Causes and Consequences of Replication Stress

PubMed Central

Zeman, Michelle K.; Cimprich, Karlene A.

2015-01-01

Replication stress is a complex phenomenon which has serious implications for genome stability, cell survival, and human disease. Generation of aberrant replication fork structures containing single-stranded DNA activates the replication stress response, primarily mediated by the kinase ATM- and Rad3-related (ATR). ATR and its downstream effectors stabilize and help to restart stalled replication forks, avoiding the generation of DNA damage and genome instability. Understanding these pathways may be key to diagnosis and treatment of human diseases caused by defective responses to replication stress. PMID:24366029

Virtual Teams in Higher Education: The Light and Dark Side

ERIC Educational Resources Information Center

Grinnell, Lynn; Sauers, Amy; Appunn, Frank; Mack, Larry

2012-01-01

Students and faculty are grappling with learning teams in the online environment - more than half of all higher education organizations offer online courses (Hoffman, 2006). As online course developers try to replicate the best practices of traditional classrooms, the asynchronous technology of the Internet has added great capability while also…

Genomic Instability in Human Pluripotent Stem Cells Arises from Replicative Stress and Chromosome Condensation Defects.

PubMed

Lamm, Noa; Ben-David, Uri; Golan-Lev, Tamar; Storchová, Zuzana; Benvenisty, Nissim; Kerem, Batsheva

2016-02-04

Human pluripotent stem cells (hPSCs) frequently acquire chromosomal aberrations such as aneuploidy in culture. These aberrations progressively increase over time and may compromise the properties and clinical utility of the cells. The underlying mechanisms that drive initial genomic instability and its continued progression are largely unknown. Here, we show that aneuploid hPSCs undergo DNA replication stress, resulting in defective chromosome condensation and segregation. Aneuploid hPSCs show altered levels of actin cytoskeletal genes controlled by the transcription factor SRF, and overexpression of SRF rescues impaired chromosome condensation and segregation defects in aneuploid hPSCs. Furthermore, SRF downregulation in diploid hPSCs induces replication stress and perturbed condensation similar to that seen in aneuploid cells. Together, these results suggest that decreased SRF expression induces replicative stress and chromosomal condensation defects that underlie the ongoing chromosomal instability seen in aneuploid hPSCs. A similar mechanism may also operate during initiation of instability in diploid cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping Cancer Cells’ Starting Lines | Center for Cancer Research

Cancer.gov

Many of the defective regulatory pathways that lead to aberrant proliferation in cancer converge on DNA replication. So replication regulatory pathways could be targeted to more specifically kill cancer cells.  Unfortunately such targeting would require knowing where and when DNA replication starts in the cancer genome.  In yeast, the locations of replication initiation sites on chromatin have been extensively mapped, but in human cancer cells only a handful of these sites have been identified.

Analyzing the dynamics of DNA replication in Mammalian cells using DNA combing.

PubMed

Bialic, Marta; Coulon, Vincent; Drac, Marjorie; Gostan, Thierry; Schwob, Etienne

2015-01-01

How cells duplicate their chromosomes is a key determinant of cell identity and genome stability. DNA replication can initiate from more than 100,000 sites distributed along mammalian chromosomes, yet a given cell uses only a subset of these origins due to inefficient origin activation and regulation by developmental or environmental cues. An impractical consequence of cell-to-cell variations in origin firing is that population-based techniques do not accurately describe how chromosomes are replicated in single cells. DNA combing is a biophysical DNA fiber stretching method which permits visualization of ongoing DNA synthesis along Mb-sized single-DNA molecules purified from cells that were previously pulse-labeled with thymidine analogues. This allows quantitative measurements of several salient features of chromosome replication dynamics, such as fork velocity, fork asymmetry, inter-origin distances, and global instant fork density. In this chapter we describe how to obtain this information from asynchronous cultures of mammalian cells.

SV40 Utilizes ATM Kinase Activity to Prevent Non-homologous End Joining of Broken Viral DNA Replication Products

PubMed Central

Sowd, Gregory A.; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L.; Fanning, Ellen

2014-01-01

Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PKcs kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PKcs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5′ to 3′ end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication. PMID:25474690

Distinct functions of human RecQ helicases during DNA replication.

PubMed

Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

2017-06-01

DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

Lamin A/C Depletion Enhances DNA Damage-Induced Stalled Replication Fork Arrest

PubMed Central

Singh, Mayank; Hunt, Clayton R.; Pandita, Raj K.; Kumar, Rakesh; Yang, Chin-Rang; Horikoshi, Nobuo; Bachoo, Robert; Serag, Sara; Story, Michael D.; Shay, Jerry W.; Powell, Simon N.; Gupta, Arun; Jeffery, Jessie; Pandita, Shruti; Chen, Benjamin P. C.; Deckbar, Dorothee; Löbrich, Markus; Yang, Qin; Khanna, Kum Kum; Worman, Howard J.

2013-01-01

The human LMNA gene encodes the essential nuclear envelope proteins lamin A and C (lamin A/C). Mutations in LMNA result in altered nuclear morphology, but how this impacts the mechanisms that maintain genomic stability is unclear. Here, we report that lamin A/C-deficient cells have a normal response to ionizing radiation but are sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with ICL agents (cisplatin, camptothecin, and mitomycin), lamin A/C-deficient cells displayed normal γ-H2AX focus formation but a higher frequency of cells with delayed γ-H2AX removal, decreased recruitment of the FANCD2 repair factor, and a higher frequency of chromosome aberrations. Similarly, following hydroxyurea-induced replication stress, lamin A/C-deficient cells had an increased frequency of cells with delayed disappearance of γ-H2AX foci and defective repair factor recruitment (Mre11, CtIP, Rad51, RPA, and FANCD2). Replicative stress also resulted in a higher frequency of chromosomal aberrations as well as defective replication restart. Taken together, the data can be interpreted to suggest that lamin A/C has a role in the restart of stalled replication forks, a prerequisite for initiation of DNA damage repair by the homologous recombination pathway, which is intact in lamin A/C-deficient cells. We propose that lamin A/C is required for maintaining genomic stability following replication fork stalling, induced by either ICL damage or replicative stress, in order to facilitate fork regression prior to DNA damage repair. PMID:23319047

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

Brandriff, B.F.; Gordon, L.A.

Human reproductive wastage is known to be a common event. One major cause of embryonic and fetal losses is chromosomal aberrations, identified by karyotyping spontaneous abortion material and in vitro fertilized human embryos. Karyotyping of human gametes has made it possible to document types and frequencies of chromosomal aberrations directly in eggs and sperm themselves. Our studies with human sperm from normal, healthy men support the view that chromosome-specific aneuploidy does in fact occur, and that frequencies of structural chromosomal aberrations appear to be person specific and stable over time. The types of structural aberrations identified suggest that normal humanmore » spermiogenesis may be vulnerable to breakage events or precursor lesions leading to such breakage events. After entry into egg cytoplasm and preceding the formation of first-cleavage mitotic chromosomes, the male as well as the female genome replicate their DNA in a pattern qualitatively similar to that in somatic cells. However, at present it is not known what relationship exists between spontaneous chromosome breaks seen at first cleavage and DNA replication activities. Limited data on survivors of radiotherapy lend support to the view that long-term effects on sperm chromosomal integrity can be identified. Studies on sperm cytogenetics thus have the potential for identifying adverse environmental effects on human spermatogenesis as monitored by this well-defined endpoint. 32 refs., 2 figs., 1 tab.« less

Human cytomegalovirus UL76 induces chromosome aberrations

PubMed Central

2009-01-01

Background Human cytomegalovirus (HCMV) is known to induce chromosome aberrations in infected cells, which can lead to congenital abnormalities in infected fetuses. HCMV UL76 belongs to a conserved protein family from herpesviruses. Some reported roles among UL76 family members include involvement in virulence determination, lytic replication, reactivation of latent virus, modulation of gene expression, induction of apoptosis, and perturbation of cell cycle progression, as well as potential nuclease activity. Previously, we have shown that stable expression of UL76 inhibits HCMV replication in glioblastoma cells. Methods To examine chromosomal integrity and the DNA damage signal γ-H2AX in cells constitutively expressing UL76, immunofluorescent cell staining and Western blotting were performed. The comet assay was employed to assess DNA breaks in cells transiently expressing UL76. Results We report that stably transfected cells expressing UL76 developed chromosome aberrations including micronuclei and misaligned chromosomes, lagging and bridging. In mitotic cells expressing UL76, aberrant spindles were increased compared to control cells. However, cells with supernumerary centrosomes were marginally increased in UL76-expressing cells relative to control cells. We further demonstrated that UL76-expressing cells activated the DNA damage signal γ-H2AX and caused foci formation in nuclei. In addition, the number of cells with DNA breaks increased in proportion to UL76 protein levels. Conclusion Our findings suggest that the virus-associated protein UL76 induces DNA damage and the accumulation of chromosome aberrations. PMID:19930723

DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

PubMed

Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

2016-06-01

A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Recruitment of DNA Replication and Damage Response Proteins to Viral Replication Centers during Infection with NS2 Mutants of Minute Virus of Mice (MVM)

PubMed Central

Ruiz, Zandra; Mihaylov, Ivailo S.; Cotmore, Susan F.; Tattersall, Peter

2010-01-01

MVM NS2 is essential for viral DNA amplification, but its mechanism of action is unknown. A classification scheme for autonomous parvovirus-associated replication (APAR) center development, based on NS1 distribution, was used to characterize abnormal APAR body maturation in NS2null mutant infections, and their organization examined for defects in host protein recruitment. Since acquisition of known replication factors appeared normal, we looked for differences in invoked DNA damage responses. We observed widespread association of H2AX/MDC1 damage response foci with viral replication centers, and sequestration and complex hyperphosphorylation of RPA32, which occurred in wildtype and mutant infections. Quantifying these responses by western transfer indicated that both wildtype and NS2 mutant MVM elicited ATM activation, while phosphorylation of ATR, already basally activated in asynchronous A9 cells, was downregulated. We conclude that MVM infection invokes multiple damage responses that influence the APAR environment, but that NS2 does not modify the recruitment of cellular proteins. PMID:21193212

Recruitment of DNA replication and damage response proteins to viral replication centers during infection with NS2 mutants of Minute Virus of Mice (MVM).

PubMed

Ruiz, Zandra; Mihaylov, Ivailo S; Cotmore, Susan F; Tattersall, Peter

2011-02-20

MVM NS2 is essential for viral DNA amplification, but its mechanism of action is unknown. A classification scheme for autonomous parvovirus-associated replication (APAR) center development, based on NS1 distribution, was used to characterize abnormal APAR body maturation in NS2null mutant infections, and their organization examined for defects in host protein recruitment. Since acquisition of known replication factors appeared normal, we looked for differences in invoked DNA damage responses. We observed widespread association of H2AX/MDC1 damage response foci with viral replication centers, and sequestration and complex hyperphosphorylation of RPA(32), which occurred in wildtype and mutant infections. Quantifying these responses by western transfer indicated that both wildtype and NS2 mutant MVM elicited ATM activation, while phosphorylation of ATR, already basally activated in asynchronous A9 cells, was downregulated. We conclude that MVM infection invokes multiple damage responses that influence the APAR environment, but that NS2 does not modify the recruitment of cellular proteins. Copyright © 2010 Elsevier Inc. All rights reserved.

Virtually-synchronous communication based on a weak failure suspector

NASA Technical Reports Server (NTRS)

Schiper, Andre; Ricciardi, Aleta

1993-01-01

Failure detectors (or, more accurately Failure Suspectors (FS)) appear to be a fundamental service upon which to build fault-tolerant, distributed applications. This paper shows that a FS with very weak semantics (i.e., that delivers failure and recovery information in no specific order) suffices to implement virtually-synchronous communication (VSC) in an asynchronous system subject to process crash failures and network partitions. The VSC paradigm is particularly useful in asynchronous systems and greatly simplifies building fault-tolerant applications that mask failures by replicating processes. We suggest a three-component architecture to implement virtually-synchronous communication: (1) at the lowest level, the FS component; (2) on top of it, a component (2a) that defines new views; and (3) a component (2b) that reliably multicasts messages within a view. The issues covered in this paper also lead to a better understanding of the various membership service semantics proposed in recent literature.

Epstein-Barr Viral Productive Amplification Reprograms Nuclear Architecture, DNA Replication and Histone Deposition

PubMed Central

Chiu, Ya-Fang; Sugden, Arthur U.; Sugden, Bill

2014-01-01

Summary The spontaneous transition of Epstein-Barr Virus (EBV) from latency to productive infection is infrequent, making its analysis in the resulting mixed cell populations difficult. We engineered cells to support this transition efficiently and developed EBV DNA variants that could be visualized and measured as fluorescent signals over multiple cell cycles. This approach revealed that EBV’s productive replication began synchronously for viral DNAs within a cell but asynchronously between cells. EBV DNA amplification was delayed until early S-phase and occurred in factories characterized by the absence of cellular DNA and histones, by a sequential redistribution of PCNA, and by localization away from the nuclear periphery. The earliest amplified DNAs lacked histones accompanying a decline in four histone chaperones. Thus, EBV transitions from being dependent on the cellular replication machinery during latency to commandeering both that machinery and nuclear structure for its own reproductive needs. PMID:24331459

ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

PubMed

Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

2016-07-15

Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria. Copyright © 2016, American Association for the Advancement of Science.

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks

PubMed Central

Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa

2016-01-01

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress. PMID:26765540

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

PubMed

Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa

2016-01-01

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.

Mechanisms and regulation of DNA replication initiation in eukaryotes

PubMed Central

Parker, Matthew W.; Botchan, Michael R.; Berger, James M.

2017-01-01

Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a given cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the Origin Recognition Complex (ORC), and subsequent activation of the helicase by incorporation into a complex known as the CMG. Recent work has begun to reveal the details of an orchestrated and sequential exchange of initiation factors on DNA that give rise to a replication-competent complex, the replisome. Here we review the molecular mechanisms that underpin eukaryotic DNA replication initiation – from selecting replication start sites to replicative helicase loading and activation – and describe how these events are often distinctly regulated across different eukaryotic model organisms. PMID:28094588

Mechanisms and regulation of DNA replication initiation in eukaryotes.

PubMed

Parker, Matthew W; Botchan, Michael R; Berger, James M

2017-04-01

Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a typical cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the origin recognition complex (ORC), and subsequent activation of the helicase by its incorporation into a complex known as the CMG. Recent work has begun to reveal the details of an orchestrated and sequential exchange of initiation factors on DNA that give rise to a replication-competent complex, the replisome. Here, we review the molecular mechanisms that underpin eukaryotic DNA replication initiation - from selecting replication start sites to replicative helicase loading and activation - and describe how these events are often distinctly regulated across different eukaryotic model organisms.

The role of ethnic identity, self-concept, and aberrant salience in psychotic-like experiences.

PubMed

Cicero, David C; Cohn, Jonathan R

2018-01-01

Social-cognitive models of psychosis suggest that aberrant salience and self-concept clarity are related to the development and maintenance of psychoticlike experiences (PLEs). People with high aberrant salience but low self-concept clarity tend to have the highest levels of PLEs. Ethnic identity may also be related to PLEs. The current research aimed to (a) replicate the interaction between aberrant salience and self-concept clarity in their association with PLEs in an ethnically diverse sample, (b) examine whether ethnic identity and aberrant salience interact in their association with PLEs, and (c) determine if self-concept clarity and ethnic identity independently interact with aberrant salience in their association with PLEs. An ethnically diverse group of undergraduates (n = 663) completed self-report measures of aberrant salience, self-concept clarity, ethnic identity, and PLEs. There was an interaction between aberrant salience and self-concept clarity such that people with high levels of aberrant salience and low levels of self-concept clarity had the highest levels of PLEs. Similarly, there was an interaction between aberrant salience and ethnic identity such that people with high aberrant salience but low ethnic identity had the highest PLEs. These interactions independently contributed to explaining variance in PLEs. This interaction was present for the Exploration but not Commitment subscales of ethnic identity. These results suggest that, in addition to low self-concept clarity, low ethnic identity may be a risk factor for the development of psychosis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of Simultaneous Radiofrequency Radiation and Chemical Exposure of Mammalian Cells. Volume 2

DTIC Science & Technology

1988-07-01

chromosome - - - - - - -I aberrations and sister chromatid exchanges (SCE). Yao (1982) exposed rat kangaroo RH5 and RH1l6 cells to 2.45 GHz radiation, and...control was reported in chromosome aberrations. Yac (1982) investigated the cytogenetic consequences of chronic microwave exposure on rat kangaroo RH5...was said to be 280C. The cells were exposed both as conidia, which are "rather inactive metabolically ," and also after DNA replication had been

Proactive Byzantine Quorum Systems

NASA Astrophysics Data System (ADS)

Alchieri, Eduardo A. P.; Bessani, Alysson Neves; Pereira, Fernando Carlos; da Silva Fraga, Joni

Byzantine Quorum Systems is a replication technique used to ensure availability and consistency of replicates data even in presence of arbitrary faults. This paper presents a Byzantine Quorum Systems protocol that provides atomic semantics despite the existence of Byzantine clients and servers. Moreover, this protocol is integrated with a protocol for proactive recovery of servers. In that way, the system tolerates any number of failures during its lifetime, since no more than f out of n servers fail during a small interval of time between recoveries. All solutions proposed in this paper can be used on asynchronous systems, which requires no time assumptions. The proposed quorum system read and write protocols have been implemented and their efficiency is demonstrated through some experiments carried out in the Emulab platform.

