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.

Genome-Wide Analysis of the Arabidopsis Replication Timing Program1[OPEN

PubMed Central

Brooks, Ashley M.; Wheeler, Emily; LeBlanc, Chantal; Lee, Tae-Jin; Martienssen, Robert A.; Thompson, William F.

2018-01-01

Eukaryotes use a temporally regulated process, known as the replication timing program, to ensure that their genomes are fully and accurately duplicated during S phase. Replication timing programs are predictive of genomic features and activity and are considered to be functional readouts of chromatin organization. Although replication timing programs have been described for yeast and animal systems, much less is known about the temporal regulation of plant DNA replication or its relationship to genome sequence and chromatin structure. We used the thymidine analog, 5-ethynyl-2′-deoxyuridine, in combination with flow sorting and Repli-Seq to describe, at high-resolution, the genome-wide replication timing program for Arabidopsis (Arabidopsis thaliana) Col-0 suspension cells. We identified genomic regions that replicate predominantly during early, mid, and late S phase, and correlated these regions with genomic features and with data for chromatin state, accessibility, and long-distance interaction. Arabidopsis chromosome arms tend to replicate early while pericentromeric regions replicate late. Early and mid-replicating regions are gene-rich and predominantly euchromatic, while late regions are rich in transposable elements and primarily heterochromatic. However, the distribution of chromatin states across the different times is complex, with each replication time corresponding to a mixture of states. Early and mid-replicating sequences interact with each other and not with late sequences, but early regions are more accessible than mid regions. The replication timing program in Arabidopsis reflects a bipartite genomic organization with early/mid-replicating regions and late regions forming separate, noninteracting compartments. The temporal order of DNA replication within the early/mid compartment may be modulated largely by chromatin accessibility. PMID:29301956

Molecular analysis of the replication program in unicellular model organisms.

PubMed

Raghuraman, M K; Brewer, Bonita J

2010-01-01

Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

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.

Genome-wide alterations of the DNA replication program during tumor progression

NASA Astrophysics Data System (ADS)

Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.

2016-08-01

Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.

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.

Genomic Analysis of the DNA Replication Timing Program during Mitotic S Phase in Maize (Zea mays) Root Tips[OPEN

PubMed Central

LeBlanc, Chantal; Lee, Tae-Jin; Mulvaney, Patrick; Allen, George C.; Martienssen, Robert A.; Thompson, William F.

2017-01-01

All plants and animals must replicate their DNA, using a regulated process to ensure that their genomes are completely and accurately replicated. DNA replication timing programs have been extensively studied in yeast and animal systems, but much less is known about the replication programs of plants. We report a novel adaptation of the “Repli-seq” assay for use in intact root tips of maize (Zea mays) that includes several different cell lineages and present whole-genome replication timing profiles from cells in early, mid, and late S phase of the mitotic cell cycle. Maize root tips have a complex replication timing program, including regions of distinct early, mid, and late S replication that each constitute between 20 and 24% of the genome, as well as other loci corresponding to ∼32% of the genome that exhibit replication activity in two different time windows. Analyses of genomic, transcriptional, and chromatin features of the euchromatic portion of the maize genome provide evidence for a gradient of early replicating, open chromatin that transitions gradually to less open and less transcriptionally active chromatin replicating in mid S phase. Our genomic level analysis also demonstrated that the centromere core replicates in mid S, before heavily compacted classical heterochromatin, including pericentromeres and knobs, which replicate during late S phase. PMID:28842533

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…

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…

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

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

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.…

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.

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

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.

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,…

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…

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.

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,…

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.

Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program

PubMed Central

Foti, Rossana; Gnan, Stefano; Cornacchia, Daniela; Dileep, Vishnu; Bulut-Karslioglu, Aydan; Diehl, Sarah; Buness, Andreas; Klein, Felix A.; Huber, Wolfgang; Johnstone, Ewan; Loos, Remco; Bertone, Paul; Gilbert, David M.; Manke, Thomas; Jenuwein, Thomas; Buonomo, Sara C.B.

2016-01-01

Summary DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control and biological function of the replication-timing program are unclear. Rif1 is required for normal genome-wide regulation of replication timing, but its molecular function is poorly understood. Here we show that in mouse embryonic stem cells, Rif1 coats late-replicating domains and, with Lamin B1, identifies most of the late-replicating genome. Rif1 is an essential determinant of replication timing of non-Lamin B1-bound late domains. We further demonstrate that Rif1 defines and restricts the interactions between replication-timing domains during the G1 phase, thereby revealing a function of Rif1 as organizer of nuclear architecture. Rif1 loss affects both number and replication-timing specificity of the interactions between replication-timing domains. In addition, during the S phase, Rif1 ensures that replication of interacting domains is temporally coordinated. In summary, our study identifies Rif1 as the molecular link between nuclear architecture and replication-timing establishment in mammals. PMID:26725008

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…

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…

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.

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…

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),…

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....

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…

Analysis of the temporal program of replication initiation in yeast chromosomes.

PubMed

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

1995-01-01

The multiple origins of eukaryotic chromosomes vary in the time of their initiation during S phase. In the chromosomes of Saccharomyces cerevisiae the presence of a functional telomere causes nearby origins to delay initiation until the second half of S phase. The key feature of telomeres that causes the replication delay is the telomeric sequence (C(1-3)A/G(1-3)T) itself and not the proximity of the origin to a DNA end. A second group of late replicating origins has been found at an internal position on chromosome XIV. Four origins, spanning approximately 140 kb, initiate replication in the second half of S phase. At least two of these internal origins maintain their late replication time on circular plasmids. Each of these origins can be separated into two functional elements: those sequences that provide origin function and those that impose late activation. Because the assay for determining replication time is costly and laborious, it has not been possible to analyze in detail these 'late' elements. We report here the development of two new assays for determining replication time. The first exploits the expression of the Escherichia coli dam methylase in yeast and the characteristic period of hemimethylation that transiently follows the passage of a replication fork. The second uses quantitative hybridization to detect two-fold differences in the amount of specific restriction fragments as a function of progress through S phase. The novel aspect of this assay is the creation in vivo of a non-replicating DNA sequence by site-specific pop-out recombination. This non-replicating fragment acts as an internal control for copy number within and between samples. Both of these techniques are rapid and much less costly than the more conventional density transfer experiments that require CsCl gradients to detect replicated DNA. With these techniques it should be possible to identify the sequences responsible for late initiation, to search for other late replicating regions in the genome, and to begin to analyze the effect that altering the temporal program has on chromosome function.

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…

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…

Promoting Peer Acceptance of Females with Higher-Functioning Autism in a Mainstream Education Setting: A Replication and Extension of the Effects of an Autism Anti-Stigma Program

ERIC Educational Resources Information Center

Ranson, Natalia J.; Byrne, Mitchell K.

2014-01-01

This study evaluated the effects of an eight-session female higher-functioning autism anti-stigma program on the knowledge, attitudes and behavioural intentions of adolescent girls. Participants were seventh-, eighth- and ninth-grade students (N = 273) in a mainstream school. Two-eighth-grade classes were randomly allocated to the intervention…

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

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

Ecosystem Consequences of Contrasting Flow Regimes in an Urban Effects Stream Mesocosm Study

EPA Science Inventory

A stream mesocosm experiment was conducted to study the ecosystem-wide effects of two replicated flow hydrograph treatments programmed in an attempt to compare a simulated predevelopment condition to the theoretical changes that new development brings, while accounting for engine...

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.

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…

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.

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…

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.

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…

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...

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.

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.

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.

Prevalence and Effects of Child Exposure to Domestic Violence.

ERIC Educational Resources Information Center

Fantuzzo, John W.; Mohr, Wanda K.

1999-01-01

Discusses the limitations of current databases documenting the prevalence and effects of child exposure to domestic violence and describes a model for the collection of reliable and valid prevalence data, the Spousal Assault Replication Program, which uses data collected by the police and university researchers. (SLD)

Topologically associating domains are stable units of replication-timing regulation.

PubMed

Pope, Benjamin D; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L; Wang, Yanli; Hansen, R Scott; Canfield, Theresa K; Thurman, Robert E; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H; Snyder, Michael P; Stamatoyannopoulos, John A; Taylor, James; Hardison, Ross C; Kahveci, Tamer; Ren, Bing; Gilbert, David M

2014-11-20

Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program. In mammals, replication timing is cell-type-specific with at least half the genome switching replication timing during development, primarily in units of 400-800 kilobases ('replication domains'), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements. Early and late replication correlate, respectively, with open and closed three-dimensional chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, late replication correlates with lamina-associated domains (LADs). Recent Hi-C mapping has unveiled substructure within chromatin compartments called topologically associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to replication domains. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure. Here we localize boundaries of replication domains to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, replication domain boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure replication domain boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type-specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell-type-specific sub-nuclear compartmentalization and replication timing with developmentally stable structural domains and offer a unified model for large-scale chromosome structure and function.

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.

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…

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…

Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

PubMed Central

Smith, Owen K.; Aladjem, Mirit I.

2014-01-01

The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

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.

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.

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.

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…

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…

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…

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.

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

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.

Project SHAL: An Analysis of Implementation in the St. Louis Public Schools--Findings from the Replication Implementation Field Test, June 1984.

ERIC Educational Resources Information Center

Young, Rufus, Jr.

The Effective Schools Program in St. Louis, Missouri, public schools expanded the concept of effective schools developed in Project SHAL (1980-1984). The following five characteristics are considered effective school factors: (1) strong administrative leadership (2) high teacher expectations; (3) positive school climate; (4) total school…

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

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

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

The Relative Effectiveness of Training Methods for Attaining Training Objectives: Current Opinion of Training Practitioners.

ERIC Educational Resources Information Center

Shoenfelt, Elizabeth L.; And Others

This study replicated the earlier survey efforts of Carroll, Paine, and Ivancevich (1972) and Neider (1981) on the relative effectiveness among practitioners of various training methods for attaining different training objectives. Ten training methods were assessed: (1) computer aided instruction (CAI); (2) programmed instruction; (3) lecture…

A Critical-Incident Stress Debriefing Program for Hospital-Based Health Care Personnel.

ERIC Educational Resources Information Center

Spitzer, William J.; Burke, Laurie

1993-01-01

Reviews individual and institutional effects of critical-incident stress on health care delivery and use of stress education, defusings, and debriefings as effective interventions with health care personnel. Presents successful efforts of social work department using these techniques in major university hospital system as model for replication in…

Effectiveness of Dialectical Behavior Therapy in a Community Mental Health Center

ERIC Educational Resources Information Center

Comtois, Katherine Anne; Elwood, Lynn; Holdcraft, Laura C.; Smith, Wayne R.; Simpson, Tracy L.

2007-01-01

Dialectical behavior therapy (DBT) has been shown to be effective in randomized controlled trials with women with borderline personality disorder and histories of chronic self-inflicted injury including suicide attempts. The present study is a pre-post replication of a comprehensive DBT program in a community mental health center for individuals…

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…

Mental Illness Training on the Internet for Nurse Aides: A Replication Study

PubMed Central

Irvine, A. Blair; Billow, Molly B.; McMahon, Edward; Eberhage, Mark G.; Seeley, John R.; Bourgeois, Michelle

2013-01-01

Internet training courses for Nurse Aides (NA) in long term care facilities (LTCs) have been shown to be effective., Little is known, however, about Internet training effects on NAs in a non-research context, or about continued utilization of an available training program. In this research, a replication study was conducted with the Internet training program Caring Skills: Working with Mental Illness. Three LTCs provided the training to all NAs, each within a one-month interval scheduled during consecutive months. Supervisors were interviewed subsequently about their experiences organizing and supervising the training. Participants in all three LTCs showed positive pre-posttests effects with large effect sizes on situational knowledge and self-efficacy, and knowledge about mental illness. Users rated the program highly, and they indicated that it would improve quality of their resident care. Supervisors praised the training, and they said NAs were using recommended training behaviors. Although available to all staff, nursing and other staff made little use of the training in subsequent months. Training for NAs on the internet thus appears feasible, and it is perceived to be beneficial for resident care. Plans for continued utilization and dissemination of best practices to other staff, however, should be integrated when planning for staff training on the Internet. PMID:23379724

Testing the Replicability of a Successful Care Management Program: Results from a Randomized Trial and Likely Explanations for Why Impacts Did Not Replicate.

PubMed

Peterson, G Greg; Zurovac, Jelena; Brown, Randall S; Coburn, Kenneth D; Markovich, Patricia A; Marcantonio, Sherry A; Clark, William D; Mutti, Anne; Stepanczuk, Cara

2016-12-01

To test whether a care management program could replicate its success in an earlier trial and determine likely explanations for why it did not. Medicare claims and nurse contact data for Medicare fee-for-service beneficiaries with chronic illnesses enrolled in the trial in eastern Pennsylvania (N = 483). A randomized trial with half of enrollees receiving intensive care management services and half receiving usual care. We developed and tested hypotheses for why impacts declined. All outcomes and covariates were derived from claims and the nurse contact data. From 2010 to 2014, the program did not reduce hospitalizations or generate Medicare savings to offset program fees that averaged $260 per beneficiary per month. These estimates are statistically different (p < .05) from the large reductions in hospitalizations and spending in the first trial (2002-2010). The treatment-control differences in the second trial disappeared because the control group's risk-adjusted hospitalization rate improved, not because the treatment group's outcomes worsened. Even if demonstrated in a randomized trial, successful results from one test may not replicate in other settings or time periods. Assessing whether gaps in care that the original program filled exist in other settings can help identify where earlier success is likely to replicate. © Health Research and Educational Trust.

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...

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…

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.

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,…

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…

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.

Welfare-to-Work Programs in America, 1980 to 2005: Meta-Analytic Evidence of the Importance of Job and Child Care Availability

PubMed Central

GOREY, KEVIN M.

2016-01-01

This meta-analysis extended a Campbell Collaboration review of welfare-to-work programs. Its synthesis of 65 randomized trials in America over the past generation replicated a small overall intervention effect. Moreover, it found (1) there was no long-term employment effect of interventions in areas where jobs were relatively unavailable, and (2) programs that provided child care were more effective than those that did not in the short and long term, even in areas of high labor market withdrawal. The availability of jobs as well as such supports as child care that enable their access seem to be key elements of welfare-to-work programs that work. PMID:27932938

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.

The effect of two kinds of role playing on self-evaluation of improved assertiveness.

PubMed

Kipper, D A

1992-03-01

The study investigated the "differential effect of role-playing enactments" hypothesis through self-evaluations of improvement in assertiveness by participants in an assertive training program. Twenty-two nonassertive Israeli students were trained in two groups: mimetic-replications (action modeling, n = 12) and spontaneous (self-produced action, n = 10) role-playing interventions. Comparisons of their scores on the Self-Expression College Scale (CSES) before and after the training showed that both groups significantly improved their self-evaluations, but the mimetic-replication group did better. In particular, this group scored significantly higher on the CSES first factor (the willingness to take risks in situations that involved other, significant persons).

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.

Use of Video Modeling to Teach Extinguishing of Cooking Related Fires to Individuals with Moderate Intellectual Disabilities

ERIC Educational Resources Information Center

Mechling, Linda C.; Gast, David L.; Gustafson, Melissa R.

2009-01-01

This study evaluated the effectiveness of video modeling to teach fire extinguishing behaviors to three young adults with moderate intellectual disabilities. A multiple probe design across three fire extinguishing behaviors and replicated across three students was used to evaluate the effectiveness of the video-based program. Results indicate that…

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

Topologically-associating domains are stable units of replication-timing regulation

PubMed Central

Pope, Benjamin D.; Ryba, Tyrone; Dileep, Vishnu; Yue, Feng; Wu, Weisheng; Denas, Olgert; Vera, Daniel L.; Wang, Yanli; Hansen, R. Scott; Canfield, Theresa K.; Thurman, Robert E.; Cheng, Yong; Gülsoy, Günhan; Dennis, Jonathan H.; Snyder, Michael P.; Stamatoyannopoulos, John A.; Taylor, James; Hardison, Ross C.; Kahveci, Tamer; Ren, Bing; Gilbert, David M.

2014-01-01

Summary Eukaryotic chromosomes replicate in a temporal order known as the replication-timing program1. During mammalian development, at least half the genome changes replication timing, primarily in units of 400–800 kb (“replication domains”; RDs), whose positions are preserved in different cell types, conserved between species, and appear to confine long-range effects of chromosome rearrangements2–7. Early and late replication correlate strongly with open and closed chromatin compartments identified by high-resolution chromosome conformation capture (Hi-C), and, to a lesser extent, lamina-associated domains (LADs)4,5,8,9. Recent Hi-C mapping has unveiled a substructure of topologically-associating domains (TADs) that are largely conserved in their positions between cell types and are similar in size to RDs8,10. However, TADs can be further sub-stratified into smaller domains, challenging the significance of structures at any particular scale11,12. Moreover, attempts to reconcile TADs and LADs to replication-timing data have not revealed a common, underlying domain structure8,9,13. Here, we localize boundaries of RDs to the early-replicating border of replication-timing transitions and map their positions in 18 human and 13 mouse cell types. We demonstrate that, collectively, RD boundaries share a near one-to-one correlation with TAD boundaries, whereas within a cell type, adjacent TADs that replicate at similar times obscure RD boundaries, largely accounting for the previously reported lack of alignment. Moreover, cell-type specific replication timing of TADs partitions the genome into two large-scale sub-nuclear compartments revealing that replication-timing transitions are indistinguishable from late-replicating regions in chromatin composition and lamina association and accounting for the reduced correlation of replication timing to LADs and heterochromatin. Our results reconcile cell type specific sub-nuclear compartmentalization with developmentally stable chromosome domains and offer a unified model for large-scale chromosome structure and function. PMID:25409831

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

Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus

PubMed Central

Kanda, Tatsuo; Nakamoto, Shingo; Wu, Shuang; Nakamura, Masato; Jiang, Xia; Haga, Yuki; Sasaki, Reina; Yokosuka, Osamu

2015-01-01

Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored. PMID:26623267

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.

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)…

[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.

Challenges Facing Successful Scaling Up of Effective Screening for Cardiovascular Disease by Community Health Workers in Mexico and South Africa: Policy Implications.

PubMed

S, Abrahams-Gessel; Denman, C A; Ta, Gaziano; Ns, Levitt; T, Puoane

The integration of community health workers (CHWs) into primary and secondary prevention functions in health programs and services delivery in Mexico and South Africa has been demonstrated to be effective. Task-sharing related to adherence and treatment, from nurses to CHWs, has also been effectively demonstrated in these areas. HIV/AIDS and TB programs in South Africa have seen similar successes in task-sharing with CHWs in the areas of screening for risk and adherence to treatment. In the area of non-communicable diseases (NCDs), there is a policy commitment to integrating CHWs into primary health care programs at public health facilities in both Mexico and South Africa in the areas of reproductive health and infant health. Yet current programs utilizing CHWs are not integrated into existing primary health care services in a comprehensive manner for primary and secondary prevention of NCDs. In a recently completed study, CHWs were trained to perform the basic diagnostic function of primary screening to assess the risk of suffering a CVD-related event in the community using a non-laboratory risk assessment tool and referring persons at moderate to high risk to local government clinics, for further assessment and management by a nurse or physician. In this paper we compare the experience with this CVD screening study to successful programs in vaccination, reproductive health, HIV/AIDS, and TB specifically to identify the barriers we identified as limitations to replicating these programs in the area of CVD diagnosis and management. We review barriers impacting the effective translation of policy into practice, including scale up issues; training and certification issues; integrating CHW to existing primary care teams and health system; funding and resource gaps. Finally, we suggest policy recommendations to replicate the demonstrated success of programs utilizing task-sharing with CHWs in infectious diseases and reproductive health, to integrated programs in NCD.

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.

The Effect of Contingent Reinforcement on the Acquisition of Sight Vocabulary. Technical Report No. 49.

ERIC Educational Resources Information Center

Brandt, Mary E.; And Others

The present study is a replication of a Lahey and Drabman study (1974) which investigated the effects of contingent versus noncontingent reinforcement on the learning of sight words. The subjects in this study were 14 Kamehameha Early Education Program (KEEP) students who composed the lowest reading group in a combined first-second grade…

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.

INVESTIGATION OF THE PERSISTENCE AND REPLICATION OF NUCLEAR POLYHEDROSIS VIRUSES IN VERTEBRATE AND INSECT CELL CULTURES BY THE USE OF HYBRIDIZATION TECHNIQUES

EPA Science Inventory

The Health Effects Research Laboratory, Research Triangle Park, conducts a coordinaged environmental health research program in toxicology, epidemiology, and clinical studies using human volunteer subjects. These studies address problems in air pollution, non-ionizing radiation, ...

PRESCHOOL INTERVENTION--A PRELIMINARY REPORT OF THE PERRY PRESCHOOL PROJECT.

ERIC Educational Resources Information Center

WEIKART, DAVID P., ED.

THE PERRY PRESCHOOL PROJECT IS AN EXPERIMENT WITH REPLICATIONS DESIGNED TO ASSESS THE LONGITUDINAL EFFECTS OF A 2-YEAR, COGNITIVELY ORIENTED, COMPENSATORY EDUCATION PROGRAM. SELECTED FROM A POPULATION WHICH IS NEGRO, FUNCTIONALLY RETARDED, AND CULTURALLY DEPRIVED, CONTROL AND EXPERIMENTAL GROUPS ARE EQUATED FOR MEAN CULTURAL-DEPRIVATION RATING AND…

"Celebrate Science" Has Formula for Hands-On Learning

ERIC Educational Resources Information Center

Brydolf, Carol

2012-01-01

Cost-effective, easily replicated program is a win-win situation for high schoolers who teach science and for their elementary students. The thank-you letter from Leslie, a grade-schooler in San Diego County's Ramona Unified School District, speaks volumes about the excitement generated by "Celebrate Science"--an innovative,…

Peer Study Groups as Catalyst for Vocational Exploration

ERIC Educational Resources Information Center

Arendale, David R.; Hane, Amanda R.

2016-01-01

Postsecondary peer assisted learning programs often cite improving academic achievement for students. This qualitative study investigated the potential effect of serving as student facilitators of a peer study group on their future vocation. This was a replication of previous studies of personal and professional outcomes for study group…

Pragmatic replication trial of health promotion coaching for obesity in serious mental illness and maintenance of outcomes.

PubMed

Bartels, Stephen J; Pratt, Sarah I; Aschbrenner, Kelly A; Barre, Laura K; Naslund, John A; Wolfe, Rosemarie; Xie, Haiyi; McHugo, Gregory J; Jimenez, Daniel E; Jue, Ken; Feldman, James; Bird, Bruce L

2015-04-01

Few studies targeting obesity in serious mental illness have reported clinically significant risk reduction, and none have been replicated in community settings or demonstrated sustained outcomes after intervention withdrawal. The authors sought to replicate positive health outcomes demonstrated in a previous randomized effectiveness study of the In SHAPE program across urban community mental health organizations serving an ethnically diverse population. Persons with serious mental illness and a body mass index (BMI) >25 receiving services in three community mental health organizations were recruited and randomly assigned either to the 12-month In SHAPE program, which included membership in a public fitness club and weekly meetings with a health promotion coach, or to fitness club membership alone. The primary outcome measures were weight and cardiorespiratory fitness (as measured with the 6-minute walk test), assessed at baseline and at 3, 6, 9, 12, and 18 months. Participants (N=210) were ethnically diverse (46% were nonwhite), with a mean baseline BMI of 36.8 (SD=8.2). At 12 months, the In SHAPE group (N=104) had greater reduction in weight and improved fitness compared with the fitness club membership only group (N=106). Primary outcomes were maintained at 18 months. Approximately half of the In SHAPE group (51% at 12 months and 46% at 18 months) achieved clinically significant cardiovascular risk reduction (a weight loss ≥5% or an increase of >50 meters on the 6-minute walk test). This is the first replication study confirming the effectiveness of a health coaching intervention in achieving and sustaining clinically significant reductions in cardiovascular risk for overweight and obese persons with serious mental illness.

Historical context for the creation of the Office of Adolescent Health and the Teen Pregnancy Prevention Program.

PubMed

Kappeler, Evelyn M; Farb, Amy Feldman

2014-03-01

In Fiscal Year 2010, Federal funds were dedicated to support evidence-based approaches to effectively target teen pregnancy prevention and resulted in the establishment of the Office of Adolescent Health (OAH) and the Teen Pregnancy Prevention (TPP) Program. Through the tiered TPP Program, OAH supports replication and evaluation of programs using models whose effectiveness has been demonstrated through rigorous evaluation and the development and testing of promising or innovative pregnancy prevention strategies and approaches. This article documents the creation of OAH and the development of the TPP Program, the identification of a TPP evidence base, current program and evaluation efforts at OAH, and government coordination and partnerships related to reducing teen pregnancy. This article is of interest to those working to improve the health and wellbeing of adolescents. Published by Elsevier Inc.

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.

School-based programs to reduce sexual risk behaviors: a review of effectiveness.

PubMed Central

Kirby, D; Short, L; Collins, J; Rugg, D; Kolbe, L; Howard, M; Miller, B; Sonenstein, F; Zabin, L S

1994-01-01

This review was undertaken in recognition of the mounting public health and social problems associated with adolescent sexual behavior and the importance of basing school-affiliated programs designed to reduce sexual risk-taking behavior on sound research. The authors were commissioned by the Division of Adolescent and School Health within the Centers for Disease Control and Prevention, Public Health Service, to review carefully the research on these programs and to assess their impact on behavior. The authors identified 23 studies of school-based programs that were published in professional journals and measured program impact on behavior. They then summarized the results of those studies, identifying the distinguishing characteristics of effective programs, and citing important research questions to be addressed in the future. Not all sex and AIDS education programs had significant effects on adolescent sexual risk-taking behavior, but specific programs did delay the initiation of intercourse, reduce the frequency of intercourse, reduce the number of sexual partners, or increase the use of condoms or other contraceptives. These effective programs have the potential to reduce exposure to unintended pregnancy and sexually transmitted disease, including HIV infection. These programs should be replicated widely in U.S. schools. Additional research is needed to improve the effectiveness of programs and to clarify the most important characteristics of effective programs. PMID:8190857

Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

NASA Astrophysics Data System (ADS)

Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

2016-03-01

We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

Training Paraprofessionals to Target Socialization in Students with ASD: Fidelity of Implementation and Social Validity

ERIC Educational Resources Information Center

Kim, Sunny; Koegel, Robert L.; Koegel, Lynn K.

2017-01-01

Although the literature suggests that it is feasible to train paraprofessionals to effectively implement social interventions for students with Autism Spectrum Disorders (ASD), there is a paucity of research that addresses the social validity of these programs. The present study replicated and extended previous research on paraprofessional…

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…

Emotion-based preventive intervention: Effectively promoting emotion knowledge and adaptive behavior among at-risk preschoolers.

PubMed

Finlon, Kristy J; Izard, Carroll E; Seidenfeld, Adina; Johnson, Stacy R; Cavadel, Elizabeth Woodburn; Ewing, E Stephanie Krauthamer; Morgan, Judith K

2015-11-01

Effectiveness studies of preschool social-emotional programs are needed in low-income, diverse populations to help promote the well-being of at-risk children. Following an initial program efficacy study 2 years prior, 248 culturally diverse Head Start preschool children participated in the current effectiveness trial and received either the Emotion-Based Prevention Program (EBP) or the I Can Problem Solve (ICPS) intervention. Pre- and postdata collection included direct child assessment, teacher report, parent interview, and independent observations. Teachers implementing the EBP intervention demonstrated good and consistent fidelity to the program. Overall, children in EBP classrooms gained more emotion knowledge and displayed greater decreases in negative emotion expressions and internalizing behaviors across the implementation period as compared to children in ICPS classrooms. In addition, cumulative risk, parental depressive symptoms, and classroom climate significantly moderated treatment effects. For children experiencing more stress or less support, EBP produced more successful outcomes than did ICPS. These results provide evidence of EBP sustainability and program effectiveness, as did previous findings that demonstrated EBP improvements in emotion knowledge, regulation skills, and behavior problems replicated under unsupervised program conditions.

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.

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.

Closing the Racial Discipline Gap in Classrooms by Changing Teacher Practice

PubMed Central

Gregory, Anne; Hafen, Christopher A.; Ruzek, Erik; Mikami, Amori Yee; Allen, Joseph P.; Pianta, Robert C.

