity and replication focus targeting sequence of DNMT1 are required for a proper DNA replication program.more » Taken together, our findings suggest that the maintenance of DNA methylation by DNMT1 plays a critical role in proper regulation of DNA replication in mammalian cells. - Highlights: • DNMT1 depletion results in an abnormal DNA replication program. • Aberrant DNA replication is independent of the DNA damage checkpoint in DNMT1cKO. • DNMT1 catalytic activity and RFT domain are required for proper DNA replication. • DNMT1 catalytic activity and RFT domain are required for cell proliferation.« less

Transcriptionally Driven DNA Replication Program of the Human Parasite Leishmania major.

PubMed

Lombraña, Rodrigo; Álvarez, Alba; Fernández-Justel, José Miguel; Almeida, Ricardo; Poza-Carrión, César; Gomes, Fábia; Calzada, Arturo; Requena, José María; Gómez, María

2016-08-09

Faithful inheritance of eukaryotic genomes requires the orchestrated activation of multiple DNA replication origins (ORIs). Although origin firing is mechanistically conserved, how origins are specified and selected for activation varies across different model systems. Here, we provide a complete analysis of the nucleosomal landscape and replication program of the human parasite Leishmania major, building on a better evolutionary understanding of replication organization in Eukarya. We found that active transcription is a driving force for the nucleosomal organization of the L. major genome and that both the spatial and the temporal program of DNA replication can be explained as associated to RNA polymerase kinetics. This simple scenario likely provides flexibility and robustness to deal with the environmental changes that impose alterations in the genetic programs during parasitic life cycle stages. Our findings also suggest that coupling replication initiation to transcription elongation could be an ancient solution used by eukaryotic cells for origin maintenance. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

A Two-Year Follow-Up of a Staff Development Program Designed to Change Teacher Behavior

ERIC Educational Resources Information Center

Schaffer, Eugene; Stringfield, Samuel; Devlin-Scherer, Roberta

2017-01-01

Two years after participating in a replication of the Stallings Effective Use of Time (EUOT) Program, ten teachers were re-observed and interviewed to determine the extent to which they had maintained the measured changes in their behavior patterns. Subjects were selected for the follow-up from a 27 EUOT teacher sample based on having exhibited…

United States Air Force Summer Faculty Research Program (1984). Program Management Report. Volume 3

DTIC Science & Technology

1984-12-01

Database Design 蕄 Raman Spectroscopy of Dr. Boake L. Plessy Glycosaminoglycans from -* Bovine Cornea 117 Study of Control Mixer Concept Dr. Kuldip S...simultaneously in polarized and non -polarized controls were repeated three times at 260-64, 368-70, 604-8-13, 735-7-40, 1277-80, 1760, 1775, and 1820 or four...times at S240-2-4, 1020 and 1874-8-90. Pooling replicates from the non -polarized components, six controls and two cAMP treatments, events repeating

RECAP (Rock County Education and Criminal Addictions Program) Program Manual Prepared to be of Assistance in Program Replication.

ERIC Educational Resources Information Center

Blackhawk Technical Coll., Janesville, WI.

This document, which is designed for practitioners involved in the vocational education/rehabilitation of incarcerated adults, contains materials to facilitate replication of the Rock County Education and Criminal Additions Program (RECAP), a comprehensive, integrated training/rehabilitation program that was developed and implemented through the…

DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression

PubMed Central

Hua, Brian L.; Orr-Weaver, Terry L.

2017-01-01

Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number changes in the genome, which include differential underreplication and gene amplification. Here, we review key findings and our current understanding of the developmental control of DNA replication in the contexts of the archetypal replication program as well as of underreplication and differential gene amplification. We focus on the use of these latter two replication systems to delineate many of the molecular mechanisms that underlie the developmental control of replication initiation and fork elongation. PMID:28874453

Replication: A "Model" Approach to the Healthy Development of Young Children

ERIC Educational Resources Information Center

Krieg, Iris; Lewis, Jan

2005-01-01

The authors, directors of the Chicago-based Pritzker Early Childhood Foundation, advocate "replication," the adaptation of a successful model program or practice to new locations or to new populations. Studies have shown that successful replications of early childhood programs that help at-risk children and their families can have long-term,…

Replicator equations, maximal cliques, and graph isomorphism.

PubMed

Pelillo, M

1999-11-15

We present a new energy-minimization framework for the graph isomorphism problem that is based on an equivalent maximum clique formulation. The approach is centered around a fundamental result proved by Motzkin and Straus in the mid-1960s, and recently expanded in various ways, which allows us to formulate the maximum clique problem in terms of a standard quadratic program. The attractive feature of this formulation is that a clear one-to-one correspondence exists between the solutions of the quadratic program and those in the original, combinatorial problem. To solve the program we use the so-called replicator equations--a class of straightforward continuous- and discrete-time dynamical systems developed in various branches of theoretical biology. We show how, despite their inherent inability to escape from local solutions, they nevertheless provide experimental results that are competitive with those obtained using more elaborate mean-field annealing heuristics.

Replicating MISTERS: an epidemiological criminology framework analysis of a program for criminal justice-involved minority males in the community.

PubMed

Potter, Roberto Hugh; Akers, Timothy A; Bowman, Daniel Richard

2013-01-01

The Men in STD Training and Empowerment Research Study (MISTERS) program and epidemiological criminology began their development in Atlanta at about the same time. MISTERS focuses on men recently released from jail to reduce both HIV/STD and crime-related risk factors through a brief educational intervention. This article examines ways in which MISTERS and epidemiological criminology have been used to inform one another in the replication of the MISTERS program in Orange County, Florida. Data from 110 MISTERS participants during the first 10 months of operation are analyzed to examine the overlapping occurrence of health and criminal risk behaviors in the men's lives. This provides a test of core hypotheses from the epidemiological criminology framework. This article also examines application of the epidemiological criminology framework to develop interventions to address health and crime risk factors simultaneously in Criminal Justice-Involved populations in the community.

Attendance Improvement and Dropout Prevention (AIDP) Demonstration and Replication Program 1989. OREA Evaluation Section Report.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Office of Research, Evaluation, and Assessment.

Each of the 1989 dropout prevention programs funded under the New York City Attendance Improvement Dropout Prevention (AIDP) Demonstration and Replication Program was successful in meeting some of its objectives, and all of the programs were viewed as valuable by principals and teachers. The program encourages the design and implementation of…

Teaching Real Science with a Microcomputer.

ERIC Educational Resources Information Center

Naiman, Adeline

1983-01-01

Discusses various ways science can be taught using microcomputers, including simulations/games which allow large-scale or historic experiments to be replicated on a manageable scale in a brief time. Examples of several computer programs are also presented, including "Experiments in Human Physiology,""Health Awareness…

Implementing three evidence-based program models: early lessons from the Teen Pregnancy Prevention Replication Study.

PubMed

Kelsey, Meredith; Layzer, Jean

2014-03-01

This article describes some of the early implementation challenges faced by nine grantees participating in the Teen Pregnancy Prevention Replication Study and their response to them. The article draws on information collected as part of a comprehensive implementation study. Sources include site and program documents; program officer reports; notes from site investigation, selection and negotiation; ongoing communications with grantees as part of putting the study into place; and semi-structured interviews with program staff. The issues faced by grantees in implementing evidence-based programs designed to prevent teen pregnancy varied by program model. Grantees implementing a classroom-based curriculum faced challenges in delivering the curriculum within the constraints of school schedules and calendars (program length and size of class). Grantees implementing a culturally tailored curriculum faced a series of challenges, including implementing the intervention as part of the regular school curriculum in schools with diverse populations; low attendance when delivered as an after-school program; and resistance on the part of schools to specific curriculum content. The third set of grantees, implementing a program in clinics, faced challenges in identifying and recruiting young women into the program and in retaining young women once they were in the program. The experiences of these grantees reflect some of the complexities that should be carefully considered when choosing to replicate evidence-based programs. The Teen Pregnancy Prevention replication study will provide important context for assessing the effectiveness of some of the more widely replicated evidence-based programs. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

Multiculturalism in Four Teacher Education Programs: For Replication or Transformation

ERIC Educational Resources Information Center

Ensign, Jacque

2009-01-01

This article describes four teacher education programs and their student teachers' responses to why some students in their classrooms were not doing well. The responses and programs fell into two categories: education for replication of inequities and education for transformation. If teacher education programs want their prospective teachers to be…

Costs by Major Program Category--A Budgetary Guide to Program Replication.

ERIC Educational Resources Information Center

Smith, Gary E.; And Others

Intended as a budgetary guide for potential replicators, this document presents a detailed discussion of estimated costs involved in setting up and operating a program similar to the Mountin-Plains Career Education Model IV, a residential, family-based education program developed to improve the economic potential and lifestyle of selected student…

Human Genome Replication Proceeds through Four Chromatin States

PubMed Central

Julienne, Hanna; Zoufir, Azedine; Audit, Benjamin; Arneodo, Alain

2013-01-01

Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and differentiation or in response to the environment. Paradoxically, the molecular mechanisms that regulate the initiation and the maintenance of the spatio-temporal replication program in higher eukaryotes, and in particular their links to epigenetic modifications, still remain elusive. By integrative analysis of the genome-wide distributions of thirteen epigenetic marks in the human cell line K562, at the 100 kb resolution of corresponding mean replication timing (MRT) data, we identify four major groups of chromatin marks with shared features. These states have different MRT, namely from early to late replicating, replication proceeds though a transcriptionally active euchromatin state (C1), a repressive type of chromatin (C2) associated with polycomb complexes, a silent state (C3) not enriched in any available marks, and a gene poor HP1-associated heterochromatin state (C4). When mapping these chromatin states inside the megabase-sized U-domains (U-shaped MRT profile) covering about 50% of the human genome, we reveal that the associated replication fork polarity gradient corresponds to a directional path across the four chromatin states, from C1 at U-domains borders followed by C2, C3 and C4 at centers. Analysis of the other genome half is consistent with early and late replication loci occurring in separate compartments, the former correspond to gene-rich, high-GC domains of intermingled chromatin states C1 and C2, whereas the latter correspond to gene-poor, low-GC domains of alternating chromatin states C3 and C4 or long C4 domains. This new segmentation sheds a new light on the epigenetic regulation of the spatio-temporal replication program in human and provides a framework for further studies in different cell types, in both health and disease. PMID:24130466

Assessment of the Impact of the Exemplary Program Project for Vocational Education. (Identification, Dissemination and Replication--1983 to 1986). Final Report.

ERIC Educational Resources Information Center

Kinter, Ona Kay; Steczak, Cheryl

A study examined the success of the Pennsylvania Department of Education's Exemplary Program Project for Vocational Education in implementing and replicating exemplary vocational education programs, disseminating information about successful programs to local education agencies, and motivating school officials and teachers to develop or replicate…

The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells

PubMed Central

McConnell, Kristopher H.; Dixon, Michael; Calvi, Brian R.

2012-01-01

DNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs. PMID:22951641

CDK activity provides temporal and quantitative cues for organizing genome duplication

PubMed Central

Perrot, Anthony; Millington, Christopher Lee; Gómez-Escoda, Blanca; Schausi-Tiffoche, Diane

2018-01-01

In eukaryotes, the spatial and temporal organization of genome duplication gives rise to distinctive profiles of replication origin usage along the chromosomes. While it has become increasingly clear that these programs are important for cellular physiology, the mechanisms by which they are determined and modulated remain elusive. Replication initiation requires the function of cyclin-dependent kinases (CDKs), which associate with various cyclin partners to drive cell proliferation. Surprisingly, although we possess detailed knowledge of the CDK regulators and targets that are crucial for origin activation, little is known about whether CDKs play a critical role in establishing the genome-wide pattern of origin selection. We have addressed this question in the fission yeast, taking advantage of a simplified cell cycle network in which cell proliferation is driven by a single cyclin-CDK module. This system allows us to precisely control CDK activity in vivo using chemical genetics. First, in contrast to previous reports, our results clearly show that distinct cyclin-CDK pairs are not essential for regulating specific subsets of origins and for establishing a normal replication program. Importantly, we then demonstrate that the timing at which CDK activity reaches the S phase threshold is critical for the organization of replication in distinct efficiency domains, while the level of CDK activity at the onset of S phase is a dose-dependent modulator of overall origin efficiencies. Our study therefore implicates these different aspects of CDK regulation as versatile mechanisms for shaping the architecture of DNA replication across the genome. PMID:29466359

Commercial Building Partnerships Replication and Diffusion

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

Antonopoulos, Chrissi A.; Dillon, Heather E.; Baechler, Michael C.

2013-09-16

This study presents findings from survey and interview data investigating replication efforts of Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered directly with 12 organizations on new and retrofit construction projects, which represented approximately 28 percent of the entire U.S. Department of Energy (DOE) CBP program. Through a feedback survey mechanism, along with personal interviews, PNNL gathered quantitative and qualitative data relating to replication efforts by each organization. These data were analyzed to provide insight into two primary research areas: 1) CBP partners’ replication efforts of technologies and approaches used inmore » the CBP project to the rest of the organization’s building portfolio (including replication verification), and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP program. The first area of this research focused specifically on replication efforts underway or planned by each CBP program participant. Factors that impact replication include motivation, organizational structure and objectives firms have for implementation of energy efficient technologies. Comparing these factors between different CBP partners revealed patterns in motivation for constructing energy efficient buildings, along with better insight into market trends for green building practices. The second area of this research develops a diffusion of innovations model to analyze potential broad market impacts of the CBP program on the commercial building industry in the United States.« less

Replication in hydroxyurea: it's a matter of time.

PubMed

Alvino, Gina M; Collingwood, David; Murphy, John M; Delrow, Jeffrey; Brewer, Bonita J; Raghuraman, M K

2007-09-01

Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.

From Discovery to Justification: Outline of an Ideal Research Program in Empirical Psychology

PubMed Central

Witte, Erich H.; Zenker, Frank

2017-01-01

The gold standard for an empirical science is the replicability of its research results. But the estimated average replicability rate of key-effects that top-tier psychology journals report falls between 36 and 39% (objective vs. subjective rate; Open Science Collaboration, 2015). So the standard mode of applying null-hypothesis significance testing (NHST) fails to adequately separate stable from random effects. Therefore, NHST does not fully convince as a statistical inference strategy. We argue that the replicability crisis is “home-made” because more sophisticated strategies can deliver results the successful replication of which is sufficiently probable. Thus, we can overcome the replicability crisis by integrating empirical results into genuine research programs. Instead of continuing to narrowly evaluate only the stability of data against random fluctuations (discovery context), such programs evaluate rival hypotheses against stable data (justification context). PMID:29163256

DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1

PubMed Central

de Bruin, R. A. M.; Kalashnikova, T. I.; Aslanian, A.; Wohlschlegel, J.; Chahwan, C.; Yates, J. R.; Russell, P.; Wittenberg, C.

2008-01-01

The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication. PMID:18682565

Get on Board the Cost Effective Way: A Tech Prep Replication Process.

ERIC Educational Resources Information Center

Moore, Wayne A.; Szul, Linda F.; Rivosecchi, Karen

1997-01-01

The Northwestern Pennsylvania Tech Prep Consortium model for replicating tech prep programs includes these steps: fact finding, local industry analysis, curriculum development, detailed description, marketing strategies, implementation, and program evaluation. (SK)

Discovery of replicating circular RNAs by RNA-seq and computational algorithms.

PubMed

Zhang, Zhixiang; Qi, Shuishui; Tang, Nan; Zhang, Xinxin; Chen, Shanshan; Zhu, Pengfei; Ma, Lin; Cheng, Jinping; Xu, Yun; Lu, Meiguang; Wang, Hongqing; Ding, Shou-Wei; Li, Shifang; Wu, Qingfa

2014-12-01

Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming. We previously described an approach for homology-independent discovery of replicating circular RNAs by analysing the total small RNA populations from samples of diseased tissues with a computational program known as progressive filtering of overlapping small RNAs (PFOR). However, PFOR written in PERL language is extremely slow and is unable to discover those subviral pathogens that do not trigger in vivo accumulation of extensively overlapping small RNAs. Moreover, PFOR is yet to identify a new viroid capable of initiating independent infection. Here we report the development of PFOR2 that adopted parallel programming in the C++ language and was 3 to 8 times faster than PFOR. A new computational program was further developed and incorporated into PFOR2 to allow the identification of circular RNAs by deep sequencing of long RNAs instead of small RNAs. PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively. GLVd was proposed as a new species in the genus Apscaviroid, because it contained the typical structural elements found in this group of viroids and initiated independent infection in grapevine seedlings. AHVd-like RNA encoded a biologically active hammerhead ribozyme in both polarities, and was not specifically associated with any of the viruses found in apple plants. We propose that these computational algorithms have the potential to discover novel circular RNAs in plants, invertebrates and vertebrates regardless of whether they replicate and/or induce the in vivo accumulation of small RNAs.

Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms

PubMed Central

Tang, Nan; Zhang, Xinxin; Chen, Shanshan; Zhu, Pengfei; Ma, Lin; Cheng, Jinping; Xu, Yun; Lu, Meiguang; Wang, Hongqing; Ding, Shou-Wei; Li, Shifang; Wu, Qingfa

2014-01-01

Replicating circular RNAs are independent plant pathogens known as viroids, or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs. The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and time-consuming. We previously described an approach for homology-independent discovery of replicating circular RNAs by analysing the total small RNA populations from samples of diseased tissues with a computational program known as progressive filtering of overlapping small RNAs (PFOR). However, PFOR written in PERL language is extremely slow and is unable to discover those subviral pathogens that do not trigger in vivo accumulation of extensively overlapping small RNAs. Moreover, PFOR is yet to identify a new viroid capable of initiating independent infection. Here we report the development of PFOR2 that adopted parallel programming in the C++ language and was 3 to 8 times faster than PFOR. A new computational program was further developed and incorporated into PFOR2 to allow the identification of circular RNAs by deep sequencing of long RNAs instead of small RNAs. PFOR2 analysis of the small RNA libraries from grapevine and apple plants led to the discovery of Grapevine latent viroid (GLVd) and Apple hammerhead viroid-like RNA (AHVd-like RNA), respectively. GLVd was proposed as a new species in the genus Apscaviroid, because it contained the typical structural elements found in this group of viroids and initiated independent infection in grapevine seedlings. AHVd-like RNA encoded a biologically active hammerhead ribozyme in both polarities, and was not specifically associated with any of the viruses found in apple plants. We propose that these computational algorithms have the potential to discover novel circular RNAs in plants, invertebrates and vertebrates regardless of whether they replicate and/or induce the in vivo accumulation of small RNAs. PMID:25503469

Getting Teachers in on the Act: Evaluation of a Theater- and Classroom-Based Youth Violence Prevention Program

ERIC Educational Resources Information Center

Zucker, Marla; Spinazzola, Joseph; Pollack, Amie Alley; Pepe, Lauren; Barry, Stephanie; Zhang, Lynda; van der Kolk, Bessel

2010-01-01

This study replicated and extended our previous evaluation of Urban Improv (UI), a theater-based youth violence prevention (YVP) program developed for urban youth. It assessed the replicability of positive program impacts when implemented by nonprogram originators, as well as the utility of a comprehensive version of the UI program that included a…

Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication.

PubMed

Haruta, Mayumi; Shimada, Midori; Nishiyama, Atsuya; Johmura, Yoshikazu; Le Tallec, Benoît; Debatisse, Michelle; Nakanishi, Makoto

2016-01-22

The mammalian maintenance methyltransferase DNMT1 [DNA (cytosine-5-)-methyltransferase 1] mediates the inheritance of the DNA methylation pattern during replication. Previous studies have shown that depletion of DNMT1 causes a severe growth defect and apoptosis in differentiated cells. However, the detailed mechanisms behind this phenomenon remain poorly understood. Here we show that conditional ablation of Dnmt1 in murine embryonic fibroblasts (MEFs) resulted in an aberrant DNA replication program showing an accumulation of late-S phase replication and causing severely defective growth. Furthermore, we found that the catalytic activity and replication focus targeting sequence of DNMT1 are required for a proper DNA replication program. Taken together, our findings suggest that the maintenance of DNA methylation by DNMT1 plays a critical role in proper regulation of DNA replication in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Using evaluation to improve program quality based on the BELL model.

PubMed

Phalen, Earl Martin; Cooper, Tiffany M

2007-01-01

Building Educated Leaders for Life (BELL) is a national not-for-profit organization whose mission is to increase the educational achievements, self-esteem, and life opportunities of elementary school children living in low-income urban communities. BELL has been engaged in formal evaluation, internally and externally, for more than five years and has built internal evaluation capacity by investing in a specialized full-time evaluation team. As part of a continuous program improvement model of evaluation, BELL uses the data to refine program implementation and replicate successful elements of the services and operations. In this chapter, the authors highlight best practices from the field by outlining BELL's approach to using evaluation data for continuous program improvement. Key strategies include (1) carefully identifying intended users of the evaluation throughout the organization and among its external stakeholders, then working closely with intended users throughout the evaluation process, ensuring full engagement at every step of the process; (2) reporting findings in a readable, user-friendly format and timing the reporting so that it is aligned with programmatic decision making and planning cycles; and (3) making and supporting explicit recommendations for the next program cycle, where intended users have agreed to recommendations and ownership is assigned. BELL's successful use of data for improvement is evidenced by the consistently strong outcomes for the students it serves as well as increased efficiency and satisfaction related to service delivery that has supported the replication of BELL's programs nationally.

45 CFR 2521.20 - What types of AmeriCorps subtitle C program grants are available for award?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., and availability of Congressional appropriations. (c) Replication Grants. The Corporation may provide assistance for the replication of an existing national service program to another geographical location. (d...

Systematic Determination of Replication Activity Type Highlights Interconnections between Replication, Chromatin Structure and Nuclear Localization

PubMed Central

Polten, Andreas; Hezroni, Hadas; Eldar, Yonina C.; Meshorer, Eran; Yakhini, Zohar; Simon, Itamar

2012-01-01

DNA replication is a highly regulated process, with each genomic locus replicating at a distinct time of replication (ToR). Advances in ToR measurement technology enabled several genome-wide profiling studies that revealed tight associations between ToR and general genomic features and a remarkable ToR conservation in mammals. Genome wide studies further showed that at the hundreds kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs) in which the replication process propagates at a faster pace due to the activation of multiple origins and temporal transition regions (TTRs) in which the replication process propagates at a slower pace. We developed a computational tool that assigns a ToR to every measured locus and determines its replication activity type (CTR versus TTR). Our algorithm, ARTO (Analysis of Replication Timing and Organization), uses signal processing methods to fit a constant piece-wise linear curve to the measured raw data. We tested our algorithm and provide performance and usability results. A Matlab implementation of ARTO is available at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to ToR data measured in multiple mouse and human samples allowed precise genome-wide ToR determination and replication activity type characterization. Analysis of the results highlighted the plasticity of the replication program. For example, we observed significant ToR differences in 10–25% of the genome when comparing different tissue types. Our analyses also provide evidence for activity type differences in up to 30% of the probes. Integration of the ToR data with multiple aspects of chromosome organization characteristics suggests that ToR plays a role in shaping the regional chromatin structure. Namely, repressive chromatin marks, are associated with late ToR both in TTRs and CTRs. Finally, characterization of the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are associated with compact chromatin and are located significantly closer to the nuclear envelope. Supplementary material is available. Raw and processed data were deposited in Geo (GSE17236). PMID:23145042

Can We Cross the Street in Time?

ERIC Educational Resources Information Center

Greenes, Carole E.; Cavanagh, Mary C.; Tsankova, Jenny K.; Glanfield, Florence A.

2013-01-01

In the authors' examination of various instructional programs, they observed that most provide all the necessary data to solve proportion problems, employ compatible numbers that are usually unrealistic, present numbers (data) in the order in which they are to be manipulated, discuss contexts that cannot be easily replicated, and present…

A Rewarding Partnership

ERIC Educational Resources Information Center

Abbott, Cheryl; Swanson, Marc

2006-01-01

A collaborating scientist--a rewarding addition to any high school science program--can help students collect and analyze data that either replicates or parallels the work of the partnering scientist. This type of partnership is beneficial for both students and scientists, and perhaps there has never been a better time to consider such a…

3D chromatin conformation correlates with replication timing and is conserved in resting cells

PubMed Central

Moindrot, Benoit; Audit, Benjamin; Klous, Petra; Baker, Antoine; Thermes, Claude; de Laat, Wouter; Bouvet, Philippe; Mongelard, Fabien; Arneodo, Alain

2012-01-01

Although chromatin folding is known to be of functional importance to control the gene expression program, less is known regarding its interplay with DNA replication. Here, using Circular Chromatin Conformation Capture combined with high-throughput sequencing, we identified megabase-sized self-interacting domains in the nucleus of a human lymphoblastoid cell line, as well as in cycling and resting peripheral blood mononuclear cells (PBMC). Strikingly, the boundaries of those domains coincide with early-initiation zones in every cell types. Preferential interactions have been observed between the consecutive early-initiation zones, but also between those separated by several tens of megabases. Thus, the 3D conformation of chromatin is strongly correlated with the replication timing along the whole chromosome. We furthermore provide direct clues that, in addition to the timing value per se, the shape of the timing profile at a given locus defines its set of genomic contacts. As this timing-related scheme of chromatin organization exists in lymphoblastoid cells, resting and cycling PBMC, this indicates that it is maintained several weeks or months after the previous S-phase. Lastly, our work highlights that the major chromatin changes accompanying PBMC entry into cell cycle occur while keeping largely unchanged the long-range chromatin contacts. PMID:22879376

Support, shape and number of replicate samples for tree foliage analysis.

PubMed

Luyssaert, Sebastiaan; Mertens, Jan; Raitio, Hannu

2003-06-01

Many fundamental features of a sampling program are determined by the heterogeneity of the object under study and the settings for the error (alpha), the power (beta), the effect size (ES), the number of replicate samples, and sample support, which is a feature that is often overlooked. The number of replicates, alpha, beta, ES, and sample support are interconnected. The effect of the sample support and its shape on the required number of replicate samples was investigated by means of a resampling method. The method was applied to a simulated distribution of Cd in the crown of a Salix fragilis L. tree. Increasing the dimensions of the sample support results in a decrease in the variance of the element concentration under study. Analysis of the variance is often the foundation of statistical tests, therefore, valid statistical testing requires the use of a fixed sample support during the experiment. This requirement might be difficult to meet in time-series analyses and long-term monitoring programs. Sample supports have their largest dimension in the direction with the largest heterogeneity, i.e. the direction representing the crown height, and this will give more accurate results than supports with other shapes. Taking the relationships between the sample support and the variance of the element concentrations in tree crowns into account provides guidelines for sampling efficiency in terms of precision and costs. In terms of time, the optimal support to test whether the average Cd concentration of the crown exceeds a threshold value is 0.405 m3 (alpha = 0.05, beta = 0.20, ES = 1.0 mg kg(-1) dry mass). The average weight of this support is 23 g dry mass, and 11 replicate samples need to be taken. It should be noted that in this case the optimal support applies to Cd under conditions similar to those of the simulation, but not necessarily all the examinations for this tree species, element, and hypothesis test.

Ingredients of a Successful Summer Learning Program: A Case Study of the Building Educated Leaders for Life (BELL) Accelerated Learning Summer Program

ERIC Educational Resources Information Center

Capizzano, Jeffrey; Bischoff, Kendra; Woodroffe, Nicola; Chaplin, Duncan

2007-01-01

Based on positive results from a previous evaluation of a summer learning intervention, the current report describes the specific elements of the successful program so it can be replicated, and investigates potential barriers to implementation and replication. The study estimated impacts of the program overall; the authors could not identify which…

Spatial distribution and specification of mammalian replication origins during G1 phase

PubMed Central

Li, Feng; Chen, Jianhua; Solessio, Eduardo; Gilbert, David M.

2003-01-01

We have examined the distribution of early replicating origins on stretched DNA fibers when nuclei from CHO cells synchronized at different times during G1 phase initiate DNA replication in Xenopus egg extracts. Origins were differentially labeled in vivo versus in vitro to allow a comparison of their relative positions and spacing. With nuclei isolated in the first hour of G1 phase, in vitro origins were distributed throughout a larger number of DNA fibers and did not coincide with in vivo origins. With nuclei isolated 1 h later, a similar total number of in vitro origins were clustered within a smaller number of DNA fibers but still did not coincide with in vivo origins. However, with nuclei isolated later in G1 phase, the positions of many in vitro origins coincided with in vivo origin sites without further change in origin number or density. These results highlight two distinct G1 steps that establish a spatial and temporal program for replication. PMID:12707307

NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

ERIC Educational Resources Information Center

O'Neill, Paul

2010-01-01

One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

G-Quadruplexes in DNA Replication: A Problem or a Necessity?

PubMed

Valton, Anne-Laure; Prioleau, Marie-Noëlle

2016-11-01

DNA replication is a highly regulated process that ensures the correct duplication of the genome at each cell cycle. A precise cell type-specific temporal program controls the duplication of complex vertebrate genomes in an orderly manner. This program is based on the regulation of both replication origin firing and replication fork progression. G-quadruplexes (G4s), DNA secondary structures displaying noncanonical Watson-Crick base pairing, have recently emerged as key controllers of genome duplication. Here we discuss the various means by which G4s affect this fundamental cellular process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluating the agreement between measurements and models of net ecosystem exchange at different times and timescales using wavelet coherence: an example using data from the North American Carbon Program Site-Level Interim Synthesis

Treesearch

P.C. Stoy; M.C. Dietze; A.D. Richardson; R. Vargas; A.G. Barr; R.S. Anderson; M.A. Arain; I.T. Baker; T.A. Black; J.M. Chen; R.B. Cook; C.M. Gough; R.F. Grant; D.Y. Hollinger; R.C. Izaurralde; C.J. Kucharik; P. Lafleur; B.E. Law; S. Liu; E. Lokupitiya; Y. Luo; J. W. Munger; C. Peng; B. Poulter; D.T. Price; D. M. Ricciuto; W. J. Riley; A. K. Sahoo; K. Schaefer; C.R. Schwalm; H. Tian; H. Verbeeck; E. Weng

2013-01-01

Earth system processes exhibit complex patterns across time, as do the models that seek to replicate these processes. Model output may or may not be significantly related to observations at different times and on different frequencies. Conventional model diagnostics provide an aggregate view of model-data agreement, but usually do not identify the time and frequency...

Replication in Practice: Lessons from Five Lead Agencies

ERIC Educational Resources Information Center

McGonigel, Mary

2005-01-01

This article describes the replication efforts of five programs funded by the Pritzker Early Childhood Foundation and determines what methods are key to replication success. Before replication can take place, the lead agency must have substantial evidence of its effectiveness and know its core elements. It must also think carefully about how its…

The Genetic Program of Pancreatic β-Cell Replication In Vivo

PubMed Central

Klochendler, Agnes; Caspi, Inbal; Corem, Noa; Moran, Maya; Friedlich, Oriel; Elgavish, Sharona; Nevo, Yuval; Helman, Aharon; Glaser, Benjamin; Eden, Amir; Itzkovitz, Shalev

2016-01-01

The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are “left behind” and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo. PMID:26993067

Virtual School, Real Experience: Simulations Replicate the World of Practice for Aspiring Principals

ERIC Educational Resources Information Center

Mann, Dale; Shakeshaft, Charol

2013-01-01

A web-enabled computer simulation program presents real-world opportunities, problems, and challenges for aspiring principals. The simulation challenges areas that are not always covered in lectures, textbooks, or workshops. For example, using the simulation requires dealing--on-screen and in real time--with demanding parents, observing…

40 CFR Appendix B to Part 136 - Definition and Procedure for the Determination of the Method Detection Limit-Revision 1.11

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) GUIDELINES ESTABLISHING TEST PROCEDURES... to a wide variety of sample types ranging from reagent (blank) water containing analyte to wastewater... times the standard deviation of replicate instrumental measurements of the analyte in reagent water. (c...

Front-End Anti-Viral Detection Mechanisms Using Replicating/Self-Replicating Software

DTIC Science & Technology

1989-10-19

Trojan Horse program, these programs were omitted from the proof of concept. Future considerations will address these type of programs directly and...which relocates in memory. 3. Trojan Horse : A program that does other than what it was intended to do. 4. Prevention: Stop the initial and subsequent...then performed a risks analysis of potential threats. Since it is impossible, using existing technologies, to detect a well-written WORM or trojan horse

Software reliability report

NASA Technical Reports Server (NTRS)

Wilson, Larry

1991-01-01

There are many software reliability models which try to predict future performance of software based on data generated by the debugging process. Unfortunately, the models appear to be unable to account for the random nature of the data. If the same code is debugged multiple times and one of the models is used to make predictions, intolerable variance is observed in the resulting reliability predictions. It is believed that data replication can remove this variance in lab type situations and that it is less than scientific to talk about validating a software reliability model without considering replication. It is also believed that data replication may prove to be cost effective in the real world, thus the research centered on verification of the need for replication and on methodologies for generating replicated data in a cost effective manner. The context of the debugging graph was pursued by simulation and experimentation. Simulation was done for the Basic model and the Log-Poisson model. Reasonable values of the parameters were assigned and used to generate simulated data which is then processed by the models in order to determine limitations on their accuracy. These experiments exploit the existing software and program specimens which are in AIR-LAB to measure the performance of reliability models.

Embryonic Stem Cell Specific “Master” Replication Origins at the Heart of the Loss of Pluripotency

PubMed Central

Julienne, Hanna; Audit, Benjamin; Arneodo, Alain

2015-01-01

Epigenetic regulation of the replication program during mammalian cell differentiation remains poorly understood. We performed an integrative analysis of eleven genome-wide epigenetic profiles at 100 kb resolution of Mean Replication Timing (MRT) data in six human cell lines. Compared to the organization in four chromatin states shared by the five somatic cell lines, embryonic stem cell (ESC) line H1 displays (i) a gene-poor but highly dynamic chromatin state (EC4) associated to histone variant H2AZ rather than a HP1-associated heterochromatin state (C4) and (ii) a mid-S accessible chromatin state with bivalent gene marks instead of a polycomb-repressed heterochromatin state. Plastic MRT regions (≲ 20% of the genome) are predominantly localized at the borders of U-shaped timing domains. Whereas somatic-specific U-domain borders are gene-dense GC-rich regions, 31.6% of H1-specific U-domain borders are early EC4 regions enriched in pluripotency transcription factors NANOG and OCT4 despite being GC poor and gene deserts. Silencing of these ESC-specific “master” replication initiation zones during differentiation corresponds to a loss of H2AZ and an enrichment in H3K9me3 mark characteristic of late replicating C4 heterochromatin. These results shed a new light on the epigenetically regulated global chromatin reorganization that underlies the loss of pluripotency and lineage commitment. PMID:25658386

Diversifying the STEM Pipeline: The Model Replication Institutions Program

ERIC Educational Resources Information Center

Cullinane, Jenna

2009-01-01

In 2006, the National Science Foundation (NSF) began funding the Model Replication Institutions (MRI) program, which sought to improve the quality, availability, and diversity of science, technology, engineering, and mathematics (STEM) education. Faced with pressing national priorities in the STEM fields and chronic gaps in postsecondary…

Regulation of DNA Replication Timing on Human Chromosome by a Cell-Type Specific DNA Binding Protein SATB1

PubMed Central

Oda, Masako; Kanoh, Yutaka; Watanabe, Yoshihisa; Masai, Hisao

2012-01-01

Background Replication timing of metazoan DNA during S-phase may be determined by many factors including chromosome structures, nuclear positioning, patterns of histone modifications, and transcriptional activity. It may be determined by Mb-domain structures, termed as “replication domains”, and recent findings indicate that replication timing is under developmental and cell type-specific regulation. Methodology/Principal Findings We examined replication timing on the human 5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent methods to determine replication timing. One is quantification of nascent replicating DNA in cell cycle-fractionated stage-specific S phase populations. The other is FISH analyses of replication foci. Although the locations of early- and late-replicating domains were common between the two cell lines, the timing transition region (TTR) between early and late domains were offset by 200-kb. We show that Special AT-rich sequence Binding protein 1 (SATB1), specifically expressed in T-cells, binds to the early domain immediately adjacent to TTR and delays the replication timing of the TTR. Measurement of the chromosome copy number along the TTR during synchronized S phase suggests that the fork movement may be slowed down by SATB1. Conclusions Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome. PMID:22879953

Regulation of DNA replication timing on human chromosome by a cell-type specific DNA binding protein SATB1.

PubMed

Oda, Masako; Kanoh, Yutaka; Watanabe, Yoshihisa; Masai, Hisao

2012-01-01

Replication timing of metazoan DNA during S-phase may be determined by many factors including chromosome structures, nuclear positioning, patterns of histone modifications, and transcriptional activity. It may be determined by Mb-domain structures, termed as "replication domains", and recent findings indicate that replication timing is under developmental and cell type-specific regulation. We examined replication timing on the human 5q23/31 3.5-Mb segment in T cells and non-T cells. We used two independent methods to determine replication timing. One is quantification of nascent replicating DNA in cell cycle-fractionated stage-specific S phase populations. The other is FISH analyses of replication foci. Although the locations of early- and late-replicating domains were common between the two cell lines, the timing transition region (TTR) between early and late domains were offset by 200-kb. We show that Special AT-rich sequence Binding protein 1 (SATB1), specifically expressed in T-cells, binds to the early domain immediately adjacent to TTR and delays the replication timing of the TTR. Measurement of the chromosome copy number along the TTR during synchronized S phase suggests that the fork movement may be slowed down by SATB1. Our results reveal a novel role of SATB1 in cell type-specific regulation of replication timing along the chromosome.

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

10 CFR 74.45 - Measurements and measurement control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... measurements, obtaining samples, and performing laboratory analyses for element concentration and isotope... of random error behavior. On a predetermined schedule, the program shall include, as appropriate: (i) Replicate analyses of individual samples; (ii) Analysis of replicate process samples; (iii) Replicate volume...

Diffusion of Energy Efficient Technology in Commercial Buildings: An Analysis of the Commercial Building Partnerships Program

NASA Astrophysics Data System (ADS)

Antonopoulos, Chrissi Argyro

This study presents findings from survey and interview data investigating replication of green building measures by Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered directly with 12 organizations on new and retrofit construction projects, which represented approximately 28 percent of the entire U.S. Department of Energy (DOE) CBP program. Through a feedback survey mechanism, along with personal interviews, quantitative and qualitative data were gathered relating to replication efforts by each organization. These data were analyzed to provide insight into two primary research areas: 1) CBP partners' replication efforts of green building approaches used in the CBP project to the rest of the organization's building portfolio, and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP program. The first area of this research focused specifically on replication efforts underway or planned by each CBP program participant. The second area of this research develops a diffusion of innovations model to analyze potential broad market impacts of the CBP program on the commercial building industry in the United States. Findings from this study provided insight into motivations and objectives CBP partners had for program participation. Factors that impact replication include motivation, organizational structure and objectives firms have for implementation of energy efficient technologies. Comparing these factors between different CBP partners revealed patterns in motivation for constructing energy efficient buildings, along with better insight into market trends for green building practices. The optimized approach to the CBP program allows partners to develop green building parameters that fit the specific uses of their building, resulting in greater motivation for replication. In addition, the diffusion model developed for this analysis indicates that this method of market prediction may be used to adequately capture cumulative construction metrics for a whole-building analysis as opposed to individual energy efficiency measures used in green building.

A Paradigm Shift From Brick and Mortar: Full-Time Nursing Faculty Off Campus.

PubMed

Beck, Marlene; Bradley, Holly B; Cook, Linda L; Leasca, Joslin B; Lampley, Tammy; Gatti-Petito, JoAnne

The organizational structure for the Master of Science in Nursing's online program at Sacred Heart University offers a remarkably different innovative faculty model. Full-time, doctorally prepared faculty reside in several different states and teach online but are fully integrated and immersed in all aspects of the college of nursing. This untraditional model, which has proven to be successful over time using best practices for online education, is replicable and offers an innovative option for online learning.

Amplified Self-replication of DNA Origami Nanostructures through Multi-cycle Fast-annealing Process

NASA Astrophysics Data System (ADS)

Zhou, Feng; Zhuo, Rebecca; He, Xiaojin; Sha, Ruojie; Seeman, Nadrian; Chaikin, Paul

We have developed a non-biological self-replication process using templated reversible association of components and irreversible linking with annealing and UV cycles. The current method requires a long annealing time, up to several days, to achieve the specific self-assembly of DNA nanostructures. In this work, we accomplished the self-replication with a shorter time and smaller replication rate per cycle. By decreasing the ramping time, we obtained the comparable replication yield within 90 min. Systematic studies show that the temperature and annealing time play essential roles in the self-replication process. In this manner, we can amplify the self-replication process to a factor of 20 by increasing the number of cycles within the same amount of time.

Diversifying the STEM Pipeline: Recommendations from the Model Replication Institutions Program

ERIC Educational Resources Information Center

Institute for Higher Education Policy, 2010

2010-01-01

Launched in 2006 to address issues of national competitiveness and equity in science, technology, engineering, and mathematics (STEM) fields, the National Science Foundation-funded Model Replication Institutions (MRI) program sought to improve the quality, availability, and diversity of STEM education. The project offered technical assistance to…

77 FR 13304 - Application for New Awards; Charter Schools Program (CSP); Grants for Replication and Expansion...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

... for each school managed by the applicant, including compliance issues in the areas of student safety... DEPARTMENT OF EDUCATION Application for New Awards; Charter Schools Program (CSP); Grants for Replication and Expansion of High-Quality Charter Schools AGENCY: Office of Innovation and Improvement...

Project UPSTART. Final Report, October 1, 1983-September 30, 1984.

ERIC Educational Resources Information Center

Frain, Joan

Project UPSTART, during this fourth year of outreach, offered assistance in replicating its developed Sequenced Neuro-Sensorimotor Program (SNSP) for severely multihandicapped infants, pre-schoolers, young adults and their families. Future replication sites were identified. Programs received outreach assistance in the areas of staff training,…

An analysis of restructuring orientation to enhance nurse retention.

PubMed

Kiel, Joan M

2012-01-01

The nursing shortage has received much media attention; however, something that contributes to it-nurse turnover-has not received the same attention. Facilities spend time and money to train new employees only to have them leave within a few months. Staff morale, money, time, and quality of care are all affected by nurse turnover. The fact that it often occurs so soon after one takes a position makes it pertinent to look at the process of transition into the new position, namely, the orientation program. This article examines the turnover statistics, costs, rationale, and orientation programs that have proven positive results. It is hoped that the findings can assist health care facilities to replicate successful orientation programs and reduce nurse turnover.

Controlling Energy Performance on the Big Stage - The New York Times Company

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

Settlemyre, Kevin; Regnier, Cindy

2015-08-01

The Times partnered with the U.S. Department of Energy (DOE) as part of DOE’s Commercial Building Partnerships (CBP) Program to develop a post-occupancy evaluation (POE) of three EEMs that were implemented during the construction of The Times building between 2004-2006. With aggressive goals to reduce energy use and carbon emissions at a national level, one strategy of the US Department of Energy is looking to exemplary buildings that have already invested in new approaches to achieving the energy performance goals that are now needed at scale. The Times building incorporated a number of innovative technologies, systems and processes that makemore » their project a model for widespread replication in new and existing buildings. The measured results from the post occupancy evaluation study, the tools and processes developed, and continuous improvements in the performance and cost of the systems studied suggest that these savings are scalable and replicable in a wide range of commercial buildings nationwide.« less

Theoretical models for the regulation of DNA replication in fast-growing bacteria

NASA Astrophysics Data System (ADS)

Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

2012-09-01

Growing in always changing environments, Escherichia coli cells are challenged by the task to coordinate growth and division. In particular, adaption of their growth program to the surrounding medium has to guarantee that the daughter cells obtain fully replicated chromosomes. Replication is therefore to be initiated at the right time, which is particularly challenging in media that support fast growth. Here, the mother cell initiates replication not only for the daughter but also for the granddaughter cells. This is possible only if replication occurs from several replication forks that all need to be correctly initiated. Despite considerable efforts during the last 40 years, regulation of this process is still unknown. Part of the difficulty arises from the fact that many details of the relevant molecular processes are not known. Here, we develop a novel theoretical strategy for dealing with this general problem: instead of analyzing a single model, we introduce a wide variety of 128 different models that make different assumptions about the unknown processes. By comparing the predictions of these models we are able to identify the key quantities that allow the experimental discrimination of the different models. Analysis of these quantities yields that out of the 128 models 94 are not consistent with available experimental data. From the remaining 34 models we are able to conclude that mass growth and DNA replication need either to be truly coupled, by coupling DNA replication initiation to the event of cell division, or to the amount of accumulated mass. Finally, we make suggestions for experiments to further reduce the number of possible regulation scenarios.

Ventures in Community Improvement (VICI): Findings from a Four-Site Replication Initiative, 1984-1987.

ERIC Educational Resources Information Center

Levin, Laurie; And Others

Ventures in Community Improvement (VICI) is a program that provides intensive training in construction skills to disadvantaged youth and at the same time allows them to produce tangible improvements in housing and public facilities in their own low-income communities. The model was tested twice previously, once in an eight-state demonstration that…

Cytology of DNA Replication Reveals Dynamic Plasticity of Large-Scale Chromatin Fibers.

PubMed

Deng, Xiang; Zhironkina, Oxana A; Cherepanynets, Varvara D; Strelkova, Olga S; Kireev, Igor I; Belmont, Andrew S

2016-09-26

In higher eukaryotic interphase nuclei, the 100- to >1,000-fold linear compaction of chromatin is difficult to reconcile with its function as a template for transcription, replication, and repair. It is challenging to imagine how DNA and RNA polymerases with their associated molecular machinery would move along the DNA template without transient decondensation of observed large-scale chromatin "chromonema" fibers [1]. Transcription or "replication factory" models [2], in which polymerases remain fixed while DNA is reeled through, are similarly difficult to conceptualize without transient decondensation of these chromonema fibers. Here, we show how a dynamic plasticity of chromatin folding within large-scale chromatin fibers allows DNA replication to take place without significant changes in the global large-scale chromatin compaction or shape of these large-scale chromatin fibers. Time-lapse imaging of lac-operator-tagged chromosome regions shows no major change in the overall compaction of these chromosome regions during their DNA replication. Improved pulse-chase labeling of endogenous interphase chromosomes yields a model in which the global compaction and shape of large-Mbp chromatin domains remains largely invariant during DNA replication, with DNA within these domains undergoing significant movements and redistribution as they move into and then out of adjacent replication foci. In contrast to hierarchical folding models, this dynamic plasticity of large-scale chromatin organization explains how localized changes in DNA topology allow DNA replication to take place without an accompanying global unfolding of large-scale chromatin fibers while suggesting a possible mechanism for maintaining epigenetic programming of large-scale chromatin domains throughout DNA replication. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dealing with incomplete and variable detectability in multi-year, multi-site monitoring of ecological populations

USGS Publications Warehouse

Converse, Sarah J.; Royle, J. Andrew; Gitzen, Robert A.; Millspaugh, Joshua J.; Cooper, Andrew B.; Licht, Daniel S.

2012-01-01

An ecological monitoring program should be viewed as a component of a larger framework designed to advance science and/or management, rather than as a stand-alone activity. Monitoring targets (the ecological variables of interest; e.g. abundance or occurrence of a species) should be set based on the needs of that framework (Nichols and Williams 2006; e.g. Chapters 2–4). Once such monitoring targets are set, the subsequent step in monitoring design involves consideration of the field and analytical methods that will be used to measure monitoring targets with adequate accuracy and precision. Long-term monitoring programs will involve replication of measurements over time, and possibly over space; that is, one location or each of multiple locations will be monitored multiple times, producing a collection of site visits (replicates). Clearly this replication is important for addressing spatial and temporal variability in the ecological resources of interest (Chapters 7–10), but it is worth considering how this replication can further be exploited to increase the effectiveness of monitoring. In particular, defensible monitoring of the majority of animal, and to a lesser degree plant, populations and communities will generally require investigators to account for imperfect detection (Chapters 4, 18). Raw indices of population state variables, such as abundance or occupancy (sensu MacKenzie et al. 2002), are rarely defensible when detection probabilities are < 1, because in those cases detection may vary over time and space in unpredictable ways. Myriad authors have discussed the risks inherent in making inference from monitoring data while failing to correct for differences in detection, resulting in indices that have an unknown relationship to the parameters of interest (e.g. Nichols 1992, Anderson 2001, MacKenzie et al. 2002, Williams et al. 2002, Anderson 2003, White 2005, Kéry and Schmidt 2008). While others have argued that indices may be preferable in some cases due to the challenges associated with estimating detection probabilities (e.g. McKelvey and Pearson 2001, Johnson 2008), we do not attempt to resolve this debate here. Rather, we are more apt to agree with MacKenzie and Kendall (2002) that the burden of proof ought to be on the assertion that detection probabilities are constant. Furthermore, given the wide variety of field methods available for estimating detection probabilities and the inability for an investigator to know, a priori, if detection probabilities will be constant over time and space, we believe that development of monitoring programs ought to include field and analytical methods to account for the imperfect detection of organisms.

Developmental regulation of DNA replication timing at the human beta globin locus.

PubMed

Simon, I; Tenzen, T; Mostoslavsky, R; Fibach, E; Lande, L; Milot, E; Gribnau, J; Grosveld, F; Fraser, P; Cedar, H

2001-11-01

The human beta globin locus replicates late in most cell types, but becomes early replicating in erythroid cells. Using FISH to map DNA replication timing around the endogenous beta globin locus and by applying a genetic approach in transgenic mice, we have demonstrated that both the late and early replication states are controlled by regulatory elements within the locus control region. These results also show that the pattern of replication timing is set up by mechanisms that work independently of gene transcription.