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.

The Rubber Hand Illusion: Feeling of Ownership and Proprioceptive Drift Do Not Go Hand in Hand

PubMed Central

Rohde, Marieke; Di Luca, Massimiliano; Ernst, Marc O.

2011-01-01

In the Rubber Hand Illusion, the feeling of ownership of a rubber hand displaced from a participant's real occluded hand is evoked by synchronously stroking both hands with paintbrushes. A change of perceived finger location towards the rubber hand (proprioceptive drift) has been reported to correlate with this illusion. To measure the time course of proprioceptive drift during the Rubber Hand Illusion, we regularly interrupted stroking (performed by robot arms) to measure perceived finger location. Measurements were made by projecting a probe dot into the field of view (using a semi-transparent mirror) and asking participants if the dot is to the left or to the right of their invisible hand (Experiment 1) or to adjust the position of the dot to that of their invisible hand (Experiment 2). We varied both the measurement frequency (every 10 s, 40 s, 120 s) and the mode of stroking (synchronous, asynchronous, just vision). Surprisingly, with frequent measurements, proprioceptive drift occurs not only in the synchronous stroking condition but also in the two control conditions (asynchronous stroking, just vision). Proprioceptive drift in the synchronous stroking condition is never higher than in the just vision condition. Only continuous exposure to asynchronous stroking prevents proprioceptive drift and thus replicates the differences in drift reported in the literature. By contrast, complementary subjective ratings (questionnaire) show that the feeling of ownership requires synchronous stroking and is not present in the asynchronous stroking condition. Thus, subjective ratings and drift are dissociated. We conclude that different mechanisms of multisensory integration are responsible for proprioceptive drift and the feeling of ownership. Proprioceptive drift relies on visuoproprioceptive integration alone, a process that is inhibited by asynchronous stroking, the most common control condition in Rubber Hand Illusion experiments. This dissociation implies that conclusions about feelings of ownership cannot be drawn from measuring proprioceptive drift alone. PMID:21738756

Elongator complex is critical for cell cycle progression and leaf patterning in Arabidopsis.

PubMed

Xu, Deyang; Huang, Weihua; Li, Yang; Wang, Hua; Huang, Hai; Cui, Xiaofeng

2012-03-01

The mitotic cell cycle in higher eukaryotes is of pivotal importance for organ growth and development. Here, we report that Elongator, an evolutionarily conserved histone acetyltransferase complex, acts as an important regulator of mitotic cell cycle to promote leaf patterning in Arabidopsis. Mutations in genes encoding Elongator subunits resulted in aberrant cell cycle progression, and the altered cell division affects leaf polarity formation. The defective cell cycle progression is caused by aberrant DNA replication and increased DNA damage, which activate the DNA replication checkpoint to arrest the cell cycle. Elongator interacts with proliferating cell nuclear antigen (PCNA) and is required for efficient histone 3 (H3) and H4 acetylation coupled with DNA replication. Levels of chromatin-bound H3K56Ac and H4K5Ac known to associate with replicons during DNA replication were reduced in the mutants of both Elongator and chromatin assembly factor 1 (CAF-1), another protein complex that physically interacts with PCNA for DNA replication-coupled chromatin assembly. Disruptions of CAF-1 also led to severe leaf polarity defects, which indicated that Elongator and CAF-1 act, at least partially, in the same pathway to promote cell cycle progression. Collectively, our results demonstrate that Elongator is an important regulator of mitotic cell cycle, and the Elongator pathway plays critical roles in promoting leaf polarity formation. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony.

PubMed

Ganter, Markus; Goldberg, Jonathan M; Dvorin, Jeffrey D; Paulo, Joao A; King, Jonas G; Tripathi, Abhai K; Paul, Aditya S; Yang, Jing; Coppens, Isabelle; Jiang, Rays H Y; Elsworth, Brendan; Baker, David A; Dinglasan, Rhoel R; Gygi, Steven P; Duraisingh, Manoj T

2017-02-17

Plasmodium parasites, the causative agents of malaria, have evolved a unique cell division cycle in the clinically relevant asexual blood stage of infection 1 . DNA replication commences approximately halfway through the intracellular development following invasion and parasite growth. The schizont stage is associated with multiple rounds of DNA replication and nuclear division without cytokinesis, resulting in a multinucleated cell. Nuclei divide asynchronously through schizogony, with only the final round of DNA replication and segregation being synchronous and coordinated with daughter cell assembly 2,3 . However, the control mechanisms for this divergent mode of replication are unknown. Here, we show that the Plasmodium-specific kinase PfCRK4 is a key cell-cycle regulator that orchestrates multiple rounds of DNA replication throughout schizogony in Plasmodium falciparum. PfCRK4 depletion led to a complete block in nuclear division and profoundly inhibited DNA replication. Quantitative phosphoproteomic profiling identified a set of PfCRK4-regulated phosphoproteins with greatest functional similarity to CDK2 substrates, particularly proteins involved in the origin of replication firing. PfCRK4 was required for initial and subsequent rounds of DNA replication during schizogony and, in addition, was essential for development in the mosquito vector. Our results identified an essential S-phase promoting factor of the unconventional P. falciparum cell cycle. PfCRK4 is required for both a prolonged period of the intraerythrocytic stage of Plasmodium infection, as well as for transmission, revealing a broad window for PfCRK4-targeted chemotherapeutics.

Rescue of replication failure by Fanconi anaemia proteins.

PubMed

Constantinou, Angelos

2012-02-01

Chromosomal aberrations are often associated with incomplete genome duplication, for instance at common fragile sites, or as a consequence of chemical alterations in the DNA template that block replication forks. Studies of the cancer-prone disease Fanconi anaemia (FA) have provided important insights into the resolution of replication problems. The repair of interstrand DNA crosslinks induced by chemotherapy drugs is coupled with DNA replication and controlled by FA proteins. We discuss here the recent discovery of new FA-associated proteins and the development of new tractable repair systems that have dramatically improved our understanding of crosslink repair. We focus also on how FA proteins protect against replication failure in the context of fragile sites and on the identification of reactive metabolites that account for the development of Fanconi anaemia symptoms.

Microenvironmental cooperation promotes early spread and bistability of a Warburg-like phenotype.

PubMed

Fernandez-de-Cossio-Diaz, Jorge; De Martino, Andrea; Mulet, Roberto

2017-06-08

We introduce an in silico model for the initial spread of an aberrant phenotype with Warburg-like overflow metabolism within a healthy homeostatic tissue in contact with a nutrient reservoir (the blood), aimed at characterizing the role of the microenvironment for aberrant growth. Accounting for cellular metabolic activity, competition for nutrients, spatial diffusion and their feedbacks on aberrant replication and death rates, we obtain a phase portrait where distinct asymptotic whole-tissue states are found upon varying the tissue-blood turnover rate and the level of blood-borne primary nutrient. Over a broad range of parameters, the spreading dynamics is bistable as random fluctuations can impact the final state of the tissue. Such a behaviour turns out to be linked to the re-cycling of overflow products by non-aberrant cells. Quantitative insight on the overall emerging picture is provided by a spatially homogeneous version of the model.

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

PubMed Central

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

2010-01-01

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

Measuring moment-to-moment pilot workload using synchronous presentations of secondary tasks in a motion-base trainer

NASA Technical Reports Server (NTRS)

Bortolussi, Michael R.; Hart, Sandra G.; Shively, Robert J.

1987-01-01

A simulation was conducted to determine whether the sensitivity of secondary task measures of pilot workload could be improved by synchronizing their presentation to the occurrence of specific events or pilot actions. This synchronous method of presentation was compared to the more typical asynchronous method, where secondary task presentations are independent of pilot's flight-related activities. Twelve pilots flew low- and high-difficulty scenarios in a motion-base trainer with and without concurrent secondary tasks (e.g., choice reaction time and time production). The difficulty of each scenario was manipulated by the addition of 21 flight-related tasks superimposed on a standard approach and landing sequence. The insertion of the secondary tasks did not affect primary flight performance. However, secondary task performance did reflect workload differences between scenarios and among flight segments within scenarios, replicating the results of an earlier study in which the secondary tasks were presented asynchronously (Bortolussi et al., 1986).

Prominent mitochondrial DNA recombination intermediates in human heart muscle.

PubMed

Kajander, O A; Karhunen, P J; Holt, I J; Jacobs, H T

2001-11-01

Recombination intermediates containing four-way (Holliday) junctions are generated during DNA repair and replication in many systems, including yeast mitochondrial DNA (mtDNA). In contrast, convincing evidence for recombination in mammalian mtDNA is lacking. We have used two-dimensional agarose-gel electrophoresis to analyse non-linear forms of mtDNA in human heart muscle. Replication intermediates from both the coupled and strand-asynchronous mtDNA replication pathways were detected. An additional class of non-linear molecules, with the electrophoretic properties of four-way junctions, was also prominent. These molecules were insensitive to topoisomerase I or RNase H, but were diminished by branch migration or RuvC treatment. Junctional molecules were detected in all regions of the mitochondrial genome, were found in myocardial DNA from young and old adults, but were present at lower levels in skeletal muscle and placenta. We suggest that they could represent intermediates of mtDNA repair, given their prevalence in the oxyradical-rich environment of heart muscle mitochondria.

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

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

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

Simple and Flexible Self-Reproducing Structures in Asynchronous Cellular Automata and Their Dynamics

NASA Astrophysics Data System (ADS)

Huang, Xin; Lee, Jia; Yang, Rui-Long; Zhu, Qing-Sheng

2013-03-01

Self-reproduction on asynchronous cellular automata (ACAs) has attracted wide attention due to the evident artifacts induced by synchronous updating. Asynchronous updating, which allows cells to undergo transitions independently at random times, might be more compatible with the natural processes occurring at micro-scale, but the dark side of the coin is the increment in the complexity of an ACA in order to accomplish stable self-reproduction. This paper proposes a novel model of self-timed cellular automata (STCAs), a special type of ACAs, where unsheathed loops are able to duplicate themselves reliably in parallel. The removal of sheath cannot only allow various loops with more flexible and compact structures to replicate themselves, but also reduce the number of cell states of the STCA as compared to the previous model adopting sheathed loops [Y. Takada, T. Isokawa, F. Peper and N. Matsui, Physica D227, 26 (2007)]. The lack of sheath, on the other hand, often tends to cause much more complicated interactions among loops, when all of them struggle independently to stretch out their constructing arms at the same time. In particular, such intense collisions may even cause the emergence of a mess of twisted constructing arms in the cellular space. By using a simple and natural method, our self-reproducing loops (SRLs) are able to retract their arms successively, thereby disentangling from the mess successfully.

Discrete gene replication events drive coupling between the cell cycle and circadian clocks

PubMed Central

Paijmans, Joris; Bosman, Mark; ten Wolde, Pieter Rein; Lubensky, David K.

2016-01-01

Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push–pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene. PMID:27035936

Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

PubMed

Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

2016-04-12

Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

Aberrant and multiaberrant (rogue) cells in peripheral lymphocytes of Hodgkin's lymphoma patients after chemotherapy.

PubMed

Ryabchenko, Nikolay I; Nasonova, Valentina A; Fesenko, Eleonora V; Kondrashova, Tatiana V; Antoschina, Margarita M; Pavlov, Vyacheslav V; Ryabikina, Natalya V

2006-10-10

We analyzed spontaneous chromosome lesions in peripheral lymphocytes cultured from Hodgkin's lymphoma (HL) patients before and after cytostatic chemotherapy. The mean aberration frequency was significantly higher in HL patients after chemotherapy (7.20+/-0.58 per 100 metaphases) than in non-treated HL patients (4.80+/-0.54), and in non-treated patients than in healthy subjects (2.12+/-0.13). In lymphocytes of HL patients, who received chemotherapy, we found, in addition to ordinary aberrant cells, a large number of multiaberrant (or rogue) cells, i.e. metaphases carrying multiple (at least four) chromosome-type exchange aberrations. Rogue cells were found in 15 out of 18 chemotherapeutically treated HL patients (in total, 60 rogue cells per 5,568 scored cells), whereas in 30 non-treated patients only 1 rogue cell was found (per 4,988 scored cells). No correlation was found between the yield of rogue cells and the aberration frequency in ordinary aberrant cells. Aberration spectra (ratios of chromatid- to chromosome-type aberrations and of breaks to exchanges) were essentially different in ordinary aberrant and multiaberrant cells. These data, as well as analysis of cellular distributions of aberrations, implied independent induction of chromosome damage in ordinary aberrant and rogue cells. Analysis of aberration patterns in diploid and polyploid rogue metaphases belonging to the first, second, and third in vitro division indicated that rogue cells could be formed both in vivo and in vitro, and could survive at least two rounds of in vitro replication, given blocked chromosome segregation. These results suggested that formation of rogue cells, unlike ordinary aberrant cells, was triggered by events other than direct DNA and/or chromosome lesions. A hypothesis regarding disrupted apoptosis as a candidate mechanism for rogue cell formation seems to be most suitable for interpretation of our data. Cultured lymphocytes of chemotherapeutically treated HL patients may represent a model system for further examination of the multiaberrancy phenomenon.

Architecture and inherent robustness of a bacterial cell-cycle control system.

PubMed

Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H

2008-08-12

A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

Defective-interfering particles of the human parvovirus adeno-associated virus. [uv radiation

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

Laughlin, C.A.; Myers, M.W.; Risin, D.L.

1979-04-15

We have previously shown that adeno-associated virus (AAV) grown in KB cells with a helper adenovirus, produced several classes of particles defined by their buoyant density in CsCl. The predominant density classes were referred to as AAV(1.45), AAV(1.41), AAV (1.35), and AAV(1.32), respectively, where the density of the particle was written in the parentheses. The AAV(1.45) and AAV(1.41) particles which contained standard genomes were the only infectious AAV these infectious AAV particles exhibited autointerference. The ligh-density AAV(1.35) and (1.32) particles contained aberrant (deleted and/or snap-back) genomes. We report here experiments which show that the light-density AAV particles were noninfectious butmore » interfered with the replication of AAV(1.41). The interference was intracellular and resulted in inhibition of synthesis of standard (14.5S) AAV genomes. In some cases there was also a concomitant increase in synthesis of aberrant, shorter AAV DNA. The inhibitory activity of the light-density particles was abolished by uv irradiation. These results show that the population of light AAV particles contained DI particles. The observed autointerference of AAV(1.45) or AAV(1.41) virus is postulated to be due to AAV DI particles. Replication of AAV DI genomes appeared to require the presence of replicating, standard AAV genomes. This is interpreted to mean that progeny strand replication of AAV requires an AAV-specified product, presumably the AAV capsid protein. In contrast to standard, infectious AAV, the AAV DI particles alone do not inhibit replication of the helper adenovirus.« less

Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers

PubMed Central

Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

2015-01-01

Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks. PMID:26563448

Mutagenic consequences of a single G-quadruplex demonstrate mitotic inheritance of DNA replication fork barriers.

PubMed

Lemmens, Bennie; van Schendel, Robin; Tijsterman, Marcel

2015-11-13

Faithful DNA replication is vital to prevent disease-causing mutations, chromosomal aberrations and malignant transformation. However, accuracy conflicts with pace and flexibility and cells rely on specialized polymerases and helicases to ensure effective and timely replication of genomes that contain DNA lesions or secondary structures. If and how cells can tolerate a permanent barrier to replication is, however, unknown. Here we show that a single unresolved G-quadruplexed DNA structure can persist through multiple mitotic divisions without changing conformation. Failed replication across a G-quadruplex causes single-strand DNA gaps that give rise to DNA double-strand breaks in subsequent cell divisions, which are processed by polymerase theta (POLQ)-mediated alternative end joining. Lineage tracing experiments further reveal that persistent G-quadruplexes cause genetic heterogeneity during organ development. Our data demonstrate that a single lesion can cause multiple unique genomic rearrangements, and that alternative end joining enables cells to proliferate in the presence of mitotically inherited replication blocks.

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

Aberration hubs in protein interaction networks highlight actionable targets in cancer.