2017-01-01

Black students are issued school discipline sanctions at rates higher than members of other racial and ethnic groups, underscoring the need for professional development that addresses this gap. In 86 secondary classrooms, a randomized controlled trial examined the effects of a 2-year teacher coaching program, My Teaching Partner Secondary (MTP-S). Results from the second year of coaching and the year after coaching was discontinued replicated previous findings from the first year of coaching—intervention teachers had no significant disparities in discipline referral between Black students and their classmates, compared to teachers in the control condition, for whom racial discipline gaps remained. Thus, MTP-S effects were replicated in the second year of coaching and maintained when coaching was withdrawn. Mediational analyses identified mechanisms for these effects; Black students had a low probability of receiving disciplinary referrals with teachers who increased skills to engage students in high-level analysis and inquiry. PMID:28190913

3D Simulation: Microgravity Environments and Applications

NASA Technical Reports Server (NTRS)

Hunter, Steve L.; Dischinger, Charles; Estes, Samantha; Parker, Nelson C. (Technical Monitor)

2001-01-01

Most, if not all, 3-D and Virtual Reality (VR) software programs are designed for one-G gravity applications. Space environments simulations require gravity effects of one one-thousandth to one one-million of that of the Earth's surface (10(exp -3) - 10(exp -6) G), thus one must be able to generate simulations that replicate those microgravity effects upon simulated astronauts. Unfortunately, the software programs utilized by the National Aeronautical and Space Administration does not have the ability to readily neutralize the one-G gravity effect. This pre-programmed situation causes the engineer or analysis difficulty during micro-gravity simulations. Therefore, microgravity simulations require special techniques or additional code in order to apply the power of 3D graphic simulation to space related applications. This paper discusses the problem and possible solutions to allow microgravity 3-D/VR simulations to be completed successfully without program code modifications.

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.

Efficacy vs effectiveness trial results of an indicated "model" substance abuse program: implications for public health.

PubMed

Hallfors, Denise; Cho, Hyunsan; Sanchez, Victoria; Khatapoush, Shereen; Kim, Hyung Min; Bauer, Daniel

2006-12-01

The US Department of Education requires schools to choose substance abuse and violence prevention programs that meet standards of effectiveness. The Substance Abuse and Mental Health Services Agency certifies "model" programs that meet this standard. We compared findings from a large, multisite effectiveness trial of 1 model program to its efficacy trial findings, upon which the certification was based. 1370 high-risk youths were randomized to experimental or control groups across 9 high schools in 2 large urban school districts. We used intent-to-treat and on-treatment approaches to examine baseline equivalence, attrition, and group differences in outcomes at the end of the program and at a 6-month follow-up. Positive efficacy trial findings were not replicated in the effectiveness trial. All main effects were either null or worse for the experimental than for the control group. These findings suggest that small efficacy trials conducted by developers provide insufficient evidence of effectiveness. Federal agencies and public health scientists must work together to raise the standards of evidence and ensure that data from new trials are incorporated into ongoing assessments of program effects.

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

Impact of the Teacher Study Group Professional Development Program on Student Vocabulary and Observed Teaching Practice: A Replication in First Grade Classrooms

ERIC Educational Resources Information Center

Gersten, Russell; Dimino, Joseph; Jayanthi, Madhavi; Newman-Gonchar, Rebecca; Taylor, Mary Jo

2013-01-01

The ESEA Blueprint for Reform states that teachers need "effective, ongoing, job-embedded, professional development that is targeted to student and school needs… [and] aligned with evidence of improvements in student learning." Unfortunately, the professional development approaches advocated, though sensible and compelling in theory,…

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.

Viral replication rate regulates clinical outcome and CD8 T cell responses during highly pathogenic H5N1 influenza virus infection in mice.

PubMed

Hatta, Yasuko; Hershberger, Karen; Shinya, Kyoko; Proll, Sean C; Dubielzig, Richard R; Hatta, Masato; Katze, Michael G; Kawaoka, Yoshihiro; Suresh, M

2010-10-07

Since the first recorded infection of humans with H5N1 viruses of avian origin in 1997, sporadic human infections continue to occur with a staggering mortality rate of >60%. Although sustained human-to-human transmission has not occurred yet, there is a growing concern that these H5N1 viruses might acquire this trait and raise the specter of a pandemic. Despite progress in deciphering viral determinants of pathogenicity, we still lack crucial information on virus/immune system interactions pertaining to severe disease and high mortality associated with human H5N1 influenza virus infections. Using two human isolates of H5N1 viruses that differ in their pathogenicity in mice, we have defined mechanistic links among the rate of viral replication, mortality, CD8 T cell responses, and immunopathology. The extreme pathogenicity of H5N1 viruses was directly linked to the ability of the virus to replicate rapidly, and swiftly attain high steady-state titers in the lungs within 48 hours after infection. The remarkably high replication rate of the highly pathogenic H5N1 virus did not prevent the induction of IFN-β or activation of CD8 T cells, but the CD8 T cell response was ineffective in controlling viral replication in the lungs and CD8 T cell deficiency did not affect viral titers or mortality. Additionally, BIM deficiency ameliorated lung pathology and inhibited T cell apoptosis without affecting survival of mice. Therefore, rapidly replicating, highly lethal H5N1 viruses could simply outpace and overwhelm the adaptive immune responses, and kill the host by direct cytopathic effects. However, therapeutic suppression of early viral replication and the associated enhancement of CD8 T cell responses improved the survival of mice following a lethal H5N1 infection. These findings suggest that suppression of early H5N1 virus replication is key to the programming of an effective host response, which has implications in treatment of this infection in humans.

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

Effects of the Positive Action program on achievement and discipline: two matched-control comparisons.

PubMed

Flay, B R; Allred, C G; Ordway, N

2001-06-01

This paper reports on the effectiveness of an integrated comprehensive school model for character development, problem behavior prevention, and academic achievement enhancement. The Positive Action program consists of a school curriculum, together with schoolwide climate, family, and community components. As evaluated here, the yearly K-6 curriculum consists of over 140 fifteen-to-twenty-minute lessons per year delivered in school classrooms on an almost daily basis. The program is based on theories of self-concept, learning, behavior, and school ecology. We use a matched control design and school-level achievement and disciplinary data to evaluate program effects on student performance and behavior in two separate school districts. The program improved achievement by 16% in one district and 52% in another, and reduced disciplinary referrals by 78% in one district and 85% in the other. We discuss implications of these replicated findings for the prevention of substance abuse and violence, the improvement of school performance, and the reform of American schools.

The Effects of Self-Esteem Enhancement on School Aged Children

DTIC Science & Technology

1999-05-17

generalized, there is evidence that it may be beneficial to offer self esteem training to children of low SES populations....This replication study examined the effect of a self esteem enhancement program on mid-western sixth graders’ self esteem scores (n=29). The...Coopersmith Self esteem Inventory (SEI) was used to determine pre and post test self esteem scores for students who participated in a four month self esteem

The Maine Savvy Caregiver Project: translating an evidence-based dementia family caregiver program within the RE-AIM Framework.

PubMed

Samia, Linda W; Aboueissa, AbouEl-Makarim; Halloran, Jan; Hepburn, Kenneth

2014-01-01

This article presents findings of a 3-year Savvy Caregiver Program translational study designed with the RE-AIM framework to create a statewide sustainable infrastructure and improve dementia family caregiver outcomes in one rural state. The RE-AIM dimensions--reach, effectiveness, adoption, implementation and maintenance--were evaluated using mixed methods. The program reached 770 caregivers and 87.7% (n = 676) participated in the study with 60.5% (n = 409) residing in rural locations. Participants demonstrated improved confidence, fewer depressive symptoms, and better managed their situation. Trainer resources, partnerships, and adequate planning were essential for program adoption and sustainability. Implications for replication are discussed.

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.

PSYCHOLOGY. Estimating the reproducibility of psychological science.

PubMed

2015-08-28

Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams. Copyright © 2015, American Association for the Advancement of Science.

The effectiveness of a school-based adolescent depression education program.

PubMed

Swartz, Karen L; Kastelic, Elizabeth A; Hess, Sally G; Cox, Todd S; Gonzales, Lizza C; Mink, Sallie P; DePaulo, J Raymond

2010-02-01

In an effort to decrease the suicide rate in adolescents, many interventions have focused on school-based suicide prevention programs. Alternatively, depression education in schools might be effective in decreasing the morbidity, mortality, and stigma associated with adolescent depression. The Adolescent Depression Awareness Program (ADAP) developed a 3-hour curriculum to teach high school students about the illness of depression. The purpose of this study was to assess the effectiveness of the ADAP curriculum in improving high school students' knowledge about depression. From 2001 to 2005, 3,538 students were surveyed on their knowledge about depression before and after exposure to the ADAP curriculum. The number of students scoring 80% or higher on the assessment tool more than tripled from pretest to posttest (701 to 2,180), suggesting the effectiveness of the ADAP curriculum. Further study and replication are required to determine if improved knowledge translates into increased treatment-seeking behavior.

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.

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.

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

What Should Researchers Expect When They Replicate Studies? A Statistical View of Replicability in Psychological Science.

PubMed

Patil, Prasad; Peng, Roger D; Leek, Jeffrey T

2016-07-01

A recent study of the replicability of key psychological findings is a major contribution toward understanding the human side of the scientific process. Despite the careful and nuanced analysis reported, the simple narrative disseminated by the mass, social, and scientific media was that in only 36% of the studies were the original results replicated. In the current study, however, we showed that 77% of the replication effect sizes reported were within a 95% prediction interval calculated using the original effect size. Our analysis suggests two critical issues in understanding replication of psychological studies. First, researchers' intuitive expectations for what a replication should show do not always match with statistical estimates of replication. Second, when the results of original studies are very imprecise, they create wide prediction intervals-and a broad range of replication effects that are consistent with the original estimates. This may lead to effects that replicate successfully, in that replication results are consistent with statistical expectations, but do not provide much information about the size (or existence) of the true effect. In this light, the results of the Reproducibility Project: Psychology can be viewed as statistically consistent with what one might expect when performing a large-scale replication experiment. © The Author(s) 2016.

Disseminating and Replicating an Effective Emerging Literacy Technology Curriculum: A Final Report

ERIC Educational Resources Information Center

Hutinger, Patricia; Bell, Carol; Daytner, Gary; Johanson, Joyce

2005-01-01

Emerging Literacy Technology Curriculum (ELiTeC 2, [referred to as E2 in this report]), housed at the Center for Best Practices in Early Childhood at Western Illinois University, was funded in 2000 by the U.S. Department of Education's Office of Special Education Programs (OSEP) as a 3-year Phase 3 Steppingstones of Technology Research on…

Evaluating Phase II of a New York City-Wide STEM Initiative Using Propensity Score Methods: A Replication Study

ERIC Educational Resources Information Center

Thomas, Ally S.; Bonner, Sarah M.; Everson, Howard T.

2014-01-01

Recently, the authors have been exploring the use of propensity score methods for developing evidence of program impact. Specifically, they have been developing evidence (after one year of implementation) of the effects of the Math Science Partnership in New York City ("MSPinNYC2") on high school students' achievement--both in terms of…

The Location and Effects of Visual Hemisphere-Specific Stimulation on Reading Fluency in Children with the Characteristics of Dyslexia

ERIC Educational Resources Information Center

Koen, Bobbie Jean; Hawkins, Jacqueline; Zhu, Xi; Jansen, Ben; Fan, Weihua; Johnson, Sharon

2018-01-01

Fluency is used as an indicator of reading proficiency. Many students with reading disabilities are unable to benefit from typical interventions. This study is designed to replicate Lorusso, Facoetti, Paganoni, Pezzani, and Molteni's (2006) work using FlashWord, a computer program that tachistoscopically presents words in the right or left visual…

Space Qualification of Laser Diode Arrays

NASA Technical Reports Server (NTRS)

Troupaki, Elisavet; Kashem, Nasir B.; Allan, Graham R.; Vasilyev, Aleksey; Stephen, Mark

2005-01-01

Laser instruments have great potential in enabling a new generation of remote-sensing scientific instruments. NASA s desire to employ laser instruments aboard satellites, imposes stringent reliability requirements under severe conditions. As a result of these requirements, NASA has a research program to understand, quantify and reduce the risk of failure to these instruments when deployed on satellites. Most of NASA s proposed laser missions have base-lined diode-pumped Nd:YAG lasers that generally use quasi-constant wave (QCW), 808 nm Laser Diode Arrays (LDAs). Our group has an on-going test program to measure the performance of these LDAs when operated in conditions replicating launch and orbit. In this paper, we report on the results of tests designed to measure the effect of vibration loads simulating launch into space and the radiation environment encountered on orbit. Our primary objective is to quantify the performance of the LDAs in conditions replicating those of a satellite instrument, determine their limitations and strengths which will enable better and more robust designs. To this end we have developed a systematic testing strategy to quantify the effect of environmental stresses on the optical and electrical properties of the LDA.

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.

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.

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.

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.

Characteristics of the original patient navigation programs to reduce disparities in the diagnosis and treatment of breast cancer.

PubMed

Vargas, Roberto B; Ryan, Gery W; Jackson, Catherine A; Rodriguez, Rian; Freeman, Harold P

2008-07-15

Patient navigation is an intervention developed to reduce disparities in cancer care that is being widely replicated and receiving considerable support for demonstration projects and research to test its effectiveness. In the current study, the authors present an in-depth descriptive analysis of the original patient navigation programs to inform current and future program development. A qualitative multistakeholder case study using interviews and site visits of the first patient navigation site and 2 sites subsequently developed by the leadership of the original site were evaluated. At these sites, patient navigation is a system, as opposed to a person, comprised primarily of navigators and directors that work together to remove barriers and facilitate access in a well-defined course of care; navigators were from the community or were culturally similar to the patient population served but were also paid employees of the clinical care site with detailed knowledge of the clinical course patients must traverse to complete care plans. Directors had administrative authority over the clinical facility and social capital across institutions, and communicated regularly and openly with navigators to implement system level changes to remove barriers to care. Contextual factors such as policies supporting breast cancer care also influenced the implementation of these programs. The first patient navigation programs combined community and culturally sensitive care-coordination with aspects of disease management programs to reduce racial, ethnic, and poverty-driven disparities in care. Future efforts to replicate and evaluate patient navigation should take into account these unique aspects of the original patient navigation programs. (c) 2008 American Cancer Society.

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…

Does a gatekeeper suicide prevention program work in a school setting? Evaluating training outcome and moderators of effectiveness.

PubMed

Tompkins, Tanya L; Witt, Jody; Abraibesh, Nadia

2009-12-01

The current study sought to evaluate the suicide prevention gatekeeper training program QPR (Question, Persuade, and Refer) among school personnel using a non-equivalent control group design. Substantial gains were demonstrated from pre- to post-test for attitudes, knowledge, and beliefs regarding suicide and suicide prevention. Exploratory analyses revealed the possible moderating effects of age, professional role, prior training, and recent contact with suicidal youth on QPR participants' general knowledge, questioning, attitudes toward suicide and suicide prevention, QPR quiz scores, and self-efficacy. The need for replication using a more rigorous experimental design in the context of strong community collaboration is discussed.

The Development of Project Information Packages for Effective Approaches in Compensatory Education. Final Report. Report No. UR-254.

ERIC Educational Resources Information Center

Tallmadge, G. Kasten

The project described herein represents an attempt by the U. S. Office of Education to take a more active role in the national dissemination and replication of those programs which have achieved the greatest success in producing reliably measured achievement benefits in reading and mathematical skills. With this general objective in mind, the U.…

Replicating the Effects of a Scaled-Up, Teacher-Scaffolded Voluntary Summer Reading Program

ERIC Educational Resources Information Center

Kim, James S.; White, Thomas G.

2014-01-01

READS (Reading Enhances Achievement During Summer) has been implemented in North Carolina schools for the past several years as part of an Investing in Innovation (i3) validation grant that began in fall 2010. This paper focuses on the Year 3 study and compares the Year 3 results to the Year 1 and Year 2 results, and the results of earlier…

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.

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

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.

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.

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

Do federal and state audits increase compliance with a grant program to improve municipal infrastructure (AUDIT study): study protocol for a randomized controlled trial.

PubMed

De La O, Ana L; Martel García, Fernando

2014-09-03

Poor governance and accountability compromise young democracies' efforts to provide public services critical for human development, including water, sanitation, health, and education. Evidence shows that accountability agencies like superior audit institutions can reduce corruption and waste in federal grant programs financing service infrastructure. However, little is know about their effect on compliance with grant reporting and resource allocation requirements, or about the causal mechanisms. This study protocol for an exploratory randomized controlled trial tests the hypothesis that federal and state audits increase compliance with a federal grant program to improve municipal service infrastructure serving marginalized households. The AUDIT study is a block randomized, controlled, three-arm parallel group exploratory trial. A convenience sample of 5 municipalities in each of 17 states in Mexico (n=85) were block randomized to be audited by federal auditors (n=17), by state auditors (n=17), and a control condition outside the annual program of audits (n=51) in a 1:1:3 ratio. Replicable and verifiable randomization was performed using publicly available lottery numbers. Audited municipalities were included in the national program of audits and received standard audits on their use of federal public service infrastructure grants. Municipalities receiving moderate levels of grant transfers were recruited, as these were outside the auditing sampling frame--and hence audit program--or had negligible probabilities of ever being audited. The primary outcome measures capture compliance with the grant program and markers for the causal mechanisms, including deterrence and information effects. Secondary outcome measure include differences in audit reports across federal and state auditors, and measures like career concerns, political promotions, and political clientelism capturing synergistic effects with municipal accountability systems. The survey firm and research assistants assessing outcomes were blind to treatment status. This study will improve our understanding of local accountability systems for public service delivery in the 17 states under study, and may have downstream policy implications. The study design also demonstrates the use of verifiable and replicable randomization, and of sequentially partitioned hypotheses to reduce the Type I error rate in multiple hypothesis tests. Controlled-trials.com Identifier ISRCTN22381841: Date registered 02/11/2012.

Eric Freed Named Deputy Director of HIV Drug Resistance Program | Poster

Cancer.gov

Editor’s note: The text for this article was adapted from an e-mail announcement to the Center for Cancer Research community from Robert Wiltrout, Ph.D., on September 8, 2014. Robert Wiltrout, Ph.D., director, NCI Center for Cancer Research (CCR), recently announced the appointment of Eric Freed, Ph.D., as deputy director of the HIV Drug Resistance Program (HIV DRP). Freed will join Stephen Hughes, Ph.D., director of HIV DRP, in leading this CCR program that focuses on understanding HIV replication and pathogenesis, with the goal of developing more effective strategies for treating HIV infections, and also builds on the existing strength of HIV and retrovirus research within NCI.

Evaluation of the US Department of Energy Weatherization Innovation Pilot Program (2010-2014)

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

Tonn, Bruce Edward; Rose, Erin M.; Hawkins, Beth A.

This report contains results from analysis conducted on each of the Weatherization Innovation Pilot Program (WIPP) grants awarded to 16 organizations by the US Department of Energy (DOE) in 2010. The purpose of WIPP was to explore the potential adoptability or replicability of innovative processes or technologies for the enhancement of DOE’s Weatherization Assistance Program (WAP). DOE initiated the WIPP grant to accelerate effective innovations in home energy efficiency and other WAP mission-related goals for income-qualifying households of low socioeconomic status. This study was performed alongside a broader, national evaluation of WAP conducted by Oak Ridge National Laboratory (ORNL) formore » DOE.« less

Aggregate and individual replication probability within an explicit model of the research process.

PubMed

Miller, Jeff; Schwarz, Wolf

2011-09-01

We study a model of the research process in which the true effect size, the replication jitter due to changes in experimental procedure, and the statistical error of effect size measurement are all normally distributed random variables. Within this model, we analyze the probability of successfully replicating an initial experimental result by obtaining either a statistically significant result in the same direction or any effect in that direction. We analyze both the probability of successfully replicating a particular experimental effect (i.e., the individual replication probability) and the average probability of successful replication across different studies within some research context (i.e., the aggregate replication probability), and we identify the conditions under which the latter can be approximated using the formulas of Killeen (2005a, 2007). We show how both of these probabilities depend on parameters of the research context that would rarely be known in practice. In addition, we show that the statistical uncertainty associated with the size of an initial observed effect would often prevent accurate estimation of the desired individual replication probability even if these research context parameters were known exactly. We conclude that accurate estimates of replication probability are generally unattainable.

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…

A 4-study replication of the moderating effects of greed on socioeconomic status and unethical behaviour.

PubMed

Balakrishnan, Anjana; Palma, Paolo A; Patenaude, Joshua; Campbell, Lorne

2017-01-31

Four replications of Piff and colleagues' study examined the moderating effects of greed attitudes on the relationship between socio-economic status (SES) and unethical behaviour (Study 7). In the original study, the researchers found that both greed and SES predicted increased propensity to engage in unethical behavior. Furthermore, this association was moderated such that the effects of SES on unethical behaviour were no longer present in the greed prime condition versus the neutral condition. In replication 1 of the original study main effects of greed attitudes and SES were found, but no interaction was found. Main effects for greed emerged in replications 3 and 4. However no main effects for SES or interactions emerged for replications 2-4. A meta-analysis was conducted with all replications and the original study, and found no moderating effect of greed on the relationship between SES and unethical behavior.

A 4-study replication of the moderating effects of greed on socioeconomic status and unethical behaviour

PubMed Central

Balakrishnan, Anjana; Palma, Paolo A.; Patenaude, Joshua; Campbell, Lorne

2017-01-01

Four replications of Piff and colleagues’ study examined the moderating effects of greed attitudes on the relationship between socio-economic status (SES) and unethical behaviour (Study 7). In the original study, the researchers found that both greed and SES predicted increased propensity to engage in unethical behavior. Furthermore, this association was moderated such that the effects of SES on unethical behaviour were no longer present in the greed prime condition versus the neutral condition. In replication 1 of the original study main effects of greed attitudes and SES were found, but no interaction was found. Main effects for greed emerged in replications 3 and 4. However no main effects for SES or interactions emerged for replications 2–4. A meta-analysis was conducted with all replications and the original study, and found no moderating effect of greed on the relationship between SES and unethical behavior. PMID:28140396

The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.

PubMed

McCune, Heather J; Danielson, Laura S; Alvino, Gina M; Collingwood, David; Delrow, Jeffrey J; Fangman, Walton L; Brewer, Bonita J; Raghuraman, M K

2008-12-01

Temporal regulation of origin activation is widely thought to explain the pattern of early- and late-replicating domains in the Saccharomyces cerevisiae genome. Recently, single-molecule analysis of replication suggested that stochastic processes acting on origins with different probabilities of activation could generate the observed kinetics of replication without requiring an underlying temporal order. To distinguish between these possibilities, we examined a clb5Delta strain, where origin firing is largely limited to the first half of S phase, to ask whether all origins nonspecifically show decreased firing (as expected for disordered firing) or if only some origins ("late" origins) are affected. Approximately half the origins in the mutant genome show delayed replication while the remainder replicate largely on time. The delayed regions can encompass hundreds of kilobases and generally correspond to regions that replicate late in wild-type cells. Kinetic analysis of replication in wild-type cells reveals broad windows of origin firing for both early and late origins. Our results are consistent with a temporal model in which origins can show some heterogeneity in both time and probability of origin firing, but clustering of temporally like origins nevertheless yields a genome that is organized into blocks showing different replication times.

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…

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…

Hierarchical cortical transcriptome disorganization in autism.

PubMed

Lombardo, Michael V; Courchesne, Eric; Lewis, Nathan E; Pramparo, Tiziano

2017-01-01

Autism spectrum disorders (ASD) are etiologically heterogeneous and complex. Functional genomics work has begun to identify a diverse array of dysregulated transcriptomic programs (e.g., synaptic, immune, cell cycle, DNA damage, WNT signaling, cortical patterning and differentiation) potentially involved in ASD brain abnormalities during childhood and adulthood. However, it remains unclear whether such diverse dysregulated pathways are independent of each other or instead reflect coordinated hierarchical systems-level pathology. Two ASD cortical transcriptome datasets were re-analyzed using consensus weighted gene co-expression network analysis (WGCNA) to identify common co-expression modules across datasets. Linear mixed-effect models and Bayesian replication statistics were used to identify replicable differentially expressed modules. Eigengene network analysis was then utilized to identify between-group differences in how co-expression modules interact and cluster into hierarchical meta-modular organization. Protein-protein interaction analyses were also used to determine whether dysregulated co-expression modules show enhanced interactions. We find replicable evidence for 10 gene co-expression modules that are differentially expressed in ASD cortex. Rather than being independent non-interacting sources of pathology, these dysregulated co-expression modules work in synergy and physically interact at the protein level. These systems-level transcriptional signals are characterized by downregulation of synaptic processes coordinated with upregulation of immune/inflammation, response to other organism, catabolism, viral processes, translation, protein targeting and localization, cell proliferation, and vasculature development. Hierarchical organization of meta-modules (clusters of highly correlated modules) is also highly affected in ASD. These findings highlight that dysregulation of the ASD cortical transcriptome is characterized by the dysregulation of multiple coordinated transcriptional programs producing synergistic systems-level effects that cannot be fully appreciated by studying the individual component biological processes in isolation.

AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system.

PubMed

Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

2013-05-01

AGO/RISC-mediated antiviral RNA silencing, an important component of the plant's immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs that specifically targeted the viral RNA, endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral RNA silencing was disabled by the viral silencing suppressor p19 when this was present early during RISC formation. Notably, with replicating viral RNA, only (+)RNA molecules were accessible to RISC, whereas (-)RNA replication intermediates were not. The vulnerability of viral RNAs to RISC activity also depended on the RNA structure of the target sequence. This was most evident when we characterized viral siRNAs (vsiRNAs) that were particularly effective in silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites, suggesting that accessible parts of the viral (+)RNA may be collectively attacked by different AGO/RISC. The in vitro system was, hence, established as a valuable tool to define and characterize individual molecular determinants of antiviral RNA silencing.

AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system

PubMed Central

Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

2013-01-01

AGO/RISC-mediated antiviral RNA silencing, an important component of the plant’s immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs that specifically targeted the viral RNA, endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral RNA silencing was disabled by the viral silencing suppressor p19 when this was present early during RISC formation. Notably, with replicating viral RNA, only (+)RNA molecules were accessible to RISC, whereas (−)RNA replication intermediates were not. The vulnerability of viral RNAs to RISC activity also depended on the RNA structure of the target sequence. This was most evident when we characterized viral siRNAs (vsiRNAs) that were particularly effective in silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites, suggesting that accessible parts of the viral (+)RNA may be collectively attacked by different AGO/RISC. The in vitro system was, hence, established as a valuable tool to define and characterize individual molecular determinants of antiviral RNA silencing. PMID:23535144

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

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…

Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

PubMed Central

Liu, XueQiao

2014-01-01

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID:24227856

Effectiveness of a program using a vehicle tracking system, incentives, and disincentives to reduce the speeding behavior of drivers with ADHD.

PubMed

Markham, Paula T; Porter, Bryan E; Ball, J D

2013-04-01

In this article, the authors investigated the effectiveness of a behavior modification program using global positioning system (GPS) vehicle tracking devices with contingency incentives and disincentives to reduce the speeding behavior of drivers with ADHD. Using an AB multiple-baseline design, six participants drove a 5-mile stable driving route weekly while GPS devices recorded speeds. The dependent variable was percentage of feet speeding. Following an initial baseline period, five participants received treatment. One participant remained at baseline. Visual inspection of individual participant graphs, reductions in mean percentages of speeding from baseline to treatment across participants (M = 82%), C-statistic analyses, and visual graphs with applied binomial formula supported a treatment effect. The between-participant analysis using R n Test of Ranks was significant, R n = 6, p < .01, and complemented a clean multiple-baseline result. Results indicated that this treatment program was effective in reducing speeding by drivers with ADHD and warrants replication.

Effects of organic matter removal, soil compaction, and vegetation control on 5-year seedling performance: a regional comparison of long-term soil productivity sites

Treesearch

Robert L. Fleming; Robert F. Powers; Neil W. Foster; J. Marty Kranabetter; D. Andrew Scott; Felix Jr. Ponder; Shannon Berch; William K. Chapman; Richard D. Kabzems; Kim H. Ludovici; David M. Morris; Deborah S. Page-Dumroese; Paul T. Sanborn; Felipe G. Sanchez; Douglas M. Stone; Allan E. Tiarks

2006-01-01

We examined fifth-year seedling response to soil disturbance and vegetation control at 42 experimental locations representing 25 replicated studies within the North American Long-Term Soil Productivity (LTSP) program. These studies share a common experimental design while encompassing a wide range of climate, site conditions, and forest types. Whole-tree harvest had...