The Interplay Between Estrogen and Replication Origins in Breast Cancer DNA Amplification

DTIC Science & Technology

2013-09-01

Replication Origins in Breast Cancer DNA Amplification PRINCIPAL INVESTIGATOR: Cinzia Casella CONTRACTING ORGANIZATION: Brown...Interplay Between Estrogen and Replication Origins in Breast Cancer DNA Amplification 5b. GRANT NUMBER W81XWH-11-1-0599 5c. PROGRAM ELEMENT NUMBER 6... amplification and oncogenes activation in breast cancer cells? This project aims to understand the role of estrogen in inducing re-replication, thus

Sociocultural variables in youth access to tobacco: replication 5 years later.

PubMed

Landrine, H; Klonoff, E A; Campbell, R; Reina-Patton, A

2000-05-01

A prior study presented the only systematic investigation of the role of sociocultural variables in youth access to tobacco. White, black, and Latino girls and boys attempted to purchase cigarettes in the same 72 stores at the same time of day. Results revealed significantly greater sales to girls than to boys and to minorities than to whites. Before concluding that sociocultural variables must be addressed in merchant intervention programs designed to reduce youth access to tobacco, this study must be replicated, particularly in light of the significant decreases in youth access in the past 5 years. This article presents that replication. The stores used in the prior study were selected, and 12 white, black, and Latino girls and boys attempted to purchase cigarettes in those stores at the same time of day. Results Youths' access rate in 1999 (12.7%) was significantly lower than in the prior (1993-1995) study (41%). No effect for minors' gender was found, but the ethnicity effect again emerged: Black and Latino youth were 2.5 times more likely to be sold cigarettes than their white counterparts. Multiple sociocultural variables affect youth access to tobacco when access rates are high, but only youth ethnicity plays a role when access rates are low. Merchant interventions designed to reduce youth access to tobacco must address ethnic issues.

PASHA: facilitating the replication and use of effective adolescent pregnancy and STI/HIV prevention programs.

PubMed

Card, Josefina J; Lessard, Laura; Benner, Tabitha

2007-03-01

It is important that interventions that have been shown effective in changing risky behavior be disseminated, so that they can be replicated (implemented in a new site) and so that their effectiveness in a new setting can be investigated. This article provides an update on an innovative resource for promoting the replication of effective teen pregnancy and STI/HIV prevention programs. The resource is called the Program Archive on Sexuality, Health & Adolescence (PASHA). A Scientist Expert Panel rates candidate adolescent pregnancy and STI/HIV prevention programs based on the strength of the evidence of their effectiveness in changing risky sexual behavior among youth ages 10-19 (10-21 for STI/HIV prevention programs). Developers of selected programs are invited to make their program and evaluation materials publicly available through PASHA. PASHA publishes and disseminates replication kits for programs it successfully acquires. Fifty-six programs have been selected by PASHA's Scientist Expert Panel as "effective" in changing one or more risky behaviors associated with adolescent pregnancy or STI/HIV. Complete program and evaluation materials from 35 of these programs are now currently available through PASHA, five are pending, 12 are publicly available from other sources, and only four are not publicly available. PASHA programs are aimed at a diverse target population and cover diverse content on many abstinence and contraception/condom-related topics. Many pedagogical techniques are used to effect behavior change, noticeably role play and group discussion. PASHA illustrates well the productive research-to-practice feedback loop that is the backbone of "translation research." The resource can be used by adolescent pregnancy and STI/HIV prevention practitioners to put what works to work to continue the lowering of the nation's adolescent pregnancy and STI/HIV rates.

45 CFR 2516.500 - How does the Corporation review the merits of an application?

Code of Federal Regulations, 2013 CFR

2013-10-01

..., innovation, replicability, and sustainability of the proposal on the basis of the following criteria: (1... from experience and replicating the approach of the program. (3) Sustainability, as indicated by the... proposal's quality, innovation, replicability, and sustainability; or (9) Address any other priority...

45 CFR 2516.500 - How does the Corporation review the merits of an application?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., innovation, replicability, and sustainability of the proposal on the basis of the following criteria: (1... from experience and replicating the approach of the program. (3) Sustainability, as indicated by the... proposal's quality, innovation, replicability, and sustainability; or (9) Address any other priority...

45 CFR 2516.500 - How does the Corporation review the merits of an application?

Code of Federal Regulations, 2014 CFR

2014-10-01

..., innovation, replicability, and sustainability of the proposal on the basis of the following criteria: (1... from experience and replicating the approach of the program. (3) Sustainability, as indicated by the... proposal's quality, innovation, replicability, and sustainability; or (9) Address any other priority...

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A postdoctoral position is available in the Viral Recombination Section (VRS), HIV Dynamics and Replication Program, CCR.  The VRS studies retroviral replication using human immunodeficiency viruses and other retroviruses, with a particular emphasis on the mechanisms of viral RNA biology, specific RNA packaging, virus assembly, and HIV replication.  Molecular tools and

Growing What Works: Lessons Learned Replicating Promising Practices for Latino Student Success

ERIC Educational Resources Information Center

Santiago, Deborah A.; Lopez, Estela

2013-01-01

How does the country accelerate Latino student success in higher education? The U.S. has to find programs and strategies that improve the success of Latino students, and then replicate or scale up those programs and strategies to serve more students. Those are the basic principles behind "Excelencia" in Education's Growing What Works (GWW)…

Replication and Extension of the Early Childhood Friendship Project: Effects on Physical and Relational Bullying

ERIC Educational Resources Information Center

Ostrov, Jamie M.; Godleski, Stephanie A.; Kamper-DeMarco, Kimberly E.; Blakely-McClure, Sarah J.; Celenza, Lauren

2015-01-01

A replication of a preventive early childhood intervention study for reducing relational and physical aggression and peer victimization was conducted (Ostrov et al., 2009). The present study expanded on the original 6-week program, and the revised Early Childhood Friendship Project (ECFP) 8-week program consisted of developmentally appropriate…

[Mediate evaluation of replicating a Training Program in Nonverbal Communication in Gerontology].

PubMed

Schimidt, Teresa Cristina Gioia; Duarte, Yeda Aparecida de Oliveira; Silva, Maria Julia Paes da

2015-04-01

Replicating the training program in non-verbal communication based on the theoretical framework of interpersonal communication; non-verbal coding, valuing the aging aspects in the perspective of active aging, checking its current relevance through the content assimilation index after 90 days (mediate) of its application. A descriptive and exploratory field study was conducted in three hospitals under direct administration of the state of São Paulo that caters exclusively to Unified Health System (SUS) patients. The training lasted 12 hours divided in three meetings, applied to 102 health professionals. Revealed very satisfactory and satisfactory mediate content assimilation index in 82.9%. The program replication proved to be relevant and updated the setting of hospital services, while remaining efficient for healthcare professionals.

UTeach Replication: Impacting Teacher Preparation at a University Near You

NASA Astrophysics Data System (ADS)

Marshall, Jill

2008-03-01

In 2007 the National Mathematics and Science Initiative, with a grant from Exxon-Mobil, launched two major programs to improve science and mathematics education in the US: an Advanced Placement initiative and replication of the UTeach program. Twelve colleges and universities, from Florida to California, have been selected to receive grants of up to 2.4 million to start UTeach-type programs. I will report on the requirements for these grants, what it really means to have a ``UTeach-type'' program and the evidence that such programs can affect the quantity and quality of physics teachers in the US.

The Effectiveness of Web-Based Foreign Exchange Trading Simulation in an International Finance Course

ERIC Educational Resources Information Center

Chou, Chen-Huei; Liu, Hao-Chen

2013-01-01

The purpose of this article is to study if trading simulation is an effective tool to increase students' knowledge of the foreign exchange market. We developed a real-time multiuser web-based trading system that replicates an electronic brokerage foreign exchange market. To assess the effectiveness of the program, we conducted surveys in three…

76 FR 16754 - Charter Schools Program (CSP) Grants for Replication and Expansion of High-Quality Charter Schools

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... Maryland Avenue, SW., Washington, DC, between the hours of 8:30 a.m. and 4 p.m., Washington, DC time... management organizations (CMOs) and other not-for-profit entities. Eligible applicants may also apply as a...: A grantee may use up to 20 percent of grant funds for initial operational costs associated with the...

Functional centromeres determine the activation time of pericentric origins of DNA replication in Saccharomyces cerevisiae.

PubMed

Pohl, Thomas J; Brewer, Bonita J; Raghuraman, M K

2012-01-01

The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in early replicating domains, a property conserved among centromeres in fungi and some higher eukaryotes. Surprisingly, little is known about the biological significance or the mechanism of early centromere replication; however, the extensive conservation suggests that it is important for chromosome maintenance. Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time. Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain. We used a modified Meselson-Stahl density transfer assay to measure the kinetics of replication for regions of chromosome XIV in which either the functional centromere or a point-mutated version had been moved near origins that reside in a late replication region. We show that a functional centromere acts in cis over a distance as great as 19 kb to advance the initiation time of origins. Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation.

Functional Centromeres Determine the Activation Time of Pericentric Origins of DNA Replication in Saccharomyces cerevisiae

PubMed Central

Pohl, Thomas J.; Brewer, Bonita J.; Raghuraman, M. K.

2012-01-01

The centromeric regions of all Saccharomyces cerevisiae chromosomes are found in early replicating domains, a property conserved among centromeres in fungi and some higher eukaryotes. Surprisingly, little is known about the biological significance or the mechanism of early centromere replication; however, the extensive conservation suggests that it is important for chromosome maintenance. Do centromeres ensure their early replication by promoting early activation of nearby origins, or have they migrated over evolutionary time to reside in early replicating regions? In Candida albicans, a neocentromere contains an early firing origin, supporting the first hypothesis but not addressing whether the new origin is intrinsically early firing or whether the centromere influences replication time. Because the activation time of individual origins is not an intrinsic property of S. cerevisiae origins, but is influenced by surrounding sequences, we sought to test the hypothesis that centromeres influence replication time by moving a centromere to a late replication domain. We used a modified Meselson-Stahl density transfer assay to measure the kinetics of replication for regions of chromosome XIV in which either the functional centromere or a point-mutated version had been moved near origins that reside in a late replication region. We show that a functional centromere acts in cis over a distance as great as 19 kb to advance the initiation time of origins. Our results constitute a direct link between establishment of the kinetochore and the replication initiation machinery, and suggest that the proposed higher-order structure of the pericentric chromatin influences replication initiation. PMID:22589733

A seabird monitoring program for the North Pacific

USGS Publications Warehouse

Hatcher, S.A.; Kaiser, G.W.; Kondratyev, Alexander V.; Byrd, G.V.

1994-01-01

Seabird monitoring is the accumulation of time series data on any aspect of seabird distribution, abundance, demography, or behavior. Typical studies include annual or less frequent measures of numbers or productivity; less commonly, the focus is on marine habitat use, phenology, food habits, or survival. The key requirement is that observations are replicated over time and made with sufficient precision and accuracy to permit the meaningful analysis of variability and trends. Along the Pacific coast of North America, seabird monitoring has consumed substantial amounts of public funding since the early 1970s. The effort has been largely uncoordinated among the many entities involved, including provincial, state, and federal agencies, some private organizations, university faculty, and students. We reaffirm the rationale for monitoring seabirds, review briefly the nature and accomplishments of the existing effort, and suggest actions needed to improve the effectiveness of seabird monitoring in the Pacific. In particular, we propose and describe a comprehensive Seabird Monitoring Database designed specifically to work with observations on seabird population parameters that are replicated over time.

Replication dynamics of the yeast genome.

PubMed

Raghuraman, M K; Winzeler, E A; Collingwood, D; Hunt, S; Wodicka, L; Conway, A; Lockhart, D J; Davis, R W; Brewer, B J; Fangman, W L

2001-10-05

Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--QA ANALYTICAL RESULTS FOR METALS IN REPLICATE SAMPLES

EPA Science Inventory

The Metals in Replicate Samples data set contains the analytical results of measurements of up to 2 metals in 172 replicate (duplicate) samples from 86 households. Measurements were made in samples of blood. Duplicate samples for a small percentage of the total number of sample...

Can Successful Schools Replicate? Evidence from Boston Charter Schools

ERIC Educational Resources Information Center

Cohodes, Sarah; Setren, Elizabeth; Walters, Christopher

2016-01-01

Can successful schools replicate? In a climate of school turnarounds, charter conversions, and new school openings, an important question is whether schools that have demonstrated success with in one or several schools can replicate their success with additional schools. The federal government's Investing in Innovation (i3) grant program has been…

The Genetic Program of Pancreatic β-Cell Replication In Vivo.

PubMed

Klochendler, Agnes; Caspi, Inbal; Corem, Noa; Moran, Maya; Friedlich, Oriel; Elgavish, Sharona; Nevo, Yuval; Helman, Aharon; Glaser, Benjamin; Eden, Amir; Itzkovitz, Shalev; Dor, Yuval

2016-07-01

The molecular program underlying infrequent replication of pancreatic β-cells remains largely inaccessible. Using transgenic mice expressing green fluorescent protein in cycling cells, we sorted live, replicating β-cells and determined their transcriptome. Replicating β-cells upregulate hundreds of proliferation-related genes, along with many novel putative cell cycle components. Strikingly, genes involved in β-cell functions, namely, glucose sensing and insulin secretion, were repressed. Further studies using single-molecule RNA in situ hybridization revealed that in fact, replicating β-cells double the amount of RNA for most genes, but this upregulation excludes genes involved in β-cell function. These data suggest that the quiescence-proliferation transition involves global amplification of gene expression, except for a subset of tissue-specific genes, which are "left behind" and whose relative mRNA amount decreases. Our work provides a unique resource for the study of replicating β-cells in vivo. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Replicating the Moderating Role of Income Status on Summer School Effects across Subject Areas: A Meta-Analysis

ERIC Educational Resources Information Center

Quinn, David M.; Lynch, Kathleen; Kim, James S.

2014-01-01

The finding that academic summer programs are effective for low income students has been replicated across meta-analytic reviews. However, these reviews have yielded contradictory evidence about whether summer programs are more effective for lower- or higher-income students. This discrepancy may be due to income-based differences in the summer…

Replicating the Effects of a Teacher-Scaffolded Voluntary Summer Reading Program: The Role of Poverty

ERIC Educational Resources Information Center

White, Thomas G.; Kim, James S.; Kingston, Helen Chen; Foster, Lisa

2014-01-01

A randomized trial involving 19 elementary schools (K-5) was conducted to replicate and extend two previous experimental studies of the effects of a voluntary summer reading program that provided (a) books matched to students' reading levels and interests and (b) teacher scaffolding in the form of end-of-year comprehension lessons. Matched…

Effects of a Pedometer-Based Telephone Coaching Intervention on Physical Activity Among People with Cardiac Disease in Urban, Rural and Semi-Rural Settings: A Replication Study.

PubMed

Sangster, Janice; Furber, Susan; Phongsavan, Philayrath; Redfern, Julie; Mark, Andrew; Bauman, Adrian

2017-04-01

This study aimed to determine the replicability of a pedometer-based telephone coaching intervention by comparing the outcomes of a study conducted in rural and urban settings to a study that previously found the same intervention effective in a semi-rural setting. Replication studies are conducted to assess whether an efficacious intervention is effective in multiple different settings. This study compared the outcomes of a pedometer-based coaching intervention implemented in urban and rural settings (replication study) with the same intervention implemented in a semi-rural setting (reference study) on physical activity levels. Improvements in total weekly physical activity time in the replication study were significant from baseline to six weeks (p<0.001 urban, p=0.006 rural) and remained significant at six months (p=0.029 urban, p=0.005 rural). These increases were comparable to those achieved in the original efficacy trial conducted in a semi-rural setting. The pedometer-based telephone coaching intervention increases physical activity levels of people with cardiac disease referred to a CR program in diverse settings. This replication study indicates the suitability of this minimal contact, low-cost intervention for further scaling-up to address unmet need in community-dwelling cardiac patients. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

The Tailored Activity Program to reduce behavioral symptoms in individuals with dementia: feasibility, acceptability, and replication potential.

PubMed

Gitlin, Laura N; Winter, Laraine; Vause Earland, Tracey; Adel Herge, E; Chernett, Nancy L; Piersol, Catherine V; Burke, Janice P

2009-06-01

The Tailored Activity Program (TAP) is a home-based occupational therapy intervention shown to reduce behavioral symptoms and caregiver burden in a randomized trial. This article describes TAP, its assessments, acceptability, and replication potential. TAP involves 8 sessions for a period of 4 months. Interventionists identify preserved capabilities, previous roles, habits, and interests of individuals with dementia; develop activities customized to individual profiles; and train families in activity use. Interventionists documented time spent and ease conducting assessments, and observed receptivity of TAP. For each implemented prescribed activity, caregivers reported the amount of time their relative spent in activity and perceived benefits. The TAP assessment, a combination of neuropsychological tests, standardized performance-based observations, and clinical interviewing, yielded information on capabilities from which to identify and tailor activities. Assessments were easy to administer, taking an average of two 1-hr sessions. Of 170 prescribed activities, 81.5% were used, for an average of 4 times for 23 min by families between treatment sessions for a period of months. Caregivers reported high confidence in using activities, being less upset with behavioral symptoms (86%), and enhanced skills (93%) and personal control (95%). Interventionists observed enhanced engagement (100%) and pleasure (98%) in individuals with dementia during sessions. TAP offers families knowledge of their relative's capabilities and easy-to-use activities. The program was well received by caregivers. Prescribed activities appeared to be pleasurable and engaging to individuals with dementia. TAP merits further evaluation to establish efficacy with larger more diverse populations and consideration as a nonpharmacological approach to manage behavioral symptoms.

Bacteria as computers making computers

PubMed Central

Danchin, Antoine

2009-01-01

Various efforts to integrate biological knowledge into networks of interactions have produced a lively microbial systems biology. Putting molecular biology and computer sciences in perspective, we review another trend in systems biology, in which recursivity and information replace the usual concepts of differential equations, feedback and feedforward loops and the like. Noting that the processes of gene expression separate the genome from the cell machinery, we analyse the role of the separation between machine and program in computers. However, computers do not make computers. For cells to make cells requires a specific organization of the genetic program, which we investigate using available knowledge. Microbial genomes are organized into a paleome (the name emphasizes the role of the corresponding functions from the time of the origin of life), comprising a constructor and a replicator, and a cenome (emphasizing community-relevant genes), made up of genes that permit life in a particular context. The cell duplication process supposes rejuvenation of the machine and replication of the program. The paleome also possesses genes that enable information to accumulate in a ratchet-like process down the generations. The systems biology must include the dynamics of information creation in its future developments. PMID:19016882

Bacteria as computers making computers.

PubMed

Danchin, Antoine

2009-01-01

Various efforts to integrate biological knowledge into networks of interactions have produced a lively microbial systems biology. Putting molecular biology and computer sciences in perspective, we review another trend in systems biology, in which recursivity and information replace the usual concepts of differential equations, feedback and feedforward loops and the like. Noting that the processes of gene expression separate the genome from the cell machinery, we analyse the role of the separation between machine and program in computers. However, computers do not make computers. For cells to make cells requires a specific organization of the genetic program, which we investigate using available knowledge. Microbial genomes are organized into a paleome (the name emphasizes the role of the corresponding functions from the time of the origin of life), comprising a constructor and a replicator, and a cenome (emphasizing community-relevant genes), made up of genes that permit life in a particular context. The cell duplication process supposes rejuvenation of the machine and replication of the program. The paleome also possesses genes that enable information to accumulate in a ratchet-like process down the generations. The systems biology must include the dynamics of information creation in its future developments.

Peripheral re-localization of constitutive heterochromatin advances its replication timing and impairs maintenance of silencing marks.

PubMed

Heinz, Kathrin S; Casas-Delucchi, Corella S; Török, Timea; Cmarko, Dusan; Rapp, Alexander; Raska, Ivan; Cardoso, M Cristina

2018-05-10

The replication of the genome is a highly organized process, both spatially and temporally. Although a lot is known on the composition of the basic replication machinery, how its activity is regulated is mostly unknown. Several chromatin properties have been proposed as regulators, but a potential role of the nuclear DNA position remains unclear. We made use of the prominent structure and well-defined heterochromatic landscape of mouse pericentric chromosome domains as a well-studied example of late replicating constitutive heterochromatin. We established a method to manipulate its nuclear position and evaluated the effect on replication timing, DNA compaction and epigenetic composition. Using time-lapse microscopy, we observed that constitutive heterochromatin, known to replicate during late S-phase, was replicated in mid S-phase when repositioned to the nuclear periphery. Out-of-schedule replication resulted in deficient post-replicative maintenance of chromatin modifications, namely silencing marks. We propose that repositioned constitutive heterochromatin was activated in trans according to the domino model of origin firing by nearby (mid S) firing origins. In summary, our data provide, on the one hand, a novel approach to manipulate nuclear DNA position and, on the other hand, establish nuclear DNA position as a novel mechanism regulating DNA replication timing and epigenetic maintenance.

Replication profile of Saccharomyces cerevisiae chromosome VI.

PubMed

Friedman, K L; Brewer, B J; Fangman, W L

1997-11-01

An understanding of the replication programme at the genome level will require the identification and characterization of origins of replication through large, contiguous regions of DNA. As a step toward this goal, origin efficiencies and replication times were determined for 10 ARSs spanning most of the 270 kilobase (kb) chromosome VI of Saccharomyces cerevisiae. Chromosome VI shows a wide variation in the percentage of cell cycles in which different replication origins are utilized. Most of the origins are activated in only a fraction of cells, suggesting that the pattern of origin usage on chromosome VI varies greatly within the cell population. The replication times of fragments containing chromosome VI origins show a temporal pattern that has been recognized on other chromosomes--the telomeres replicate late in S phase, while the central region of the chromosome replicates early. As demonstrated here for chromosome VI, analysis of the direction of replication fork movement along a chromosome and determination of replication time by measuring a period of hemimethylation may provide an efficient means of surveying origin activity over large regions of the genome.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

A postdoctoral position is available in the Viral Recombination Section (VRS), HIV Dynamics and Replication Program, CCR.  The VRS studies retroviral replication using human immunodeficiency viruses and other retroviruses, with a particular emphasis on the mechanisms of viral RNA biology, specific RNA packaging, virus assembly, and HIV replication.  Molecular tools and advanced imaging approaches are used to dissect various aspects of viral replication mechanisms.  A more complete description of the projects can be found at http://home.ncifcrf.gov/hivdrp/Hu_res.html.

Replicating Social Programmes: Approaches, Strategies and Conceptual Issues. Management of Social Transformations (MOST) Discussion Paper Series, No. 18.

ERIC Educational Resources Information Center

van Oudenhoven, Nico; Wazir, Rekha

This paper reviews the key issues and methodologies involved in the replication of social programs, as they pertain to non-profit sector development in the United States and in international development. The related process of knowledge transfer and dissemination, as well as the more specific strategies involved in replication and going-to-scale…

Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site.

PubMed

Letessier, Anne; Millot, Gaël A; Koundrioukoff, Stéphane; Lachagès, Anne-Marie; Vogt, Nicolas; Hansen, R Scott; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle

2011-02-03

Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

How and why multiple MCMs are loaded at origins of DNA replication.

PubMed

Das, Shankar P; Rhind, Nicholas

2016-07-01

Recent work suggests that DNA replication origins are regulated by the number of multiple mini-chromosome maintenance (MCM) complexes loaded. Origins are defined by the loading of MCM - the replicative helicase which initiates DNA replication and replication kinetics determined by origin's location and firing times. However, activation of MCM is heterogeneous; different origins firing at different times in different cells. Also, more MCMs are loaded in G1 than are used in S phase. These aspects of MCM biology are explained by the observation that multiple MCMs are loaded at origins. Having more MCMs at early origins makes them more likely to fire, effecting differences in origin efficiency that define replication timing. Nonetheless, multiple MCM loading raises new questions, such as how they are loaded, where these MCMs reside at origins, and how their presence affects replication timing. In this review, we address these questions and discuss future avenues of research. © 2016 WILEY Periodicals, Inc.

Estimating replicate time shifts using Gaussian process regression

PubMed Central

Liu, Qiang; Andersen, Bogi; Smyth, Padhraic; Ihler, Alexander

2010-01-01

Motivation: Time-course gene expression datasets provide important insights into dynamic aspects of biological processes, such as circadian rhythms, cell cycle and organ development. In a typical microarray time-course experiment, measurements are obtained at each time point from multiple replicate samples. Accurately recovering the gene expression patterns from experimental observations is made challenging by both measurement noise and variation among replicates' rates of development. Prior work on this topic has focused on inference of expression patterns assuming that the replicate times are synchronized. We develop a statistical approach that simultaneously infers both (i) the underlying (hidden) expression profile for each gene, as well as (ii) the biological time for each individual replicate. Our approach is based on Gaussian process regression (GPR) combined with a probabilistic model that accounts for uncertainty about the biological development time of each replicate. Results: We apply GPR with uncertain measurement times to a microarray dataset of mRNA expression for the hair-growth cycle in mouse back skin, predicting both profile shapes and biological times for each replicate. The predicted time shifts show high consistency with independently obtained morphological estimates of relative development. We also show that the method systematically reduces prediction error on out-of-sample data, significantly reducing the mean squared error in a cross-validation study. Availability: Matlab code for GPR with uncertain time shifts is available at http://sli.ics.uci.edu/Code/GPRTimeshift/ Contact: ihler@ics.uci.edu PMID:20147305

Linker Histone Phosphorylation Regulates Global Timing of Replication Origin Firing*S⃞

PubMed Central

Thiriet, Christophe; Hayes, Jeffrey J.

2009-01-01

Despite the presence of linker histone in all eukaryotes, the primary function(s) of this histone have been difficult to clarify. Knock-out experiments indicate that H1s play a role in regulation of only a small subset of genes but are an essential component in mouse development. Here, we show that linker histone (H1) is involved in the global regulation of DNA replication in Physarum polycephalum. We find that genomic DNA of H1 knock-down cells is more rapidly replicated, an effect due at least in part to disruption of the native timing of replication fork firing. Immunoprecipitation experiments demonstrate that H1 is transiently lost from replicating chromatin via a process facilitated by phosphorylation. Our results suggest that linker histones generate a chromatin environment refractory to replication and that their transient removal via protein phosphorylation during S phase is a critical step in the epigenetic regulation of replication timing. PMID:19015270

A Practical Approach to Replication of Abstract Data Objects

DTIC Science & Technology

1990-05-01

rigorous torture testing. Torture testing was done with the aid of a basher program that allows the user to configure an object and perform a specified...number of transactions, each containing a specified number of operations on the object. There are separate basher programs for RSMs and MRSMs. The...modify the object (Writes and Erases, for RSMs). The basher maintains a local, non- replicated table that tracks the RSM that is under test. Each

Providing Teachers with Research- and Cognitive Learning Theory-Based Instructional Materials for Promoting Students' Metacognition: A Replication Study of a Community College Mathematics Teacher and Curriculum Reformation Program

ERIC Educational Resources Information Center

Nall, Katherine Ligon

2011-01-01

The purpose of this study was to assess the effect of a 3-stage community college mathematics teacher and curriculum conceptual change program on student achievement. The study, which was a replication and extension of Lake (2008), was conducted during Fall 2009 and Spring 2010 terms and focused on teachers' instructional practices relative to…

Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET).

PubMed

Sridhar, Devi; Car, Josip; Chopra, Mickey; Campbell, Harry; Woods, Ngaire; Rudan, Igor

2015-12-01

International development assistance for health (DAH) quadrupled between 1990 and 2012, from US$ 5.6 billion to US$ 28.1 billion. This generates an increasing need for transparent and replicable tools that could be used to set investment priorities, monitor the distribution of funding in real time, and evaluate the impact of those investments. In this paper we present a methodology that addresses these three challenges. We call this approach PLANET, which stands for planning, monitoring and evaluation tool. Fundamentally, PLANET is based on crowdsourcing approach to obtaining information relevant to deployment of large-scale programs. Information is contributed in real time by a diverse group of participants involved in the program delivery. PLANET relies on real-time information from three levels of participants in large-scale programs: funders, managers and recipients. At each level, information is solicited to assess five key risks that are most relevant to each level of operations. The risks at the level of funders involve systematic neglect of certain areas, focus on donor's interests over that of program recipients, ineffective co-ordination between donors, questionable mechanisms of delivery and excessive loss of funding to "middle men". At the level of managers, the risks are corruption, lack of capacity and/or competence, lack of information and /or communication, undue avoidance of governmental structures / preference to non-governmental organizations and exclusion of local expertise. At the level of primary recipients, the risks are corruption, parallel operations / "verticalization", misalignment with local priorities and lack of community involvement, issues with ethics, equity and/or acceptability, and low likelihood of sustainability beyond the end of the program's implementation. PLANET is intended as an additional tool available to policy-makers to prioritize, monitor and evaluate large-scale development programs. In this, it should complement tools such as LiST (for health care/interventions), EQUIST (for health care/interventions) and CHNRI (for health research), which also rely on information from local experts and on local context to set priorities in a transparent, user-friendly, replicable, quantifiable and specific, algorithmic-like manner.

Replication Origins and Timing of Temporal Replication in Budding Yeast: How to Solve the Conundrum?

PubMed Central

Barberis, Matteo; Spiesser, Thomas W.; Klipp, Edda

2010-01-01

Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicates its genome with a defined timing. In this organism, well-defined, site-specific origins, are efficient and fire in almost every round of DNA replication. However, this strategy is neither conserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophila embryos, nor in higher eukaryotes, in which DNA replication initiates asynchronously throughout S phase at random sites. Temporal and spatial controls can contribute to the timing of replication such as Cdk activity, origin localization, epigenetic status or gene expression. However, a debate is going on to answer the question how individual origins are selected to fire in budding yeast. Two opposing theories were proposed: the “replicon paradigm” or “temporal program” vs. the “stochastic firing”. Recent data support the temporal regulation of origin activation, clustering origins into temporal blocks of early and late replication. Contrarily, strong evidences suggest that stochastic processes acting on origins can generate the observed kinetics of replication without requiring a temporal order. In mammalian cells, a spatiotemporal model that accounts for a partially deterministic and partially stochastic order of DNA replication has been proposed. Is this strategy the solution to reconcile the conundrum of having both organized replication timing and stochastic origin firing also for budding yeast? In this review we discuss this possibility in the light of our recent study on the origin activation, suggesting that there might be a stochastic component in the temporal activation of the replication origins, especially under perturbed conditions. PMID:21037857

Mobile and replicated alignment of arrays in data-parallel programs

NASA Technical Reports Server (NTRS)

Chatterjee, Siddhartha; Gilbert, John R.; Schreiber, Robert

1993-01-01

When a data-parallel language like FORTRAN 90 is compiled for a distributed-memory machine, aggregate data objects (such as arrays) are distributed across the processor memories. The mapping determines the amount of residual communication needed to bring operands of parallel operations into alignment with each other. A common approach is to break the mapping into two stages: first, an alignment that maps all the objects to an abstract template, and then a distribution that maps the template to the processors. We solve two facets of the problem of finding alignments that reduce residual communication: we determine alignments that vary in loops, and objects that should have replicated alignments. We show that loop-dependent mobile alignment is sometimes necessary for optimum performance, and we provide algorithms with which a compiler can determine good mobile alignments for objects within do loops. We also identify situations in which replicated alignment is either required by the program itself (via spread operations) or can be used to improve performance. We propose an algorithm based on network flow that determines which objects to replicate so as to minimize the total amount of broadcast communication in replication. This work on mobile and replicated alignment extends our earlier work on determining static alignment.

Statistical security for Social Security.

PubMed

Soneji, Samir; King, Gary

2012-08-01

The financial viability of Social Security, the single largest U.S. government program, depends on accurate forecasts of the solvency of its intergenerational trust fund. We begin by detailing information necessary for replicating the Social Security Administration's (SSA's) forecasting procedures, which until now has been unavailable in the public domain. We then offer a way to improve the quality of these procedures via age- and sex-specific mortality forecasts. The most recent SSA mortality forecasts were based on the best available technology at the time, which was a combination of linear extrapolation and qualitative judgments. Unfortunately, linear extrapolation excludes known risk factors and is inconsistent with long-standing demographic patterns, such as the smoothness of age profiles. Modern statistical methods typically outperform even the best qualitative judgments in these contexts. We show how to use such methods, enabling researchers to forecast using far more information, such as the known risk factors of smoking and obesity and known demographic patterns. Including this extra information makes a substantial difference. For example, by improving only mortality forecasting methods, we predict three fewer years of net surplus, $730 billion less in Social Security Trust Funds, and program costs that are 0.66% greater for projected taxable payroll by 2031 compared with SSA projections. More important than specific numerical estimates are the advantages of transparency, replicability, reduction of uncertainty, and what may be the resulting lower vulnerability to the politicization of program forecasts. In addition, by offering with this article software and detailed replication information, we hope to marshal the efforts of the research community to include ever more informative inputs and to continue to reduce uncertainties in Social Security forecasts.

Collecting Response Times using Amazon Mechanical Turk and Adobe Flash

PubMed Central

Simcox, Travis; Fiez, Julie A.

2017-01-01

Crowdsourcing systems like Amazon's Mechanical Turk (AMT) allow data to be collected from a large sample of people in a short amount of time. This use has garnered considerable interest from behavioral scientists. So far, most experiments conducted on AMT have focused on survey-type instruments because of difficulties inherent in running many experimental paradigms over the Internet. This article investigated the viability of presenting stimuli and collecting response times using Adobe Flash to run ActionScript 3 code in conjunction with AMT. First, the timing properties of Adobe Flash were investigated using a phototransistor and two desktop computers running under several conditions mimicking those that may be present in research using AMT. This experiment revealed some strengths and weaknesses of the timing capabilities of this method. Next, a flanker task and a lexical decision task implemented in Adobe Flash were administered to participants recruited with AMT. The expected effects in these tasks were replicated. Power analyses were conducted to describe the number of participants needed to replicate these effects. A questionnaire was used to investigate previously undescribed computer use habits of 100 participants on AMT. We conclude that a Flash program in conjunction with AMT can be successfully used for running many experimental paradigms that rely on response times, although experimenters must understand the limitations of the method. PMID:23670340

Back to the Origin

PubMed Central

Evertts, Adam G.

2012-01-01

In bacteria, replication is a carefully orchestrated event that unfolds the same way for each bacterium and each cell division. The process of DNA replication in bacteria optimizes cell growth and coordinates high levels of simultaneous replication and transcription. In metazoans, the organization of replication is more enigmatic. The lack of a specific sequence that defines origins of replication has, until recently, severely limited our ability to define the organizing principles of DNA replication. This question is of particular importance as emerging data suggest that replication stress is an important contributor to inherited genetic damage and the genomic instability in tumors. We consider here the replication program in several different organisms including recent genome-wide analyses of replication origins in humans. We review recent studies on the role of cytosine methylation in replication origins, the role of transcriptional looping and gene gating in DNA replication, and the role of chromatin’s 3-dimensional structure in DNA replication. We use these new findings to consider several questions surrounding DNA replication in metazoans: How are origins selected? What is the relationship between replication and transcription? How do checkpoints inhibit origin firing? Why are there early and late firing origins? We then discuss whether oncogenes promote cancer through a role in DNA replication and whether errors in DNA replication are important contributors to the genomic alterations and gene fusion events observed in cancer. We conclude with some important areas for future experimentation. PMID:23634256

Teaching communication skills in clinical settings: comparing two applications of a comprehensive program with standardized and real patients

PubMed Central

2014-01-01

Background Communication is important for the quality of clinical practice, and programs have been implemented to improve healthcare providers’ communication skills. However, the consistency of programs teaching communication skills has received little attention, and debate exists about the application of acquired skills to real patients. This study inspects whether (1) results from a communication program are replicated with different samples, and (2) results with standardized patients apply to interviews with real patients. Methods A structured, nine-month communication program was applied in two consecutive years to two different samples of healthcare professionals (25 in the first year, 20 in the second year). Results were assessed at four different points in time, each year, regarding participants’ confidence levels (self-rated), basic communication skills in interviews with standardized patients, and basic communication skills in interviews with real patients. Data were analyzed using GLM Repeated-Measures procedures. Results Improvements were statistically significant in both years in all measures except in simulated patients’ assessment of the 2008 group. Differences between the two samples were non-significant. Differences between interviews with standardized and with real patients were also non-significant. Conclusions The program’s positive outcomes were replicated in different samples, and acquired skills were successfully applied to real-patient interviews. This reinforces this type of program structure as a valuable training tool, with results translating into real situations. It also adds to the reliability of the assessment instruments employed, though these may need adaptation in the case of real patients. PMID:24886341

SECURE MATHEMATICALLY- ASSURED COMPOSITION OF CONTROL MODELS

DTIC Science & Technology

2017-09-27

and in fact, often introduces new vulnerabilities that can be exploited. The situation is even worse for em - bedded software because it is often...fork- bomb is a program which continuously replicates itself, thus making it very hard to kill off all instances of the forkbomb. This causes the...binaries. In Eduardo Tovar, editor, IEEE Real-Time and Em - bedded Technology and Applications Symposium (RTAS), pages 97–106, Philadelphia, USA, April 2013

Chromosomal context and replication properties of ARS plasmids in Schizosaccharomyces pombe.

PubMed

Pratihar, Aditya S; Tripathi, Vishnu P; Yadav, Mukesh P; Dubey, Dharani D

2015-12-01

Short, specific DNA sequences called as Autonomously Replicating Sequence (ARS) elements function as plasmid as well as chromosomal replication origins in yeasts. As compared to ARSs, different chromosomal origins vary greatly in their efficiency and timing of replication probably due to their wider chromosomal context. The two Schizosaccharomyces pombe ARS elements, ars727 and ars2004, represent two extremities in their chromosomal origin activity - ars727 is inactive and late replicating, while ars2004 is a highly active, early-firing origin. To determine the effect of chromosomal context on the activity of these ARS elements, we have cloned them with their extended chromosomal context as well as in the context of each other in both orientations and analysed their replication efficiency by ARS and plasmid stability assays. We found that these ARS elements retain their origin activity in their extended/altered context. However, deletion of a 133-bp region of the previously reported ars727- associated late replication enforcing element (LRE) caused advancement in replication timing of the resulting plasmid. These results confirm the role of LRE in directing plasmid replication timing and suggest that the plasmid origin efficiency of ars2004 or ars727 remains unaltered by the extended chromosomal context.

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

Torchia, B.S.; Call, L.M.; Migeon, B.R.

The relationship between the transcriptional state of a locus and the time when it replicates during DNA synthesis is increasingly apparent. Active autosomal genes tend to replicate early, whereas inactive ones are more permissive and frequently replicate later. Although the inactive X chromosome replicates later than its active homologue, little is known about the replication of X-linked genes. The authors have used FISH to examine the replication of loci on the active X chromosome that are not transcribed, either because the tissue analyzed was not the expressing tissue (F8C), because the locus is silent on all active X chromosomes (XIST),more » or because it has been mutated by expansion and methylation of a CpG island (FMR1). In this assay, an unreplicated locus is characterized by a single hybridization signal, and a replicated locus is characterized by a doublet hybridization signal. The percentage of doublets is used as a measure of relative time of replication in S phase. The results show that the FMR1 gene replicates relatively later in fragile X(fraX) males with the full mutation than in normal males, irrespective of the probe used. The F8C locus is late replicating in both normal and fraX males and replicates at nearly the same time on active and inactive X in females. The XIST locus replicates late in all the males studied and asynchronously in female cells. From the late replication of the locus on the active X in males, the authors deduce that the locus on the active X is the later replicating locus in female cells. They conclude that (1) the expansion of the FMR1 locus leads to late replication, (2) silence of the XIST gene in males is associated with late replication of the locus, and (3) this assay will be useful for further studies of the relationship between transcription and replication. 32 refs., 2 figs., 5 tabs.« less

The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation.

PubMed

Arbona, Jean-Michel; Goldar, Arach; Hyrien, Olivier; Arneodo, Alain; Audit, Benjamin

2018-06-01

The time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris . We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics. © 2018, Arbona et al.

Similarity in replication timing between polytene and diploid cells is associated with the organization of the Drosophila genome

PubMed Central

Goncharov, Fedor P.; Zhimulev, Igor F.

2018-01-01

Morphologically, polytene chromosomes of Drosophila melanogaster consist of compact “black” bands alternating with less compact “grey” bands and interbands. We developed a comprehensive approach that combines cytological mapping data of FlyBase-annotated genes and novel tools for predicting cytogenetic features of chromosomes on the basis of their protein composition and determined the genomic coordinates for all black bands of polytene chromosome 2R. By a PCNA immunostaining assay, we obtained the replication timetable for all the bands mapped. The results allowed us to compare replication timing between polytene chromosomes in salivary glands and chromosomes from cultured diploid cell lines and to observe a substantial similarity in the global replication patterns at the band resolution level. In both kinds of chromosomes, the intervals between black bands correspond to early replication initiation zones. Black bands are depleted of replication initiation events and are characterized by a gradient of replication timing; therefore, the time of replication completion correlates with the band length. The bands are characterized by low gene density, contain predominantly tissue-specific genes, and are represented by silent chromatin types in various tissues. The borders of black bands correspond well to the borders of topological domains as well as to the borders of the zones showing H3K27me3, SUUR, and LAMIN enrichment. In conclusion, the characteristic pattern of polytene chromosomes reflects partitioning of the Drosophila genome into two global types of domains with contrasting properties. This partitioning is conserved in different tissues and determines replication timing in Drosophila. PMID:29659604

Selfish cells in altruistic cell society - a theoretical oncology.

PubMed

Chigira, M

1993-09-01

In multicellular organisms, internal evolution of individual cells is strictly forbidden and 'evolutional' DNA replication should be performed only by the sexual reproduction system. Wholistic negative control system called 'homeostasis' serves all service to germ line cells. All somatic cells are altruistic to the germ line cells. However, in malignant tumors, it seems that individual cells replicate and behave 'selfishly' and evolve against the internal microenvironment. Tumor cells only express the occult selfishness which is programmed in normal cells a priori. This phenomenon is based on the failure of identical DNA replication, and results in 'autonomy' and 'anomie' of cellular society as shown in tumor cells. Genetic programs of normal cells connote this cellular autonomy and anomie introduced by the deletion of regulators on structure genes. It is rather paradoxical that the somatic cells get their freedom from wholistic negative regulation programmed internally. However, this is not a true paradox, since multicellular organisms have clearly been evolved from 'monads' in which cells proliferate without wholistic regulation. Somatic cells revolt against germ cell DNA, called 'selfish replicator' by Dawkins. It is an inevitable destiny that the 'selfishness' coded in genome should be revenged by itself. Selfish replicator in germ cell line should be revolted by its selfishness in the expansion of somatic cells, since they have an orthogenesis to get more selfishness in order to increase their genome. Tumor heterogeneity and progression can be fully explained by this self-contradictory process which produces heterogeneous gene copies different from the original clone in the tumor, although 'selfish' gene replication is the final target of being. Furthermore, we have to discard the concept of clonality of tumor cells since genetic instability is a fundamental feature of tumors. Finally, tumor cells and proto-oncogenes can be considered as the ultimate parasite to germ line cells.

Algorithm-Based Fault Tolerance Integrated with Replication

NASA Technical Reports Server (NTRS)

Some, Raphael; Rennels, David

2008-01-01

In a proposed approach to programming and utilization of commercial off-the-shelf computing equipment, a combination of algorithm-based fault tolerance (ABFT) and replication would be utilized to obtain high degrees of fault tolerance without incurring excessive costs. The basic idea of the proposed approach is to integrate ABFT with replication such that the algorithmic portions of computations would be protected by ABFT, and the logical portions by replication. ABFT is an extremely efficient, inexpensive, high-coverage technique for detecting and mitigating faults in computer systems used for algorithmic computations, but does not protect against errors in logical operations surrounding algorithms.

Time-temperature-stress capabilities of composite materials for advanced supersonic technology application, phase 1

NASA Technical Reports Server (NTRS)

Kerr, J. R.; Haskins, J. F.

1980-01-01

Implementation of metal and resin matrix composites into supersonic vehicle usage is contingent upon accelerating the demonstration of service capacity and design technology. Because of the added material complexity and lack of extensive service data, laboratory replication of the flight service will provide the most rapid method of documenting the airworthiness of advanced composite systems. A program in progress to determine the time temperature stress capabilities of several high temperature composite materials includes thermal aging, environmental aging, fatigue, creep, fracture, and tensile tests as well as real time flight simulation exposure. The program has two parts. The first includes all the material property determinations and aging and simulation exposures up through 10,000 hours. The second continues these tests up to 50,000 cumulative hours. Results are presented of the 10,000 hour phase, which has now been completed.

The dynamics of genome replication using deep sequencing

PubMed Central

Müller, Carolin A.; Hawkins, Michelle; Retkute, Renata; Malla, Sunir; Wilson, Ray; Blythe, Martin J.; Nakato, Ryuichiro; Komata, Makiko; Shirahige, Katsuhiko; de Moura, Alessandro P.S.; Nieduszynski, Conrad A.

2014-01-01

Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number during a synchronous S-phase allowed the precise determination of genome replication. To map origin locations, replication forks were stalled close to their initiation sites; therefore, copy number enrichment was limited to origins. Replication timing profiles were generated from asynchronous cultures using fluorescence-activated cell sorting. Applying this technique we show that the replication profiles of haploid and diploid cells are indistinguishable, indicating that both cell types use the same cohort of origins with the same activities. Finally, increasing sequencing depth allowed the direct measure of replication dynamics from an exponentially growing culture. This is the first time this approach, called marker frequency analysis, has been successfully applied to a eukaryote. These data provide a high-resolution resource and methodological framework for studying genome biology. PMID:24089142

Research with Large Area Imaging X-Ray Telescope Sounding Rocket Program

NASA Technical Reports Server (NTRS)

Gorenstein, Paul

1999-01-01

We are engaged in a program to develop focussing hard X-ray telescopes in a double conical or Wolter 1 geometry that function up to 100 keV by employing small graze angles and multilayer coatings. Directly polished substrates are not an option because they are too thick to be nested efficiently. The only alternative is to fabricate the very thin substrates by replication. Our objective is the production of integral cylindrical substrates because they should result in better angular resolution than segmented foil geometries. In addition, integral cylinders would be more resistant to possible stress from deep multilayer coatings than segmented ones. Both electroforming of nickel (method of SkX, JET-X, and XMM) and epoxy replication are under consideration. Both processes can utilize the same types of mandrels and separation agents- While electroforming can produce substrates that are thin, the high density of the nickel may result in high weight optics for some missions. For convenience, experimentation with replication and coating is being carried out initially on flats. Our replication studies include trials with gold and carbon separation agents. This paper reports on our efforts with epoxy replicated optics.

NAC/NINE Program Building Radio Jove's and Brining Radio Astronomy to the Community

NASA Astrophysics Data System (ADS)

Ramona Gallego, Angelina; Paul Gueye, Al Amin Kabir,

2018-01-01

During the course of the 8-week program, (NINE, National and International Non-Traditional Exchange Program), the summer was spent in Socorro, New Mexico, working on building a Radio Jove, and making observations with the Radio Jove as well as working on learning project management practices in order to take the CAPM PMI Exam. The NINE built the Radio Jove’s at the same time and in doing so learned to replicate it to teach it to others. The final portion of the program that was worked on was to create a NINE hub and do outreach with the community teaching them about radio astronomy and teaching students how to build their own Radio Jove’s and make observations. An important aspect of the summer program was to bring back the knowledge received about radio astronomy and teach it to high school students with the help of the institution each NINE participants came from.

Improving health aid for a better planet: The planning, monitoring and evaluation tool (PLANET)

PubMed Central

Sridhar, Devi; Car, Josip; Chopra, Mickey; Campbell, Harry; Woods, Ngaire; Rudan, Igor

2015-01-01

Background International development assistance for health (DAH) quadrupled between 1990 and 2012, from US$ 5.6 billion to US$ 28.1 billion. This generates an increasing need for transparent and replicable tools that could be used to set investment priorities, monitor the distribution of funding in real time, and evaluate the impact of those investments. Methods In this paper we present a methodology that addresses these three challenges. We call this approach PLANET, which stands for planning, monitoring and evaluation tool. Fundamentally, PLANET is based on crowdsourcing approach to obtaining information relevant to deployment of large–scale programs. Information is contributed in real time by a diverse group of participants involved in the program delivery. Findings PLANET relies on real–time information from three levels of participants in large–scale programs: funders, managers and recipients. At each level, information is solicited to assess five key risks that are most relevant to each level of operations. The risks at the level of funders involve systematic neglect of certain areas, focus on donor’s interests over that of program recipients, ineffective co–ordination between donors, questionable mechanisms of delivery and excessive loss of funding to “middle men”. At the level of managers, the risks are corruption, lack of capacity and/or competence, lack of information and /or communication, undue avoidance of governmental structures / preference to non–governmental organizations and exclusion of local expertise. At the level of primary recipients, the risks are corruption, parallel operations / “verticalization”, misalignment with local priorities and lack of community involvement, issues with ethics, equity and/or acceptability, and low likelihood of sustainability beyond the end of the program’s implementation. Interpretation PLANET is intended as an additional tool available to policy–makers to prioritize, monitor and evaluate large–scale development programs. In this, it should complement tools such as LiST (for health care/interventions), EQUIST (for health care/interventions) and CHNRI (for health research), which also rely on information from local experts and on local context to set priorities in a transparent, user–friendly, replicable, quantifiable and specific, algorithmic–like manner. PMID:26322228

Colloquium: Toward living matter with colloidal particles

NASA Astrophysics Data System (ADS)

Zeravcic, Zorana; Manoharan, Vinothan N.; Brenner, Michael P.