PubMed

Karimzadeh, Mehran; Jandaghi, Pouria; Papadakis, Andreas I; Trainor, Sebastian; Rung, Johan; Gonzàlez-Porta, Mar; Scelo, Ghislaine; Vasudev, Naveen S; Brazma, Alvis; Huang, Sidong; Banks, Rosamonde E; Lathrop, Mark; Najafabadi, Hamed S; Riazalhosseini, Yasser

2018-05-18

Despite efforts for extensive molecular characterization of cancer patients, such as the international cancer genome consortium (ICGC) and the cancer genome atlas (TCGA), the heterogeneous nature of cancer and our limited knowledge of the contextual function of proteins have complicated the identification of targetable genes. Here, we present Aberration Hub Analysis for Cancer (AbHAC) as a novel integrative approach to pinpoint aberration hubs, i.e. individual proteins that interact extensively with genes that show aberrant mutation or expression. Our analysis of the breast cancer data of the TCGA and the renal cancer data from the ICGC shows that aberration hubs are involved in relevant cancer pathways, including factors promoting cell cycle and DNA replication in basal-like breast tumors, and Src kinase and VEGF signaling in renal carcinoma. Moreover, our analysis uncovers novel functionally relevant and actionable targets, among which we have experimentally validated abnormal splicing of spleen tyrosine kinase as a key factor for cell proliferation in renal cancer. Thus, AbHAC provides an effective strategy to uncover novel disease factors that are only identifiable by examining mutational and expression data in the context of biological networks.

Effects of altered auditory feedback across effector systems: production of melodies by keyboard and singing.

PubMed

Pfordresher, Peter Q; Mantell, James T

2012-01-01

We report an experiment that tested whether effects of altered auditory feedback (AAF) during piano performance differ from its effects during singing. These effector systems differ with respect to the mapping between motor gestures and pitch content of auditory feedback. Whereas this action-effect mapping is highly reliable during phonation in any vocal motor task (singing or speaking), mapping between finger movements and pitch occurs only in limited situations, such as piano playing. Effects of AAF in both tasks replicated results previously found for keyboard performance (Pfordresher, 2003), in that asynchronous (delayed) feedback slowed timing whereas alterations to feedback pitch increased error rates, and the effect of asynchronous feedback was similar in magnitude across tasks. However, manipulations of feedback pitch had larger effects on singing than on keyboard production, suggesting effector-specific differences in sensitivity to action-effect mapping with respect to feedback content. These results support the view that disruption from AAF is based on abstract, effector independent, response-effect associations but that the strength of associations differs across effector systems. Copyright © 2011. Published by Elsevier B.V.

Sequential replication-coupled destruction at G1/S ensures genome stability

PubMed Central

Coleman, Kate E.; Grant, Gavin D.; Haggerty, Rachel A.; Brantley, Kristen; Shibata, Etsuko; Workman, Benjamin D.; Dutta, Anindya; Varma, Dileep; Purvis, Jeremy E.; Cook, Jeanette Gowen

2015-01-01

Timely ubiquitin-mediated protein degradation is fundamental to cell cycle control, but the precise degradation order at each cell cycle phase transition is still unclear. We investigated the degradation order among substrates of a single human E3 ubiquitin ligase, CRL4Cdt2, which mediates the S-phase degradation of key cell cycle proteins, including Cdt1, PR-Set7, and p21. Our analysis of synchronized cells and asynchronously proliferating live single cells revealed a consistent order of replication-coupled destruction during both S-phase entry and DNA repair; Cdt1 is destroyed first, whereas p21 destruction is always substantially later than that of Cdt1. These differences are attributable to the CRL4Cdt2 targeting motif known as the PIP degron, which binds DNA-loaded proliferating cell nuclear antigen (PCNADNA) and recruits CRL4Cdt2. Fusing Cdt1's PIP degron to p21 causes p21 to be destroyed nearly concurrently with Cdt1 rather than consecutively. This accelerated degradation conferred by the Cdt1 PIP degron is accompanied by more effective Cdt2 recruitment by Cdt1 even though p21 has higher affinity for PCNADNA. Importantly, cells with artificially accelerated p21 degradation display evidence of stalled replication in mid-S phase and sensitivity to replication arrest. We therefore propose that sequential degradation ensures orderly S-phase progression to avoid replication stress and genome instability. PMID:26272819

Suppression of the DHX9 Helicase Induces Premature Senescence in Human Diploid Fibroblasts in a p53-dependent Manner*

PubMed Central

Lee, Teresa; Di Paola, Domenic; Malina, Abba; Mills, John R.; Kreps, Amina; Grosse, Frank; Tang, Hengli; Zannis-Hadjopoulos, Maria; Larsson, Ola; Pelletier, Jerry

2014-01-01

DHX9 is an ATP-dependent DEXH box helicase with a multitude of cellular functions. Its ability to unwind both DNA and RNA, as well as aberrant, noncanonical polynucleotide structures, has implicated it in transcriptional and translational regulation, DNA replication and repair, and maintenance of genome stability. We report that loss of DHX9 in primary human fibroblasts results in premature senescence, a state of irreversible growth arrest. This is accompanied by morphological defects, elevation of senescence-associated β-galactosidase levels, and changes in gene expression closely resembling those encountered during replicative (telomere-dependent) senescence. Activation of the p53 signaling pathway was found to be essential to this process. ChIP analysis and investigation of nascent DNA levels revealed that DHX9 is associated with origins of replication and that its suppression leads to a reduction of DNA replication. Our results demonstrate an essential role of DHX9 in DNA replication and normal cell cycle progression. PMID:24990949

Replication asynchrony and differential condensation of X chromosomes in female platypus (Ornithorhynchus anatinus).

PubMed

Ho, Kristen K K; Deakin, Janine E; Wright, Megan L; Graves, Jennifer A Marshall; Grützner, Frank

2009-01-01

A common theme in the evolution of sex chromosomes is the massive loss of genes on the sex-specific chromosome (Y or W), leading to a gene imbalance between males (XY) and females (XX) in a male heterogametic species, or between ZZ and ZW in a female heterogametic species. Different mechanisms have evolved to compensate for this difference in dosage of X-borne genes between sexes. In therian mammals, one of the X chromosomes is inactivated, whereas bird dosage compensation is partial and gene-specific. In therian mammals, hallmarks of the inactive X are monoallelic gene expression, late DNA replication and chromatin condensation. Platypuses have five pairs of X chromosomes in females and five X and five Y chromosomes in males. Gene expression analysis suggests a more bird-like partial and gene-specific dosage compensation mechanism. We investigated replication timing and chromosome condensation of three of the five X chromosomes in female platypus. Our data suggest asynchronous replication of X-specific regions on X(1), X(3) and X(5) but show significantly different condensation between homologues for X(3) only, and not for X(1) or X(5). We discuss these results in relation to recent gene expression analysis of X-linked genes, which together give us insights into possible mechanisms of dosage compensation in platypus.

Replication of each copy of the yeast 2 micron DNA plasmid occurs during the S phase.

PubMed

Zakian, V A; Brewer, B J; Fangman, W L

1979-08-01

Saccharomyces cerevisiae contains 50-100 copies per cell of a circular plasmid called 2 micron DNA. Replication of this DNA was studied in two ways. The distribution of replication events among 2 micron DNA molecules was examined by density transfer experiments with asynchronous cultures. The data show that 2 micron DNA replication is similar to chromosomal DNA replication: essentially all 2 micron duplexes were of hybrid density at one cell doubling after the density transfer, with the majority having one fully dense strand and one fully light strand. The results show that replication of 2 micron DNA occurs by a semiconservative mechanism where each of the plasmid molecules replicates once each cell cycle. 2 micron DNA is the only known example of a multiple-copy, extrachromosomal DNA in which every molecule replicates in each cell cycle. Quantitative analysis of the data indicates that 2 micron DNA replication is limited to a fraction of the cell cycle. The period in the cell cycle when 2 micron DNA replicates was examined directly with synchronous cell cultures. Synchronization was accomplished by sequentially arresting cells in G1 phase using the yeast pheromone alpha-factor and incubating at the restrictive temperature for a cell cycle (cdc 7) mutant. Replication was monitored by adding 3H-uracil to cells previously labeled with 14C-uracil, and determining the 3H/14C ratio for purified DNA species. 2 micron DNA replication did not occur during the G1 arrest periods. However, the population of 2 micron DNA doubled during the synchronous S phase at the permissive temperature, with most of the replication occurring in the first third of S phase. Our results indicate that a mechanism exists which insures that the origin of replication of each 2 micron DNA molecule is activated each S phase. As with chromosomal DNA, further activation is prevented until the next cell cycle. We propose that the mechanism which controls the replication initiation of each 2 micron DNA molecule is identical to that which controls the initiation of chromosomal DNA.

Endonuclease EEPD1 Is a Gatekeeper for Repair of Stressed Replication Forks*

PubMed Central

Kim, Hyun-Suk; Nickoloff, Jac A.; Wu, Yuehan; Williamson, Elizabeth A.; Sidhu, Gurjit Singh; Reinert, Brian L.; Jaiswal, Aruna S.; Srinivasan, Gayathri; Patel, Bhavita; Kong, Kimi; Burma, Sandeep; Lee, Suk-Hee; Hromas, Robert A.

2017-01-01

Replication is not as continuous as once thought, with DNA damage frequently stalling replication forks. Aberrant repair of stressed replication forks can result in cell death or genome instability and resulting transformation to malignancy. Stressed replication forks are most commonly repaired via homologous recombination (HR), which begins with 5′ end resection, mediated by exonuclease complexes, one of which contains Exo1. However, Exo1 requires free 5′-DNA ends upon which to act, and these are not commonly present in non-reversed stalled replication forks. To generate a free 5′ end, stalled replication forks must therefore be cleaved. Although several candidate endonucleases have been implicated in cleavage of stalled replication forks to permit end resection, the identity of such an endonuclease remains elusive. Here we show that the 5′-endonuclease EEPD1 cleaves replication forks at the junction between the lagging parental strand and the unreplicated DNA parental double strands. This cleavage creates the structure that Exo1 requires for 5′ end resection and HR initiation. We observed that EEPD1 and Exo1 interact constitutively, and Exo1 repairs stalled replication forks poorly without EEPD1. Thus, EEPD1 performs a gatekeeper function for replication fork repair by mediating the fork cleavage that permits initiation of HR-mediated repair and restart of stressed forks. PMID:28049724

Developmental increase of asynchronic glutamate release from hippocampal synapses in mutant taiep rat.

PubMed

Fuenzalida, Marco; Aliaga, Esteban; Olivares, Virginia; Roncagliolo, Manuel; Bonansco, Christian

2009-06-01

During development, regulation of the strength of synaptic transmission plays a central role in the formation of mammalian brain circuitries. In taiep rat, a neurological mutant with severe reactive astrogliosis and demyelination, we have described alterations in the synaptic transmission in central neurons, characterized by asynchronous excitatory postsynaptic currents ((ASYN)EPSCs), because of delayed neurotransmitter release. This hippocampal synaptic dysfunction has been described in juvenile mutants, concomitantly with the appearance of their main glial alterations. However, it is unknown whether this abnormal synaptic activity is correlated with some alterations of synaptic maturation during the postnatal development. Using intracellular electrophysiological recordings and immunohistochemistry assays, we studied the maturation of CA3-CA1 synapses in taiep rats. In taiep, the number of (ASYN)EPSCs evoked by conventional stimulation of Schaffer collaterals increases with age (P7-P30) and can be evoked by stimulation of single fiber. The amplitude and frequency of spontaneous EPSC (sEPSC) increased during the postnatal development in both control and taiep rats. However, in taiep, the increase of sEPSC frequency was significantly higher than in the control rats. The frequency of miniature EPSC (mEPSC) increased over the studied age range, without differences between taiep and control rats. In both control and taiep groups, the synaptophysin immunostaining (SYP-IR) in the stratum radiatum of CA1 region was significantly lower in the juvenile (P30) than in the neonatal (P10) rats, suggesting that synaptic pruning is normally occurring in taiep, even when SYP-IR was higher in taiep than control in both ages studied. These results suggest that, in taiep mutants, the asynchronic transmission is due to a dysfunction in the glutamate release mechanisms that progressively increases during development, which is not attributable to the existence of aberrant synaptic contacts. Synapse 63:502-509, 2009. (c) 2009 Wiley-Liss, Inc.

Asynchronous accumulation of lettuce infectious yellows virus RNAs 1 and 2 and identification of an RNA 1 trans enhancer of RNA 2 accumulation.

PubMed

Yeh, H H; Tian, T; Rubio, L; Crawford, B; Falk, B W

2000-07-01

Time course and mutational analyses were used to examine the accumulation in protoplasts of progeny RNAs of the bipartite Crinivirus, Lettuce infectious yellow virus (LIYV; family Closteroviridae). Hybridization analyses showed that simultaneous inoculation of LIYV RNAs 1 and 2 resulted in asynchronous accumulation of progeny LIYV RNAs. LIYV RNA 1 progeny genomic and subgenomic RNAs could be detected in protoplasts as early as 12 h postinoculation (p.i.) and accumulated to high levels by 24 h p.i. The LIYV RNA 1 open reading frame 2 (ORF 2) subgenomic RNA was the most abundant of all LIYV RNAs detected. In contrast, RNA 2 progeny were not readily detected until ca. 36 h p.i. Mutational analyses showed that in-frame stop codons introduced into five of seven RNA 2 ORFs did not affect accumulation of progeny LIYV RNA 1 or RNA 2, confirming that RNA 2 does not encode proteins necessary for LIYV RNA replication. Mutational analyses also supported that LIYV RNA 1 encodes proteins necessary for replication of LIYV RNAs 1 and 2. A mutation introduced into the LIYV RNA 1 region encoding the overlapping ORF 1B and ORF 2 was lethal. However, mutations introduced into only LIYV RNA 1 ORF 2 resulted in accumulation of progeny RNA 1 near or equal to wild-type RNA 1. In contrast, the RNA 1 ORF 2 mutants did not efficiently support the trans accumulation of LIYV RNA 2. Three distinct RNA 1 ORF 2 mutants were analyzed and all exhibited a similar phenotype for progeny LIYV RNA accumulation. These data suggest that the LIYV RNA 1 ORF 2 encodes a trans enhancer for RNA 2 accumulation.

Asynchronous Accumulation of Lettuce Infectious Yellows Virus RNAs 1 and 2 and Identification of an RNA 1 trans Enhancer of RNA 2 Accumulation

PubMed Central

Yeh, Hsin-Hung; Tian, Tongyan; Rubio, Luis; Crawford, Brett; Falk, Bryce W.

2000-01-01

Time course and mutational analyses were used to examine the accumulation in protoplasts of progeny RNAs of the bipartite Crinivirus, Lettuce infectious yellow virus (LIYV; family Closteroviridae). Hybridization analyses showed that simultaneous inoculation of LIYV RNAs 1 and 2 resulted in asynchronous accumulation of progeny LIYV RNAs. LIYV RNA 1 progeny genomic and subgenomic RNAs could be detected in protoplasts as early as 12 h postinoculation (p.i.) and accumulated to high levels by 24 h p.i. The LIYV RNA 1 open reading frame 2 (ORF 2) subgenomic RNA was the most abundant of all LIYV RNAs detected. In contrast, RNA 2 progeny were not readily detected until ca. 36 h p.i. Mutational analyses showed that in-frame stop codons introduced into five of seven RNA 2 ORFs did not affect accumulation of progeny LIYV RNA 1 or RNA 2, confirming that RNA 2 does not encode proteins necessary for LIYV RNA replication. Mutational analyses also supported that LIYV RNA 1 encodes proteins necessary for replication of LIYV RNAs 1 and 2. A mutation introduced into the LIYV RNA 1 region encoding the overlapping ORF 1B and ORF 2 was lethal. However, mutations introduced into only LIYV RNA 1 ORF 2 resulted in accumulation of progeny RNA 1 near or equal to wild-type RNA 1. In contrast, the RNA 1 ORF 2 mutants did not efficiently support the trans accumulation of LIYV RNA 2. Three distinct RNA 1 ORF 2 mutants were analyzed and all exhibited a similar phenotype for progeny LIYV RNA accumulation. These data suggest that the LIYV RNA 1 ORF 2 encodes a trans enhancer for RNA 2 accumulation. PMID:10846054

The Competitive Interplay between Allosteric HIV-1 Integrase Inhibitor BI/D and LEDGF/p75 during the Early Stage of HIV-1 Replication Adversely Affects Inhibitor Potency.