The Building Assets-Reducing Risks Program: Replication and Expansion of an Effective Strategy to Turn Around Low-Achieving Schools. i3 Development Grant. Final Report

ERIC Educational Resources Information Center

Corsello, Maryann; Sharma, Anu

2015-01-01

The Building Assets Reducing Risks (BARR) Model BARR is a comprehensive model that addresses the challenges that are part of the 9th grade transition year. BARR employs eight different school-wide and individual strategies that are built on positive relationships and ongoing monitoring of student data. In 2010, BARR received an Investing in…

A Replication and Extension of the PEERS Intervention: Examining Effects on Social Skills and Social Anxiety in Adolescents with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Schohl, Kirsten A.; Van Hecke, Amy V.; Carson, Audrey Meyer; Dolan, Bridget; Karst, Jeffrey; Stevens, Sheryl

2014-01-01

This study aimed to evaluate the Program for the Education and Enrichment of Relational Skills (PEERS: Laugeson et al. in "J Autism Dev Disord" 39(4):596-606, 2009). PEERS focuses on improving friendship quality and social skills among adolescents with higher-functioning ASD. 58 participants aged 11-16 years-old were randomly assigned to…

Replicated Findings of an Evaluation of a Brief Intervention Designed to Prevent High-Risk Drinking among First-Year College Students: Implications for Social Norming Theory

ERIC Educational Resources Information Center

Stamper, Georgia Ann; Smith, Bradley H.; Gant, Rick; Bogle, Kristin E.

2004-01-01

College students were randomly assigned to receive either (a) standard alcohol programming (SAP) or (b) SAP plus an intervention designed to change perceptions of alcohol norms (PAN). Effects of the intervention delivered during one class period (i.e., 55 minutes) were assessed using pre- and post-intervention surveys about personal alcohol use…

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.

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.

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.

DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states.

PubMed

White, Eric J; Emanuelsson, Olof; Scalzo, David; Royce, Thomas; Kosak, Steven; Oakeley, Edward J; Weissman, Sherman; Gerstein, Mark; Groudine, Mark; Snyder, Michael; Schübeler, Dirk

2004-12-21

Duplication of the genome during the S phase of the cell cycle does not occur simultaneously; rather, different sequences are replicated at different times. The replication timing of specific sequences can change during development; however, the determinants of this dynamic process are poorly understood. To gain insights into the contribution of developmental state, genomic sequence, and transcriptional activity to replication timing, we investigated the timing of DNA replication at high resolution along an entire human chromosome (chromosome 22) in two different cell types. The pattern of replication timing was correlated with respect to annotated genes, gene expression, novel transcribed regions of unknown function, sequence composition, and cytological features. We observed that chromosome 22 contains regions of early- and late-replicating domains of 100 kb to 2 Mb, many (but not all) of which are associated with previously described chromosomal bands. In both cell types, expressed sequences are replicated earlier than nontranscribed regions. However, several highly transcribed regions replicate late. Overall, the DNA replication-timing profiles of the two different cell types are remarkably similar, with only nine regions of difference observed. In one case, this difference reflects the differential expression of an annotated gene that resides in this region. Novel transcribed regions with low coding potential exhibit a strong propensity for early DNA replication. Although the cellular function of such transcripts is poorly understood, our results suggest that their activity is linked to the replication-timing program.

The Efficacy of Stuttering Measurement Training: Evaluating Two Training Programs

PubMed Central

Bainbridge, Lauren A.; Stavros, Candace; Ebrahimian, Mineh; Wang, Yuedong

2015-01-01

Purpose Two stuttering measurement training programs currently used for training clinicians were evaluated for their efficacy in improving the accuracy of total stuttering event counting. Method Four groups, each with 12 randomly allocated participants, completed a pretest–posttest design training study. They were evaluated by their counts of stuttering events on eight 3-min audiovisual speech samples from adults and children who stutter. Stuttering judgment training involved use of either the Stuttering Measurement System (SMS), Stuttering Measurement Assessment and Training (SMAAT) programs, or no training. To test for the reliability of any training effect, SMS training was repeated with the 4th group. Results Both SMS-trained groups produced approximately 34% improvement, significantly better than no training or the SMAAT program. The SMAAT program produced a mixed result. Conclusions The SMS program was shown to produce a “medium” effect size improvement in the accuracy of stuttering event counts, and this improvement was almost perfectly replicated in a 2nd group. Half of the SMAAT judges produced a 36% improvement in accuracy, but the other half showed no improvement. Additional studies are needed to demonstrate the durability of the reported improvements, but these positive effects justify the importance of stuttering measurement training. PMID:25629956

The efficacy of stuttering measurement training: evaluating two training programs.

PubMed

Bainbridge, Lauren A; Stavros, Candace; Ebrahimian, Mineh; Wang, Yuedong; Ingham, Roger J

2015-04-01

Two stuttering measurement training programs currently used for training clinicians were evaluated for their efficacy in improving the accuracy of total stuttering event counting. Four groups, each with 12 randomly allocated participants, completed a pretest-posttest design training study. They were evaluated by their counts of stuttering events on eight 3-min audiovisual speech samples from adults and children who stutter. Stuttering judgment training involved use of either the Stuttering Measurement System (SMS), Stuttering Measurement Assessment and Training (SMAAT) programs, or no training. To test for the reliability of any training effect, SMS training was repeated with the 4th group. Both SMS-trained groups produced approximately 34% improvement, significantly better than no training or the SMAAT program. The SMAAT program produced a mixed result. The SMS program was shown to produce a "medium" effect size improvement in the accuracy of stuttering event counts, and this improvement was almost perfectly replicated in a 2nd group. Half of the SMAAT judges produced a 36% improvement in accuracy, but the other half showed no improvement. Additional studies are needed to demonstrate the durability of the reported improvements, but these positive effects justify the importance of stuttering measurement training.

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…

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.

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

Impact of a universal school-based violence prevention program on violent delinquency: distinctive benefits for youth with maltreatment histories.

PubMed

Crooks, Claire V; Scott, Katreena; Ellis, Wendy; Wolfe, David A

2011-06-01

Child maltreatment constitutes a strong risk factor for violent delinquency in adolescence, with cumulative experiences of maltreatment creating increasingly greater risk. Our previous work demonstrated that a universal school-based violence prevention program could provide a protective impact for youth at risk for violent delinquency due to child maltreatment history. In this study we conducted a follow-up to determine if participation in a school-based violence prevention program in grade 9 continued to provide a buffering effect on engaging in acts of violent delinquency for maltreated youth, 2 years post-intervention. Secondary analyses were conducted using data from a cluster randomized controlled trial of a comprehensive school-based violence prevention program. Students (N=1,722; 52.8% female) from 20 schools participated in 21 75-min lessons in grade 9 health classes. Individual data (i.e., gender, child maltreatment experiences, and violent delinquency in grade 9) and school-level data (i.e., student perception of safety averaged across students in each school) were entered in a multilevel model to predict violent delinquency at the end of grade 11. Individual- and school-level factors predicting violent delinquency in grade 11 replicated previous findings from grade 9: being male, experiencing child maltreatment, being violent in grade 9, and attending a school with a lower perceived sense of safety among the entire student body increased violent delinquency. The cross-level interaction of individual maltreatment history and school-level intervention was also replicated: in non-intervention schools, youth with more maltreatment in their background were increasingly likely to engage in violent delinquency. The strength of this relationship was significantly attenuated in intervention schools. Follow-up findings are consistent with the buffering effect of the prevention program previously found post-intervention for the subsample of youth with maltreatment histories. A relative inexpensive school-based violence prevention program that has been shown to reduce dating violence among the whole student body also creates a protective effect for maltreated youth with respect to lowering their likelihood of engaging in violent delinquency. Copyright © 2011 Elsevier Ltd. All rights reserved.

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'.

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…

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.

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.

Energy efficiency in nonprofit agencies: Creating effective program models

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

Brown, M.A.; Prindle, B.; Scherr, M.I.

Nonprofit agencies are a critical component of the health and human services system in the US. It has been clearly demonstrated by programs that offer energy efficiency services to nonprofits that, with minimal investment, they can educe their energy consumption by ten to thirty percent. This energy conservation potential motivated the Department of Energy and Oak Ridge National Laboratory to conceive a project to help states develop energy efficiency programs for nonprofits. The purpose of the project was two-fold: (1) to analyze existing programs to determine which design and delivery mechanisms are particularly effective, and (2) to create model programsmore » for states to follow in tailoring their own plans for helping nonprofits with energy efficiency programs. Twelve existing programs were reviewed, and three model programs were devised and put into operation. The model programs provide various forms of financial assistance to nonprofits and serve as a source of information on energy efficiency as well. After examining the results from the model programs (which are still on-going) and from the existing programs, several replicability factors'' were developed for use in the implementation of programs by other states. These factors -- some concrete and practical, others more generalized -- serve as guidelines for states devising program based on their own particular needs and resources.« less

Mindfulness-Based Stress Release Program for University Employees: A Pilot, Waitlist-Controlled Trial and Implementation Replication.

PubMed

Koncz, Rebecca; Wolfenden, Fiona; Hassed, Craig; Chambers, Richard; Cohen, Julia; Glozier, Nicholas

2016-10-01

The aim of this study was to evaluate the effectiveness of a 6-week mindfulness-based stress release program (SRP) on stress and work engagement in fulltime university employees. Perceived stress, workplace wellbeing, and engagement were measured at baseline and within 1 week of the SRP completion, and contemporaneously 6 weeks apart for a waitlist control group. A second program was implemented to examine reproducibility of results. Fifty participants undertook the SRPs, and 29 participants were waitlisted. A significant improvement in distress, workplace wellbeing, and vigor was observed within the first SRP group, when compared with the control group. The improvement in distress and wellbeing was reproduced in the second SRP group. This study adds to the growing body of research that mindfulness may be an effective method for reducing workplace stress, improving employee wellbeing, and enhancing work engagement.

Rif1 is a global regulator of timing of replication origin firing in fission yeast

PubMed Central

Hayano, Motoshi; Kanoh, Yutaka; Matsumoto, Seiji; Renard-Guillet, Claire; Shirahige, Katsuhiko; Masai, Hisao

2012-01-01

One of the long-standing questions in eukaryotic DNA replication is the mechanisms that determine where and when a particular segment of the genome is replicated. Cdc7/Hsk1 is a conserved kinase required for initiation of DNA replication and may affect the site selection and timing of origin firing. We identified rif1Δ, a null mutant of rif1+, a conserved telomere-binding factor, as an efficient bypass mutant of fission yeast hsk1. Extensive deregulation of dormant origins over a wide range of the chromosomes occurs in rif1Δ in the presence or absence of hydroxyurea (HU). At the same time, many early-firing, efficient origins are suppressed or delayed in firing timing in rif1Δ. Rif1 binds not only to telomeres, but also to many specific locations on the arm segments that only partially overlap with the prereplicative complex assembly sites, although Rif1 tends to bind in the vicinity of the late/dormant origins activated in rif1Δ. The binding to the arm segments occurs through M to G1 phase in a manner independent of Taz1 and appears to be essential for the replication timing program during the normal cell cycle. Our data demonstrate that Rif1 is a critical determinant of the origin activation program on the fission yeast chromosomes. PMID:22279046

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

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.

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims.

PubMed

Barnes, Ralph M; Tobin, Stephanie J; Johnston, Heather M; MacKenzie, Noah; Taglang, Chelsea M

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect.

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…

What Works to Reduce Victimization? Synthesizing What We Know and Where to Go From Here.

PubMed

Fox, Kathleen A; Shjarback, John A

2016-01-01

While some attention has been paid to "what works" to reduce crime, little is known about the effectiveness of programs designed to reduce victimization. This study systematically reviews 83 program evaluations to identify what works to (a) reduce victimization, (b) enhance beliefs/attitudes about victims, and (c) improve knowledge/awareness of victimization issues. Evidence-based findings are organized around 4 major forms of victimization, including bullying, intimate partner violence, sexual abuse, and other general forms of victimization. Determining whether certain types of programs can reduce the risk of victimization has important implications for improving people's quality of life. Based on our findings, we offer several promising directions for the next generation of research on evaluating victimization programs. The goal of this study is to improve the strength of future program evaluations, replications, and other systematic reviews as researchers and practitioners continue to learn what works to reduce victimization.

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…

Improving the Nurse–Family Partnership in Community Practice

PubMed Central

Donelan-McCall, Nancy; O’Brien, Ruth; MacMillan, Harriet; Jack, Susan; Jenkins, Thomas; Dunlap, Wallace P.; O’Fallon, Molly; Yost, Elly; Thorland, Bill; Pinto, Francesca; Gasbarro, Mariarosa; Baca, Pilar; Melnick, Alan; Beeber, Linda

2013-01-01

BACKGROUND: Evidence-based preventive interventions are rarely final products. They have reached a stage of development that warrant public investment but require additional research and development to strengthen their effects. The Nurse-Family Partnership (NFP), a program of nurse home visiting, is grounded in findings from replicated randomized controlled trials. OBJECTIVE: Evidence-based programs require replication in accordance with the models tested in the original randomized controlled trials in order to achieve impacts comparable to those found in those trials, and yet they must be changed in order to improve their impacts, given that interventions require continuous improvement. This article provides a framework and illustrations of work our team members have developed to address this tension. METHODS: Because the NFP is delivered in communities outside of research contexts, we used quantitative and qualitative research to identify challenges with the NFP program model and its implementation, as well as promising approaches for addressing them. RESULTS: We describe a framework used to address these issues and illustrate its use in improving nurses’ skills in retaining participants, reducing closely spaced subsequent pregnancies, responding to intimate partner violence, observing and promoting caregivers’ care of their children, addressing parents’ mental health problems, classifying families’ risks and strengths as a guide for program implementation, and collaborating with indigenous health organizations to adapt and evaluate the program for their populations. We identify common challenges encountered in conducting research in practice settings and translating findings from these studies into ongoing program implementation. CONCLUSIONS: The conduct of research focused on quality improvement, model improvement, and implementation in NFP practice settings is challenging, but feasible, and holds promise for improving the impact of the NFP. PMID:24187112

Failure to Replicate a Genetic Association May Provide Important Clues About Genetic Architecture

PubMed Central

Greene, Casey S.; Penrod, Nadia M.; Williams, Scott M.; Moore, Jason H.

2009-01-01

Replication has become the gold standard for assessing statistical results from genome-wide association studies. Unfortunately this replication requirement may cause real genetic effects to be missed. A real result can fail to replicate for numerous reasons including inadequate sample size or variability in phenotype definitions across independent samples. In genome-wide association studies the allele frequencies of polymorphisms may differ due to sampling error or population differences. We hypothesize that some statistically significant independent genetic effects may fail to replicate in an independent dataset when allele frequencies differ and the functional polymorphism interacts with one or more other functional polymorphisms. To test this hypothesis, we designed a simulation study in which case-control status was determined by two interacting polymorphisms with heritabilities ranging from 0.025 to 0.4 with replication sample sizes ranging from 400 to 1600 individuals. We show that the power to replicate the statistically significant independent main effect of one polymorphism can drop dramatically with a change of allele frequency of less than 0.1 at a second interacting polymorphism. We also show that differences in allele frequency can result in a reversal of allelic effects where a protective allele becomes a risk factor in replication studies. These results suggest that failure to replicate an independent genetic effect may provide important clues about the complexity of the underlying genetic architecture. We recommend that polymorphisms that fail to replicate be checked for interactions with other polymorphisms, particularly when samples are collected from groups with distinct ethnic backgrounds or different geographic regions. PMID:19503614

BK Polyomavirus Replication in Renal Tubular Epithelial Cells Is Inhibited by Sirolimus, but Activated by Tacrolimus Through a Pathway Involving FKBP-12.

PubMed

Hirsch, H H; Yakhontova, K; Lu, M; Manzetti, J

2016-03-01

BK polyomavirus (BKPyV) replication causes nephropathy and premature kidney transplant failure. Insufficient BKPyV-specific T cell control is regarded as a key mechanism, but direct effects of immunosuppressive drugs on BKPyV replication might play an additional role. We compared the effects of mammalian target of rapamycin (mTOR)- and calcineurin-inhibitors on BKPyV replication in primary human renal tubular epithelial cells. Sirolimus impaired BKPyV replication with a 90% inhibitory concentration of 4 ng/mL by interfering with mTOR-SP6-kinase activation. Sirolimus inhibition was rapid and effective up to 24 h postinfection during viral early gene expression, but not thereafter, during viral late gene expression. The mTORC-1 kinase inhibitor torin-1 showed a similar inhibition profile, supporting the notion that early steps of BKPyV replication depend on mTOR activity. Cyclosporine A also inhibited BKPyV replication, while tacrolimus activated BKPyV replication and reversed sirolimus inhibition. FK binding protein 12kda (FKBP-12) siRNA knockdown abrogated sirolimus inhibition and increased BKPyV replication similar to adding tacrolimus. Thus, sirolimus and tacrolimus exert opposite effects on BKPyV replication in renal tubular epithelial cells by a mechanism involving FKBP-12 as common target. Immunosuppressive drugs may therefore contribute directly to the risk of BKPyV replication and nephropathy besides suppressing T cell functions. The data provide rationales for clinical trials aiming at reducing the risk of BKPyV replication and disease in kidney transplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

PubMed Central

Gasper, David J.; Neldner, Brandon; Plisch, Erin H.; Rustom, Hani; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M.

2016-01-01

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the respiratory tract. PMID:27997610

Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

PubMed

Gasper, David J; Neldner, Brandon; Plisch, Erin H; Rustom, Hani; Carrow, Emily; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M

2016-12-01

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the respiratory tract.

Role of the Adenovirus DNA-Binding Protein in In Vitro Adeno-Associated Virus DNA Replication

PubMed Central

Ward, Peter; Dean, Frank B.; O’Donnell, Michael E.; Berns, Kenneth I.

1998-01-01

A basic question in adeno-associated virus (AAV) biology has been whether adenovirus (Ad) infection provided any function which directly promoted replication of AAV DNA. Previously in vitro assays for AAV DNA replication, using linear duplex AAV DNA as the template, uninfected or Ad-infected HeLa cell extracts, and exogenous AAV Rep protein, demonstrated that Ad infection provides a direct helper effect for AAV DNA replication. It was shown that the nature of this helper effect was to increase the processivity of AAV DNA replication. Left unanswered was the question of whether this effect was the result of cellular factors whose activity was enhanced by Ad infection or was the result of direct participation of Ad proteins in AAV DNA replication. In this report, we show that in the in vitro assay, enhancement of processivity occurs with the addition of either the Ad DNA-binding protein (Ad-DBP) or the human single-stranded DNA-binding protein (replication protein A [RPA]). Clearly Ad-DBP is present after Ad infection but not before, whereas the cellular level of RPA is not apparently affected by Ad infection. However, we have not measured possible modifications of RPA which might occur after Ad infection and affect AAV DNA replication. When the substrate for replication was an AAV genome inserted into a plasmid vector, RPA was not an effective substitute for Ad-DBP. Extracts supplemented with Ad-DBP preferentially replicated AAV sequences rather than adjacent vector sequences; in contrast, extracts supplemented with RPA preferentially replicated vector sequences. PMID:9420241

Spatial aspects of prebiotic replicator coexistence and community stability in a surface-bound RNA world model

PubMed Central

2013-01-01

Background The coexistence of macromolecular replicators and thus the stability of presumed prebiotic replicator communities have been shown to critically depend on spatially constrained catalytic cooperation among RNA-like modular replicators. The necessary spatial constraints might have been supplied by mineral surfaces initially, preceding the more effective compartmentalization in membrane vesicles which must have been a later development of chemical evolution. Results Using our surface-bound RNA world model – the Metabolic Replicator Model (MRM) platform – we show that the mobilities on the mineral substrate surface of both the macromolecular replicators and the small molecules of metabolites they produce catalytically are the key factors determining the stable persistence of an evolvable metabolic replicator community. Conclusion The effects of replicator mobility and metabolite diffusion on different aspects of replicator coexistence in MRM are determined, including the maximum attainable size of the metabolic replicator system and its resistance to the invasion of parasitic replicators. We suggest a chemically plausible hypothetical scenario for the evolution of the first protocell starting from the surface-bound MRM system. PMID:24053177

The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists

PubMed Central

Fetterman, Adam K.; Sassenberg, Kai

2015-01-01

Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one’s reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one’s own work versus the work of another. Given these findings, we then present potential ways forward in these discussions. PMID:26650842

The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists.

PubMed

Fetterman, Adam K; Sassenberg, Kai

2015-01-01

Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one's reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one's own work versus the work of another. Given these findings, we then present potential ways forward in these discussions.

Making an APPropriate Care Program for Indigenous Cardiac Disease: Customization of an Existing Cardiac Rehabilitation Program.

PubMed

Bradford, DanaKai; Hansen, David; Karunanithi, Mohan

2015-01-01

Cardiovascular disease is a major health problem for all Australians and is the leading cause of death in Aboriginal and Torres Strait Islanders. In 2010, more then 50% of all heart attack deaths were due to repeated events. Cardiac rehabilitation programs have been proven to be effective in preventing the recurrence of cardiac events and readmission to hospitals. There are however, many barriers to the use of these programs. To address these barriers, CSIRO developed an IT enabled cardiac rehabilitation program delivered by mobile phone through a smartphone app and succesfully trialed it in an urban general population. If these results can be replicated in Indigenous populations, the program has the potential to significantly improve life expectancy and help close the gap in health outcomes. The challenge described in this paper is customizing the existing cardiac health program to make it culturally relevant and suitable for Indigenous Australians living in urban and remote communities.

Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

PubMed Central

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

2011-01-01

Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general model for their replication kinetics. PMID:22219720

Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims

PubMed Central

Barnes, Ralph M.; Tobin, Stephanie J.; Johnston, Heather M.; MacKenzie, Noah; Taglang, Chelsea M.

2016-01-01

A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect. PMID:27920743

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,

A Computer Program to Model Passive Acoustic Antisubmarine Search Using Monte Carlo Simulation Techniques.

DTIC Science & Technology

1983-09-01

duplicate a continuous function on a digital computer, and thus the machine representatic- of the GMA is only a close approximation of the continuous...error process. Thus, the manner in which the GMA process is digitally replicated has an effect on the results of the simulation. The parameterization of...Information Center 2 Cameron Station Alexandria, Virginia 22314 2. Libary , Code 0142 2 Naval Postgraduate School Monterey, California 93943 3. Professor

Heterogeneous VM Replication: A New Approach to Intrusion Detection, Active Response and Recovery in Cloud Data Centers

DTIC Science & Technology

2015-08-17

from the same execution history, and cost-effective active response by proactively setting up standby VM replicas: migration from a compromised VM...the guest OSes system call code to be reused inside a “shadowed” portion of the context of the out-of- guest inspection program. Besides...by the rootkits in cloud environments. RootkitDet detects rootkits by identifying suspicious code region in the kernel space of guest OSes through

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.

Testing support for an evaluation of a Houston physical and functional inspection/maintenance program. Final report

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

Not Available

1980-10-01

The standard mass emission (Federal Test Procedure) was performed for determination of the effects of inspection and maintenance on a sample of passenger cars operating in the Houston area. This sample was also used for obtaining abbreviated emission test (short cycle test), fuel economy, and emission component system maladjustment and disablement and other data. Four-hundred eighty vehicles were inspected under the program: one-hundred from the 1980 model year, one-hundred 1979 vehicles, one-hundred 1978 vehicles, sixty 1977 vehicles, sixty 1976 vehicles and sixty from the 1975 model year. Both domestic and imported auto makes were examined. All vehicles which failed anmore » initial inspection, a total of 206 vehicles, were subject to a baseline and set of replicate test sequences comprised of the FTP, the 50 Cruise Test, the Highway Fuel Economy Test, the Loaded Two Mode Test and the Four Speed Idle Test. A prescribed maintenance step preceded each of the replicate sequences. Failed vehicles were further subject to an emission control system maladjustment/disablement and status inspection, driveability evaluations and owner-interviews to obtain vehicle maintenance and useage data.« less

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…

TEAM-HF Cost-Effectiveness Model: A Web-Based Program Designed to Evaluate the Cost-Effectiveness of Disease Management Programs in Heart Failure

PubMed Central

Reed, Shelby D.; Neilson, Matthew P.; Gardner, Matthew; Li, Yanhong; Briggs, Andrew H.; Polsky, Daniel E.; Graham, Felicia L.; Bowers, Margaret T.; Paul, Sara C.; Granger, Bradi B.; Schulman, Kevin A.; Whellan, David J.; Riegel, Barbara; Levy, Wayne C.

2015-01-01

Background Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. Methods We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure (TEAM-HF) Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics, use of evidence-based medications, and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model (SHFM). Projections of resource use and quality of life are modeled using relationships with time-varying SHFM scores. The model can be used to evaluate parallel-group and single-cohort designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. Results The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. Conclusion The TEAM-HF Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure. PMID:26542504

Multiple animal studies for medical chemical defense program in soldier/patient decontamination and drug development. Task order 85-10. Final report, 1 December 1984-1 April 1987

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

Joiner, R.L.; Harroff, H.H.; Snider, H.

1987-12-04

A rabbit model has been developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the organophosphage chemical surety materiel (CSM), GD, polymer-thickened GD (TGD), and VX. CSM was applied to rabbits in groups of 8 on their clipped dorsa over a range of doses. Dose sites were decontaminated beginning 2 minutes after exposure with both components of the M258A1 standard field kit in the recommended sequence. Replicate LD50s were calculated for each CSM with probit analyses of the doses and lethality rates from replicate studies. A composite LD50 was calculated from the datamore » pooled across replicates for each CSM. The composite LD50 was validated for each CSM by comparing the lethality rate obtained in three replicates of 8 animals each with the population mean of 50 percent. The LD50 values obtained for the three CSM tested produced valid mortality ratios when compared to the population mean. Thus the screen is ready to test candidate decontamination systems. The screen compares the lethality rate obtained from 8 animals each dosed at the established M258A1 LD50 and decontaminated according to the manufacturer's instructions with a candidate system against the population mean of 50 percent. An M258A1-decontaminated control group of 8 animals is included to check for drift via a control chart method. Any candidate decontamination system that is as effective as or more effective than the dual-component M258A1 standard passes the screen and is a candidate for further testing.« less

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

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.

Meta-analysis of correlations revisited: attempted replication and extension of Field's (2001) simulation studies.

PubMed

Hafdahl, Adam R; Williams, Michelle A

2009-03-01

In 2 Monte Carlo studies of fixed- and random-effects meta-analysis for correlations, A. P. Field (2001) ostensibly evaluated Hedges-Olkin-Vevea Fisher-z and Schmidt-Hunter Pearson-r estimators and tests in 120 conditions. Some authors have cited those results as evidence not to meta-analyze Fisher-z correlations, especially with heterogeneous correlation parameters. The present attempt to replicate Field's simulations included comparisons with analytic values as well as results for efficiency and confidence-interval coverage. Field's results under homogeneity were mostly replicable, but those under heterogeneity were not: The latter exhibited up to over .17 more bias than ours and, for tests of the mean correlation and homogeneity, respectively, nonnull rejection rates up to .60 lower and .65 higher. Changes to Field's observations and conclusions are recommended, and practical guidance is offered regarding simulation evidence and choices among methods. Most cautions about poor performance of Fisher-z methods are largely unfounded, especially with a more appropriate z-to-r transformation. The Appendix gives a computer program for obtaining Pearson-r moments from a normal Fisher-z distribution, which is used to demonstrate distortion due to direct z-to-r transformation of a mean Fisher-z correlation.

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture▿

PubMed Central

Yano, Masahiko; Ikeda, Masanori; Abe, Ken-ichi; Dansako, Hiromichi; Ohkoshi, Shogo; Aoyagi, Yutaka; Kato, Nobuyuki

2007-01-01

To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients—β-carotene, vitamin D2, and linoleic acid—inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, β-carotene, vitamin D2, and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy. PMID:17420205

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.