2017-07-01

A fundamental unsolved problem is to understand the differences between inanimate matter and living matter. Although this question might be framed as philosophical, there are many fundamental and practical reasons to pursue the development of synthetic materials with the properties of living ones. There are three fundamental properties of living materials that we seek to reproduce: The ability to spontaneously assemble complex structures, the ability to self-replicate, and the ability to perform complex and coordinated reactions that enable transformations impossible to realize if a single structure acted alone. The conditions that are required for a synthetic material to have these properties are currently unknown. This Colloquium examines whether these phenomena could emerge by programming interactions between colloidal particles, an approach that bootstraps off of recent advances in DNA nanotechnology and in the mathematics of sphere packings. The argument is made that the essential properties of living matter could emerge from colloidal interactions that are specific—so that each particle can be programmed to bind or not bind to any other particle—and also time dependent—so that the binding strength between two particles could increase or decrease in time at a controlled rate. There is a small regime of interaction parameters that gives rise to colloidal particles with lifelike properties, including self-assembly, self-replication, and metabolism. The parameter range for these phenomena can be identified using a combinatorial search over the set of known sphere packings.

Genome complexity, robustness and genetic interactions in digital organisms

NASA Astrophysics Data System (ADS)

Lenski, Richard E.; Ofria, Charles; Collier, Travis C.; Adami, Christoph

1999-08-01

Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined `metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

Genome complexity, robustness and genetic interactions in digital organisms.

PubMed

Lenski, R E; Ofria, C; Collier, T C; Adami, C

1999-08-12

Digital organisms are computer programs that self-replicate, mutate and adapt by natural selection. They offer an opportunity to test generalizations about living systems that may extend beyond the organic life that biologists usually study. Here we have generated two classes of digital organism: simple programs selected solely for rapid replication, and complex programs selected to perform mathematical operations that accelerate replication through a set of defined 'metabolic' rewards. To examine the differences in their genetic architecture, we introduced millions of single and multiple mutations into each organism and measured the effects on the organism's fitness. The complex organisms are more robust than the simple ones with respect to the average effects of single mutations. Interactions among mutations are common and usually yield higher fitness than predicted from the component mutations assuming multiplicative effects; such interactions are especially important in the complex organisms. Frequent interactions among mutations have also been seen in bacteria, fungi and fruitflies. Our findings support the view that interactions are a general feature of genetic systems.

Sampling design trade-offs in occupancy studies with imperfect detection: examples and software

USGS Publications Warehouse

Bailey, L.L.; Hines, J.E.; Nichols, J.D.

2007-01-01

Researchers have used occupancy, or probability of occupancy, as a response or state variable in a variety of studies (e.g., habitat modeling), and occupancy is increasingly favored by numerous state, federal, and international agencies engaged in monitoring programs. Recent advances in estimation methods have emphasized that reliable inferences can be made from these types of studies if detection and occupancy probabilities are simultaneously estimated. The need for temporal replication at sampled sites to estimate detection probability creates a trade-off between spatial replication (number of sample sites distributed within the area of interest/inference) and temporal replication (number of repeated surveys at each site). Here, we discuss a suite of questions commonly encountered during the design phase of occupancy studies, and we describe software (program GENPRES) developed to allow investigators to easily explore design trade-offs focused on particularities of their study system and sampling limitations. We illustrate the utility of program GENPRES using an amphibian example from Greater Yellowstone National Park, USA.

Lessons learned from the implementation of a time-limited, large-scale nicotine replacement therapy giveaway program in New York City.

PubMed

Davis, Karen A; Coady, Micaela H; Mbamalu, Ijeoma G; Sacks, Rachel; Kilgore, Elizabeth A

2013-09-01

Since 2006, the New York City (NYC) Department of Health and Mental Hygiene has conducted the Nicotine Patch and Gum Program (NPGP) in collaboration with 311, NYC's non-emergency information line. In two prior years, the program was conducted in collaboration with the New York State (NYS) Smokers' Quitline and with community-based organizations. The NPGP is an annual, brief, population-based nicotine replacement therapy (NRT) giveaway for NYC residents, complementing the NYS Quitline's year-round NRT distribution program. Since 2006, 168,000 smokers have enrolled, with the largest number of enrollees in 2010 (n = 40,000) and the smallest number in 2009 (n = 28,000). A 2003 program evaluation demonstrated that smokers who received NRT through the NPGP had higher quit rates than smokers who did not receive NRT; these results were replicated in 2006 and 2008. Lessons learned from implementing the NPGP include: 1) time-limited NRT interventions are important complements to year-round NRT distribution; 2) expanding NRT distribution to light smokers increases treatment reach; and 3) employing multiple enrollment mechanisms, including telephone and online options, extends program reach to diverse groups of smokers. The NPGP provides a model for other jurisdictions considering implementing time-limited, population-based NRT programs as a complementary strategy to enhance ongoing tobacco control efforts.

Title I, Higher Education Act Program Abstracts.

ERIC Educational Resources Information Center

Miller, Lorna M., Ed.

The 1979 edition of the Title I, Higher Education Act Program Abstracts is presented. Directed toward state Title I, HEA administrators, the program abstracts are made available in order to encourage nationwide program replication of those tested and evaluated programs that have been conducted with Title I support by institutions of higher…

Evidence for a Dual Antiviral Role of the Major Nuclear Domain 10 Component Sp100 during the Immediate-Early and Late Phases of the Human Cytomegalovirus Replication Cycle ▿

PubMed Central

Tavalai, Nina; Adler, Martina; Scherer, Myriam; Riedl, Yvonne; Stamminger, Thomas

2011-01-01

In recent studies, the nuclear domain 10 (ND10) components PML and hDaxx were identified as cellular restriction factors that inhibit the initiation of human cytomegalovirus (HCMV) replication. The antiviral function of ND10, however, is antagonized by the IE1 protein, which induces ND10 disruption. Here we show that IE1 not only de-SUMOylates PML immediately upon infection but also directly targets Sp100. IE1 expression alone was sufficient to downregulate endogenous Sp100 independently of the presence of PML. Moreover, cotransfection experiments revealed that IE1 negatively interferes with the SUMOylation of all Sp100 isoforms. The modulation of Sp100 at immediate-early (IE) times of infection, indeed, seemed to have an in vivo relevance for HCMV replication, since knockdown of Sp100 resulted in more cells initiating the viral gene expression program. In addition, we observed that Sp100 was degraded in a proteasome-dependent manner at late times postinfection, suggesting that Sp100 may play an additional antiviral role during the late phase. Infection experiments conducted with Sp100 knockdown human foreskin fibroblasts (HFFs) confirmed this hypothesis: depletion of Sp100 resulted in augmented release of progeny virus particles compared to that from control cells. Consistent with this observation, we noted increased amounts of viral late gene products in the absence of Sp100. Importantly, this elevated late gene expression was not dependent on enhanced viral IE gene expression. Taken together, our data provide evidence that Sp100 is the first ND10-related factor identified that not only possesses the potential to restrict the initial stage of infection but also inhibits HCMV replication during the late phase. PMID:21734036

Space Optic Manufacturing - X-ray Mirror

NASA Technical Reports Server (NTRS)

1998-01-01

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery and materials to replicate electro-formed nickel mirrors. The process allows fabricating precisely shaped mandrels to be used and reused as masters for replicating high-quality mirrors. This image shows a lightweight replicated x-ray mirror with gold coatings applied.

Space Science

NASA Image and Video Library

1998-08-31

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery and materials to replicate electro-formed nickel mirrors. The process allows fabricating precisely shaped mandrels to be used and reused as masters for replicating high-quality mirrors. This image shows a lightweight replicated x-ray mirror with gold coatings applied.

Space Science

NASA Image and Video Library

1999-04-01

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies to the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. The process allows fabricating precisely shaped mandrels to be used and reused as masters for replicating high-quality mirrors. Photograph shows J.R. Griffith inspecting a replicated x-ray mirror mandrel.

Self-replicating systems: A systems engineering approach

NASA Technical Reports Server (NTRS)

Vontiesenhausen, G.; Darbro, W. A.

1980-01-01

A first approach to conceptualize self-replicating systems was developed from past and present abstract theories. The engineering elements of self-replicating systems are defined in terms of a basic reference system. A number of options are investigated. The growth characteristics and their problems are analyzed, the mathematics of various exponential growth options are outlined, and the problems of universal parts production and systems closure are discussed. Selected areas of further study are defined and a 20 year development and demonstration program is presented.

The impact of worksite wellness in a small business setting.

PubMed

Merrill, Ray M; Aldana, Steven G; Vyhlidal, Tonya P; Howe, Greg; Anderson, David R; Whitmer, R William

2011-02-01

This study evaluates the level of participation and effectiveness of a worksite wellness program in a small business setting. Three years of wellness participation and risk data from Lincoln Industries was analyzed. All Lincoln Industry employees participated in at least some level of wellness programming. Significant improvements in body fat, blood pressure, and flexibility were observed across time. The largest improvements in risk were seen among older employees and those with the highest baseline values. This small business was able to improve the health of the entire workforce population by integrating wellness deeply into their culture and operations. Replication of this program in other small business settings could have a large impact on public health since 60 million adults in the United States work in small businesses.

A role for the replication proteins PCNA, RF-C, polymerase epsilon and Cdc45 in transcriptional silencing in Saccharomyces cerevisiae.

PubMed Central

Ehrenhofer-Murray, A E; Kamakaka, R T; Rine, J

1999-01-01

Transcriptional silencing in the budding yeast Saccharomyces cerevisiae may be linked to DNA replication and cell cycle progression. In this study, we have surveyed the effect of 41 mutations in genes with a role in replication, the cell cycle, and DNA repair on silencing at HMR. Mutations in PCNA (POL30), RF-C (CDC44), polymerase epsilon (POL2, DPB2, DPB11), and CDC45 were found to restore silencing at a mutant HMR silencer allele that was still a chromosomal origin of replication. Replication timing experiments indicated that the mutant HMR locus was replicated late in S-phase, at the same time as wild-type HMR. Restoration of silencing by PCNA and CDC45 mutations required the origin recognition complex binding site of the HMR-E silencer. Several models for the precise role of these replication proteins in silencing are discussed. PMID:10545450

Trajectory of Externalizing Child Behaviors in a KEEP Replication

ERIC Educational Resources Information Center

Uretsky, Mathew C.; Lee, Bethany R.; Greeno, Elizabeth J.; Barth, Richard P.

2017-01-01

Objective: The purpose of this study is to examine the correlates of child behavior change over time in a replication of the KEEP intervention. Method: The study sample was drawn from the treatment group of the Maryland replication of KEEP (n=65). Change over time was analyzed using multilevel linear mixed modeling. Results: Parents' use of…

The effects of gardening on quality of life in people with stroke.

PubMed

Ho, Sui-Hua; Lin, Chiuhsiang Joe; Kuo, Fen-Ling

2016-06-27

Compared with traditional rehabilitation, gardening has been viewed as a more occupation-based intervention to help patients improve functional performance. However, there is still a need for evidence-based research into what factors interact to create the beneficial effects of gardening for people who have sustained a cerebral vascular accident (CVA). To explore how plant, gender, and the time after stroke onset influenced improvements in the quality of life of patients in a gardening program. One treatment of tending short-term plants, and another treatment of tending long-term plants were compared. Quality of life improvement was evaluated according to three factors: plant, gender, and the time after stroke onset. The data were analyzed with 2k replicated factorial designs. The 2k factorial design with replication indicated significant effects on both the social role and the family role. For the social role, the interaction of plant and gender difference was significant. For the family role, the significant effects were found on interaction of plant with both gender and the time after stroke onset. Tending plants with different life cycles has varied effects on the quality of life of people who have sustained a CVA. Factors related to gender and the time after stroke onset influenced role competency in this sample.

From egg to gastrula: How the cell cycle is remodeled during the Drosophila mid-blastula transition

PubMed Central

Farrell, Jeffrey A.; O’Farrell, Patrick H.

2015-01-01

Many, if not most, embryos begin development with extremely short cell cycles that exhibit unusually rapid DNA replication and no gap phases. The commitment to the cell cycle in the early embryo appears to preclude many other cellular processes which only emerge as the cell cycle slows, at a major embryonic transition known as the mid-blastula transition (MBT) just prior to gastrulation. As reviewed here, genetic and molecular studies in Drosophila have identified changes that extend S phase and introduce a post-replicative gap phase, G2, to slow the cell cycle. While many mysteries remain about the upstream regulators of these changes, we review the core mechanisms of the change in cell cycle regulation and discuss advances in our understanding of how these might be timed and triggered. Finally, we consider how the elements of this program may be conserved or changed in other organisms. PMID:25195504

Repliscan: a tool for classifying replication timing regions.

PubMed

Zynda, Gregory J; Song, Jawon; Concia, Lorenzo; Wear, Emily E; Hanley-Bowdoin, Linda; Thompson, William F; Vaughn, Matthew W

2017-08-07

Replication timing experiments that use label incorporation and high throughput sequencing produce peaked data similar to ChIP-Seq experiments. However, the differences in experimental design, coverage density, and possible results make traditional ChIP-Seq analysis methods inappropriate for use with replication timing. To accurately detect and classify regions of replication across the genome, we present Repliscan. Repliscan robustly normalizes, automatically removes outlying and uninformative data points, and classifies Repli-seq signals into discrete combinations of replication signatures. The quality control steps and self-fitting methods make Repliscan generally applicable and more robust than previous methods that classify regions based on thresholds. Repliscan is simple and effective to use on organisms with different genome sizes. Even with analysis window sizes as small as 1 kilobase, reliable profiles can be generated with as little as 2.4x coverage.

Evaluation of a Worksite Diabetes Education Program at a Large Urban Medical Center.

PubMed

Renda, Susan; Baernholdt, Marianne; Becker, Kathleen

2016-01-01

Evidence suggests that diabetes education can be delivered at the worksite to better support employees' diabetes self-management and improve productivity and health care costs. This study was conducted to address the feasibility of a diabetes worksite education program for employees at a large urban academic health care institution. The diabetes education program was delivered in the diabetes center at the institution, a resource that was previously underutilized by employees. Through collaboration with groups in the institution, 20 employees of diverse ethnicity participated in the worksite diabetes education program with positive outcomes: improved glycemic control measured (HbA1c), attainment of self-management goals, and satisfaction with the program. Work absences trended downward, but numbers of hospitalizations and emergency department visits were unchanged in the 3 months following education. Recommendations include replication of the study with more employee participation and program evaluation over a longer period of time to continue assessment of employees' educational needs. © 2015 The Author(s).

Adult Literacy: Industry-Based Training Programs. Research and Development Series No. 265C.

ERIC Educational Resources Information Center

Fields, Ernest L.; And Others

Nine industry-based adult literacy programs across the country were studied to identify exemplary training programs and practices that business and industry trainers, planners, and policymakers and individuals in the public education sector alike could replicate in designing adult literacy programs. Training programs offered by the following…

Measles virus: Background and oncolytic virotherapy.

PubMed

Bhattacharjee, Sankhajit; Yadava, Pramod Kumar

2018-03-01

Measles is a highly transmissible disease caused by measles virus and remains a major cause of child mortality in developing countries. Measles virus nucleoprotein (N) encapsidates the RNA genome of the virus for providing protection from host cell endonucleases and for specific recognition of viral RNA as template for transcription and replication. This protein is over-expressed at the time of viral replication. The C-terminal of N protein is intrinsically disordered, which enables this protein to interact with several host cell proteins. It was previously proved in our laboratory that N expressing human cancerous cells undergo programmed cell death because of reactive oxygen species (ROS) generation as well as Caspase 3 activation. The phosphoprotein (P) along with N protein enclosed viral genomic RNA forming a ribonucleoprotein complex (RNP). It also establishes interaction with the large protein (L) i.e. viral RNA dependent RNA polymerase to ensure viral replication within host cells. The host cell receptors of this virus are CD46, SLAM/CD150 and PVRL4. Measles virus is latently oncotropic in nature and possesses oncolytic property by syncytia formation. We try to highlight the application of this property in developing a virotherapeutic vehicle.

RENP Replication Unlikely Without Federal Support. Technical Appendices Supporting RMC Report UR 327.

ERIC Educational Resources Information Center

Errecart, Michael T.

The Response to Educational Needs Project (RENP) focuses on training teachers as a vehicle for promoting student achievement in a compensatory education program. This document supplements a report on RENP replication and provides information on cost analysis, methodology, and sample and data collection. In Appendix A the following questions are…

"Project ALERT's" Effects on Adolescents' Prodrug Beliefs: A Replication and Extension Study

ERIC Educational Resources Information Center

Clark, Heddy Kovach; Ringwalt, Chris L.; Hanley, Sean; Shamblen, Stephen R.

2010-01-01

This article represents a replication and extension of previous studies of the effects of "Project ALERT", a school-based substance use prevention program, on the prodrug beliefs of adolescents. Specifically, the authors' research examined "Project ALERT's" effects on adolescents' intentions to use substances in the future, beliefs about substance…

Computer Virus Protection

ERIC Educational Resources Information Center

Rajala, Judith B.

2004-01-01

A computer virus is a program--a piece of executable code--that has the unique ability to replicate. Like biological viruses, computer viruses can spread quickly and are often difficult to eradicate. They can attach themselves to just about any type of file, and are spread by replicating and being sent from one individual to another. Simply having…

Sexual Harassment in a New Jersey High School: A Replication Study.

ERIC Educational Resources Information Center

New Jersey Equity Research Bulletin, 1995

1995-01-01

Confronted with the problem of sexual harassment, a public high school in New Jersey implemented an awareness program. To document the extent of sexual harassment, the administration arranged for the Career Equity and Assistance Center for Research and Evaluation at Montclair State University to conduct a replication of the American Association of…

Interdisciplinary treatment of diabetes mellitus in a military treatment facility.

PubMed

Earles, J E; Hartung, G H; Dickert, J M; Moriyama, H H; Coll, K J; Aiello, L M; Jackson, R; Polonsky, W

2001-10-01

The American Diabetes Association emphasizes interdisciplinary management as the standard of care for patients with diabetes. Many times, however, interdisciplinary means various health care professionals treating a patient but not necessarily interacting with each other regarding the patient's care. Recently, Tripler Army Medical Center replicated the Joslin Diabetes Center's diabetes outpatient intensive treatment program as part of a Joslin Diabetes Center/Department of Defense/Veteran's Administration research collaboration. Tripler Army Medical Center named this interdisciplinary program Holopono, which is Hawaiian for success. Holopono is a team of health care professionals providing integrated care and education to a group of diabetes patients over 3.5 days. Individual care management, aided by an Internet-based telemedicine system, then continues for 1 year after entry into the program. This article describes the Holopono program, the role of each team member, and how the team functions together to provide comprehensive diabetes care.

Next generation of preventive interventions.

PubMed

Rotheram-Borus, Mary Jane; Duan, Naihua

2003-05-01

With increasing numbers of efficacious prevention programs, the field needs strategies to disseminate the interventions broadly. The authors examined the life course of prevention programs, identified barriers to dissemination, and outlined an alternative dissemination model. Private enterprise models of product development can be viable strategies for increasing the dissemination of the intervention to the general public. Market principles suggest that the next generation of interventions would be facilitated if interventions are initiated by teams committed to a specific problem and investigators receive training in management; if the acceptability of the program's design features to consumers, providers, and funding agencies is established prior to the development and evaluation of the program; if data from national marketing surveys are used to tailor intervention designs and delivery formats for different subgroups; if essential ingredients of the intervention are identified to facilitate adaptation of the program; if the program is implemented with a goal to maintain change over extended periods of time; if the implementation plan includes program evolution over time, rather than replication with fidelity; and if interventions are branded and certified by a credible agency. Private enterprise models may be useful; however, investigators are likely to be resistant given a priori biases, potential ethical conflicts of interest, and the challenges presented by new technologies (e.g., the Internet and Human Genome Project).

De novo identification of replication-timing domains in the human genome by deep learning.

PubMed

Liu, Feng; Ren, Chao; Li, Hao; Zhou, Pingkun; Bo, Xiaochen; Shu, Wenjie

2016-03-01

The de novo identification of the initiation and termination zones-regions that replicate earlier or later than their upstream and downstream neighbours, respectively-remains a key challenge in DNA replication. Building on advances in deep learning, we developed a novel hybrid architecture combining a pre-trained, deep neural network and a hidden Markov model (DNN-HMM) for the de novo identification of replication domains using replication timing profiles. Our results demonstrate that DNN-HMM can significantly outperform strong, discriminatively trained Gaussian mixture model-HMM (GMM-HMM) systems and other six reported methods that can be applied to this challenge. We applied our trained DNN-HMM to identify distinct replication domain types, namely the early replication domain (ERD), the down transition zone (DTZ), the late replication domain (LRD) and the up transition zone (UTZ), using newly replicated DNA sequencing (Repli-Seq) data across 15 human cells. A subsequent integrative analysis revealed that these replication domains harbour unique genomic and epigenetic patterns, transcriptional activity and higher-order chromosomal structure. Our findings support the 'replication-domain' model, which states (1) that ERDs and LRDs, connected by UTZs and DTZs, are spatially compartmentalized structural and functional units of higher-order chromosomal structure, (2) that the adjacent DTZ-UTZ pairs form chromatin loops and (3) that intra-interactions within ERDs and LRDs tend to be short-range and long-range, respectively. Our model reveals an important chromatin organizational principle of the human genome and represents a critical step towards understanding the mechanisms regulating replication timing. Our DNN-HMM method and three additional algorithms can be freely accessed at https://github.com/wenjiegroup/DNN-HMM The replication domain regions identified in this study are available in GEO under the accession ID GSE53984. shuwj@bmi.ac.cn or boxc@bmi.ac.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Catholic Teacher Recruitment and Formation. Conversations in Excellence, 2001.

ERIC Educational Resources Information Center

Cimino, Carol, Ed.; Haney, Regina M., Ed.; O'Keefe, Joseph M., Ed.

This collection of papers highlights worthy Catholic education programs for replication. "About SPICE" (Carol Cimino, Regina Haney, and Joseph O'Keefe), describes the work of Selected Programs for Improving Catholic Education, noting its recent emphasis on recruitment and retention. "Model Programs" (Carol Cimino), describes the 13 programs chosen…

FISH-detected delay in replication timing of mutated FMR1 alleles on both active and inactive X-chromosomes.

PubMed

Yeshaya, J; Shalgi, R; Shohat, M; Avivi, L

1999-01-01

X-chromosome inactivation and the size of the CGG repeat number are assumed to play a role in the clinical, physical, and behavioral phenotype of female carriers of a mutated FMR1 allele. In view of the tight relationship between replication timing and the expression of a given DNA sequence, we have examined the replication timing of FMR1 alleles on active and inactive X-chromosomes in cell samples (lymphocytes or amniocytes) of 25 females: 17 heterozygous for a mutated FMR1 allele with a trinucleotide repeat number varying from 58 to a few hundred, and eight homozygous for a wild-type allele. We have applied two-color fluorescence in situ hybridization (FISH) with FMR1 and X-chromosome alpha-satellite probes to interphase cells of the various genotypes: the alpha-satellite probe was used to distinguish between early replicating (active) and late replicating (inactive) X-chromosomes, and the FMR1 probe revealed the replication pattern of this locus. All samples, except one with a large trinucleotide expansion, showed an early replicating FMR1 allele on the active X-chromosome and a late replicating allele on the inactive X-chromosome. In samples of mutation carriers, both the early and the late alleles showed delayed replication compared with normal alleles, regardless of repeat size. We conclude therefore that: (1) the FMR1 locus is subjected to X-inactivation; (2) mutated FMR1 alleles, regardless of repeat size, replicate later than wild-type alleles on both the active and inactive X-chromosomes; and (3) the delaying effect of the trinucleotide expansion, even with a low repeat size, is superimposed on the delay in replication associated with X-inactivation.

Grazing Incidence Optics Technology

NASA Technical Reports Server (NTRS)

Ramsey, Brian; Smith, W. Scott; Gubarev, Mikhail; McCracken, Jeff

2015-01-01

This project is to demonstrate the capability to directly fabricate lightweight, high-resolution, grazing-incidence x-ray optics using a commercially available robotic polishing machine. Typical x-ray optics production at NASA Marshall Space Flight Center (MSFC) uses a replication process in which metal mirrors are electroformed on to figured and polished mandrels from which they are later removed. The attraction of this process is that multiple copies can be made from a single master. The drawback is that the replication process limits the angular resolution that can be attained. By directly fabricating each shell, errors inherent in the replication process are removed. The principal challenge now becomes how to support the mirror shell during all aspects of fabrication, including the necessary metrology to converge on the required mirror performance specifications. This program makes use of a Zeeko seven-axis computer-controlled polishing machine (see fig. 1) and supporting fabrication, metrology, and test equipment at MSFC. The overall development plan calls for proof-of-concept demonstration with relatively thick mirror shells (5-6 mm, fig. 2) which are straightforward to support and then a transition to much thinner shells (2-3 mm), which are an order of magnitude thinner than those used for Chandra. Both glass and metal substrates are being investigated. Currently, a thick glass shell is being figured. This has enabled experience to be gained with programming and operating the polishing machine without worrying about shell distortions or breakage. It has also allowed time for more complex support mechanisms for figuring/ polishing and metrology to be designed for the more challenging thinner shells. These are now in fabrication. Figure 1: Zeeko polishing machine.

Secretome Screening Reveals Fibroblast Growth Factors as Novel Inhibitors of Viral Replication.

PubMed

van Asten, Saskia D; Raaben, Matthijs; Nota, Benjamin; Spaapen, Robbert M

2018-06-13

Cellular antiviral programs can efficiently inhibit viral infection. These programs are often initiated through signaling cascades induced by secreted proteins such as type I interferons, IL-6 or TNF-α. Here, we generated an arrayed library of 756 human secreted proteins to perform a secretome screen focused on the discovery of novel modulators of viral entry and/or replication. The individual secreted proteins were tested for their capacity to inhibit infection by two replication-competent recombinant vesicular stomatitis viruses (VSV) with distinct glycoproteins utilizing different entry pathways. Fibroblast growth factor 16 (FGF16) was identified and confirmed as the most prominent novel inhibitor of both VSVs and therefore of viral replication and not entry. Importantly, an antiviral interferon signature was completely absent in FGF16 treated cells. Nevertheless, the antiviral effect of FGF16 is broad as it was evident on multiple cell types and also on infection of Coxsackievirus. In addition, other members of the FGF family also inhibited viral infection. Thus, our unbiased secretome screen revealed a novel protein family capable of inducing a cellular antiviral state. This previously unappreciated role of the FGF family may have implications for the development of new antivirals and the efficacy of oncolytic virus therapy. Importance Viruses infect human cells in order to replicate, while human cells aim to resist infection. Several cellular antiviral programs have therefore evolved to resist infection. Knowledge of these programs is essential for the design of antiviral therapeutics in the future. The induction of antiviral programs is often initiated by secreted proteins such as interferons. We hypothesized that other secreted proteins may also promote resistance to viral infection. Thus we tested 756 human secreted proteins for their capacity to inhibit two pseudotypes of vesicular stomatitis virus (VSV). In this first secretome screen on viral infection we identified fibroblast growth factor 16 (FGF16) as a novel antiviral against multiple VSV pseudotypes as well as Coxsackievirus. Subsequent testing of other FGF family members revealed that FGF signaling generally inhibits viral infection. This finding may lead to the development of new antivirals and may also be applicable to enhance oncolytic virus therapy. Copyright © 2018 American Society for Microbiology.

A study of an adaptive replication framework for orchestrated composite web services.

PubMed

Mohamed, Marwa F; Elyamany, Hany F; Nassar, Hamed M

2013-01-01

Replication is considered one of the most important techniques to improve the Quality of Services (QoS) of published Web Services. It has achieved impressive success in managing resource sharing and usage in order to moderate the energy consumed in IT environments. For a robust and successful replication process, attention should be paid to suitable time as well as the constraints and capabilities in which the process runs. The replication process is time-consuming since outsourcing some new replicas into other hosts is lengthy. Furthermore, nowadays, most of the business processes that might be implemented over the Web are composed of multiple Web services working together in two main styles: Orchestration and Choreography. Accomplishing a replication over such business processes is another challenge due to the complexity and flexibility involved. In this paper, we present an adaptive replication framework for regular and orchestrated composite Web services. The suggested framework includes a number of components for detecting unexpected and unhappy events that might occur when consuming the original published web services including failure or overloading. It also includes a specific replication controller to manage the replication process and select the best host that would encapsulate a new replica. In addition, it includes a component for predicting the incoming load in order to decrease the time needed for outsourcing new replicas, enhancing the performance greatly. A simulation environment has been created to measure the performance of the suggested framework. The results indicate that adaptive replication with prediction scenario is the best option for enhancing the performance of the replication process in an online business environment.

Going Global: A Model for Evaluating Empirically Supported Family-Based Interventions in New Contexts.

PubMed

Sundell, Knut; Ferrer-Wreder, Laura; Fraser, Mark W

2014-06-01

The spread of evidence-based practice throughout the world has resulted in the wide adoption of empirically supported interventions (ESIs) and a growing number of controlled trials of imported and culturally adapted ESIs. This article is informed by outcome research on family-based interventions including programs listed in the American Blueprints Model and Promising Programs. Evidence from these controlled trials is mixed and, because it is comprised of both successful and unsuccessful replications of ESIs, it provides clues for the translation of promising programs in the future. At least four explanations appear plausible for the mixed results in replication trials. One has to do with methodological differences across trials. A second deals with ambiguities in the cultural adaptation process. A third explanation is that ESIs in failed replications have not been adequately implemented. A fourth source of variation derives from unanticipated contextual influences that might affect the effects of ESIs when transported to other cultures and countries. This article describes a model that allows for the differential examination of adaptations of interventions in new cultural contexts. © The Author(s) 2012.

Hard X-Ray and Wide Focusing Telescopes

NASA Technical Reports Server (NTRS)

Gorenstein, Paul

1998-01-01

Studies are being carried out to compare the performance of several different separation materials used in the replication process. This report presents the results obtained during the second year of a program which consists of replicating smooth, thin substrates, depositing multilayer coatings upon them, and evaluating their performance. Replication and multilayer coatings are both critically important to the development of focussing hard X-ray telescopes that function up to 100 keV. The activities of the current year include extending the comparison between sputtered amorphous carbon and evaporated gold to include sputtered as well as evaporated gold. The figure of merit being the smoothness of the replica which has a direct effect on the specular reflectivity. These results were obtained with epoxy replication, but they should be applicable to electroformed nickel, the process we expect to use for the ultimate replicated optics.

The replication domain model: regulating replicon firing in the context of large-scale chromosome architecture.

PubMed

Pope, Benjamin D; Gilbert, David M

2013-11-29

The "Replicon Theory" of Jacob, Brenner, and Cuzin has reliably served as the paradigm for regulating the sites where individual replicons initiate replication. Concurrent with the replicon model was Taylor's demonstration that plant and animal chromosomes replicate segmentally in a defined temporal sequence, via cytologically defined units too large to be accounted for by a single replicon. Instead, there seemed to be a program to choreograph when chromosome units replicate during S phase, executed by initiation at clusters of individual replicons within each segment. Here, we summarize recent molecular evidence for the existence of such units, now known as "replication domains", and discuss how the organization of large chromosomes into structural units has added additional layers of regulation to the original replicon model. Copyright © 2012 Elsevier Ltd. All rights reserved.

How Do Implementation Efforts Relate to Program Adherence? Examining the Role of Organizational, Implementer, and Program Factors

ERIC Educational Resources Information Center

Dariotis, Jacinda K.; Bumbarger, Brian K.; Duncan, Larissa G.; Greenberg, Mark T.

2008-01-01

Widespread replications of evidence-based prevention programs (EBPPs) prompt prevention scientists to examine program implementation adherence in real world settings. Based on Chen's model (1990), we identified five key factors of the implementation system and assessed which characteristics related to program adherence. The sample included 32…

Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

PubMed Central

Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

2016-01-01

ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

Teen Outreach: Data from the Second Year of a National Replication.

ERIC Educational Resources Information Center

Philliber, Susan

Teen Outreach is a school-based teenage pregnancy prevention program designed to decrease the incidence of teenage pregnancy and to increase the number of at-risk teenagers who successfully complete their high school education. Begun in 1981 in St. Louis, Missouri, Teen Outreach was implemented as a national replication study in 1983. There are…

The Prevalence and Correlates of Workplace Depression in the National Comorbidity Survey Replication

PubMed Central

Kessler, Ronald C.; Merikangas, Kathleen R.; Wang, Philip S.

2009-01-01

Objective To review evidence on the workplace prevalence and correlates of major depressive episodes, with a particular focus on the National Comorbidity Survey Replication, the most recent national survey to focus on these issues. Method Nationally representative survey of Diagnostic and Statistical Manual, 4th Revision Mental Disorders. Results A total of 6.4% of employed National Comorbidity Survey Replication respondents had 12-month major depressive disorder. An additional 1.1% had major depressive episodes due to bipolar disorder or mania– hypomania. Only about half of depressed workers received treatment. Fewer than half of treated workers received care consistent with published treatment guidelines. Conclusions Depression disease management programs can have a positive return-on-investment from the employer perspective, but only when they are based on best practices. Given the generally low depression treatment quality documented here, treatment quality guarantees are needed before expanding workplace depression screening, outreach, and treatment programs. PMID:18404010

Replicated x-ray optics for space applications

NASA Astrophysics Data System (ADS)

Hudec, René; Pína, Ladislav; Inneman, Adolf

2017-11-01

We report on the program of design and development of X-ray optics for space applications in the Czech Republic. Having more than 30 years background in X-ray optics development for space applications (for use in astronomical X-ray telescopes onboard spacecrafts, before 1989 mostly for Soviet and East European INTERKOSMOS program), we focus nowadays on novel technologies and approaches, thin shell replicated mirrors, as well as studies of light-weight mirrors based on innovative materials such as ceramics. The collaboration includes teams from the Academy of Sciences, Universities, and industry. We will describe and discuss both the history of the development of Xray optics in the Czech Republic and the developed technologies and approaches (with focus on replication technology) as well as recent activities and developments including our participation on the ESA XEUS mirror technology development based on the Agreement between ESA and Czech Government.

Dedicated education unit: implementing an innovation in replication sites.

PubMed

Moscato, Susan R; Nishioka, Vicki M; Coe, Michael T

2013-05-01

An important measure of an innovation is the ease of replication and achievement of the same positive outcomes. The dedicated education unit (DEU) clinical education model uses a collaborative academic-service partnership to develop an optimal learning environment for students. The University of Portland adapted this model from Flinders University, Australia, to increase the teaching capacity and quality of nursing education. This article identifies DEU implementation essentials and reports on the outcomes of two replication sites that received consultation support from the University of Portland. Program operation information, including education requirements for clinician instructors, types of patient care units, and clinical faculty-to-student ratios is presented. Case studies of the three programs suggest the DEU model is adaptable to a range of different clinical settings and continues to show promise as one strategy for addressing the nurse faculty shortage and strengthening academic-clinical collaborations while maintaining quality clinical education for students. Copyright 2013, SLACK Incorporated.

Software reliability: Additional investigations into modeling with replicated experiments

NASA Technical Reports Server (NTRS)

Nagel, P. M.; Schotz, F. M.; Skirvan, J. A.

1984-01-01

The effects of programmer experience level, different program usage distributions, and programming languages are explored. All these factors affect performance, and some tentative relational hypotheses are presented. An analytic framework for replicated and non-replicated (traditional) software experiments is presented. A method of obtaining an upper bound on the error rate of the next error is proposed. The method was validated empirically by comparing forecasts with actual data. In all 14 cases the bound exceeded the observed parameter, albeit somewhat conservatively. Two other forecasting methods are proposed and compared to observed results. Although demonstrated relative to this framework that stages are neither independent nor exponentially distributed, empirical estimates show that the exponential assumption is nearly valid for all but the extreme tails of the distribution. Except for the dependence in the stage probabilities, Cox's model approximates to a degree what is being observed.

Creating the Public Connection: Interactive Experiences with Real-Time Earth and Space Science Data

NASA Technical Reports Server (NTRS)

Reiff, Patricia H.; Ledley, Tamara S.; Sumners, Carolyn; Wyatt, Ryan

1995-01-01

The Houston Museum of Natural Sciences is less than two miles from Rice University, a major hub on the Internet. This project links these two institutions so that NASA real-time data and imagery can flow via Rice to the Museum where it reaches the public in the form of planetarium programs, computer based interactive kiosks, and space and Earth science problem solving simulation. Through this program at least 200,000 visitors annually (including every 4th and 7th grader in the Houston Independent School District) will have direct exposure to the Earth and space research being conducted by NASA and available over the Internet. Each information conduit established between Rice University and the Houston Museum of Natural Science will become a model for public information dissemination that can be replicated nationally in museums, planetariums, Challenger Centers, and schools.

Open chromatin encoded in DNA sequence is the signature of ‘master’ replication origins in human cells

PubMed Central

Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain

2009-01-01

For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions ∼300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as ‘master’ replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these ‘master’ origins are likely to play a key role in genome dynamics during evolution and in pathological situations. PMID:19671527

Origin of life in a digital microcosm

NASA Astrophysics Data System (ADS)

C G, Nitash; LaBar, Thomas; Hintze, Arend; Adami, Christoph

2017-11-01

While all organisms on Earth share a common descent, there is no consensus on whether the origin of the ancestral self-replicator was a one-off event or whether it only represented the final survivor of multiple origins. Here, we use the digital evolution system Avida to study the origin of self-replicating computer programs. By using a computational system, we avoid many of the uncertainties inherent in any biochemical system of self-replicators (while running the risk of ignoring a fundamental aspect of biochemistry). We generated the exhaustive set of minimal-genome self-replicators and analysed the network structure of this fitness landscape. We further examined the evolvability of these self-replicators and found that the evolvability of a self-replicator is dependent on its genomic architecture. We also studied the differential ability of replicators to take over the population when competed against each other, akin to a primordial-soup model of biogenesis, and found that the probability of a self-replicator outcompeting the others is not uniform. Instead, progenitor (most-recent common ancestor) genotypes are clustered in a small region of the replicator space. Our results demonstrate how computational systems can be used as test systems for hypotheses concerning the origin of life. This article is part of the themed issue 'Reconceptualizing the origins of life'.

Changes in knowledge, attitudes, and behavior as a result of a community-based AIDS prevention program.

PubMed

Miller, T E; Booraem, C; Flowers, J V; Iversen, A E

1990-01-01

The study evaluates the outcome of a California-based AIDS prevention program, "Stop AIDS." Community discussion groups focusing on information, attitudes, and behavior associated with HIV infection and transmission were conducted in one-time, 3 1/2-hour sessions. Participants completed different versions of the AIDS Prevention Test before and after the discussion group. Significant positive shifts in information, attitudes, and behavior were observed as a function of the discussion group participation. Whereas pretest knowledge correlated with pretest behavior and posttest knowledge, only pretest behavior correlated with the crucial variable of posttest intended behavior. When changes from pretest to posttest were analyzed, both information and attitude change correlated to changes in behavior. The intervention and evaluation procedures are proposed as a replicable national model for community-based AIDS prevention programs.

Morphological, Biochemical, and Functional Study of Viral Replication Compartments Isolated from Adenovirus-Infected Cells

PubMed Central

Hidalgo, Paloma; Anzures, Lourdes; Hernández-Mendoza, Armando; Guerrero, Adán; Wood, Christopher D.; Valdés, Margarita; Dobner, Thomas

2016-01-01

ABSTRACT Adenovirus (Ad) replication compartments (RC) are nuclear microenvironments where the viral genome is replicated and a coordinated program of late gene expression is established. These virus-induced nuclear sites seem to behave as central hubs for the regulation of virus-host cell interactions, since proteins that promote efficient viral replication as well as factors that participate in the antiviral response are coopted and concentrated there. To gain further insight into the activities of viral RC, here we report, for the first time, the morphology, composition, and activities of RC isolated from Ad-infected cells. Morphological analyses of isolated RC particles by superresolution microscopy showed that they were indistinguishable from RC within infected cells and that they displayed a dynamic compartmentalization. Furthermore, the RC-containing fractions (RCf) proved to be functional, as they directed de novo synthesis of viral DNA and RNA as well as RNA splicing, activities that are associated with RC in vivo. A detailed analysis of the production of viral late mRNA from RCf at different times postinfection revealed that viral mRNA splicing occurs in RC and that the synthesis, posttranscriptional processing, and release from RC to the nucleoplasm of individual viral late transcripts are spatiotemporally separate events. The results presented here demonstrate that RCf are a powerful system for detailed study into RC structure, composition, and activities and, as a result, the determination of the molecular mechanisms that induce the formation of these viral sites of adenoviruses and other nuclear-replicating viruses. IMPORTANCE RC may represent molecular hubs where many aspects of virus-host cell interaction are controlled. Here, we show by superresolution microscopy that RCf have morphologies similar to those of RC within Ad-infected cells and that they appear to be compartmentalized, as nucleolin and DBP display different localization in the periphery of these viral sites. RCf proved to be functional, as they direct de novo synthesis of viral DNA and mRNA, allowing the detailed study of the regulation of viral genome replication and expression. Furthermore, we show that the synthesis and splicing of individual viral late mRNA occurs in RC and that they are subject to different temporal patterns of regulation, from their synthesis to their splicing and release from RC to the nucleoplasm. Hence, RCf represent a novel system to study molecular mechanisms that are orchestrated in viral RC to take control of the infected cell and promote an efficient viral replication cycle. PMID:26764008

B-WEST Regional Workforce Training Center. Building Workers Entering Skilled Trades. Program Development Guide.

ERIC Educational Resources Information Center

Portland Community Coll., OR.

This program development guide outlines the procedures for replicating the B-WEST (Building Workers Entering Skilled Trades) program, a two-term professional certificate program designed to prepare women for skilled jobs in the traditionally male-dominated electrical, mechanical, and construction trades. The components and major activities of the…

Very high pressure liquid chromatography using core-shell particles: quantitative analysis of fast gradient separations without post-run times.

PubMed

Stankovich, Joseph J; Gritti, Fabrice; Stevenson, Paul G; Beaver, Lois A; Guiochon, Georges

2014-01-17

Five methods for controlling the mobile phase flow rate for gradient elution analyses using very high pressure liquid chromatography (VHPLC) were tested to determine thermal stability of the column during rapid gradient separations. To obtain rapid separations, instruments are operated at high flow rates and high inlet pressure leading to uneven thermal effects across columns and additional time needed to restore thermal equilibrium between successive analyses. The purpose of this study is to investigate means to minimize thermal instability and obtain reliable results by measuring the reproducibility of the results of six replicate gradient separations of a nine component RPLC standard mixture under various experimental conditions with no post-run times. Gradient separations under different conditions were performed: constant flow rates, two sets of constant pressure operation, programmed flow constant pressure operation, and conditions which theoretically should yield a constant net heat loss at the column's wall. The results show that using constant flow rates, programmed flow constant pressures, and constant heat loss at the column's wall all provide reproducible separations. However, performing separations using a high constant pressure with programmed flow reduces the analysis time by 16% compared to constant flow rate methods. For the constant flow rate, programmed flow constant pressure, and constant wall heat experiments no equilibration time (post-run time) was required to obtain highly reproducible data. Copyright © 2013 Elsevier B.V. All rights reserved.

Low cost management of replicated data in fault-tolerant distributed systems

NASA Technical Reports Server (NTRS)

Joseph, Thomas A.; Birman, Kenneth P.

1990-01-01

Many distributed systems replicate data for fault tolerance or availability. In such systems, a logical update on a data item results in a physical update on a number of copies. The synchronization and communication required to keep the copies of replicated data consistent introduce a delay when operations are performed. A technique is described that relaxes the usual degree of synchronization, permitting replicated data items to be updated concurrently with other operations, while at the same time ensuring that correctness is not violated. The additional concurrency thus obtained results in better response time when performing operations on replicated data. How this technique performs in conjunction with a roll-back and a roll-forward failure recovery mechanism is also discussed.

Replication-associated mutational asymmetry in the human genome.

PubMed

Chen, Chun-Long; Duquenne, Lauranne; Audit, Benjamin; Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Huvet, Maxime; d'Aubenton-Carafa, Yves; Hyrien, Olivier; Arneodo, Alain; Thermes, Claude

2011-08-01

During evolution, mutations occur at rates that can differ between the two DNA strands. In the human genome, nucleotide substitutions occur at different rates on the transcribed and non-transcribed strands that may result from transcription-coupled repair. These mutational asymmetries generate transcription-associated compositional skews. To date, the existence of such asymmetries associated with replication has not yet been established. Here, we compute the nucleotide substitution matrices around replication initiation zones identified as sharp peaks in replication timing profiles and associated with abrupt jumps in the compositional skew profile. We show that the substitution matrices computed in these regions fully explain the jumps in the compositional skew profile when crossing initiation zones. In intergenic regions, we observe mutational asymmetries measured as differences between complementary substitution rates; their sign changes when crossing initiation zones. These mutational asymmetries are unlikely to result from cryptic transcription but can be explained by a model based on replication errors and strand-biased repair. In transcribed regions, mutational asymmetries associated with replication superimpose on the previously described mutational asymmetries associated with transcription. We separate the substitution asymmetries associated with both mechanisms, which allows us to determine for the first time in eukaryotes, the mutational asymmetries associated with replication and to reevaluate those associated with transcription. Replication-associated mutational asymmetry may result from unequal rates of complementary base misincorporation by the DNA polymerases coupled with DNA mismatch repair (MMR) acting with different efficiencies on the leading and lagging strands. Replication, acting in germ line cells during long evolutionary times, contributed equally with transcription to produce the present abrupt jumps in the compositional skew. These results demonstrate that DNA replication is one of the major processes that shape human genome composition.

Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

PubMed

Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

2013-01-01

In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

Choreography of the Mycobacterium Replication Machinery during the Cell Cycle

PubMed Central

Trojanowski, Damian; Ginda, Katarzyna; Pióro, Monika; Hołówka, Joanna; Skut, Partycja; Jakimowicz, Dagmara

2015-01-01

ABSTRACT It has recently been demonstrated that bacterial chromosomes are highly organized, with specific positioning of the replication initiation region. Moreover, the positioning of the replication machinery (replisome) has been shown to be variable and dependent on species-specific cell cycle features. Here, we analyzed replisome positions in Mycobacterium smegmatis, a slow-growing bacterium that exhibits characteristic asymmetric polar cell extension. Time-lapse fluorescence microscopy analyses revealed that the replisome is slightly off-center in mycobacterial cells, a feature that is likely correlated with the asymmetric growth of Mycobacterium cell poles. Estimates of the timing of chromosome replication in relation to the cell cycle, as well as cell division and chromosome segregation events, revealed that chromosomal origin-of-replication (oriC) regions segregate soon after the start of replication. Moreover, our data demonstrate that organization of the chromosome by ParB determines the replisome choreography. PMID:25691599

Synchronous termination of replication of the two chromosomes is an evolutionary selected feature in Vibrionaceae

PubMed Central

Kemter, Franziska S.; Messerschmidt, Sonja J.; Schallopp, Nadine; Sobetzko, Patrick; Bunk, Boyke; Spröer, Cathrin; Teschler, Jennifer K.; Yildiz, Fitnat H.

2018-01-01

Vibrio cholerae, the causative agent of the cholera disease, is commonly used as a model organism for the study of bacteria with multipartite genomes. Its two chromosomes of different sizes initiate their DNA replication at distinct time points in the cell cycle and terminate in synchrony. In this study, the time-delayed start of Chr2 was verified in a synchronized cell population. This replication pattern suggests two possible regulation mechanisms for other Vibrio species with different sized secondary chromosomes: Either all Chr2 start DNA replication with a fixed delay after Chr1 initiation, or the timepoint at which Chr2 initiates varies such that termination of chromosomal replication occurs in synchrony. We investigated these two models and revealed that the two chromosomes of various Vibrionaceae species terminate in synchrony while Chr2-initiation timing relative to Chr1 is variable. Moreover, the sequence and function of the Chr2-triggering crtS site recently discovered in V. cholerae were found to be conserved, explaining the observed timing mechanism. Our results suggest that it is beneficial for bacterial cells with multiple chromosomes to synchronize their replication termination, potentially to optimize chromosome related processes as dimer resolution or segregation. PMID:29505558

A Drop in the Bucket or a Pebble in a Pond: Commercial Building Partners’ Replication of EEMs Across Their Portfolios

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

Antonopoulos, Chrissi A.; Baechler, Michael C.; Dillon, Heather E.

This study presents findings from questionnaire and interview data investigating replication efforts of Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered with 12 organizations on new and retrofit construction projects as part of the U.S. Department of Energy (DOE) CBP program. PNNL and other national laboratories collaborate with industry leaders that own large portfolios of buildings to develop high performance projects for new construction and renovation. This project accelerates market adoption of commercially available energy saving technologies into the design process for new and upgraded commercial buildings. The labs provide assistancemore » to the partners’ design teams and make a business case for energy investments. From the owner’s perspective, a sound investment results in energy savings based on corporate objectives and design. Through a feedback questionnaire, along with personal interviews, PNNL gathered qualitative and quantitative information relating to replication efforts by each organization. Data through this process were analyzed to provide insight into two primary research areas: 1) CBP partners’ replication efforts of technologies and approaches used in the CBP project to the rest of the organization’s building portfolio (including replication verification), and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP entire program.« less

Benthic macrofauna data for San Francisco Bay, California, September 1986

USGS Publications Warehouse

Schemel, Laurence E.; Thompson, J.K.; Harmon, J.G.; Yost, B.T.