PubMed

Feng, Lei; Dharmarajan, Venkatasubramanian; Serrao, Erik; Hoyte, Ashley; Larue, Ross C; Slaughter, Alison; Sharma, Amit; Plumb, Matthew R; Kessl, Jacques J; Fuchs, James R; Bushman, Frederic D; Engelman, Alan N; Griffin, Patrick R; Kvaratskhelia, Mamuka

2016-05-20

Allosteric HIV-1 integrase inhibitors (ALLINIs) have recently emerged as a promising class of antiretroviral agents and are currently in clinical trials. In infected cells, ALLINIs potently inhibit viral replication by impairing virus particle maturation but surprisingly exhibit a reduced EC50 for inhibiting HIV-1 integration in target cells. To better understand the reduced antiviral activity of ALLINIs during the early stage of HIV-1 replication, we investigated the competitive interplay between a potent representative ALLINI, BI/D, and LEDGF/p75 with HIV-1 integrase. While the principal binding sites of BI/D and LEDGF/p75 overlap at the integrase catalytic core domain dimer interface, we show that the inhibitor and the cellular cofactor induce markedly different multimerization patterns of full-length integrase. LEDGF/p75 stabilizes an integrase tetramer through the additional interactions with the integrase N-terminal domain, whereas BI/D induces protein-protein interactions in C-terminal segments that lead to aberrant, higher-order integrase multimerization. We demonstrate that LEDGF/p75 binds HIV-1 integrase with significantly higher affinity than BI/D and that the cellular protein is able to reverse the inhibitor induced aberrant, higher-order integrase multimerization in a dose-dependent manner in vitro. Consistent with these observations, alterations of the cellular levels of LEDGF/p75 markedly affected BI/D EC50 values during the early steps of HIV-1 replication. Furthermore, genome-wide sequencing of HIV-1 integration sites in infected cells demonstrate that LEDGF/p75-dependent integration site selection is adversely affected by BI/D treatment. Taken together, our studies elucidate structural and mechanistic details of the interplay between LEDGF/p75 and BI/D during the early stage of HIV-1 replication.

P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance.

PubMed

Loll-Krippleber, Raphael; Brown, Grant W

2017-09-15

mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.P-bodies form in response to stress and act as sites of mRNA storage and degradation. Here the authors identify the mRNA targets of P-bodies during DNA replication stress, and show that P-body proteins act to prevent toxic accumulation of these target transcripts.

pelo Is Required for High Efficiency Viral Replication

PubMed Central

Wu, Xiurong; He, Wan-Ting; Tian, Shuye; Meng, Dan; Li, Yuanyue; Chen, Wanze; Li, Lisheng; Tian, Lili; Zhong, Chuan-Qi; Han, Felicia; Chen, Jianming; Han, Jiahuai

2014-01-01

Viruses hijack host factors for their high speed protein synthesis, but information about these factors is largely unknown. In searching for genes that are involved in viral replication, we carried out a forward genetic screen for Drosophila mutants that are more resistant or sensitive to Drosophila C virus (DCV) infection-caused death, and found a virus-resistant line in which the expression of pelo gene was deficient. Our mechanistic studies excluded the viral resistance of pelo deficient flies resulting from the known Drosophila anti-viral pathways, and revealed that pelo deficiency limits the high level synthesis of the DCV capsid proteins but has no or very little effect on the expression of some other viral proteins, bulk cellular proteins, and transfected exogenous genes. The restriction of replication of other types of viruses in pelo deficient flies was also observed, suggesting pelo is required for high level production of capsids of all kinds of viruses. We show that both pelo deficiency and high level DCV protein synthesis increase aberrant 80S ribosomes, and propose that the preferential requirement of pelo for high level synthesis of viral capsids is at least partly due to the role of pelo in dissociation of stalled 80S ribosomes and clearance of aberrant viral RNA and proteins. Our data demonstrated that pelo is a host factor that is required for high efficiency translation of viral capsids and targeting pelo could be a strategy for general inhibition of viral infection. PMID:24722736

Both High-Fidelity Replicative and Low-Fidelity Y-Family Polymerases Are Involved in DNA Rereplication

PubMed Central

Sekimoto, Takayuki; Oda, Tsukasa; Kurashima, Kiminori; Hanaoka, Fumio

2014-01-01

DNA rereplication is a major form of aberrant replication that causes genomic instabilities, such as gene amplification. However, little is known about which DNA polymerases are involved in the process. Here, we report that low-fidelity Y-family polymerases (Y-Pols), Pol η, Pol ι, Pol κ, and REV1, significantly contribute to DNA synthesis during rereplication, while the replicative polymerases, Pol δ and Pol ε, play an important role in rereplication, as expected. When rereplication was induced by depletion of geminin, these polymerases were recruited to rereplication sites in human cell lines. This finding was supported by RNA interference (RNAi)-mediated knockdown of the polymerases, which suppressed rereplication induced by geminin depletion. Interestingly, epistatic analysis indicated that Y-Pols collaborate in a common pathway, independently of replicative polymerases. We also provide evidence for a catalytic role for Pol η and the involvement of Pol η and Pol κ in cyclin E-induced rereplication. Collectively, our findings indicate that, unlike normal S-phase replication, rereplication induced by geminin depletion and oncogene activation requires significant contributions of both Y-Pols and replicative polymerases. These findings offer important mechanistic insights into cancer genomic instability. PMID:25487575

A p53-independent damage-sensing mechanism that functions as a checkpoint at the G1/S transition in Chinese hamster ovary cells

PubMed Central

Lee, Hoyun; Larner, James M.; Hamlin, Joyce L.

1997-01-01

In response to a moderate dose of radiation, asynchronous mammalian cell populations rapidly and transiently down-regulate the rate of DNA synthesis to ≈50% of preirradiation values. We show here that only half of the reduction in overall replication rate can be accounted for by direct inhibition of initiation at origins in S-phase cells. The other half results from the operation of a newly defined cell cycle checkpoint that functions at the G1/S transition. This checkpoint senses damage incurred at any time during the last 2 hr of G1 and effectively prevents entry into the S period. The G1/S and S-phase checkpoints are both p53-independent and, unlike the p53-mediated G1 checkpoint, respond rapidly to radiation, suggesting that they may represent major damage-sensing mechanisms connecting the replication machinery with DNA repair pathways. PMID:9012817

Interactional synchrony and the origins of infant-mother attachment: a replication study.

PubMed

Isabella, R A; Belsky, J

1991-04-01

This study sought to replicate previous work in testing the hypothesis that interactions of dyads developing secure attachment relationships would be characterized by disproportionately synchronous and those of dyads developing insecure relationships by disproportionately asynchronous exchanges. Additionally, a priori hypotheses were tested regarding expected differences in the interactional histories of dyads developing insecure-avoidant and insecure-resistant attachments. Results supported the study's predictions in all cases. Dyads developing secure attachments were observed at 3 and 9 months to interact in a disproportionately well-timed, reciprocal, and mutually rewarding manner; dyads developing insecure relationships were disproportionately characterized by interactions in which mothers were minimally involved, unresponsive to infant signals, or intrusive. Within the insecure group, as predicted, 3- and 9-month interactions of avoidant dyads were characterized by maternal intrusiveness and overstimulation; resistant dyads were characterized at both ages by poorly coordinated interactions in which mothers were underinvolved and inconsistent. These findings are discussed as they lend to a growing body of evidence concerning associations between differential interactional histories and attachment quality.

Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX

PubMed Central

Clynes, David; Jelinska, Clare; Xella, Barbara; Ayyub, Helena; Scott, Caroline; Mitson, Matthew; Taylor, Stephen; Higgs, Douglas R.; Gibbons, Richard J.

2015-01-01

Fifteen per cent of cancers maintain telomere length independently of telomerase by the homologous recombination (HR)-associated alternative lengthening of telomeres (ALT) pathway. A unifying feature of these tumours are mutations in ATRX. Here we show that expression of ectopic ATRX triggers a suppression of the pathway and telomere shortening. Importantly ATRX-mediated ALT suppression is dependent on the histone chaperone DAXX. Re-expression of ATRX is associated with a reduction in replication fork stalling, a known trigger for HR and loss of MRN from telomeres. A G-quadruplex stabilizer partially reverses the effect of ATRX, inferring ATRX may normally facilitate replication through these sequences that, if they persist, promote ALT. We propose that defective telomere chromatinization through loss of ATRX promotes the persistence of aberrant DNA secondary structures, which in turn present a barrier to DNA replication, leading to replication fork stalling, collapse, HR and subsequent recombination-mediated telomere synthesis in ALT cancers. PMID:26143912

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis)

PubMed Central

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-01-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. PMID:25720734

Relationship between individual neuron and network spontaneous activity in developing mouse cortex.

PubMed

Barnett, Heather M; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L; Moody, William J

2014-12-15

Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407-414, 2009). In this study, we used Ca(2+) imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. Copyright © 2014 the American Physiological Society.

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

Sadowski, Greg

In one form, a logic circuit includes an asynchronous logic circuit, a synchronous logic circuit, and an interface circuit coupled between the asynchronous logic circuit and the synchronous logic circuit. The asynchronous logic circuit has a plurality of asynchronous outputs for providing a corresponding plurality of asynchronous signals. The synchronous logic circuit has a plurality of synchronous inputs corresponding to the plurality of asynchronous outputs, a stretch input for receiving a stretch signal, and a clock output for providing a clock signal. The synchronous logic circuit provides the clock signal as a periodic signal but prolongs a predetermined state ofmore » the clock signal while the stretch signal is active. The asynchronous interface detects whether metastability could occur when latching any of the plurality of the asynchronous outputs of the asynchronous logic circuit using said clock signal, and activates the stretch signal while the metastability could occur.« less

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

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

Hood, Iris V.; Berger, James M.

Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of theStaphylococcus aureusreplicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled tomore » a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.« less

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maintaining High Assurance in Asynchronous Messaging

DTIC Science & Technology

2015-10-24

Assurance in Asynchronous Messaging Kevin E. Foltz and William R. Simpson Abstract—Asynchronous messaging is the delivery of a message without... integrity , and confidentiality guarantees. End-to-end security for asynchronous messaging must be provided by the asynchronous messaging layer itself... continuing its processing. At the completion of message transmission, the sender does not know when or whether the receiver received it. The message

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

PubMed

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

2018-05-04

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

Temporal Expression of a Master Regulator Drives Synchronous Sporulation in Budding Yeast.

PubMed

Chia, Minghao; van Werven, Folkert J

2016-09-07

Yeast cells enter and undergo gametogenesis relatively asynchronously, making it technically challenging to perform stage-specific genomic and biochemical analyses. Cell-to-cell variation in the expression of the master regulator of entry into sporulation IME1, has been implicated to be the underlying cause of asynchronous sporulation. Here we find that timing of IME1 expression is of critical importance for inducing cells to undergo sporulation synchronously. When we force expression of IME1 from an inducible promoter in cells incubated in sporulation medium for two hours, the vast majority of cells exhibit synchrony during pre-meiotic DNA replication and meiotic divisions. Inducing IME1 expression too early or too late affects the synchrony of sporulation. Surprisingly, our approach for synchronous sporulation does not require growth in acetate containing medium, but can be achieved in cells grown in rich medium until saturation. Our system solely requires IME1 because the expression of the N6-methyladenosine methyltransferase IME4, another key regulator of early sporulation, is controlled by IME1 itself. The approach described here can be easily combined with other stage specific synchronization methods, and thereby applied to study specific stages of sporulation or the complete sporulation program. Copyright © 2016 Author et al.

The expanding polymerase universe.

PubMed

Goodman, M F; Tippin, B

2000-11-01

Over the past year, the number of known prokaryotic and eukaryotic DNA polymerases has exploded. Many of these newly discovered enzymes copy aberrant bases in the DNA template over which 'respectable' polymerases fear to tread. The next step is to unravel their functions, which are thought to range from error-prone copying of DNA lesions, somatic hypermutation and avoidance of skin cancer, to restarting stalled replication forks and repairing double-stranded DNA breaks.

hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ*

PubMed Central

Xu, Yang; Wu, Xiling; Her, Chengtao

2015-01-01

Replication stress from stalled or collapsed replication forks is a major challenge to genomic integrity. The anticancer agent camptothecin (CPT) is a DNA topoisomerase I inhibitor that causes fork collapse and double-strand breaks amid DNA replication. Here we report that hMSH5 promotes cell survival in response to CPT-induced DNA damage. Cells deficient in hMSH5 show elevated CPT-induced γ-H2AX and RPA2 foci with concomitant reduction of Rad51 foci, indicative of impaired homologous recombination. In addition, CPT-treated hMSH5-deficient cells exhibit aberrant activation of Chk1 and Chk2 kinases and therefore abnormal cell cycle progression. Furthermore, the hMSH5-FANCJ chromatin recruitment underlies the effects of hMSH5 on homologous recombination and Chk1 activation. Intriguingly, FANCJ depletion desensitizes hMSH5-deficient cells to CPT-elicited cell killing. Collectively, our data point to the existence of a functional interplay between hMSH5 and FANCJ in double-strand break repair induced by replication stress. PMID:26055704

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis).

PubMed

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-06-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Acceptability of an Asynchronous Learning Forum on Mobile Devices

ERIC Educational Resources Information Center

Chang, Chih-Kai

2010-01-01

Mobile learning has recently become noteworthy because mobile devices have become popular. To construct an asynchronous learning forum on mobile devices is important because an asynchronous learning forum is always an essential part of networked asynchronous distance learning. However, the input interface in handheld learning devices, which is…

The Influence of Asynchronous Video Communication on Learner Social Presence: A Narrative Analysis of Four Cases

ERIC Educational Resources Information Center

Borup, Jered; West, Richard E.; Graham, Charles R.

2013-01-01

Online courses are increasingly using asynchronous video communication. However, little is known about how asynchronous video communication influences students' communication patterns. This study presents four narratives of students with varying characteristics who engaged in asynchronous video communication. The extrovert valued the efficiency of…

Pharmacists' perception of synchronous versus asynchronous distance learning for continuing education programs.

PubMed

Buxton, Eric C

2014-02-12

To evaluate and compare pharmacists' satisfaction with the content and learning environment of a continuing education program series offered as either synchronous or asynchronous webinars. An 8-lecture series of online presentations on the topic of new drug therapies was offered to pharmacists in synchronous and asynchronous webinar formats. Participants completed a 50-question online survey at the end of the program series to evaluate their perceptions of the distance learning experience. Eighty-two participants completed the survey instrument (41 participants from the live webinar series and 41 participants from the asynchronous webinar series.) Responses indicated that while both groups were satisfied with the program content, the asynchronous group showed greater satisfaction with many aspects of the learning environment. The synchronous and asynchronous webinar participants responded positively regarding the quality of the programming and the method of delivery, but asynchronous participants rated their experience more positively overall.

Pharmacists’ Perception of Synchronous Versus Asynchronous Distance Learning for Continuing Education Programs

PubMed Central

2014-01-01

Objective. To evaluate and compare pharmacists’ satisfaction with the content and learning environment of a continuing education program series offered as either synchronous or asynchronous webinars. Methods. An 8-lecture series of online presentations on the topic of new drug therapies was offered to pharmacists in synchronous and asynchronous webinar formats. Participants completed a 50-question online survey at the end of the program series to evaluate their perceptions of the distance learning experience. Results. Eighty-two participants completed the survey instrument (41 participants from the live webinar series and 41 participants from the asynchronous webinar series.) Responses indicated that while both groups were satisfied with the program content, the asynchronous group showed greater satisfaction with many aspects of the learning environment. Conclusion. The synchronous and asynchronous webinar participants responded positively regarding the quality of the programming and the method of delivery, but asynchronous participants rated their experience more positively overall. PMID:24558276

Comparing the force ripple during asynchronous and conventional stimulation.

PubMed

Downey, Ryan J; Tate, Mark; Kawai, Hiroyuki; Dixon, Warren E

2014-10-01

Asynchronous stimulation has been shown to reduce fatigue during electrical stimulation; however, it may also exhibit a force ripple. We quantified the ripple during asynchronous and conventional single-channel transcutaneous stimulation across a range of stimulation frequencies. The ripple was measured during 5 asynchronous stimulation protocols, 2 conventional stimulation protocols, and 3 volitional contractions in 12 healthy individuals. Conventional 40 Hz and asynchronous 16 Hz stimulation were found to induce contractions that were as smooth as volitional contractions. Asynchronous 8, 10, and 12 Hz stimulation induced contractions with significant ripple. Lower stimulation frequencies can reduce fatigue; however, they may also lead to increased ripple. Future efforts should study the relationship between force ripple and the smoothness of the evoked movements in addition to the relationship between stimulation frequency and NMES-induced fatigue to elucidate an optimal stimulation frequency for asynchronous stimulation. © 2014 Wiley Periodicals, Inc.

Synchronous Office Hours in an Asynchronous Course: Making the Connection

ERIC Educational Resources Information Center

Gibbons-Kunka, Beatrice

2017-01-01

The notion of synchronous office hours in an asynchronous course seems counterintuitive. After all, one of the tenets of asynchronous education is to not require students to be online and participating at any time during the course. Having taught higher education online asynchronous courses for twenty years, the researcher experimented with online…

β2-spectrin depletion impairs DNA damage repair

PubMed Central

Horikoshi, Nobuo; Pandita, Raj K.; Mujoo, Kalpana; Hambarde, Shashank; Sharma, Dharmendra; Mattoo, Abid R.; Chakraborty, Sharmistha; Charaka, Vijaya; Hunt, Clayton R.; Pandita, Tej K.