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

Osborn, C.S.; Osborn, D.E.

Through a small grant from the Center for Renewable Resources and a matching grant from the Arizona Solar Energy Commission, the Arizona Solar Energy Association has produced a state-wide catalogue of model solar projects. This catalogue presents some of the best solar and conservation projects in the state. It includes solar buildings, educational programs, community development programs, agricultural and industrial projects, state and legislative efforts, and commercial and business programs. Project selection was based on five main considerations: (1) cost-effectiveness, (2) valuable use of resources, (3) generation of jobs and transfer of skills, (4) replicability, and (5) scope. Shorter descriptionsmore » of significant projects not meeting the selection criteria were also included. The development of the catalogue program, its use and impact as a networking tool and the development and implementation of a regular updating program are described. The success of this type of program on information exchange, public education, and cross fertilization are explored. Special emphasis projects from the catalogue are also described.« less

A replication and extension of the PEERS intervention: examining effects on social skills and social anxiety in adolescents with autism spectrum disorders.

PubMed

Schohl, Kirsten A; Van Hecke, Amy V; Carson, Audrey Meyer; Dolan, Bridget; Karst, Jeffrey; Stevens, Sheryl

2014-03-01

This study aimed to evaluate the Program for the Education and Enrichment of Relational Skills (PEERS: Laugeson et al. in J Autism Dev Disord 39(4):596-606, 2009). PEERS focuses on improving friendship quality and social skills among adolescents with higher-functioning ASD. 58 participants aged 11-16 years-old were randomly assigned to either an immediate treatment or waitlist comparison group. Results revealed, in comparison to the waitlist group, that the experimental treatment group significantly improved their knowledge of PEERS concepts and friendship skills, increased in their amount of get-togethers, and decreased in their levels of social anxiety, core autistic symptoms, and problem behaviors from pre-to post-PEERS. This study provides the first independent replication and extension of the empirically-supported PEERS social skills intervention for adolescents with ASD.

Transdiagnostic versus disorder-specific internet-delivered cognitive behaviour therapy for anxiety and depression in primary care.

PubMed

Newby, Jill M; Mewton, Louise; Andrews, Gavin

2017-03-01

Disorder-specific and transdiagnostic internet cognitive behaviour therapy (iCBT) programs are effective for anxiety and depression, but no studies have compared their effectiveness in primary care. Patient characteristics, adherence and effectiveness of Transdiagnostic iCBT (n=1005) were compared to disorder-specific programs for generalized anxiety disorder (GAD) (n=738) and depression (n=366) in a naturalistic non-randomised comparison study. Patients completed their iCBT program in primary care. The PHQ-9 (depression), GAD-7 (generalized anxiety), K-10 (distress), and the WHODAS-II (disability) were measured at pre- and post-treatment. Patients in the Transdiagnostic program had higher comorbidity rates and baseline distress. All programs were associated with medium to large within-group effect sizes for improving anxiety, depression and distress between pre- and post-treatment (d's=0.64-1.39). Controlling for baseline group differences in severity, we found small effect sizes favoring the Transdiagnostic program over the GAD program in reducing PHQ-9 (d=0.44, 95%CI: 0.34-0.53), K-10 (d=0.21, 95%CI: 0.16-0.35) and WHODAS scores (d=0.20, 95%CI: 0.10-0.29), and small effect sizes favoring the Transdiagnostic program over the Depression program in reducing GAD-7 scores (d=0.48, 95%CI: 0.36-0.60). A smaller proportion of patients completed the Transdiagnostic program (44.9%) compared to the depression (51.6%) and GAD (49.2%) programs, which was attributable to baseline differences in age and symptom severity. Both Transdiagnostic iCBT and disorder-specific iCBT programs are effective in primary care, but there appears to be small effects favoring Transdiagnostic iCBT. Methods to increase adherence are needed to optimize the benefits to patients, and these findings await replication in a RCT. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Is psychology suffering from a replication crisis? What does "failure to replicate" really mean?

PubMed

Maxwell, Scott E; Lau, Michael Y; Howard, George S

2015-09-01

Psychology has recently been viewed as facing a replication crisis because efforts to replicate past study findings frequently do not show the same result. Often, the first study showed a statistically significant result but the replication does not. Questions then arise about whether the first study results were false positives, and whether the replication study correctly indicates that there is truly no effect after all. This article suggests these so-called failures to replicate may not be failures at all, but rather are the result of low statistical power in single replication studies, and the result of failure to appreciate the need for multiple replications in order to have enough power to identify true effects. We provide examples of these power problems and suggest some solutions using Bayesian statistics and meta-analysis. Although the need for multiple replication studies may frustrate those who would prefer quick answers to psychology's alleged crisis, the large sample sizes typically needed to provide firm evidence will almost always require concerted efforts from multiple investigators. As a result, it remains to be seen how many of the recently claimed failures to replicate will be supported or instead may turn out to be artifacts of inadequate sample sizes and single study replications. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies

PubMed Central

Pe’er, Itsik

2017-01-01

Genome-wide association studies (GWAS) have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10−14), even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner’s Curse (p < 10−16). We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94). In contrast, ancestry differences between replication and discovery (13 studies, 385 loci) cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium. PMID:28715421

An alternating treatment comparison of oral and total communications training programs with echolalic autistic children.

PubMed Central

Barrera, R D; Sulzer-Azaroff, B

1983-01-01

An alternating treatment comparison was conducted of the relative effectiveness of oral and total communication training models for teaching expressive labeling skills to three echolalic autistic children. The results of this comparison demonstrated that total communication proved to be the most successful approach with each of the subjects. In addition, the replication of these findings both within and across subjects suggest that total communication may be, in general, the most effective of these two training models for teaching basic vocal language skills to echolalic children. A number of hypotheses are presented that may provide a basis for the demonstrated effect. PMID:6654770

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.

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

Suppression of Poxvirus Replication by Resveratrol.

PubMed

Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

2017-01-01

Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

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)

Review of Interventions to Improve Family Engagement and Retention in Parent and Child Mental Health Programs

PubMed Central

2010-01-01

Engaging and retaining families in mental health prevention and intervention programs is critically important to insure maximum public health impact. We evaluated randomized-controlled trials testing methods to improve family engagement and retention in child mental health programs published since 1980 (N = 17). Brief, intensive engagement interventions in which providers explicitly addressed families’ practical (e.g. schedules, transportation) and psychological (e.g. family members’ resistance, beliefs about the treatment process) barriers as they entered treatment were effective in improving engagement in early sessions. The few interventions found to produce long-term impact on engagement and retention integrated motivational interviewing, family systems, and enhanced family stress and coping support strategies at multiple points throughout treatment. Few interventions have been tested in the context of prevention programs. There are promising approaches to increasing engagement and retention; they should be replicated and used as a foundation for future research in this area. PMID:20823946

Context Matters for Social-Emotional Learning: Examining Variation in Program Impact by Dimensions of School Climate.

PubMed

McCormick, Meghan P; Cappella, Elise; O'Connor, Erin E; McClowry, Sandee G

2015-09-01

This paper examines whether three dimensions of school climate-leadership, accountability, and safety/respect-moderated the impacts of the INSIGHTS program on students' social-emotional, behavioral, and academic outcomes. Twenty-two urban schools and N = 435 low-income racial/ethnic minority students were enrolled in the study and received intervention services across the course of 2 years, in both kindergarten and first grade. Intervention effects on math and reading achievement were larger for students enrolled in schools with lower overall levels of leadership, accountability, and safety/respect at baseline. Program impacts on disruptive behaviors were greater in schools with lower levels of accountability at baseline; impacts on sustained attention were greater in schools with lower levels of safety/respect at baseline. Implications for Social-Emotional Learning program implementation, replication, and scale-up are discussed.

Genome-wide interaction study of dust mite allergen on lung function in children with asthma.

PubMed

Forno, Erick; Sordillo, Joanne; Brehm, John; Chen, Wei; Benos, Takis; Yan, Qi; Avila, Lydiana; Soto-Quirós, Manuel; Cloutier, Michelle M; Colón-Semidey, Angel; Alvarez, Maria; Acosta-Pérez, Edna; Weiss, Scott T; Litonjua, Augusto A; Canino, Glorisa; Celedón, Juan C

2017-10-01

Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes. We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure. A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study. Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV 1 with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10 -8 ), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10 -9 for all cohorts). Rs117902240 was positively associated with FEV 1 in children exposed to low dust mite allergen levels, but negatively associated with FEV 1 in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV 1 /forced vital capacity replicated in the independent cohorts. Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV 1 in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

Suppression of Zika Virus Infection and Replication in Endothelial Cells and Astrocytes by PKA Inhibitor PKI 14-22.

PubMed

Cheng, Fan; Ramos da Silva, Suzane; Huang, I-Chueh; Jung, Jae U; Gao, Shou-Jiang

2018-02-15

The recent outbreak of Zika virus (ZIKV), a reemerging flavivirus, and its associated neurological disorders, such as Guillain-Barré (GB) syndrome and microcephaly, have generated an urgent need to develop effective ZIKV vaccines and therapeutic agents. Here, we used human endothelial cells and astrocytes, both of which represent key cell types for ZIKV infection, to identify potential inhibitors of ZIKV replication. Because several pathways, including the AMP-activated protein kinase (AMPK), protein kinase A (PKA), and mitogen-activated protein kinase (MAPK) signaling pathways, have been reported to play important roles in flavivirus replication, we tested inhibitors and agonists of these pathways for their effects on ZIKV replication. We identified the PKA inhibitor PKI 14-22 (PKI) to be a potent inhibitor of ZIKV replication. PKI effectively suppressed the replication of ZIKV from both the African and Asian/American lineages with a high efficiency and minimal cytotoxicity. While ZIKV infection does not induce PKA activation, endogenous PKA activity is essential for supporting ZIKV replication. Interestingly, in addition to PKA, PKI also inhibited another unknown target(s) to block ZIKV replication. PKI inhibited ZIKV replication at the postentry stage by preferentially affecting negative-sense RNA synthesis as well as viral protein translation. Together, these results have identified a potential inhibitor of ZIKV replication which could be further explored for future therapeutic application. IMPORTANCE There is an urgent need to develop effective vaccines and therapeutic agents against Zika virus (ZIKV) infection, a reemerging flavivirus associated with neurological disorders, including Guillain-Barré (GB) syndrome and microcephaly. By screening for inhibitors of several cellular pathways, we have identified the PKA inhibitor PKI 14-22 (PKI) to be a potent inhibitor of ZIKV replication. We show that PKI effectively suppresses the replication of all ZIKV strains tested with minimal cytotoxicity to human endothelial cells and astrocytes, two key cell types for ZIKV infection. Furthermore, we show that PKI inhibits ZIKV negative-sense RNA synthesis and viral protein translation. This study has identified a potent inhibitor of ZIKV infection which could be further explored for future therapeutic application. Copyright © 2018 American Society for Microbiology.

Reduced-risk pest management programs for eastern U.S. peach orchards: effects on arthropod predators, parasitoids, and select pests.

PubMed

Biddinger, David J; Leslie, Timothy W; Joshi, Neelendra K

2014-06-01

We developed new integrated pest management programs for eastern U.S. peaches with minimal use of organophosphates. From 2002-2005, we assessed the ecological impacts of these reduced-risk programs versus grower standard conventional programs that still relied primarily on the use of organophosphorous and carbamate insecticides. Using a split-plot design replicated at four commercial Pennsylvania peach orchards, we quantified pesticide rates, environmental impact, and arthropod community response. We used Environmental Impact Quotient (EIQ) analysis based on the growers' pesticide records from each orchard to calculate seasonal cumulative EIQ field ratings for all years. Ecological effects of the reduced-risk and conventional program were also measured as the abundance and diversity of nontarget arthropod predators, parasitoids, and selected pest taxa. Pesticide inputs and EIQ values were substantially lower in reduced-risk programs compared with conventional spray programs. Arthropod arrays differed significantly between pest management programs: most beneficial predator and parasitoid taxa were positively associated with the reduced-risk program and negatively associated with the standard grower program. Regardless of the pest management program, we observed significant differences in species arrays in the peach tree canopy compared with the ground cover of the orchards, but the arthropod community did not differ among the field sites or based on distance from the edge of the orchard. We conclude that reduced-risk programs not only provide control comparable with that of conventional programs, but they also reduce negative environmental effects while conserving key arthropod biological control agents within eastern U.S. peach orchards.

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…

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…

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…

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…

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.

Realigning Shared Governance With Magnet® and the Organization's Operating System to Achieve Clinical Excellence.

PubMed

Moreno, Janette V; Girard, Anita S; Foad, Wendy

2018-03-01

In 2012, an academic medical center successfully overhauled a 15-year-old shared governance to align 6 house-wide and 30 unit-based councils with the new Magnet Recognition Program® and the organization's operating system, using the processes of LEAN methodology. The redesign improved cross-council communication structures, facilitated effective shared decision-making processes, increased staff engagement, and improved clinical outcomes. The innovative structural and process elements of the new model are replicable in other health institutions.

Direct effects of food cues seen during TV viewing on energy intake in young women.

PubMed

van Nee, Roselinde L; Larsen, Junilla K; Fisher, Jennifer O

2016-06-01

Few studies have examined direct effects of food cues presented within television (TV) programs on eating behavior in adults. This research experimentally determined whether exposure to food cues in TV programs affects energy intake during TV viewing among young women, independently from food cues presented in TV advertisements. The experiment involved a 2 (TV program with or without food cues) by 2 (TV advertisements with or without food cues) between-participants design. While watching TV, participants could freely eat peanut chocolate candies and crisps (potato chips). Participants were 121 young women (mean age = 19.6 years; mean BMI = 22.5). Participants who watched a TV program with food cues tended to have a lower total energy intake and ate significantly less peanut chocolate candies than participants who watched the same TV program without food cues. This effect was particularly pronounced among participants with a higher BMI. Food advertisements did not affect energy intake. Findings may indicate that subtle continuous food cues during TV programs could make young females more aware of their own eating and/or weight, leading to reduced intake of particularly sweet snack foods during TV viewing. Considering the non-significant trend for the effect of the TV program with food cues on total energy intake, findings should be replicated to provide possible tools for prevention campaigns using food cue reminders to watch one's intake. Copyright © 2016 Elsevier Ltd. All rights reserved.

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)

Diverse Effects of Cyclosporine on Hepatitis C Virus Strain Replication

PubMed Central

Ishii, Naoto; Watashi, Koichi; Hishiki, Takayuki; Goto, Kaku; Inoue, Daisuke; Hijikata, Makoto; Wakita, Takaji; Kato, Nobuyuki; Shimotohno, Kunitada

2006-01-01

Recently, a production system for infectious particles of hepatitis C virus (HCV) utilizing the genotype 2a JFH1 strain has been developed. This strain has a high capacity for replication in the cells. Cyclosporine (CsA) has a suppressive effect on HCV replication. In this report, we characterize the anti-HCV effect of CsA. We observe that the presence of viral structural proteins does not influence the anti-HCV activity of CsA. Among HCV strains, the replication of genotype 1b replicons was strongly suppressed by treatment with CsA. In contrast, JFH1 replication was less sensitive to CsA and its analog, NIM811. Replication of JFH1 did not require the cellular replication cofactor, cyclophilin B (CyPB). CyPB stimulated the RNA binding activity of NS5B in the genotype 1b replicon but not the genotype 2a JFH1 strain. These findings provide an insight into the mechanisms of diversity governing virus-cell interactions and in the sensitivity of these strains to antiviral agents. PMID:16611911

Testing a Theory-Based Health Communication Program: A Replication of Go Sun Smart in Outdoor Winter Recreation

PubMed Central

ANDERSEN, PETER A.; BULLER, DAVID B.; WALKOSZ, BARBARA J.; MALOY, JULIE; SCOTT, MICHAEL D.; CUTTER, GARY R.; DIGNAN, MARK B.

2010-01-01

The epidemic of preventable skin cancer in the United States creates an urgent need for health communication campaigns to improve sun protection. Go Sun Smart (GSS), a theory-driven multichannel health communication campaign showed positive effects on sun safety behaviors of employees and guests in a randomized trial at high-altitude ski areas. In this article we report findings from the North American GSS campaign for guests at ski areas that comprosed the original control-group resorts, replicating the results of the original guest intervention. Results showed that after GSS was deployed, guests at the original control group ski areas increased sun protection and reported greater recall of sun safety messages. Conversely, GSS had no effect on sunburning attitudes or self-efficacy beliefs. Like the original GSS guest intervention, the present study found that greater exposure to GSS messages was associated with greater use of sunscreen, sunscreen lip balm, and face covering, but not gloves or overall sun protection. There was no evidence that GSS decreased sunburning or attitudes and self-efficacy beliefs regarding sun safety. PMID:19466647

Effects of a Universal Classroom Behavior Management Program in First and Second Grades on Young Adult Behavioral, Psychiatric, and Social Outcomes*

PubMed Central

Kellam, Sheppard G.; Brown, C. Hendricks; Poduska, Jeanne; Ialongo, Nicholas; Wang, Wei; Toyinbo, Peter; Petras, Hanno; Ford, Carla; Windham, Amy; Wilcox, Holly C.

2008-01-01

Background The Good Behavior Game (GBG), a method of classroom behavior management used by teachers, was tested in first- and second-grade classrooms in 19 Baltimore City Public Schools beginning in the 1985–1986 school year. The intervention was directed at the classroom as a whole to socialize children to the student role and reduce aggressive, disruptive behaviors, confirmed antecedents of later substance abuse and dependence disorders, smoking, and antisocial personality disorder. This article reports on impact to age 19–21. Methods In five poor to lower-middle class, mainly African American urban areas, three or four schools were matched and within each set randomly assigned to one of three conditions: 1) GBG, 2) a curriculum-and-instruction program directed at reading achievement, or 3) the standard program. Balanced assignment of children to classrooms was made, and then, within intervention schools, classrooms and teachers were randomly assigned to intervention or control. Results By young adulthood significant impact was found among males, particularly those in first grade who were more aggressive, disruptive, in reduced drug and alcohol abuse/dependence disorders, regular smoking, and antisocial personality disorder. These results underline the value of a first-grade universal prevention intervention. Replication A replication was implemented with the next cohort of first-grade children with the same teachers during the following school year, but with diminished mentoring and monitoring of teachers. The results showed significant GBG impact for males on drug abuse/dependence disorders with some variation. For other outcomes the effects were generally smaller but in the same direction. PMID:18343607

Complementary Public Service Announcements as a Strategy for Enhancing the Impact of Health-Promoting Messages in Fictional Television Programs.

PubMed

Bavin, Lynda M; Owens, R Glynn

2018-05-01

Research suggests that health-promoting storylines in developed nations' fictional television programs can have a beneficial impact on viewers' beliefs, attitudes, intentions, or behaviors. The sizes of the effects are generally modest; however, the audience reach is substantial. Given that many fictional programs may hold the prolonged attention of millions of viewers, it is of value to examine potential strategies for enhancing the persuasive impact of their health-promoting storylines. Complementary public service announcements may be a promising strategy. This randomized experimental study (N = 310) examined the effects of viewing a complementary public service announcement after an organ donation story in an episode of Grey's Anatomy. Results indicated that the public service announcement enhanced the beneficial impact of the story on viewers' discussion behavior (about one's organ donor wishes), discussion intention, and perceived learning. This experimental study is the first to examine the effects of viewing a non-character public service announcement after a health-related storyline in a developed nation's fictional program compared to viewing the same episode of the program on its own. It is important for future research to examine whether these findings replicate for different health issues and with a nationally representative sample.

The combination effects of licl and the active leflunomide metabolite, A771726, on viral-induced interleukin 6 production and EV-A71 replication.

PubMed

Hung, Hui-Chen; Shih, Shin-Ru; Chang, Teng-Yuan; Fang, Ming-Yu; Hsu, John T-A

2014-01-01

Enterovirus 71 (EV-A71) is a neurotropic virus that can cause severe complications involving the central nervous system. No effective antiviral therapeutics are available for treating EV-A71 infection and drug discovery efforts are rarely focused to target this disease. Thus, the main goal of this study was to discover existing drugs with novel indications that may effectively inhibit EV-A71 replication and the inflammatory cytokines elevation. In this study, we showed that LiCl, a GSK3β inhibitor, effectively suppressed EV-A71 replication, apoptosis and inflammatory cytokines production (Interleukin 6, Interleukin-1β) in infected cells. Furthermore, LiCl and an immunomodular agent were shown to strongly synergize with each other in suppressing EV-A71 replication. The results highlighted potential new treatment regimens in suppressing sequelae caused by EV-A71 replication.

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

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

Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model: A Web-based program designed to evaluate the cost-effectiveness of disease management programs in heart failure.

PubMed

Reed, Shelby D; Neilson, Matthew P; Gardner, Matthew; Li, Yanhong; Briggs, Andrew H; Polsky, Daniel E; Graham, Felicia L; Bowers, Margaret T; Paul, Sara C; Granger, Bradi B; Schulman, Kevin A; Whellan, David J; Riegel, Barbara; Levy, Wayne C

2015-11-01

Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying Seattle Heart Failure Model scores. The model can be used to evaluate parallel-group and single-cohort study designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. The Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

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

Lessons learned: a pilot study on occupational therapy effectiveness for children with sensory modulation disorder.

PubMed

Miller, Lucy Jane; Schoen, Sarah A; James, Katherine; Schaaf, Roseann C

2007-01-01

The purpose of this pilot study was to prepare for a randomized controlled study of the effectiveness of occupational therapy using a sensory integration approach (OT-SI) with children who have sensory processing disorders (SPD). A one-group pretest, posttest design with 30 children was completed with a subset of children with SPD, those with sensory modulation disorder. Lessons learned relate to (a) identifying a homogeneous sample with quantifiable inclusion criteria, (b) developing an intervention manual for study replication and a fidelity to treatment measure, (c) determining which outcomes are sensitive to change and relate to parents' priorities, and (d) clarifying rigorous methodologies (e.g., blinded examiners, randomization, power). A comprehensive program of research is needed, including multiple pilot studies to develop enough knowledge that high-quality effectiveness research in occupational therapy can be completed. Previous effectiveness studies in OT-SI have been single projects not based on a unified long-term program of research.

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…

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.

Development and evaluation of an educational intervention program for pre-professional adolescent ballet dancers: nutrition for optimal performance.

PubMed

Doyle-Lucas, Ashley F; Davy, Brenda M

2011-06-01

The purpose of this investigation was to develop, implement, and evaluate a theoretically based nutritional education intervention through a DVD lecture series (three 30-minute classes) in summer intensive programs for pre-professional, adolescent ballet dancers. Objectives of this intervention program were to increase knowledge of basic sports nutrition principles and the Female Athlete Triad and promote self-efficacy for adopting healthier dietary habits. Dancers ranging from 13 to 18 years old who were attending summer intensive programs affiliated with professional ballet companies were recruited. Group One (n = 231) participated in the nutrition education program, while Group Two the control participants (n = 90) did not. Assessments of the participants' dietary status consisted of a demographic questionnaire, a Sports Nutrition Knowledge and Behavior Questionnaire, and a Food Frequency Questionnaire. The intervention group was assessed at baseline, immediately post-program, and at six weeks post-program. The control group was assessed at baseline and at six weeks post-baseline. The intervention program was effective at increasing nutrition knowledge, perceived susceptibility to the Female Athlete Triad, and self-efficacy constructs. Improvements in dietary intake were also observed among intervention group participants. To improve overall health and performance nutrition education should be incorporated into the training regimens of adolescent dancers. This potentially replicable DVD-based program may be an effective, low-cost mechanism for doing that.

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.

TakeCARE, a Video to Promote Bystander Behavior on College Campuses: Replication and Extension.

PubMed

Jouriles, Ernest N; Sargent, Kelli S; Salis, Katie Lee; Caiozzo, Christina; Rosenfield, David; Cascardi, Michele; Grych, John H; O'Leary, K Daniel; McDonald, Renee

2017-08-01

Previous research has demonstrated that college students who view TakeCARE, a video bystander program designed to encourage students to take action to prevent sexual and relationship violence (i.e., bystander behavior), display more bystander behavior relative to students who view a control video. The current study aimed to replicate and extend these findings by testing two different methods of administering TakeCARE and examining moderators of TakeCARE's effects on bystander behavior. Students at four universities ( n = 557) were randomly assigned to one of three conditions: (a) view TakeCARE in a monitored computer lab, (b) view TakeCARE at their own convenience after receiving an email link to the video, or (c) view a video about study skills (control group). Participants completed measures of bystander behavior at baseline and at a 1-month follow-up. Participants in both TakeCARE conditions reported more bystander behavior at follow-up assessments, compared with participants in the control condition. The beneficial effect of TakeCARE did not differ significantly across administration methods. However, the effects of TakeCARE on bystander behavior were moderated by students' perceptions of campus responsiveness to sexual violence, with more potent effects when students perceived their institution as responsive to reports of sexual violence.

Aggregate and Individual Replication Probability within an Explicit Model of the Research Process

ERIC Educational Resources Information Center

Miller, Jeff; Schwarz, Wolf

2011-01-01

We study a model of the research process in which the true effect size, the replication jitter due to changes in experimental procedure, and the statistical error of effect size measurement are all normally distributed random variables. Within this model, we analyze the probability of successfully replicating an initial experimental result by…

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…

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…

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...

A cross-validation trial of an Internet-based prevention program for alcohol and cannabis: Preliminary results from a cluster randomised controlled trial.

PubMed

Champion, Katrina E; Newton, Nicola C; Stapinski, Lexine; Slade, Tim; Barrett, Emma L; Teesson, Maree

2016-01-01

Replication is an important step in evaluating evidence-based preventive interventions and is crucial for establishing the generalizability and wider impact of a program. Despite this, few replications have occurred in the prevention science field. This study aims to fill this gap by conducting a cross-validation trial of the Climate Schools: Alcohol and Cannabis course, an Internet-based prevention program, among a new cohort of Australian students. A cluster randomized controlled trial was conducted among 1103 students (Mage: 13.25 years) from 13 schools in Australia in 2012. Six schools received the Climate Schools course and 7 schools were randomized to a control group (health education as usual). All students completed a self-report survey at baseline and immediately post-intervention. Mixed-effects regressions were conducted for all outcome variables. Outcomes assessed included alcohol and cannabis use, knowledge and intentions to use these substances. Compared to the control group, immediately post-intervention the intervention group reported significantly greater alcohol (d = 0.67) and cannabis knowledge (d = 0.72), were less likely to have consumed any alcohol (even a sip or taste) in the past 6 months (odds ratio = 0.69) and were less likely to intend on using alcohol in the future (odds ratio = 0.62). However, there were no effects for binge drinking, cannabis use or intentions to use cannabis. These preliminary results provide some support for the Internet-based Climate Schools: Alcohol and Cannabis course as a feasible way of delivering alcohol and cannabis prevention. Intervention effects for alcohol and cannabis knowledge were consistent with results from the original trial; however, analyses of longer-term follow-up data are needed to provide a clearer indication of the efficacy of the intervention, particularly in relation to behavioral changes. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes.

PubMed

Chung, Aeri; Jin, Bora; Han, Kwang-Hyub; Ahn, Sang Hoon; Kim, Seungtaek

2017-01-01

Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

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

Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn; Zhou, Ling; Zhang, Yan-ling

2013-12-13

Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endomore » via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.« less

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.

Replication Proteins and Human Disease

PubMed Central

Jackson, Andrew P.; Laskey, Ronald A.; Coleman, Nicholas

2014-01-01

In this article, we discuss the significance of DNA replication proteins in human disease. There is a broad range of mutations in genes encoding replication proteins, which result in several distinct clinical disorders that share common themes. One group of replication proteins, the MCMs, has emerged as effective biomarkers for early detection of a range of common cancers. They offer practical and theoretical advantages over other replication proteins and have been developed for widespread clinical use. PMID:23881941

DNA Damage and Genomic Instability Induced by Inappropriate DNA Re-replication

DTIC Science & Technology

2006-04-01

replication in yeast cells. In the prior reporting period we demonstrated that re-replication induces a rapid and significant decrease in cell viability...repair, DNA replication, checkpoint, cell cycle, yeast , RAD9 16. SECURITY CLASSIFICATION OF: 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...initiation, our laboratory has been able to conditionally induce varying amounts of re- replication in yeast cells. Effectively, cells enter, but do not

Implementation of a training program for low-literacy promotoras in oral rehydration therapy.