1995-01-01

Benthic macrofauna were collected during September 1986 to evaluate locations for long-term monitoring stations as part of the U.S. Geological Survey Regional Effects Monitoring Program in San Francisco Bay, California. Three to ten replicate samples were collected with a modified Van Veen sampler (0.05 m2 area) at ten locations. One box core sample (0.06 m2 area) was collected at seven to the ten locations. Six of the box core samples were split into an upper 10 cm sample and a deeper sample before analysis. Macrofauna specimens were identified to the lowest possible taxon, usually genus and species, then counted. An average of 88 percent of the benthic macrofauna specimens were identified to the species level. The fraction identified varied among stations from 54 to 98 percent. Nematodes and oligochaetes accounted for most of the unidentified specimens. Relative to the total number of species identified in five replicates at each location, an average of 90 percent of the species were collected with three replicates. In general, species with high to moderate abundances were present in all replicates, and species collected only after three or more replicates averaged less than one specimen per replicate. Results from the box cores showed that the dominant species were most abundant in the upper 10 cm, the depth of sediment that can be adequately sampled with a modified Van Veen sampler. On the basis of the number of species and their abundances at each location, seven of the ten locations were selected for sampling in the regular program, which began in March 1987.

Minority Teacher Recruitment and Retention Strategies

ERIC Educational Resources Information Center

Kearney-Gissendaner, Janet E.

2010-01-01

The tools and resources in this book help school leaders seamlessly incorporate minority teacher recruitment and retention programs into current human-resources activities. With details about exemplary minority teacher recruitment and retention programs, this book also showcases strategies for how to replicate such programs in your own school or…

Shell Separation for Mirror Replication

NASA Technical Reports Server (NTRS)

1999-01-01

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. Optics replication uses reusable forms, called mandrels, to make telescope mirrors ready for final finishing. MSFC optical physicist Bill Jones monitors a device used to chill a mandrel, causing it to shrink and separate from the telescope mirror without deforming the mirror's precisely curved surface.

Spatial-pattern-induced evolution of a self-replicating loop network.

PubMed

Suzuki, Keisuke; Ikegami, Takashi

2006-01-01

We study a system of self-replicating loops in which interaction rules between individuals allow competition that leads to the formation of a hypercycle-like network. The main feature of the model is the multiple layers of interaction between loops, which lead to both global spatial patterns and local replication. The network of loops manifests itself as a spiral structure from which new kinds of self-replicating loops emerge at the boundaries between different species. In these regions, larger and more complex self-replicating loops live for longer periods of time, managing to self-replicate in spite of their slower replication. Of particular interest is how micro-scale interactions between replicators lead to macro-scale spatial pattern formation, and how these macro-scale patterns in turn perturb the micro-scale replication dynamics.

NoSQL Data Store Technologies

DTIC Science & Technology

2014-09-01

NoSQL Data Store Technologies John Klein, Software Engineering Institute Patrick Donohoe, Software Engineering Institute Neil Ernst...REPORT TYPE N/A 3. DATES COVERED 4. TITLE AND SUBTITLE NoSQL Data Store Technologies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...distribute data 4. Data Replication – determines how a NoSQL database facilitates reliable, high performance data replication to build

Self-Administered Cued Naming Therapy: A Single-Participant Investigation of a Computer-Based Therapy Program Replicated in Four Cases

ERIC Educational Resources Information Center

Ramsberger, Gail; Marie, Basem

2007-01-01

Purpose: This study examined the benefits of a self-administered, clinician-guided, computer-based, cued naming therapy. Results of intense and nonintense treatment schedules were compared. Method: A single-participant design with multiple baselines across behaviors and varied treatment intensity for 2 trained lists was replicated over 4…

Health Care Merged With Senior Housing: Description and Evaluation of a Successful Program.

PubMed

Barry, Theresa Teta

2017-01-01

Objective: This article describes and evaluates a successful partnership between a large health care organization and housing for seniors. The program provides on-site, primary care visits by a physician and a nurse in addition to intensive social services to residents in an affordable senior housing apartment building located in Pennsylvania. Per Donabedian's "Structure-Process-Outcome" model, the program demonstrated positive health care outcomes for its participants via a prescribed structure. To provide guidance for replication in similar settings, we qualitatively evaluated the processes by which successful outcomes were obtained. Methods: With program structures in place and outcomes measured, this case study collected and analyzed qualitative information taken from key informant interviews on care processes involved in the program. Themes were extracted from semistructured interviews and used to describe the processes that helped and hindered the program. Results and Discussion: Common processes were identified across respondents; however, the nuanced processes that lead to successful outcomes suggest that defined structures and processes may not be sufficient to produce similar outcomes in other settings. Further research is needed to determine the program's replicability and policy implications.

Using Curriculum-Based Measurements for Program Evaluation: Expanding Roles for School Psychologists

ERIC Educational Resources Information Center

Tusing, Mary E.; Breikjern, Nicholle A.

2017-01-01

Educators increasingly need to evaluate schoolwide reform efforts; however, complex program evaluations often are not feasible in schools. Through a case example, we provide a heuristic for program evaluation that is easily replicated in schools. Criterion-referenced interpretations of schoolwide screening data were used to evaluate outcomes…

Eating for Your Eyes

ERIC Educational Resources Information Center

Stastny, Sherri Nordstrom; Garden-Robinson, Julie

2011-01-01

An educational program targeting older adults was developed to increase knowledge regarding nutrition and eye health. With age, the chance for eye disease increases, so prevention is critical. The Eating for Your Eyes program has promoted behavior changes regarding eye health among the participants. This program is easily replicated and use is…

Creatively Financing and Resourcing Catholic Schools: Conversations in Excellence.

ERIC Educational Resources Information Center

Haney, Regina, Ed.; O'Keefe, Joseph, Ed.

Ten exemplary program descriptions arose from the 1998 conference hosted by Selected Programs for Improving Catholic Education (SPICE), an organization created to assist Catholic school leaders to choose and replicate programs that successfully meet the needs of the contemporary Catholic school. Chapter 1 provides an overview of the annual…

Child Services Demonstration Center Evaluation. Summary Report. (ESEA VI-G).

ERIC Educational Resources Information Center

Colorado State Dept. of Education, Denver.

Presented is the final report of Colorado's Child Services Demonstration Project, designed to develop, implement, and evaluate a team staffing program to aid children with specific learning disabilities. The program is described in terms of rationale, replication, children served, staff activities (educational diagnosis, prescriptive programing,…

Proposed Social Spending Innovation Research (SSIR) Program: Harnessing American Entrepreneurial Talent to Solve Major U.S. Social Problems

ERIC Educational Resources Information Center

Coalition for Evidence-Based Policy, 2015

2015-01-01

The Social Spending Innovation Research (SSIR) proposal seeks to replicate, in social spending, the great success of the Small Business Innovation Research (SBIR) program in technology development. The SBIR program funds technology development by entrepreneurial small companies. The program has spawned breakthrough technologies in diverse areas…

The MELD for Young Moms Program: A National Study of Demographics and Program Outcomes.

ERIC Educational Resources Information Center

Treichel, Christa J.

The MELD for Young Moms (MYM) program serves adolescent mothers by providing support and information about parenting in groups that are facilitated by women who were once adolescent mothers themselves. This study focused on gathering two types of information about the nationally replicated MYM program: (1) demographics of parent group facilitators…

Ethnic Heritage Studies Program: Assessment of the First Year, July 1, 1974-June 30, 1975.

ERIC Educational Resources Information Center

National Education Association, Washington, DC.

The report explains how the federal Ethnic Heritage Studies Program was created, gives an overview of the 1974 program, and makes recommendations for future development of the program. Summaries of the 1974 projects, bibliographies of replicable materials produced by the projects, and ethnic and regional indexes are included. The overview…

Multiple determinants controlling activation of yeast replication origins late in S phase.

PubMed

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

Replication fidelity improvement of PMMA microlens array based on weight evaluation and optimization

NASA Astrophysics Data System (ADS)

Jiang, Bing-yan; Shen, Long-jiang; Peng, Hua-jiang; Yin, Xiang-lin

2007-12-01

High replication fidelity is a prerequisite of high quality plastic microlens array in injection molding. But, there's not an economical and practical method to evaluate and improve the replication fidelity until now. Based on part weight evaluation and optimization, this paper presents a new method of replication fidelity improvement. Firstly, a simplified analysis model of PMMA micro columns arrays (5×16) with 200μm diameter was set up. And then, Flow (3D) module of Moldflow MPI6.0 based on Navier-Stokes equations was used to calculate the weight of the micro columns arrays in injection molding. The effects of processing parameters (melt temperature, mold temperature, injection time, packing pressure and packing time) on the part weight were investigated in the simulations. The simulation results showed that the mold temperature and the injection time have important effects on the filling of micro columns; the optimal mold temperature and injection time for better replication fidelity could be determined by the curves of mold temperature vs part weight and injection time vs part weight. At last, the effects of processing parameters on part weight of micro columns array were studied experimentally. The experimental results showed that the increase of melt temperature and mold temperature can make the packing pressure transfer to micro cavity more effectively through runner system, and increase the part weight. From the observation results of the image measuring apparatus, it was discovered that the higher the part weight, the better the filling of the microstructures. In conclusion, part weight can be used to evaluate the replication fidelity of micro-feature structured parts primarily; which is an economical and practical method to improve the replication fidelity of microlens arrays based on weight evaluation and optimization.

A reminder on millisecond timing accuracy and potential replication failure in computer-based psychology experiments: An open letter.

PubMed

Plant, Richard R

2016-03-01

There is an ongoing 'replication crisis' across the field of psychology in which researchers, funders, and members of the public are questioning the results of some scientific studies and the validity of the data they are based upon. However, few have considered that a growing proportion of research in modern psychology is conducted using a computer. Could it simply be that the hardware and software, or experiment generator, being used to run the experiment itself be a cause of millisecond timing error and subsequent replication failure? This article serves as a reminder that millisecond timing accuracy in psychology studies remains an important issue and that care needs to be taken to ensure that studies can be replicated on current computer hardware and software.

Central timing deficits in subtypes of primary speech disorders.

PubMed

Peter, Beate; Stoel-Gammon, Carol

2008-03-01

Childhood apraxia of speech (CAS) is a proposed speech disorder subtype that interferes with motor planning and/or programming, affecting prosody in many cases. Pilot data (Peter & Stoel-Gammon, 2005) were consistent with the notion that deficits in timing accuracy in speech and music-related tasks may be associated with CAS. This study replicated and expanded earlier findings. Eleven children with speech disorders and age-and gender-matched controls participated in non-word imitation, clapped rhythm imitation, and paced repetitive tapping tasks. Results suggest a central timing deficit, expressed in both the oral and the limb modality, and observable in two different types of timing measures, overall rhythmic structures and small-scale durations. Associations among timing measures were strongest in the participants with speech disorders, who also showed lower timing accuracy than the controls in all measures. The number of observed CAS characteristics was associated with timing deficits.

Establishing an Integrative Medicine Program Within an Academic Health Center: Essential Considerations.

PubMed

Eisenberg, David M; Kaptchuk, Ted J; Post, Diana E; Hrbek, Andrea L; O'Connor, Bonnie B; Osypiuk, Kamila; Wayne, Peter M; Buring, Julie E; Levy, Donald B

2016-09-01

Integrative medicine (IM) refers to the combination of conventional and "complementary" medical services (e.g., chiropractic, acupuncture, massage, mindfulness training). More than half of all medical schools in the United States and Canada have programs in IM, and more than 30 academic health centers currently deliver multidisciplinary IM care. What remains unclear, however, is the ideal delivery model (or models) whereby individuals can responsibly access IM care safely, effectively, and reproducibly in a coordinated and cost-effective way.Current models of IM across existing clinical centers vary tremendously in their organizational settings, principal clinical focus, and services provided; practitioner team composition and training; incorporation of research activities and educational programs; and administrative organization (e.g., reporting structure, use of medical records, scope of clinical practice) and financial strategies (i.e., specific business plans and models for sustainability).In this article, the authors address these important strategic issues by sharing lessons learned from the design and implementation of an IM facility within an academic teaching hospital, the Brigham and Women's Hospital at Harvard Medical School; and review alternative options based on information about IM centers across the United States.The authors conclude that there is currently no consensus as to how integrative care models should be optimally organized, implemented, replicated, assessed, and funded. The time may be right for prospective research in "best practices" across emerging models of IM care nationally in an effort to standardize, refine, and replicate them in preparation for rigorous cost-effectiveness evaluations.

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program.

PubMed

Perrin, Karen M; Burke, Somer Goad; O'Connor, Danielle; Walby, Gary; Shippey, Claire; Pitt, Seraphine; McDermott, Robert J; Forthofer, Melinda S

2006-10-26

Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity.

Evaluation of the dating skills program for improving heterosocial interactions in people with mental retardation.

PubMed

Valenti-Hein, D C; Yarnold, P R; Mueser, K T

1994-01-01

The effectiveness of a social skills training program for improving heterosocial interactions in persons with mental retardation was examined. Moderate to borderline mentally retarded subjects were selected based on problems with social anxiety and social skill deficits. Subjects were then randomly assigned to either a 12-session Dating Skills Program (DSP) or a wait list control (WLC) group. Assessments of social skills in a role-play test, knowledge about social/sexual situations, and social anxiety were obtained for all subjects at baseline, posttreatment, and at an 8-week follow-up. In addition, naturalistic observations were made of interactions of subjects in the DSP group. Subjects who participated in the DSP showed improvements in social skill and social/sexual knowledge at posttest and at follow-up compared to subjects in the WLC group. Social anxiety did not change over time for either group of subjects. Subjects who received the DSP increased interactions with persons of the opposite gender over time, while same-gender interactions decreased. The results replicate and extend previous research on the Dating Skills Program, and suggest that social skills training interventions may improve the heterosocial interactions of adults with mental retardation.

Evaluating a bilingual patient navigation program for uninsured women with abnormal screening tests for breast and cervical cancer: implications for future navigator research.

PubMed

Simon, Melissa A; Tom, Laura S; Nonzee, Narissa J; Murphy, Kara R; Endress, Richard; Dong, XinQi; Feinglass, Joe

2015-05-01

The DuPage Patient Navigation Collaborative evaluated the Patient Navigation Research Program (PNRP) model for uninsured women receiving free breast or cervical cancer screening through the Illinois Breast and Cervical Cancer Program in DuPage County, Illinois. We used medical records review and patient surveys of 477 women to compare median follow-up times with external Illinois Breast and Cervical Cancer Program and Chicago PNRP benchmarks of performance. We examined the extent to which we mitigated community-defined timeliness risk factors for delayed follow-up, with a focus on Spanish-speaking participants. Median follow-up time (29.0 days for breast and 56.5 days for cervical screening abnormalities) compared favorably to external benchmarks. Spanish-speaking patients had lower health literacy, lower patient activation, and more health care system distrust than did English-speaking patients, but despite the prevalence of timeliness risk factors, we observed no differences in likelihood of delayed (> 60 days) follow-up by language. Our successful replication and scaling of the PNRP navigation model to DuPage County illustrates a promising approach for future navigator research.

Evaluating a Bilingual Patient Navigation Program for Uninsured Women With Abnormal Screening Tests for Breast and Cervical Cancer: Implications for Future Navigator Research

PubMed Central

Tom, Laura S.; Nonzee, Narissa J.; Murphy, Kara R.; Endress, Richard; Dong, XinQi; Feinglass, Joe

2015-01-01

Objectives. The DuPage Patient Navigation Collaborative evaluated the Patient Navigation Research Program (PNRP) model for uninsured women receiving free breast or cervical cancer screening through the Illinois Breast and Cervical Cancer Program in DuPage County, Illinois. Methods. We used medical records review and patient surveys of 477 women to compare median follow-up times with external Illinois Breast and Cervical Cancer Program and Chicago PNRP benchmarks of performance. We examined the extent to which we mitigated community-defined timeliness risk factors for delayed follow-up, with a focus on Spanish-speaking participants. Results. Median follow-up time (29.0 days for breast and 56.5 days for cervical screening abnormalities) compared favorably to external benchmarks. Spanish-speaking patients had lower health literacy, lower patient activation, and more health care system distrust than did English-speaking patients, but despite the prevalence of timeliness risk factors, we observed no differences in likelihood of delayed (> 60 days) follow-up by language. Conclusions. Our successful replication and scaling of the PNRP navigation model to DuPage County illustrates a promising approach for future navigator research. PMID:25713942

Fidelity of DNA Replication in Normal and Malignant Human Breast Cells

DTIC Science & Technology

1998-07-01

synthesome has been extensively demonstrated to carry out full length DNA replication in vitro, and to accurately depict the DNA replication process as it...occurs in the intact cell. By examining the fidelity of the DNA replication process carried out by the DNA synthesome from a number of breast cell types...we have demonstrated for the first time, that the cellular DNA replication machinery of malignant human breast cells is significantly more error-prone than that of non- malignant human breast cells.

RCT of a high-protein diet on hunger motivation and weight-loss in obese children: an extension and replication.

PubMed

Duckworth, Lauren C; Gately, Paul J; Radley, Duncan; Cooke, Carlton B; King, Roderick F G J; Hill, Andrew J

2009-09-01

This study aimed to evaluate the weight loss and hunger motivation effects of an energy-restricted high-protein (HP) diet in overweight and obese children. In total, 95 overweight and obese children attended an 8-week (maximum) program of physical activity, reduced-energy intake, and behavior change education. Children were randomly assigned to one of two isoenergetic diets (standard (SP): 15% protein; HP: 25% protein), based on individually estimated energy requirements. Anthropometry and body composition were assessed at the start and end of the program and appetite and mood ratings completed on the first 3 consecutive weekdays of each week children attended camp. The HP diet had no greater effect on weight loss, body composition, or changes in appetite or mood when compared to the SP diet. Overall, campers lost 5.2 +/- 3.0 kg in body weight and reduced their BMI standard deviation score (sds) by 0.25. Ratings of desire to eat increased significantly over the duration of the intervention, irrespective of diet. This is the third time we have reported an increase in hunger motivation in weight-loss campers and replicates our previous failure to block this with a higher protein diet. Further work is warranted into the management of hunger motivation as a result of negative energy balance.

Escherichia coli sampling reliability at a frequently closed Chicago beach: monitoring and management implications

USGS Publications Warehouse

Whitman, Richard L.; Nevers, Meredith B.

2004-01-01

Monitoring beaches for recreational water quality is becoming more common, but few sampling designs or policy approaches have evaluated the efficacy of monitoring programs. The authors intensively sampled water for E. coli (N=1770) at 63rd Street Beach, Chicago for 6 months in 2000 in order to (1) characterize spatial-temporal trends, (2) determine between and within transect variation, and (3) estimate sample size requirements and determine sampling reliability.E. coli counts were highly variable within and between sampling sites but spatially and diurnally autocorrelated. Variation in counts decreased with water depth and time of day. Required number of samples was high for 70% precision around the critical closure level (i.e., 6 within or 24 between transect replicates). Since spatial replication may be cost prohibitive, composite sampling is an alternative once sources of error have been well defined. The results suggest that beach monitoring programs may be requiring too few samples to fulfill management objectives desired. As the recreational water quality national database is developed, it is important that sampling strategies are empirically derived from a thorough understanding of the sources of variation and the reliability of collected data. Greater monitoring efficacy will yield better policy decisions, risk assessments, programmatic goals, and future usefulness of the information.

Standardized classroom management program: Social validation and replication studies in Utah and Oregon

PubMed Central

Greenwood, Charles R.; Hops, Hyman; Walker, Hill M.; Guild, Jacqueline J.; Stokes, Judith; Young, K. Richard; Keleman, Kenneth S.; Willardson, Marlyn

1979-01-01

A comprehensive validation study was conducted of the Program for Academic Survival Skills (PASS), a consultant-based, teacher-mediated program for student classroom behavior. The study addressed questions related to: (a) brief consultant training, (b) subsequent teacher training by consultants using PASS manuals, (c) contrasts between PASS experimental teachers and students and equivalent controls on measures of teacher management skills, student classroom behavior, teacher ratings of student problem behaviors, and academic achievement, (d) reported satisfaction of participants, and (e) replication of effects across two separate school sites. Results indicated that in both sites significant effects were noted in favor of the PASS experimental group for (a) teacher approval, (b) student appropriate classroom behavior, and (c) four categories of student inappropriate behavior. Program satisfaction ratings of students, teachers, and consultants were uniformly positive, and continued use of the program was reported a year later. Discussion focused upon issues of cost-effectiveness, differential site effects, and the relationship between appropriate classroom behavior and academic achievement. PMID:16795604

Standardized classroom management program: Social validation and replication studies in Utah and Oregon.

PubMed

Greenwood, C R; Hops, H; Walker, H M; Guild, J J; Stokes, J; Young, K R; Keleman, K S; Willardson, M

1979-01-01

A comprehensive validation study was conducted of the Program for Academic Survival Skills (PASS), a consultant-based, teacher-mediated program for student classroom behavior. The study addressed questions related to: (a) brief consultant training, (b) subsequent teacher training by consultants using PASS manuals, (c) contrasts between PASS experimental teachers and students and equivalent controls on measures of teacher management skills, student classroom behavior, teacher ratings of student problem behaviors, and academic achievement, (d) reported satisfaction of participants, and (e) replication of effects across two separate school sites. Results indicated that in both sites significant effects were noted in favor of the PASS experimental group for (a) teacher approval, (b) student appropriate classroom behavior, and (c) four categories of student inappropriate behavior. Program satisfaction ratings of students, teachers, and consultants were uniformly positive, and continued use of the program was reported a year later. Discussion focused upon issues of cost-effectiveness, differential site effects, and the relationship between appropriate classroom behavior and academic achievement.

Mimicking subsecond neurotransmitter dynamics with femtosecond laser stimulated nanosystems.

PubMed

Nakano, Takashi; Chin, Catherine; Myint, David Mo Aung; Tan, Eng Wui; Hale, Peter John; Krishna M, Bala Murali; Reynolds, John N J; Wickens, Jeff; Dani, Keshav M

2014-06-23

Existing nanoscale chemical delivery systems target diseased cells over long, sustained periods of time, typically through one-time, destructive triggering. Future directions lie in the development of fast and robust techniques capable of reproducing the pulsatile chemical activity of living organisms, thereby allowing us to mimic biofunctionality. Here, we demonstrate that by applying programmed femtosecond laser pulses to robust, nanoscale liposome structures containing dopamine, we achieve sub-second, controlled release of dopamine--a key neurotransmitter of the central nervous system--thereby replicating its release profile in the brain. The fast delivery system provides a powerful new interface with neural circuits, and to the larger range of biological functions that operate on this short timescale.

Inadequate prescription-drug coverage for Medicare enrollees--a call to action.

PubMed

Soumerai, S B; Ross-Degnan, D

1999-03-04

In summary, most low-income elderly and disabled persons lack coverage for important medications, resulting in avoidable deterioration of health among those with chronic illnesses and use of expensive institutional services. Rapidly escalating drug costs, more restrictive drug-coverage policies, and a dramatic increase in the population of elderly and disabled persons will exacerbate these problems. With the current budget surplus, as well as bipartisan concern about health care needs and public concern about drug costs and coverage, it is time to act responsibly and aggressively. We recommend a national replication of the best features of state pharmacy-assistance programs in a federal-state insurance program for low-income Medicare enrollees, either alone or in combination with expanded Medicare coverage. Such a program will reduce the current inequitable situation in which the most vulnerable patients have the least access to medications, with serious medical and economic consequences.

Problem severity and motivation for treatment in incarcerated substance abusers.

PubMed

Hiller, Matthew L; Narevic, Egle; Webster, J Matthew; Rosen, Paul; Staton, Michele; Leukefeld, Carl; Garrity, Thomas F; Kayo, Rebecca

2009-01-01

Studies of community-based treatment programs for substance users document that motivation for treatment is a consistent predictor of clients remaining under treatment for a longer period of time. Recent research has replicated this in prison-based treatment programs, implying that motivation is clinically important regardless of setting. The current study examines predictors of treatment motivation using data collected from 661 male drug-involved inmates during in-depth interviews that include components of the Addiction Severity Index, TCU Motivation Scale, and the Heath Services Research Instrument. Findings showed treatment motivation can be measured effectively in prison-based settings. Motivation scores were not significantly different between individuals in a prison-based treatment program and those in the general prison population. Furthermore, higher motivation for treatment scores were associated with greater levels of problem severity, suggesting that individuals with more drug-use related life problems may recognize this need and desire help for beginning long-term recovery.

Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus

DTIC Science & Technology

2007-10-01

Crimean Congo Hemorrhagic Fever Virus PRINCIPAL INVESTIGATOR: Adolfo García-Sastre, Ph.D. CONTRACTING...Diversity, Replication, Pathogenicity and Cell Biology of Crimean Congo Hemorrhagic Fever Virus 5b. GRANT NUMBER W81XWH-04-1-0876 5c. PROGRAM ELEMENT...localization and antigenic characterization of Crimean - Congo hemorrhagic fever virus glycoproteins. J.Virol. 79: 6152-61. Ahmed, A., McFalls,

Form and function of topologically associating genomic domains in budding yeast.

PubMed

Eser, Umut; Chandler-Brown, Devon; Ay, Ferhat; Straight, Aaron F; Duan, Zhijun; Noble, William Stafford; Skotheim, Jan M

2017-04-11

The genome of metazoan cells is organized into topologically associating domains (TADs) that have similar histone modifications, transcription level, and DNA replication timing. Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the long-known effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins.

Programming your way out of the past: ISIS and the META Project

NASA Technical Reports Server (NTRS)

Birman, Kenneth P.; Marzullo, Keith

1989-01-01

The ISIS distributed programming system and the META Project are described. The ISIS programming toolkit is an aid to low-level programming that makes it easy to build fault-tolerant distributed applications that exploit replication and concurrent execution. The META Project is reexamining high-level mechanisms such as the filesystem, shell language, and administration tools in distributed systems.

Crystallization and preliminary X-ray characterization of the eukaryotic replication terminator Reb1-Ter DNA complex.

PubMed

Jaiswal, Rahul; Singh, Samarendra K; Bastia, Deepak; Escalante, Carlos R

2015-04-01

The Reb1 protein from Schizosaccharomyces pombe is a member of a family of proteins that control programmed replication termination and/or transcription termination in eukaryotic cells. These events occur at naturally occurring replication fork barriers (RFBs), where Reb1 binds to termination (Ter) DNA sites and coordinates the polar arrest of replication forks and transcription approaching in opposite directions. The Reb1 DNA-binding and replication-termination domain was expressed in Escherichia coli, purified and crystallized in complex with a 26-mer DNA Ter site. Batch crystallization under oil was required to produce crystals of good quality for data collection. Crystals grew in space group P2₁, with unit-cell parameters a = 68.9, b = 162.9, c = 71.1 Å, β = 94.7°. The crystals diffracted to a resolution of 3.0 Å. The crystals were mosaic and required two or three cycles of annealing. This study is the first to yield structural information about this important family of proteins and will provide insights into the mechanism of replication and transcription termination.

The simulation of the geosynchronous Earth orbit plasma environment in Chamber A: An assessment of possible experimental investigations

NASA Technical Reports Server (NTRS)

Bernstein, W.

1981-01-01

The possible use of Chamber A for the replication or simulation of space plasma physics processes which occur in the geosynchronous Earth orbit (GEO) environment is considered. It is shown that replication is not possible and that scaling of the environmental conditions is required for study of the important instability processes. Rules for such experimental scaling are given. At the present time, it does not appear technologically feasible to satisfy these requirements in Chamber A. It is, however, possible to study and qualitatively evaluate the problem of vehicle charging at GEO. In particular, Chamber A is sufficiently large that a complete operational spacecraft could be irradiated by beams and charged to high potentials. Such testing would contribute to the assessment of the operational malfunctions expected at GEO and their possible correction. However, because of the many tabulated limitations in such a testing programs, its direct relevance to conditions expected in the geo environment remains questionable.

Outreach and Orientation for ESL Students and Bilingual Welding and Automotive Programs. Vocational Education Resource Package.

ERIC Educational Resources Information Center

Evaluation and Training Inst., Los Angeles, CA.

This Vocational Education Resource Package (VERP) was developed to provide materials useful in replicating an exemplary vocational education program for special student populations in the California Community Colleges. This VERP provides information on two programs for limited English proficient students developed at Santa Barbara City College…

Tales of Refusal, Adoption, and Maintenance: Evidence-Based Substance Abuse Prevention via School-Extension Collaborations

ERIC Educational Resources Information Center

St. Pierre, Tena L.; Kaltreider, D. Lynne

2004-01-01

Despite availability of empirically supported school-based substance abuse prevention programs, adoption and implementation fidelity of such programs appear to be low. A replicated case study was conducted to investigate school adoption and implementation processes of the EXSELS model (Project ALERT delivered by program leaders through Cooperative…

The Evaluation of Vocational Programming in Secondary School Settings: A Suggested Protocol

ERIC Educational Resources Information Center

George, Jennifer C.; Seruya, Francine M.

2018-01-01

The primary purpose of this project was to determine if a therapist-created protocol to develop a prevocational program provided sufficient information for a practitioner to implement a vocational program within another high school setting. The developed protocol was evaluated on feasibility and efficacy for replication within another setting by…

A peer education program: delivering highly reliable sexual health promotion messages in schools.

PubMed

Layzer, Carolyn; Rosapep, Lauren; Barr, Sherry

2014-03-01

This article describes preliminary findings from an implementation study of a school-based peer education program on sexual health for high-school youth. The responses of youth participants are described. Qualitative data were collected across one semester in two successive waves of participants (N = 4 schools), including observations of program activities, in-depth interviews of stakeholders, focus groups with youth participants (N = 62 peer educators and 60 ninth graders), and brief surveys of youth participants (N = 678). Grounded theory methodology informed data collection and analysis. Teen Prevention Education Program (Teen PEP) was adapted and replicated with fidelity to the model in North Carolina high schools. All program "inputs" and five core model components (outputs) were implemented. The principal accommodation made was to implement the entire curriculum within one half of a school year rather than across the entire school year although still using the same amount of instructional time. Youth participants attributed high value to the experience, noting that the sexual health information they received was both new and important for their lives and that they felt they learned it better from their peers than from instruction in traditional health class. The majority of participants reported that the program helped them across a range of areas related to both social well-being and sexual health. Teen PEP developers have been able to successfully adapt and replicate it in North Carolina, in settings that need sexual health education services for youth both because of the paucity of existing services in many areas and because of the evidence of risk in the form of high rates of pregnancy and sexually transmitted infections, including human immunodeficiency virus or AIDS in youth 15-19 years of age. Youth reported benefits across a range of social and sexual health-related areas. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Genome-wide analysis of replication timing by next-generation sequencing with E/L Repli-seq.

PubMed

Marchal, Claire; Sasaki, Takayo; Vera, Daniel; Wilson, Korey; Sima, Jiao; Rivera-Mulia, Juan Carlos; Trevilla-García, Claudia; Nogues, Coralin; Nafie, Ebtesam; Gilbert, David M

2018-05-01

This protocol is an extension to: Nat. Protoc. 6, 870-895 (2014); doi:10.1038/nprot.2011.328; published online 02 June 2011Cycling cells duplicate their DNA content during S phase, following a defined program called replication timing (RT). Early- and late-replicating regions differ in terms of mutation rates, transcriptional activity, chromatin marks and subnuclear position. Moreover, RT is regulated during development and is altered in diseases. Here, we describe E/L Repli-seq, an extension of our Repli-chip protocol. E/L Repli-seq is a rapid, robust and relatively inexpensive protocol for analyzing RT by next-generation sequencing (NGS), allowing genome-wide assessment of how cellular processes are linked to RT. Briefly, cells are pulse-labeled with BrdU, and early and late S-phase fractions are sorted by flow cytometry. Labeled nascent DNA is immunoprecipitated from both fractions and sequenced. Data processing leads to a single bedGraph file containing the ratio of nascent DNA from early versus late S-phase fractions. The results are comparable to those of Repli-chip, with the additional benefits of genome-wide sequence information and an increased dynamic range. We also provide computational pipelines for downstream analyses, for parsing phased genomes using single-nucleotide polymorphisms (SNPs) to analyze RT allelic asynchrony, and for direct comparison to Repli-chip data. This protocol can be performed in up to 3 d before sequencing, and requires basic cellular and molecular biology skills, as well as a basic understanding of Unix and R.

Automation of the anthrone assay for carbohydrate concentration determinations.

PubMed

Turula, Vincent E; Gore, Thomas; Singh, Suddham; Arumugham, Rasappa G

2010-03-01

Reported is the adaptation of a manual polysaccharide assay applicable for glycoconjugate vaccines such as Prevenar to an automated liquid handling system (LHS) for improved performance. The anthrone assay is used for carbohydrate concentration determinations and was scaled to the microtiter plate format with appropriate mixing, dispensing, and measuring operations. Adaptation and development of the LHS platform was performed with both dextran polysaccharides of various sizes and pneumococcal serotype 6A polysaccharide (PnPs 6A). A standard plate configuration was programmed such that the LHS diluted both calibration standards and a test sample multiple times with six replicate preparations per dilution. This extent of replication minimized the effect of any single deviation or delivery error that might have occurred. Analysis of the dextran polymers ranging in size from 214 kDa to 3.755 MDa showed that regardless of polymer chain length the hydrolysis was complete, as evident by uniform concentration measurements. No plate positional absorbance bias was observed; of 12 plates analyzed to examine positional bias the largest deviation observed was 0.02% percent relative standard deviation (%RSD). The high purity dextran also afforded the opportunity to assess LHS accuracy; nine replicate analyses of dextran yielded a mean accuracy of 101% recovery. As for precision, a total of 22 unique analyses were performed on a single lot of PnPs 6A, and the resulting variability was 2.5% RSD. This work demonstrated the capability of a LHS to perform the anthrone assay consistently and a reduced assay cycle time for greater laboratory capacity.

Integrated Structural Analysis and Test Program

NASA Technical Reports Server (NTRS)

Kaufman, Daniel

2005-01-01

An integrated structural-analysis and structure-testing computer program is being developed in order to: Automate repetitive processes in testing and analysis; Accelerate pre-test analysis; Accelerate reporting of tests; Facilitate planning of tests; Improve execution of tests; Create a vibration, acoustics, and shock test database; and Integrate analysis and test data. The software package includes modules pertaining to sinusoidal and random vibration, shock and time replication, acoustics, base-driven modal survey, and mass properties and static/dynamic balance. The program is commanded by use of ActiveX controls. There is minimal need to generate command lines. Analysis or test files are selected by opening a Windows Explorer display. After selecting the desired input file, the program goes to a so-called analysis data process or test data process, depending on the type of input data. The status of the process is given by a Windows status bar, and when processing is complete, the data are reported in graphical, tubular, and matrix form.

Management of fluorescent lamps in controlled environment chambers

NASA Technical Reports Server (NTRS)

Romer, Mark

1994-01-01

Management of fluorescent lights is recommended to (1) maintain uniformity of light intensity over time and (2) permit reproducibility of lighting conditions during experimental replications. At the McGill Phytotron, the lighting intensity can be controlled to desired level because any individual pair of the 40 lamps in each chamber can be set to be 'on' at any particular time. A lamp canopy service history is maintained for each experiment permitting accurate replication of lighting conditions for subsequent replicate trials.

A distinct first replication cycle of DNA introduced in mammalian cells

PubMed Central

Chandok, Gurangad S.; Kapoor, Kalvin K.; Brick, Rachel M.; Sidorova, Julia M.; Krasilnikova, Maria M.

2011-01-01

Many mutation events in microsatellite DNA sequences were traced to the first embryonic divisions. It was not known what makes the first replication cycles of embryonic DNA different from subsequent replication cycles. Here we demonstrate that an unusual replication mode is involved in the first cycle of replication of DNA introduced in mammalian cells. This alternative replication starts at random positions, and occurs before the chromatin is fully assembled. It is detected in various cell lines and primary cells. The presence of single-stranded regions increases the efficiency of this alternative replication mode. The alternative replication cannot progress through the A/T-rich FRA16B fragile site, while the regular replication mode is not affected by it. A/T-rich microsatellites are associated with the majority of chromosomal breakpoints in cancer. We suggest that the alternative replication mode may be initiated at the regions with immature chromatin structure in embryonic and cancer cells resulting in increased genomic instability. This work demonstrates, for the first time, differences in the replication progression during the first and subsequent replication cycles in mammalian cells. PMID:21062817

The Temporal Regulation of S Phase Proteins During G1

PubMed Central

Grant, Gavin D.; Cook, Jeanette G.

2018-01-01

Successful DNA replication requires intimate coordination with cell cycle progression. Prior to DNA replication initiation in S phase, a series of essential preparatory events in G1 phase ensures timely, complete, and precise genome duplication. Among the essential molecular processes are regulated transcriptional upregulation of genes that encode replication proteins, appropriate post-transcriptional control of replication factor abundance and activity, and the assembly of DNA-loaded protein complexes to license replication origins. In this chapter we describe these critical G1 events necessary for DNA replication and their regulation in the context of both cell cycle entry and cell cycle progression. PMID:29357066

Concise Review: Geminin-A Tale of Two Tails: DNA Replication and Transcriptional/Epigenetic Regulation in Stem Cells.

PubMed

Patmanidi, Alexandra L; Champeris Tsaniras, Spyridon; Karamitros, Dimitris; Kyrousi, Christina; Lygerou, Zoi; Taraviras, Stavros

2017-02-01

Molecular mechanisms governing maintenance, commitment, and differentiation of stem cells are largely unexploited. Molecules involved in the regulation of multiple cellular processes are of particular importance for stem cell physiology, as they integrate different signals and coordinate cellular decisions related with self-renewal and fate determination. Geminin has emerged as a critical factor in DNA replication and stem cell differentiation in different stem cell populations. Its inhibitory interaction with Cdt1, a member of the prereplicative complex, ensures the controlled timing of DNA replication and, consequently, genomic stability in actively proliferating cells. In embryonic as well as somatic stem cells, Geminin has been shown to interact with transcription factors and epigenetic regulators to drive gene expression programs and ultimately guide cell fate decisions. An ever-growing number of studies suggests that these interactions of Geminin and proteins regulating transcription are conserved among metazoans. Interactions between Geminin and proteins modifying the epigenome, such as members of the repressive Polycomb group and the SWI/SNF proteins of the permissive Trithorax, have long been established. The complexity of these interactions, however, is only just beginning to unravel, revealing key roles on maintaining stem cell self-renewal and fate specification. In this review, we summarize current knowledge and give new perspectives for the role of Geminin on transcriptional and epigenetic regulation, alongside with its regulatory activity in DNA replication and their implication in the regulation of stem and progenitor cell biology. Stem Cells 2017;35:299-310. © 2016 AlphaMed Press.

The longevity in the yeast Saccharomyces cerevisiae: A comparison of two approaches for assessment the lifespan.

PubMed

Molon, Mateusz; Zadrag-Tecza, Renata; Bilinski, Tomasz

2015-05-08

Longevity of the selected "longevity mutants" of yeast was studied using two methods. The standard method was based on counting the number of daughter cells produced. Modification of that method allowed for establishing the length of life expressed in units of time. It appeared that all the studied "deletion longevity mutants" showed a statistically meaningful increase in the number of daughters produced (replicative lifespan), whereas only one of the mutants, previously regarded as "short lived", showed a meaningful increase in the time of life. The analysis of the available data shows that the time of life of most yeast strains is similar irrespective of their genetic background and mutations, which suggests a quasi-programmed nature of yeast death. Copyright © 2015 Elsevier Inc. All rights reserved.

Testing the Efficacy of a Tier 2 Mathematics Intervention: A Conceptual Replication Study

ERIC Educational Resources Information Center

Doabler, Christian T.; Clarke, Ben; Kosty, Derek B.; Kurtz-Nelson, Evangeline; Fien, Hank; Smolkowski, Keith; Baker, Scott K.

2016-01-01

The purpose of this closely aligned conceptual replication study was to investigate the efficacy of a Tier 2 kindergarten mathematics intervention. The replication study differed from the initial randomized controlled trial on three important elements: geographical region, timing of the intervention, and instructional context of the…

Exploiting replication in distributed systems

NASA Technical Reports Server (NTRS)

Birman, Kenneth P.; Joseph, T. A.

1989-01-01

Techniques are examined for replicating data and execution in directly distributed systems: systems in which multiple processes interact directly with one another while continuously respecting constraints on their joint behavior. Directly distributed systems are often required to solve difficult problems, ranging from management of replicated data to dynamic reconfiguration in response to failures. It is shown that these problems reduce to more primitive, order-based consistency problems, which can be solved using primitives such as the reliable broadcast protocols. Moreover, given a system that implements reliable broadcast primitives, a flexible set of high-level tools can be provided for building a wide variety of directly distributed application programs.

Algorithms for Automatic Alignment of Arrays

NASA Technical Reports Server (NTRS)

Chatterjee, Siddhartha; Gilbert, John R.; Oliker, Leonid; Schreiber, Robert; Sheffler, Thomas J.

1996-01-01

Aggregate data objects (such as arrays) are distributed across the processor memories when compiling a data-parallel language for a distributed-memory machine. The mapping determines the amount of communication needed to bring operands of parallel operations into alignment with each other. A common approach is to break the mapping into two stages: an alignment that maps all the objects to an abstract template, followed by a distribution that maps the template to the processors. This paper describes algorithms for solving the various facets of the alignment problem: axis and stride alignment, static and mobile offset alignment, and replication labeling. We show that optimal axis and stride alignment is NP-complete for general program graphs, and give a heuristic method that can explore the space of possible solutions in a number of ways. We show that some of these strategies can give better solutions than a simple greedy approach proposed earlier. We also show how local graph contractions can reduce the size of the problem significantly without changing the best solution. This allows more complex and effective heuristics to be used. We show how to model the static offset alignment problem using linear programming, and we show that loop-dependent mobile offset alignment is sometimes necessary for optimum performance. We describe an algorithm with for determining mobile alignments for objects within do loops. We also identify situations in which replicated alignment is either required by the program itself or can be used to improve performance. We describe an algorithm based on network flow that replicates objects so as to minimize the total amount of broadcast communication in replication.

Human replication protein Cdc6 is selectively cleaved by caspase 3 during apoptosis

PubMed Central

Pelizon, Cristina; d’Adda di Fagagna, Fabrizio; Farrace, Lorena; Laskey, Ronald A.

2002-01-01

In eukaryotes, the initiation of DNA replication involves the ordered assembly on chromatin of pre-replicative complexes (pre-RCs), including the origin recognition complex (ORC), Cdc6, Cdt1 and the minichromosome maintenance proteins (MCMs). In light of its indispensable role in the formation of pre-RCs, Cdc6 binding to chromatin represents a key step in the regulation of DNA replication and cell proliferation. Here, we study the human Cdc6 (HuCdc6) protein during programmed cell death (apoptosis). We find that HuCdc6, but not HuOrc2 (a member of the ORC) or HuMcm5 (one of the MCMs), is specifically cleaved in several human cell lines induced to undergo apoptosis by a variety of stimuli. Expression of caspase-uncleavable mutant HuCdc6 attenuates apoptosis, delaying cell death. Therefore, an important function for cleavage of HuCdc6 is to prevent a wounded cell from replicating and to facilitate death. PMID:12151338

Registered report: the androgen receptor induces a distinct transcriptional program in castration-resistant prostate cancer in man

PubMed Central

Chronscinski, Denise; Cherukeri, Srujana; Tan, Fraser; Lomax, Joelle; Iorns, Elizabeth

2015-01-01

The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative (PCFMFRI) seeks to address growing concerns about reproducibility in scientific research by conducting replications of recent papers in the field of prostate cancer. This Registered Report describes the proposed replication plan of key experiments from “The Androgen Receptor Induces a Distinct Transcriptional Program in Castration-Resistant Prostate Cancer in Man” by Sharma and colleagues (2013), published in Cancer Cell in 2013. Of thousands of targets for the androgen receptor (AR), the authors elucidated a subset of 16 core genes that were consistently downregulated with castration and re-emerged with castration resistance. These 16 AR binding sites were distinct from those observed in cells in culture. The authors suggested that cellular context can have dramatic effects on downstream transcriptional regulation of AR binding sites. The present study will attempt to replicate Fig. 7C by comparing gene expression of the 16 core genes identified by Sharma and colleagues in xenograft tumor tissue compared to androgen treated LNCaP cells in vitro. The Prostate Cancer Foundation-Movember Foundation Reproducibility Initiative is a collaboration between the Prostate Cancer Foundation, the Movember Initiative, and Science Exchange, and the results of the replications will be published by PeerJ. PMID:26401447

VERIFYING THE SOCIAL, ENVIRONMENTAL, AND ECONOMIC PROMISE OF BROWNFIELD PROGRAMS

EPA Science Inventory

The purpose of this research is to develop a nationally replicable methodology to empirically assess the social, economic, and environmental benefits of brownfields redevelopment for low-to-moderate income communities. Using the City of Charlottes (NC) brownfields program, we i...

Safe Computing: An Overview of Viruses.

ERIC Educational Resources Information Center

Wodarz, Nan

2001-01-01

A computer virus is a program that replicates itself, in conjunction with an additional program that can harm a computer system. Common viruses include boot-sector, macro, companion, overwriting, and multipartite. Viruses can be fast, slow, stealthy, and polymorphic. Anti-virus products are described. (MLH)

Extended local similarity analysis (eLSA) of microbial community and other time series data with replicates.

PubMed

Xia, Li C; Steele, Joshua A; Cram, Jacob A; Cardon, Zoe G; Simmons, Sheri L; Vallino, Joseph J; Fuhrman, Jed A; Sun, Fengzhu

2011-01-01

The increasing availability of time series microbial community data from metagenomics and other molecular biological studies has enabled the analysis of large-scale microbial co-occurrence and association networks. Among the many analytical techniques available, the Local Similarity Analysis (LSA) method is unique in that it captures local and potentially time-delayed co-occurrence and association patterns in time series data that cannot otherwise be identified by ordinary correlation analysis. However LSA, as originally developed, does not consider time series data with replicates, which hinders the full exploitation of available information. With replicates, it is possible to understand the variability of local similarity (LS) score and to obtain its confidence interval. We extended our LSA technique to time series data with replicates and termed it extended LSA, or eLSA. Simulations showed the capability of eLSA to capture subinterval and time-delayed associations. We implemented the eLSA technique into an easy-to-use analytic software package. The software pipeline integrates data normalization, statistical correlation calculation, statistical significance evaluation, and association network construction steps. We applied the eLSA technique to microbial community and gene expression datasets, where unique time-dependent associations were identified. The extended LSA analysis technique was demonstrated to reveal statistically significant local and potentially time-delayed association patterns in replicated time series data beyond that of ordinary correlation analysis. These statistically significant associations can provide insights to the real dynamics of biological systems. The newly designed eLSA software efficiently streamlines the analysis and is freely available from the eLSA homepage, which can be accessed at http://meta.usc.edu/softs/lsa.

Extended local similarity analysis (eLSA) of microbial community and other time series data with replicates

PubMed Central

2011-01-01

Background The increasing availability of time series microbial community data from metagenomics and other molecular biological studies has enabled the analysis of large-scale microbial co-occurrence and association networks. Among the many analytical techniques available, the Local Similarity Analysis (LSA) method is unique in that it captures local and potentially time-delayed co-occurrence and association patterns in time series data that cannot otherwise be identified by ordinary correlation analysis. However LSA, as originally developed, does not consider time series data with replicates, which hinders the full exploitation of available information. With replicates, it is possible to understand the variability of local similarity (LS) score and to obtain its confidence interval. Results We extended our LSA technique to time series data with replicates and termed it extended LSA, or eLSA. Simulations showed the capability of eLSA to capture subinterval and time-delayed associations. We implemented the eLSA technique into an easy-to-use analytic software package. The software pipeline integrates data normalization, statistical correlation calculation, statistical significance evaluation, and association network construction steps. We applied the eLSA technique to microbial community and gene expression datasets, where unique time-dependent associations were identified. Conclusions The extended LSA analysis technique was demonstrated to reveal statistically significant local and potentially time-delayed association patterns in replicated time series data beyond that of ordinary correlation analysis. These statistically significant associations can provide insights to the real dynamics of biological systems. The newly designed eLSA software efficiently streamlines the analysis and is freely available from the eLSA homepage, which can be accessed at http://meta.usc.edu/softs/lsa. PMID:22784572

From Turing machines to computer viruses.

PubMed

Marion, Jean-Yves

2012-07-28

Self-replication is one of the fundamental aspects of computing where a program or a system may duplicate, evolve and mutate. Our point of view is that Kleene's (second) recursion theorem is essential to understand self-replication mechanisms. An interesting example of self-replication codes is given by computer viruses. This was initially explained in the seminal works of Cohen and of Adleman in the 1980s. In fact, the different variants of recursion theorems provide and explain constructions of self-replicating codes and, as a result, of various classes of malware. None of the results are new from the point of view of computability theory. We now propose a self-modifying register machine as a model of computation in which we can effectively deal with the self-reproduction and in which new offsprings can be activated as independent organisms.