2016-01-01

β2-Spectrin (β2SP/SPTBN1, gene SPTBN1) is a key TGF-β/SMAD3/4 adaptor and transcriptional cofactor that regulates TGF-β signaling and can contribute to liver cancer development. Here we report that cells deficient in β2-Spectrin (β2SP) are moderately sensitive to ionizing radiation (IR) and extremely sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with IR or ICL agents (formaldehyde, cisplatin, camptothecin, mitomycin), β2SP deficient cells displayed a higher frequency of cells with delayed γ-H2AX removal and a higher frequency of residual chromosome aberrations. Following hydroxyurea (HU)-induced replication stress, β2SP-deficient cells displayed delayed disappearance of γ-H2AX foci along with defective repair factor recruitment (MRE11, CtIP, RAD51, RPA, and FANCD2) as well as defective restart of stalled replication forks. Repair factor recruitment is a prerequisite for initiation of DNA damage repair by the homologous recombination (HR) pathway, which was also defective in β2SP deficient cells. We propose that β2SP is required for maintaining genomic stability following replication fork stalling, whether induced by either ICL damage or replicative stress, by facilitating fork regression as well as DNA damage repair by homologous recombination. PMID:27248179

Role of the nuclear migration protein Lis1 in cell morphogenesis in Ustilago maydis

PubMed Central

Valinluck, Michael; Ahlgren, Sara; Sawada, Mizuho; Locken, Kristopher; Banuett, Flora

2010-01-01

Ustilago maydis is a basidiomycete fungus that exhibits a yeast-like and a filamentous form. Growth of the fungus in the host leads to additional morphological transitions. The different morphologies are characterized by distinct nuclear movements. Dynein and α-tubulin are required for nuclear movements and for cell morphogenesis of the yeast-like form. Lis1 is a microtubule plus-end tracking protein (+TIPs) conserved in eukaryotes and required for nuclear migration and spindle positioning. Defects in nuclear migration result in altered cell fate and aberrant development in metazoans, slow growth in fungi and disease in humans (e.g. lissencephaly). Here we investigate the role of the human LIS1 homolog in U. maydis and demonstrate that it is essential for cell viability, not previously seen in other fungi. With a conditional null mutation we show that lis1 is necessary for nuclear migration in the yeast-like cell and during the dimorphic transition. Studies of asynchronous exponentially growing cells and time-lapse microscopy uncovered novel functions of lis1: It is necessary for cell morphogenesis, positioning of the septum and cell wall integrity. lis1-depleted cells exhibit altered axes of growth and loss of cell polarity leading to grossly aberrant cells with clusters of nuclei and morphologically altered buds devoid of nuclei. Altered septum positioning and cell wall deposition contribute to the aberrant morphology. lis1-depleted cells lyse, indicative of altered cell wall properties or composition. We also demonstrate, with indirect immunofluorescence to visualize tubulin, that lis1 is necessary for the normal organization of the microtubule cytoskeleton: lis1-depleted cells contain more and longer microtubules that can form coils perpendicular to the long axis of the cell. We propose that lis1 controls microtubule dynamics and thus the regulated delivery of vesicles to growth sites and other cell domains that govern nuclear movements. PMID:20524583

DNA polymerase-α regulates type I interferon activation through cytosolic RNA:DNA synthesis

PubMed Central

Starokadomskyy, Petro; Gemelli, Terry; Rios, Jonathan J.; Xing, Chao; Wang, Richard C.; Li, Haiying; Pokatayev, Vladislav; Dozmorov, Igor; Khan, Shaheen; Miyata, Naoteru; Fraile, Guadalupe; Raj, Prithvi; Xu, Zhe; Xu, Zigang; Ma, Lin; Lin, Zhimiao; Wang, Huijun; Yang, Yong; Ben-Amitai, Dan; Orenstein, Naama; Mussaffi, Huda; Baselga, Eulalia; Tadini, Gianluca; Grunebaum, Eyal; Sarajlija, Adrijan; Krzewski, Konrad; Wakeland, Edward K.; Yan, Nan; de la Morena, Maria Teresa; Zinn, Andrew R.; Burstein, Ezra

2016-01-01

Aberrant nucleic acids generated during viral replication are the main trigger for antiviral immunity, and mutations disrupting nucleic acid metabolism can lead to autoinflammatory disorders. Here we investigated the etiology of X-linked reticulate pigmentary disorder (XLPDR), a primary immunodeficiency with autoinflammatory features. We discovered that XLPDR is caused by an intronic mutation that disrupts expression of POLA1, the gene encoding the catalytic subunit of DNA polymerase-α. Unexpectedly, POLA1 deficiency results in increased type I interferon production. This enzyme is necessary for RNA:DNA primer synthesis during DNA replication and strikingly, POLA1 is also required for the synthesis of cytosolic RNA:DNA, which directly modulates interferon activation. Altogether, this work identified POLA1 as a critical regulator of the type I interferon response. PMID:27019227

A Phenomenological Synapse Model for Asynchronous Neurotransmitter Release

PubMed Central

Wang, Tao; Yin, Luping; Zou, Xiaolong; Shu, Yousheng; Rasch, Malte J.; Wu, Si

2016-01-01

Neurons communicate with each other via synapses. Action potentials cause release of neurotransmitters at the axon terminal. Typically, this neurotransmitter release is tightly time-locked to the arrival of an action potential and is thus called synchronous release. However, neurotransmitter release is stochastic and the rate of release of small quanta of neurotransmitters can be considerably elevated even long after the ceasing of spiking activity, leading to asynchronous release of neurotransmitters. Such asynchronous release varies for tissue and neuron types and has been shown recently to be pronounced in fast-spiking neurons. Notably, it was found that asynchronous release is enhanced in human epileptic tissue implicating a possibly important role in generating abnormal neural activity. Current neural network models for simulating and studying neural activity virtually only consider synchronous release and ignore asynchronous transmitter release. Here, we develop a phenomenological model for asynchronous neurotransmitter release, which, on one hand, captures the fundamental features of the asynchronous release process, and, on the other hand, is simple enough to be incorporated in large-size network simulations. Our proposed model is based on the well-known equations for short-term dynamical synaptic interactions and includes an additional stochastic term for modeling asynchronous release. We use experimental data obtained from inhibitory fast-spiking synapses of human epileptic tissue to fit the model parameters, and demonstrate that our model reproduces the characteristics of realistic asynchronous transmitter release. PMID:26834617

TopoIIα prevents telomere fragility and formation of ultra thin DNA bridges during mitosis through TRF1-dependent binding to telomeres.

PubMed

d'Alcontres, Martina Stagno; Palacios, Jose Alejandro; Mejias, Diego; Blasco, Maria A

2014-01-01

Telomeres are repetitive nucleoprotein structures at the ends of chromosomes. Like most genomic regions consisting of repetitive DNA, telomeres are fragile sites prone to replication fork stalling and generation of chromosomal instability. In particular, abrogation of the TRF1 telomere binding protein leads to stalled replication forks and aberrant telomere structures known as "multitelomeric signals". Here, we report that TRF1 deficiency also leads to the formation of "ultra-fine bridges" (UFB) during mitosis, and to an increased time to complete mitosis mediated by the spindle assembly checkpoint proteins (SAC). We find that topoisomerase IIα (TopoIIα), an enzyme essential for resolution of DNA replication intermediates, binds telomeres in a TRF1-mediated manner. Indeed, similar to TRF1 abrogation, TopoIIα downregulation leads to telomere fragility and UFB, suggesting that these phenotypes are due to decreased TopoIIα at telomeres. We find that SAC proteins bind telomeres in vivo, and that this is disrupted upon TRF1 deletion. These findings suggest that TRF1 links TopoIIα and SAC proteins in a pathway that ensures correct telomere replication and mitotic segregation, unveiling how TRF1 protects from telomere fragility and mitotic defects.

Human MLH1 suppresses the insertion of telomeric sequences at intra-chromosomal sites in telomerase-expressing cells

PubMed Central

Jia, Pingping; Chastain, Megan; Zou, Ying; Her, Chengtao

2017-01-01

Abstract Aberrant formation of interstitial telomeric sequences (ITSs) promotes genome instabilities. However, it is unclear how aberrant ITS formation is suppressed in human cells. Here, we report that MLH1, a key protein involved in mismatch repair (MMR), suppresses telomeric sequence insertion (TSI) at intra-chromosomal regions. The frequency of TSI can be elevated by double-strand break (DSB) inducer and abolished by ATM/ATR inhibition. Suppression of TSI requires MLH1 recruitment to DSBs, indicating that MLH1's role in DSB response/repair is important for suppressing TSI. Moreover, TSI requires telomerase activity but is independent of the functional status of p53 and Rb. Lastly, we show that TSI is associated with chromosome instabilities including chromosome loss, micronuclei formation and chromosome breakage that are further elevated by replication stress. Our studies uncover a novel link between MLH1, telomerase, telomere and genome stability. PMID:28180301

Admixture Aberration Analysis: Application to Mapping in Admixed Population Using Pooled DNA

NASA Astrophysics Data System (ADS)

Bercovici, Sivan; Geiger, Dan

Admixture mapping is a gene mapping approach used for the identification of genomic regions harboring disease susceptibility genes in the case of recently admixed populations such as African Americans. We present a novel method for admixture mapping, called admixture aberration analysis (AAA), that uses a DNA pool of affected admixed individuals. We demonstrate through simulations that AAA is a powerful and economical mapping method under a range of scenarios, capturing complex human diseases such as hypertension and end stage kidney disease. The method has a low false-positive rate and is robust to deviation from model assumptions. Finally, we apply AAA on 600 prostate cancer-affected African Americans, replicating a known risk locus. Simulation results indicate that the method can yield over 96% reduction in genotyping. Our method is implemented as a Java program called AAAmap and is freely available.

The yield of radiation-induced chromosomal aberrations in first division human lymphocytes depends on the culture time.

PubMed

Hone, P A; Edwards, A A; Lloyd, D C; Moquet, J E

2005-07-01

To investigate two long-held beliefs in radiation cytogenetics that were seemingly contradicted by reports that: (a) protracting gamma-ray exposures over 0.5 h halves the induced aberration yield compared with acute exposure, and (b) that induced aberration yields in guaranteed first in vitro division metaphases (M1) vary with culture time. Replicate blood samples were exposed for 3 min to 3.0 Gy gamma-rays and standard phytohaemagglutinin stimulated lymphocyte cultures were harvested at 10 times ranging from 45-72 h. Forty-eight hour cultures were also made from blood exposed to 3.0 Gy for 30 min. Slides were differentially stained, combining the harlequin method with fluorescent in-situ hybridization (FISH) painting of chromosomes 2, 3 and 5. M1 metaphases were scored for 1- and 2-way translocations involving the painted chromosomes and all unstable aberrations in the full genomes. Dicentric and translocation yields from the 30 min exposure were approximately 10% lower than in 48 h cultures from cells exposed for 3 min, although this reduction is not significant. Dicentric aberration yields from the 3 min exposed cells cultured over the range 45-72 h remained constant up to 51 h then rose to a different constant value beyond 60 h. The increase at 60-70 h compared with the yield at 48 h was about 50%. A marginal increase at later times was also observed for translocations. The protracted exposure experiment produced results consistent with the G-function hypothesis that models the dose rate effect. Therefore the previous report of a marked departure from this model was not confirmed. The reports of aberration yields increasing with time of arrival at metaphase were confirmed. Possible explanations are discussed; the intercellular distributions of aberrations, or of doses to the cells or heterogeneous radiosensitivity of lymphocyte sub-populations. None alone seems sufficient quantitatively to explain the magnitude of the effect. The implications for biological dosimetry, which employs cultures times of approximately 48 h, are considered to be minor.

Designing Asynchronous Communication Tools for Optimization of Patient-Clinician Coordination

PubMed Central

Eschler, Jordan; Liu, Leslie S.; Vizer, Lisa M.; McClure, Jennifer B.; Lozano, Paula; Pratt, Wanda; Ralston, James D.

2015-01-01

Asynchronous communication outside the clinical setting has both enriched and complicated patient-clinician interactions. Many patients can now interact with a patient portal 24 hours a day, asking questions of their clinicians via secure message, checking lab results, ordering medication refills, or making appointments. However, the mode of communication (asynchronous) and the nature of the interaction (lacking tone or body language) strip valuable information from each side of patient-clinician asynchronous communication. Using interviews with 34 individuals who actively manage a chronic illness of their own, or for a child or partner, we elicited narratives about patients’ experiences and expectations for using asynchronous communication to address medical issues with their clinicians. Based on these perspectives, we present opportunities for designing asynchronous communication tools to better facilitate understanding of and coordination around care activities between patients and clinicians. PMID:26958188

Asynchronous Video Streaming vs. Synchronous Videoconferencing for Teaching a Pharmacogenetic Pharmacotherapy Course

PubMed Central

2007-01-01

Objectives To compare students' performance and course evaluations for a pharmacogenetic pharmacotherapy course taught by synchronous videoconferencing method via the Internet and for the same course taught via asynchronous video streaming via the Internet. Methods In spring 2005, a pharmacogenetic therapy course was taught to 73 students located on Amarillo, Lubbock, and Dallas campuses using synchronous videoconferencing, and in spring 2006, to 78 students located on the same 3 campuses using asynchronous video streaming. A course evaluation was administered to each group at the end of the courses. Results Students in the asynchronous setting had final course grades of 89% ± 7% compared to the mean final course grade of 87% ± 7% in the synchronous group (p = 0.05). Regardless of which technology was used, average course grades did not differ significantly among the 3 campus sites. Significantly more of the students in the asynchronous setting agreed (57%) with the statement that they could read the lecture notes and absorb the content on their own without attending the class than students in the synchronous class (23%; chi-square test; p < 0.001). Conclusions Students in both asynchronous and synchronous settings performed well. However, students taught using asynchronous videotaped lectures had lower satisfaction with the method of content delivery, and preferred live interactive sessions or a mix of interactive sessions and asynchronous videos over delivery of content using the synchronous or asynchronous method alone. PMID:17429516

Genotoxicity assessment of raw and treated water samples using Allium cepa assay: evidence from Perak River, Malaysia.

PubMed

Malakahmad, Amirhossein; Manan, Teh Sabariah Binti Abd; Sivapalan, Subarna; Khan, Taimur

2018-02-01

Allium cepa assay was carried out in this study to evaluate genotoxic effects of raw and treated water samples from Perak River in Perak state, Malaysia. Samples were collected from three surface water treatment plants along the river, namely WTPP, WTPS, and WTPK. Initially, triplicates of equal size Allium cepa (onions) bulbs, 25-30 mm in diameter and average weight of 20 g, were set up in distilled water for 24 h at 20 ± 2 °C and protected from direct sunlight, to let the roots to grow. After germination of roots (0.5-1.0 cm in length), bulbs were transferred to collected water samples each for a 96-h period of exposure. The root physical deformations were observed. Genotoxicity quantification was based on mitotic index and genotoxicity level. Statistical analysis using cross-correlation function for replicates from treated water showed that root length has inverse correlation with mitotic indices (r = - 0.969) and frequencies of cell aberrations (r = - 0.976) at lag 1. Mitotic indices and cell aberrations of replicates from raw water have shown positive correlation at lag 1 (r = 0.946). Genotoxicity levels obtained were 23.4 ± 1.98 (WTPP), 26.68 ± 0.34 (WTPS), and 30.4 ± 1.13 (WTPK) for treated water and 17.8 ± 0.18 (WTPP), 37.15 ± 0.17 (WTPS), and 47.2 ± 0.48 (WTPK) for raw water. The observed cell aberrations were adherence, chromosome delay, C-metaphase, chromosome loss, chromosome bridge, chromosome breaks, binucleated cell, mini cell, and lobulated nuclei. The morphogenetic deformations obtained were likely due to genotoxic substances presence in collected water samples. Thus, water treatment in Malaysia does not remove genotoxic compounds.