PubMed

Amerson, Roxanne; Hall-Clifford, Rachel; Thompson, Beti; Comninellas, Nicholas

2015-01-01

The purpose of this study was to ascertain the effectiveness of a culturally appropriate promotora training program related to oral rehydration therapy and diarrheal management. Factors that influenced the development, implementation, and evaluation of the program provided to low-literacy women in Guatemala are explored. Promotora training was conducted with 15 Mayan women from a rural community in the highlands of Guatemala. Women were selected by leaders of the community to participate in the program. Quantitative data were collected and analyzed to determine descriptive statistics and reliability coefficients for the pretests and posttests. A nonparametric Wilcoxon test for paired-samples was conducted. The qualitative data from the program evaluations were analyzed for themes. Mean scores increased from 41.73 (SD = 9.65) to 70.33 (SD = 21.29) on the pretest and posttest. The Cronbach's alpha was 0.54 on the pretest with 0.65 on the posttest. The Wilcoxon test demonstrated a significant difference between the pretest and posttest scores (Z = 3.040, p < .05). Extremely low-literacy levels played a major role in the ability of the women to successfully complete the requirements of the training program. The curriculum demonstrated effectiveness, but will benefit from replication with a larger sample. © 2014 Wiley Periodicals, Inc.

Peer Training of Community Health Workers to Improve Heart Health Among African American Women

PubMed Central

Willock, Robina Josiah; Mayberry, Robert M.; Yan, Fengxia; Daniels, Pamela

2015-01-01

Introduction Training community health workers (CHWs) builds a workforce that is essential to addressing the chronic disease crisis. This article describes a highly replicable CHW training program that targets heart disease risk among African American women. Background African American women suffer disproportionately from heart disease mortality and morbidity. Well-trained CHWs are uniquely positioned to close this disparity gap. Method We used a Learning Circle approach to train CHWs in heart health education. The curriculum blended web-based, self-directed learning and in-person peer coaching. CHWs learned through (a) peer-to-peer sharing, (b) problem solving and brainstorming, and (c) leadership and experiential activities. Training evaluation measures were CHWs' (a) self-confidence, (b) heart health knowledge, (c) satisfaction with training, (d) training retention, and (e) replication of training within 90 days after training. Results This training resulted in appreciable effects on four of five outcome measures. Heart health knowledge increased significantly among experienced CHWs (p = .011). CHWs were satisfied with training and retention was 100%. CHWs initiated and subsequently delivered 122 person hours of community heart health education and CHW training in their communities. Discussion/Conclusion CHW heart health training using Learning Circles is a practical and replicable method of training CHWs and holds significant potential for building capacity in resource-poor community organizations. PMID:24891525

Peer training of community health workers to improve heart health among African American women.

PubMed

Josiah Willock, Robina; Mayberry, Robert M; Yan, Fengxia; Daniels, Pamela

2015-01-01

Training community health workers (CHWs) builds a workforce that is essential to addressing the chronic disease crisis. This article describes a highly replicable CHW training program that targets heart disease risk among African American women. African American women suffer disproportionately from heart disease mortality and morbidity. Well-trained CHWs are uniquely positioned to close this disparity gap. Method. We used a Learning Circle approach to train CHWs in heart health education. The curriculum blended web-based, self-directed learning and in-person peer coaching. CHWs learned through (a) peer-to-peer sharing, (b) problem solving and brainstorming, and (c) leadership and experiential activities. Training evaluation measures were CHWs' (a) self-confidence, (b) heart health knowledge, (c) satisfaction with training, (d) training retention, and (e) replication of training within 90 days after training. This training resulted in appreciable effects on four of five outcome measures. Heart health knowledge increased significantly among experienced CHWs (p = .011). CHWs were satisfied with training and retention was 100%. CHWs initiated and subsequently delivered 122 person hours of community heart health education and CHW training in their communities. CHW heart health training using Learning Circles is a practical and replicable method of training CHWs and holds significant potential for building capacity in resource-poor community organizations. © 2014 Society for Public Health Education.

Differential Effects of the Putative GBF1 Inhibitors Golgicide A and AG1478 on Enterovirus Replication▿

PubMed Central

van der Linden, Lonneke; van der Schaar, Hilde M.; Lanke, Kjerstin H. W.; Neyts, Johan; van Kuppeveld, Frank J. M.

2010-01-01

The genus Enterovirus, belonging to the family Picornaviridae, includes well-known pathogens, such as poliovirus, coxsackievirus, and rhinovirus. Brefeldin A (BFA) impedes replication of several enteroviruses through inhibition of Golgi-specific BFA resistance factor 1 (GBF1), a regulator of secretory pathway integrity and transport. GBF1 mediates the GTP exchange of Arf1, which in activated form recruits coatomer protein complex I (COP-I) to Golgi vesicles, a process important in transport between the endoplasmic reticulum and Golgi vesicles. Recently, the drugs AG1478 and Golgicide A (GCA) were put forward as new inhibitors of GBF1. In this study, we investigated the effects of these putative GBF1 inhibitors on secretory pathway function and enterovirus replication. We show that both drugs induced fragmentation of the Golgi vesicles and caused dissociation of Arf1 and COP-I from Golgi membranes, yet they differed in their effect on GBF1 localization. The effects of AG1478, but not those of GCA, could be countered by overexpression of Arf1, indicating a difference in their molecular mechanism of action. Consistent with this idea, we observed that GCA drastically reduced replication of coxsackievirus B3 (CVB3) and other human enterovirus species, whereas AG1478 had no effect at all on enterovirus replication. Time-of-addition studies and analysis of RNA replication using a subgenomic replicon both showed that GCA suppresses RNA replication of CVB3, which could be countered by overexpression of GBF1. These results indicate that, in contrast to AG1478, GCA inhibits CVB3 RNA replication by targeting GBF1. AG1478 and GCA may be valuable tools to further dissect enterovirus replication. PMID:20504936

Interprofessional education through service-learning: lessons from a student-led free clinic.

PubMed

Farlow, Janice L; Goodwin, Charles; Sevilla, Javier

2015-05-01

The academic community must replicate and strengthen existing models for interprofessional education (IPE) to meet widespread calls for team-based patient-centered care. One effective but under-explored possibility for IPE is through student-led clinics, which now exist in the majority of medical schools. This short report presents the Indiana University Student Outreach Clinic (IU-SOC), which involves seven different professional programs across three institutions, as a model for how IPE can be delivered formally through service learning. Lessons learned, such as nurturing an intentional interprofessional program, structured orientation and reflection, and resource and knowledge sharing between the clinic and academic institutions, can be applied to all student-led clinics, but also can inform other IPE initiatives in health professional curricula.

Astragalus polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway.

PubMed

Xue, Hongxia; Gan, Fang; Zhang, Zheqian; Hu, Junfa; Chen, Xingxiang; Huang, Kehe

2015-11-01

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Astragalus polysaccharide (APS), as one kind of biological macromolecule extracted from Astragalus, has antiviral activities. This study was undertaken to explore the effect of APS on PCV2 replication in vitro and the underlying mechanisms. Our results showed that adding APS before PCV2 infection decreased significantly PCV2 DNA copies, the number of infected cells, MDA level, ROS level and NF-κB activation in PK15 cells and increased significantly GSH contents and SOD activity compared to control without APS. Oxidative stress induced by BSO could eliminate the effect of PCV2 replication inhibition by APS. LPS, as a NF-κB activator, could attenuate the effect of PCV2 replication inhibition by APS. BAY 11-7082, as a NF-κB inhibitor, could increase the effect of PCV2 replication inhibition by APS. In conclusion, APS inhibits PCV2 replication by decreasing oxidative stress and the activation of NF-κB signaling pathway, which suggests that APS might be employed for the prevention of PCV2 infection. Copyright © 2015 Elsevier B.V. All rights reserved.

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…

An evaluation of Teaching-Family (Achievement Place) group homes for juvenile offenders.

PubMed

Kirigin, K A; Braukmann, C J; Atwater, J D; Wolf, M M

1982-01-01

Juvenile crime is a serious problem for which treatment approach has been found to be reliably effective. This outcome evaluation assessed during and posttreatment effectiveness of Teaching-Family group home treatment programs for juvenile offenders. The evaluation included the original Achievement Place program, which was the prototype for the development of the Teaching-Family treatment approach, 12 replications of Achievement Place, and 9 comparison group home programs. Primary dependent measures were retrieved from court and police files and included number of alleged offenses, percentage of youths involved in those alleged offenses, and percentage of youths institutionalized. Other dependent measures were subjective ratings of effectiveness obtained from the program consumers, including the group home residents. The results showed difference during treatment favoring the Teaching-Family programs on rate of alleged criminal offenses, percentage of youths involved in those offenses, and consumer ratings of the programs. The consumer ratings provided by the youths and their school teachers were found to be inversely and significantly correlated with the reduction of criminal offenses during treatment. There were no significant differences during treatment on measures of noncriminal offenses (e.g., truancy, runaway, and curfew violations). In the posttreatment year, none of the differences between the groups was significant on any of the outcome measures. The results are discussed in terms of measurement and design issues in the evaluation of delinquency treatment programs and in relation to the evaluation; of Teaching-Family group homes by Richard Jones and his colleagues.

An evaluation of Teaching-Family (Achievement Place) group homes for juvenile offenders.

PubMed Central

Kirigin, K A; Braukmann, C J; Atwater, J D; Wolf, M M

1982-01-01

Juvenile crime is a serious problem for which treatment approach has been found to be reliably effective. This outcome evaluation assessed during and posttreatment effectiveness of Teaching-Family group home treatment programs for juvenile offenders. The evaluation included the original Achievement Place program, which was the prototype for the development of the Teaching-Family treatment approach, 12 replications of Achievement Place, and 9 comparison group home programs. Primary dependent measures were retrieved from court and police files and included number of alleged offenses, percentage of youths involved in those alleged offenses, and percentage of youths institutionalized. Other dependent measures were subjective ratings of effectiveness obtained from the program consumers, including the group home residents. The results showed difference during treatment favoring the Teaching-Family programs on rate of alleged criminal offenses, percentage of youths involved in those offenses, and consumer ratings of the programs. The consumer ratings provided by the youths and their school teachers were found to be inversely and significantly correlated with the reduction of criminal offenses during treatment. There were no significant differences during treatment on measures of noncriminal offenses (e.g., truancy, runaway, and curfew violations). In the posttreatment year, none of the differences between the groups was significant on any of the outcome measures. The results are discussed in terms of measurement and design issues in the evaluation of delinquency treatment programs and in relation to the evaluation; of Teaching-Family group homes by Richard Jones and his colleagues. PMID:7096223

Replication and contradiction of highly cited research papers in psychiatry: 10-year follow-up.

PubMed

Tajika, Aran; Ogawa, Yusuke; Takeshima, Nozomi; Hayasaka, Yu; Furukawa, Toshi A

2015-10-01

Contradictions and initial overestimates are not unusual among highly cited studies. However, this issue has not been researched in psychiatry. Aims: To assess how highly cited studies in psychiatry are replicated by subsequent studies. We selected highly cited studies claiming effective psychiatric treatments in the years 2000 through 2002. For each of these studies we searched for subsequent studies with a better-controlled design, or with a similar design but a larger sample. Among 83 articles recommending effective interventions, 40 had not been subject to any attempt at replication, 16 were contradicted, 11 were found to have substantially smaller effects and only 16 were replicated. The standardised mean differences of the initial studies were overestimated by 132%. Studies with a total sample size of 100 or more tended to produce replicable results. Caution is needed when a study with a small sample size reports a large effect. © The Royal College of Psychiatrists 2015.

3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression.

PubMed

Löb, D; Lengert, N; Chagin, V O; Reinhart, M; Casas-Delucchi, C S; Cardoso, M C; Drossel, B

2016-04-07

DNA replication dynamics in cells from higher eukaryotes follows very complex but highly efficient mechanisms. However, the principles behind initiation of potential replication origins and emergence of typical patterns of nuclear replication sites remain unclear. Here, we propose a comprehensive model of DNA replication in human cells that is based on stochastic, proximity-induced replication initiation. Critical model features are: spontaneous stochastic firing of individual origins in euchromatin and facultative heterochromatin, inhibition of firing at distances below the size of chromatin loops and a domino-like effect by which replication forks induce firing of nearby origins. The model reproduces the empirical temporal and chromatin-related properties of DNA replication in human cells. We advance the one-dimensional DNA replication model to a spatial model by taking into account chromatin folding in the nucleus, and we are able to reproduce the spatial and temporal characteristics of the replication foci distribution throughout S-phase.

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.

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.

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).

Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.

PubMed

Chen, Xingxiang; Shi, Xiuli; Gan, Fang; Huang, Da; Huang, Kehe

2015-03-18

Glutamine has a positive effect on ameliorating reproductive failure caused by porcine circovirus type 2 (PCV2). However, the mechanism by which glutamine affects PCV2 replication remains unclear. This study was conducted to investigate the effects of glutamine on PCV2 replication and its underlying mechanisms in vitro. The results show that glutamine promoted PK-15 cell viability. Surprisingly, glutamine starvation significantly increased PCV2 replication. The promotion of PCV2 replication by glutamine starvation disappeared after fresh media with 4 mM glutamine was added. Likewise, promotion of PCV2 was observed after adding buthionine sulfoximine (BSO). Glutamine starvation or BSO treatment increased the level of p38 MAPK phosphorylation and PCV2 replication in PK-15 cells. Meanwhile, p38 MAPK phosphorylation and PCV2 replication significantly decreased in p38-knockdown PK-15 cells. Promotion of PCV2 replication caused by glutamine starvation could be blocked in p38-knockdown PK-15 cells. Therefore, glutamine starvation increased PCV2 replication by promoting p38 MAPK activation, which was associated with the down regulation of intracellular glutathione levels. Our findings may contribute toward interpreting the possible pathogenic mechanism of PCV2 and provide a theoretical reference for application of glutamine in controlling porcine circovirus-associated diseases.

Sequential steps in DNA replication are inhibited to ensure reduction of ploidy in meiosis

PubMed Central

Hua, Hui; Namdar, Mandana; Ganier, Olivier; Gregan, Juraj; Méchali, Marcel; Kearsey, Stephen E.

2013-01-01

Meiosis involves two successive rounds of chromosome segregation without an intervening S phase. Exit from meiosis I is distinct from mitotic exit, in that replication origins are not licensed by Mcm2-7 chromatin binding, but spindle disassembly occurs during a transient interphase-like state before meiosis II. The absence of licensing is assumed to explain the block to DNA replication, but this has not been formally tested. Here we attempt to subvert this block by expressing the licensing control factors Cdc18 and Cdt1 during the interval between meiotic nuclear divisions. Surprisingly, this leads only to a partial round of DNA replication, even when these factors are overexpressed and effect clear Mcm2-7 chromatin binding. Combining Cdc18 and Cdt1 expression with modulation of cyclin-dependent kinase activity, activation of Dbf4-dependent kinase, or deletion of the Spd1 inhibitor of ribonucleotide reductase has little additional effect on the extent of DNA replication. Single-molecule analysis indicates this partial round of replication results from inefficient progression of replication forks, and thus both initiation and elongation replication steps may be inhibited in late meiosis. In addition, DNA replication or damage during the meiosis I–II interval fails to arrest meiotic progress, suggesting absence of checkpoint regulation of meiosis II entry. PMID:23303250

Core-oscillator model of Caulobacter crescentus

NASA Astrophysics Data System (ADS)

Vandecan, Yves; Biondi, Emanuele; Blossey, Ralf

2016-06-01

The gram-negative bacterium Caulobacter crescentus is a powerful model organism for studies of bacterial cell cycle regulation. Although the major regulators and their connections in Caulobacter have been identified, it still is a challenge to properly understand the dynamics of its circuitry which accounts for both cell cycle progression and arrest. We show that the key decision module in Caulobacter is built from a limit cycle oscillator which controls the DNA replication program. The effect of an induced cell cycle arrest is demonstrated to be a key feature to classify the underlying dynamics.

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…

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…

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)

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…

Integrating Parenting Support Within and Beyond the Pediatric Medical Home.

PubMed

Linton, Julie M; Stockton, Maria Paz; Andrade, Berta; Daniel, Stephanie

2018-01-01

Positive parenting programs, developmental support services, and evidence-based home visiting programs can effectively provide parenting support and improve health and developmental outcomes for at-risk children. Few models, however, have integrated referrals for on-site support and home visiting programs into the provision of routine pediatric care within a medical home. This article describes an innovative approach, through partnership with a community-based organization, to deliver on-site and home visiting support services for children and families within and beyond the medical home. Our model offers a system of on-site services, including parenting, behavior, and/or development support, with optional intensive home visiting services. Assessment included description of the population served, delineation of services provided, and qualitative identification of key themes of the impact of services, illustrated by case examples. This replicable model describes untapped potential of the pediatric medical home as a springboard to mitigate risk and optimize children's health and development.

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.

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.

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.

Addressing the "Replication Crisis": Using Original Studies to Design Replication Studies with Appropriate Statistical Power.

PubMed

Anderson, Samantha F; Maxwell, Scott E

2017-01-01

Psychology is undergoing a replication crisis. The discussion surrounding this crisis has centered on mistrust of previous findings. Researchers planning replication studies often use the original study sample effect size as the basis for sample size planning. However, this strategy ignores uncertainty and publication bias in estimated effect sizes, resulting in overly optimistic calculations. A psychologist who intends to obtain power of .80 in the replication study, and performs calculations accordingly, may have an actual power lower than .80. We performed simulations to reveal the magnitude of the difference between actual and intended power based on common sample size planning strategies and assessed the performance of methods that aim to correct for effect size uncertainty and/or bias. Our results imply that even if original studies reflect actual phenomena and were conducted in the absence of questionable research practices, popular approaches to designing replication studies may result in a low success rate, especially if the original study is underpowered. Methods correcting for bias and/or uncertainty generally had higher actual power, but were not a panacea for an underpowered original study. Thus, it becomes imperative that 1) original studies are adequately powered and 2) replication studies are designed with methods that are more likely to yield the intended level of power.

An enhanced cluster analysis program with bootstrap significance testing for ecological community analysis

USGS Publications Warehouse

McKenna, J.E.

2003-01-01

The biosphere is filled with complex living patterns and important questions about biodiversity and community and ecosystem ecology are concerned with structure and function of multispecies systems that are responsible for those patterns. Cluster analysis identifies discrete groups within multivariate data and is an effective method of coping with these complexities, but often suffers from subjective identification of groups. The bootstrap testing method greatly improves objective significance determination for cluster analysis. The BOOTCLUS program makes cluster analysis that reliably identifies real patterns within a data set more accessible and easier to use than previously available programs. A variety of analysis options and rapid re-analysis provide a means to quickly evaluate several aspects of a data set. Interpretation is influenced by sampling design and a priori designation of samples into replicate groups, and ultimately relies on the researcher's knowledge of the organisms and their environment. However, the BOOTCLUS program provides reliable, objectively determined groupings of multivariate data.

Usability and Navigability of an HIV/AIDS Internet Intervention for Adolescents in a Resource Limited Setting

PubMed Central

Ybarra, Michele; Biringi, Ruth; Prescott, Tonya; Bull, Sheana S.

2012-01-01

Use of Internet is growing in Sub Saharan Africa. Evidence of computer and Internet effectiveness for reduction in risk behaviors associated with HIV shown in U.S. settings has yet to be replicated in Africa. We describe the development, usability and navigability testing of an Internet-based HIV prevention program for secondary school students in Uganda, called CyberSenga. For this work, we used four data collection activities, including observation of (a) computer skills and (b) navigation, (c) focus group discussions, and (d) field assessments to document comprehension and usability of program content. We document limited skills among students, but youth with basic computers skills were able to navigate the program after instruction. Youth were most interested in activities with more interaction. Field-testing illustrated the importance of using a stand-alone electrical source during program delivery. This work suggests delivery of Internet-based health promotion content in Africa requires attention to user preparedness and literacy, bandwidth, Internet connection, and electricity. PMID:22918136

Student achievement and attitudes in astronomy: An experimental comparison of two planetarium programs

NASA Astrophysics Data System (ADS)

Mallon, Gerald L.; Bruce, Matthew H.

Of the 1100 planetariums in the U.S., approximately 96% are smaller facilities. The majority of these use a program type called the Star Show, whereas some have advocated a different type called the Participatory Oriented Planetarium. The purpose of this study was to investigate the following question: In a smaller educational planetarium, with a capacity of between 15-75 people, is a traditional Star Show planetarium program, or a Participatory Oriented Planetarium program the most effective method of instruction and attitude change? A large scale investigation was conducted in Pennsylvania, with four smaller replications in Texas, Minnesota, California, and Nevada. In each planetarium, a group of 8-10 year old students were identified and randomly assigned to groups. 556 students were tested. The testing instruments included a paper-and-pencil content test and a Likert-style science opinionnaire. The instructional programs were chosen from existing scripts to avoid bias in their construction. Both programs dealt with constellation study. Correlated t tests were used to compare pretest to posttest scores and two-way factorial analyses of variance were used to compare the groups' posttest scores. It was concluded that, The Participatory Oriented Planetarium program, utilizing an activity-based format and extensive verbal interaction, is clearly the more effective utilization of a small planetarium facility for teaching constellation study and possibly for improving students' attitudes towards astronomy and the planetarium.

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.

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,…

Programs to improve adolescent sexual and reproductive health in the US: a review of the evidence.

PubMed

Manlove, Jennifer; Fish, Heather; Moore, Kristin Anderson

2015-01-01

US adolescents have high rates of teen pregnancy, childbearing, and sexually transmitted infections (STIs), highlighting the need to identify and implement effective programs that will help improve teen sexual and reproductive health. This review identified 103 random-assignment evaluations of 85 programs that incorporated intent-to-treat analyses and assessed impacts on pregnancy, childbearing, STIs, and their key determinants - sexual activity, number of sexual partners, condom use, and other contraceptive use - among teens. This review describes the evidence base for five broad program approaches, including abstinence education, comprehensive sex education, clinic-based programs, youth development programs, and parent-youth relationship programs. We also describe programs with impacts on key outcomes, including pregnancy/childbearing, STIs, and those that found impacts on both sexual activity and contraceptive use. Our review identified 52 effective programs: 38 with consistent impacts on reproductive health outcomes, and 14 with mixed findings (across subpopulations, follow-ups, or multiple measures of a single outcome). We found that a variety of program approaches produced impacts on sexual and reproductive health outcomes. Parent-youth relationship programs and clinic-based program evaluations more frequently showed impacts than other program approaches, although we also identified a number of abstinence-education, comprehensive sex education, and youth-development programs with impacts on sexual and reproductive health outcomes. Overall, we identified nine program evaluations with impacts on teen pregnancies or births, five with impacts on reducing STIs, and 15 with impacts on both delaying/reducing sexual activity and increasing contraceptive use (including condom use). Future efforts should conduct replications of existing program evaluations, identify implementation components linked to impacts, rigorously evaluate programs that appear promising, and expand the evidence base on programs that impact hormonal and long-acting contraceptive method use.

Using Replicates in Information Retrieval Evaluation.

PubMed

Voorhees, Ellen M; Samarov, Daniel; Soboroff, Ian

2017-09-01

This article explores a method for more accurately estimating the main effect of the system in a typical test-collection-based evaluation of information retrieval systems, thus increasing the sensitivity of system comparisons. Randomly partitioning the test document collection allows for multiple tests of a given system and topic (replicates). Bootstrap ANOVA can use these replicates to extract system-topic interactions-something not possible without replicates-yielding a more precise value for the system effect and a narrower confidence interval around that value. Experiments using multiple TREC collections demonstrate that removing the topic-system interactions substantially reduces the confidence intervals around the system effect as well as increases the number of significant pairwise differences found. Further, the method is robust against small changes in the number of partitions used, against variability in the documents that constitute the partitions, and the measure of effectiveness used to quantify system effectiveness.

DNA replication depends on photosynthetic electron transport in cyanobacteria.

PubMed

Ohbayashi, Ryudo; Watanabe, Satoru; Kanesaki, Yu; Narikawa, Rei; Chibazakura, Taku; Ikeuchi, Masahiko; Yoshikawa, Hirofumi

2013-07-01

The freshwater cyanobacterium Synechococcus elongatus PCC 7942 exhibits light-dependent growth. Although it has been reported that DNA replication also depends on light irradiation in S. elongatus 7942, the involvement of the light in the regulation of DNA replication remains unclear. To elucidate the regulatory pathway of DNA replication by light, we studied the effect of several inhibitors, including two electron transport inhibitors, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), on DNA replication in S. elongatus 7942. DCMU inhibited only DNA replication initiation, whereas DBMIB blocked both the initiation and progression of DNA replication. These results suggest that DNA replication depends on the photosynthetic electron transport activity and initiation and progression of DNA replication are regulated in different ways. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

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.

Role of MAPK/MNK1 signaling in virus replication.

PubMed

Kumar, Ram; Khandelwal, Nitin; Thachamvally, Riyesh; Tripathi, Bhupendra Nath; Barua, Sanjay; Kashyap, Sudhir Kumar; Maherchandani, Sunil; Kumar, Naveen

2018-06-01

Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication. Some of the host factors might be dispensable for the host but may be critical for virus replication; therefore such cellular factors may serve as targets for development of antiviral therapeutics. Mitogen activated protein kinase (MAPK) is a major cell signaling pathway that is known to be activated by diverse group of viruses. MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation. In this review we have discuss the role of MAPK in virus replication, particularly the role of MNK1 in replication and translation of viral genome. Copyright © 2018 Elsevier B.V. All rights reserved.

Gause's Principle and the Effect of Resource Partitioning on the Dynamical Coexistence of Replicating Templates

PubMed Central

Szilágyi, András; Zachar, István; Szathmáry, Eörs

2013-01-01

Models of competitive template replication, although basic for replicator dynamics and primordial evolution, have not yet taken different sequences explicitly into account, neither have they analyzed the effect of resource partitioning (feeding on different resources) on coexistence. Here we show by analytical and numerical calculations that Gause's principle of competitive exclusion holds for template replicators if resources (nucleotides) affect growth linearly and coexistence is at fixed point attractors. Cases of complementary or homologous pairing between building blocks with parallel or antiparallel strands show no deviation from the rule that the nucleotide compositions of stably coexisting species must be different and there cannot be more coexisting replicator species than nucleotide types. Besides this overlooked mechanism of template coexistence we show also that interesting sequence effects prevail as parts of sequences that are copied earlier affect coexistence more strongly due to the higher concentration of the corresponding replication intermediates. Template and copy always count as one species due their constraint of strict stoichiometric coupling. Stability of fixed-point coexistence tends to decrease with the length of sequences, although this effect is unlikely to be detrimental for sequences below 100 nucleotides. In sum, resource partitioning (niche differentiation) is the default form of competitive coexistence for replicating templates feeding on a cocktail of different nucleotides, as it may have been the case in the RNA world. Our analysis of different pairing and strand orientation schemes is relevant for artificial and potentially astrobiological genetics. PMID:23990769

SeMet attenuates OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR signaling pathway.

PubMed

Qian, Gang; Liu, Dandan; Hu, Junfa; Gan, Fang; Hou, Lili; Zhai, Nianhui; Chen, Xingxiang; Huang, Kehe

2018-02-13

Porcine circovirus type 2 (PCV2) is recognized as the causative agent of porcine circovirus-associated diseases. PCV2 replication could be promoted by low doses of ochratoxin A (OTA) as in our previous study and selenium has been shown to attenuate PCV2 replication. However, the underlying mechanism remains unclear. The aim of the study was to investigate the effects of selenomethionine (SeMet), the major component of organic selenium, on OTA-induced PCV2 replication promotion and its potential mechanism. The present study demonstrates that OTA could promote PCV2 replication as measured by cap protein expression, viral titer, viral DNA copies and the number of infected cells. In addition, OTA could activate autophagy as indicated by up-regulated light chain 3 (LC3)-II and autophagy-related protein 5 expressions and autophagosome formation. Further, OTA could down-regulate p-AKT and p-mTOR expressions and OTA-induced autophagy was inhibited when insulin was applied. SeMet at 2, 4 and 6 μM had significant inhibiting effects against OTA-induced PCV2 replication promotion. Furthermore, SeMet could attenuate OTA-induced autophagy and up-regulate OTA-induced p-AKT and p-mTOR expression inhibition. Rapamycin, an inhibitor of AKT/mTOR, could reverse the effects of SeMet on OTA-induced autophagy and the PCV2 replication promotion. In conclusion, SeMet could block OTA-induced PCV2 replication promotion by inhibiting autophagy by activating the AKT/mTOR pathway. Therefore, SeMet supplementation could be an effective prophylactic strategy against PCV2 infections and autophagy may be a potential marker to develop novel anti-PCV2 drugs.