Space Science

NASA Image and Video Library

1999-04-21

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. The process allows fabricating precisely shaped mandrels to be used and reused as masters for replicating high-quality mirrors. Dr. Joe Ritter examines a replicated electro-formed nickel-alloy mirror which exemplifies the improvements in mirror fabrication techniques, with benefits such as dramtic weight reduction that have been achieved at the Marshall Space Flight Center's Space Optics Manufacturing Technology Center (SOMTC).

Process and Outcomes of School Nurse Case Management for Students with Asthma

ERIC Educational Resources Information Center

Engelke, Martha Keehner; Swanson, Melvin; Guttu, Martha

2014-01-01

There have been many studies that have examined the impact of school-based asthma programs on students with asthma. However, most studies do not provide adequate elaboration on the components of the program. Therefore, replication of these programs is difficult. This study examines the process of school nurse case management, which includes the…

Program Evaluation and Replications of School-Based Mental Health Services and Family-Community Interventions with Chronically Disruptive Students

ERIC Educational Resources Information Center

Carpenter-Aeby, Tracy; Aeby, Victor G.

2005-01-01

Although outcomes for alternative schools may be mixed, it is generally agreed that counseling, therapy, group work, case management, and family-community involvement have been credited in some effective programs. This study examined program evaluations from 1994-1999 for an alternative school for chronically disruptive students (599 students,…

Measuring the Impact of a Pilot Geospatial Technology Apprenticeship Program for the Department of Labor

ERIC Educational Resources Information Center

Gaudet, Cyndi; Annulis, Heather; Kmiec, John

2010-01-01

The Geospatial Technology Apprenticeship Program (GTAP) pilot was designed as a replicable and sustainable program to enhance workforce skills in geospatial technologies to best leverage a $30 billion market potential. The purpose of evaluating GTAP was to ensure that investment in this high-growth industry was adding value. Findings from this…

The Business Profession: A Mandatory, Noncredit, Cocurricular Career Preparation Program for Undergraduate Business Majors

ERIC Educational Resources Information Center

Clark, Thomas

2005-01-01

Designed to guide those who want to replicate a similar program at their institutions, this article examines Xavier University's experience with The Business Profession, a required, noncredit series of career-related events that business majors take over a 4-year period. This program was developed in response to research indicating that early…

Demonstrating Impact through Replicable Analysis: Implications of an Evaluation of Arkansas's Expanded Food and Nutrition Education Program

ERIC Educational Resources Information Center

Phelps, Josh; Brite-Lane, Allison; Crook, Tina; Hakkak, Reza; Fuller, Serena

2017-01-01

The evaluation described in this article focused on the effectiveness of Arkansas's Extension-based Expanded Food and Nutrition Education Program (EFNEP) but demonstrates an analytic approach that may be useful across Extension programs. We analyzed data from 1,810 Arkansas EFNEP participants' entry and exit Behavior Checklists to assess…

Evaluation of the Preschool Life Skills Program in Head Start Classrooms: A Systematic Replication

ERIC Educational Resources Information Center

Hanley, Gregory P.; Fahmie, Tara A.; Heal, Nicole A.

2014-01-01

In an attempt to address risk factors associated with extensive nonfamilial child care, we implemented the preschool life skills (PLS) program (Hanley, Heal, Tiger, & Ingvarsson, 2007) in two community-based Head Start classrooms. A multiple baseline design across classrooms, repeated across skills, showed that the program resulted in a 5-fold…

Bridging from Replication to Translation with a Thermal, Autonomous Replicator Made from Transfer RNA

NASA Astrophysics Data System (ADS)

Braun, Dieter; Möller, Friederike M.; Krammer, Hubert

2013-03-01

Central to the understanding of living systems is the interplay between DNA/RNA and proteins. Known as Eigen paradox, proteins require genetic information while proteins are needed for the replication of genes. RNA world scenarios focus on a base by base replication disconnected from translation. Here we used strategies from DNA machines to demonstrate a tight connection between a basic replication mechanism and translation. A pool of hairpin molecules replicate a two-letter code. The replication is thermally driven: the energy and negative entropy to drive replication is initially stored in metastable hairpins by kinetic cooling. Both are released by a highly specific and exponential replication reaction that is solely implemented by base hybridization. The duplication time is 30s. The reaction is monitored by fluorescence and described by a detailed kinetic model. The RNA hairpins usetransfer RNA sequences and the replication is driven by the simple disequilibrium setting of a thermal gradient The experiments propose a physical rather than a chemical scenario for the autonomous replication of protein encoding information. Supported by the NanoSystems Initiative Munich and ERC.

A method for estimating cost savings for population health management programs.

PubMed

Murphy, Shannon M E; McGready, John; Griswold, Michael E; Sylvia, Martha L

2013-04-01

To develop a quasi-experimental method for estimating Population Health Management (PHM) program savings that mitigates common sources of confounding, supports regular updates for continued program monitoring, and estimates model precision. Administrative, program, and claims records from January 2005 through June 2009. Data are aggregated by member and month. Study participants include chronically ill adult commercial health plan members. The intervention group consists of members currently enrolled in PHM, stratified by intensity level. Comparison groups include (1) members never enrolled, and (2) PHM participants not currently enrolled. Mixed model smoothing is employed to regress monthly medical costs on time (in months), a history of PHM enrollment, and monthly program enrollment by intensity level. Comparison group trends are used to estimate expected costs for intervention members. Savings are realized when PHM participants' costs are lower than expected. This method mitigates many of the limitations faced using traditional pre-post models for estimating PHM savings in an observational setting, supports replication for ongoing monitoring, and performs basic statistical inference. This method provides payers with a confident basis for making investment decisions. © Health Research and Educational Trust.

Time-temperature-stress capabilities of composite materials for advanced supersonic technology application

NASA Technical Reports Server (NTRS)

Kerr, James R.; Haskins, James F.

1987-01-01

Advanced composites will play a key role in the development of the technology for the design and fabrication of future supersonic vehicles. However, incorporating the material into vehicle usage is contingent on accelerating the demonstration of service capacity and design technology. Because of the added material complexity and lack of extensive data, laboratory replication of the flight service will provide the most rapid method to document the airworthiness of advanced composite systems. Consequently, a laboratory program was conducted to determine the time-temperature-stress capabilities of several high temperature composites. Tests included were thermal aging, environmental aging, fatigue, creep, fracture, tensile, and real-time flight simulation exposure. The program had two phases. The first included all the material property determinations and aging and simulation exposures up through 10,000 hours. The second continued these tests up to 50,000 cumulative hours. This report presents the results of the Phase 1 baseline and 10,000-hr aging and flight simulation studies, the Phase 2 50,000-hr aging studies, and the Phase 2 flight simulation tests, some of which extended to almost 40,000 hours.

A Replication of Failure, Not a Failure to Replicate

ERIC Educational Resources Information Center

Holden, Gary; Barker, Kathleen; Kuppens, Sofie; Rosenberg, Gary; LeBreton, Jonathan

2015-01-01

Purpose: The increasing role of systematic reviews in knowledge production demands greater rigor in the literature search process. The performance of the Social Work Abstracts (SWA) database has been examined multiple times over the past three decades. The current study is a replication within this line of research. Method: Issue-level coverage…

76 FR 53901 - Agency Information Collection Request; 30-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

.... Proposed Project: The Office of Adolescent Health (OAH) Teen Pregnancy Prevention Performance Measure... grantees to conduct teen pregnancy prevention programs. Grantees are funded to either replicate evidence-based teen pregnancy prevention programs (75 OAH grantees) or to implement research and demonstration...

Rehabilitation Counseling Information: Programmed Instruction for the Practitioner. Final Report.

ERIC Educational Resources Information Center

Phelps, William R.

This programmed instruction rehabilitation counseling information test attempts to cover six areas as follows: testing, psychological information, medical information, counseling concepts, history of rehabilitation, and counselor-agency functioning. The information may be utilized for research purposes and/or replicated by others. (Author)

Novel electric power-driven hydrodynamic injection system for gene delivery: safety and efficacy of human factor IX delivery in rats.

PubMed

Yokoo, T; Kamimura, K; Suda, T; Kanefuji, T; Oda, M; Zhang, G; Liu, D; Aoyagi, Y

2013-08-01

The development of a safe and reproducible gene delivery system is an essential step toward the clinical application of the hydrodynamic gene delivery (HGD) method. For this purpose, we have developed a novel electric power-driven injection system called the HydroJector-EM, which can replicate various time-pressure curves preloaded into the computer program before injection. The assessment of the reproducibility and safety of gene delivery system in vitro and in vivo demonstrated the precise replication of intravascular time-pressure curves and the reproducibility of gene delivery efficiency. The highest level of luciferase expression (272 pg luciferase per mg of proteins) was achieved safely using the time-pressure curve, which reaches 30 mm Hg in 10 s among various curves tested. Using this curve, the sustained expression of a therapeutic level of human factor IX protein (>500 ng ml(-1)) was maintained for 2 months after the HGD of the pBS-HCRHP-FIXIA plasmid. Other than a transient increase in liver enzymes that recovered in a few days, no adverse events were seen in rats. These results confirm the effectiveness of the HydroJector-EM for reproducible gene delivery and demonstrate that long-term therapeutic gene expression can be achieved by automatic computer-controlled hydrodynamic injection that can be performed by anyone.

Tissue-specific profile of DNA replication in the swimming larvae of Ciona intestinalis.

PubMed

Nakayama, Akie; Satoh, Nori; Sasakura, Yasunori

2005-03-01

The cell cycle is strictly regulated during development and its regulation is essential for organ formation and developmental timing. Here we observed the pattern of DNA replication in swimming larvae of an ascidian, Ciona intestinalis. Usually, Ciona swimming larvae obtain competence for metamorphosis at about 4-5 h after hatching, and these competent larvae initiate metamorphosis soon after they adhere to substrate with their papillae. In these larvae, three major tissues (epidermis, endoderm and mesenchyme) showed extensive DNA replication with distinct pattern and timing, suggesting tissue-specific cell cycle regulation. However, DNA replication did not continue in aged larvae which kept swimming for several days, suggesting that the cell cycle is arrested in these larvae at a certain time to prevent further growth of adult organ rudiments until the initiation of metamorphosis. Inhibition of the cell cycle by aphidicolin during the larval stage affects only the speed of metamorphosis, and not the formation of adult organ rudiments or the timing of the initiation of metamorphosis. However, after the completion of tail resorption, DNA replication is necessary for further metamorphic events. Our data showed that DNA synthesis in the larval trunk is not directly associated with the organization of adult organs, but it contributes to the speed of metamorphosis after settlement.

ScriptingRT: A Software Library for Collecting Response Latencies in Online Studies of Cognition

PubMed Central

Schubert, Thomas W.; Murteira, Carla; Collins, Elizabeth C.; Lopes, Diniz

2013-01-01

ScriptingRT is a new open source tool to collect response latencies in online studies of human cognition. ScriptingRT studies run as Flash applets in enabled browsers. ScriptingRT provides the building blocks of response latency studies, which are then combined with generic Apache Flex programming. Six studies evaluate the performance of ScriptingRT empirically. Studies 1–3 use specialized hardware to measure variance of response time measurement and stimulus presentation timing. Studies 4–6 implement a Stroop paradigm and run it both online and in the laboratory, comparing ScriptingRT to other response latency software. Altogether, the studies show that Flash programs developed in ScriptingRT show a small lag and an increased variance in response latencies. However, this did not significantly influence measured effects: The Stroop effect was reliably replicated in all studies, and the found effects did not depend on the software used. We conclude that ScriptingRT can be used to test response latency effects online. PMID:23805326

Full Parallel Implementation of an All-Electron Four-Component Dirac-Kohn-Sham Program.

PubMed

Rampino, Sergio; Belpassi, Leonardo; Tarantelli, Francesco; Storchi, Loriano

2014-09-09

A full distributed-memory implementation of the Dirac-Kohn-Sham (DKS) module of the program BERTHA (Belpassi et al., Phys. Chem. Chem. Phys. 2011, 13, 12368-12394) is presented, where the self-consistent field (SCF) procedure is replicated on all the parallel processes, each process working on subsets of the global matrices. The key feature of the implementation is an efficient procedure for switching between two matrix distribution schemes, one (integral-driven) optimal for the parallel computation of the matrix elements and another (block-cyclic) optimal for the parallel linear algebra operations. This approach, making both CPU-time and memory scalable with the number of processors used, virtually overcomes at once both time and memory barriers associated with DKS calculations. Performance, portability, and numerical stability of the code are illustrated on the basis of test calculations on three gold clusters of increasing size, an organometallic compound, and a perovskite model. The calculations are performed on a Beowulf and a BlueGene/Q system.

Factors contributing to intervention fidelity in a multi-site chronic disease self-management program

PubMed Central

Perrin, Karen M; Burke, Somer Goad; O'Connor, Danielle; Walby, Gary; Shippey, Claire; Pitt, Seraphine; McDermott, Robert J; Forthofer, Melinda S

2006-01-01

Background and objectives Disease self-management programs have been a popular approach to reducing morbidity and mortality from chronic disease. Replicating an evidence-based disease management program successfully requires practitioners to ensure fidelity to the original program design. Methods The Florida Health Literacy Study (FHLS) was conducted to investigate the implementation impact of the Pfizer, Inc. Diabetes Mellitus and Hypertension Disease Self-Management Program based on health literacy principles in 14 community health centers in Florida. The intervention components discussed include health educator recruitment and training, patient recruitment, class sessions, utilization of program materials, translation of program manuals, patient retention and follow-up, and technical assistance. Results This report describes challenges associated with achieving a balance between adaptation for cultural relevance and fidelity when implementing the health education program across clinic sites. This balance was necessary to achieve effectiveness of the disease self-management program. The FHLS program was implemented with a high degree of fidelity to the original design and used original program materials. Adaptations identified as advantageous to program participation are discussed, such as implementing alternate methods for recruiting patients and developing staff incentives for participation. Conclusion Effective program implementation depends on the talent, skill and willing participation of clinic staff. Program adaptations that conserve staff time and resources and recognize their contribution can increase program effectiveness without jeopardizing its fidelity. PMID:17067388

Replication licensing and the DNA damage checkpoint

PubMed Central

Cook, Jeanette Gowen

2011-01-01

Accurate and timely duplication of chromosomal DNA requires that replication be coordinated with processes that ensure genome integrity. Significant advances in determining how the earliest steps in DNA replication are affected by DNA damage have highlighted some of the mechanisms to establish that coordination. Recent insights have expanded the relationship between the ATM and ATR-dependent checkpoint pathways and the proteins that bind and function at replication origins. These findings suggest that checkpoints and replication are more intimately associated than previously appreciated, even in the absence of exogenous DNA damage. This review summarizes some of these developments. PMID:19482602

Retrovirus XMRV Is Inhibited by Host Proteins and Anti-HIV Drugs AZT, Tenofovir, and Raltegravir | Center for Cancer Research

Cancer.gov

A newly discovered retrovirus, XMRV, isolated from prostate cancer tissues for the first time in 2006, has recently been reported in patients with this cancer, as well as in patients with chronic fatigue syndrome (CFS). However, five subsequent studies could not validate these reports. Since XMRV was isolated from the T and B cells of CFS patients, Vinay Pathak and his colleagues in the HIV Drug Resistance Program sought to determine how XMRV was countering intracellular defense mechanisms that inhibit retroviral replication in human cells.

Evidence of Ebola Virus Replication and High Concentration in Semen of a Patient During Recovery.

PubMed

Barnes, Kayla G; Kindrachuk, Jason; Lin, Aaron E; Wohl, Shirlee; Qu, James; Tostenson, Samantha D; Dorman, William R; Busby, Michele; Siddle, Katherine J; Luo, Cynthia Y; Matranga, Christian B; Davey, Richard T; Sabeti, Pardis C; Chertow, Daniel S

2017-10-15

In one patient over time, we found that concentration of Ebola virus RNA in semen during recovery is remarkably higher than blood at peak illness. Virus in semen is replication-competent with no change in viral genome over time. Presence of sense RNA suggests replication in cells present in semen. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A pilot study evaluating a one-session attention modification training to decrease overeating in obese children.

PubMed

Boutelle, Kerri N; Kuckertz, Jennie M; Carlson, Jordan; Amir, Nader

2014-05-01

There are a number of neurocognitive and behavioral mechanisms that contribute to overeating and obesity, including an attentional bias to food cues. Attention modification programs, which implicitly train attention away from specific cues, have been used in anxiety and substance abuse, and could logically be applied to food cues. The purpose of this study was to evaluate the initial efficacy of a single session attention modification training for food cues (AMP) on overeating in overweight and obese children. Twenty-four obese children who eat in the absence of hunger participated in two visits and were assigned to an attention modification program (AMP) or attentional control program (ACC). The AMP program trained attention away 100% of the time from food words to neutral words. The ACC program trained attention 50% of the time to neutral and 50% of the time to food. Outcome measures included the eating in the absence of hunger free access session, and measures of craving, liking and salivation. Results revealed significant treatment effects for EAH percent and EAH kcal (group by time interactions p<.05). Children in the ACC condition showed a significant increase over time in the number of calories consumed in the free access session (within group t=3.09, p=.009) as well as the percent of daily caloric needs consumed in free access (within group t=3.37, p=.006), whereas children in the AMP group demonstrated slight decreases in these variables (within group t=-0.75 and -0.63, respectively). There was a trend suggesting a beneficial effect of AMP as compared to ACC for attentional bias (group by time interaction p=.073). Changes in craving, liking and saliva were not significantly different between groups (ps=.178-.527). This is the first study to demonstrate that an AMP program can influence eating in obese children. Larger studies are needed to replicate and extend these results. Copyright © 2014. Published by Elsevier Ltd.

Multiprocessor Real-Time Locking Protocols for Replicated Resources

DTIC Science & Technology

2016-07-01

circular buffer of slots, each representing a discrete segment of time . For example, if the maintenance of a timing wheel occurs af- ter an interrupt ...Experimental Evaluation To evaluate Algs. 2, 3, and 4, we conducted a series of ex- periments in which we measured relevant overheads and blocking times . We...Multiprocessor Real- Time Locking Protocols for Replicated Resources ∗ Catherine E. Jarrett1, Kecheng Yang1, Ming Yang1, Pontus Ekberg2, and James H

Slingshot dynamics for self-replicating probes and the effect on exploration timescales

NASA Astrophysics Data System (ADS)

Nicholson, Arwen; Forgan, Duncan

2013-10-01

Interstellar probes can carry out slingshot manoeuvres around the stars they visit, gaining a boost in velocity by extracting energy from the star's motion around the Galactic Centre. These manoeuvres carry little to no extra energy cost, and in previous work it has been shown that a single Voyager-like probe exploring the Galaxy does so 100 times faster when carrying out these slingshots than when navigating purely by powered flight (Forgan et al. 2012). We expand on these results by repeating the experiment with self-replicating probes. The probes explore a box of stars representative of the local Solar neighbourhood, to investigate how self-replication affects exploration timescales when compared with a single non-replicating probe. We explore three different scenarios of probe behaviour: (i) standard powered flight to the nearest unvisited star (no slingshot techniques used), (ii) flight to the nearest unvisited star using slingshot techniques and (iii) flight to the next unvisited star that will give the maximum velocity boost under a slingshot trajectory. In all three scenarios, we find that as expected, using self-replicating probes greatly reduces the exploration time, by up to three orders of magnitude for scenarios (i) and (iii) and two orders of magnitude for (ii). The second case (i.e. nearest-star slingshots) remains the most time effective way to explore a population of stars. As the decision-making algorithms for the fleet are simple, unanticipated `race conditions' among probes are set up, causing the exploration time of the final stars to become much longer than necessary. From the scaling of the probes' performance with star number, we conclude that a fleet of self-replicating probes can indeed explore the Galaxy in a sufficiently short time to warrant the existence of the Fermi Paradox.

Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication.

PubMed

Feng, Wenyi; Collingwood, David; Boeck, Max E; Fox, Lindsay A; Alvino, Gina M; Fangman, Walton L; Raghuraman, Mosur K; Brewer, Bonita J

2006-02-01

During DNA replication one or both strands transiently become single stranded: first at the sites where initiation of DNA synthesis occurs (known as origins of replication) and subsequently on the lagging strands of replication forks as discontinuous Okazaki fragments are generated. We report a genome-wide analysis of single-stranded DNA (ssDNA) formation in the presence of hydroxyurea during DNA replication in wild-type and checkpoint-deficient rad53 Saccharomyces cerevisiae cells. In wild-type cells, ssDNA was first observed at a subset of replication origins and later 'migrated' bi-directionally, suggesting that ssDNA formation is associated with continuously moving replication forks. In rad53 cells, ssDNA was observed at virtually every known origin, but remained there over time, suggesting that replication forks stall. Telomeric regions seemed to be particularly sensitive to the loss of Rad53 checkpoint function. Replication origins in Schizosaccharomyces pombe were also mapped using our method.

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2015-08-01

1 AD_________________ Award Number: W81XWH-10-1-0558 TITLE: Characterizing and Targeting Replication Stress Response Defects in Breast Cancer ...PRINCIPAL INVESTIGATOR: Shiaw-Yih Lin, Ph.D. CONTRACTING ORGANIZATION: University of Texas M. D. Anderson Cancer Center Houston, TX 77030 REPORT...Response Defects in Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER Chun-Jen Lin, Hui Dai

Effects of genetic variants previously associated with fasting glucose and insulin in the Diabetes Prevention Program.

PubMed

Florez, Jose C; Jablonski, Kathleen A; McAteer, Jarred B; Franks, Paul W; Mason, Clinton C; Mather, Kieren; Horton, Edward; Goldberg, Ronald; Dabelea, Dana; Kahn, Steven E; Arakaki, Richard F; Shuldiner, Alan R; Knowler, William C

2012-01-01

Common genetic variants have been recently associated with fasting glucose and insulin levels in white populations. Whether these associations replicate in pre-diabetes is not known. We extended these findings to the Diabetes Prevention Program, a clinical trial in which participants at high risk for diabetes were randomized to placebo, lifestyle modification or metformin for diabetes prevention. We genotyped previously reported polymorphisms (or their proxies) in/near G6PC2, MTNR1B, GCK, DGKB, GCKR, ADCY5, MADD, CRY2, ADRA2A, FADS1, PROX1, SLC2A2, GLIS3, C2CD4B, IGF1, and IRS1 in 3,548 Diabetes Prevention Program participants. We analyzed variants for association with baseline glycemic traits, incident diabetes and their interaction with response to metformin or lifestyle intervention. We replicated associations with fasting glucose at MTNR1B (P<0.001), G6PC2 (P = 0.002) and GCKR (P = 0.001). We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B (P<0.001), and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 (P<0.001). The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait, indicating a sustained deleterious effect at this locus. We also replicated the association of MADD with fasting proinsulin levels (P<0.001). We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions. The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons. These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program.

MatTAP: A MATLAB toolbox for the control and analysis of movement synchronisation experiments.

PubMed

Elliott, Mark T; Welchman, Andrew E; Wing, Alan M

2009-02-15

Investigating movement timing and synchronisation at the sub-second range relies on an experimental setup that has high temporal fidelity, is able to deliver output cues and can capture corresponding responses. Modern, multi-tasking operating systems make this increasingly challenging when using standard PC hardware and programming languages. This paper describes a new free suite of tools (available from http://www.snipurl.com/mattap) for use within the MATLAB programming environment, compatible with Microsoft Windows and a range of data acquisition hardware. The toolbox allows flexible generation of timing cues with high temporal accuracy, the capture and automatic storage of corresponding participant responses and an integrated analysis module for the rapid processing of results. A simple graphical user interface is used to navigate the toolbox and so can be operated easily by users not familiar with programming languages. However, it is also fully extensible and customisable, allowing adaptation for individual experiments and facilitating the addition of new modules in future releases. Here we discuss the relevance of the MatTAP (MATLAB Timing Analysis Package) toolbox to current timing experiments and compare its use to alternative methods. We validate the accuracy of the analysis module through comparison to manual observation methods and replicate a previous sensorimotor synchronisation experiment to demonstrate the versatility of the toolbox features demanded by such movement synchronisation paradigms.

rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data.

PubMed

Shen, Shihao; Park, Juw Won; Lu, Zhi-xiang; Lin, Lan; Henry, Michael D; Wu, Ying Nian; Zhou, Qing; Xing, Yi

2014-12-23

Ultra-deep RNA sequencing (RNA-Seq) has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We previously developed multivariate analysis of transcript splicing (MATS), a statistical method for detecting differential alternative splicing between two RNA-Seq samples. Here we describe a new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data. rMATS uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates. In addition to the analysis of unpaired replicates, rMATS also includes a model specifically designed for paired replicates between sample groups. The hypothesis-testing framework of rMATS is flexible and can assess the statistical significance over any user-defined magnitude of splicing change. The performance of rMATS is evaluated by the analysis of simulated and real RNA-Seq data. rMATS outperformed two existing methods for replicate RNA-Seq data in all simulation settings, and RT-PCR yielded a high validation rate (94%) in an RNA-Seq dataset of prostate cancer cell lines. Our data also provide guiding principles for designing RNA-Seq studies of alternative splicing. We demonstrate that it is essential to incorporate biological replicates in the study design. Of note, pooling RNAs or merging RNA-Seq data from multiple replicates is not an effective approach to account for variability, and the result is particularly sensitive to outliers. The rMATS source code is freely available at rnaseq-mats.sourceforge.net/. As the popularity of RNA-Seq continues to grow, we expect rMATS will be useful for studies of alternative splicing in diverse RNA-Seq projects.

Cell Cycle-Dependent Expression of Adeno-Associated Virus 2 (AAV2) Rep in Coinfections with Herpes Simplex Virus 1 (HSV-1) Gives Rise to a Mosaic of Cells Replicating either AAV2 or HSV-1

PubMed Central

Franzoso, Francesca D.; Seyffert, Michael; Vogel, Rebecca; Yakimovich, Artur; de Andrade Pereira, Bruna; Meier, Anita F.; Sutter, Sereina O.; Tobler, Kurt; Vogt, Bernd; Greber, Urs F.; Büning, Hildegard; Ackermann, Mathias

2017-01-01

ABSTRACT Adeno-associated virus 2 (AAV2) depends on the simultaneous presence of a helper virus such as herpes simplex virus 1 (HSV-1) for productive replication. At the same time, AAV2 efficiently blocks the replication of HSV-1, which would eventually limit its own replication by diminishing the helper virus reservoir. This discrepancy begs the question of how AAV2 and HSV-1 can coexist in a cell population. Here we show that in coinfected cultures, AAV2 DNA replication takes place almost exclusively in S/G2-phase cells, while HSV-1 DNA replication is restricted to G1 phase. Live microscopy revealed that not only wild-type AAV2 (wtAAV2) replication but also reporter gene expression from both single-stranded and double-stranded (self-complementary) recombinant AAV2 vectors preferentially occurs in S/G2-phase cells, suggesting that the preference for S/G2 phase is independent of the nature of the viral genome. Interestingly, however, a substantial proportion of S/G2-phase cells transduced by the double-stranded but not the single-stranded recombinant AAV2 vectors progressed through mitosis in the absence of the helper virus. We conclude that cell cycle-dependent AAV2 rep expression facilitates cell cycle-dependent AAV2 DNA replication and inhibits HSV-1 DNA replication. This may limit competition for cellular and viral helper factors and, hence, creates a biological niche for either virus to replicate. IMPORTANCE Adeno-associated virus 2 (AAV2) differs from most other viruses, as it requires not only a host cell for replication but also a helper virus such as an adenovirus or a herpesvirus. This situation inevitably leads to competition for cellular resources. AAV2 has been shown to efficiently inhibit the replication of helper viruses. Here we present a new facet of the interaction between AAV2 and one of its helper viruses, herpes simplex virus 1 (HSV-1). We observed that AAV2 rep gene expression is cell cycle dependent and gives rise to distinct time-controlled windows for HSV-1 replication. High Rep protein levels in S/G2 phase support AAV2 replication and inhibit HSV-1 replication. Conversely, low Rep protein levels in G1 phase permit HSV-1 replication but are insufficient for AAV2 replication. This allows both viruses to productively replicate in distinct sets of dividing cells. PMID:28515305

Route to Success: A Leader School's Youth Consultant Program. Linking Learning with Life.

ERIC Educational Resources Information Center

Kelley, Jennifer; Specter, Joanna; Young, Jamaal

This booklet explains how high schools can replicate the service learning youth consultant program that was originally formed at Spring Valley High School (SVHS) in Columbia, South Carolina, in 1996 to assume governance of SVHS's service learning program, which is called VikingServe. The booklet begins with an overview of VikingServe and a listing…

Effects of the "TOUCHMATH" Program Compared to a Number Line Strategy to Teach Addition Facts to Middle School Students with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Fletcher, Dale; Boon, Richard T.; Cihak, David F.

2010-01-01

The purpose of this study was to systematically replicate and extend previous studies of the TOUCHMATH program, a multi-sensory mathematics program (Bullock, Pierce, & McClellan, 1989). Three middle school students with moderate and multiple disabilities (e.g., autism and moderate intellectual disabilities) participated. Students were taught how…

Being Smart Is Not Enough--Easing the Way on the Long Hard Journey from Urban Poverty to College Graduation

ERIC Educational Resources Information Center

Hare, Mark

2013-01-01

The RocCity Scholars Program was developed to establish the efficacy of replicating the Rosen Scholars Program (ERIC #ED451789). Both programs were offered in inner-city environments, (New York City and Rochester) and both targeted the same under-served populations: college-bound academic achievers who were culturally, socially and financially…

A Microswitch-Cluster Program to Foster Adaptive Responses and Head Control in Students with Multiple Disabilities: Replication and Validation Assessment

ERIC Educational Resources Information Center

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Oliva, Doretta; Gatti, Michela; Manfredi, Francesco; Megna, Gianfranco; La Martire, Maria L.; Tota, Alessia; Smaldone, Angela; Groeneweg, Jop

2008-01-01

A program relying on microswitch clusters (i.e., combinations of microswitches) and preferred stimuli was recently developed to foster adaptive responses and head control in persons with multiple disabilities. In the last version of this program, preferred stimuli (a) are scheduled for adaptive responses occurring in combination with head control…

The USAID/DOE Mexico Renewable Energy Program: Using technology to build new markets

NASA Astrophysics Data System (ADS)

Hanley, Charles J.

1997-02-01

Under the Mexico Renewable Energy Program, managed by Sandia National Laboratories, sustainable markets for renewable energy technologies are developed through the implementation of pilot projects. Sandia provides technical assistance to several Mexican rural development organizations so they can gain the technical and institutional capability to appropriately utilize renewables within their ongoing programs. Activities in the area of water pumping have shown great replication potential, where the tremendous rural demand for water represents a potential renewable market of over 2 billion. Thirty-six photovoltaic water pumping projects have been installed thus far in the Mexican states of Chihuahua, Sonora, Baja California Sur, and Quintana Roo, and 60 more will be implemented this year. The majority of these projects are in partnership with the Mexican Trust for Shared Risk (FIRCO), which has asked Sandia for assistance in extending the program nationwide. This replication is beginning in five new states, and will continue to grow. Sandia is keeping the U.S. renewable energy industry involved in the program through facilitating partnerships between U.S. and Mexican vendors, and through commercialization assistance with new systems technologies. The program is sponsored by the Department of Energy and the U.S. Agency for International Development.

Genetic Interaction Mapping in Schizosaccharomyces pombe Using the Pombe Epistasis Mapper (PEM) System and a ROTOR HDA Colony Replicating Robot in a 1536 Array Format.

PubMed

Roguev, Assen; Xu, Jiewei; Krogan, Nevan

2018-02-01

This protocol describes an optimized high-throughput procedure for generating double deletion mutants in Schizosaccharomyces pombe using the colony replicating robot ROTOR HDA and the PEM (pombe epistasis mapper) system. The method is based on generating high-density colony arrays (1536 colonies per agar plate) and passaging them through a series of antidiploid and mating-type selection (ADS-MTS) and double-mutant selection (DMS) steps. Detailed program parameters for each individual replication step are provided. Using this procedure, batches of 25 or more screens can be routinely performed. © 2018 Cold Spring Harbor Laboratory Press.

The role of technical assistance in the replication of effective HIV interventions.

PubMed

O'Donnell, L; Scattergood, P; Adler, M; Doval, A S; Barker, M; Kelly, J A; Kegeles, S M; Rebchook, G M; Adams, J; Terry, M A; Neumann, M S

2000-01-01

This article examines the role of technical assistance (TA) in supporting the replication of proven HIV interventions. A case study of the replication of the VOICES/VOCES intervention elucidates the level and types of TA provided to support new users through the adoption process. TA included help in garnering administrative support, identifying target audiences, recruiting groups for sessions, maintaining fidelity to the intervention's core elements, tailoring the intervention to meet clients' needs, strengthening staff members' facilitation skills, troubleshooting challenges, and devising strategies to sustain the intervention. Two to four hours per month of TA were provided to each agency adopting the intervention, at an estimated monthly cost of $206 to $412. Findings illustrate how TA supports replication by establishing a conversation between the researcher TA providers experienced with the intervention and new users. This communication helps preserve key program elements and contributes to ongoing refinement of the intervention.

Induction of Oxidation in Living Cells by Time-Varying Electromagnetic Fields

NASA Technical Reports Server (NTRS)

Stolc, Viktor

2015-01-01

We are studying how biological systems can harness quantum effects of time varying electromagnetic (EM) waves as the time-setting basis for universal biochemical organization via the redox cycle. The effects of extremely weak EM field on the biochemical redox cycle can be monitored through real-time detection of oxidation-induced light emissions of reporter molecules in living cells. It has been shown that EM fields can also induce changes in fluid transport rates through capillaries (approximately 300 microns inner diameter) by generating annular proton gradients. This effect may be relevant to understanding cardiovascular dis-function in spaceflight, beyond the ionosphere. Importantly, we show that these EM effects can be attenuated using an active EM field cancellation device. Central for NASA's Human Research Program is the fact that the absence of ambient EM field in spaceflight can also have a detrimental influence, namely via increased oxidative damage, on DNA replication, which controls heredity.

Simple systems that exhibit self-directed replication

NASA Technical Reports Server (NTRS)

Reggia, James A.; Armentrout, Steven L.; Chou, Hui-Hsien; Peng, Yun

1993-01-01

Biological experience and intuition suggest that self-replication is an inherently complex phenomenon, and early cellular automata models support that conception. More recently, simpler computational models of self-directed replication called sheathed loops have been developed. It is shown here that 'unsheathing' these structures and altering certain assumptions about the symmetry of their components leads to a family of nontrivial self-replicating structures some substantially smaller and simpler than those previously reported. The dependence of replication time and transition function complexity on initial structure size, cell state symmetry, and neighborhood are examined. These results support the view that self-replication is not an inherently complex phenomenon but rather an emergent property arising from local interactions in systems that can be much simpler than is generally believed.

Assessing the relationship between computational speed and precision: a case study comparing an interpreted versus compiled programming language using a stochastic simulation model in diabetes care.

PubMed

McEwan, Phil; Bergenheim, Klas; Yuan, Yong; Tetlow, Anthony P; Gordon, Jason P

2010-01-01

Simulation techniques are well suited to modelling diseases yet can be computationally intensive. This study explores the relationship between modelled effect size, statistical precision, and efficiency gains achieved using variance reduction and an executable programming language. A published simulation model designed to model a population with type 2 diabetes mellitus based on the UKPDS 68 outcomes equations was coded in both Visual Basic for Applications (VBA) and C++. Efficiency gains due to the programming language were evaluated, as was the impact of antithetic variates to reduce variance, using predicted QALYs over a 40-year time horizon. The use of C++ provided a 75- and 90-fold reduction in simulation run time when using mean and sampled input values, respectively. For a series of 50 one-way sensitivity analyses, this would yield a total run time of 2 minutes when using C++, compared with 155 minutes for VBA when using mean input values. The use of antithetic variates typically resulted in a 53% reduction in the number of simulation replications and run time required. When drawing all input values to the model from distributions, the use of C++ and variance reduction resulted in a 246-fold improvement in computation time compared with VBA - for which the evaluation of 50 scenarios would correspondingly require 3.8 hours (C++) and approximately 14.5 days (VBA). The choice of programming language used in an economic model, as well as the methods for improving precision of model output can have profound effects on computation time. When constructing complex models, more computationally efficient approaches such as C++ and variance reduction should be considered; concerns regarding model transparency using compiled languages are best addressed via thorough documentation and model validation.

A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae

PubMed Central

Val, Marie-Eve; Marbouty, Martial; de Lemos Martins, Francisco; Kennedy, Sean P.; Kemble, Harry; Bland, Michael J.; Possoz, Christophe; Koszul, Romain; Skovgaard, Ole; Mazel, Didier

2016-01-01

Bacteria with multiple chromosomes represent up to 10% of all bacterial species. Unlike eukaryotes, these bacteria use chromosome-specific initiators for their replication. In all cases investigated, the machineries for secondary chromosome replication initiation are of plasmid origin. One of the important differences between plasmids and chromosomes is that the latter replicate during a defined period of the cell cycle, ensuring a single round of replication per cell. Vibrio cholerae carries two circular chromosomes, Chr1 and Chr2, which are replicated in a well-orchestrated manner with the cell cycle and coordinated in such a way that replication termination occurs at the same time. However, the mechanism coordinating this synchrony remains speculative. We investigated this mechanism and revealed that initiation of Chr2 replication is triggered by the replication of a 150-bp locus positioned on Chr1, called crtS. This crtS replication–mediated Chr2 replication initiation mechanism explains how the two chromosomes communicate to coordinate their replication. Our study reveals a new checkpoint control mechanism in bacteria, and highlights possible functional interactions mediated by contacts between two chromosomes, an unprecedented observation in bacteria. PMID:27152358

Formal design and verification of a reliable computing platform for real-time control. Phase 1: Results

NASA Technical Reports Server (NTRS)

Divito, Ben L.; Butler, Ricky W.; Caldwell, James L.

1990-01-01

A high-level design is presented for a reliable computing platform for real-time control applications. Design tradeoffs and analyses related to the development of the fault-tolerant computing platform are discussed. The architecture is formalized and shown to satisfy a key correctness property. The reliable computing platform uses replicated processors and majority voting to achieve fault tolerance. Under the assumption of a majority of processors working in each frame, it is shown that the replicated system computes the same results as a single processor system not subject to failures. Sufficient conditions are obtained to establish that the replicated system recovers from transient faults within a bounded amount of time. Three different voting schemes are examined and proved to satisfy the bounded recovery time conditions.

Independent replication of mitochondrial genes supports the transcriptional program in developing fiber cells of cotton (Gossypium hirsutum L.).

PubMed

Thyssen, Gregory N; Song, Xianliang; Naoumkina, Marina; Kim, Hee-Jin; Fang, David D

2014-07-01

The mitochondrial genomes of flowering plants exist both as a "master circle" chromosome and as numerous subgenomic sublimons that are generated by intramolecular recombination. Differential stability or replication of these sublimons allows individual mitochondrial gene copy numbers to vary independently between different cell types and developmental stages. Our objective was to determine the relationship between mitochondrial gene copy number and transcript abundance in the elongating fiber cells of Upland cotton (Gossypium hirsutum L.). We compared RNA and DNA from cotton fiber cells at five developmental time points from early elongation through secondary cell wall thickening from the Ligon-lintless 2 (Li2) short fiber mutant and its wild type near isogenic line (NIL) DP5690. Mitochondrial gene copy number decreased from 3 to 8-DPA in the developing cotton fiber cells while transcript levels remained low. As secondary cell wall biosynthesis began in developing fibers, the expression levels and copy numbers of mitochondrial genes involved in energy production and respiration were up-regulated in wild type cotton DP5690. However, the short fiber mutant Li2, failed to increase expression of these genes, which include three subunits of ATP synthase, atp1, atp8 and atp9 and two cytochrome genes cox1 and cob. At the same time, Li2 failed to increase the copy numbers of these highly expressed genes. Surprisingly, we found that when mitochondrial genes were highly transcribed, they also had very high copy numbers. This observation suggests that in developing cotton fibers, increased mitochondrial sublimon replication may support increases in gene transcription. Published by Elsevier B.V.

Allele-specific control of replication timing and genome organization during development.

PubMed

Rivera-Mulia, Juan Carlos; Dimond, Andrew; Vera, Daniel; Trevilla-Garcia, Claudia; Sasaki, Takayo; Zimmerman, Jared; Dupont, Catherine; Gribnau, Joost; Fraser, Peter; Gilbert, David M

2018-05-07

DNA replication occurs in a defined temporal order known as the replication-timing (RT) program. RT is regulated during development in discrete chromosomal units, coordinated with transcriptional activity and 3D genome organization. Here, we derived distinct cell types from F1 hybrid musculus X castaneus mouse crosses and exploited the high single nucleotide polymorphism (SNP) density to characterize allelic differences in RT (Repli-seq), genome organization (Hi-C and promoter-capture Hi-C), gene expression (total nuclear RNA-seq) and chromatin accessibility (ATAC-seq). We also present HARP: a new computational tool for sorting SNPs in phased genomes to efficiently measure allele-specific genome-wide data. Analysis of six different hybrid mESC clones with different genomes (C57BL/6, 129/sv and CAST/Ei), parental configurations and gender revealed significant RT asynchrony between alleles across ~12% of the autosomal genome linked to sub-species genomes but not to parental origin, growth conditions or gender. RT asynchrony in mESCs strongly correlated with changes in Hi-C compartments between alleles but not SNP density, gene expression, imprinting or chromatin accessibility. We then tracked mESC RT asynchronous regions during development by analyzing differentiated cell types including extraembryonic endoderm stem (XEN) cells, 4 male and female primary mouse embryonic fibroblasts (MEFs) and neural precursor cells (NPCs) differentiated in vitro from mESCs with opposite parental configurations. We found that RT asynchrony and allelic discordance in Hi-C compartments seen in mESCs was largely lost in all differentiated cell types, coordinated with a more uniform Hi-C compartment arrangement, suggesting that genome organization of homologues converges to similar folding patterns during cell fate commitment. Published by Cold Spring Harbor Laboratory Press.

Cardiovascular disease prevention in low resource settings: lessons from the Heartfile experience in Pakistan.

PubMed

Nishtar, Sania

2003-01-01

This paper outlines activities of the Heartfile Program in Pakistan (http://heartfile.org). The program focuses on cardiovascular disease prevention and health promotion, and includes several initiatives that encompass building policy, reorienting health services, and developing community interventions that utilize the print and electronic media and outreach at the grass-root level to incorporate social marketing approaches. Initiated by the nonprofit private sector, the program now links with major public sector primary healthcare programs, and is currently spearheading formulation of the National Action Plan on Noncommunicable Disease Prevention and Control in Pakistan. In addition, the program is being refined, validated, and packaged as a replicable model for other developing countries and in low resource settings, utilizing appropriate principles of franchising with inbuilt components sensitive to cultural and social adaptations. A review of the planning process, implementation strategy, and fund-raising experience is presented. Strategies unique to low resource settings, such as the development of cost- and time-efficient strategic alliances and partnerships, have also been highlighted. In addition, specific caveats are identified as being helpful to private sector development of chronic disease prevention programs in resource-constrained settings, and a road map to a sustainable public-private sector partnership is provided.

A macro-level fetal alcohol syndrome prevention program for Native Americans and Alaska Natives: description and evaluation.

PubMed

May, P A; Hymbaugh, K J

1989-11-01

Presented here are a detailed description and outcome evaluation of a comprehensive, macro-level Fetal Alcohol Syndrome prevention program for Native Americans and Alaska Natives. The program was designed to provide native communities throughout the United States with the knowledge, skills and strategies to initiate primary, secondary and tertiary prevention measures on their own. The key to the program was the training of a cadre of trainers/advocates in all local Native American and Alaska Native communities served by the Indian Health Service. These people were then supported and assisted in their efforts through a variety of means. Evaluation results of knowledge gained indicate that the local trainers had substantial success in imparting FAS information to a variety of audiences (prenatal groups, school children and community groups). Further, the evaluation samples also indicate that the knowledge was retained by the groups over time (2-4 months) and that there may have been some general diffusion of knowledge among peers in local communities. This program is presented in the hope that it will be replicated and improved upon by similar programs using this model as a base.

Cost-benefit estimates of an elderly exercise program on Kaua'i.

PubMed

Sugihara, Naomi; Watanabe, Marisa; Tomioka, Michiyo; Braun, Kathryn L; Pang, Lorrin

2011-06-01

The elderly consume a disproportionate amount of health care resources, and the recent trend in obesity will only escalate costs. EnhanceFitness® (EF) is an exercise program designed to increase the strength, flexibility, and balance of older adults. A comprehensive controlled study in Washington state of an elderly population has shown that participants who attend at least one EF class per week reduce healthcare costs by 20% per year. The present study reports the costs and potential benefits of replicating EF on Kaua'i. For Kaua'i the annual cost of an EF pilot program for 132 clients would be $204,735. Attendance records of the Kaua'i program showed that 96 (73%) of those enrolled attended at least weekly. Based on national reports of healthcare costs for the elderly, averting 20% of the costs for these 96 elderly would save $344,256 per year. The expected investment to return ratio, I-R ratio, for EF on Kaua'i is about 1-1.8. On economic grounds, a case can be made to support and expand these types of programs. In these times of budget cuts, cost-benefit analysis provides a common economic "language" to prioritize among different programs.

Extinction rates in tumour public goods games.

PubMed

Gerlee, Philip; Altrock, Philipp M

2017-09-01

Cancer evolution and progression are shaped by cellular interactions and Darwinian selection. Evolutionary game theory incorporates both of these principles, and has been proposed as a framework to understand tumour cell population dynamics. A cornerstone of evolutionary dynamics is the replicator equation, which describes changes in the relative abundance of different cell types, and is able to predict evolutionary equilibria. Typically, the replicator equation focuses on differences in relative fitness. We here show that this framework might not be sufficient under all circumstances, as it neglects important aspects of population growth. Standard replicator dynamics might miss critical differences in the time it takes to reach an equilibrium, as this time also depends on cellular turnover in growing but bounded populations. As the system reaches a stable manifold, the time to reach equilibrium depends on cellular death and birth rates. These rates shape the time scales, in particular, in coevolutionary dynamics of growth factor producers and free-riders. Replicator dynamics might be an appropriate framework only when birth and death rates are of similar magnitude. Otherwise, population growth effects cannot be neglected when predicting the time to reach an equilibrium, and cell-type-specific rates have to be accounted for explicitly. © 2017 The Authors.

Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

PubMed Central

Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

2016-01-01

Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility. DOI: http://dx.doi.org/10.7554/eLife.12765.001 PMID:27228154

Interpreting the Dependence of Mutation Rates on Age and Time

PubMed Central

Gao, Ziyue; Wyman, Minyoung J.; Sella, Guy; Przeworski, Molly

2016-01-01

Mutations can originate from the chance misincorporation of nucleotides during DNA replication or from DNA lesions that arise between replication cycles and are not repaired correctly. We introduce a model that relates the source of mutations to their accumulation with cell divisions, providing a framework for understanding how mutation rates depend on sex, age, and cell division rate. We show that the accrual of mutations should track cell divisions not only when mutations are replicative in origin but also when they are non-replicative and repaired efficiently. One implication is that observations from diverse fields that to date have been interpreted as pointing to a replicative origin of most mutations could instead reflect the accumulation of mutations arising from endogenous reactions or exogenous mutagens. We further find that only mutations that arise from inefficiently repaired lesions will accrue according to absolute time; thus, unless life history traits co-vary, the phylogenetic “molecular clock” should not be expected to run steadily across species. PMID:26761240

Physical Activity and Psychological Correlates during an After-School Running Club

ERIC Educational Resources Information Center

Kahan, David; McKenzie, Thomas L.

2018-01-01

Background: After-school programs (ASPs) have the potential to contribute to moderate-to-vigorous physical activity (MVPA), but there is limited empirical evidence to guide their development and implementation. Purpose: This study assessed the replication of an elementary school running program and identified psychological correlates of children's…

Understanding Effective Program Improvement Schools through a Distributed Leadership Task Context Model

ERIC Educational Resources Information Center

Gipson, Frances Marie

2012-01-01

Federal, state, and local agencies face challenges organizing resources that create the conditions necessary to create, sustain, and replicate effective high performing schools. Knowing that leadership does impact achievement outcomes and that school districts tackle growing numbers of sanctioned Program Improvement schools, a distributed…

Television in the Lives of the Elderly: Attitudes and Opinions.

ERIC Educational Resources Information Center

Davis, Richard H.; Westbrook, G. Jay

1985-01-01

This replication of a 1969 study surveyed audience attitudes of 274 elderly adults about television and its importance in their lives. The report focuses on the issues of television as entertainment, companionship function, influence of commercials on buying decisions, preferred programing, objectionable programing, and television's portrayal of…

A Formal Language Selection Process for Introductory Programming Courses

ERIC Educational Resources Information Center

Parker, Kevin R.; Chao, Joseph T.; Ottaway, Thomas A.; Chang, Jane

2006-01-01

The selection of a programming language for introductory courses has long been an informal process involving faculty evaluation, discussion, and consensus. As the number of faculty, students, and language options grows, this process becomes increasingly unwieldy. As it stands, the process currently lacks structure and replicability. Establishing a…

A Culturally Responsive Approach to Improving Replication of a Youth Sexual Health Program.