TGMS in Rapeseed (Brassica napus) Resulted in Aberrant Transcriptional Regulation, Asynchronous Microsporocyte Meiosis, Defective Tapetum, and Fused Sexine

PubMed Central

Liu, Xi-Qiong; Liu, Zhi-Quan; Yu, Cheng-Yu; Dong, Jun-Gang; Hu, Sheng-Wu; Xu, Ai-Xia

2017-01-01

The thermo-sensitive genic male sterility (TGMS) line SP2S is a spontaneous rapeseed mutation with several traits that are favorable for the production of two-line hybrids. To uncover the key cellular events and genetic regulation associated with TGMS expression, a combined study using cytological observation, transcriptome profiling, and gene expression analysis was conducted for SP2S and its near-isogenic line SP2F grown under warm conditions. Asynchronous microsporocyte meiosis and abnormal tapetal plastids and elaioplasts were demonstrated in the anther of SP2S. The tetrad microspore did not undergo mitosis before the cytoplasm degenerated. Delayed degradation of the tetrad wall, which led to tetrad microspore aggregation, resulted in postponement of sexine (outer layer of pollen exine) formation and sexine fusion in the tetrad. The nexine (foot layer of exine) was also absent. The delay of tetrad wall degradation and abnormality of the exine structure suggested that the defective tapetum lost important functions. Based on transcriptomic comparisons between young flower buds of SP2S and SP2F plants, a total of 465 differentially expressed transcripts (DETs) were identified, including 303 up-regulated DETs and 162 down-regulated DETs in SP2S. Several genes encoding small RNA degrading nuclease 2, small RNA 2′-O-methyltransferase, thioredoxin reductase 2, regulatory subunit A alpha isoform of serine/threonine-protein phosphatase 2A, glycine rich protein 1A, transcription factor bHLH25, leucine-rich repeat receptor kinase At3g14840 like, and fasciclin-like arabinogalactan proteins FLA19 and FLA20 were greatly depressed in SP2S. Interestingly, a POLLENLESS3-LIKE 2 gene encoding the Arabidopsis MS5 homologous protein, which is necessary for microsporocyte meiosis, was down-regulated in SP2S. Other genes that were up-regulated in SP2S encoded glucanase A6, ethylene-responsive transcription factor 1A-like, pollen-specific SF3, stress-associated endoplasmic reticulum protein 2, WRKY transcription factors and pentatricopeptide repeat (PPR) protein At1g07590. The tapetum-development-related genes, including BnEMS1, BnDYT1, and BnAMS, were slightly up-regulated in 3-mm-long flower buds or their anthers, and their downstream genes, BnMS1 and BnMYB80, which affect callose dissolution and exine formation, were greatly up-regulated in SP2S. This aberrant genetic regulation corresponded well with the cytological abnormalities. The results suggested that expression of TGMS associates with complex transcriptional regulation. PMID:28775729

Building asynchronous geospatial processing workflows with web services

NASA Astrophysics Data System (ADS)

Zhao, Peisheng; Di, Liping; Yu, Genong

2012-02-01

Geoscience research and applications often involve a geospatial processing workflow. This workflow includes a sequence of operations that use a variety of tools to collect, translate, and analyze distributed heterogeneous geospatial data. Asynchronous mechanisms, by which clients initiate a request and then resume their processing without waiting for a response, are very useful for complicated workflows that take a long time to run. Geospatial contents and capabilities are increasingly becoming available online as interoperable Web services. This online availability significantly enhances the ability to use Web service chains to build distributed geospatial processing workflows. This paper focuses on how to orchestrate Web services for implementing asynchronous geospatial processing workflows. The theoretical bases for asynchronous Web services and workflows, including asynchrony patterns and message transmission, are examined to explore different asynchronous approaches to and architecture of workflow code for the support of asynchronous behavior. A sample geospatial processing workflow, issued by the Open Geospatial Consortium (OGC) Web Service, Phase 6 (OWS-6), is provided to illustrate the implementation of asynchronous geospatial processing workflows and the challenges in using Web Services Business Process Execution Language (WS-BPEL) to develop them.

Cell cycle- and chaperone-mediated regulation of H3K56ac incorporation in yeast.

PubMed

Kaplan, Tommy; Liu, Chih Long; Erkmann, Judith A; Holik, John; Grunstein, Michael; Kaufman, Paul D; Friedman, Nir; Rando, Oliver J

2008-11-01

Acetylation of histone H3 lysine 56 is a covalent modification best known as a mark of newly replicated chromatin, but it has also been linked to replication-independent histone replacement. Here, we measured H3K56ac levels at single-nucleosome resolution in asynchronously growing yeast cultures, as well as in yeast proceeding synchronously through the cell cycle. We developed a quantitative model of H3K56ac kinetics, which shows that H3K56ac is largely explained by the genomic replication timing and the turnover rate of each nucleosome, suggesting that cell cycle profiles of H3K56ac should reveal most first-time nucleosome incorporation events. However, since the deacetylases Hst3/4 prevent use of H3K56ac as a marker for histone deposition during M phase, we also directly measured M phase histone replacement rates. We report a global decrease in turnover rates during M phase and a further specific decrease in turnover at several early origins of replication, which switch from rapidly replaced in G1 phase to stably bound during M phase. Finally, by measuring H3 replacement in yeast deleted for the H3K56 acetyltransferase Rtt109 and its two co-chaperones Asf1 and Vps75, we find evidence that Rtt109 and Asf1 preferentially enhance histone replacement at rapidly replaced nucleosomes, whereas Vps75 appears to inhibit histone turnover at those loci. These results provide a broad perspective on histone replacement/incorporation throughout the cell cycle and suggest that H3K56 acetylation provides a positive-feedback loop by which replacement of a nucleosome enhances subsequent replacement at the same location.

DNA replication stress induces deregulation of the cell cycle events in root meristems of Allium cepa

PubMed Central

Żabka, Aneta; Polit, Justyna Teresa; Maszewski, Janusz

2012-01-01

Background and Aims Prolonged treatment of Allium cepa root meristems with changing concentrations of hydroxyurea (HU) results in either premature chromosome condensation or cell nuclei with an uncommon form of biphasic chromatin organization. The aim of the current study was to assess conditions that compromise cell cycle checkpoints and convert DNA replication stress into an abnormal course of mitosis. Methods Interphase-mitotic (IM) cells showing gradual changes of chromatin condensation were obtained following continuous 72 h treatment of seedlings with 0·75 mm HU (without renewal of the medium). HU-treated root meristems were analysed using histochemical stainings (DNA-DAPI/Feulgen; starch-iodide and DAB staining for H2O2 production), Western blotting [cyclin B-like (CBL) proteins] and immunochemistry (BrdU incorporation, detection of γ-H2AX and H3S10 phosphorylation). Key Results Continuous treatment of onion seedlings with a low concentration of HU results in shorter root meristems, enhanced production of H2O2, γ-phosphorylation of H2AX histones and accumulation of CBL proteins. HU-induced replication stress gives rise to axially elongated cells with half interphase/half mitotic structures (IM-cells) having both decondensed and condensed domains of chromatin. Long-term HU treatment results in cell nuclei resuming S phase with gradients of BrdU labelling. This suggests a polarized distribution of factors needed to re-initiate stalled replication forks. Furthermore, prolonged HU treatment extends both the relative time span and the spatial scale of H3S10 phosphorylation known in plants. Conclusions The minimum cell length and a threshold level of accumulated CBL proteins are both determining factors by which the nucleus attains commitment to induce an asynchronous course of chromosome condensation. Replication stress-induced alterations in an orderly route of the cell cycle events probably reflect a considerable reprogramming of metabolic functions of chromatin combined with gradients of morphological changes spread along the nucleus. PMID:23087128

Synchronization of Hierarchical Time-Varying Neural Networks Based on Asynchronous and Intermittent Sampled-Data Control.

PubMed

Xiong, Wenjun; Patel, Ragini; Cao, Jinde; Zheng, Wei Xing

In this brief, our purpose is to apply asynchronous and intermittent sampled-data control methods to achieve the synchronization of hierarchical time-varying neural networks. The asynchronous and intermittent sampled-data controllers are proposed for two reasons: 1) the controllers may not transmit the control information simultaneously and 2) the controllers cannot always exist at any time . The synchronization is then discussed for a kind of hierarchical time-varying neural networks based on the asynchronous and intermittent sampled-data controllers. Finally, the simulation results are given to illustrate the usefulness of the developed criteria.In this brief, our purpose is to apply asynchronous and intermittent sampled-data control methods to achieve the synchronization of hierarchical time-varying neural networks. The asynchronous and intermittent sampled-data controllers are proposed for two reasons: 1) the controllers may not transmit the control information simultaneously and 2) the controllers cannot always exist at any time . The synchronization is then discussed for a kind of hierarchical time-varying neural networks based on the asynchronous and intermittent sampled-data controllers. Finally, the simulation results are given to illustrate the usefulness of the developed criteria.

Influenza-Induced Inflammation Drives Pneumococcal Otitis Media

PubMed Central

Reading, Patrick C.; Brown, Lorena E.; Pedersen, John; Gilbertson, Brad; Job, Emma R.; Edenborough, Kathryn M.; Habets, Marrit N.; Zomer, Aldert; Hermans, Peter W. M.; Diavatopoulos, Dimitri A.; Wijburg, Odilia L.

2013-01-01

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM. PMID:23319557

Polymorphism in the GALNT1 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women: The Ovarian Cancer Association Consortium

PubMed Central

Phelan, Catherine M.; Tsai, Ya-Yu; Goode, Ellen L.; Vierkant, Robert A.; Fridley, Brooke L.; Beesley, Jonathan; Chen, Xiao Qing; Webb, Penelope M.; Chanock, Stephen; Cramer, Daniel W.; Moysich, Kirsten; Edwards, Robert P.; Chang-Claude, Jenny; Garcia-Closas, Montserrat; Yang, Hannah; Wang-Gohrke, Shan; Hein, Rebecca; Green, Adele C.; Lissowska, Jolanta; Carney, Michael E.; Lurie, Galina; Wilkens, Lynne R.; Ness, Roberta B.; Pearce, Celeste Leigh; Wu, Anna H.; Van Den Berg, David J.; Stram, Daniel O.; Terry, Kathryn L.; Whiteman, David C.; Whittemore, Alice S.; DiCioccio, Richard A.; McGuire, Valerie; Doherty, Jennifer A.; Rossing, Mary Anne; Anton-Culver, Hoda; Ziogas, Argyrios; Hogdall, Claus; Hogdall, Estrid; Kjaer, Susanne Krüger; Blaakaer, Jan; Quaye, Lydia; Ramus, Susan J.; Jacobs, Ian; Song, Honglin; Pharoah, Paul D.P.; Iversen, Edwin S.; Marks, Jeffrey R.; Pike, Malcolm C.; Gayther, Simon A.; Cunningham, Julie M.; Goodman, Marc T.; Schildkraut, Joellen M.; Chenevix-Trench, Georgia; Berchuck, Andrew; Sellers, Thomas A.

2010-01-01

Aberrant glycosylation is a well-described hallmark of cancer. In a previous ovarian cancer case control study that examined polymorphisms in 26 glycosylation-associated genes, we found strong statistical evidence (P = 0.00017) that women who inherited two copies of a single-nucleotide polymorphism in the UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase, GALNT1, had decreased ovarian cancer risk. The current study attempted to replicate this observation. The GALNT1 single-nucleotide polymorphism rs17647532 was genotyped in 6,965 cases and 8,377 controls from 14 studies forming the Ovarian Cancer Association Consortium. The fixed effects estimate per rs17647532 allele was null (odds ratio, 0.99; 95% confidence interval, 0.92–1.07). When a recessive model was fit, the results were unchanged. Test for hetero geneity of the odds ratios revealed consistency across the 14 replication sites but significant differences compared with the original study population (P = 0.03). This study underscores the need for replication of putative findings in genetic association studies. PMID:20142253

RPA and POT1: friends or foes at telomeres?

PubMed

Flynn, Rachel Litman; Chang, Sandy; Zou, Lee

2012-02-15

Telomere maintenance in cycling cells relies on both DNA replication and capping by the protein complex shelterin. Two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomere 1 (POT1) play critical roles in DNA replication and telomere capping, respectively. While RPA binds to ssDNA in a non-sequence-specific manner, POT1 specifically recognizes singlestranded TTAGGG telomeric repeats. Loss of POT1 leads to aberrant accumulation of RPA at telomeres and activation of the ataxia telangiectasia and Rad3-related kinase (ATR)-mediated checkpoint response, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. The requirement for both POT1 and RPA in telomere maintenance and the antagonism between the two proteins raises the important question of how they function in concert on telomeric ssDNA. Two interesting models were proposed by recent studies to explain the regulation of POT1 and RPA at telomeres. Here, we discuss how these models help unravel the coordination, and also the antagonism, between POT1 and RPA during the cell cycle.

Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1.

PubMed

Boddy, M N; Lopez-Girona, A; Shanahan, P; Interthal, H; Heyer, W D; Russell, P

2000-12-01

Cds1, a serine/threonine kinase, enforces the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. Cds1 is required for survival of replicational stress caused by agents that stall replication forks, but how Cds1 performs these functions is largely unknown. Here we report that the forkhead-associated-1 (FHA1) protein-docking domain of Cds1 interacts with Mus81, an evolutionarily conserved damage tolerance protein. Mus81 has an endonuclease homology domain found in the XPF nucleotide excision repair protein. Inactivation of mus81 reveals a unique spectrum of phenotypes. Mus81 enables survival of deoxynucleotide triphosphate starvation, UV radiation, and DNA polymerase impairment. Mus81 is essential in the absence of Bloom's syndrome Rqh1 helicase and is required for productive meiosis. Genetic epistasis studies suggest that Mus81 works with recombination enzymes to properly replicate damaged DNA. Inactivation of Mus81 triggers a checkpoint-dependent delay of mitosis. We propose that Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes.

The Effects of Asynchronous Visual Delays on Simulator Flight Performance and the Development of Simulator Sickness Symptomatology

DTIC Science & Technology

1986-12-26

NAVAL TRAINING SYSTEMS CENTER ORLANDO. FLORIDA IT FILE COPY THE EFFECTS OF ASYNCHRONOUS VISUAL DELAYS ON SIMULATOR FLIGHT PERFORMANCE AND THE...ASYNCHRONOUS VISUAL. DELAYS ON SI.WLATOR FLIGHT PERF OMANCE AND THE DEVELOPMENT OF SIMLATOR SICKNESS SYMPTOMATOLOGY K. C. Uliano, E. Y. Lambert, R. S. Kennedy...ACCESSION NO. N63733N SP-01 0785-7P6 I. 4780 11. TITLE (Include Security Classification) The Effects of Asynchronous Visual Delays on Simulator Flight

Modeling and Analysis of Mixed Synchronous/Asynchronous Systems

NASA Technical Reports Server (NTRS)

Driscoll, Kevin R.; Madl. Gabor; Hall, Brendan

2012-01-01

Practical safety-critical distributed systems must integrate safety critical and non-critical data in a common platform. Safety critical systems almost always consist of isochronous components that have synchronous or asynchronous interface with other components. Many of these systems also support a mix of synchronous and asynchronous interfaces. This report presents a study on the modeling and analysis of asynchronous, synchronous, and mixed synchronous/asynchronous systems. We build on the SAE Architecture Analysis and Design Language (AADL) to capture architectures for analysis. We present preliminary work targeted to capture mixed low- and high-criticality data, as well as real-time properties in a common Model of Computation (MoC). An abstract, but representative, test specimen system was created as the system to be modeled.

A novel comparator featured with input data characteristic

NASA Astrophysics Data System (ADS)

Jiang, Xiaobo; Ye, Desheng; Xu, Xiangmin; Zheng, Shuai

2016-03-01

Two types of low-power asynchronous comparators featured with input data statistical characteristic are proposed in this article. The asynchronous ripple comparator stops comparing at the first unequal bit but delivers the result to the least significant bit. The pre-stop asynchronous comparator can completely stop comparing and obtain results immediately. The proposed and contrastive comparators were implemented in SMIC 0.18 μm process with different bit widths. Simulation shows that the proposed pre-stop asynchronous comparator features the lowest power consumption, shortest average propagation delay and highest area efficiency among the comparators. Data path of low-density parity check decoder using the proposed pre-stop asynchronous comparators are most power efficient compared with other data paths with synthesised, clock gating and bitwise competition logic comparators.

Impaired TIP60-mediated H4K16 acetylation accounts for the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia pathway-deficient cells.

PubMed

Renaud, Emilie; Barascu, Aurelia; Rosselli, Filippo

2016-01-29

To rescue collapsed replication forks cells utilize homologous recombination (HR)-mediated mechanisms to avoid the induction of gross chromosomal abnormalities that would be generated by non-homologous end joining (NHEJ). Using DNA interstrand crosslinks as a replication barrier, we investigated how the Fanconi anemia (FA) pathway promotes HR at stalled replication forks. FA pathway inactivation results in Fanconi anemia, which is associated with a predisposition to cancer. FANCD2 monoubiquitination and assembly in subnuclear foci appear to be involved in TIP60 relocalization to the chromatin to acetylates histone H4K16 and prevents the binding of 53BP1 to its docking site, H4K20Me2. Thus, FA pathway loss-of-function results in accumulation of 53BP1, RIF1 and RAP80 at damaged chromatin, which impair DNA resection at stalled replication fork-associated DNA breaks and impede HR. Consequently, DNA repair in FA cells proceeds through the NHEJ pathway, which is likely responsible for the accumulation of chromosome abnormalities. We demonstrate that the inhibition of NHEJ or deacetylase activity rescue HR in FA cells. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Interactional Coherence in Asynchronous Learning Networks: A Rhetorical Approach

ERIC Educational Resources Information Center

Potter, Andrew

2008-01-01

Numerous studies have affirmed the value of asynchronous online communication as a learning resource. Several investigations, however, have indicated that discussions in asynchronous environments are often neither interactive nor coherent. The research reported sought to develop an enhanced understanding of interactional coherence, argumentation,…

Identification of a New Human Adenovirus Protein Encoded by a Novel Late l-Strand Transcription Unit▿

PubMed Central

Tollefson, Ann E.; Ying, Baoling; Doronin, Konstantin; Sidor, Peter D.; Wold, William S. M.