Selenizing astragalus polysaccharide attenuates PCV2 replication promotion caused by oxidative stress through autophagy inhibition via PI3K/AKT activation.

PubMed

Liu, Dandan; Xu, Jing; Qian, Gang; Hamid, Mohammed; Gan, Fang; Chen, Xingxiang; Huang, Kehe

2018-03-01

Our previous studies have shown that oxidative stress could promote the porcine circovirus type 2 (PCV2) replication, and astragalus polysaccharide (APS)/selenium could suppress PCV2 replication. However, whether selenizing astragalus polysaccharide (sAPS) provides protection against oxidative stress-induced PCV2 replication promotion and the mechanism involved remain unclear. The present study aimed to explore the mechanism of the PCV2 replication promotion induced by oxidative stress and a novel pharmacotherapeutic approach involving the regulation of autophagy of sAPS. Our results showed that H 2 O 2 promoted PCV2 replication via enhancing autophagy by using 3-methyladenine (3-MA) and autophagy-related gene 5 (ATG5) knockdown. Sodium selenite, APS, the mixture of sodium selenite and APS, and sAPS significantly inhibited H 2 O 2 -induced PCV2 replication promotion, respectively. Among these, sAPS exerted maximal inhibitory effect. sAPS could also significantly inhibit autophagy activated by H 2 O 2 and increase the Akt and mTOR phosphorylation. Moreover, LY294002, the specific phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor, significantly alleviated the effects of sAPS on autophagy and PCV2 replication. Taken together, we conclude that H 2 O 2 promotes PCV2 replication by inducing autophagy and sAPS attenuates the PCV2 replication promotion through autophagy inhibition via PI3K/AKT activation. Copyright © 2017 Elsevier B.V. All rights reserved.

The utility of the FIM+FAM for assessing traumatic brain injury day program outcomes.

PubMed

Seel, Ronald T; Wright, Greg; Wallace, Tracey; Newman, Sary; Dennis, Leanne

2007-01-01

To evaluate the effectiveness of the FIM+FAM as a primary outcome measure for traumatic brain injury (TBI) comprehensive day programs. Retrospective data analysis. Single center, TBI comprehensive day program facility. A demographically and regionally diverse sample of 105 persons with moderate or severe TBI admitted to the Shepherd Pathways comprehensive TBI day rehabilitation program. Functional Independence Measure + Functional Assessment Measure (FIM+FAM). Twenty-eight percent or fewer of participants reached ceiling effects on 25 of the 30 FIM+FAM items at day program admission with only 2% of clients rated above ceiling score levels on the FIM+FAM total score. The criteria of Guyatt et al showed that 20 of the 30 FIM+FAM items showed clinically meaningful improvements in 60% or more of clients. On average, clients with TBI improved over 27 points on the FIM+FAM total score. Fifteen of 30 items showed ceiling effects of 33% or less at discharge where only 25% of clients exceeded the FIM+FAM total score ceiling threshold. Discharge FIM+FAM motor scale was a very good predictor of the need for additional single service physical therapy. However, reaching ceiling rating on the FIM+FAM cognitive scale demonstrated poor specificity (0.28) and negative predictive power (0.42) for the need for additional speech/cognitive therapy services. The FIM+FAM demonstrated utility as an outcome measure for TBI comprehensive day program treatment in the current milieu. Future research is required to replicate and extend the current findings.

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

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

Cancer therapy and replication stress: forks on the road to perdition.

PubMed

Kotsantis, Panagiotis; Jones, Rebecca M; Higgs, Martin R; Petermann, Eva

2015-01-01

Deregulated DNA replication occurs in cancer where it contributes to genomic instability. This process is a target of cytotoxic therapies. Chemotherapies exploit high DNA replication in cancer cells by modifying the DNA template or by inhibiting vital enzymatic activities that lead to slowing or stalling replication fork progression. Stalled replication forks can be converted into toxic DNA double-strand breaks resulting in cell death, i.e., replication stress. While likely crucial for many cancer treatments, replication stress is poorly understood due to its complexity. While we still know relatively little about the role of replication stress in cancer therapy, technical advances in recent years have shed new light on the effect that cancer therapeutics have on replication forks and the molecular mechanisms that lead from obstructed fork progression to cell death. This chapter will give an overview of our current understanding of replication stress in the context of cancer therapy. © 2015 Elsevier Inc. All rights reserved.

3D replicon distributions arise from stochastic initiation and domino-like DNA replication progression

PubMed Central

Löb, D.; Lengert, N.; Chagin, V. O.; Reinhart, M.; Casas-Delucchi, C. S.; Cardoso, M. C.; Drossel, B.

2016-01-01

DNA replication dynamics in cells from higher eukaryotes follows very complex but highly efficient mechanisms. However, the principles behind initiation of potential replication origins and emergence of typical patterns of nuclear replication sites remain unclear. Here, we propose a comprehensive model of DNA replication in human cells that is based on stochastic, proximity-induced replication initiation. Critical model features are: spontaneous stochastic firing of individual origins in euchromatin and facultative heterochromatin, inhibition of firing at distances below the size of chromatin loops and a domino-like effect by which replication forks induce firing of nearby origins. The model reproduces the empirical temporal and chromatin-related properties of DNA replication in human cells. We advance the one-dimensional DNA replication model to a spatial model by taking into account chromatin folding in the nucleus, and we are able to reproduce the spatial and temporal characteristics of the replication foci distribution throughout S-phase. PMID:27052359

The Effectiveness of the Within Our Reach Relationship Education Program for Couples: Findings from a Federal Randomized Trial.

PubMed

Rhoades, Galena K

2015-12-01

This study examined the effectiveness of a couple-based relationship education program, Within Our Reach. Secondary data (n = 3,609) were analyzed from the federal Supporting Healthy Marriage project. Couples were randomly assigned to receive Within Our Reach and associated services or to a no-treatment (treatment-as-usual) control group. Those assigned to Within Our Reach reported better couple and individual outcomes on 8 of 12 outcomes measured (M ES = .15) at the 12-month follow-up and 6 of 10 outcomes measured at the 30-month follow-up (M ES = .14), including higher relationship happiness, more warmth and support, more positive communication, less negative behavior and emotion, less psychological abuse, less physical assault (for men), lower psychological distress (for women), and less infidelity. They were also less likely to report that their marriage was in trouble. These effects were generally small in size and many were replicated across the two follow-ups. There were no significant differences between those assigned to Within Our Reach versus control on cooperative parenting, severe psychological assault, or percent married. Implications for future research, programming, and policy are discussed. © 2015 Family Process Institute.

Impact of an Intervention Designed to Reduce Sexual Health Risk Behaviors of African American Adolescents: Results of a Randomized Controlled Trial

PubMed Central

Jenner, Lynne W.; Walsh, Sarah; Demby, Hilary; Gregory, Alethia; Davis, Erin

2016-01-01

Objectives. To replicate an evidence-based HIV risk reduction program and assess its impact on 2 behavioral outcomes—inconsistency of condom use and frequency of sex—6 months after the program. Methods. The study was an individual-level randomized controlled trial in which we randomly assigned 850 youths (aged 14–18 years) to 1 of 2 conditions. The treatment (Becoming a Responsible Teen) is a group-level sociocognitive and skills training sexual education course; the control is a general health intervention that includes the same initial informational component as the treatment. Participants were recruited over 3 summers (2012–2014) from a summer employment program in New Orleans, Louisiana, that serves primarily African American adolescents. Results. Six months after program exposure, we found no statistically significant difference between treatment and control group members’ self-reported inconsistency of condom use or frequency of sex (P > .05). Conclusions. Although previous evidence has indicated that this particular program can be effective, this study’s findings indicate that it was not effective in this setting with this specific population. Results should provide an incentive to learn why the intervention works in some cases and what conditions are necessary for causal impacts. PMID:27689499

Veterans Affairs Geriatric Scholars Program: Enhancing Existing Primary Care Clinician Skills in Caring for Older Veterans.

PubMed

Kramer, B Josea; Creekmur, Beth; Howe, Judith L; Trudeau, Scott; Douglas, Joseph R; Garner, Kimberly; Bales, Connie; Callaway-Lane, Carol; Barczi, Steven

2016-11-01

The Veterans Affairs Geriatric Scholars Program (GSP) is a continuing professional development program to integrate geriatrics into the clinical practices of primary care providers and select associated health professions that support primary care teams. GSP uses a blended program educational format, and the minimal requirements are to attend an intensive course in geriatrics, participate in an interactive workshop on quality improvement (QI), and initiate a local QI project to demonstrate application of new knowledge to benefit older veterans. Using a retrospective post/pre survey design, the effect of GSP on clinical practices and behaviors and variation of that effect on clinicians working in rural and nonrural settings were evaluated. Significant improvement was found in the frequency of using evidence-based brief standardized assessments, clinical decision-making, and standards of care. Significant subgroup differences were observed in peer-to-peer information sharing between rural and nonrural clinicians. Overall, 77% of the sample reported greater job satisfaction after participating in GSP. The program is a successful model for advancing postgraduate education in geriatrics and a model that might be replicated to increase access to quality health care, particularly in rural areas. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Hemin potentiates the anti-hepatitis C virus activity of the antimalarial drug artemisinin

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

Paeshuyse, Jan; Coelmont, Lotte; Vliegen, Inge

2006-09-15

We report that the antimalarial drug artemisinin inhibits hepatitis C virus (HCV) replicon replication in a dose-dependent manner in two replicon constructs at concentrations that have no effect on the proliferation of the exponentially growing host cells. The 50% effective concentration (EC{sub 5}) for inhibition of HCV subgenomic replicon replication in Huh 5-2 cells (luciferase assay) by artemisinin was 78 {+-} 21 {mu}M. Hemin, an iron donor, was recently reported to inhibit HCV replicon replication [mediated by inhibition of the viral polymerase (C. Fillebeen, A.M. Rivas-Estilla, M. Bisaillon, P. Ponka, M. Muckenthaler, M.W. Hentze, A.E. Koromilas, K. Pantopoulos, Iron inactivatesmore » the RNA polymerase NS5B and suppresses subgenomic replication of hepatitis C virus, J. Biol. Chem. 280 (2005) 9049-9057.)] at a concentration that had no adverse effect on the host cells. When combined, artemisinin and hemin resulted, over a broad concentration range, in a pronounced synergistic antiviral activity. Also at a concentration (2 {mu}M) that alone had no effect on HCV replication, hemin still potentiated the anti-HCV activity of artemisinin.« less

Free fatty acids or high-concentration glucose enhances hepatitis A virus replication in association with a reduction in glucose-regulated protein 78 expression.

PubMed

Nwe Win, Nan; Kanda, Tatsuo; Nakamura, Masato; Nakamoto, Shingo; Okamoto, Hiroaki; Yokosuka, Osamu; Shirasawa, Hiroshi

2017-01-29

Although the interaction between host and hepatitis A virus (HAV) factors could lead to severe hepatitis A, the exact mechanism of acute liver failure caused by HAV infection is not yet fully understood. The effects of metabolic diseases such as dyslipidemia or diabetes mellitus on HAV replication are still unknown. Here, we examined the effects of free fatty acids or high-concentration glucose on HAV replication and the effects on mitogen-activated protein kinase signaling pathway-related genes in human hepatocytes. We discovered a novel effect of free fatty acids or high-concentration glucose on HAV replication in association with a reduction in the expression of glucose-regulated protein 78 (GRP78). We also observed that thapsigargin induced GRP78 expression and inhibited HAV replication. These findings may provide a new interpretation of the relationship between metabolic diseases and severity of hepatitis A and suggest a new understanding of the mechanism of severe HAV infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Effectiveness of an intensive multidisciplinary headache treatment program.

PubMed

Gunreben-Stempfle, Birgit; Griessinger, Norbert; Lang, Eberhard; Muehlhans, Barbara; Sittl, Reinhard; Ulrich, Kathrin

2009-07-01

To investigate if the effectiveness of a 96-hour multidisciplinary headache treatment program exceeds the effectiveness of a 20-hour program and primary care. When dealing with chronic back pain, low-intensity multidisciplinary treatment yields no significantly better results than standard care and monodisciplinary therapy; however, high-intensity treatment does. For multidisciplinary headache treatment, such comparisons are not yet available. In a previous study undertaken by our Pain Center, the outcome of a minimal multidisciplinary intervention model (20-hour) did not exceed primary care. Forty-two patients suffering from frequent headaches (20 +/- 9 headache days/month; range: 8-30) were treated and evaluated in a 96-hour group program. The results were compared with the outcomes of the previous study. Subjects who had undergone either the 20-hour multidisciplinary program or the primary care were used as historical control groups. A significant reduction in migraine days (P < .001), tension-type headache days (P < .001), frequency of migraine attacks (P = .004), and depression score (P < .001) was seen at the follow-up after 22 (+/-2) weeks. Comparing the intensive multidisciplinary program with primary care, repeated measures ANOVAs revealed significant time x group interactions for migraine days (P = .020), tension-type headache days (P = .016), and frequency of migraine attacks (P = .016). In comparison with the 20-hour multidisciplinary program, the 96-hour program showed significantly better effects only in the reduction of migraine days (P = .037) and depression score (P = .003). The responder-rates (> or =50% improvement) in the 96-hour program were significantly higher than in the 20-hour program (migraine days, P = .008; tension-type headache days, P = .044) and primary care (migraine days, P = .007; tension-type headache days, P = .003; tension-type headache intensity, P = .037). The effect sizes were small to medium in the 96-hour program. Particularly with the reduction of migraine symptomatology, the 96-hour program performed better than the 20-hour program, which produced only negligible or small effects. Intensive multidisciplinary headache treatment is highly effective for patients with chronic headaches. Furthermore, migraine symptomatology responds especially well to this intensive treatment program, whereas effects on tension-type headaches were realized by both multidisciplinary programs. Randomized controlled trials and subgroup analysis are needed to find out if these results can be replicated and which patient characteristics allow for sufficient improvements for headache sufferers even with less complex treatment.

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...

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.

When is a failure to replicate not a type II error?

PubMed

Vasconcelos, Marco; Urcuioli, Peter J; Lionello-DeNolf, Karen M

2007-05-01

Zentall and Singer (2007) challenge our conclusion that the work-ethic effect reported by Clement, Feltus, Kaiser, and Zentall (2000) may have been a Type I error by arguing that (a) the effect has been extensively replicated and (b) the amount of overtraining our pigeons received may not have been sufficient to produce it. We believe that our conclusion is warranted because (a) the original effect has not been replicated despite multiple attempts to do so and (b) the statement that more extended overtraining may be needed itself suggests that the original effect is not reliable.

When Is a Failure to Replicate Not a Type II Error?

PubMed Central

Vasconcelos, Marco; Urcuioli, Peter J; Lionello-DeNolf, Karen M

2007-01-01

Zentall and Singer (2007) challenge our conclusion that the work-ethic effect reported by Clement, Feltus, Kaiser, and Zentall (2000) may have been a Type I error by arguing that (a) the effect has been extensively replicated and (b) the amount of overtraining our pigeons received may not have been sufficient to produce it. We believe that our conclusion is warranted because (a) the original effect has not been replicated despite multiple attempts to do so and (b) the statement that more extended overtraining may be needed itself suggests that the original effect is not reliable. PMID:17575905

Cyclophilin B facilitates the replication of Orf virus.

PubMed

Zhao, Kui; Li, Jida; He, Wenqi; Song, Deguang; Zhang, Ximu; Zhang, Di; Zhou, Yanlong; Gao, Feng

2017-06-15

Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored. Suppression subtractive hybridization (SSH) technique was applied to identify genes differentially expressed in the ORFV-infected MDBK cells at an early phase of infection. Cellular CypB was confirmed to be significantly up-regulated by quantitative reverse transcription-PCR (qRT-PCR) analysis and Western blotting. The role of CypB in ORFV infection was further determined using Cyclosporin A (CsA) and RNA interference (RNAi). Effect of CypB gene silencing on ORFV replication by 50% tissue culture infectious dose (TCID 50 ) assay and qRT-PCR detection. In the present study, CypB was found to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection. Cyclosporin A (CsA) exhibited suppressive effects on ORFV replication through the inhibition of CypB. Silencing of CypB gene inhibited the replication of ORFV in MDBK cells. In conclusion, these data suggest that CypB is critical for the efficient replication of the ORFV genome. Cellular CypB was confirmed to be significantly up-regulated in the ORFV-infected MDBK cells at an early phase of infection, which could effectively facilitate the replication of ORFV.

Replication Stress: A Lifetime of Epigenetic Change

PubMed Central

Khurana, Simran; Oberdoerffer, Philipp

2015-01-01

DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs) and has been linked to both genome instability and irreversible cell cycle arrest (senescence). Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function. PMID:26378584

The evolution of replicators.

PubMed Central

Szathmáry, E

2000-01-01

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators. PMID:11127914

The evolution of replicators.

PubMed

Szathmáry, E

2000-11-29

Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators.

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…

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…

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,…

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…

Training basic teaching skills to community and institutional support staff for people with severe disabilities: a one-day program.

PubMed

Parsons, M B; Reid, D H; Green, C W

1996-01-01

Shortcomings in the technology for training support staff in methods of teaching people with severe disabilities recently have resulted in calls to improve the technology. We evaluated a program for training basic teaching skills within one day. The program entailed classroom-based verbal and video instruction, practice, and feedback followed by on-the-job feedback. In Study I, four undergraduate interns participated in the program, and all four met the mastery criterion for teaching skills. Three teacher aides participated in Study 2, with results indicating that when the staff applied their newly acquired teaching skills, students with profound disabilities made progress in skill acquisition. Clinical replications occurred in Study 3, involving 17 staff in school classrooms, group homes, and an institution. Results of Studies 2 and 3 also indicated staff were accepting of the program and improved their verbal skills. Results are discussed regarding advantages of training staff in one day. Future research suggestions are offered, focusing on identifying means of rapidly training other teaching skills in order to develop the most effective, acceptable, and efficient technology for staff training.

Barriers to Participation in a Community-Based Program to Control Transmission of Taenia solium in Peru.

PubMed

Beam, Michelle; Spencer, Angela; Fernandez, Lauralee; Atto, Ruth; Muro, Claudio; Vilchez, Percy; Gamboa, Ricardo; Olaya, Sandra; Ayvar, Viterbo; Gonzalez, Armando E; Garcia, Hector H; O'Neal, Seth E; For The Cysticercosis Working Group In Peru

2018-04-16

Infection of the brain with Taenia solium larvae (neurocysticercosis) is a leading cause of preventable epilepsy worldwide. Effective and sustainable strategies to control parasite transmission in rural endemic communities are needed to prevent the disease. Surveillance and targeted intervention around infected pigs (ring control strategy) have been shown to be effective when carried out by research teams. However, this strategy has not been implemented or tested as a community-based program. In this small trial in northern Peru, eight villages were randomly assigned to community-led surveillance and treatment (five villages, 997 residents) or control (three villages, 1,192 residents). In intervention villages, community-led surveillance and reporting were promoted by community health workers, radio advertisement, and school and household education. Each suspected pig infection was verified, with confirmed cases resulting in treatment with niclosamide for taeniasis and oxfendazole for pigs in clusters of homes nearby. No incentives beyond human and pig treatment were offered. Control villages received basic disease education but no treatment intervention in response to reports. Despite 14 case reports, community-based replication of ring control strategy did not replicate prior results. After 12 months, there was no change in seroincidence in intervention villages between the baseline and study end, and no difference compared with control villages. There was no difference in prevalence of taeniasis or porcine cysticercosis at study end. Community members described lack of knowledge as the main reason for not reporting infected pigs. Further exploration of methods to transfer ring strategy and other control interventions for cysticercosis to the community is needed.

Mink parvoviruses and interferons: in vitro studies.

PubMed Central

Wiedbrauk, D L; Bloom, M E; Lodmell, D L

1986-01-01

Although interferons can inhibit the replication of a number of viruses, little is known about their ability to inhibit parvovirus replication. Therefore, in vitro experiments were done to determine if Aleutian disease virus and mink enteritis virus, two autonomously replicating mink parvoviruses, induced interferon, were sensitive to the effects of interferon, or inhibited the production of interferon. The results indicated that these parvoviruses neither induced nor were sensitive to the effects of interferon. Furthermore, preexisting parvovirus infections did not inhibit poly(I).poly(C)-induced interferon production. This independence from the interferon system may, therefore, be a general property of the autonomously replicating parvoviruses. PMID:2431162

Manualization of Occupational Therapy Interventions: Illustrations from the Pressure Ulcer Prevention Research Program

PubMed Central

Blanche, Erna Imperatore; Fogelberg, Donald; Diaz, Jesus; Carlson, Mike; Clark, Florence

2011-01-01

The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Towards this latter end, intervention manuals are essential for assuring trustworthiness and replicability of randomized controlled trials (RCT’s) that aim to provide evidence of the effectiveness of occupational therapy. In this paper, literature on the process of intervention manualization is reviewed. The prescribed steps are then illustrated through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project (PUPP). In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce incidence of medically serious pressure ulcers in people with SCI. PMID:22214116

Cytologic Effects of Air Force Chemicals

DTIC Science & Technology

1980-11-01

Studies of DNA replication and repair in cell cultures have shown that hydrazine, although highly toxic to cells, does not damage DNA and thus...interfere directly with DNA replication in Chinese hamster ovary cells grown in vitro, nor does it affect DNA repair synthesis in CCL-185 human lung cells...vitro with chemicals and monitoring their effect on DNA replication and repair. This method has been used to show that the alkylating agents MMS and 4

Replication of genetic associations as pseudoreplication due to shared genealogy.

PubMed

Rosenberg, Noah A; Vanliere, Jenna M

2009-09-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

Replication of genetic associations as pseudoreplication due to shared genealogy

PubMed Central

Rosenberg, Noah A.; VanLiere, Jenna M.

2009-01-01

The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered “pseudoreplicates” rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence. PMID:19191270

Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.

PubMed

Gauson, Elaine J; Donaldson, Mary M; Dornan, Edward S; Wang, Xu; Bristol, Molly; Bodily, Jason M; Morgan, Iain M

2015-05-01

To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease burden on the current, and future, generations. Targeting viral DNA replication that is mediated by two viral proteins, E1 and E2, in association with cellular proteins such as TopBP1 and Brd4 would have therapeutic benefits. This report suggests a role for these cellular proteins in the initiation of viral DNA replication by HPV16 E1-E2 but not for continuing replication. This is important if viral replication is to be effectively targeted; we need to understand the viral and cellular proteins required at each phase of viral DNA replication so that it can be effectively disrupted. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Evidence Supporting a Role for TopBP1 and Brd4 in the Initiation but Not Continuation of Human Papillomavirus 16 E1/E2-Mediated DNA Replication

PubMed Central

Gauson, Elaine J.; Donaldson, Mary M.; Dornan, Edward S.; Wang, Xu; Bristol, Molly; Bodily, Jason M.

2015-01-01

ABSTRACT To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. IMPORTANCE Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease burden on the current, and future, generations. Targeting viral DNA replication that is mediated by two viral proteins, E1 and E2, in association with cellular proteins such as TopBP1 and Brd4 would have therapeutic benefits. This report suggests a role for these cellular proteins in the initiation of viral DNA replication by HPV16 E1-E2 but not for continuing replication. This is important if viral replication is to be effectively targeted; we need to understand the viral and cellular proteins required at each phase of viral DNA replication so that it can be effectively disrupted. PMID:25694599

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.

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work.

Project EX: A Program of Empirical Research on Adolescent Tobacco Use Cessation

PubMed Central

Sussman, Steve; McCuller, William J; Zheng, Hong; Pfingston, Yvonne M; Miyano, James; Dent, Clyde W

2004-01-01

This paper presents the Project EX research program. The historical background for Project EX is presented, including a brief summary of reasons youth fail to quit tobacco use, the disappointing status of previous cessation research, and the teen cessation trial that provided the template for the current project (Project TNT). Next, program development studies for Project EX are described. Through use of focus groups, a theme study (concept evaluation of written activity descriptions), a component study, and pilot studies, an eight-session program was developed. This program involves novel activities (e.g., "talk show enactments," games, and alternative medicine-type activities such as yoga and meditation) in combination with motivation enhancement and cognitive-behavioral strategies to motivate and instruct in cessation initiation and maintenance efforts. The outcomes of the first experimental trial of Project EX, a school-based clinic program, are described, followed by a posthoc analysis of its effects mediation. A second EX study, a multiple baseline single group pilot study design in Wuhan, China, is described next. Description of a second experimental trial follows, which tested EX with nicotine gum versus a natural herb. A third experimental trial that tests a classroom prevention/cessation version of EX is then introduced. Finally, the implications of this work are discussed. The intent-to-treat quit rate for Project EX is approximately 15% across studies, double that of a standard care comparison. Effects last up to a six-month post-program at regular and alternative high schools. Through a systematic protocol of empirical program development and field trials, an effective and replicable model teen tobacco use cessation program is established. Future cessation work might expand on this work. PMID:19570278

A randomised controlled trial of a web-based educational program in child mental health for schoolteachers.

PubMed

Pereira, Celina Andrade; Wen, Chao Lung; Miguel, Eurípedes Constantino; Polanczyk, Guilherme V

2015-08-01

Children affected by mental disorders are largely unrecognised and untreated across the world. Community resources, including the school system and teachers, are important elements in actions directed to promoting child mental health and preventing and treating mental disorders, especially in low- and middle-income countries. We developed a web-based program to educate primary school teachers on mental disorders in childhood and conducted a cluster-randomised controlled trial to test the effectiveness of the web-based program intervention in comparison with the same program based on text and video materials only and to a waiting-list control group. All nine schools of a single city in the state of São Paulo, Brazil, were randomised to the three groups, and teachers completed the educational programs during 3 weeks. Data were analysed according to complete cases and intention-to-treat approaches. In terms of gains of knowledge about mental disorders, the web-based program intervention was superior to the intervention with text and video materials, and to the waiting-list control group. In terms of beliefs and attitudes about mental disorders, the web-based program intervention group presented less stigmatised concepts than the text and video group and more non-stigmatised concepts than the waiting-list group. No differences were detected in terms of teachers' attitudes. This study demonstrated initial data on the effectiveness of a web-based program in educating schoolteachers on child mental disorders. Future studies are necessary to replicate and extend the findings.

Genomic Trajectories to Desiccation Resistance: Convergence and Divergence Among Replicate Selected Drosophila Lines

PubMed Central

Griffin, Philippa C.; Hangartner, Sandra B.; Fournier-Level, Alexandre; Hoffmann, Ary A.

2017-01-01

Adaptation to environmental stress is critical for long-term species persistence. With climate change and other anthropogenic stressors compounding natural selective pressures, understanding the nature of adaptation is as important as ever in evolutionary biology. In particular, the number of alternative molecular trajectories available for an organism to reach the same adaptive phenotype remains poorly understood. Here, we investigate this issue in a set of replicated Drosophila melanogaster lines selected for increased desiccation resistance—a classical physiological trait that has been closely linked to Drosophila species distributions. We used pooled whole-genome sequencing (Pool-Seq) to compare the genetic basis of their selection responses, using a matching set of replicated control lines for characterizing laboratory (lab-)adaptation, as well as the original base population. The ratio of effective population size to census size was high over the 21 generations of the experiment at 0.52–0.88 for all selected and control lines. While selected SNPs in replicates of the same treatment (desiccation-selection or lab-adaptation) tended to change frequency in the same direction, suggesting some commonality in the selection response, candidate SNP and gene lists often differed among replicates. Three of the five desiccation-selection replicates showed significant overlap at the gene and network level. All five replicates showed enrichment for ovary-expressed genes, suggesting maternal effects on the selected trait. Divergence between pairs of replicate lines for desiccation-candidate SNPs was greater than between pairs of control lines. This difference also far exceeded the divergence between pairs of replicate lines for neutral SNPs. Overall, while there was overlap in the direction of allele frequency changes and the network and functional categories affected by desiccation selection, replicates showed unique responses at all levels, likely reflecting hitchhiking effects, and highlighting the challenges in identifying candidate genes from these types of experiments when traits are likely to be polygenic. PMID:28007884

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.