PubMed

Mwaria, Mercy; Chen, ChiaChing; Coppola, Nanci; Maurice, Ingrid; Phifer, Mary

2016-11-01

Youth-serving agencies continually turn to evidence-based interventions that have been empirically assessed for effectiveness in influencing young people's lives, particularly those living in communities with considerable health inequities. Replicating promising evidence-based interventions requires thoughtful adaptation and modification to better fit participants' sociocultural context and to enhance their learning experiences. Due to the restrictive nature of a replication model, adaptations to the intervention curriculum must be minimized during full implementation. Implementers must find innovative ways to ensure content is relevant and engaging to participants without altering core elements of the curriculum. This article describes practical best practice strategies used in implementing a sexual health education program among socioculturally diverse youth in a northeastern city in the United States. The implementing agency applied Richard, Brown and Forde's framework for culturally responsive pedagogy as a heuristic approach to describe the application of implementation practices across three dimensions: institutional, personal, and instructional. The results not only highlight successful culturally responsive practices that enhanced the implementation process but also acknowledge areas in which such practices proved daunting to implement. © 2016 Society for Public Health Education.

Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila.

PubMed

Brüggemann, Holger; Hagman, Arne; Jules, Matthieu; Sismeiro, Odile; Dillies, Marie-Agnès; Gouyette, Catherine; Kunst, Frank; Steinert, Michael; Heuner, Klaus; Coppée, Jean-Yves; Buchrieser, Carmen

2006-08-01

Adaptation to the host environment and exploitation of host cell functions are critical to the success of intracellular pathogens. Here, insight to these virulence mechanisms was obtained for the first time from the transcriptional program of the human pathogen Legionella pneumophila during infection of its natural host, Acanthamoeba castellanii. The biphasic life cycle of L. pneumophila was reflected by a major shift in gene expression from replicative to transmissive phase, concerning nearly half of the genes predicted in the genome. However, three different L. pneumophila strains showed similar in vivo gene expression patterns, indicating that common regulatory mechanisms govern the Legionella life cycle, despite the plasticity of its genome. During the replicative phase, in addition to components of aerobic metabolism and amino acid catabolism, the Entner-Doudoroff pathway, a NADPH producing mechanism used for sugar and/or gluconate assimilation, was expressed, suggesting for the first time that intracellular L. pneumophila may also scavenge host carbohydrates as nutrients and not only proteins. Identification of genes only upregulated in vivo but not in vitro, may explain higher virulence of in vivo grown L. pneumophila. Late in the life cycle, L. pneumophila upregulates genes predicted to promote transmission and manipulation of a new host cell, therewith priming it for the next attack. These including substrates of the Dot/Icm secretion system, other factors associated previously with invasion and virulence, the motility and the type IV pilus machineries, and > 90 proteins not characterized so far. Analysis of a fliA (sigma28) deletion mutant identified genes coregulated with the flagellar regulon, including GGDEF/EAL regulators and factors that promote host cell entry and survival.

Histone H4K20 tri-methylation at late-firing origins ensures timely heterochromatin replication.

PubMed

Brustel, Julien; Kirstein, Nina; Izard, Fanny; Grimaud, Charlotte; Prorok, Paulina; Cayrou, Christelle; Schotta, Gunnar; Abdelsamie, Alhassan F; Déjardin, Jérôme; Méchali, Marcel; Baldacci, Giuseppe; Sardet, Claude; Cadoret, Jean-Charles; Schepers, Aloys; Julien, Eric

2017-09-15

Among other targets, the protein lysine methyltransferase PR-Set7 induces histone H4 lysine 20 monomethylation (H4K20me1), which is the substrate for further methylation by the Suv4-20h methyltransferase. Although these enzymes have been implicated in control of replication origins, the specific contribution of H4K20 methylation to DNA replication remains unclear. Here, we show that H4K20 mutation in mammalian cells, unlike in Drosophila , partially impairs S-phase progression and protects from DNA re-replication induced by stabilization of PR-Set7. Using Epstein-Barr virus-derived episomes, we further demonstrate that conversion of H4K20me1 to higher H4K20me2/3 states by Suv4-20h is not sufficient to define an efficient origin per se , but rather serves as an enhancer for MCM2-7 helicase loading and replication activation at defined origins. Consistent with this, we find that Suv4-20h-mediated H4K20 tri-methylation (H4K20me3) is required to sustain the licensing and activity of a subset of ORCA/LRWD1-associated origins, which ensure proper replication timing of late-replicating heterochromatin domains. Altogether, these results reveal Suv4-20h-mediated H4K20 tri-methylation as a critical determinant in the selection of active replication initiation sites in heterochromatin regions of mammalian genomes. © 2017 The Authors.

RepExplore: addressing technical replicate variance in proteomics and metabolomics data analysis.

PubMed

Glaab, Enrico; Schneider, Reinhard

2015-07-01

High-throughput omics datasets often contain technical replicates included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using robust averages may help to reduce the influence of noise on downstream data analysis, the information on the variance across the replicate measurements is lost in the averaging process and therefore typically disregarded in subsequent statistical analyses.We introduce RepExplore, a web-service dedicated to exploit the information captured in the technical replicate variance to provide more reliable and informative differential expression and abundance statistics for omics datasets. The software builds on previously published statistical methods, which have been applied successfully to biomedical omics data but are difficult to use without prior experience in programming or scripting. RepExplore facilitates the analysis by providing a fully automated data processing and interactive ranking tables, whisker plot, heat map and principal component analysis visualizations to interpret omics data and derived statistics. Freely available at http://www.repexplore.tk enrico.glaab@uni.lu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

Control of Initiation of DNA Replication in Bacillus subtilis and Escherichia coli

PubMed Central

Jameson, Katie H.; Wilkinson, Anthony J.

2017-01-01

Initiation of DNA Replication is tightly regulated in all cells since imbalances in chromosomal copy number are deleterious and often lethal. In bacteria such as Bacillus subtilis and Escherichia coli, at the point of cytokinesis, there must be two complete copies of the chromosome to partition into the daughter cells following division at mid-cell during vegetative growth. Under conditions of rapid growth, when the time taken to replicate the chromosome exceeds the doubling time of the cells, there will be multiple initiations per cell cycle and daughter cells will inherit chromosomes that are already undergoing replication. In contrast, cells entering the sporulation pathway in B. subtilis can do so only during a short interval in the cell cycle when there are two, and only two, chromosomes per cell, one destined for the spore and one for the mother cell. Here, we briefly describe the overall process of DNA replication in bacteria before reviewing initiation of DNA replication in detail. The review covers DnaA-directed assembly of the replisome at oriC and the multitude of mechanisms of regulation of initiation, with a focus on the similarities and differences between E. coli and B. subtilis. PMID:28075389

Maintaining replication origins in the face of genomic change.

PubMed

Di Rienzi, Sara C; Lindstrom, Kimberly C; Mann, Tobias; Noble, William S; Raghuraman, M K; Brewer, Bonita J

2012-10-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

Maintaining replication origins in the face of genomic change

PubMed Central

Di Rienzi, Sara C.; Lindstrom, Kimberly C.; Mann, Tobias; Noble, William S.; Raghuraman, M.K.; Brewer, Bonita J.

2012-01-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved. PMID:22665441

The Inherent Asymmetry of DNA Replication.

PubMed

Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

2017-10-06

Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

The Alleged Crisis and the Illusion of Exact Replication.

PubMed

Stroebe, Wolfgang; Strack, Fritz

2014-01-01

There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a "replication crisis" in psychology. Psychologists are encouraged to conduct more "exact" replications of published studies to assess the reproducibility of psychological research. This article argues that the alleged "crisis of replicability" is primarily due to an epistemological misunderstanding that emphasizes the phenomenon instead of its underlying mechanisms. As a consequence, a replicated phenomenon may not serve as a rigorous test of a theoretical hypothesis because identical operationalizations of variables in studies conducted at different times and with different subject populations might test different theoretical constructs. Therefore, we propose that for meaningful replications, attempts at reinstating the original circumstances are not sufficient. Instead, replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study. © The Author(s) 2013.

ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication.

PubMed

Koo, Seong Joo; Fernández-Montalván, Amaury E; Badock, Volker; Ott, Christopher J; Holton, Simon J; von Ahsen, Oliver; Toedling, Joern; Vittori, Sarah; Bradner, James E; Gorjánácz, Mátyás

2016-10-25

ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.

Using an Experimental Evaluation of Charter Schools to Test Whether Nonexperimental Comparison Group Methods Can Replicate Experimental Impact Estimates. NCEE 2012-4019

ERIC Educational Resources Information Center

Fortson, Kenneth; Verbitsky-Savitz, Natalya; Kopa, Emma; Gleason, Philip

2012-01-01

Randomized controlled trials (RCTs) are widely considered to be the gold standard in evaluating the impacts of a social program. When an RCT is infeasible, researchers often estimate program impacts by comparing outcomes of program participants with those of a nonexperimental comparison group, adjusting for observable differences between the two…

1991 Nature Educators of the Year Recognized by the Roger Tory Peterson Institute of Natural History. Award Winners and Noteworthy Programs.

ERIC Educational Resources Information Center

Baldwin, Mark, Comp.; Seaberg, Anita, Comp.

The Roger Tory Peterson Institute's Nature Educators of the Year program recognizes teachers who have successfully implemented education programs that effectively connect children to nature, and that can be replicated by others. Two awards of $1,000 each were given in 1991. One of the recipients, Steven Prchal, is executive director of Sonoran…

Dental hygiene students' perceptions of distance learning: do they change over time?

PubMed

Sledge, Rhonda; Vuk, Jasna; Long, Susan

2014-02-01

The University of Arkansas for Medical Sciences dental hygiene program established a distant site where the didactic curriculum was broadcast via interactive video from the main campus to the distant site, supplemented with on-line learning via Blackboard. This study compared the perceptions of students towards distance learning as they progressed through the 21 month curriculum. Specifically, the study sought to answer the following questions: Is there a difference in the initial perceptions of students on the main campus and at the distant site toward distance learning? Do students' perceptions change over time with exposure to synchronous distance learning over the course of the curriculum? All 39 subjects were women between the ages of 20 and 35 years. Of the 39 subjects, 37 were Caucasian and 2 were African-American. A 15-question Likert scale survey was administered at 4 different periods during the 21 month program to compare changes in perceptions toward distance learning as students progressed through the program. An independent sample t-test and ANOVA were utilized for statistical analysis. At the beginning of the program, independent samples t-test revealed that students at the main campus (n=34) perceived statistically significantly higher effectiveness of distance learning than students at the distant site (n=5). Repeated measures of ANOVA revealed that perceptions of students at the main campus on effectiveness and advantages of distance learning statistically significantly decreased whereas perceptions of students at distant site statistically significantly increased over time. Distance learning in the dental hygiene program was discussed, and replication of the study with larger samples of students was recommended.

Effects of RNA interference therapy against herpes simplex virus type 1 encephalitis.

PubMed

da Silva, Alexandre S; Raposo, Jéssica V; Pereira, Tiago C; Pinto, Marcelo A; de Paula, Vanessa S

2016-01-01

Herpetic encephalitis (HSE) is caused mainly by herpes simplex virus type 1 (HSV-1) with an annual incidence of 1-4 cases/million inhabitants. Currently, HSE treatment faces difficulties such as the use of antivirals with elevated toxicity, metabolic side effects and HSV-1 resistance. An alternative to antivirals is the use of small interfering RNA (siRNA) as a viral replication inhibitor. In this work, siRNA targeting the UL-39 region was evaluated for HSE treatment in vivo. BALB/c mice were inoculated with HSV-1 and treated with siRNA. The treatment was evaluated through kinetics of HSV-1 replication inhibition, number of siRNA doses administered and treatment with siRNA plus acyclovir. All groups were evaluated for signs of HSE, mortality and HSV-1 replication inhibition. The treated group of the kinetic experiment demonstrated a reduction of HSE signs and an HSV-1 replication inhibition of 43.6-99.9% in the brain and 53-98% in trigeminal ganglia (TG). Animals treated with one or two doses of siRNA had a prolonged survival time, reduced clinical signs of HSE and HSV-1 replication inhibition of 67.7% in brains and 85.7% in TG of animals treated with two doses of siRNA. Also, animals treated with siRNA plus acyclovir demonstrated reduced signs of HSE and mortality, as well as HSV-1 replication inhibition in the brain (83.2%) and TG (74.5%). These findings demonstrated that siRNA was capable of reducing HSE clinical signs, prolonging survival time and inhibiting HSV-1 replication in mice. Thus, siRNA can be a potential alternative to the standard HSE treatment especially to reduce clinical signs and extend survival time in vivo.

Rif1 acts through Protein Phosphatase 1 but independent of replication timing to suppress telomere extension in budding yeast.

PubMed

Kedziora, Sylwia; Gali, Vamsi K; Wilson, Rosemary H C; Clark, Kate R M; Nieduszynski, Conrad A; Hiraga, Shin-Ichiro; Donaldson, Anne D

2018-05-04

The Rif1 protein negatively regulates telomeric TG repeat length in the budding yeast Saccharomyces cerevisiae, but how it prevents telomere over-extension is unknown. Rif1 was recently shown to control DNA replication by acting as a Protein Phosphatase 1 (PP1)-targeting subunit. Therefore, we investigated whether Rif1 controls telomere length by targeting PP1 activity. We find that a Rif1 mutant defective for PP1 interaction causes a long-telomere phenotype, similar to that of rif1Δ cells. Tethering PP1 at a specific telomere partially substitutes for Rif1 in limiting TG repeat length, confirming the importance of PP1 in telomere length control. Ablating Rif1-PP1 interaction is known to cause precocious activation of telomere-proximal replication origins and aberrantly early telomere replication. However, we find that Rif1 still limits telomere length even if late replication is forced through deletion of nearby replication origins, indicating that Rif1 can control telomere length independent of replication timing. Moreover we find that, even at a de novo telomere created after DNA synthesis during a mitotic block, Rif1-PP1 interaction is required to suppress telomere lengthening and prevent inappropriate recruitment of Tel1 kinase. Overall, our results show that Rif1 controls telomere length by recruiting PP1 to directly suppress telomerase-mediated TG repeat lengthening.

Replication cycle of duck hepatitis A virus type 1 in duck embryonic hepatocytes

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

Yao, Fangke; Chen, Yun; Shi, Jintong

Duck hepatitis A virus type 1 (DHAV-1) is an important agent of duck viral hepatitis. Until recently, the replication cycle of DHAV-1 is still unknown. Here duck embryonic hepatocytes infected with DHAV-1 were collected at different time points, and dynamic changes of the relative DHAV-1 gene expression during replication were detected by real-time PCR. And the morphology of hepatocytes infected with DHAV was evaluated by electron microscope. The result suggested that the adsorption of DHAV-1 saturated at 90 min post-infection, and the virus particles with size of about 50 nm including more than 20 nm of vacuum drying gold weremore » observed on the infected cells surface. What's more, the replication lasted around 13 h after the early protein synthesis for about 5 h, and the release of DHAV-1 was in steady state after 32 h. The replication cycle will enrich the data for DVH control and provide the foundation for future studies. - Highlights: • This is the first description of the replication cycle of DHAV-1. • Firstly find that DHAV-1 adsorption saturated at 90 min post-infection. • The replication lasted around 13 h after early protein synthesis for about 5 h. • The release of DHAV-1 was in steady state after 32 h.« less

Nucleosome occupancy as a novel chromatin parameter for replication origin functions

PubMed Central

Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

2017-01-01

Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

PubMed Central

Bii, Victor M.; Trobridge, Grant D.

2016-01-01

Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. PMID:27792127

Methadone enhances human influenza A virus replication.

PubMed

Chen, Yun-Hsiang; Wu, Kuang-Lun; Tsai, Ming-Ta; Chien, Wei-Hsien; Chen, Mao-Liang; Wang, Yun

2017-01-01

Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in target cells. However, it is unknown whether opioids can enhance replication of other clinically important viral pathogens. In this study, the interaction of opioid agonists and human influenza A/WSN/33 (H1N1) virus was examined in human lung epithelial A549 cells. Cells were exposed to morphine, methadone or buprenorphine followed by human H1N1 viral infection. Exposure to methadone differentially enhanced viral propagation, consistent with an increase in virus adsorption, susceptibility to virus infection and viral protein synthesis. In contrast, morphine or buprenorphine did not alter H1N1 replication. Because A549 cells do not express opioid receptors, methadone-enhanced H1N1 replication in human lung cells may not be mediated through these receptors. The interaction of methadone and H1N1 virus was also examined in adult mice. Treatment with methadone significantly increased H1N1 viral replication in lungs. Our data suggest that use of methadone facilitates influenza A viral infection in lungs and might raise concerns regarding the possible consequence of an increased risk of serious influenza A virus infection in people who receive treatment in methadone maintenance programs. © 2015 Society for the Study of Addiction.

Space Science

NASA Image and Video Library

1999-04-01

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. Optics replication uses reusable forms, called mandrels, to make telescope mirrors ready for final finishing. MSFC optical physicist Bill Jones monitors a device used to chill a mandrel, causing it to shrink and separate from the telescope mirror without deforming the mirror's precisely curved surface.

Biological effects of radiation, metabolic and replication kinetics alterations

NASA Technical Reports Server (NTRS)

Post, J.

1972-01-01

The biological effects of radiation upon normal and cancerous tissues were studied. A macromolecular precursor of DNA, 3ETdR, was incorporated into the cell nucleus during synthesis and provided intranuclear beta radiation. Tritium labeled cells were studied with autoradiographic methods; cell cycle kinetics were determined and cell functions modified by radiation dosage or by drugs were also evaluated. The long term program has included; (1) effects of radiation on cell replication and the correlation with incorporated dose levels, (2) radiation induced changes in cell function, viz., the response of beta irradiated spleen lymphocytes to antigenic stimulation by sheep red blood cells (SRBC), (3) kinetics of tumor and normal cell replication; and (4) megakaryocyte formation and modification by radiomimetic drugs.

Space Science

NASA Image and Video Library

1999-04-01

NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. The process allows fabricating precisely shaped mandrels to be used and reused as masters for replicating high-quality mirrors. Image shows Dr. Alan Shapiro cleaning mirror mandrel to be applied with highly reflective and high-density coating in the Large Aperture Coating Chamber, MFSC Space Optics Manufacturing Technology Center (SOMTC).

Performance analysis of static locking in replicated distributed database systems

NASA Technical Reports Server (NTRS)

Kuang, Yinghong; Mukkamala, Ravi

1991-01-01

Data replication and transaction deadlocks can severely affect the performance of distributed database systems. Many current evaluation techniques ignore these aspects, because it is difficult to evaluate through analysis and time consuming to evaluate through simulation. A technique is used that combines simulation and analysis to closely illustrate the impact of deadlock and evaluate performance of replicated distributed database with both shared and exclusive locks.

City of San Antonio, Texas Better Buildings Program

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

Meyer, Liza C.; Hammer, Mary C.

2014-06-30

The San Antonio Better Buildings Program is a unified single-point-of-service energy efficiency delivery mechanism targeting residential, commercial, institutional, industrial and public buildings. This comprehensive and replicable energy efficiency program is designed to be an effective demand side management initiative to provide a seamless process for program participants to have turn-key access to expert analysis, support and incentives to improve the performance of their in-place energy using systems, while reducing electrical energy use and demand.

Introduction of English Immersion in China: A Transplant with Modifications

ERIC Educational Resources Information Center

Qiang, Haiyan; Siegel, Linda S.

2012-01-01

This article presents an overview of replicating the French immersion model used in Canada to English immersion programs in China. It provides the Chinese context of this program highlighting the importance of English education and the defect of traditional English teaching and learning. The paper explains the borrowable features of the French…

Adapting Stanford's Chronic Disease Self-Management Program to Hawaii's Multicultural Population

ERIC Educational Resources Information Center

Tomioka, Michiyo; Braun, Kathryn L.; Compton, Merlita; Tanoue, Leslie

2012-01-01

Purpose of the Study: Stanford's Chronic Disease Self-Management Program (CDSMP) has been proven to increase patients' ability to manage distress. We describe how we replicated CDSMP in Asian and Pacific Islander (API) communities. Design and Methods: We used the "track changes" tool to deconstruct CDSMP into its various components…

Crossing the Divide: An Emerging Typology of Postsecondary Bridging for Opportunity Youth

ERIC Educational Resources Information Center

Almeida, Cheryl; Allen, Lili

2016-01-01

Through Job For the Future's (JFF's) work with communities around the country on the Back on Track model, postsecondary bridging strategies have emerged as a particularly critical and especially replicable component of programming for vulnerable youth. This issue brief offers a typology of evidence-informed bridge programming, drawing on…

Liberal Arts Catch-Up Revisited

ERIC Educational Resources Information Center

Goyder, John

2014-01-01

This paper replicates the work of Giles and Drewes from the 1990s. They showed a catch-up effect whereby graduates of liberal arts undergraduate programs, although at an early-career disadvantage compared with graduates of applied programs, had higher incomes by mid-career. Working with the Panel 5 Survey of Labour and Income Dynamics (2005-2010),…

Project Success Environment: A Positive Contingency Program for Elementary Teachers Management.

ERIC Educational Resources Information Center

Thompson, Marion; And Others

The third year of the project, funded under Elementary Secondary Education Act Title III, was essentially a replication of Year Two. Second Year results indicated that the success technique had provided inner-city teachers with both an effective classroom management system, and an effective program for the acceleration of academic performance.…

Comprehensive School Reform: A Multi-Site Replicated Experiment.

ERIC Educational Resources Information Center

Sterbinsky, Allan; Ross, Steven; Redfield, Doris

For schools to spend Title I funds on comprehensive school reform (CSR) programs under the No Child Left Behind Act, there must be empirical evidence of significant improvement in the academic achievement of CSR students. Unfortunately, there is a dearth of convincing evidence that CSR programs have a positive impact on student achievement. Over a…

Pesticides used against Cydia pomonella disrupt biological control of secondary pests of apple

USDA-ARS?s Scientific Manuscript database

The effects of codling moth management programs on secondary pests of apple were examined from 2008 to 2011 in five replicated large-plot trials. The orchards were chosen for a history of Eriosoma lanigerum and tetranychid mite outbreaks. Programs covered the first, second, or both generations of C....

Factors Influencing the Successful Completion of the General Educational Development (GED) Preparation Program as Perceived by the Students

ERIC Educational Resources Information Center

Styles, Theresa

2011-01-01

This replicated study (A. Tucho, 2000, "Factors Influencing the General Educational Development [GED] Program at Community College of Philadelphia as Perceived by the GED Students") determined which of the 3 types of educational barriers (institutional, situational, and dispositional) represented the major difficulty preventing adult…

75 FR 28789 - Office of Innovation and Improvement; Overview Information; Charter Schools Program (CSP) Grants...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-24

... Schools Program (CSP) Grants for Replication and Expansion of High-Quality Charter Schools; Notice... purpose of the CSP is to increase national understanding of the charter school model and to expand the number of high-quality charter schools available to students across the Nation by providing financial...

Using Data in the School Library

ERIC Educational Resources Information Center

Langhorne, Mary Jo

2004-01-01

Teacher-librarians are awash in data. Studies on the impact of school library programs on student achievement have now been replicated in 12 states (more are in the works) with amazingly consistent results, these are added to studies dating from the early 1960s that support the importance of school library programs to student achievement and the…

Promoting the Development of Mentor Teachers: Theory and Research Programs Using Guided Reflection.

ERIC Educational Resources Information Center

Reiman, Alan J.; Thies-Sprinthall, Lois

1993-01-01

Describes theory and a research program that uses guided reflection to promote the development of mentor teachers. Significant findings from a quasi-experimental study and a replication study are presented. The paper can assist teacher educators, policymakers, and school personnel who are searching for a teacher induction model. (GLR)

A Randomized Evaluation of the Success for All Middle School Reading Program

ERIC Educational Resources Information Center

Chamberlain, Anne; Daniels, Cecelia; Madden, Nancy A.; Slavin, Robert E.

2007-01-01

This article describes a randomized evaluation of The Reading Edge, a reading program for middle school students. The Reading Edge was designed to integrate findings of research on cooperative learning and metacognitive reading strategies into a replicable reading instructional package that could be implemented effectively in Title I middle…

Technical Report of: Assessing Teacher Preparation Program Effectiveness--A Pilot Examination of Value Added Approaches

ERIC Educational Resources Information Center

Noell, George H.

2005-01-01

Analyses were conducted replicating pilot work examining the feasibility of using the Louisiana's educational assessment data in concert with the Louisiana Educational Assessment Data System (LEADS) database and other associated databases to assess teacher preparation programs. The degree of matching across years and the degree of matching between…

Asthma Management in Minority Children: Practical Insights for Clinicians, Researchers, and Public Health Planners.

ERIC Educational Resources Information Center

National Heart, Lung, and Blood Inst. (DHHS/NIH), Bethesda, MD.

This monograph summarizes asthma management conclusions developed by five studies funded under a 5-year federal program titled "Interventions for the Control of Asthma among Black and Hispanic Children." The research goals were to develop model, replicable programs to reduce asthma morbidity; decrease inappropriate use of health care…

Interrogating the Escherichia coli cell cycle by cell dimension perturbations

PubMed Central

Zheng, Hai; Ho, Po-Yi; Jiang, Meiling; Tang, Bin; Liu, Weirong; Li, Dengjin; Yu, Xuefeng; Kleckner, Nancy E.; Amir, Ariel; Liu, Chenli

2016-01-01

Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter’s growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Here, we sought to test the robustness of the growth law to systematic perturbations in cell dimensions achieved by varying the expression levels of mreB and ftsZ. We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. Moreover, the growth law remained valid over a range of growth conditions and dimension perturbations. The growth law can be quantitatively interpreted as a consequence of a tight coupling of cell division to replication initiation. Thus, its robustness to perturbations in cell dimensions strongly supports models in which the timing of replication initiation governs that of cell division, and cell volume is the key phenomenological variable governing the timing of replication initiation. These conclusions are discussed in the context of our recently proposed “adder-per-origin” model, in which cells add a constant volume per origin between initiations and divide a constant time after initiation. PMID:27956612

Interrogating the Escherichia coli cell cycle by cell dimension perturbations.

PubMed

Zheng, Hai; Ho, Po-Yi; Jiang, Meiling; Tang, Bin; Liu, Weirong; Li, Dengjin; Yu, Xuefeng; Kleckner, Nancy E; Amir, Ariel; Liu, Chenli

2016-12-27

Bacteria tightly regulate and coordinate the various events in their cell cycles to duplicate themselves accurately and to control their cell sizes. Growth of Escherichia coli, in particular, follows a relation known as Schaechter's growth law. This law says that the average cell volume scales exponentially with growth rate, with a scaling exponent equal to the time from initiation of a round of DNA replication to the cell division at which the corresponding sister chromosomes segregate. Here, we sought to test the robustness of the growth law to systematic perturbations in cell dimensions achieved by varying the expression levels of mreB and ftsZ We found that decreasing the mreB level resulted in increased cell width, with little change in cell length, whereas decreasing the ftsZ level resulted in increased cell length. Furthermore, the time from replication termination to cell division increased with the perturbed dimension in both cases. Moreover, the growth law remained valid over a range of growth conditions and dimension perturbations. The growth law can be quantitatively interpreted as a consequence of a tight coupling of cell division to replication initiation. Thus, its robustness to perturbations in cell dimensions strongly supports models in which the timing of replication initiation governs that of cell division, and cell volume is the key phenomenological variable governing the timing of replication initiation. These conclusions are discussed in the context of our recently proposed "adder-per-origin" model, in which cells add a constant volume per origin between initiations and divide a constant time after initiation.

Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans

PubMed Central

Sierra, Crystal S.; Haase, Steven B.

2016-01-01

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation. PMID:27918582

Therapeutic Assessment for Preadolescent Boys with Oppositional Defiant Disorder: A Replicated Single-Case Time-Series Design

ERIC Educational Resources Information Center

Smith, Justin D.; Handler, Leonard; Nash, Michael R.

2010-01-01

The Therapeutic Assessment (TA) model is a relatively new treatment approach that fuses assessment and psychotherapy. The study examines the efficacy of this model with preadolescent boys with oppositional defiant disorder and their families. A replicated single-case time-series design with daily measures is used to assess the effects of TA and to…

Functional network mediates age-related differences in reaction time: a replication and extension study

PubMed Central

Gazes, Yunglin; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza R; Steffener, Jason; Stern, Yaakov

2015-01-01

Introduction A functional activation (i.e., ordinal trend) pattern was previously identified in both young and older adults during task-switching performance, the expression of which correlated with reaction time. The current study aimed to (1) replicate this functional activation pattern in a new group of fMRI activation data, and (2) extend the previous study by specifically examining whether the effect of aging on reaction time can be explained by differences in the activation of the functional activation pattern. Method A total of 47 young and 50 older participants were included in the extension analysis. Participants performed task-switching as the activation task and were cued by the color of the stimulus for the task to be performed in each block. To test for replication, two approaches were implemented. The first approach tested the replicability of the predictive power of the previously identified functional activation pattern by forward applying the pattern to the Study II data and the second approach was rederivation of the activation pattern in the Study II data. Results Both approaches showed successful replication in the new data set. Using mediation analysis, expression of the pattern from the first approach was found to partially mediate age-related effects on reaction time such that older age was associated with greater activation of the brain pattern and longer reaction time, suggesting that brain activation efficiency (defined as “the rate of activation increase with increasing task difficulty” in Neuropsychologia 47, 2009, 2015) of the regions in the Ordinal trend pattern directly accounts for age-related differences in task performance. Discussion The successful replication of the functional activation pattern demonstrates the versatility of the Ordinal Trend Canonical Variates Analysis, and the ability to summarize each participant's brain activation map into one number provides a useful metric in multimodal analysis as well as cross-study comparisons. PMID:25874162

Histone acetylation regulates the time of replication origin firing.

PubMed

Vogelauer, Maria; Rubbi, Liudmilla; Lucas, Isabelle; Brewer, Bonita J; Grunstein, Michael

2002-11-01

The temporal firing of replication origins throughout S phase in yeast depends on unknown determinants within the adjacent chromosomal environment. We demonstrate here that the state of histone acetylation of surrounding chromatin is an important regulator of temporal firing. Deletion of RPD3 histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins. In addition, increased acetylation of histones in the vicinity of the late origin ARS1412 by recruitment of the histone acetyltransferase Gcn5p causes ARS1412 alone to fire earlier. These data indicate that histone acetylation is a direct determinant of the timing of origin firing.

Passive chevron replicator

NASA Technical Reports Server (NTRS)

Oeffinger, Thomas R. (Inventor); Tocci, Leonard R. (Inventor)

1977-01-01

There is described a passive replicator device to be used in magnetic bubble domain systems. The replicator is passive, i.e., does not require an active element such as a current source or the like, and both propagates and replicates bubble domains. In a preferred embodiment, the replicator uses chevron type elements arranged in an appropriate pattern so as to interact with a pair of propagation paths wherein bubble domains are propagated. A bubble in one propagation path is routinely transferred therealong and, concurrently, replicated by the instant device into another propagation path. A plurality of elements arranged in juxtaposition to the chevrons assists in controlling the propagation of the bubbles through the respective propagation paths and, at the appropriate time, provides a cutting action wherein a bubble which is elongated between the chevrons of the two propagation paths is split into two separate bubbles.

Using Model Replication to Improve the Reliability of Agent-Based Models

NASA Astrophysics Data System (ADS)

Zhong, Wei; Kim, Yushim

The basic presupposition of model replication activities for a computational model such as an agent-based model (ABM) is that, as a robust and reliable tool, it must be replicable in other computing settings. This assumption has recently gained attention in the community of artificial society and simulation due to the challenges of model verification and validation. Illustrating the replication of an ABM representing fraudulent behavior in a public service delivery system originally developed in the Java-based MASON toolkit for NetLogo by a different author, this paper exemplifies how model replication exercises provide unique opportunities for model verification and validation process. At the same time, it helps accumulate best practices and patterns of model replication and contributes to the agenda of developing a standard methodological protocol for agent-based social simulation.

Applying a multi-replication framework to support dynamic situation assessment and predictive capabilities

NASA Astrophysics Data System (ADS)

Lammers, Craig; McGraw, Robert M.; Steinman, Jeffrey S.

2005-05-01

Technological advances and emerging threats reduce the time between target detection and action to an order of a few minutes. To effectively assist with the decision-making process, C4I decision support tools must quickly and dynamically predict and assess alternative Courses Of Action (COAs) to assist Commanders in anticipating potential outcomes. These capabilities can be provided through the faster-than-real-time predictive simulation of plans that are continuously re-calibrating with the real-time picture. This capability allows decision-makers to assess the effects of re-tasking opportunities, providing the decision-maker with tremendous freedom to make time-critical, mid-course decisions. This paper presents an overview and demonstrates the use of a software infrastructure that supports DSAP capabilities. These DSAP capabilities are demonstrated through the use of a Multi-Replication Framework that supports (1) predictivie simulations using JSAF (Joint Semi-Automated Forces); (2) real-time simulation, also using JSAF, as a state estimation mechanism; and, (3) real-time C4I data updates through TBMCS (Theater Battle Management Core Systems). This infrastructure allows multiple replications of a simulation to be executed simultaneously over a grid faster-than-real-time, calibrated with live data feeds. A cost evaluator mechanism analyzes potential outcomes and prunes simulations that diverge from the real-time picture. In particular, this paper primarily serves to walk a user through the process for using the Multi-Replication Framework providing an enhanced decision aid.

Increasing Reading Fluency Using "Read Naturally"® with Two Third Grade Students with Specific Learning Disabilities: A Replication of Erickson et al., 2015

ERIC Educational Resources Information Center

Morgan, Sarah V.; McLaughlin, T. F.; Weber, Kimberly P.; Bolich, Barbara

2016-01-01

The purpose of this research was to determine the effectiveness of the "Read Naturally"® program. The program was used in hopes to improve each student's ability in reading fluency. The study used "Read Naturally"® as an intervention for two struggling readers identified as two third grade students. The program included passage…

Evaluating Why and How the Teen Outreach Program Works: Years 3-5 of the Teen Outreach National Replication (1986/87-1988/89).

ERIC Educational Resources Information Center

Allen, Joseph P.; Philliber, Susan

An evaluative study was done of the Teen Outreach Program, a national, multi-site effort to reduce teenage pregnancy, school failure, and dropout. The study sought to identify the critical "active ingredients" of the program responsible for its success. The study was based on analyses of data collected at 114 different sites nationally,…

On your time: online training for the public health workforce.

PubMed

Kenefick, Hope Worden; Ravid, Sharon; MacVarish, Kathleen; Tsoi, Jennifer; Weill, Kenny; Faye, Elizabeth; Fidler, Anne

2014-03-01

The need for competency-based training for the public health workforce is well documented. However, human and financial resource limitations within public health agencies often make it difficult for public health practitioners to attend classroom-based training programs. The Internet is an increasingly popular way of extending training beyond the workforce. Although research describes attributes of effective online learning modules, much of the available training delivered via the Internet does not incorporate such attributes. The authors describe the On Your Time training series, an effective distance education program and training model for public health practitioners, which includes a standardized process for development, review, evaluation, and continuous quality improvement. On Your Time is a series of awareness-level (i.e., addressing what practitioners should know), competency-based training modules that address topics related to regulatory responsibilities of public health practitioners (e.g., assuring compliance with codes and regulations governing housing, retail food safety, private water supplies, hazardous and solid waste, on-site wastewater systems, etc.), public health surveillance, case investigation, disease prevention, health promotion, and emergency preparedness. The replicable model incorporates what is known about best practices for online training and maximizes available resources in the interests of sustainability.

Laser-induced heating integrated with a microfluidic platform for real-time DNA replication and detection

NASA Astrophysics Data System (ADS)

Hung, Min-Sheng; Ho, Chia-Chin; Chen, Chih-Pin

2016-08-01

This study developed a microfluidic platform for replicating and detecting DNA in real time by integrating a laser and a microfluidic device composed of polydimethylsiloxane. The design of the microchannels consisted of a laser-heating area and a detection area. An infrared laser was used as the heating source for DNA replication, and the laser power was adjusted to heat the solutions directly. In addition, strong biotin-avidin binding was used to capture and detect the replicated products. The biotin on one end was bound to avidin and anchored to the surface of the microchannels, whereas the biotin on the other end was bound to the quantum dots (Qdots). The results showed that the fluorescent intensity of the Qdots bound to the replicated products in the detection area increased with the number of thermal cycles created by the laser. When the number of thermal cycles was ≥10, the fluorescent intensity of the Qdots was directly detectable on the surface of the microchannels. The proposed method is more sensitive than detection methods entailing gel electrophoresis.

Links between genome replication and chromatin landscapes.

PubMed

Sequeira-Mendes, Joana; Gutierrez, Crisanto

2015-07-01

Post-embryonic organogenesis in plants requires the continuous production of cells in the organ primordia, their expansion and a coordinated exit to differentiation. Genome replication is one of the most important processes that occur during the cell cycle, as the maintenance of genomic integrity is of primary relevance for development. As it is chromatin that must be duplicated, a strict coordination occurs between DNA replication, the deposition of new histones, and the introduction of histone modifications and variants. In turn, the chromatin landscape affects several stages during genome replication. Thus, chromatin accessibility is crucial for the initial stages and to specify the location of DNA replication origins with different chromatin signatures. The chromatin landscape also determines the timing of activation during the S phase. Genome replication must occur fully, but only once during each cell cycle. The re-replication avoidance mechanisms rely primarily on restricting the availability of certain replication factors; however, the presence of specific histone modifications are also revealed as contributing to the mechanisms that avoid re-replication, in particular for heterochromatin replication. We provide here an update of genome replication mostly focused on data from Arabidopsis, and the advances that genomic approaches are likely to provide in the coming years. The data available, both in plants and animals, point to the relevance of the chromatin landscape in genome replication, and require a critical evaluation of the existing views about the nature of replication origins, the mechanisms of origin specification and the relevance of epigenetic modifications for genome replication. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Rapid biotic homogenization of marine fish assemblages

PubMed Central

Magurran, Anne E.; Dornelas, Maria; Moyes, Faye; Gotelli, Nicholas J.; McGill, Brian

2015-01-01

The role human activities play in reshaping biodiversity is increasingly apparent in terrestrial ecosystems. However, the responses of entire marine assemblages are not well-understood, in part, because few monitoring programs incorporate both spatial and temporal replication. Here, we analyse an exceptionally comprehensive 29-year time series of North Atlantic groundfish assemblages monitored over 5° latitude to the west of Scotland. These fish assemblages show no systematic change in species richness through time, but steady change in species composition, leading to an increase in spatial homogenization: the species identity of colder northern localities increasingly resembles that of warmer southern localities. This biotic homogenization mirrors the spatial pattern of unevenly rising ocean temperatures over the same time period suggesting that climate change is primarily responsible for the spatial homogenization we observe. In this and other ecosystems, apparent constancy in species richness may mask major changes in species composition driven by anthropogenic change. PMID:26400102

Checkpoints: it takes more than time to heal some wounds.

PubMed

Rhind, N; Russell, P

The S-phase DNA damage checkpoint seems to provide a twist on the checkpoint theme. Instead of delaying replication and allowing repair as a consequence, it may activate repair and delay replication as a consequence.

Performance analysis of static locking in replicated distributed database systems

NASA Technical Reports Server (NTRS)

Kuang, Yinghong; Mukkamala, Ravi

1991-01-01

Data replications and transaction deadlocks can severely affect the performance of distributed database systems. Many current evaluation techniques ignore these aspects, because it is difficult to evaluate through analysis and time consuming to evaluate through simulation. Here, a technique is discussed that combines simulation and analysis to closely illustrate the impact of deadlock and evaluate performance of replicated distributed databases with both shared and exclusive locks.

Development of factors to convert frequency to rate for β-cell replication and apoptosis quantified by time-lapse video microscopy and immunohistochemistry

PubMed Central

Saisho, Yoshifumi; Manesso, Erica; Gurlo, Tatyana; Huang, Chang-jiang; Toffolo, Gianna M.; Cobelli, Claudio; Butler, Peter C.

2009-01-01

An obstacle to development of methods to quantify β-cell turnover from pancreas tissue is the lack of conversion factors for the frequency of β-cell replication or apoptosis detected by immunohistochemistry to rates of replication or apoptosis. We addressed this obstacle in islets from 1-mo-old rats by quantifying the relationship between the rate of β-cell replication observed directly by time-lapse video microscopy (TLVM) and the frequency of β-cell replication in the same islets detected by immunohistochemistry using antibodies against Ki67 and insulin in the same islets fixed immediately after TLVM. Similarly, we quantified the rate of β-cell apoptosis by TLVM and then the frequency of apoptosis in the same islets using TdT-mediated dUTP nick-end labeling and insulin. Conversion factors were developed by regression analysis. The conversion factor from Ki67 labeling frequency (%) to actual replication rate (%events/h) is 0.025 ± 0.003 h−1. The conversion factor from TdT-mediated dUTP nick-end labeling frequency (%) to actual apoptosis rate (%events/h) is 0.41 ± 0.05 h−1. These conversion factors will permit development of models to evaluate β-cell turnover in fixed pancreas tissue. PMID:18940937

The activities of eukaryotic replication origins in chromatin.

PubMed

Weinreich, Michael; Palacios DeBeer, Madeleine A; Fox, Catherine A

2004-03-15

DNA replication initiates at chromosomal positions called replication origins. This review will focus on the activity, regulation and roles of replication origins in Saccharomyces cerevisiae. All eukaryotic cells, including S. cerevisiae, depend on the initiation (activity) of hundreds of replication origins during a single cell cycle for the duplication of their genomes. However, not all origins are identical. For example, there is a temporal order to origin activation with some origins firing early during the S-phase and some origins firing later. Recent studies provide evidence that posttranslational chromatin modifications, heterochromatin-binding proteins and nucleosome positioning can control the efficiency and/or timing of chromosomal origin activity in yeast. Many more origins exist than are necessary for efficient replication. The availability of excess replication origins leaves individual origins free to evolve distinct forms of regulation and/or roles in chromosomes beyond their fundamental role in DNA synthesis. We propose that some origins have acquired roles in controlling chromatin structure and/or gene expression. These roles are not linked obligatorily to replication origin activity per se, but instead exploit multi-subunit replication proteins with the potential to form context-dependent protein-protein interactions.

Prereplicative events involving simian virus 40 DNA in permissive cells

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

Rinaldy, A.; Feunteun, J.; Rosenberg, B.H.

1982-01-01

Simian virus 40 DNA molecules were found to be unable to replicate for 9 h after infection, even in cells that were already replicating the DNA of preinfecting simian virus 40; after 9 h, the ability of the DNA to replicate began to rise sharply. The kinetics of activation indicated that each DNA molecule undergoes a series of slow consecutive reactions, not involving T-antigen, before it can replicate. These pre-replicative molecular transformations probably involve configurational changes; their nature and their relation to the initiation of viral DNA synthesis is discussed. Observation of the replicative behavior of one viral DNA inmore » the presence of another was made possible by the use of two different mutants with distinguishable DNAs: a viable deletion mutant containing DNA insensitive to TaqI restriction enzyme was used to provide viral functions required for replication, and is a tsA mutant with TaqI-sensitive DNA was introduced at various times as a probe to determine the ability of the DNA to replicate under different conditions.« less

Bridging evidence-practice gaps: improving use of medicines in elderly Australian veterans.

PubMed

Roughead, Elizabeth E; Kalisch Ellett, Lisa M; Ramsay, Emmae N; Pratt, Nicole L; Barratt, John D; LeBlanc, Vanessa T; Ryan, Philip; Peck, Robert; Killer, Graeme; Gilbert, Andrew L

2013-12-12

The Australian Government Department of Veterans' Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. The Veterans' MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings.

CDK1 promotes nascent DNA synthesis and induces resistance of cancer cells to DNA-damaging therapeutic agents

PubMed Central

Liao, Hongwei; Ji, Fang; Geng, Xinwei; Xing, Meichun; Li, Wen; Chen, Zhihua; Shen, Huahao; Ying, Songmin

2017-01-01

Cyclin dependent kinase 1 (CDK1) is essential for cell viability and plays a vital role in many biological events including cell cycle control, DNA damage repair, and checkpoint activation. Here, we identify an unanticipated role for CDK1 in promoting nascent DNA synthesis during S-phase. We report that a short duration of CDK1 inhibition, which does not perturb cell cycle progression, triggers a replication-associated DNA damage response (DDR). This DDR is associated with a disruption of replication fork progression and leads to genome instability. Moreover, we show that compromised CDK1 activity dramatically increases the efficacy of chemotherapeutic agents that kill cancer cells through perturbing DNA replication, including Olaparib, an FDA approved PARP inhibitor. Our study has revealed an important role for CDK1 in the DNA replication program, and suggests that the therapeutic targeting CDK1 may be a novel approach for combination chemotherapy. PMID:29207595

Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication

PubMed Central

Trask, Shane D.; McDonald, Sarah M.; Patton, John T.

2013-01-01

Preface Viral replication is rapid and robust, but it is far from a chaotic process. Instead, successful production of infectious progeny requires that events occur in the correct place and at the correct time. Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, seems to govern its replication through ordered disassembly and assembly of a triple-layered icosahedral capsid. In recent years, high-resolution structural data have provided unprecedented insight into these events. In this Review, we explore the current understanding of rotavirus replication and how it compares to other Reoviridae family members. PMID:22266782

Replication and Pedagogy in the History of Psychology V: The Metronome and Wilhelm Wundt's Search for the Components of Consciousness

NASA Astrophysics Data System (ADS)

Ayala, Christopher; Borawski, Steven; Miller, Jonathon

2008-05-01

Wilhelm Wundt (1832 1920) believed that consciousness was represented by the interconnection of psychical processes comprised of temporal elements and compounds. To explore these processes, Wundt used a metronome to measure the amount of information that passed into consciousness across time. The current project replicated some of his procedures, to better understand the role of introspection and the complexity of the metronome task for experimenters and observers. The results of the replication were mixed, but the replication helped provide insights into Wundt’s procedures and their relationship to his theories.

Speeding Up Non-Parametric Bootstrap Computations for Statistics Based on Sample Moments in Small/Moderate Sample Size Applications

PubMed Central

Chaibub Neto, Elias

2015-01-01

In this paper we propose a vectorized implementation of the non-parametric bootstrap for statistics based on sample moments. Basically, we adopt the multinomial sampling formulation of the non-parametric bootstrap, and compute bootstrap replications of sample moment statistics by simply weighting the observed data according to multinomial counts instead of evaluating the statistic on a resampled version of the observed data. Using this formulation we can generate a matrix of bootstrap weights and compute the entire vector of bootstrap replications with a few matrix multiplications. Vectorization is particularly important for matrix-oriented programming languages such as R, where matrix/vector calculations tend to be faster than scalar operations implemented in a loop. We illustrate the application of the vectorized implementation in real and simulated data sets, when bootstrapping Pearson’s sample correlation coefficient, and compared its performance against two state-of-the-art R implementations of the non-parametric bootstrap, as well as a straightforward one based on a for loop. Our investigations spanned varying sample sizes and number of bootstrap replications. The vectorized bootstrap compared favorably against the state-of-the-art implementations in all cases tested, and was remarkably/considerably faster for small/moderate sample sizes. The same results were observed in the comparison with the straightforward implementation, except for large sample sizes, where the vectorized bootstrap was slightly slower than the straightforward implementation due to increased time expenditures in the generation of weight matrices via multinomial sampling. PMID:26125965

Nucleosomes influence multiple steps during replication initiation

PubMed Central

Azmi, Ishara F; Watanabe, Shinya; Maloney, Michael F; Kang, Sukhyun; Belsky, Jason A; MacAlpine, David M; Peterson, Craig L; Bell, Stephen P

2017-01-01

Eukaryotic replication origin licensing, activation and timing are influenced by chromatin but a mechanistic understanding is lacking. Using reconstituted nucleosomal DNA replication assays, we assessed the impact of nucleosomes on replication initiation. To generate distinct nucleosomal landscapes, different chromatin-remodeling enzymes (CREs) were used to remodel nucleosomes on origin-DNA templates. Nucleosomal organization influenced two steps of replication initiation: origin licensing and helicase activation. Origin licensing assays showed that local nucleosome positioning enhanced origin specificity and modulated helicase loading by influencing ORC DNA binding. Interestingly, SWI/SNF- and RSC-remodeled nucleosomes were permissive for origin licensing but showed reduced helicase activation. Specific CREs rescued replication of these templates if added prior to helicase activation, indicating a permissive chromatin state must be established during origin licensing to allow efficient origin activation. Our studies show nucleosomes directly modulate origin licensing and activation through distinct mechanisms and provide insights into the regulation of replication initiation by chromatin. DOI: http://dx.doi.org/10.7554/eLife.22512.001 PMID:28322723

Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

PubMed

Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

2009-12-01

Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

Nucleosomes in the neighborhood

PubMed Central

Dorn, Elizabeth Suzanne

2011-01-01

The importance of local chromatin structure in regulating replication initiation has become increasingly apparent. Most recently, histone methylation and nucleosome positioning have been added to the list of modifications demonstrated to regulate origins. In particular, the methylation states of H3K4, H3K36 and H4K20 have been associated with establishing active, repressed or poised origins depending on the timing and extent of methylation. The stability and precise positioning of nucleosomes has also been demonstrated to affect replication efficiency. Although it is not yet clear how these modifications alter the behavior of specific replication factors, ample evidence establishes their role in maintaining coordinated replication. This review will summarize recent advances in understanding these aspects of chromatin structure in DNA replication origin control. PMID:21364325

Physical Assessment Techniques in Nursing Education: A Replicated Study.