2007-01-01

A short open reading frame named the “U exon,” located on the adenovirus (Ad) l-strand (for leftward transcription) between the early E3 region and the fiber gene, is conserved in mastadenoviruses. We have observed that Ad5 mutants with large deletions in E3 that infringe on the U exon display a mild growth defect, as well as an aberrant Ad E2 DNA-binding protein (DBP) intranuclear localization pattern and an apparent failure to organize replication centers during late infection. Mutants in which the U exon DNA is reconstructed have a reversed phenotype. Chow et al. (L. T. Chow et al., J. Mol. Biol. 134:265-303, 1979) described mRNAs initiating in the region of the U exon and spliced to downstream sequences in the late DBP mRNA leader and the DBP-coding region. We have cloned this mRNA (as cDNA) from Ad5 late mRNA; the predicted protein is 217 amino acids, initiating in the U exon and continuing in frame in the DBP leader and in the DBP-coding region but in a different reading frame from DBP. Polyclonal and monoclonal antibodies generated against the predicted U exon protein (UXP) showed that UXP is ∼24K in size by immunoblot and is a late protein. At 18 to 24 h postinfection, UXP is strongly associated with nucleoli and is found throughout the nucleus; later, UXP is associated with the periphery of replication centers, suggesting a function relevant to Ad DNA replication or RNA transcription. UXP is expressed by all four species C Ads. When expressed in transient transfections, UXP complements the aberrant DBP localization pattern of UXP-negative Ad5 mutants. Our data indicate that UXP is a previously unrecognized protein derived from a novel late l-strand transcription unit. PMID:17881437

Labeled Postings for Asynchronous Interaction

ERIC Educational Resources Information Center

ChanLin, Lih-Juan; Chen, Yong-Ting; Chan, Kung-Chi

2009-01-01

The Internet promotes computer-mediated communications, and so asynchronous learning network systems permit more flexibility in time, space, and interaction than synchronous mode of learning. The key point of asynchronous learning is the materials for web-aided teaching and the flow of knowledge. This research focuses on improving online…

An Asynchronous Augmentation to Traditional Course Delivery.

ERIC Educational Resources Information Center

Wolverton, Marvin L.; Wolverton, Mimi

Asynchronous augmentation facilitates distributed learning, which relies heavily on technology and self-learning. This paper reports the results of delivering a real estate principles course using an asynchronous course delivery format. It highlights one of many ways to enhance learning using technology, and it provides information concerning how…

A Taxonomy of Learning through Asynchronous Discussion

ERIC Educational Resources Information Center

Knowlton, Dave S.

2005-01-01

This article presents a five-tiered taxonomy that describes the nature of participation in, and learning through, asynchronous discussion. The taxonomy is framed by a constructivist view of asynchronous discussion. The five tiers of the taxonomy include the following: (a) passive participation, (b) developmental participation, (c) generative…

Designing Asynchronous Online Discussion Environments: Recent Progress and Possible Future Directions

ERIC Educational Resources Information Center

Gao, Fei; Zhang, Tianyi; Franklin, Teresa

2013-01-01

Asynchronous online discussion environments are important platforms to support learning. Research suggests, however, threaded forums, one of the most popular asynchronous discussion environments, do not often foster productive online discussions naturally. This paper explores how certain properties of threaded forums have affected or constrained…

Integrating Asynchronous Digital Design Into the Computer Engineering Curriculum

ERIC Educational Resources Information Center

Smith, S. C.; Al-Assadi, W. K.; Di, J.

2010-01-01

As demand increases for circuits with higher performance, higher complexity, and decreased feature size, asynchronous (clockless) paradigms will become more widely used in the semiconductor industry, as evidenced by the International Technology Roadmap for Semiconductors' (ITRS) prediction of a likely shift from synchronous to asynchronous design…

Development and validation of the Current Opioid Misuse Measure.

PubMed

Butler, Stephen F; Budman, Simon H; Fernandez, Kathrine C; Houle, Brian; Benoit, Christine; Katz, Nathaniel; Jamison, Robert N

2007-07-01

Clinicians recognize the importance of monitoring aberrant medication-related behaviors of chronic pain patients while being prescribed opioid therapy. The purpose of this study was to develop and validate the Current Opioid Misuse Measure (COMM) for those pain patients already on long-term opioid therapy. An initial pool of 177 items was developed with input from 26 pain management and addiction specialists. Concept mapping identified six primary concepts underlying medication misuse, which were used to develop an initial item pool. Twenty-two pain and addiction specialists rated the items on importance and relevance, resulting in selection of a 40-item alpha COMM. Final item selection was based on empirical evaluation of items with patients taking opioids for chronic, noncancer pain (N=227). One-week test-retest reliability was examined with 55 participants. All participants were administered the alpha version of the COMM, the Prescription Drug Use Questionnaire (PDUQ) interview, and submitted a urine sample for toxicology screening. Physician ratings of patient aberrant behaviors were also obtained. Of the 40 items, 17 items appeared to adequately measure aberrant behavior, demonstrating excellent internal consistency and test-retest reliability. Cutoff scores were examined using ROC curve analysis and reasonable sensitivity and specificity were established. To evaluate the COMM's ability to capture change in patient status, it was tested on a subset of patients (N=86) that were followed and reassessed three months later. The COMM was found to have promise as a brief, self-report measure of current aberrant drug-related behavior. Further cross-validation and replication of these preliminary results is pending.

Actively Engaging Students in Asynchronous Online Classes. IDEA Paper #64

ERIC Educational Resources Information Center

Riggs, Shannon A.; Linder, Kathryn E.

2016-01-01

Active learning activities and pedagogical strategies can look different in online learning environments, particularly in asynchronous courses when students are not interacting with the instructor, or with each other, in real time. This paper suggests a three-pronged approach for conceptualizing active learning in the online asynchronous class:…

Exploring Asynchronous and Synchronous Tool Use in Online Courses

ERIC Educational Resources Information Center

Oztok, Murat; Zingaro, Daniel; Brett, Clare; Hewitt, Jim

2013-01-01

While the independent contributions of synchronous and asynchronous interaction in online learning are clear, comparatively less is known about the pedagogical consequences of using both modes in the same environment. In this study, we examine relationships between students' use of asynchronous discussion forums and synchronous private messages…

Teaching Presence and Communication Timeliness in Asynchronous Online Courses

ERIC Educational Resources Information Center

Skramstad, Erik; Schlosser, Charles; Orellana, Anymir

2012-01-01

This study examined student perceptions of teaching presence and communication timeliness in asynchronous online courses. Garrison, Anderson, and Archer's (2000) community of inquiry model provided the framework for the survey research methodology used. Participants were 59 student volunteers taking 1 or more asynchronous online graduate courses.…

Two Studies Examining Argumentation in Asynchronous Computer Mediated Communication

ERIC Educational Resources Information Center

Joiner, Richard; Jones, Sarah; Doherty, John

2008-01-01

Asynchronous computer mediated communication (CMC) would seem to be an ideal medium for supporting development in student argumentation. This paper investigates this assumption through two studies. The first study compared asynchronous CMC with face-to-face discussions. The transactional and strategic level of the argumentation (i.e. measures of…

Using Television Sitcoms to Facilitate Asynchronous Discussions in the Online Communication Course

ERIC Educational Resources Information Center

Tolman, Elizabeth; Asbury, Bryan

2012-01-01

Asynchronous discussions are a useful instructional resource in the online communication course. In discussion groups students have the opportunity to actively participate and interact with students and the instructor. Asynchronous communication allows for flexibility because "participants can interact with significant amounts of time between…

Asynchronous Discussion Board Facilitation and Rubric Use in a Blended Learning Environment

ERIC Educational Resources Information Center

Giacumo, Lisa

2012-01-01

The purpose of this study was to investigate the effects of instructor response prompts and rubrics on students' performance in an asynchronous discussion-board assignment, their learning achievement on an objective-type posttest, and their reported satisfaction levels. Researchers who have studied asynchronous computer-mediated student…

Designing Asynchronous, Text-Based Computer Conferences: Ten Research-Based Suggestions

ERIC Educational Resources Information Center

Choitz, Paul; Lee, Doris

2006-01-01

Asynchronous computer conferencing refers to the use of computer software and a network enabling participants to post messages that allow discourse to continue even though interactions may be extended over days and weeks. Asynchronous conferences are time-independent, adapting to multiple time zones and learner schedules. Such activities as…

Asynchronous Learning Forums for Business Acculturation

ERIC Educational Resources Information Center

Pence, Christine Cope; Wulf, Catharina

2009-01-01

The use of IT as a facilitator for student collaboration in higher business education has grown rapidly since 2000. Asynchronous discussion forums are used abundantly for collaborative training purposes and for teaching students business-relevant tools for their future careers. This article presents an analysis of the asynchronous discussion forum…

Comparing face-to-face, synchronous, and asynchronous learning: postgraduate dental resident preferences.

PubMed

Kunin, Marc; Julliard, Kell N; Rodriguez, Tobias E

2014-06-01

The Department of Dental Medicine of Lutheran Medical Center has developed an asynchronous online curriculum consisting of prerecorded PowerPoint presentations with audio explanations. The focus of this study was to evaluate if the new asynchronous format satisfied the educational needs of the residents compared to traditional lecture (face-to-face) and synchronous (distance learning) formats. Lectures were delivered to 219 dental residents employing face-to-face and synchronous formats, as well as the new asynchronous format; 169 (77 percent) participated in the study. Outcomes were assessed with pretests, posttests, and individual lecture surveys. Results found the residents preferred face-to-face and asynchronous formats to the synchronous format in terms of effectiveness and clarity of presentations. This preference was directly related to the residents' perception of how well the technology worked in each format. The residents also rated the quality of student-instructor and student-student interactions in the synchronous and asynchronous formats significantly higher after taking the lecture series than they did before taking it. However, they rated the face-to-face format as significantly more conducive to student-instructor and student-student interaction. While the study found technology had a major impact on the efficacy of this curricular model, the results suggest that the asynchronous format can be an effective way to teach a postgraduate course.

Asynchronous glimpsing of speech: Spread of masking and task set-size

PubMed Central

Ozmeral, Erol J.; Buss, Emily; Hall, Joseph W.

2012-01-01

Howard-Jones and Rosen [(1993). J. Acoust. Soc. Am. 93, 2915–2922] investigated the ability to integrate glimpses of speech that are separated in time and frequency using a “checkerboard” masker, with asynchronous amplitude modulation (AM) across frequency. Asynchronous glimpsing was demonstrated only for spectrally wide frequency bands. It is possible that the reduced evidence of spectro-temporal integration with narrower bands was due to spread of masking at the periphery. The present study tested this hypothesis with a dichotic condition, in which the even- and odd-numbered bands of the target speech and asynchronous AM masker were presented to opposite ears, minimizing the deleterious effects of masking spread. For closed-set consonant recognition, thresholds were 5.1–8.5 dB better for dichotic than for monotic asynchronous AM conditions. Results were similar for closed-set word recognition, but for open-set word recognition the benefit of dichotic presentation was more modest and level dependent, consistent with the effects of spread of masking being level dependent. There was greater evidence of asynchronous glimpsing in the open-set than closed-set tasks. Presenting stimuli dichotically supported asynchronous glimpsing with narrower frequency bands than previously shown, though the magnitude of glimpsing was reduced for narrower bandwidths even in some dichotic conditions. PMID:22894234

Asynchronous vs didactic education: it's too early to throw in the towel on tradition.

PubMed

Jordan, Jaime; Jalali, Azadeh; Clarke, Samuel; Dyne, Pamela; Spector, Tahlia; Coates, Wendy

2013-08-08

Asynchronous, computer based instruction is cost effective, allows self-directed pacing and review, and addresses preferences of millennial learners. Current research suggests there is no significant difference in learning compared to traditional classroom instruction. Data are limited for novice learners in emergency medicine. The objective of this study was to compare asynchronous, computer-based instruction with traditional didactics for senior medical students during a week-long intensive course in acute care. We hypothesized both modalities would be equivalent. This was a prospective observational quasi-experimental study of 4th year medical students who were novice learners with minimal prior exposure to curricular elements. We assessed baseline knowledge with an objective pre-test. The curriculum was delivered in either traditional lecture format (shock, acute abdomen, dyspnea, field trauma) or via asynchronous, computer-based modules (chest pain, EKG interpretation, pain management, trauma). An interactive review covering all topics was followed by a post-test. Knowledge retention was measured after 10 weeks. Pre and post-test items were written by a panel of medical educators and validated with a reference group of learners. Mean scores were analyzed using dependent t-test and attitudes were assessed by a 5-point Likert scale. 44 of 48 students completed the protocol. Students initially acquired more knowledge from didactic education as demonstrated by mean gain scores (didactic: 28.39% ± 18.06; asynchronous 9.93% ± 23.22). Mean difference between didactic and asynchronous = 18.45% with 95% CI [10.40 to 26.50]; p = 0.0001. Retention testing demonstrated similar knowledge attrition: mean gain scores -14.94% (didactic); -17.61% (asynchronous), which was not significantly different: 2.68% ± 20.85, 95% CI [-3.66 to 9.02], p = 0.399. The attitudinal survey revealed that 60.4% of students believed the asynchronous modules were educational and 95.8% enjoyed the flexibility of the method. 39.6% of students preferred asynchronous education for required didactics; 37.5% were neutral; 23% preferred traditional lectures. Asynchronous, computer-based instruction was not equivalent to traditional didactics for novice learners of acute care topics. Interactive, standard didactic education was valuable. Retention rates were similar between instructional methods. Students had mixed attitudes toward asynchronous learning but enjoyed the flexibility. We urge caution in trading in traditional didactic lectures in favor of asynchronous education for novice learners in acute care.

Heterochromatin-Encoded Satellite RNAs Induce Breast Cancer.

PubMed

Zhu, Quan; Hoong, Nien; Aslanian, Aaron; Hara, Toshiro; Benner, Christopher; Heinz, Sven; Miga, Karen H; Ke, Eugene; Verma, Sachin; Soroczynski, Jan; Yates, John R; Hunter, Tony; Verma, Inder M

2018-06-07

Heterochromatic repetitive satellite RNAs are extensively transcribed in a variety of human cancers, including BRCA1 mutant breast cancer. Aberrant expression of satellite RNAs in cultured cells induces the DNA damage response, activates cell cycle checkpoints, and causes defects in chromosome segregation. However, the mechanism by which satellite RNA expression leads to genomic instability is not well understood. Here we provide evidence that increased levels of satellite RNAs in mammary glands induce tumor formation in mice. Using mass spectrometry, we further show that genomic instability induced by satellite RNAs occurs through interactions with BRCA1-associated protein networks required for the stabilization of DNA replication forks. Additionally, de-stabilized replication forks likely promote the formation of RNA-DNA hybrids in cells expressing satellite RNAs. These studies lay the foundation for developing novel therapeutic strategies that block the effects of non-coding satellite RNAs in cancer cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Phase space methods in HMD systems

NASA Astrophysics Data System (ADS)

Babington, James

2017-06-01

We consider using phase space techniques and methods in analysing optical ray propagation in head mounted display systems. Two examples are considered that illustrate the concepts and methods. Firstly, a shark tooth freeform geometry, and secondly, a waveguide geometry that replicates a pupil in one dimension. Classical optics and imaging in particular provide a natural stage to employ phase space techniques, albeit as a constrained system. We consider how phase space provides a global picture of the physical ray trace data. As such, this gives a complete optical world history of all of the rays propagating through the system. Using this data one can look at, for example, how aberrations arise on a surface by surface basis. These can be extracted numerically from phase space diagrams in the example of a freeform imaging prism. For the waveguide geometry, phase space diagrams provide a way of illustrating how replicated pupils behave and what these imply for design considerations such as tolerances.