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

PubMed Central

Müller, Christian; Schillert, Arne; Röthemeier, Caroline; Trégouët, David-Alexandre; Proust, Carole; Binder, Harald; Pfeiffer, Norbert; Beutel, Manfred; Lackner, Karl J.; Schnabel, Renate B.; Tiret, Laurence; Wild, Philipp S.; Blankenberg, Stefan

2016-01-01

Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data. PMID:27272489

Sustainability and scalability of the hospital elder life program at a community hospital.

PubMed

Rubin, Fred H; Neal, Kelly; Fenlon, Kerry; Hassan, Shuja; Inouye, Sharon K

2011-02-01

The Hospital Elder Life Program (HELP), an effective intervention to prevent delirium in older hospitalized adults, has been successfully replicated in a community teaching hospital as a quality improvement project. This article reports on successfully sustaining the program over 7 years and expanding its scale from one to six inpatient units at the same hospital. The program currently serves more than 7,000 older patients annually and is accepted as the standard of care throughout the hospital. Innovations that enhanced scalability and widespread implementation included ensuring dedicated staffing for the program, local adaptations to streamline protocols, continuous recruitment of volunteers, and more-efficient data collection. Outcomes include a lower rate of incident delirium; shorter length of stay (LOS); greater satisfaction of patients, families, and nursing staff; and significantly lower costs for the hospital. The financial return of the program, estimated at more than $7.3 million per year during 2008, comprises cost savings from delirium prevention and revenue generated from freeing up hospital beds (shorter LOS of HELP patients with and without delirium). Delirium poses a major challenge for hospital quality of care, patient safety, Medicare no-pay conditions, and costs of hospital care for older persons. Faced with rising numbers of elderly patients, hospitals can use HELP to improve the quality and cost-effectiveness of care. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

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

Matrix Conditions and KLF2-Dependent Induction of Heme Oxygenase-1 Modulate Inhibition of HCV Replication by Fluvastatin

PubMed Central

Singethan, Katrin; Sirma, Hüseyin; Keller, Amelie Dorothea; Rosal, Sergio René Perez; Schrader, Jörg; Loscher, Christine; Volz, Tassilo; Bartenschlager, Ralf; Lohmann, Volker; Protzer, Ulrike; Dandri, Maura; Lohse, Ansgar W.; Tiegs, Gisa; Sass, Gabriele

2014-01-01

Background & Aims HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication. Methods HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue. Results All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease. Conclusions Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease. PMID:24801208

Effect of sex steroid hormones on replication and transmission of major HIV subtypes.

PubMed

Ragupathy, Viswanath; Devadas, Krishnakumar; Tang, Shixing; Wood, Owen; Lee, Sherwin; Dastyer, Armeta; Wang, Xue; Dayton, Andrew; Hewlett, Indira

2013-11-01

The HIV epidemic is expanding worldwide with an increasing number of distinct viral subtypes and circulating recombinant forms (CRFs). Out of 34 million adults living with HIV and AIDS, women account for one half of all HIV-1 infections worldwide. These gender differences in HIV pathogenesis may be attributed to sex hormones. Little is known about the role of sex hormone effects on HIV Subtypes pathogenesis. The aim of our study was to determine sex hormone effects on replication and transmissibility of HIV subtypes. Peripheral blood mononuclear cells (PBMC) and monocyte derived dendritic cells (MDDC) from male and female donors were infected with HIV subtypes A-D and CRF02_AG, CRF01_AE, MN (lab adapted), Group-O, Group-N and HIV-2 at a concentration of 5ng/ml of p24 or p27. Virus production was evaluated by measuring p24 and p27 levels in culture supernatants. Similar experiments were carried out in the presence of physiological concentrations of sex steroid hormones. R5/X4 expressions measured by flow cytometry and transmissibility was evaluated by transfer of HIV from primary dendritic cells (DC) to autologous donor PBMC. Our results from primary PBMC and MDDC from male and female donors indicate in the absence of physiological concentrations of hormone treatment virus production was observed in three clusters; high replicating virus (subtype B and C), moderate replicative virus (subtype A, D, CRF01_AE, Group_N) and least replicative virus (strain MN). However, dose of sex steroid hormone treatment influenced HIV replication and transmission kinetics in PBMC, DCs and cell lines. Such effects were inconsistent between donors and HIV subtypes. Sex hormone effects on HIV entry receptors (CCR5/CXCR4) did not correlate with virus production. Subtypes B and C showed higher replication in PBMC from males and females and were transmitted more efficiently through DC to male and female PBMC compared with other HIV-1 subtypes, HIV-1 Group O and HIV-2. These findings are consistent with increased worldwide prevalence of subtype B and C compared to other subtypes. Sex steroid hormones had variable effect on replication or transmission of different subtypes. These findings suggest that subtype, gender and sex hormones may play a crucial role in the replication and transmission of HIV. Published by Elsevier Ltd.

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.

Psychology, Science, and Knowledge Construction: Broadening Perspectives from the Replication Crisis.

PubMed

Shrout, Patrick E; Rodgers, Joseph L

2018-01-04

Psychology advances knowledge by testing statistical hypotheses using empirical observations and data. The expectation is that most statistically significant findings can be replicated in new data and in new laboratories, but in practice many findings have replicated less often than expected, leading to claims of a replication crisis. We review recent methodological literature on questionable research practices, meta-analysis, and power analysis to explain the apparently high rates of failure to replicate. Psychologists can improve research practices to advance knowledge in ways that improve replicability. We recommend that researchers adopt open science conventions of preregi-stration and full disclosure and that replication efforts be based on multiple studies rather than on a single replication attempt. We call for more sophisticated power analyses, careful consideration of the various influences on effect sizes, and more complete disclosure of nonsignificant as well as statistically significant findings.

Feline coronavirus replication is affected by both cyclophilin A and cyclophilin B.

PubMed

Tanaka, Yoshikazu; Sato, Yuka; Sasaki, Takashi

2017-02-01

Feline coronavirus (FCoV) causes the fatal disease feline infectious peritonitis, which is currently incurable by drug treatment, and no effective vaccines are available. Cyclosporin A (CsA), a cyclophilin (Cyp) inhibitor, inhibits the replication of FCoV in vitro and in vivo as well as the replication of human and animal coronaviruses. However, the mechanism underlying the regulation of coronavirus replication by CsA is unknown. In this study, we analysed the role of Cyps in FCoV replication using knockdown and knockout cells specific to Cyps. Inhibition of CypA and CypB reduced FCoV replication, with replication in knockout cells being much less than that in knockdown cells. Furthermore, the proteins expressed by CypA and CypB harbouring mutations in their respective predicted peptidyl-prolyl cis-transisomerase active sites, which also alter the affinities between Cyps and CsA, inhibited FCoV replication. These findings indicate that the peptidyl-prolyl cis-transisomerase active sites of Cyps might be required for FCoV replication.

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

Inhibition of hepatitis C virus replication through adenosine monophosphate-activated protein kinase-dependent and -independent pathways.

PubMed

Nakashima, Kenji; Takeuchi, Kenji; Chihara, Kazuyasu; Hotta, Hak; Sada, Kiyonao

2011-11-01

Persistent infection with hepatitis C virus (HCV) is closely correlated with type 2 diabetes. In this study, replication of HCV at different glucose concentrations was investigated by using J6/JFH1-derived cell-adapted HCV in Huh-7.5 cells and the mechanism of regulation of HCV replication by AMP-activated protein kinase (AMPK) as an energy sensor of the cell analyzed. Reducing the glucose concentration in the cell culture medium from 4.5 to 1.0 g/L resulted in suppression of HCV replication, along with activation of AMPK. Whereas treatment of cells with AMPK activator 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) suppressed HCV replication, compound C, a specific AMPK inhibitor, prevented AICAR's effect, suggesting that AICAR suppresses the replication of HCV by activating AMPK in Huh-7.5 cells. In contrast, compound C induced further suppression of HCV replication when the cells were cultured in low glucose concentrations or with metformin. These results suggest that low glucose concentrations and metformin have anti-HCV effects independently of AMPK activation. © 2011 The Societies and Blackwell Publishing Asia Pty Ltd.

Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

PubMed Central

Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

2012-01-01

Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

The Regulatory Interactions of p21 and PCNA in Human Breast Cancer

DTIC Science & Technology

2000-07-01

To better understand the role of DNA replication in breast cancer, it is essential to examine the machinery that carries out the DNA synthetic...origin specific DNA replication in vitro, which we have termed the DNA synthesome. Analysis of the constituent proteins of the DNA synthesome of...and effectively competes away polymerase 8 leading to the efficient inhibition of DNA replication . This inhibition impedes the replication of damaged

Replication of Psycholinguistic Experiments and the Resolution of Inconsistencies

ERIC Educational Resources Information Center

Rákosi, Csilla

2017-01-01

Non-exact replications are regarded as effective tools of problem solving in psycholinguistic research because they lead to more plausible experimental results; however, they are also ineffective tools of problem solving because they trigger cumulative contradictions among different replications of an experiment. This paper intends to resolve this…

Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G/sub 0//G/sub 1/

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

Freytag, S.O.

1988-04-01

A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, the authors examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G/sub 0//G/sub 1/, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to loose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell linesmore » expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSV myc mRNA arrested in G/sub 0//G/sub 1/ at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G/sub 0//G/sub 1/. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G/sub 0//G/sub 1/ or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate.« less

Biases in research: risk factors for non-replicability in psychotherapy and pharmacotherapy research.

PubMed

Leichsenring, F; Abbass, A; Hilsenroth, M J; Leweke, F; Luyten, P; Keefe, J R; Midgley, N; Rabung, S; Salzer, S; Steinert, C

2017-04-01

Replicability of findings is an essential prerequisite of research. For both basic and clinical research, however, low replicability of findings has recently been reported. Replicability may be affected by research biases not sufficiently controlled for by the existing research standards. Several biases such as researcher allegiance or selective reporting are well-known for affecting results. For psychotherapy and pharmacotherapy research, specific additional biases may affect outcome (e.g. therapist allegiance, therapist effects or impairments in treatment implementation). For meta-analyses further specific biases are relevant. In psychotherapy and pharmacotherapy research these biases have not yet been systematically discussed in the context of replicability. Using a list of 13 biases as a starting point, we discuss each bias's impact on replicability. We illustrate each bias by selective findings of recent research, showing that (1) several biases are not yet sufficiently controlled for by the presently applied research standards, (2) these biases have a pernicious effect on replicability of findings. For the sake of research credibility, it is critical to avoid these biases in future research. To control for biases and to improve replicability, we propose to systematically implement several measures in psychotherapy and pharmacotherapy research, such as adversarial collaboration (inviting academic rivals to collaborate), reviewing study design prior to knowing the results, triple-blind data analysis (including subjects, investigators and data managers/statisticians), data analysis by other research teams (crowdsourcing), and, last not least, updating reporting standards such as CONSORT or the Template for Intervention Description and Replication (TIDieR).

Publication bias and the failure of replication in experimental psychology.

PubMed

Francis, Gregory

2012-12-01

Replication of empirical findings plays a fundamental role in science. Among experimental psychologists, successful replication enhances belief in a finding, while a failure to replicate is often interpreted to mean that one of the experiments is flawed. This view is wrong. Because experimental psychology uses statistics, empirical findings should appear with predictable probabilities. In a misguided effort to demonstrate successful replication of empirical findings and avoid failures to replicate, experimental psychologists sometimes report too many positive results. Rather than strengthen confidence in an effect, too much successful replication actually indicates publication bias, which invalidates entire sets of experimental findings. Researchers cannot judge the validity of a set of biased experiments because the experiment set may consist entirely of type I errors. This article shows how an investigation of the effect sizes from reported experiments can test for publication bias by looking for too much successful replication. Simulated experiments demonstrate that the publication bias test is able to discriminate biased experiment sets from unbiased experiment sets, but it is conservative about reporting bias. The test is then applied to several studies of prominent phenomena that highlight how publication bias contaminates some findings in experimental psychology. Additional simulated experiments demonstrate that using Bayesian methods of data analysis can reduce (and in some cases, eliminate) the occurrence of publication bias. Such methods should be part of a systematic process to remove publication bias from experimental psychology and reinstate the important role of replication as a final arbiter of scientific findings.

Bayesian evaluation of effect size after replicating an original study

PubMed Central

van Aert, Robbie C. M.; van Assen, Marcel A. L. M.

2017-01-01

The vast majority of published results in the literature is statistically significant, which raises concerns about their reliability. The Reproducibility Project Psychology (RPP) and Experimental Economics Replication Project (EE-RP) both replicated a large number of published studies in psychology and economics. The original study and replication were statistically significant in 36.1% in RPP and 68.8% in EE-RP suggesting many null effects among the replicated studies. However, evidence in favor of the null hypothesis cannot be examined with null hypothesis significance testing. We developed a Bayesian meta-analysis method called snapshot hybrid that is easy to use and understand and quantifies the amount of evidence in favor of a zero, small, medium and large effect. The method computes posterior model probabilities for a zero, small, medium, and large effect and adjusts for publication bias by taking into account that the original study is statistically significant. We first analytically approximate the methods performance, and demonstrate the necessity to control for the original study’s significance to enable the accumulation of evidence for a true zero effect. Then we applied the method to the data of RPP and EE-RP, showing that the underlying effect sizes of the included studies in EE-RP are generally larger than in RPP, but that the sample sizes of especially the included studies in RPP are often too small to draw definite conclusions about the true effect size. We also illustrate how snapshot hybrid can be used to determine the required sample size of the replication akin to power analysis in null hypothesis significance testing and present an easy to use web application (https://rvanaert.shinyapps.io/snapshot/) and R code for applying the method. PMID:28388646

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.

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 comparison of methods for teaching receptive language to toddlers with autism.

PubMed

Vedora, Joseph; Grandelski, Katrina

2015-01-01

The use of a simple-conditional discrimination training procedure, in which stimuli are initially taught in isolation with no other comparison stimuli, is common in early intensive behavioral intervention programs. Researchers have suggested that this procedure may encourage the development of faulty stimulus control during training. The current study replicated previous work that compared the simple-conditional and the conditional-only methods to teach receptive labeling of pictures to young children with autism spectrum disorder. Both methods were effective, but the conditional-only method required fewer sessions to mastery. © Society for the Experimental Analysis of Behavior.

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

Replication of Heliothis virescens ascovirus in insect cell lines.

PubMed

Asgari, S

2006-09-01

Ascoviruses (AVs) infect larvae of various insect pests belonging to the family Noctuidae. The result of AV infection in the hosts is cleavage of infected cells into vesicles, a unique feature of AV infection. Since insect cell lines facilitate the study of virus life cycles, attempts were made to analyze Heliothis virescens AV (HvAV3e) infection in several cell lines and compare cell pathology to larval infection. In this study, replication and cytopathological effects of HvAV3e on four different cell lines were investigated. HvAV3e replication was confirmed in three noctuid cell lines from Spodoptera frugiperda (Sf9) and Helicoverpa zea (BCIRL-Hz-AM1 and FB33). However, the virus did not replicate in the non-noctuid insect cell line from Pieris rapae (Pieridae). Despite replication of the virus in the three permissive cell lines, the cytopathological effects of the virus were significantly different from that of larval infection.

Role of Replication and CpG Methylation in Fragile X Syndrome CGG Deletions in Primate Cells

PubMed Central

Nichol Edamura, Kerrie; Leonard, Michelle R.; Pearson, Christopher E.

2005-01-01

Instability of the fragile X CGG repeat involves both maternally derived expansions and deletions in the gametes of full-mutation males. It has also been suggested that the absence of aberrant CpG methylation may enhance repeat deletions through an unknown process. The effect of CGG tract length, DNA replication direction, location of replication initiation, and CpG methylation upon CGG stability were investigated using an SV40 primate replication system. Replication-dependant deletions with 53 CGG repeats were observed when replication was initiated proximal to the repeat, with CGG as the lagging-strand template. When we initiated replication further from the repeat, while maintaining CGG as the lagging-strand template or using CCG as the lagging-strand template, significant instability was not observed. CpG methylation of the unstable template stabilized the repeat, decreasing both the frequency and the magnitude of deletion events. Furthermore, CpG methylation slowed the efficiency of replication for all templates. Interestingly, replication forks displayed no evidence of a block at the CGG repeat tract, regardless of replication direction or CpG methylation status. Templates with 20 CGG repeats were stable under all circumstances. These results reveal that CGG deletions occur during replication and are sensitive to replication-fork dynamics, tract length, and CpG methylation. PMID:15625623

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)

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

Wakui, Yuta; Inoue, Jun; Ueno, Yoshiyuki, E-mail: yueno@mail.tains.tohoku.ac.jp

Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-{alpha}, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPAR{alpha} ligand, bezafibrate, and a PPAR{gamma} ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced themore » amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPAR{gamma}, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-{alpha}-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.« less

Failing the Future: Three Unsuccessful Attempts to Replicate Bem's ‘Retroactive Facilitation of Recall’ Effect

PubMed Central

Ritchie, Stuart J.; Wiseman, Richard; French, Christopher C.

2012-01-01

Nine recently reported parapsychological experiments appear to support the existence of precognition. We describe three pre-registered independent attempts to exactly replicate one of these experiments, ‘retroactive facilitation of recall’, which examines whether performance on a memory test can be influenced by a post-test exercise. All three replication attempts failed to produce significant effects (combined n = 150; combined p = .83, one-tailed) and thus do not support the existence of psychic ability. PMID:22432019

[Development and Application of an Overcoming Compassion Fatigue Program for Emergency Nurses].

PubMed

Kim, Yeong Ah; Park, Jeong Sook

2016-04-01

This study was conducted to develop a program to help emergency nurses overcome compassion fatigue, and to analyze the effects of the program. A nonequivalent control group pretest-posttest design was used. There were 14 participants in the experimental group and 18 subjects in the control group. The program was comprised of five, weekly 80-minute sessions including understanding and assessment of compassion fatigue, enhancing positive affect, balancing work-life, planning self care, training in relaxation techniques and cognitive restructuring, and getting social support. Research variables were ego-resiliency, compassion satisfaction and compassion fatigue of the ProQOL 5, and salivary cortisol. Data were analyzed using Chi-square test, independent t-test, and paired t-test. The first hypothesis, "There will be a difference in scores for ego resiliency between the experimental group and the control group". was not supported. The second hypothesis, "There will be a difference in scores for compassion satisfaction between the experimental group and the control group" was supported (t=2.15, p=.046). The third hypothesis, "There will be a difference in scores for compassion fatigue between the experimental group and the control group" was not supported. The first program for emergency nurses to overcome compassion fatigue in Korea was effective in increasing emergency nurses' compassion satisfaction and decreasing salivary cortisol level in the experimental group. Therefore, this program for overcoming compassion fatigue is useful to increase emergency nurses' compassion satisfaction. However replication studies of short-term intensive program reflecting emergency nurses' opinion are needed.

Endonuclease G promotes mitochondrial genome cleavage and replication

PubMed Central

Wiehe, Rahel Stefanie; Gole, Boris; Chatre, Laurent; Walther, Paul; Calzia, Enrico; Ricchetti, Miria; Wiesmüller, Lisa

2018-01-01

Endonuclease G (EndoG) is a nuclear-encoded endonuclease, mostly localised in mitochondria. In the nucleus EndoG participates in site-specific cleavage during replication stress and genome-wide DNA degradation during apoptosis. However, the impact of EndoG on mitochondrial DNA (mtDNA) metabolism is poorly understood. Here, we investigated whether EndoG is involved in the regulation of mtDNA replication and removal of aberrant copies. We applied the single-cell mitochondrial Transcription and Replication Imaging Protocol (mTRIP) and PCR-based strategies on human cells after knockdown/knockout and re-expression of EndoG. Our analysis revealed that EndoG stimulates both mtDNA replication initiation and mtDNA depletion, the two events being interlinked and dependent on EndoG's nuclease activity. Stimulation of mtDNA replication by EndoG was independent of 7S DNA processing at the replication origin. Importantly, both mtDNA-directed activities of EndoG were promoted by oxidative stress. Inhibition of base excision repair (BER) that repairs oxidative stress-induced DNA damage unveiled a pronounced effect of EndoG on mtDNA removal, reminiscent of recently discovered links between EndoG and BER in the nucleus. Altogether with the downstream effects on mitochondrial transcription, protein expression, redox status and morphology, this study demonstrates that removal of damaged mtDNA by EndoG and compensatory replication play a critical role in mitochondria homeostasis. PMID:29719607

Double silencing of relevant genes suggests the existence of the direct link between DNA replication/repair and central carbon metabolism in human fibroblasts.

PubMed

Wieczorek, Aneta; Fornalewicz, Karolina; Mocarski, Łukasz; Łyżeń, Robert; Węgrzyn, Grzegorz

2018-04-15

Genetic evidence for a link between DNA replication and glycolysis has been demonstrated a decade ago in Bacillus subtilis, where temperature-sensitive mutations in genes coding for replication proteins could be suppressed by mutations in genes of glycolytic enzymes. Then, a strong influence of dysfunctions of particular enzymes from the central carbon metabolism (CCM) on DNA replication and repair in Escherichia coli was reported. Therefore, we asked if such a link occurs only in bacteria or it is a more general phenomenon. Here, we demonstrate that effects of silencing (provoked by siRNA) of expression of genes coding for proteins involved in DNA replication and repair (primase, DNA polymerase ι, ligase IV, and topoisomerase IIIβ) on these processes (less efficient entry into the S phase of the cell cycle and decreased level of DNA synthesis) could be suppressed by silencing of specific genes of enzymes from CMM. Silencing of other pairs of replication/repair and CMM genes resulted in enhancement of the negative effects of lower expression levels of replication/repair genes. We suggest that these results may be proposed as a genetic evidence for the link between DNA replication/repair and CMM in human cells, indicating that it is a common biological phenomenon, occurring from bacteria to humans. Copyright © 2018 Elsevier B.V. All rights reserved.

Youth–adult partnership: exploring contributions to empowerment, agency and community connections in Malaysian youth programs.

PubMed

Krauss, Steven Eric; Collura, Jessica; Zeldin, Shepherd; Ortega, Adriana; Abdullah, Haslinda; Sulaiman, Abdul Hadi

2014-09-01

Youth–adult partnership (Y–AP) has emerged as a key practice for enacting two features of effective developmental settings: supportive adult relationships and support for efficacy and mattering. Previous studies have shown that when youth, supported by adults, actively participate in organizational and community decision making they are likely to show greater confidence and agency, empowerment and critical consciousness, and community connections. Most of the extant research on Y–AP is limited to qualitative studies and the identification of organizational best practices. Almost all research focuses on Western sociocultural settings. To address these gaps, 299 youth, age 15 to 24, were sampled from established afterschool and community programs in Malaysia to explore the contribution of Y–AP (operationalized as having two components: youth voice in decision-making and supportive adult relationships) to empowerment, agency and community connections. As hypothesized, hierarchical regressions indicated that program quality (Y–AP, safe environment and program engagement) contributed to agency, empowerment and community connections beyond the contribution of family, school and religion. Additionally, the Y–AP measures contributed substantially more variance than the other measures of program quality on each outcome. Interaction effects indicated differences by age for empowerment and agency but not for community connections. The primary findings in this inquiry replicate those found in previous interview and observational-oriented studies. The data suggests fertile ground for future research while demonstrating that Y–AP may be an effective practice for positive youth development outside of Western settings.

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.

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.

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.

Building Sustainable Professional Development Programs: Applying Strategies From Implementation Science to Translate Evidence Into Practice.

PubMed

Baldwin, Constance D; Chandran, Latha; Gusic, Maryellen E

2017-01-01

Multisite and national professional development (PD) programs for educators are challenging to establish. Use of implementation science (IS) frameworks designed to convert evidence-based intervention methods into effective health care practice may help PD developers translate proven educational methods and models into successful, well-run programs. Implementation of the national Educational Scholars Program (ESP) is used to illustrate the value of the IS model. Four adaptable elements of IS are described: (1) replication of an evidence-based model, (2) systematic stages of implementation, (3) management of implementation using three implementation drivers, and (4) demonstration of program success through measures of fidelity to proven models and sustainability. Implementation of the ESP was grounded on five established principles and methods for successful PD. The process was conducted in four IS stages over 10 years: Exploration, Installation, Initial Implementation, and Full Implementation. To ensure effective and efficient processes, attention to IS implementation drivers helped to manage organizational relationships, build competence in faculty and scholars, and address leadership challenges. We describe the ESP's fidelity to evidence-based structures and methods, and offer three examples of sustainability efforts that enabled achievement of targeted program outcomes, including academic productivity, strong networking, and career advancement of scholars. Application of IS frameworks to program implementation may help other PD programs to translate evidence-based methods into interventions with enhanced impact. A PD program can follow systematic developmental stages and be operationalized by practical implementation drivers, thereby creating successful and sustainable interventions that promote the academic vitality of health professions educators.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases.

PubMed

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and "others"). We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and "true" effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains.

Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

PubMed Central

Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

2016-01-01

Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains. PMID:27336301

Building Evidence in Early Childhood Special Education: A Systematic Review of Replication Intervention Studies

ERIC Educational Resources Information Center

Banerjee, Rashida; Movahedazarhouligh, Sara; Millen, Kaitlyn; Luckner, John L.

2018-01-01

Valid and evidence-informed practices are critical to help young children with disabilities and their families with highly effective interventions and instruction to reach their potentials. Replication research is critical for appraising research and identifying evidence-based practices. The purpose of this study was to replicate the methods used…

Metabolism Goes Viral

PubMed Central

Miyake-Stoner, Shigeki J.; O’Shea, Clodagh C.

2014-01-01

Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. PMID:24703688

Controlled Experiment Replication in Evaluation of E-Learning System's Educational Influence

ERIC Educational Resources Information Center

Grubisic, Ani; Stankov, Slavomir; Rosic, Marko; Zitko, Branko

2009-01-01

We believe that every effectiveness evaluation should be replicated at least in order to verify the original results and to indicate evaluated e-learning system's advantages or disadvantages. This paper presents the methodology for conducting controlled experiment replication, as well as, results of a controlled experiment and an internal…

Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

PubMed

Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

2014-01-01

Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Hepatitis B virus (HBV)-specific short hairpin RNA is capable of reducing the formation of HBV covalently closed circular (CCC) DNA but has no effect on established CCC DNA in vitro.

PubMed

Starkey, Jason L; Chiari, Estelle F; Isom, Harriet C

2009-01-01

Hepatitis B virus (HBV) covalently closed circular (CCC) DNA is the source of HBV transcripts and persistence in chronically infected patients. The novel aspect of this study was to determine the effect of RNA interference (RNAi) on HBV CCC DNA when administered prior to establishment of HBV replication or during chronic HBV infection. HBV replication was initiated in HepG2 cells by transduction with HBV baculovirus. Subculture of HBV-expressing HepG2 cells at 10 days post-transduction generates a system in which HBV replication is ongoing and HBV is expressed largely from CCC DNA, thus simulating chronic HBV infection. HepG2 cells were transduced with short hairpin RNA (shRNA)-expressing baculovirus prior to initiation of HBV replication or during chronic HBV replication, and the levels of HBV RNA, HBV surface antigens (HBsAg) and replicative intermediates (RI), extracellular (EC) and CCC DNA species were measured. HBsAg, HBV RNA and DNA levels were markedly reduced until day 8 whether cells were transduced with shRNA prior to or during a chronic infection; however, the CCC DNA species were only affected when shRNA was administered prior to initiation of infection. We conclude that RNAi may have a therapeutic value for controlling HBV replication at the level of RI and EC DNA and for reducing establishment of CCC DNA during HBV infection. Our data support previous findings demonstrating the stability of HBV CCC DNA following antiviral therapy. This study also reports the development of a novel HBV baculovirus subculture system that can be used to evaluate antiviral effects on chronic HBV replication.

Effective/efficient mental health programs for school-age children: a synthesis of reviews.