PubMed

Kohtz, Cindy; Brown, Suzanne C; Williams, Ryan; O'Connor, Patricia A

2017-05-01

It has been nearly a decade since findings revealed that a sample of U.S. nurses routinely used only 30 physical assessment techniques in clinical practice. In a time of differentiating nice-to-know from need-to-know knowledge and skills, what has changed in nursing education? This cross-sectional, descriptive study examines the physical assessment skills taught and used among nursing students at one baccalaureate nursing education program located in the midwestern United States. Findings highlight the similarities and differences from previous studies and offer insight as to how closely nursing education mirrors the skills needed for clinical practice. Nurse educators must continue to discriminate content taught in prelicensure nursing education programs and should consider the attainment of competency of those essential skills that most lend to optimal patient outcomes. [J Nurs Educ. 2017;56(5):287-291.]. Copyright 2017, SLACK Incorporated.

Evaluation of the William S. Hall Psychiatric Institute Clinical Psychology Internship: a replication and extension.

PubMed

Stader, Sandra R; Myers, DeRosset; Forand, Angela Q; Holmes, George R; McNulty, George F; Frey, Linda; Bolton, Staci S

2010-12-01

This study extends three earlier investigations involving participants who completed their predoctoral clinical psychology internship at the William S. Hall Psychiatric Institute. Intern graduates (N = 37) evaluated how effectively their internship training prepared them for seven aspects of their current work as practicing psychologists. Participants also rated the relevancy of 24 different internship training experiences to their current work and how much these experiences contributed to their development as clinical psychologists. The present study, in conjunction with the three previous studies, covers most of the 40-year period since the inception of the internship program. Analysis of the current data indicates the internship has improved over time and was deemed an exceptional training experience by its graduates. Findings may be of particular interest to internship directors and faculty interested in improving their training program and those who plan to conduct a self-study to maintain their accreditation for clinical psychology internship.

34 CFR 611.11 - What are the program's general selection criteria?

Code of Federal Regulations, 2011 CFR

2011-07-01

...; (ii) Project outcomes lead directly to improvements in teaching quality and student achievement as... after federal funding ends; and (iv) Project strategies, methods, and accomplishments are replicable...

Strengthening senior tax credit programs in Massachusetts.

PubMed

Kiesel, Kristin

2002-01-01

In the last decade, property taxes have increased, creating a financial burden on senior homeowners. In Massachusetts, senior property tax credit programs have arisen to address this problem, as well as to provide cost-effective volunteer assistance for municipal departments, offer seniors meaningful work that otherwise would not have been attempted, and foster involvement in municipal government among seniors. The success of the programs in retaining senior homeowners in the community remains to be evaluated. Program specifics are detailed, policy options are considered, and recommendations are made to strengthen existing programs and assist replication.

Yeast for virus research

PubMed Central

Zhao, Richard Yuqi

2017-01-01

Budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) are two popular model organisms for virus research. They are natural hosts for viruses as they carry their own indigenous viruses. Both yeasts have been used for studies of plant, animal and human viruses. Many positive sense (+) RNA viruses and some DNA viruses replicate with various levels in yeasts, thus allowing study of those viral activities during viral life cycle. Yeasts are single cell eukaryotic organisms. Hence, many of the fundamental cellular functions such as cell cycle regulation or programed cell death are highly conserved from yeasts to higher eukaryotes. Therefore, they are particularly suited to study the impact of those viral activities on related cellular activities during virus-host interactions. Yeasts present many unique advantages in virus research over high eukaryotes. Yeast cells are easy to maintain in the laboratory with relative short doubling time. They are non-biohazardous, genetically amendable with small genomes that permit genome-wide analysis of virologic and cellular functions. In this review, similarities and differences of these two yeasts are described. Studies of virologic activities such as viral translation, viral replication and genome-wide study of virus-cell interactions in yeasts are highlighted. Impacts of viral proteins on basic cellular functions such as cell cycle regulation and programed cell death are discussed. Potential applications of using yeasts as hosts to carry out functional analysis of small viral genome and to develop high throughput drug screening platform for the discovery of antiviral drugs are presented. PMID:29082230

Optimal therapies of a virus replication model with pharmacological delays based on reverse transcriptase inhibitors and protease inhibitors

NASA Astrophysics Data System (ADS)

Pei, Yongzhen; Li, Changguo; Liang, Xiyin

2017-11-01

A short delay in the pharmacological effect on account of the time required for drug absorption, distribution, and penetration into target cells after application of any anti-viral drug, is defined by the pharmacological delay (Herz et al 1996 Proc. Natl Acad. Sci. USA 93 7247-51). In this paper, a virus replication model with Beddington-DeAngelis incidence rate and the pharmacological and intracellular delays is presented to describe the treatment to cure the virus infection. The optimal controls represent the efficiency of reverse transcriptase inhibitors and protease inhibitors in suppressing viral production and prohibiting new infections. Due to the fact that both the control and state variables contain delays, we derive a necessary conditions for our optimal problem. Based on these results, numerical simulations are implemented not only to show the optimal therapeutic schedules for different infection and release rates, but also to compare the effective of three treatment programs. Furthermore, comparison of therapeutic effects under different maximum tolerable dosages is shown. Our research indicates that (1) the proper and specific treatment program should be determined according to the infection rates of different virus particles; (2) the optimal combined drug treatment is the most efficient; (3) the appropriate proportion of medicament must be formulated during the therapy due to the non-monotonic relationship between maximum tolerable dosages and therapeutic effects; (4) the therapeutic effect is advantageous when the pharmacological delay is considered.

Discrepancy Reporting Management System

NASA Technical Reports Server (NTRS)

Cooper, Tonja M.; Lin, James C.; Chatillon, Mark L.

2004-01-01

Discrepancy Reporting Management System (DRMS) is a computer program designed for use in the stations of NASA's Deep Space Network (DSN) to help establish the operational history of equipment items; acquire data on the quality of service provided to DSN customers; enable measurement of service performance; provide early insight into the need to improve processes, procedures, and interfaces; and enable the tracing of a data outage to a change in software or hardware. DRMS is a Web-based software system designed to include a distributed database and replication feature to achieve location-specific autonomy while maintaining a consistent high quality of data. DRMS incorporates commercial Web and database software. DRMS collects, processes, replicates, communicates, and manages information on spacecraft data discrepancies, equipment resets, and physical equipment status, and maintains an internal station log. All discrepancy reports (DRs), Master discrepancy reports (MDRs), and Reset data are replicated to a master server at NASA's Jet Propulsion Laboratory; Master DR data are replicated to all the DSN sites; and Station Logs are internal to each of the DSN sites and are not replicated. Data are validated according to several logical mathematical criteria. Queries can be performed on any combination of data.

The Impact of Donor Viral Replication at Transplant on Recipient Infections Posttransplant: A Prospective Study

PubMed Central

Verghese, Priya S.; Schmeling, David O.; Knight, Jennifer A.; Matas, Arthur J.; Balfour, Henry H.

2014-01-01

Background Organ donors are often implicated as the source of posttransplant recipient infection. We prospectively studied kidney and liver donor-recipient pairs to determine if donor viral replication of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) at transplant was a risk factor for posttransplant recipient infection and disease. Methods Donors and recipients were studied for antibodies against CMV and EBV and for quantitative viral replication of CMV, EBV and BKV in oral washes, urine, and whole blood pretransplant. Recipient testing continued every 3 months posttransplant. Demographic and clinical data on infections and graft and subject outcomes were obtained. Results The 98 donor-recipient pairs included 15 liver and 83 kidney transplants (18 of whom were children). No donor had detectable CMV replication; therefore its impact on recipient CMV replication could not be analyzed. Donor EBV replication occurred in 22%, mostly in the oral wash and had no impact on posttransplant recipient EBV replication (p 0.9) or EBV viremia (p 0.6) in kidney or liver recipients. Donor BKV replication occurred in 17%, mostly in the urine and although not associated with posttransplant recipient urinary BKV replication in recipients, it was associated with BKV viremia (p 0.02), and a significantly shorter time to BKV viremia (p 0.01) in kidney recipients. Conclusion Donor replication of CMV or EBV did not impact posttransplant recipient viral replication in kidney/liver transplants. Donor urinary BKV replication is associated with recipient BKV viremia in kidney transplants. PMID:25148381

Mathematics intervention for children with fetal alcohol spectrum disorder: A replication and extension of the math interactive learning experience (MILE) program.

PubMed

Kully-Martens, Katrina; Pei, Jacqueline; Kable, Julie; Coles, Claire D; Andrew, Gail; Rasmussen, Carmen

2018-07-01

Individuals with fetal alcohol spectrum disorders (FASD) experience deficits in behavior, cognition, and academic functioning resulting from prenatal alcohol exposure (PAE). Although receiving intervention for developmental disabilities is a strong protective factor against negative outcomes in FASD, intervention research in this population is in its infancy. The purpose of this study was to replicate and extend a mathematics intervention, the Math Interactive Learning Experience (MILE) program, which was developed in the USA specifically for children with FASD. Twenty-eight Canadian children aged 4-10 years with confirmed PAE or an FASD diagnosis were assigned to either the MILE intervention or a contrast intervention. Following a relatively brief, individualized, one-on-one intervention, children in the MILE group demonstrated significantly greater changes in math achievement compared to the contrast group. Significant changes in other cognitive functions were not observed. Older age, lower IQ, and confirmed PAE but no FASD diagnosis were associated with greater math achievement change in the MILE group. The replication and extension of the math intervention appears to have significant, positive impact on mathematics achievement scores of children with PAE and FASD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Internship Experiences Contribute to Confident Career Decision Making for Doctoral Students in the Life Sciences

ERIC Educational Resources Information Center

Schnoes, Alexandra M.; Caliendo, Anne; Morand, Janice; Dillinger, Teresa; Naffziger-Hirsch, Michelle; Moses, Bruce; Gibeling, Jeffery C.; Yamamoto, Keith R.; Lindstaedt, Bill; McGee, Richard; O'Brien, Theresa C.

2018-01-01

The Graduate Student Internships for Career Exploration (GSICE) program at the University of California, San Francisco (UCSF), offers structured training and hands-on experience through internships for a broad range of PhD-level careers. The GSICE program model was successfully replicated at the University of California, Davis (UC Davis). Here, we…

Replication of Effects of the "Positive Action" Program in Randomized Trials in Hawai'i and Chicago Schools

ERIC Educational Resources Information Center

Flay, Brian R.

2014-01-01

Several social-emotional learning (SEL) or social-emotional and character development (SECD) programs have been shown to be effective at improving SEL/SECD skills, and some have also provided evidence of effectiveness in improving student behavior and academic achievement (Durlak, Weissberg, Dymnicki, Taylor, & Schellinger, 2011). Very few SEL…

Comprehensive Evaluation Report for the Canadian Replication of the Families and Schools Together (FAST) Program.

ERIC Educational Resources Information Center

Sass, James S.

Families and Schools Together (FAST) is a 2-year program beginning with 8 weeks of multiple family meetings and transitioning into a long-term follow-up segment called FASTWORKS. FAST uses tested family therapy principles, delinquency and substance-abuse strategies, psychiatric techniques, family systems theory, and group dynamics to give parents…

Choosing a Truly External Evaluator

ERIC Educational Resources Information Center

Ray, Marilyn

2006-01-01

This scenario discusses a situation in which a proposal has been published by a consortium of foundations for an "external" evaluator to evaluate a replication at two new sites of a program they have been funding for many years. A proposal is received from Dr. Porto-Novo, who has been the external evaluator of the initial program for about 10…

Replication of an Inter-Disciplinary Approach to Early Education of Handicapped Children 0-3 Years.

ERIC Educational Resources Information Center

Smiley, Constance J.; And Others

Presented is the guide to the Illinois project entitled "An Inter-Disciplinary Approach to Early Education of Handicapped Children Ages 0 - 3 Years" which includes information on funding and public awareness, diagnosis and evaluation, child development-home program, speech and language, structuring the day program, job descriptions and training,…

Chief Dull Knife Community Is Strengthening the Northern Cheyenne Language and Culture.

ERIC Educational Resources Information Center

Littlebear, Richard E.

2003-01-01

Language revitalization programs should focus on whether they want to teach the language, teach about the language, teach with the language, or teach the language for academic credit. A program at Chief Dull Knife College (Montana) teaches the Cheyenne language using the Total Physical Response method, which replicates the manner in which first…

Asset-building, financial self-management service model: piecing together consumer financial independence.

PubMed

Swarbrick, Margaret

2006-10-01

This program represents an innovative approach to traditional money-management services. This asset-building, financial self-management service model has the potential to positively affect recovery, self-sufficiency, and community integration for people with mental illnesses. It is hoped this program will be replicated by other providers in a way that may effect systems change.

Toward High Quality Family Day Care for Infants and Toddlers. Final Report.

ERIC Educational Resources Information Center

Rauch, Marian D.; Crowell, Doris C.

Reported were the results of a project which established a cluster of family day care homes in Hawaii in which caregivers were selected, trained, and provided with supportive services and salaries. The primary objective of the program was to provide a replicable, high quality program for preschool children that would maximize social, emotional,…

The Effects of Nonverbal Skill on Dimensions of Global Personality: Six Correlational and Nine Experimental Replicated Studies

ERIC Educational Resources Information Center

Klinzing, Hans Gerhard; Aloisio, Bernadette Gerada

2007-01-01

A research-based program was designed for the improvement of decoding and encoding nonverbal cues as they are important aspects of successful communication and teaching. To extend the scientific base of the program, six correlational studies (N=784) investigated relationships between nonverbal skill and personality dimensions. Low non-significant…

Reading Improvement through Art Replicator Manual of Instruction, 3rd Edition

ERIC Educational Resources Information Center

Corwin, Sylvia K., Ed.

2013-01-01

Reading Improvement Through Art (RITA) program is an interdisciplinary approach to literacy that blends visual art with reading comprehension, evaluated in nine New York City urban high schools. 240 problem readers participating in the pilot program were pre- and post-tested in the Fall 1975 and Spring 1976 semesters. The testing showed the 9th…

Checkpoints: It takes more than time to heal some wounds

PubMed Central

Rhind, Nicholas; Russell, Paul

2010-01-01

The S-phase DNA damage checkpoint seems to provide a twist on the checkpoint theme. Instead of delaying replication and allowing repair as a consequence, it may activate repair and delay replication as a consequence. PMID:11137027

Prospective elementary teachers' conceptions of multidigit number: exemplifying a replication framework for mathematics education

NASA Astrophysics Data System (ADS)

Jacobson, Erik; Simpson, Amber

2018-04-01

Replication studies play a critical role in scientific accumulation of knowledge, yet replication studies in mathematics education are rare. In this study, the authors replicated Thanheiser's (Educational Studies in Mathematics 75:241-251, 2010) study of prospective elementary teachers' conceptions of multidigit number and examined the main claim that most elementary pre-service teachers think about digits incorrectly at least some of the time. Results indicated no statistically significant difference in the distribution of conceptions between the original and replication samples and, moreover, no statistically significant differences in the distribution of sub-conceptions among prospective teachers with the most common conception. These results suggest confidence is warranted both in the generality of the main claim and in the utility of the conceptions framework for describing prospective elementary teachers' conceptions of multidigit number. The report further contributes a framework for replication of mathematics education research adapted from the field of psychology.

Autophagy Facilitates Salmonella Replication in HeLa Cells

PubMed Central

Yu, Hong B.; Croxen, Matthew A.; Marchiando, Amanda M.; Ferreira, Rosana B. R.; Cadwell, Ken; Foster, Leonard J.; Finlay, B. Brett

2014-01-01

ABSTRACT Autophagy is a process whereby a double-membrane structure (autophagosome) engulfs unnecessary cytosolic proteins, organelles, and invading pathogens and delivers them to the lysosome for degradation. We examined the fate of cytosolic Salmonella targeted by autophagy and found that autophagy-targeted Salmonella present in the cytosol of HeLa cells correlates with intracellular bacterial replication. Real-time analyses revealed that a subset of cytosolic Salmonella extensively associates with autophagy components p62 and/or LC3 and replicates quickly, whereas intravacuolar Salmonella shows no or very limited association with p62 or LC3 and replicates much more slowly. Replication of cytosolic Salmonella in HeLa cells is significantly decreased when autophagy components are depleted. Eventually, hyperreplication of cytosolic Salmonella potentiates cell detachment, facilitating the dissemination of Salmonella to neighboring cells. We propose that Salmonella benefits from autophagy for its cytosolic replication in HeLa cells. PMID:24618251

Effectiveness of a peer-delivered dissonance-based program in reducing eating disorder risk factors in high school girls.

PubMed

Ciao, Anna C; Latner, Janet D; Brown, Krista E; Ebneter, Daria S; Becker, Carolyn B

2015-09-01

This pilot study investigated the feasibility, acceptability, and effectiveness of a peer-led dissonance-based eating disorders (ED) prevention/risk factor reduction program with high school girls. Ninth grade girls (n = 50) received the peer-led program within the school curriculum. A quasi-experimental design was used to assess changes in ED risk factors preintervention and postintervention compared with waitlist control. Participants were followed through 3-month follow-up. Peer-leader adherence to an intervention manual tailored for this age group was high. The intervention was rated as highly acceptable, with a large proportion of participants reporting that they enjoyed the program and learned and applied new information. Intervention participants exhibited significantly greater pre-post reductions in a majority of risk-factor outcomes compared to waitlist controls. When groups were combined to assess program effects over time there were significant pre-post reductions in a majority of outcomes that were sustained through 3-month follow-up. This pilot study provides tentative support for the effectiveness of using peer leaders to implement an empirically supported ED risk factor reduction program in a high school setting. Additional research is needed to replicate results in larger, better-controlled trials with longer follow-up. © 2015 Wiley Periodicals, Inc.

TRI University Challenge

EPA Pesticide Factsheets

Details about the TRI University Challenge, in which EPA is looking to academic institutions to help build a diverse portfolio of practical and replicable projects that benefit communities, the environment, academic institutions, and the TRI Program.

Rapid Communication: Effect of machine, anatomical location, and replication on instrumental color of boneless pork loins.

PubMed

Barkley, K E; Fields, B; Dilger, A C; Boler, D D

2018-06-07

The objective was to determine the effect of machine, anatomical location and replication (multiple readings) on instrumental color and to characterize the amount of variation each factor contributed to overall color. Instrumental color was measured 3 times on the anterior and 3 times on the posterior end of 250 pork loins with 2 different Minolta CR-400 Chroma meter devices. Each Minolta was programed to use a D65 illuminant, 2º observer with an 8 mm aperture, and calibrated with white tiles specific to each machine. Therefore, a total of 12 instrumental color measurements were collected on each loin. The VARCOMP procedure in SAS was used to estimate the proportion of variation contributed by each factor to CIE L*, a*, b*, chroma and hue. Based on previous research, the average untrained consumer is able to distinguish between 3-L* units, 0.4-a* units, and 0.9-hue angle units. Loins evaluated with machine 1 were 0.71 L* units darker (P < 0.01), 1.09 b* units more yellow (P < 0.01), 0.47 chroma units more saturated (P < 0.01), and had a hue angle 5.12 units greater (P < 0.01) than when evaluated with machine 2 but did not differ (P = 0.24) in redness. The anterior portion of the loin was lighter, less red, more yellow, more saturated and had a greater hue angle than the posterior end (P < 0.01). All color trait values decreased (P < 0.01) as replication number increased. Inherent color differences among loins contributed the greatest proportion of variability for lightness (58%), redness (57%), yellowness (70%), saturation (70%) and hue angle (49%). Machine contributed 1% variability to lightness 3% to saturation, 23% to yellowness and 31% to hue angle (31%) but did not contribute to variability for redness. Anatomical location contributed 41% to lightness, 43% to redness, 7% to yellowness, 27% to saturation and 31% to hue angle. Replication did not contribute to total variation for any color traits, even though it did differ among measurements. Overall, there were differences in instrumental color values between the two machines tested but those differences were likely less than the threshold for detection by a consumer. Even so, inherent color differences between loins were a greater contributor to total variability than the differences between the 2 machines. Therefore, it is more important to define the location of measurements than replication or machine when using a Minolta CR-400 when performing color evaluations, assuming the settings are the same.

Uncovering the genetic signature of quantitative trait evolution with replicated time series data.

PubMed

Franssen, S U; Kofler, R; Schlötterer, C

2017-01-01

The genetic architecture of adaptation in natural populations has not yet been resolved: it is not clear to what extent the spread of beneficial mutations (selective sweeps) or the response of many quantitative trait loci drive adaptation to environmental changes. Although much attention has been given to the genomic footprint of selective sweeps, the importance of selection on quantitative traits is still not well studied, as the associated genomic signature is extremely difficult to detect. We propose 'Evolve and Resequence' as a promising tool, to study polygenic adaptation of quantitative traits in evolving populations. Simulating replicated time series data we show that adaptation to a new intermediate trait optimum has three characteristic phases that are reflected on the genomic level: (1) directional frequency changes towards the new trait optimum, (2) plateauing of allele frequencies when the new trait optimum has been reached and (3) subsequent divergence between replicated trajectories ultimately leading to the loss or fixation of alleles while the trait value does not change. We explore these 3 phase characteristics for relevant population genetic parameters to provide expectations for various experimental evolution designs. Remarkably, over a broad range of parameters the trajectories of selected alleles display a pattern across replicates, which differs both from neutrality and directional selection. We conclude that replicated time series data from experimental evolution studies provide a promising framework to study polygenic adaptation from whole-genome population genetics data.

Warning times for species extinctions due to climate change.

PubMed

Stanton, Jessica C; Shoemaker, Kevin T; Pearson, Richard G; Akçakaya, H Resit

2015-03-01

Climate change is likely to become an increasingly major obstacle to slowing the rate of species extinctions. Several new assessment approaches have been proposed for identifying climate-vulnerable species, based on the assumption that established systems such as the IUCN Red List need revising or replacing because they were not developed to explicitly consider climate change. However, no assessment approach has been tested to determine its ability to provide advanced warning time for conservation action for species that might go extinct due to climate change. To test the performance of the Red List system in this capacity, we used linked niche-demographic models with habitat dynamics driven by a 'business-as-usual' climate change scenario. We generated replicate 100-year trajectories for range-restricted reptiles and amphibians endemic to the United States. For each replicate, we categorized the simulated species according to IUCN Red List criteria at annual, 5-year, and 10-year intervals (the latter representing current practice). For replicates that went extinct, we calculated warning time as the number of years the simulated species was continuously listed in a threatened category prior to extinction. To simulate data limitations, we repeated the analysis using a single criterion at a time (disregarding other listing criteria). Results show that when all criteria can be used, the Red List system would provide several decades of warning time (median = 62 years; >20 years for 99% of replicates), but suggest that conservation actions should begin as soon as a species is listed as Vulnerable, because 50% of replicates went extinct within 20 years of becoming uplisted to Critically Endangered. When only one criterion was used, warning times were substantially shorter, but more frequent assessments increased the warning time by about a decade. Overall, we found that the Red List criteria reliably provide a sensitive and precautionary way to assess extinction risk under climate change. © 2014 John Wiley & Sons Ltd.

Concurrent micro-RNA mediated silencing of tick-borne flavivirus replication in tick vector and in the brain of vertebrate host.

PubMed

Tsetsarkin, Konstantin A; Liu, Guangping; Kenney, Heather; Hermance, Meghan; Thangamani, Saravanan; Pletnev, Alexander G

2016-09-13

Tick-borne viruses include medically important zoonotic pathogens that can cause life-threatening diseases. Unlike mosquito-borne viruses, whose impact can be restrained via mosquito population control programs, for tick-borne viruses only vaccination remains the reliable means of disease prevention. For live vaccine viruses a concern exists, that spillovers from viremic vaccinees could result in introduction of genetically modified viruses into sustainable tick-vertebrate host transmission cycle in nature. To restrict tick-borne flavivirus (Langat virus, LGTV) vector tropism, we inserted target sequences for tick-specific microRNAs (mir-1, mir-275 and mir-279) individually or in combination into several distant regions of LGTV genome. This caused selective attenuation of viral replication in tick-derived cells. LGTV expressing combinations of target sequences for tick- and vertebrate CNS-specific miRNAs were developed. The resulting viruses replicated efficiently and remained stable in simian Vero cells, which do not express these miRNAs, however were severely restricted to replicate in tick-derived cells. In addition, simultaneous dual miRNA targeting led to silencing of virus replication in live Ixodes ricinus ticks and abolished virus neurotropism in highly permissive newborn mice. The concurrent restriction of adverse replication events in vertebrate and invertebrate hosts will, therefore, ensure the environmental safety of live tick-borne virus vaccine candidates.

Replication stress affects the fidelity of nucleosome-mediated epigenetic inheritance

PubMed Central

Li, Wenzhu; Yi, Jia; Agbu, Pamela; Zhou, Zheng; Kelley, Richard L.; Jia, Songtao

2017-01-01

The fidelity of epigenetic inheritance or, the precision by which epigenetic information is passed along, is an essential parameter for measuring the effectiveness of the process. How the precision of the process is achieved or modulated, however, remains largely elusive. We have performed quantitative measurement of epigenetic fidelity, using position effect variegation (PEV) in Schizosaccharomyces pombe as readout, to explore whether replication perturbation affects nucleosome-mediated epigenetic inheritance. We show that replication stresses, due to either hydroxyurea treatment or various forms of genetic lesions of the replication machinery, reduce the inheritance accuracy of CENP-A/Cnp1 nucleosome positioning within centromere. Mechanistically, we demonstrate that excessive formation of single-stranded DNA, a common molecular abnormality under these conditions, might have correlation with the reduction in fidelity of centromeric chromatin duplication. Furthermore, we show that replication stress broadly changes chromatin structure at various loci in the genome, such as telomere heterochromatin expanding and mating type locus heterochromatin spreading out of the boundaries. Interestingly, the levels of inheritable expanding at sub-telomeric heterochromatin regions are highly variable among independent cell populations. Finally, we show that HU treatment of the multi-cellular organisms C. elegans and D. melanogaster affects epigenetically programmed development and PEV, illustrating the evolutionary conservation of the phenomenon. Replication stress, in addition to its demonstrated role in genetic instability, promotes variable epigenetic instability throughout the epigenome. PMID:28749973

Mutation Rates across Budding Yeast Chromosome VI Are Correlated with Replication Timing

PubMed Central

Lang, Gregory I.; Murray, Andrew W.

2011-01-01

Previous experimental studies suggest that the mutation rate is nonuniform across the yeast genome. To characterize this variation across the genome more precisely, we measured the mutation rate of the URA3 gene integrated at 43 different locations tiled across Chromosome VI. We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis. This model is supported by the observation that eliminating translesion synthesis decreases this variation. PMID:21666225

Early viral replication and induced or constitutive immunity in rainbow trout families with differential resistance to Infectious hematopoietic necrosis virus (IHNV)

USGS Publications Warehouse

Purcell, M.K.; LaPatra, S.E.; Woodson, J.C.; Kurath, G.; Winton, J.R.

2010-01-01

The main objective of this study was to assess correlates of innate resistance in rainbow trout full-sibling families that differ in susceptibility to Infectious hematopoietic necrosis virus (IHNV). As part of a commercial breeding program, full-sibling families were challenged with IHNV by waterborne exposure at the 1 g size to determine susceptibility to IHNV. Progeny from select families (N = 7 families) that varied in susceptibility (ranging from 32 to 90% cumulative percent mortality (CPM)) were challenged again at the 10 g size by intra-peritoneal injection and overall mortality, early viral replication and immune responses were evaluated. Mortality challenges included 20–40 fish per family while viral replication and immune response studies included 6 fish per family at each time point (24, 48 and 72 h post-infection (hpi)). CPM at the 1 g size was significantly correlated with CPM at the 10 g size, indicating that inherent resistance was a stable trait irrespective of size. In the larger fish, viral load was measured by quantitative reverse-transcriptase PCR in the anterior kidney and was a significant predictor of family disease outcome at 48 hpi. Type I interferon (IFN) transcript levels were significantly correlated with an individual's viral load at 48 and 72 hpi, while type II IFN gene expression was significantly correlated with an individual's viral load at 24 and 48 hpi. Mean family type I but not type II IFN gene expression was weakly associated with susceptibility at 72 hpi. There was no association between mean family susceptibility and the constitutive expression of a range of innate immune genes (e.g. type I and II IFN pathway genes, cytokine and viral recognition receptor genes). The majority of survivors from the challenge had detectable serum neutralizing antibody titers but no trend was observed among families. This result suggests that even the most resistant families experienced sufficient levels of viral replication to trigger specific immunity. In summary, disease outcome for each family was determined very early in the infection process and resistance was associated with lower early viral replication.

Single Cell Mathematical Model Successfully Replicates Key Features of GBM: Go-Or-Grow Is Not Necessary.

PubMed

Scribner, Elizabeth; Fathallah-Shaykh, Hassan M

2017-01-01

Glioblastoma (GBM) is a malignant brain tumor that continues to be associated with neurological morbidity and poor survival times. Brain invasion is a fundamental property of malignant glioma cells. The Go-or-Grow (GoG) phenotype proposes that cancer cell motility and proliferation are mutually exclusive. Here, we construct and apply a single glioma cell mathematical model that includes motility and angiogenesis and lacks the GoG phenotype. Simulations replicate key features of GBM including its multilayer structure (i.e.edema, enhancement, and necrosis), its progression patterns associated with bevacizumab treatment, and replicate the survival times of GBM treated or untreated with bevacizumab. These results suggest that the GoG phenotype is not a necessary property for the formation of the multilayer structure, recurrence patterns, and the poor survival times of patients diagnosed with GBM.

Adapting Stanford’s Chronic Disease Self-Management Program to Hawaii’s Multicultural Population

PubMed Central

Tomioka, Michiyo; Braun, Kathryn L.; Compton, Merlita; Tanoue, Leslie

2012-01-01

Purpose of the Study: Stanford’s Chronic Disease Self-Management Program (CDSMP) has been proven to increase patients’ ability to manage distress. We describe how we replicated CDSMP in Asian and Pacific Islander (API) communities. Design and Methods: We used the “track changes” tool to deconstruct CDSMP into its various components (e.g., recruitment and staffing) and the “adaptation traffic light” to identify allowable modifications to the original program. We monitored local leaders’ fidelity of delivery of CDSMP and tracked participants’ attendance, satisfaction, and 6-month outcomes. Results: Between July 2007 and February 2010, 584 completed a CDSMP workshop. Baseline and 6-month data were available for 422 (72%), including 53 Caucasians, 177 Asians, and 194 Pacific Islanders. All 3 groups realized significant decreases in social and role activity limitations and significant increases in communication with physicians. Asians and Pacific Islanders also realized significant increases in self-rated health and time spent engaging in stretching/strengthening exercise. Asians also reported significant reductions in health distress and self-reported physician visits and increases in time spent in aerobic exercise, ability to cope with symptoms, and self-efficacy. Implications: Our experience suggests that CDSMP can be modified for increased cultural appropriateness for API communities while maintaining the key components responsible for behavior change. PMID:21719630

Competing Death Programs in Poliovirus-Infected Cells: Commitment Switch in the Middle of the Infectious Cycle

PubMed Central

Agol, Vadim I.; Belov, George A.; Bienz, Kurt; Egger, Denise; Kolesnikova, Marina S.; Romanova, Lyudmila I.; Sladkova, Larissa V.; Tolskaya, Elena A.

2000-01-01

Productive poliovirus infection of HeLa cells leads to the canonical cytopathic effect (CPE), whereas certain types of abortive infection result in apoptosis. To define the time course of commitment to the different types of poliovirus-induced death, inhibitors of viral replication (guanidine HCl) or translation (cycloheximide) were added at different times postinfection (p.i.). Early in the infection (during the first ∼2 h p.i.), predominantly proapoptotic viral function was expressed, rendering the cells committed to apoptosis, which developed several hours after viral expression was arrested. In the middle of infection, concomitantly with the onset of fast generation of viral progeny, the implementation of the viral apoptotic program was abruptly interrupted. In particular, activation of an Asp-Glu-Val-Asp (DEVD)-specific caspase(s) occurring in the apoptosis-committed cells was prevented by the ongoing productive infection. Simultaneously, the cells retaining normal or nearly normal morphology became committed to CPE, which eventually developed regardless of whether or not further viral expression was allowed to proceed. The implementation of the poliovirus-induced apoptotic program was suppressed in HeLa cells overexpressing the Bcl-2 protein, indicating that the fate of poliovirus-infected cells depends on the balance of host and viral pro- and antiapoptotic factors. PMID:10823859

The Mars Science Laboratory Touchdown Test Facility

NASA Technical Reports Server (NTRS)

White, Christopher; Frankovich, John; Yates, Phillip; Wells Jr, George H.; Losey, Robert

2009-01-01

In the Touchdown Test Program for the Mars Science Laboratory (MSL) mission, a facility was developed to use a full-scale rover vehicle and an overhead winch system to replicate the Skycrane landing event.

Computer Center: BASIC String Models of Genetic Information Transfer.

ERIC Educational Resources Information Center

Spain, James D., Ed.

1984-01-01

Discusses some of the major genetic information processes which may be modeled by computer program string manipulation, focusing on replication and transcription. Also discusses instructional applications of using string models. (JN)

34 CFR 428.21 - What selection criteria does the Secretary use?

Code of Federal Regulations, 2012 CFR

2012-07-01

... individuals enrolled in vocational education programs, and how those needs should influence teaching... available to help others replicate project activities, and the methods to be used to make the materials...

Live or let die: manipulation of cellular suicide programs by murine cytomegalovirus.

PubMed

Handke, Wiebke; Krause, Eva; Brune, Wolfram

2012-11-01

Cytomegaloviruses (CMVs) are large double-stranded DNA viruses that replicate slowly and cause life-long persisting infections in their hosts. To achieve this, the CMVs had to evolve numerous countermeasures against innate and adaptive immune responses. Induction of programmed cell death is one important host defense mechanism against intracellular pathogens such as viruses. For a multicellular organism, it is advantageous to let infected cells die in order to thwart viral replication and dissemination. For a virus, by contrast, it is better to inhibit cell death and keep infected cells alive until the viral replication cycle has been completed. As a matter of fact, the CMVs encode a number of proteins devoted to interfering with different forms of programmed cell death: apoptosis and necroptosis. In this review, we summarize the known functions of the four best characterized cell death inhibitors of murine cytomegalovirus (MCMV), which are encoded by open reading frames, M36, m38.5, m41.1, and M45. The viral proteins interact with key molecules within different cell death pathways, namely caspase-8, Bax, Bak, and RIP1/RIP3. In addition, we discuss which events during MCMV infection might trigger apoptosis or necrosis and how MCMV's countermeasures compare to those of other herpesviruses. Since both, MCMV and its natural host, are amenable to genetic manipulation, the mouse model for CMV infection provides a particularly suitable system to study mechanisms of cell death induction and inhibition.

Prenatal and infancy home visiting by nurses: from randomized trials to community replication.

PubMed

Olds, David L

2002-09-01

This paper summarizes a 25-year program of research that has attempted to improve the early health and development of low-income mothers and children and their future life trajectories with prenatal and infancy home visiting by nurses. The program has been tested in two separate large-scale randomized controlled trials with different populations living in different contexts. The program has been successful in improving parental care of the child as reflected in fewer injuries and ingestions that may be associated with child abuse and neglect; and maternal life-course, reflected in fewer subsequent pregnancies, greater work force participation, and reduced use of public assistance and food stamps. In the first trial, the program also produced long-term effects on the number of arrests, convictions, emergent substance use, and promiscuous sexual activity of 15-year-old children whose nurse-visited mothers were low-income and unmarried when they registered in the study during pregnancy. Since 1996, the program has been offered for public investment outside of research contexts. Careful attention has been given to ensuring that the program is replicated with fidelity to the model tested in the scientifically controlled studies by working with community leaders to ensure that organization and community contexts are favorable for the program; by providing the nurses with excellent training and technical assistance and detailed visit-by-visit guidelines; and by providing organizations with a web-based clinical information system that creates a basis for monitoring program performance and continuous quality improvement.

A replication study of priorities and attitudes of two nursing programs' communities of interest: an appreciative inquiry.

PubMed

Farrell, Marie; Wallis, Nancy C; Evans, Marci Tyler

2007-01-01

American universities and nursing faculties, caught between the imperatives of community demand and university financial constraints, need to analyze their communities of interests' shared priorities for nursing education. This replication study's objective was to compare the priorities and attitudes of two nursing programs' communities of interest using appreciative inquiry (AI). The researchers used AI to conduct a qualitative, comparative analysis of data from two nursing programs. They used one-on-one and focus group interviews to examine stakeholders' views of the best of the nursing program's past, their vision and approaches to realizing the vision, and their roles in contributing to the vision they created. The researchers analyzed the qualitative data using a standardized codebook and content analysis. Respondents' priorities for both academic programs were similar, with the western respondents emphasizing nursing's contribution to quality care and the southern respondents emphasizing its leadership and commitment to diversity. Both identified the role of legislators and the community in partnering with nursing to secure funds for expansion. Both programs' respondents viewed nursing as a major part of the university and considered their role as supporters of the university's academic and financial goals. The two nursing programs appeared to harness external and internal support in their respective communities. While some priorities differed between the two nursing programs, respondents were aware of the ripple effect of decreased funding for nursing education on the delivery of nursing services to the community. Differences among the undergraduate and graduate students, which reflect a nursing program's student mix, underscore the priorities that nursing programs must emphasize.

Different rates of DNA replication at early versus late S-phase sections: multiscale modeling of stochastic events related to DNA content/EdU (5-ethynyl-2'deoxyuridine) incorporation distributions.

PubMed

Li, Biao; Zhao, Hong; Rybak, Paulina; Dobrucki, Jurek W; Darzynkiewicz, Zbigniew; Kimmel, Marek

2014-09-01

Mathematical modeling allows relating molecular events to single-cell characteristics assessed by multiparameter cytometry. In the present study we labeled newly synthesized DNA in A549 human lung carcinoma cells with 15-120 min pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was measured by laser scanning cytometry. The frequency of cells in the ascending (left) side of the "horseshoe"-shaped EdU/DAPI bivariate distributions reports the rate of DNA replication at the time of entrance to S phase while their frequency in the descending (right) side is a marker of DNA replication rate at the time of transition from S to G2 phase. To understand the connection between molecular-scale events and scatterplot asymmetry, we developed a multiscale stochastic model, which simulates DNA replication and cell cycle progression of individual cells and produces in silico EdU/DAPI scatterplots. For each S-phase cell the time points at which replication origins are fired are modeled by a non-homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for durations of cell cycle phases (G1, S and G2 M), Depending on the rate of DNA synthesis being an increasing or decreasing function, simulated EdU/DAPI bivariate graphs show predominance of cells in left (early-S) or right (late-S) side of the horseshoe distribution. Assuming NHPP rate estimated from independent experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those experimentally observed. This finding proves consistency between the S-phase DNA-replication rate based on molecular-scale analyses, and cell population kinetics ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate at entrance to S is relatively slow compared with its rather abrupt termination during S to G2 transition. Our approach opens a possibility of similar modeling to study the effect of anticancer drugs on DNA replication/cell cycle progression and also to quantify other kinetic events that can be measured during S-phase. © 2014 International Society for Advancement of Cytometry.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies.

PubMed

Ying, B; Toth, K; Spencer, J F; Meyer, J; Tollefson, A E; Patra, D; Dhar, D; Shashkova, E V; Kuppuswamy, M; Doronin, K; Thomas, M A; Zumstein, L A; Wold, W S M; Lichtenstein, D L

2009-08-01

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors.

Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription

PubMed Central

Cifuentes-Muñoz, Nicolás; Branttie, Jean; Slaughter, Kerri Beth

2017-01-01

ABSTRACT Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications. IMPORTANCE Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets. PMID:28978704

Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription.

PubMed

Cifuentes-Muñoz, Nicolás; Branttie, Jean; Slaughter, Kerri Beth; Dutch, Rebecca Ellis

2017-12-15

Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications. IMPORTANCE Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets. Copyright © 2017 American Society for Microbiology.

Regulatory Mechanisms That Prevent Re-initiation of DNA Replication Can Be Locally Modulated at Origins by Nearby Sequence Elements

PubMed Central

Richardson, Christopher D.; Li, Joachim J.

2014-01-01

Eukaryotic cells must inhibit re-initiation of DNA replication at each of the thousands of origins in their genome because re-initiation can generate genomic alterations with extraordinary frequency. To minimize the probability of re-initiation from so many origins, cells use a battery of regulatory mechanisms that reduce the activity of replication initiation proteins. Given the global nature of these mechanisms, it has been presumed that all origins are inhibited identically. However, origins re-initiate with diverse efficiencies when these mechanisms are disabled, and this diversity cannot be explained by differences in the efficiency or timing of origin initiation during normal S phase replication. This observation raises the possibility of an additional layer of replication control that can differentially regulate re-initiation at distinct origins. We have identified novel genetic elements that are necessary for preferential re-initiation of two origins and sufficient to confer preferential re-initiation on heterologous origins when the control of re-initiation is partially deregulated. The elements do not enhance the S phase timing or efficiency of adjacent origins and thus are specifically acting as re-initiation promoters (RIPs). We have mapped the two RIPs to ∼60 bp AT rich sequences that act in a distance- and sequence-dependent manner. During the induction of re-replication, Mcm2-7 reassociates both with origins that preferentially re-initiate and origins that do not, suggesting that the RIP elements can overcome a block to re-initiation imposed after Mcm2-7 associates with origins. Our findings identify a local level of control in the block to re-initiation. This local control creates a complex genomic landscape of re-replication potential that is revealed when global mechanisms preventing re-replication are compromised. Hence, if re-replication does contribute to genomic alterations, as has been speculated for cancer cells, some regions of the genome may be more susceptible to these alterations than others. PMID:24945837

From the chromatin interaction network to the organization of the human genome into replication N/U-domains

NASA Astrophysics Data System (ADS)

Boulos, Rasha E.; Julienne, Hanna; Baker, Antoine; Chen, Chun-Long; Petryk, Nataliya; Kahli, Malik; dʼAubenton-Carafa, Yves; Goldar, Arach; Jensen, Pablo; Hyrien, Olivier; Thermes, Claude; Arneodo, Alain; Audit, Benjamin

2014-11-01

The three-dimensional (3D) architecture of the mammalian nucleus is now being unraveled thanks to the recent development of chromatin conformation capture (3C) technologies. Here we report the results of a combined multiscale analysis of genome-wide mean replication timing and chromatin conformation data that reveal some intimate relationships between chromatin folding and human DNA replication. We previously described megabase replication N/U-domains as mammalian multiorigin replication units, and showed that their borders are ‘master’ replication initiation zones that likely initiate cascades of origin firing responsible for the stereotypic replication of these domains. Here, we demonstrate that replication N/U-domains correspond to the structural domains of self-interacting chromatin, and that their borders act as insulating regions both in high-throughput 3C (Hi-C) data and high-resolution 3C (4C) experiments. Further analyses of Hi-C data using a graph-theoretical approach reveal that N/U-domain borders are long-distance, interconnected hubs of the chromatin interaction network. Overall, these results and the observation that a well-defined ordering of chromatin states exists from N/U-domain borders to centers suggest that ‘master’ replication initiation zones are at the heart of a high-order, epigenetically controlled 3D organization of the human genome.

Monitoring of the spatial and temporal dynamics of BER/SSBR pathway proteins, including MYH, UNG2, MPG, NTH1 and NEIL1-3, during DNA replication.

PubMed

Bj Rås, Karine Ø; Sousa, Mirta M L; Sharma, Animesh; Fonseca, Davi M; S Gaard, Caroline K; Bj Rås, Magnar; Otterlei, Marit

2017-08-21

Base lesions in DNA can stall the replication machinery or induce mutations if bypassed. Consequently, lesions must be repaired before replication or in a post-replicative process to maintain genomic stability. Base excision repair (BER) is the main pathway for repair of base lesions and is known to be associated with DNA replication, but how BER is organized during replication is unclear. Here we coupled the iPOND (isolation of proteins on nascent DNA) technique with targeted mass-spectrometry analysis, which enabled us to detect all proteins required for BER on nascent DNA and to monitor their spatiotemporal orchestration at replication forks. We demonstrate that XRCC1 and other BER/single-strand break repair (SSBR) proteins are enriched in replisomes in unstressed cells, supporting a cellular capacity of post-replicative BER/SSBR. Importantly, we identify for the first time the DNA glycosylases MYH, UNG2, MPG, NTH1, NEIL1, 2 and 3 on nascent DNA. Our findings suggest that a broad spectrum of DNA base lesions are recognized and repaired by BER in a post-replicative process. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Computational methods for yeast prion curing curves.

PubMed

Ridout, Martin S

2008-10-01

If the chemical guanidine hydrochloride is added to a dividing culture of yeast cells in which some of the protein Sup35p is in its prion form, the proportion of cells that carry replicating units of the prion, termed propagons, decreases gradually over time. Stochastic models to describe this process of 'curing' have been developed in earlier work. The present paper investigates the use of numerical methods of Laplace transform inversion to calculate curing curves and contrasts this with an alternative, more direct, approach that involves numerical integration. Transform inversion is found to provide a much more efficient computational approach that allows different models to be investigated with minimal programming effort. The method is used to investigate the robustness of the curing curve to changes in the assumed distribution of cell generation times. Matlab code is available for carrying out the calculations.

Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei.

PubMed

Bass, Hank W; Hoffman, Gregg G; Lee, Tae-Jin; Wear, Emily E; Joseph, Stacey R; Allen, George C; Hanley-Bowdoin, Linda; Thompson, William F

2015-11-01

Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. Here we report findings from 3D quantitative analysis of DNA replication and endoreduplication in nuclei from pulse-labeled developing maize root tips. In both early and middle S phase nuclei, flow-sorted on the basis of DNA content, replicative labeling was widely distributed across euchromatic regions of the nucleoplasm. We did not observe the perinuclear or perinucleolar replicative labeling patterns characteristic of middle S phase in mammals. Instead, the early versus middle S phase patterns in maize could be distinguished cytologically by correlating two quantitative, continuous variables, replicative labeling and DAPI staining. Early S nuclei exhibited widely distributed euchromatic labeling preferentially localized to regions with weak DAPI signals. Middle S nuclei also exhibited widely distributed euchromatic labeling, but the label was preferentially localized to regions with strong DAPI signals. Highly condensed heterochromatin, including knobs, replicated during late S phase as previously reported. Similar spatiotemporal replication patterns were observed for both mitotic and endocycling maize nuclei. These results revealed that maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with "gene islands" mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.

Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication.

PubMed

Karamese, Murat; Aydogdu, Sabiha; Karamese, Selina Aksak; Altoparlak, Ulku; Gundogdu, Cemal

2015-01-01

Hepatitis B virus infection is one of the major world health problems. Epigallocatechin-3 gallate is the major component of the polyphenolic fraction of green tea and it has an anti-viral, anti-mutagenic, anti- tumorigenic, anti-angiogenic, anti-proliferative, and/or pro-apoptotic effects on mammalian cells. In this study, our aim was to investigate the inhibition of HBV replication by epigallocatechin-3 gallate in the Hep3B2.1-7 hepatocellular carcinoma cell line. HBV-replicating Hep3B2.1-7 cells were used to investigate the preventive effects of epigallocatechin-3 gallate on HBV DNA replication. The expression levels of HBsAg and HBeAg were determined using ELISA. Quantitative real-time-PCR was applied for the determination of the expression level of HBV DNA. Cytotoxicity of epigallocathechin-3-gallate was not observed in the hepatic carcinoma cell line when the dose was lower than 100 μM. The ELISA method demonstrated that epigallocatechin-3 gallate have strong effects on HBsAg and HBeAg levels. Also it was detected by real-time PCR that epigallocatechin-3 gallate could prevent HBV DNA replication. The obtained data pointed out that although the exact mechanism of HBV DNA replication and related diseases remains unclear, epigallocatechin-3 gallate has a potential as an effective anti-HBV agent with low toxicity.

DNA replication after mutagenic treatment in Hordeum vulgare.

PubMed

Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka

2016-12-01

The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright © 2016 Elsevier B.V. All rights reserved.

Initiation preference at a yeast origin of replication.

PubMed

Brewer, B J; Fangman, W L

1994-04-12

Replication origins in the yeast Saccharomyces cerevisiae are identified as autonomous replication sequence (ARS) elements. To examine the effect of origin density on replication initiation, we have analyzed the replication of a plasmid that contains two copies of the same origin, ARS1. The activation of origins and the direction that replication forks move through flanking sequences can be physically determined by analyzing replication intermediates on two-dimensional agarose gels. We find that only one of the two identical ARSs on the plasmid initiates replication on any given plasmid molecule; that is, this close spacing of ARSs results in an apparent interference between the potential origins. Moreover, in the particular plasmid that we constructed, one of the two identical copies of ARS1 is used four times more frequently than the other one. These results show that the plasmid context is critical for determining the preferred origin. This origin preference is also exhibited when the tandem copies of ARS1 are introduced into a yeast chromosome. The sequences responsible for establishing the origin preference have been identified by deletion analysis and are found to reside in a portion of the yeast URA3 gene.