PubMed

Browne, Gina; Gafni, Amiram; Roberts, Jacqueline; Byrne, Carolyn; Majumdar, Basanti

2004-04-01

The prevalence of mental health problems, some of which seem to be occurring among younger cohorts, leads researchers and policy-makers to search for practical solutions to reduce the burden of suffering on children and their families, and the costs to society both immediate and long term. Numerous programs are in place to reduce or alleviate problem behaviour or disorders and/or assist positive youth development. Evaluated results are dispersed throughout the literature. To assess findings and determine common elements of effective children's services, a literature search was undertaken for evidence-based evaluations of non-clinical programs for school-age children. Prescriptive comments aim to inform service-providers, policy-makers and families about best practices for effective services such as: early, long-term intervention including reinforcement, follow-up and an ecological focus with family and community sector involvement; consistent adult staffing; and interactive, non-didactic programming adapted to gender, age and cultural needs. Gaps are identified in our understanding of efficiencies that result from effective programs. Policy implications include the need to develop strategies for intersectoral interventions, including: new financing arrangements to encourage (not penalize) interagency cooperation and, to ensure services reach appropriate segments of the population; replication of best practices; and publicizing information about benefits and cost savings. In many jurisdictions legislative changes could create incentives for services to collaborate on service delivery. Joint decision-making would require intersectoral governance, pooling of some funding, and policy changes to retain savings at the local level. Savings could finance expansion of services for additional youth.

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

Replication and characterization of the compound eye of a fruit fly for imaging purpose

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

Li, Hefu; University of Chinese Academy of Sciences, Beijing 10039; Gong, Xianwei

In this work, we report the replication and characterization of the compound eye of a fruit fly for imaging purpose. In the replication, soft lithography method was employed to replicate the compound eye of a fruit fly into a UV-curable polymer. The method was demonstrated to be effective and the compound eye is replicated into the polymer (NOA78) where each ommatidium has a diameter of about 30 μm and a sag height of about 7 μm. To characterize its optical property, the point spread function of the compound eye was tested and a NA of 0.386 has been obtained for the replicatedmore » polymeric ommatidium. Comparing with the NA of a real fruit fly ommatidium which was measured to be about 0.212, the replicated polymeric ommatidium has a much larger NA due to the refractive index of NOA78 is much higher than that of the material used to form the real fruit fly ommatidium. Furthermore, the replicated compound eye was used to image a photomask patterned with grating structures to test its imaging property. It is shown that the grating with a line width of 20 μm can be clearly imaged. The image of the grating formed by the replicated compound eye was shrunk by about 10 times and therefore a line width of about 2.2 μm in the image plane has been obtained, which is close to the diffraction limited resolution calculated through the measured NA. In summary, the replication method demonstrated is effective and the replicated compound eye has the great potential in optical imaging.« less

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.

Antiviral effects of artesunate on polyomavirus BK replication in primary human kidney cells.

PubMed

Sharma, Biswa Nath; Marschall, Manfred; Henriksen, Stian; Rinaldo, Christine Hanssen

2014-01-01

Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2'-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G0 or G2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions.

Antiviral Effects of Artesunate on Polyomavirus BK Replication in Primary Human Kidney Cells

PubMed Central

Sharma, Biswa Nath; Marschall, Manfred; Henriksen, Stian

2014-01-01

Polyomavirus BK (BKV) causes polyomavirus-associated nephropathy (PyVAN) and hemorrhagic cystitis (PyVHC) in renal and bone marrow transplant patients, respectively. Antiviral drugs with targeted activity against BKV are lacking. Since the antimalarial drug artesunate was recently demonstrated to have antiviral activity, the possible effects of artesunate on BKV replication in human primary renal proximal tubular epithelial cells (RPTECs), the host cells in PyVAN, were explored. At 2 h postinfection (hpi), RPTECs were treated with artesunate at concentrations ranging from 0.3 to 80 μM. After one viral replication cycle (approximately 72 hpi), the loads of extracellular BKV DNA, reflecting viral progeny production, were reduced in a concentration-dependent manner. Artesunate at 10 μM reduced the extracellular BKV load by 65%; early large T antigen mRNA and protein expression by 30% and 75%, respectively; DNA replication by 73%; and late VP1 mRNA and protein expression by 47% and 64%, respectively. Importantly, the proliferation of RPTECs was also inhibited in a concentration-dependent manner. At 72 hpi, artesunate at 10 μM reduced cellular DNA replication by 68% and total metabolic activity by 47%. Cell impedance and lactate dehydrogenase measurements indicated a cytostatic but not a cytotoxic mechanism. Flow cytometry and 5-ethynyl-2′-deoxyuridine incorporation revealed a decreased number of cells in S phase and suggested cell cycle arrest in G0 or G2 phase. Both the antiproliferative and antiviral effects of artesunate at 10 μM were reversible. Thus, artesunate inhibits BKV replication in RPTECs in a concentration-dependent manner by inhibiting BKV gene expression and genome replication. The antiviral mechanism appears to be closely connected to cytostatic effects on the host cell, underscoring the dependence of BKV on host cell proliferative functions. PMID:24145549

Replication RCT of Early Universal Prevention Effects on Young Adult Substance Misuse

PubMed Central

Spoth, Richard; Trudeau, Linda; Redmond, Cleve; Shin, Chungyeol

2014-01-01

Objective For many substances, more frequent and problematic use occurs in young adulthood; these types of use are predicted by the timing of initiation during adolescence. We replicated and extended an earlier study examining whether delayed substance initiation during adolescence, resulting from universal preventive interventions implemented in middle school, reduces problematic use in young adulthood. Method Participants were middle school students from 36 Iowa schools randomly assigned to the Strengthening Families Program plus Life Skills Training (SFP 10–14 + LST), LST-only, or a control condition. Self-report questionnaires were collected at 11 time points, including four during young adulthood. The intercept (average level) and rate of change (slope) in young adult frequency measures (drunkenness, alcohol-related problems, cigarettes, and illicit drugs) across ages 19–22 were modeled as outcomes influenced by growth factors describing substance initiation during adolescence. Analyses entailed testing a two-step hierarchical latent growth curve model; models included the effects of baseline risk, intervention condition assignment, and their interaction. Results Analyses showed significant indirect intervention effects on the average levels of all young adult outcomes, through effects on adolescent substance initiation growth factors, along with intervention by risk interaction effects favoring the higher-risk subsample. Additional direct effects on young adult use were observed in some cases. Relative reduction rates were larger for the higher-risk subsample at age 22, ranging from 5.8% to 36.4% on outcomes showing significant intervention effects. Conclusions Universal preventive interventions implemented during early adolescence have the potential to decrease the rates of substance use and associated problems, into young adulthood. PMID:24821095

Empiric validation of a process for behavior change.

PubMed

Elliot, Diane L; Goldberg, Linn; MacKinnon, David P; Ranby, Krista W; Kuehl, Kerry S; Moe, Esther L

2016-09-01

Most behavior change trials focus on outcomes rather than deconstructing how those outcomes related to programmatic theoretical underpinnings and intervention components. In this report, the process of change is compared for three evidence-based programs' that shared theories, intervention elements and potential mediating variables. Each investigation was a randomized trial that assessed pre- and post- intervention variables using survey constructs with established reliability. Each also used mediation analyses to define relationships. The findings were combined using a pattern matching approach. Surprisingly, knowledge was a significant mediator in each program (a and b path effects [p<0.01]). Norms, perceived control abilities, and self-monitoring were confirmed in at least two studies (p<0.01 for each). Replication of findings across studies with a common design but varied populations provides a robust validation of the theory and processes of an effective intervention. Combined findings also demonstrate a means to substantiate process aspects and theoretical models to advance understanding of behavior change.

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.

Why are Tailored Messages More Effective? A Multiple Mediation Analysis of a Breast Cancer Screening Intervention.

PubMed

Jensen, Jakob D; King, Andy J; Carcioppolo, Nicholas; Davis, LaShara

2012-10-01

Past research has found that tailoring increases the persuasive effectiveness of a message. However, the observed effect has been small and the explanatory mechanism remains unknown. To address these shortcomings, a tailoring software program was created that personalized breast cancer screening pamphlets according to risk, health belief model constructs, and visual preference. Women aged 40 and older ( N = 119) participated in a 2 (tailored vs. stock message) × 2 (charts/graphs vs. illustrated visuals) × 3 (nested replications of the visuals) experiment. Participants provided with tailored illustrated pamphlets expressed greater breast cancer screening intentions than those provided with other pamphlets. In a test of 10 different mediators, perceived message relevance was found to fully mediate the tailoring × visual interaction.

Update and expansion of the HIV/AIDS prevention program archive (HAPPA)

PubMed Central

Card, Josefina J.; Cunningham, Shayna D.; Newman, Emily N.; Golden, Rachel E.

2017-01-01

Established in 1996 with funding from CDC and NIH, the HIV/AIDS Prevention Program Archive (HAPPA) is now the biggest private sector collection of HIV-related evidence-based behavioral interventions (EBIs). Each EBI in HAPPA has been determined by a distinguished Scientist Expert Panel to have demonstrated efficacy in preventing HIV or its risk-related behaviors in the United States. The multimedia replications kits contain everything that a new site would need to implement an EBI such as a user guide that gives an overview of the program and the evidence of its effectiveness; a facilitator’s manual that gives step-by-step implementation protocols for each session; and session implementation materials referenced in the facilitator's manual such as slides, video clips, participant handouts, activity masters, checklists, and homework assignments for the next session. The program packages also contain evaluation materials such as surveys and questionnaires that were used in the original demonstration of effectiveness and that may be used to re-evaluate the program as implemented in a new setting. Recently, we have expanded HAPPA’s scope to include HIV EBIs developed globally and to include evidence-based structural interventions (effective in modifying the physical, social, cultural, political, economic, legal, and/or policy aspects of the HIV risk environment). This paper describes HAPPA’s procedures for identifying, selecting, acquiring and packaging HIV EBIs. It also provides comprehensive lists of evidence-based HIV behavioral and structural interventions and gives information on how to access EBI program packages for implementation in new settings. PMID:28781971

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

PubMed

Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

2004-09-15

The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development of antiviral strategies utilizing non-psychoactive derivatives of THC.

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.

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.

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)

DNA replication machinery is required for development in Drosophila.

PubMed

Kohzaki, Hidetsugu; Asano, Maki; Murakami, Yota

2018-01-01

 In Drosophila , some factors involved in chromosome replication seem to be involved in gene amplification and endoreplication, which are actively utilized in particular tissue development, but direct evidence has not been shown. Therefore, we examined the effect of depletion of replication factors on these processes. First, we confirmed RNAi knockdown can be used for the depletion of replication factors by comparing the phenotypes of RNAi knockdown and deletion or point mutants of the components of DNA licensing factor, MCM2, MCM4 and Cdt1. Next, we found that tissue-specific RNAi knockdown of replication factors caused tissue-specific defects, probably due to defects in DNA replication. In particular, we found that depletion inhibited gene amplification of the chorion gene in follicle cells and endoreplication in salivary glands, showing that chromosomal DNA replication factors are required for these processes. Finally, using RNAi, we screened the genes for chromosomal DNA replication that affected tissue development. Interestingly, wing specific knockdown of Mcm10 induced wing formation defects. These results suggest that some components of chromosomal replication machinery are directly involved in tissue development.

Development of a Novel Anti-HIV-1 Agent from within: Effect of Chimeric Vpr-Containing Protease Cleavage Site Residues on Virus Replication

NASA Astrophysics Data System (ADS)

Serio, D.; Rizvi, T. A.; Cartas, M.; Kalyanaraman, V. S.; Weber, I. T.; Koprowski, H.; Srinivasan, A.

1997-04-01

Effective antiviral agents will be of great value in controlling virus replication and delaying the onset of HIV-1-related disease symptoms. Current therapy involves the use of antiviral agents that target the enzymatic functions of the virus, resulting in the emergence of resistant viruses to these agents, thus lowering their effectiveness. To overcome this problem, we have considered the idea of developing novel agents from within HIV-1 as inhibitors of virus replication. The specificity of the Vpr protein for the HIV-1 virus particle makes it an attractive molecule for the development of antiviral agents targeting the events associated with virus maturation. We have generated chimeric Vpr proteins containing HIV-1-specific sequences added to the C terminus of Vpr. These sequences correspond to nine cleavage sites of the Gag and Gag-Pol precursors of HIV-1. The chimeric Vpr constructs were introduced into HIV-1 proviral DNA to assess their effect on virus infectivity using single- and multiple-round replication assays. The virus particles generated exhibited a variable replication pattern depending on the protease cleavage site used as a fusion partner. Interestingly, the chimeric Vpr containing the cleavage sequences from the junction of p24 and p2, 24/2, completely abolished virus infectivity. These results show that chimeric proteins generated from within HIV-1 have the ability to suppress HIV-1 replication and make ideal agents for gene therapy or intracellular immunization to treat HIV-1 infection.

Flexibility of nucleic acids: From DNA to RNA

NASA Astrophysics Data System (ADS)

Lei, Bao; Xi, Zhang; Lei, Jin; Zhi-Jie, Tan

2016-01-01

The structural flexibility of nucleic acids plays a key role in many fundamental life processes, such as gene replication and expression, DNA-protein recognition, and gene regulation. To obtain a thorough understanding of nucleic acid flexibility, extensive studies have been performed using various experimental methods and theoretical models. In this review, we will introduce the progress that has been made in understanding the flexibility of nucleic acids including DNAs and RNAs, and will emphasize the experimental findings and the effects of salt, temperature, and sequence. Finally, we will discuss the major unanswered questions in understanding the flexibility of nucleic acids. Project supported by the National Basic Research Program of China (Grant No. 2011CB933600), the National Natural Science Foundation of China (Grant Nos. 11175132, 11575128, and 11374234), and the Program for New Century Excellent Talents, China (Grant No. NCET 08-0408).

A Randomized Controlled Trial to Improve Social Skills in Young Adults with Autism Spectrum Disorder: The UCLA PEERS(®) Program.

PubMed

Laugeson, Elizabeth A; Gantman, Alexander; Kapp, Steven K; Orenski, Kaely; Ellingsen, Ruth

2015-12-01

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 adults with ASD. Using a randomized controlled design, 22 young adults 18-24 years of age were randomly assigned to a treatment (n = 12) or delayed treatment control (n = 10) group. Results revealed that the treatment group improved significantly in overall social skills, frequency of social engagement, and social skills knowledge, and significantly reduced ASD symptoms related to social responsiveness following PEERS. Most treatment gains were maintained at a 16-week follow-up assessment with new improvements observed.

H3K9me3 demethylase Kdm4d facilitates the formation of pre-initiative complex and regulates DNA replication

PubMed Central

Wu, Rentian; Wang, Zhiquan; Zhang, Honglian; Gan, Haiyun; Zhang, Zhiguo

2017-01-01

DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase δ, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex. PMID:27679476

The mammalian INO80 chromatin remodeling complex is required for replication stress recovery

PubMed Central

Vassileva, Ivelina; Yanakieva, Iskra; Peycheva, Michaela; Gospodinov, Anastas; Anachkova, Boyka

2014-01-01

A number of studies have implicated the yeast INO80 chromatin remodeling complex in DNA replication, but the function of the human INO80 complex during S phase remains poorly understood. Here, we have systematically investigated the involvement of the catalytic subunit of the human INO80 complex during unchallenged replication and under replication stress by following the effects of its depletion on cell survival, S-phase checkpoint activation, the fate of individual replication forks, and the consequences of fork collapse. We report that INO80 was specifically needed for efficient replication elongation, while it was not required for initiation of replication. In the absence of the Ino80 protein, cells became hypersensitive to hydroxyurea and displayed hyperactive ATR-Chk1 signaling. Using bulk and fiber labeling of DNA, we found that cells deficient for Ino80 and Arp8 had impaired replication restart after treatment with replication inhibitors and accumulated double-strand breaks as evidenced by the formation of γ-H2AX and Rad51 foci. These data indicate that under conditions of replication stress mammalian INO80 protects stalled forks from collapsing and allows their subsequent restart. PMID:25016522

[The effects of TorR protein on initiation of DNA replication in Escherichia coli].

PubMed

Yuan, Yao; Jiaxin, Qiao; Jing, Li; Hui, Li; Morigen, Morigen

2015-03-01

The two-component systems, which could sense and respond to environmental changes, widely exist in bacteria as a signal transduction pathway. The bacterial CckA/CtrA, ArcA/ArcB and PhoP/PhoQ two-component systems are associated with initiation of DNA replication and cell division, however, the effects of the TorS/TorR system on cell cycle and DNA replication remains unknown. The TorS/TorR system in Escherichia coli can sense changes in trimethylamine oxide (TMAO) concentration around the cells. However, it is unknown if it also affects initiation of DNA replication. We detected DNA replication patterns in ΔtorS and ΔtorR mutant strains by flow cytometry. We found that the average number of replication origins (oriCs) per cell and doubling time in ΔtorS mutants were the same while the average number of oriCs in ΔtorR mutants was increased compared with that in wild-type cells. These results indicated that absence of TorR led to an earlier initiation of DNA replication than that in wild-type cells. Strangely, neither overexpression of TorR nor co-expression of TorR and TorS could restore ΔtorR mutant phenotype to the wild type. However, overexpression of SufD in both wild type and ΔtorR mutants promoted initiation of DNA replication, while mutation of SufD delayed it in ΔtorR mutants. Thus, TorR may affect initiation of DNA replication indirectly through regulating gene expression of sufD.

Inhibition of Human Immunodeficiency Virus Replication by Antisense Oligodeoxynucleotides

NASA Astrophysics Data System (ADS)

Goodchild, John; Agrawal, Sudhir; Civeira, Maria P.; Sarin, Prem S.; Sun, Daisy; Zamecnik, Paul C.

1988-08-01

Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.

The PLA2R1-JAK2 pathway upregulates ERRα and its mitochondrial program to exert tumor-suppressive action.

PubMed

Griveau, A; Devailly, G; Eberst, L; Navaratnam, N; Le Calvé, B; Ferrand, M; Faull, P; Augert, A; Dante, R; Vanacker, J M; Vindrieux, D; Bernard, D

2016-09-22

Little is known about the biological role of the phospholipase A2 receptor (PLA2R1) transmembrane protein. In recent years, PLA2R1 has been shown to have an important role in regulating tumor-suppressive responses via JAK2 activation, but the underlying mechanisms are largely undeciphered. In this study, we observed that PLA2R1 increases the mitochondrial content, judged by increased levels of numerous mitochondrial proteins, of the mitochondrial structural component cardiolipin, of the mitochondrial DNA content, and of the mitochondrial DNA replication and transcription factor TFAM. This effect of PLA2R1 relies on a transcriptional program controlled by the estrogen-related receptor alpha1 (ERRα) mitochondrial master regulator. Expression of ERRα and of its nucleus-encoded mitochondrial targets is upregulated upon PLA2R1 ectopic expression, and this effect is mediated by JAK2. Conversely, downregulation of PLA2R1 decreases the level of ERRα and of its nucleus-encoded mitochondrial targets. Finally, blocking the ERRα-controlled mitochondrial program largely inhibits the PLA2R1-induced tumor-suppressive response. Together, our data document ERRα and its mitochondrial program as downstream effectors of the PLA2R1-JAK2 pathway leading to oncosuppression.

Transforming the organizational culture of a school of nursing through innovative program development.

PubMed

Lange, Jean W; Ingersoll, Gail; Novotny, Jeanne M

2008-01-01

This article illustrates how a grant designed to promote new program development provided a vehicle for organizational transformation. The collaboration surrounding this initiative created a common focus within the school that more effectively channeled its resources and resulted in an unprecedented level of scholarly achievement and recognition. Faculty leveraged the success of this initial grant to procure additional funding for related projects. The importance of partnerships and teamwork were two valuable lessons learned. We believe that our experience is replicable in other schools of nursing interested in organizational transformation. Gibson and Barsade's model of managed change guided the project's implementation and evaluation processes. Recommendations for engaging faculty, gaining support, and developing a collaborative network are discussed in the article, with findings from a stakeholder-focused evaluation demonstrating new program goal achievement as well as the transformative changes that occurred in the organizational culture. A focused, theory-derived program plan, with comprehensive process and outcome evaluation components resulted in a major transformation of one school of nursing. Unanticipated outcomes included renewed synergy among faculty; the development of a preferred vision for the future; scholarly collaboration around a central theme that effectively channeled limited resources and dramatically increased productivity; increased regional and national recognition; and the creation of regional, national, and international partnerships.

Improvement and Optimization of Two Engineered Phage Resistance Mechanisms in Lactococcus lactis

PubMed Central

McGrath, Stephen; Fitzgerald, Gerald F.; van Sinderen, Douwe

2001-01-01

Homologous replication module genes were identified for four P335 type phages. DNA sequence analysis revealed that all four phages exhibited more than 90% DNA homology for at least two genes, designated rep2009 and orf17. One of these genes, rep2009, codes for a putative replisome organizer protein and contains an assumed origin of phage DNA replication (ori2009), which was identical for all four phages. DNA fragments representing the ori2009 sequence confer a phage-encoded resistance (Per) phenotype on lactococcal hosts when they are supplied on a high-copy-number vector. Furthermore, cloning multiple copies of the ori2009 sequence was found to increase the effectiveness of the Per phenotype conferred. A number of antisense plasmids targeting specific genes of the replication module were constructed. Two separate plasmids targeting rep2009 and orf17 were found to efficiently inhibit proliferation of all four phages by interfering with intracellular phage DNA replication. These results represent two highly effective strategies for inhibiting bacteriophage proliferation, and they also identify a novel gene, orf17, which appears to be important for phage DNA replication. Furthermore, these results indicate that although the actual mechanisms of DNA replication are very similar, if not identical, for all four phages, expression of the replication genes is significantly different in each case. PMID:11157223

Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression.

PubMed

Bernhoff, E; Gutteberg, T J; Sandvik, K; Hirsch, H H; Rinaldo, C H

2008-07-01

The human polyomavirus BK (BKV) causes nephropathy and hemorrhagic cystitis in kidney and bone marrow transplant patients, respectively. The anti-viral cidofovir (CDV) has been used in small case series but the effects on BKV replication are unclear, since polyomaviruses do not encode viral DNA polymerases. We investigated the effects of CDV on BKV(Dunlop) replication in primary human renal proximal tubule epithelial cells (RPTECs). CDV inhibited the generation of viral progeny in a dose-dependent manner yielding a 90% reduction at 40 microg/mL. Early steps such as receptor binding and entry seemed unaffected. Initial large T-antigen transcription and expression were also unaffected, but subsequent intra-cellular BKV DNA replication was reduced by >90%. Late viral mRNA and corresponding protein levels were also 90% reduced. In uninfected RPTECs, CDV 40 microg/mL reduced cellular DNA replication and metabolic activity by 7% and 11% in BrdU and WST-1 assays, respectively. BKV infection increased DNA replication to 142% and metabolic activity to 116%, respectively, which were reduced by CDV 40 microg/mL to levels of uninfected untreated RPTECs. Our results show that CDV inhibits BKV DNA replication downstream of large T-antigen expression and involves significant host cell toxicity. This should be considered in current treatment and drug development.

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

PubMed

Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

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.

Replication of Merkel cell polyomavirus induces reorganization of promyelocytic leukemia nuclear bodies.

PubMed

Neumann, Friederike; Czech-Sioli, Manja; Dobner, Thomas; Grundhoff, Adam; Schreiner, Sabrina; Fischer, Nicole

2016-11-01

Merkel cell polyomavirus (MCPyV) is associated with Merkel cell carcinoma (MCC), a rare but aggressive skin cancer. The virus is highly prevalent: 60-80 % of adults are seropositive; however, cells permissive for MCPyV infection are unknown. Consequently, very little information about the MCPyV life cycle is available. Until recently, MCPyV replication could only be studied using a semi-permissive in vitro replication system (Neumann et al., 2011; Feng et al., 2011, Schowalter et al., 2011). MCPyV replication most likely depends on subnuclear structures such as promyelocytic leukemia protein nuclear bodies (PML-NBs), which are known to play regulatory roles in the infection of many DNA viruses. Here, we investigated PML-NB components as candidate host factors to control MCPyV DNA replication. We showed that PML-NBs change in number and size in cells actively replicating MCPyV proviral DNA. We observed a significant increase in PML-NBs in cells positive for MCPyV viral DNA replication. Interestingly, a significant amount of cells actively replicating MCPyV did not show any Sp100 expression. While PML and Daxx had no effect on MCPyV DNA replication, MCPyV replication was increased in cells depleted for Sp100, strongly suggesting that Sp100 is a negative regulator of MCPyV DNA replication.

R-loop-mediated genomic instability is caused by impairment of replication fork progression

PubMed Central

Gan, Wenjian; Guan, Zhishuang; Liu, Jie; Gui, Ting; Shen, Keng; Manley, James L.; Li, Xialu

2011-01-01

Transcriptional R loops are anomalous RNA:DNA hybrids that have been detected in organisms from bacteria to humans. These structures have been shown in eukaryotes to result in DNA damage and rearrangements; however, the mechanisms underlying these effects have remained largely unknown. To investigate this, we first show that R-loop formation induces chromosomal DNA rearrangements and recombination in Escherichia coli, just as it does in eukaryotes. More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells. Our findings thus provide a direct demonstration that R-loop formation impairs DNA replication and that this is responsible for the deleterious effects of R loops on genome stability from bacteria to humans. PMID:21979917

Evaluation of an edible blue-green alga, Aphanothece sacrum, for its inhibitory effect on replication of herpes simplex virus type 2 and influenza virus type A.

PubMed

Ogura, Fumie; Hayashi, Kyoko; Lee, Jung-Bum; Kanekiyo, Kenji; Hayashi, Toshimitsu

2010-01-01

A hot-water extract of Aphanothece sacrum, an edible aquacultured blue-green alga, was found to show a remarkable inhibitory effect on the replication of enveloped viruses including herpes simplex virus type 2 (HSV-2) and influenza virus type A (IFV-A, H1N1) in vitro. The main active components were suggested to be sulfated polysaccharides in non-dialyzable portion (ASWPH). ASWPH was found to inhibit the viral adsorption to the receptor of the host cells involved in the replication process of HSV-2 and IFV-A. In addition, while the penetration stage of HSV-2 was also significantly suppressed with ASWPH, no such effect was observed in the replication of IFV-A. These results suggest that ASWPH might be useful in the prevention of infectious diseases caused by HSV-2 as well as IFV-A.

Tracing the tracks of genotoxicity by trivalent and hexavalent chromium in Drosophila melanogaster.

PubMed

Mishra, Manish; Sharma, Anurag; Negi, M P S; Dwivedi, U N; Chowdhuri, D Kar

2011-05-18

Mutagen sensitive strains (mus) in Drosophila are known for their hypersensitivity to mutagens and environmental carcinogens. Accordingly, these mutants were grouped in pre- and post-replication repair pathways. However, studying mutants belonging to one particular repair pathway may not be adequate for examining chemical-induced genotoxicity when other repair pathways may neutralize its effect. To test whether both pre-and post-replication pathways are involved and effect of Cr(III)- and Cr(VI)-induced genotoxicity in absence or presence of others, we used double mutant approach in D. melanogaster. We observed DNA damage as evident by changes in Comet assay DNA migration in cells of larvae of Oregon R(+) and single mutants of pre- (mei-9, mus201 and mus210) and post- (mei-41, mus209 and mus309) replication repair pathways and also in double mutants of different combinations (pre-pre, pre-post and post-post replication repair) exposed to increasing concentrations of Cr(VI) (0.0, 5.0, 10.0 and 20.0 μg/ml) for 48 h. The damage was greater in pre-replication repair mutants after exposure to 5.0 μg/ml Cr(VI), while effects on Oregon R(+) and post replication repair mutants were insignificant. Post-replication repair mutants revealed significant DNA damage after exposure to 20.0 μg/ml Cr(VI). Further, double mutants generated in the above repair categories were examined for DNA damage following Cr(VI) exposure and a comparison of damage was studied between single and double mutants. Combinations of double mutants generated in the pre-pre replication repair pathways showed an indifferent interaction between the two mutants after Cr(VI) exposure while a synergistic interaction was evident in exposed post-post replication repair double mutants. Cr(III) (20.0 μg/ml) exposure to these strains did not induce any significant DNA damage in their cells. The study suggests that both pre- and post-replication pathways are affected in Drosophila by Cr(VI) leading to genotoxicity, which may have consequences for metal-induced carcinogenesis. 2011 Elsevier B.V. All rights reserved.

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