High-throughput analysis of yeast replicative aging using a microfluidic system

PubMed Central

Jo, Myeong Chan; Liu, Wei; Gu, Liang; Dang, Weiwei; Qin, Lidong

2015-01-01

Saccharomyces cerevisiae has been an important model for studying the molecular mechanisms of aging in eukaryotic cells. However, the laborious and low-throughput methods of current yeast replicative lifespan assays limit their usefulness as a broad genetic screening platform for research on aging. We address this limitation by developing an efficient, high-throughput microfluidic single-cell analysis chip in combination with high-resolution time-lapse microscopy. This innovative design enables, to our knowledge for the first time, the determination of the yeast replicative lifespan in a high-throughput manner. Morphological and phenotypical changes during aging can also be monitored automatically with a much higher throughput than previous microfluidic designs. We demonstrate highly efficient trapping and retention of mother cells, determination of the replicative lifespan, and tracking of yeast cells throughout their entire lifespan. Using the high-resolution and large-scale data generated from the high-throughput yeast aging analysis (HYAA) chips, we investigated particular longevity-related changes in cell morphology and characteristics, including critical cell size, terminal morphology, and protein subcellular localization. In addition, because of the significantly improved retention rate of yeast mother cell, the HYAA-Chip was capable of demonstrating replicative lifespan extension by calorie restriction. PMID:26170317

Structure, replication efficiency and fragility of yeast ARS elements.

PubMed

Dhar, Manoj K; Sehgal, Shelly; Kaul, Sanjana

2012-05-01

DNA replication in eukaryotes initiates at specific sites known as origins of replication, or replicators. These replication origins occur throughout the genome, though the propensity of their occurrence depends on the type of organism. In eukaryotes, zones of initiation of replication spanning from about 100 to 50,000 base pairs have been reported. The characteristics of eukaryotic replication origins are best understood in the budding yeast Saccharomyces cerevisiae, where some autonomously replicating sequences, or ARS elements, confer origin activity. ARS elements are short DNA sequences of a few hundred base pairs, identified by their efficiency at initiating a replication event when cloned in a plasmid. ARS elements, although structurally diverse, maintain a basic structure composed of three domains, A, B and C. Domain A is comprised of a consensus sequence designated ACS (ARS consensus sequence), while the B domain has the DNA unwinding element and the C domain is important for DNA-protein interactions. Although there are ∼400 ARS elements in the yeast genome, not all of them are active origins of replication. Different groups within the genus Saccharomyces have ARS elements as components of replication origin. The present paper provides a comprehensive review of various aspects of ARSs, starting from their structural conservation to sequence thermodynamics. All significant and conserved functional sequence motifs within different types of ARS elements have been extensively described. Issues like silencing at ARSs, their inherent fragility and factors governing their replication efficiency have also been addressed. Progress in understanding crucial components associated with the replication machinery and timing at these ARS elements is discussed in the section entitled "The replicon revisited". Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Developing the next generation of nurse scientists.

PubMed

Burkhart, Patricia V; Hall, Lynne A

2015-01-01

This article describes an undergraduate nursing research internship program in which students are engaged in research with a faculty mentor. Since 2002, more than 130 undergraduate nursing students have participated. Interns coauthored publications, presented papers and posters at conferences, and received awards. This highly successful program provides a model that can be easily replicated to foster the development of future nurse scientists.

Describing Characteristics of Pennsylvania's "Schools to Watch®": Focusing on Social Equity and Developmental Responsiveness

ERIC Educational Resources Information Center

Parke, Carol S.; Generett, Gretchen Givens; de Almeida Ramos, Renata

2017-01-01

The purpose of this study was to understand how schools address two specific criteria of the Schools to Watch® (STW) program: Social equity and developmental responsiveness. Descriptions of replicable practices, program/school characteristics, and initiatives created by each of the STW sites in Pennsylvania were analyzed. The data also includes…

POOLMS: A computer program for fitting and model selection for two level factorial replication-free experiments

NASA Technical Reports Server (NTRS)

Amling, G. E.; Holms, A. G.

1973-01-01

A computer program is described that performs a statistical multiple-decision procedure called chain pooling. It uses a number of mean squares assigned to error variance that is conditioned on the relative magnitudes of the mean squares. The model selection is done according to user-specified levels of type 1 or type 2 error probabilities.

Building on Best Practices in Youth Employment: What Works, How Do We Know, How Do We Sustain and Replicate Them.

ERIC Educational Resources Information Center

Weinbaum, Sandy; Wirmusky, Frank

The 14 Job Training Partnership Act (JTPA)-funded youth employment programs to which the Academy for Educational Development (AED) has delivered technical assistance for the past 5 years illustrate several important conditions for effective programming and "best practices" in the field of youth employment and training. Four of the JTPA…

Working to My Potential: The Postsecondary Experiences of CPS Students in the International Baccalaureate Diploma Programme

ERIC Educational Resources Information Center

Coca, Vanessa; Johnson, David; Kelley-Kemple, Thomas; Roderick, Melissa; Moeller, Eliza; Williams, Nicole; Moragne, Kafi

2012-01-01

In 1997, Chicago Public Schools (CPS) announced an ambitious plan to open 13 International Baccalaureate Diploma Programs (IBDP) in neighborhood high schools throughout the city. Hoping to replicate the success achieved in the long-standing IB program at Lincoln Park High School, the scale of the IB experiment was unmatched by any other school…

A Randomized Controlled Trial to Improve Social Skills in Young Adults with Autism Spectrum Disorder: The UCLA PEERS® Program

ERIC Educational Resources Information Center

Laugeson, Elizabeth A.; Gantman, Alexander; Kapp, Steven K.; Orenski, Kaely; Ellingsen, Ruth

2015-01-01

Research suggests that impaired social skills are often the most significant challenge for those with autism spectrum disorder (ASD), yet few evidence-based social skills interventions exist for adults on the spectrum. This replication trial tested the effectiveness of PEERS, a caregiver-assisted social skills program for high-functioning young…

"FRIENDS for Life": The Results of a Resilience-Building, Anxiety-Prevention Program in a Canadian Elementary School

ERIC Educational Resources Information Center

Rose, Heather; Miller, Lynn; Martinez, Yvonne

2009-01-01

The purpose of the study in this article was to replicate past findings showing the effectiveness of a cognitive, behavioral resilience-building/anxiety-prevention program, "FRIENDS for Life." The results of the controlled study of two Grade 4 classrooms in Canada (N = 52) indicate that all children reported reduced levels of anxiety…

Creating new realities: program development and dissemination.

PubMed Central

Fixsen, D L; Blase, K A

1993-01-01

Program development and dissemination in human services present challenges and opportunities for social scientists. Over the past 27 years the Teaching-Family Model of group home treatment has moved from prototype development to widespread dissemination across North America. Reviewing concepts in industry related to product development and dissemination, the application of these concepts to a human services delivery system, and program replication and dissemination data offer information about how innovative human services can be widely adapted and adopted. PMID:8307838

A Basketball Simulation.

ERIC Educational Resources Information Center

Noone, E. T., Jr.

1991-01-01

Presented is an activity in which probability and percents are taught using a basketball computer simulation. Computer programs that replicate the free-throw accuracy of college and professional stars and allow students to compete with those stars are included. (KR)

Distinct contributions of replication and transcription to mutation rate variation of human genomes.

PubMed

Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

2012-02-01

Here, we evaluate the contribution of two major biological processes--DNA replication and transcription--to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes. Copyright © 2012 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.

SURPHEX (tm): New dry photopolymers for replication of surface relief diffractive optics

NASA Technical Reports Server (NTRS)

Shvartsman, Felix P.

1993-01-01

High efficiency, deep groove, surface relief Diffractive Optical Elements (DOE) with various optical functions can be recorded in a photoresist using conventional interferometric holographic and computer generated photolithographic recording techniques. While photoresist recording media are satisfactory for recording individual surface relief DOE, a reliable and precise method is needed to replicate these diffractive microstructures to maintain the high aspect ratio in each replicated DOE. The term 'high aspect ratio' means that the depth of a groove is substantially greater, i.e. 2, 3, or more times greater, than the width of the groove. A new family of dry photopolymers SURPHEX was developed recently at Du Pont to replicate such highly efficient, deep groove DOE's. SURPHEX photopolymers are being utilized in Du Pont's proprietary Dry Photopolymer Embossing (DPE) technology to replicate with very high degree of precision almost any type of surface relief DOE. Surfaces relief microstructures with width/depth aspect ratio of 1:20 (0.1 micron/2.0 micron) were faithfully replicated by DPE technology. Several types of plastic and glass/quartz optical substrates can be used for economical replication of DOE.

Accelerated Self-Replication under Non-Equilibrium, Periodic Energy Delivery

NASA Astrophysics Data System (ADS)

Zhang, Rui; Olvera de La Cruz, Monica

2014-03-01

Self-replication is a remarkable phenomenon in nature that has fascinated scientists for decades. In a self-replicating system, the original units are attracted to a template, which induce their binding. In equilibrium, the energy required to disassemble the newly assembled copy from the mother template is supplied by thermal energy. The possibility of optimizing self-replication is explored by controlling the frequency at which energy is supplied to the system. A model system inspired by a class of light switchable colloids is considered where light is used to control the interactions. Conditions under which self-replication can be significantly more effective under non-equilibrium, cyclic energy delivery than under equilibrium constant energy conditions are identified. Optimal self-replication does not require constant energy expenditure. Instead, the proper timing at which energy is delivered to the system is an essential controllable parameter to induce high replication rates. This work was supported by the Non-Equilibrium Energy Research Center (NERC), which is an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0000989.

ISIS and META projects

NASA Technical Reports Server (NTRS)

Birman, Kenneth; Cooper, Robert; Marzullo, Keith

1990-01-01

The ISIS project has developed a new methodology, virtual synchony, for writing robust distributed software. High performance multicast, large scale applications, and wide area networks are the focus of interest. Several interesting applications that exploit the strengths of ISIS, including an NFS-compatible replicated file system, are being developed. The META project is distributed control in a soft real-time environment incorporating feedback. This domain encompasses examples as diverse as monitoring inventory and consumption on a factory floor, and performing load-balancing on a distributed computing system. One of the first uses of META is for distributed application management: the tasks of configuring a distributed program, dynamically adapting to failures, and monitoring its performance. Recent progress and current plans are reported.

Active role of a human genomic insert in replication of a yeast artificial chromosome.

PubMed

van Brabant, A J; Fangman, W L; Brewer, B J

1999-06-01

Yeast artificial chromosomes (YACs) are a common tool for cloning eukaryotic DNA. The manner by which large pieces of foreign DNA are assimilated by yeast cells into a functional chromosome is poorly understood, as is the reason why some of them are stably maintained and some are not. We examined the replication of a stable YAC containing a 240-kb insert of DNA from the human T-cell receptor beta locus. The human insert contains multiple sites that serve as origins of replication. The activity of these origins appears to require the yeast ARS consensus sequence and, as with yeast origins, additional flanking sequences. In addition, the origins in the human insert exhibit a spacing, a range of activation efficiencies, and a variation in times of activation during S phase similar to those found for normal yeast chromosomes. We propose that an appropriate combination of replication origin density, activation times, and initiation efficiencies is necessary for the successful maintenance of YAC inserts.

Partners in policymaking: the first five years.

PubMed

Zirpoli, T J; Wieck, C; Hancox, D; Skarnulis, E R

1994-12-01

Many individuals with disabilities and their families are becoming empowered by learning effective self-advocacy strategies. In this article one enpowerment and self-advocacy training program, Partners in Policymaking, for parents of young children and adults with disabilities was described. Initially developed in Minnesota, the Partners program has completed its fifth year, has 163 graduates, and is being replicated in several other states. Follow-up data, qualitative and quantitative, were collected from program graduates. Results indicated both satisfaction with the program and the presence of many active citizen-advocates in the community.

Paranoia.Ada: Sample output reports

NASA Technical Reports Server (NTRS)

1986-01-01

Paranoia.Ada is a program to diagnose floating point arithmetic in the context of the Ada programming language. The program evaluates the quality of a floating point arithmetic implementation with respect to the proposed IEEE Standards P754 and P854. Paranoia.Ada is derived from the original BASIC programming language version of Paranoia. The Paranoia.Ada replicates in Ada the test algorithms originally implemented in BASIC and adheres to the evaluation criteria established by W. M. Kahan. Paranoia.Ada incorporates a major structural redesign and employs applicable Ada architectural and stylistic features.

A Randomized Controlled Trial of Koru: A Mindfulness Program for College Students and Other Emerging Adults

PubMed Central

Greeson, Jeffrey M.; Juberg, Michael K.; Maytan, Margaret; James, Kiera; Rogers, Holly

2014-01-01

Objective To evaluate the effectiveness of Koru, a mindfulness training program for college students and other emerging adults. Participants Ninety students (66% female, 62% white, 71% graduate students) participated between Fall 2012 and Spring 2013. Methods Randomized controlled trial. We hypothesized that Koru, compared to a wait-list control group, would reduce perceived stress and sleep problems, and increase mindfulness, self-compassion, and gratitude. Results As hypothesized, results showed significant Group (Koru, wait-list) X Time (pre, post) interactions for improvements in perceived stress (F=4.50, df [1, 76.40], p=.037, d=.45), sleep problems (F= 4.71, df [1,79.49], p=.033, d=.52), mindfulness (F=26.80, df [1, 79.09], p<.001, d=.95), and self-compassion (F=18.08, df [1, 74.77], p<.001, d=.75). All significant effects were replicated in the wait-list group. Significant correlations were observed among changes in perceived stress, sleep problems, mindfulness, and self-compassion. Conclusions Results support the effectiveness of the Koru program for emerging adults in the university setting. PMID:24499130

Quantifying Limits on Replication, Death, and Quiescence of Mycobacterium tuberculosis in Mice

PubMed Central

McDaniel, Margaret M.; Krishna, Nitin; Handagama, Winode G.; Eda, Shigetoshi; Ganusov, Vitaly V.

2016-01-01

When an individual is exposed to Mycobacterium tuberculosis (Mtb) three outcomes are possible: bacterial clearance, active disease, or latent infection. It is generally believed that most individuals exposed to Mtb become latently infected and carry the mycobacteria for life. How Mtb is maintained during this latent infection remains largely unknown. During an Mtb infection in mice, there is a phase of rapid increase in bacterial numbers in the murine lungs within the first 3 weeks, and then bacterial numbers either stabilize or increase slowly over the period of many months. It has been debated whether the relatively constant numbers of bacteria in the chronic infection result from latent (dormant, quiescent), non-replicating bacteria, or whether the observed Mtb cell numbers are due to balance between rapid replication and death. A recent study of mice, infected with a Mtb strain carrying an unstable plasmid, showed that during the chronic phase, Mtb was replicating at significant rates. Using experimental data from this study and mathematical modeling we investigated the limits of the rates of bacterial replication, death, and quiescence during Mtb infection of mice. First, we found that to explain the data the rates of bacterial replication and death could not be constant and had to decrease with time since infection unless there were large changes in plasmid segregation probability over time. While a decrease in the rate of Mtb replication with time since infection was expected due to depletion of host's resources, a decrease in the Mtb death rate was counterintuitive since Mtb-specific immune response, appearing in the lungs 3–4 weeks after infection, should increase removal of bacteria. Interestingly, we found no significant correlation between estimated rates of Mtb replication and death suggesting the decline in these rates was driven by independent mechanisms. Second, we found that the data could not be explained by assuming that bacteria do not die, suggesting that some removal of bacteria from lungs of these mice had to occur even though the total bacterial counts in these mice always increased over time. Third and finally, we showed that to explain the data the majority of bacterial cells (at least ~60%) must be replicating in the chronic phase of infection further challenging widespread belief of nonreplicating Mtb in latency. Our predictions were robust to some changes in the structure of the model, for example, when the loss of plasmid-bearing cells was mainly due to high fitness cost of the plasmid. Further studies should determine if more mechanistic models for Mtb dynamics are also able to accurately explain these data. PMID:27379030

Phosphorylation of CMG helicase and Tof1 is required for programmed fork arrest

PubMed Central

Bastia, Deepak; Srivastava, Pankaj; Zaman, Shamsu; Choudhury, Malay; Mohanty, Bidyut K.; Bacal, Julien; Langston, Lance D.; Pasero, Philippe; O’Donnell, Michael E.

2016-01-01

Several important physiological transactions, including control of replicative life span (RLS), prevention of collision between replication and transcription, and cellular differentiation, require programmed replication fork arrest (PFA). However, a general mechanism of PFA has remained elusive. We previously showed that the Tof1–Csm3 fork protection complex is essential for PFA by antagonizing the Rrm3 helicase that displaces nonhistone protein barriers that impede fork progression. Here we show that mutations of Dbf4-dependent kinase (DDK) of Saccharomyces cerevisiae, but not other DNA replication factors, greatly reduced PFA at replication fork barriers in the spacer regions of the ribosomal DNA array. A key target of DDK is the mini chromosome maintenance (Mcm) 2–7 complex, which is known to require phosphorylation by DDK to form an active CMG [Cdc45 (cell division cycle gene 45), Mcm2–7, GINS (Go, Ichi, Ni, and San)] helicase. In vivo experiments showed that mutational inactivation of DDK caused release of Tof1 from the chromatin fractions. In vitro binding experiments confirmed that CMG and/or Mcm2–7 had to be phosphorylated for binding to phospho-Tof1–Csm3 but not to its dephosphorylated form. Suppressor mutations that bypass the requirement for Mcm2–7 phosphorylation by DDK restored PFA in the absence of the kinase. Retention of Tof1 in the chromatin fraction and PFA in vivo was promoted by the suppressor mcm5-bob1, which bypassed DDK requirement, indicating that under this condition a kinase other than DDK catalyzed the phosphorylation of Tof1. We propose that phosphorylation regulates the recruitment and retention of Tof1–Csm3 by the replisome and that this complex antagonizes the Rrm3 helicase, thereby promoting PFA, by preserving the integrity of the Fob1–Ter complex. PMID:27298353

Exogenous JH and ecdysteroid applications alter initiation of polydnaviral replication in an endoparasitoid wasp, Cotesia plutellae (Braconidae: Hymenoptera).

PubMed

Park, Bokri; Kim, Yonggyun

2011-06-01

Polydnaviruses are a group of double-stranded DNA viruses and are symbiotically associated with some ichneumonoid wasps. As proviruses, the replication of polydnaviruses occurs in the female reproductive organ at the pupal stage. This study analyzed the effects of two developmental hormones, juvenile hormone (JH) and ecdysteroid, on the viral replication of Cotesia plutellae bracovirus (CpBV). All 23 CpBV segments identified contained a conserved excision/rejoining site ('AGCTTT') from their proviral segments. Using quantitative real-time PCR based on this excision/rejoining site marker, initiation of CpBV replication was determined to have occurred on day 4 on the pupal stage. Pyriproxyfen, a JH agonist, significantly inhibited adult emergence of C. plutellae, whereas RH5992, an ecdysteroid agonist, had no inhibitory effect. Although RH5992 had no effect dose on adult development, it significantly accelerated viral replication. The results of immunoblotting assays against viral coat proteins support the effects of the hormone agonists on viral replication.

Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers

PubMed Central

Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

2015-01-01

Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks. PMID:26563448

Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers.

PubMed

Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

2015-11-13

Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks.

Sample-interpolation timing: an optimized technique for the digital measurement of time of flight for γ rays and neutrons at relatively low sampling rates

NASA Astrophysics Data System (ADS)

Aspinall, M. D.; Joyce, M. J.; Mackin, R. O.; Jarrah, Z.; Boston, A. J.; Nolan, P. J.; Peyton, A. J.; Hawkes, N. P.

2009-01-01

A unique, digital time pick-off method, known as sample-interpolation timing (SIT) is described. This method demonstrates the possibility of improved timing resolution for the digital measurement of time of flight compared with digital replica-analogue time pick-off methods for signals sampled at relatively low rates. Three analogue timing methods have been replicated in the digital domain (leading-edge, crossover and constant-fraction timing) for pulse data sampled at 8 GSa s-1. Events arising from the 7Li(p, n)7Be reaction have been detected with an EJ-301 organic liquid scintillator and recorded with a fast digital sampling oscilloscope. Sample-interpolation timing was developed solely for the digital domain and thus performs more efficiently on digital signals compared with analogue time pick-off methods replicated digitally, especially for fast signals that are sampled at rates that current affordable and portable devices can achieve. Sample interpolation can be applied to any analogue timing method replicated digitally and thus also has the potential to exploit the generic capabilities of analogue techniques with the benefits of operating in the digital domain. A threshold in sampling rate with respect to the signal pulse width is observed beyond which further improvements in timing resolution are not attained. This advance is relevant to many applications in which time-of-flight measurement is essential.

Mec1/ATR, the Program Manager of Nucleic Acids Inc.

PubMed

Feng, Wenyi

2016-12-28

Eukaryotic cells are equipped with surveillance mechanisms called checkpoints to ensure proper execution of cell cycle events. Among these are the checkpoints that detect DNA damage or replication perturbations and coordinate cellular activities to maintain genome stability. At the forefront of damage sensing is an evolutionarily conserved molecule, known respectively in budding yeast and humans as Mec1 (Mitosis entry checkpoint 1) and ATR (Ataxia telangiectasia and Rad3-related protein). Through phosphorylation, Mec1/ATR activates downstream components of a signaling cascade to maintain nucleotide pool balance, protect replication fork integrity, regulate activation of origins of replication, coordinate DNA repair, and implement cell cycle delay. This list of functions continues to expand as studies have revealed that Mec1/ATR modularly interacts with various protein molecules in response to different cellular cues. Among these newly assigned functions is the regulation of RNA metabolism during checkpoint activation and the coordination of replication-transcription conflicts. In this review, I will highlight some of these new functions of Mec1/ATR with a focus on the yeast model organism.

Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages

PubMed Central

Lathrop, Stephanie K.; Binder, Kelsey A.; Starr, Tregei; Cooper, Kendal G.; Chong, Audrey; Carmody, Aaron B.

2015-01-01

Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages. PMID:25895967

Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages.

PubMed

Lathrop, Stephanie K; Binder, Kelsey A; Starr, Tregei; Cooper, Kendal G; Chong, Audrey; Carmody, Aaron B; Steele-Mortimer, Olivia

2015-07-01

Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Top2 and Sgs1-Top3 Act Redundantly to Ensure rDNA Replication Termination

PubMed Central

Fredsøe, Jacob; Nielsen, Ida; Pedersen, Jakob Madsen; Bentsen, Iben Bach; Lisby, Michael; Bjergbaek, Lotte; Andersen, Anni H

2015-01-01

Faithful DNA replication with correct termination is essential for genome stability and transmission of genetic information. Here we have investigated the potential roles of Topoisomerase II (Top2) and the RecQ helicase Sgs1 during late stages of replication. We find that cells lacking Top2 and Sgs1 (or Top3) display two different characteristics during late S/G2 phase, checkpoint activation and accumulation of asymmetric X-structures, which are both independent of homologous recombination. Our data demonstrate that checkpoint activation is caused by a DNA structure formed at the strongest rDNA replication fork barrier (RFB) during replication termination, and consistently, checkpoint activation is dependent on the RFB binding protein, Fob1. In contrast, asymmetric X-structures are formed independent of Fob1 at less strong rDNA replication fork barriers. However, both checkpoint activation and formation of asymmetric X-structures are sensitive to conditions, which facilitate fork merging and progression of replication forks through replication fork barriers. Our data are consistent with a redundant role of Top2 and Sgs1 together with Top3 (Sgs1-Top3) in replication fork merging at rDNA barriers. At RFB either Top2 or Sgs1-Top3 is essential to prevent formation of a checkpoint activating DNA structure during termination, but at less strong rDNA barriers absence of the enzymes merely delays replication fork merging, causing an accumulation of asymmetric termination structures, which are solved over time. PMID:26630413

Hypothesis-Testing Demands Trustworthy Data—A Simulation Approach to Inferential Statistics Advocating the Research Program Strategy

PubMed Central

Krefeld-Schwalb, Antonia; Witte, Erich H.; Zenker, Frank

2018-01-01

In psychology as elsewhere, the main statistical inference strategy to establish empirical effects is null-hypothesis significance testing (NHST). The recent failure to replicate allegedly well-established NHST-results, however, implies that such results lack sufficient statistical power, and thus feature unacceptably high error-rates. Using data-simulation to estimate the error-rates of NHST-results, we advocate the research program strategy (RPS) as a superior methodology. RPS integrates Frequentist with Bayesian inference elements, and leads from a preliminary discovery against a (random) H0-hypothesis to a statistical H1-verification. Not only do RPS-results feature significantly lower error-rates than NHST-results, RPS also addresses key-deficits of a “pure” Frequentist and a standard Bayesian approach. In particular, RPS aggregates underpowered results safely. RPS therefore provides a tool to regain the trust the discipline had lost during the ongoing replicability-crisis. PMID:29740363

Hypothesis-Testing Demands Trustworthy Data-A Simulation Approach to Inferential Statistics Advocating the Research Program Strategy.

PubMed

Krefeld-Schwalb, Antonia; Witte, Erich H; Zenker, Frank

2018-01-01

In psychology as elsewhere, the main statistical inference strategy to establish empirical effects is null-hypothesis significance testing (NHST). The recent failure to replicate allegedly well-established NHST-results, however, implies that such results lack sufficient statistical power, and thus feature unacceptably high error-rates. Using data-simulation to estimate the error-rates of NHST-results, we advocate the research program strategy (RPS) as a superior methodology. RPS integrates Frequentist with Bayesian inference elements, and leads from a preliminary discovery against a (random) H 0 -hypothesis to a statistical H 1 -verification. Not only do RPS-results feature significantly lower error-rates than NHST-results, RPS also addresses key-deficits of a "pure" Frequentist and a standard Bayesian approach. In particular, RPS aggregates underpowered results safely. RPS therefore provides a tool to regain the trust the discipline had lost during the ongoing replicability-crisis.

Analysis of the low molecular weight fraction of serum by LC-dual ESI-FT-ICR mass spectrometry: precision of retention time, mass, and ion abundance.

PubMed

Johnson, Kenneth L; Mason, Christopher J; Muddiman, David C; Eckel, Jeanette E

2004-09-01

This study quantifies the experimental uncertainty for LC retention time, mass measurement precision, and ion abundance obtained from replicate nLC-dual ESI-FT-ICR analyses of the low molecular weight fraction of serum. We used ultrafiltration to enrich the < 10-kDa fraction of components from the high-abundance proteins in a pooled serum sample derived from ovarian cancer patients. The THRASH algorithm for isotope cluster detection was applied to five replicate nLC-dual ESI-FT-ICR chromatograms. A simple two-level grouping algorithm was applied to the more than 7000 isotope clusters found in each replicate and identified 497 molecular species that appeared in at least four of the replicates. In addition, a representative set of 231 isotope clusters, corresponding to 188 unique molecular species, were manually interpreted to verify the automated algorithm and to set its tolerances. For nLC retention time reproducibility, 95% of the 497 species had a 95% confidence interval of the mean of +/- 0.9 min or less without the use of chromatographic alignment procedures. Furthermore, 95% of the 497 species had a mass measurement precision of < or = 3.2 and < or = 6.3 ppm for internally and externally calibrated spectra, respectively. Moreover, 95% of replicate ion abundance measurements, covering an ion abundance range of approximately 3 orders of magnitude, had a coefficient of variation of less than 62% without using any normalization functions. The variability of ion abundance was independent of LC retention time, mass, and ion abundance quartile. These measures of analytical reproducibility establish a statistical rationale for differentiating healthy and disease patient populations for the elucidation of biomarkers in the low molecular fraction of serum. Copyright 2004 American Chemical Society

The impact of sampling, PCR, and sequencing replication on discerning changes in drinking water bacterial community over diurnal time-scales.

PubMed

Bautista-de Los Santos, Quyen Melina; Schroeder, Joanna L; Blakemore, Oliver; Moses, Jonathan; Haffey, Mark; Sloan, William; Pinto, Ameet J

2016-03-01

High-throughput and deep DNA sequencing, particularly amplicon sequencing, is being increasingly utilized to reveal spatial and temporal dynamics of bacterial communities in drinking water systems. Whilst the sampling and methodological biases associated with PCR and sequencing have been studied in other environments, they have not been quantified for drinking water. These biases are likely to have the greatest effect on the ability to characterize subtle spatio-temporal patterns influenced by process/environmental conditions. In such cases, intra-sample variability may swamp any underlying small, systematic variation. To evaluate this, we undertook a study with replication at multiple levels including sampling sites, sample collection, PCR amplification, and high throughput sequencing of 16S rRNA amplicons. The variability inherent to the PCR amplification and sequencing steps is significant enough to mask differences between bacterial communities from replicate samples. This was largely driven by greater variability in detection of rare bacteria (relative abundance <0.01%) across PCR/sequencing replicates as compared to replicate samples. Despite this, we captured significant changes in bacterial community over diurnal time-scales and find that the extent and pattern of diurnal changes is specific to each sampling location. Further, we find diurnal changes in bacterial community arise due to differences in the presence/absence of the low abundance bacteria and changes in the relative abundance of dominant bacteria. Finally, we show that bacterial community composition is significantly different across sampling sites for time-periods during which there are typically rapid changes in water use. This suggests hydraulic changes (driven by changes in water demand) contribute to shaping the bacterial community in bulk drinking water over diurnal time-scales. Copyright © 2015 Elsevier Ltd. All rights reserved.

INGN 007, an oncolytic adenovirus vector, replicates in Syrian hamsters but not mice: comparison of biodistribution studies

PubMed Central

Ying, B; Toth, K; Spencer, JF; Meyer, J; Tollefson, AE; Patra, D; Dhar, D; Shashkova, EV; Kuppuswamy, M; Doronin, K; Thomas, MA; Zumstein, LA; Wold, WSM; Lichtenstein, DL

2012-01-01

Preclinical biodistribution studies with INGN 007, an oncolytic adenovirus (Ad) vector, supporting an early stage clinical trial were conducted in Syrian hamsters, which are permissive for Ad replication, and mice, which are a standard model for assessing toxicity and biodistribution of replication-defective (RD) Ad vectors. Vector dissemination and pharmacokinetics following intravenous administration were examined by real-time PCR in nine tissues and blood at five time points spanning 1 year. Select organs were also examined for the presence of infectious vector/virus. INGN 007 (VRX-007), wild-type Ad5 and AdCMVpA (an RD vector) were compared in the hamster model, whereas only INGN 007 was examined in mice. DNA of all vectors was widely disseminated early after injection, but decayed rapidly in most organs. In the hamster model, DNA of INGN 007 and Ad5 was more abundant than that of the RD vector AdCMVpA at early times after injection, but similar levels were seen later. An increased level of INGN 007 and Ad5 DNA but not AdCMVpA DNA in certain organs early after injection, and the presence of infectious INGN 007 and Ad5 in lung and liver samples at early times after injection, strongly suggests that replication of INGN 007 and Ad5 occurred in several Syrian hamster organs. There was no evidence of INGN 007 replication in mice. In addition to providing important information about INGN 007, the results underscore the utility of the Syrian hamster as a permissive immunocompetent model for Ad5 pathogenesis and oncolytic Ad vectors. PMID:19197322

Visualization and Measurement of ATP Levels in Living Cells Replicating Hepatitis C Virus Genome RNA

PubMed Central

Ando, Tomomi; Imamura, Hiromi; Suzuki, Ryosuke; Aizaki, Hideki; Watanabe, Toshiki; Wakita, Takaji; Suzuki, Tetsuro

2012-01-01

Adenosine 5′-triphosphate (ATP) is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energized by ATP is controlled. In this study, we investigated the fluctuation and distribution of ATP in cells during RNA replication of the hepatitis C virus (HCV), a member of the Flaviviridae family. We demonstrated that cells involved in viral RNA replication actively consumed ATP, thereby reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at putative subcellular sites of HCV RNA replication in living cells was developed by introducing a recently-established Förster resonance energy transfer (FRET)-based ATP indicator, called ATeam, into the NS5A coding region of the HCV replicon. Using this method, we were able to observe the formation of ATP-enriched dot-like structures, which co-localize with non-structural viral proteins, within the cytoplasm of HCV-replicating cells but not in non-replicating cells. The obtained FRET signals allowed us to estimate ATP concentrations within HCV replicating cells as ∼5 mM at possible replicating sites and ∼1 mM at peripheral sites that did not appear to be involved in HCV replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells were estimated as ∼2 mM. To our knowledge, this is the first study to demonstrate changes in ATP concentration within cells during replication of the HCV genome and increased ATP levels at distinct sites within replicating cells. ATeam may be a powerful tool for the study of energy metabolism during replication of the viral genome. PMID:22396648

BAX inhibitor-1 silencing suppresses white spot syndrome virus replication in red swamp crayfish, Procambarus clarkii.

PubMed

Du, Zhi-Qiang; Lan, Jiang-Feng; Weng, Yu-Ding; Zhao, Xiao-Fan; Wang, Jin-Xing

2013-07-01

BAX inhibitor-1 (BI-1) was originally described as an anti-apoptotic protein in both animal and plant cells. BI-1 overexpression suppresses ER stress-induced apoptosis in animal cells. Inhibition of BI-1 activity could induce the cell death in mammals and plants. However, the function of BI-1 in crustacean immunity was unclear. In this paper, the full-length cDNA of a BI-1 protein in red swamp crayfish, Procambarus clarkii (PcBI-1) was cloned and its expression profiles in normal and infected crayfish were analyzed. The results showed that PcBI-1 was expressed in hemocytes, heart, hepatopancreas, gills, stomach, and intestines of the crayfish and was upregulated after challenged with Vibrio anguillarum and with white spot syndrome virus (WSSV). To determine the function of PcBI-1 in the innate immunity of the crayfish, the RNA interference against PcBI-1 was performed and the results indicated the hemocyte programmed cell death rate was increased significantly and WSSV replication was declined after PcBI-1 knocked down. Altogether, PcBI-1 plays an anti-apoptotic role, wherein high PcBI-1 expression suppresses programmed cell death, which is beneficial for WSSW replication in crayfish. Copyright © 2013 Elsevier Ltd. All rights reserved.

Universal Temporal Profile of Replication Origin Activation in Eukaryotes

NASA Astrophysics Data System (ADS)

Goldar, Arach

2011-03-01

The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

Oxford International Conference on the Mechanical Properties of Materials at High Rates of Strain (4th) Held in Oxford, United Kingdom on 19-22 March 1989

DTIC Science & Technology

1989-03-22

models are used in the computer program EPIC2 to describe the structural response in the cylinder impact test are compared and the differences are...Inc. 8600 Le Salle Road Suite 614, Oxford Building Towson, Maryland 21204 This paper describes the development and application of a computer program ...performed using a dynamic viscoplastic finite element computer program . The resolution of the procedure has been investigated by obtaining replicate

Feedback 2.0 in Online Writing Instruction: Combining Audio-Visual and Text-Based Commentary to Enhance Student Revision and Writing Competency

ERIC Educational Resources Information Center

Grigoryan, Anna

2017-01-01

The continued increase in the number of students participating in online degree programs has led to an increase in the number of students taking online composition courses. Currently, most online writing programs replicate approaches used in face-to-face composition courses and simply transfer them to the online learning environment. However,…

Protecting You/Protecting Me: Evaluation of a Student-Led Alcohol Prevention and Traffic Safety Program for Elementary Students

ERIC Educational Resources Information Center

Bell, Mary Lou; Baker, Tara Kelley; Falb, Timothy; Roberts-Gray, Cindy

2005-01-01

Pre- and post-surveys of self-protective knowledge and skills in third, fourth, and fifth grade classrooms (n = 24) randomly assigned to a model program for alcohol prevention and traffic safety or to comparison group (n = 24 classrooms) were analyzed to evaluate replicability of immediate positive effects of first-year exposure and to test…

Dropout Prevention Programs in Nine Mid-Atlantic Region School Districts: Additions to a Dropout Prevention Database. Issues & Answers. REL 2011-No. 103

ERIC Educational Resources Information Center

Burzichelli, Claudia; Mackey, Philip E.; Bausmith, Jennifer

2011-01-01

The current study replicates work of Regional Educational Laboratory (REL) Northeast and Islands. It describes dropout prevention programs in nine Mid-Atlantic Region (Delaware, the District of Columbia, Maryland, New Jersey, and Pennsylvania) school districts serving communities with populations of 24,742-107,250 (as of July 2008). All nine…

Dropout Prevention Programs in Nine Mid-Atlantic Region School Districts: Additions to a Dropout Prevention Database. Summary. Issues & Answers. REL 2011-No. 103

ERIC Educational Resources Information Center

Burzichelli, Claudia; Mackey, Philip E.; Bausmith, Jennifer

2011-01-01

The current study replicates work of Regional Educational Laboratory (REL) Northeast and Islands. It describes dropout prevention programs in nine Mid-Atlantic Region (Delaware, the District of Columbia, Maryland, New Jersey, and Pennsylvania) school districts serving communities with populations of 24,742-107,250 (as of July 2008). All nine…

Wind Powering America's Wind for Schools Project: Summary Report

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

Baring-Gould, I.; Newcomb, C.

This report provides an overview of the U.S. Department of Energy, Wind Powering America, Wind for Schools project. It outlines teacher-training activities and curriculum development; discusses the affiliate program that allows school districts and states to replicate the program; and contains reports that provide an update on activities and progress in the 11 states in which the Wind for Schools project operates.

Improving Struggling Readers' Early Literacy Skills through a Tier 2 Professional Development Program for Rural Classroom Teachers: The Targeted Reading Intervention

ERIC Educational Resources Information Center

Vernon-Feagans, Lynne; Bratsch-Hines, Mary; Varghese, Cheryl; Cutrer, Elizabeth A.; Garwood, Justin D.

2018-01-01

This article reports the results of a randomized controlled trial that replicated and extended research on the Targeted Reading Intervention (TRI), a professional development program for kindergarten and first-grade teachers in low-wealth rural schools that helps enhance literacy skills of struggling readers. In weekly webcam coaching sessions,…

Effect of a transactional model education program on coping effectiveness in women with multiple sclerosis.

PubMed

Sanaeinasab, Hormoz; Saffari, Mohsen; Hashempour, Mahrokh; Karimi Zarchi, Ali-Akbar; Alghamdi, Waleed A; Koenig, Harold G

2017-10-01

Multiple sclerosis (MS) is a chronic and progressive disease that causes stress due to its unpredictability and lack of definitive treatments. This study examined the effects of an educational program using a transactional model to help women with MS cope with their disease. In a randomized clinical trial, 80 female patients from the MS Society of Iran were randomized to the intervention ( n  = 40) or a control group ( n  = 40). Outcomes were assessed using Cohen's Perceived Stress Scale (PSS) and the Jalowiec Coping Scale (JCS), which were completed by both groups at baseline, 1 month, and 3 months after the intervention. The intervention consisted of six educational sessions administered over 2 months based on a transactional model. The data were analyzed using repeated measures ANOVA. Average PSS scores decreased significantly over time in the intervention group, while increasing in the control group. Between-group differences were significant at both 1-month and 3-month follow-up ( p  < .001). Both problem-focused and emotion-focused coping styles improved over time in use and effectiveness in the intervention group, whereas little or no change occurred in these coping behaviors in the control group. The transactional model-based education program tested here was successful in reducing stress levels and increasing healthy coping styles in women with MS. If these findings are replicated in future studies, widespread adoption of this program may help women with MS cope more successfully with their disease.

Evidence-based fitness promotion in an afterschool setting: implementation fidelity and its policy implications.

PubMed

Thaw, Jean M; Villa, Manuela; Reitman, David; DeLucia, Christian; Gonzalez, Vanessa; Hanson, K Lori

2014-01-01

Little is known about how the adoption of evidence-based physical activity (PA) curricula by out-of-school time (OST) programs affects children's physical fitness, and there are no clear guidelines of what constitutes reasonable gains given the types of PA instruction currently offered in these programs. Using a three-wave, quasi-experimental, naturalistic observation design, this study evaluated the implementation of an evidence-based PA instruction curriculum (Sports, Play, and Active Recreation for Kids [SPARK]) and examined whether the potential health benefits of evidence-based PA instruction can be replicated in this context when compared to OST programs that do not use evidence-based PA curricula. Quality of PA instruction and SPARK implementation fidelity were also assessed. Results indicated that children in the non-evidence-based/standard PA instruction programs engaged in higher levels of moderate-to-vigorous PA (MVPA) and showed greater improvements in fitness levels over time. The findings from this chapter suggest that while it is generally accepted that evidence-based approaches yield higher levels of PA when implemented by researchers under controlled conditions, findings are inconsistent when evidence-based PA instruction is implemented in the field, under presumably less controlled conditions. It appears that when it comes to PA instruction in afterschool, either less structured activities or well-implemented evidence-based practices could be the key to promoting higher PA levels and greater health and fitness for school-aged children. © 2014 WILEY PERIODICALS, INC.

Hierarchical Bayesian modelling of gene expression time series across irregularly sampled replicates and clusters.

PubMed

Hensman, James; Lawrence, Neil D; Rattray, Magnus

2013-08-20

Time course data from microarrays and high-throughput sequencing experiments require simple, computationally efficient and powerful statistical models to extract meaningful biological signal, and for tasks such as data fusion and clustering. Existing methodologies fail to capture either the temporal or replicated nature of the experiments, and often impose constraints on the data collection process, such as regularly spaced samples, or similar sampling schema across replications. We propose hierarchical Gaussian processes as a general model of gene expression time-series, with application to a variety of problems. In particular, we illustrate the method's capacity for missing data imputation, data fusion and clustering.The method can impute data which is missing both systematically and at random: in a hold-out test on real data, performance is significantly better than commonly used imputation methods. The method's ability to model inter- and intra-cluster variance leads to more biologically meaningful clusters. The approach removes the necessity for evenly spaced samples, an advantage illustrated on a developmental Drosophila dataset with irregular replications. The hierarchical Gaussian process model provides an excellent statistical basis for several gene-expression time-series tasks. It has only a few additional parameters over a regular GP, has negligible additional complexity, is easily implemented and can be integrated into several existing algorithms. Our experiments were implemented in python, and are available from the authors' website: http://staffwww.dcs.shef.ac.uk/people/J.Hensman/.

Claspin Promotes Normal Replication Fork Rates in Human Cells

PubMed Central

Helleday, Thomas; Caldecott, Keith W.

2008-01-01

The S phase-specific adaptor protein Claspin mediates the checkpoint response to replication stress by facilitating phosphorylation of Chk1 by ataxia-telangiectasia and Rad3-related (ATR). Evidence suggests that these components of the ATR pathway also play a critical role during physiological S phase. Chk1 is required for high rates of global replication fork progression, and Claspin interacts with the replication machinery and might therefore monitor normal DNA replication. Here, we have used DNA fiber labeling to investigate, for the first time, whether human Claspin is required for high rates of replication fork progression during normal S phase. We report that Claspin-depleted HeLa and HCT116 cells display levels of replication fork slowing similar to those observed in Chk1-depleted cells. This was also true in primary human 1BR3 fibroblasts, albeit to a lesser extent, suggesting that Claspin is a universal requirement for high replication fork rates in human cells. Interestingly, Claspin-depleted cells retained significant levels of Chk1 phosphorylation at both Ser317 and Ser345, raising the possibility that Claspin function during normal fork progression may extend beyond facilitating phosphorylation of either individual residue. Consistent with this possibility, depletion of Chk1 and Claspin together doubled the percentage of very slow forks, compared with depletion of either protein alone. PMID:18353973

G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV

PubMed Central

Madireddy, Advaitha; Purushothaman, Pravinkumar; Loosbroock, Christopher P.; Robertson, Erle S.; Schildkraut, Carl L.; Verma, Subhash C.

2016-01-01

Kaposi's sarcoma associated herpesvirus (KSHV) establishes life-long latent infection by persisting as an extra-chromosomal episome in the infected cells and by maintaining its genome in dividing cells. KSHV achieves this by tethering its epigenome to the host chromosome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of the viral genome. Sequence analysis of the TR, a GC-rich DNA element, identified several potential Quadruplex G-Rich Sequences (QGRS). Since quadruplexes have the tendency to obstruct DNA replication, we used G-quadruplex stabilizing compounds to examine their effect on latent DNA replication and the persistence of viral episomes. Our results showed that these G-quadruplex stabilizing compounds led to the activation of dormant origins of DNA replication, with preferential bi-directional pausing of replications forks moving out of the TR region, implicating the role of the G-rich TR in the perturbation of episomal DNA replication. Over time, treatment with PhenDC3 showed a loss of viral episomes in the infected cells. Overall, these data show that G-quadruplex stabilizing compounds retard the progression of replication forks leading to a reduction in DNA replication and episomal maintenance. These results suggest a potential role for G-quadruplex stabilizers in the treatment of KSHV-associated diseases. PMID:26837574

Efficient Parvovirus Replication Requires CRL4Cdt2-Targeted Depletion of p21 to Prevent Its Inhibitory Interaction with PCNA

PubMed Central

Pintel, David J.

2014-01-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA. PMID:24699724

Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA.

PubMed

Adeyemi, Richard O; Fuller, Matthew S; Pintel, David J

2014-04-01

Infection by the autonomous parvovirus minute virus of mice (MVM) induces a vigorous DNA damage response in host cells which it utilizes for its efficient replication. Although p53 remains activated, p21 protein levels remain low throughout the course of infection. We show here that efficient MVM replication required the targeting for degradation of p21 during this time by the CRL4Cdt2 E3-ubiquitin ligase which became re-localized to MVM replication centers. PCNA provides a molecular platform for substrate recognition by the CRL4Cdt2 E3-ubiquitin ligase and p21 targeting during MVM infection required its interaction both with Cdt2 and PCNA. PCNA is also an important co-factor for MVM replication which can be antagonized by p21 in vitro. Expression of a stable p21 mutant that retained interaction with PCNA inhibited MVM replication, while a stable p21 mutant which lacked this interaction did not. Thus, while interaction with PCNA was important for targeting p21 to the CRL4Cdt2 ligase re-localized to MVM replication centers, efficient viral replication required subsequent depletion of p21 to abrogate its inhibition of PCNA.

Re-Evaluating Evidence for Linguistic Relativity: Reply to Boroditsky (2001)

ERIC Educational Resources Information Center

January, David; Kako, Edward

2007-01-01

Six unsuccessful attempts at replicating a key finding in the linguistic relativity literature [Boroditsky, L. (2001). Does language shape thought?: Mandarin and English speakers' conceptions of time. "Cognitive Psychology," 43, 1-22] are reported. In addition to these empirical issues in replicating the original finding, theoretical issues…

Tolerance of Sir1p/Origin Recognition Complex-Dependent Silencing for Enhanced Origin Firing at HMRa

PubMed Central

McConnell, Kristopher H.; Müller, Philipp; Fox, Catherine A.

2006-01-01

The HMR-E silencer is a DNA element that directs the formation of silent chromatin at the HMRa locus in Saccharomyces cerevisiae. Sir1p is one of four Sir proteins required for silent chromatin formation at HMRa. Sir1p functions by binding the origin recognition complex (ORC), which binds to HMR-E, and recruiting the other Sir proteins (Sir2p to -4p). ORCs also bind to hundreds of nonsilencer positions distributed throughout the genome, marking them as replication origins, the sites for replication initiation. HMR-E also acts as a replication origin, but compared to many origins in the genome, it fires extremely inefficiently and late during S phase. One postulate to explain this observation is that ORC's role in origin firing is incompatible with its role in binding Sir1p and/or the formation of silent chromatin. Here we examined a mutant HMR-E silencer and fusions between robust replication origins and HMR-E for HMRa silencing, origin firing, and replication timing. Origin firing within HMRa and from the HMR-E silencer itself could be significantly enhanced, and the timing of HMRa replication during an otherwise normal S phase advanced, without a substantial reduction in SIR1-dependent silencing. However, although the robust origin/silencer fusions silenced HMRa quite well, they were measurably less effective than a comparable silencer containing HMR-E's native ORC binding site. PMID:16479013

Saccharomyces cerevisiae as a Model to Study Replicative Senescence Triggered by Telomere Shortening

PubMed Central

Teixeira, M. Teresa

2013-01-01

In many somatic human tissues, telomeres shorten progressively because of the DNA-end replication problem. Consequently, cells cease to proliferate and are maintained in a metabolically viable state called replicative senescence. These cells are characterized by an activation of DNA damage checkpoints stemming from eroded telomeres, which are bypassed in many cancer cells. Hence, replicative senescence has been considered one of the most potent tumor suppressor pathways. However, the mechanism through which short telomeres trigger this cellular response is far from being understood. When telomerase is removed experimentally in Saccharomyces cerevisiae, telomere shortening also results in a gradual arrest of population growth, suggesting that replicative senescence also occurs in this unicellular eukaryote. In this review, we present the key steps that have contributed to the understanding of the mechanisms underlying the establishment of replicative senescence in budding yeast. As in mammals, signals stemming from short telomeres activate the DNA damage checkpoints, suggesting that the early cellular response to the shortest telomere(s) is conserved in evolution. Yet closer analysis reveals a complex picture in which the apparent single checkpoint response may result from a variety of telomeric alterations expressed in the absence of telomerase. Accordingly, the DNA replication of eroding telomeres appears as a critical challenge for senescing budding yeast cells and the easy manipulation of S. cerevisiae is providing insights into the way short telomeres are integrated into their chromatin and nuclear environments. Finally, the loss of telomerase in budding yeast triggers a more general metabolic alteration that remains largely unexplored. Thus, telomerase-deficient S. cerevisiae cells may have more common points than anticipated with somatic cells, in which telomerase depletion is naturally programed, thus potentially inspiring investigations in mammalian cells. PMID:23638436