Escherichia coli DnaE Polymerase Couples Pyrophosphatase Activity to DNA Replication

PubMed Central

Lapenta, Fabio; Montón Silva, Alejandro; Brandimarti, Renato; Lanzi, Massimiliano; Gratani, Fabio Lino; Vellosillo Gonzalez, Perceval; Perticarari, Sofia; Hochkoeppler, Alejandro

2016-01-01

DNA Polymerases generate pyrophosphate every time they catalyze a step of DNA elongation. This elongation reaction is generally believed as thermodynamically favoured by the hydrolysis of pyrophosphate, catalyzed by inorganic pyrophosphatases. However, the specific action of inorganic pyrophosphatases coupled to DNA replication in vivo was never demonstrated. Here we show that the Polymerase-Histidinol-Phosphatase (PHP) domain of Escherichia coli DNA Polymerase III α subunit features pyrophosphatase activity. We also show that this activity is inhibited by fluoride, as commonly observed for inorganic pyrophosphatases, and we identified 3 amino acids of the PHP active site. Remarkably, E. coli cells expressing variants of these catalytic residues of α subunit feature aberrant phenotypes, poor viability, and are subject to high mutation frequencies. Our findings indicate that DNA Polymerases can couple DNA elongation and pyrophosphate hydrolysis, providing a mechanism for the control of DNA extension rate, and suggest a promising target for novel antibiotics. PMID:27050298

Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

PubMed Central

Graham, Deborah S Cunninghame; Pinder, Christopher L; Tombleson, Philip; Behrens, Timothy W; Martín, Javier; Fairfax, Benjamin P; Knight, Julian C; Chen, Lingyan; Replogle, Joseph; Syvänen, Ann-Christine; Rönnblom, Lars; Graham, Robert R; Wither, Joan E; Rioux, John D; Alarcón-Riquelme, Marta E; Vyse, Timothy J

2015-01-01

Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry: a new GWAS, meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including 10 novel associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n=16) of transcription factors among SLE susceptibility genes. This supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE. PMID:26502338

The effects of boric acid on sister chromatid exchanges and chromosome aberrations in cultured human lymphocytes.

PubMed

Arslan, Mehmet; Topaktas, Mehmet; Rencuzogullari, Eyyüp

2008-02-01

The aim of this study was to determine the possible genotoxic effects of boric acid (BA) (E284), which is used as an antimicrobial agent in food, by using sister chromatid exchange (SCEs) and chromosome aberration (CAs) tests in human peripheral lymphocytes. The human lymphocytes were treated with 400, 600, 800, and 1000 mug/mL concentrations of BA dissolved in dimethyl sulfoxide (DMSO), for 24 h and 48 h treatment periods. BA did not increase the SCEs for all the concentrations and treatment periods when compared to control and solvent control (DMSO). BA induced structural and total CAs at all the tested concentrations for 24 and 48 h treatment periods. The induction of the total CAs was dose dependent for the 24 h treatment period. However, BA did not cause numerical CAs. BA showed a cytotoxic effect by decreasing the replication index (RI) and mitotic index (MI). BA decreased the MI in a dose-dependent manner for the 24 h treatment period.

Fostering Critical Reflection in a Computer-Based, Asynchronously Delivered Diversity Training Course

ERIC Educational Resources Information Center

Givhan, Shawn T.

2013-01-01

This dissertation study chronicles the creation of a computer-based, asynchronously delivered diversity training course for a state agency. The course format enabled efficient delivery of a mandatory curriculum to the Massachusetts Department of State Police workforce. However, the asynchronous format posed a challenge to achieving the learning…

Anonymity and Motivation in Asynchronous Discussions and L2 Vocabulary Learning

ERIC Educational Resources Information Center

Polat, Nihat; Mancilla, Rae; Mahalingappa, Laura

2013-01-01

This study investigates L2 attainment in asynchronous online environments, specifically possible relationships among anonymity, L2 motivation, participation in discussions, quality of L2 production, and success in L2 vocabulary learning. It examines, in asynchronous discussions, (a) if participation and (b) motivation contribute to L2 vocabulary…

Exploring the Effect of Scripted Roles on Cognitive Presence in Asynchronous Online Discussions

ERIC Educational Resources Information Center

Olesova, Larisa; Slavin, Margaret; Lim, Jieun

2016-01-01

The purpose of this study was to identify the effect of scripted roles on students' level of cognitive presence in asynchronous online threaded discussions. A quantitative content analysis was used to investigate: (1) what level of cognitive presence is achieved by students' assigned roles in asynchronous online discussions; (2) differences…

A Multi-Perspective Investigation into Learners' Interaction in Asynchronous Computer-Mediated Communication (CMC)

ERIC Educational Resources Information Center

Çardak, Çigdem Suzan

2016-01-01

This article focusses on graduate level students' interactions during asynchronous CMC activities of an online course about the teaching profession in Turkey. The instructor of the course designed and facilitated a semester-long asynchronous CMC on forum discussions, and investigated the interaction of learners in multiple perspectives: learners'…

The Negotiation Model in Asynchronous Computer-Mediated Communication (CMC): Negotiation in Task-Based Email Exchanges

ERIC Educational Resources Information Center

Kitade, Keiko

2006-01-01

Based on recent studies, computer-mediated communication (CMC) has been considered a tool to aid in language learning on account of its distinctive interactional features. However, most studies have referred to "synchronous" CMC and neglected to investigate how "asynchronous" CMC contributes to language learning. Asynchronous CMC possesses…

Integrating the Intangibles into Asynchronous Online Instruction: Strategies for Improving Interaction and Social Presence

ERIC Educational Resources Information Center

McGuire, Beverley Foulks

2016-01-01

This paper considers how instructors of asynchronous online courses in the Humanities might integrate intangibles associated with face-to-face instruction into their online environments. It presents a case study of asynchronous online instruction in a philosophy and religion department at a midsize public university in the southeastern United…

Postgraduate Students' Knowledge Construction during Asynchronous Computer Conferences in a Blended Learning Environment: A Malaysian Experience

ERIC Educational Resources Information Center

Kian-Sam, Hong; Lee, Julia Ai Cheng

2008-01-01

Blended learning, using e-learning tools to supplement existing on campus learning, often incorporates asynchronous computer conferencing as a means of augmenting knowledge construction among students. This case study reports findings about levels of knowledge construction amongst adult postgraduate students in six asynchronous computer…

Asynchronous Learning Sources in a High-Tech Organization

ERIC Educational Resources Information Center

Bouhnik, Dan; Giat, Yahel; Sanderovitch, Yafit

2009-01-01

Purpose: The purpose of this study is to characterize learning from asynchronous sources among research and development (R&D) personnel. It aims to examine four aspects of asynchronous source learning: employee preferences regarding self-learning; extent of source usage; employee satisfaction with these sources and the effect of the sources on the…

Asynchronous reference frame agreement in a quantum network

NASA Astrophysics Data System (ADS)

Islam, Tanvirul; Wehner, Stephanie

2016-03-01

An efficient implementation of many multiparty protocols for quantum networks requires that all the nodes in the network share a common reference frame. Establishing such a reference frame from scratch is especially challenging in an asynchronous network where network links might have arbitrary delays and the nodes do not share synchronised clocks. In this work, we study the problem of establishing a common reference frame in an asynchronous network of n nodes of which at most t are affected by arbitrary unknown error, and the identities of the faulty nodes are not known. We present a protocol that allows all the correctly functioning nodes to agree on a common reference frame as long as the network graph is complete and not more than t\\lt n/4 nodes are faulty. As the protocol is asynchronous, it can be used with some assumptions to synchronise clocks over a network. Also, the protocol has the appealing property that it allows any existing two-node asynchronous protocol for reference frame agreement to be lifted to a robust protocol for an asynchronous quantum network.

Pediatric emergency medicine asynchronous e-learning: a multicenter randomized controlled Solomon four-group study.

PubMed

Chang, Todd P; Pham, Phung K; Sobolewski, Brad; Doughty, Cara B; Jamal, Nazreen; Kwan, Karen Y; Little, Kim; Brenkert, Timothy E; Mathison, David J

2014-08-01

Asynchronous e-learning allows for targeted teaching, particularly advantageous when bedside and didactic education is insufficient. An asynchronous e-learning curriculum has not been studied across multiple centers in the context of a clinical rotation. We hypothesize that an asynchronous e-learning curriculum during the pediatric emergency medicine (EM) rotation improves medical knowledge among residents and students across multiple participating centers. Trainees on pediatric EM rotations at four large pediatric centers from 2012 to 2013 were randomized in a Solomon four-group design. The experimental arms received an asynchronous e-learning curriculum consisting of nine Web-based, interactive, peer-reviewed Flash/HTML5 modules. Postrotation testing and in-training examination (ITE) scores quantified improvements in knowledge. A 2 × 2 analysis of covariance (ANCOVA) tested interaction and main effects, and Pearson's correlation tested associations between module usage, scores, and ITE scores. A total of 256 of 458 participants completed all study elements; 104 had access to asynchronous e-learning modules, and 152 were controls who used the current education standards. No pretest sensitization was found (p = 0.75). Use of asynchronous e-learning modules was associated with an improvement in posttest scores (p < 0.001), from a mean score of 18.45 (95% confidence interval [CI] = 17.92 to 18.98) to 21.30 (95% CI = 20.69 to 21.91), a large effect (partial η(2) = 0.19). Posttest scores correlated with ITE scores (r(2) = 0.14, p < 0.001) among pediatric residents. Asynchronous e-learning is an effective educational tool to improve knowledge in a clinical rotation. Web-based asynchronous e-learning is a promising modality to standardize education among multiple institutions with common curricula, particularly in clinical rotations where scheduling difficulties, seasonality, and variable experiences limit in-hospital learning. © 2014 by the Society for Academic Emergency Medicine.

Modeling and Analysis of Asynchronous Systems Using SAL and Hybrid SAL

NASA Technical Reports Server (NTRS)

Tiwari, Ashish; Dutertre, Bruno

2013-01-01

We present formal models and results of formal analysis of two different asynchronous systems. We first examine a mid-value select module that merges the signals coming from three different sensors that are each asynchronously sampling the same input signal. We then consider the phase locking protocol proposed by Daly, Hopkins, and McKenna. This protocol is designed to keep a set of non-faulty (asynchronous) clocks phase locked even in the presence of Byzantine-faulty clocks on the network. All models and verifications have been developed using the SAL model checking tools and the Hybrid SAL abstractor.

Detection of Failure in Asynchronous Motor Using Soft Computing Method

NASA Astrophysics Data System (ADS)

Vinoth Kumar, K.; Sony, Kevin; Achenkunju John, Alan; Kuriakose, Anto; John, Ano P.

2018-04-01

This paper investigates the stator short winding failure of asynchronous motor also their effects on motor current spectrums. A fuzzy logic approach i.e., model based technique possibly will help to detect the asynchronous motor failure. Actually, fuzzy logic similar to humanoid intelligent methods besides expected linguistic empowering inferences through vague statistics. The dynamic model is technologically advanced for asynchronous motor by means of fuzzy logic classifier towards investigate the stator inter turn failure in addition open phase failure. A hardware implementation was carried out with LabVIEW for the online-monitoring of faults.

Asynchronous discrete control of continuous processes

NASA Astrophysics Data System (ADS)

Kaliski, M. E.; Johnson, T. L.

1984-07-01

The research during this second contract year continued to deal with the development of sound theoretical models for asynchronous systems. Two criteria served to shape the research pursued: the first, that the developed models extend and generalize previously developed research for synchronous discrete control; the second, that the models explicitly address the question of how to incorporate system transition times into themselves. The following sections of this report concisely delineate this year's work. Our original proposal for this research identified four general tasks of investigation: (1.1) Analysis of Qualitative Properties of Asynchronous Hybrid Systems; (1.2) Acceptance and Control for Asynchronous Hybrid Systems.

Combining Live Video and Audio Broadcasting, Synchronous Chat, and Asynchronous Open Forum Discussions in Distance Education

ERIC Educational Resources Information Center

Teng, Tian-Lih; Taveras, Marypat

2004-01-01

This article outlines the evolution of a unique distance education program that began as a hybrid--combining face-to-face instruction with asynchronous online teaching--and evolved to become an innovative combination of synchronous education using live streaming video, audio, and chat over the Internet, blended with asynchronous online discussions…

Utilizing Spectrum Efficiently (USE)

DTIC Science & Technology

2011-02-28

18 4.8 Space-Time Coded Asynchronous DS - CDMA with Decentralized MAI Suppression: Performance and...numerical results. 4.8 Space-Time Coded Asynchronous DS - CDMA with Decentralized MAI Suppression: Performance and Spectral Efficiency In [60] multiple...supported at a given signal-to-interference ratio in asynchronous direct-sequence code-division multiple-access ( DS - CDMA ) sys- tems was examined. It was

The Development, Validity, and Reliability of Communication Satisfaction in an Online Asynchronous Discussion Scale

ERIC Educational Resources Information Center

Hung, Min-Ling; Chou, Chien

2014-01-01

The purpose of this study was to identify dimensions of students' communication satisfaction in an asynchronous discussion forum. An asynchronous discussion may be defined as text-based human-to-human communication via computer networks that provides a platform for the participants to interact with one another to exchange ideas, insights, and…

Web-based Cases in Teaching and Learning - the Quality of Discussions and a Stage of Perspective Taking in Asynchronous Communication.

ERIC Educational Resources Information Center

Jarvela, Sanna; Hakkinen, Paivi

2002-01-01

Examines the quality of asynchronous interaction in Web-based conferencing among preservice teachers. The study combines asynchronous conferencing with peer and mentor collaboration to electronically apprentice student learning. Results point out different levels of Web-based discussion: higher-level, progressive, and lower-level discussion. A…

Asynchronous vs didactic education: it’s too early to throw in the towel on tradition

PubMed Central

2013-01-01

Background Asynchronous, computer based instruction is cost effective, allows self-directed pacing and review, and addresses preferences of millennial learners. Current research suggests there is no significant difference in learning compared to traditional classroom instruction. Data are limited for novice learners in emergency medicine. The objective of this study was to compare asynchronous, computer-based instruction with traditional didactics for senior medical students during a week-long intensive course in acute care. We hypothesized both modalities would be equivalent. Methods This was a prospective observational quasi-experimental study of 4th year medical students who were novice learners with minimal prior exposure to curricular elements. We assessed baseline knowledge with an objective pre-test. The curriculum was delivered in either traditional lecture format (shock, acute abdomen, dyspnea, field trauma) or via asynchronous, computer-based modules (chest pain, EKG interpretation, pain management, trauma). An interactive review covering all topics was followed by a post-test. Knowledge retention was measured after 10 weeks. Pre and post-test items were written by a panel of medical educators and validated with a reference group of learners. Mean scores were analyzed using dependent t-test and attitudes were assessed by a 5-point Likert scale. Results 44 of 48 students completed the protocol. Students initially acquired more knowledge from didactic education as demonstrated by mean gain scores (didactic: 28.39% ± 18.06; asynchronous 9.93% ± 23.22). Mean difference between didactic and asynchronous = 18.45% with 95% CI [10.40 to 26.50]; p = 0.0001. Retention testing demonstrated similar knowledge attrition: mean gain scores −14.94% (didactic); -17.61% (asynchronous), which was not significantly different: 2.68% ± 20.85, 95% CI [−3.66 to 9.02], p = 0.399. The attitudinal survey revealed that 60.4% of students believed the asynchronous modules were educational and 95.8% enjoyed the flexibility of the method. 39.6% of students preferred asynchronous education for required didactics; 37.5% were neutral; 23% preferred traditional lectures. Conclusions Asynchronous, computer-based instruction was not equivalent to traditional didactics for novice learners of acute care topics. Interactive, standard didactic education was valuable. Retention rates were similar between instructional methods. Students had mixed attitudes toward asynchronous learning but enjoyed the flexibility. We urge caution in trading in traditional didactic lectures in favor of asynchronous education for novice learners in acute care. PMID:23927420

[A novel proposal explaining sleep disturbance of children in Japan--asynchronization].

PubMed

Kohyama, Jun

2008-07-01

It has been reported that more than half of the children in Japan suffer from daytime sleepiness. In contrast, about one quarter of junior high-school students in Japan complain of insomnia. According to the International Classification of Sleep Disorders (Second edition), these children could be diagnosed as having behaviorally-induced insufficient sleep syndrome due to inadequate sleeping habits. Getting on adequate amount of sleep should solve such problems;however, such a therapeutic approach often fails. Although social factors are involved in these sleep disturbances, I feel that a novel notion - asynchronization - leads to an understanding of the pathophysiology of disturbances in these children. Further, it could contribute to resolve their problems. The essence of asynchronization is a disturbance of various aspects (e.g., cycle, amplitude, phase, and interrelationship) of the biological rhythms that normally exhibits circadian oscillation. The main cause of asynchronization is hypothesized to be the combination of light exposure during night and the lack of light exposure in the morning. Asynchronization results in the disturbance of variable systems. Thus, symptoms of asynchronization include disturbances of the autonomic nervous system (sleepiness, insomnia, disturbance of hormonal excretion, gastrointestinal problems, etc.) and higher brain function (disorientation, loss of sociality, loss of will or motivation, impaired alertness and performance, etc.). Neurological (attention deficit, aggression, impulsiveness, hyperactivity, etc.), psychiatric (depressive disorders, personality disorders, anxiety disorders, etc.) and somatic (tiredness, fatigue, etc.) disturbances could also be symptoms of asynchronization. At the initial phase of asynchronization, disturbances are functional and can be resolved relatively easily, such as by the establishment of a regular sleep-wakefulness cycle;however, without adequate intervention the disturbances could gradually worsen and become hard to resolve.

Stand-Alone and Hybrid Positioning Using Asynchronous Pseudolites

PubMed Central

Gioia, Ciro; Borio, Daniele

2015-01-01

global navigation satellite system (GNSS) receivers are usually unable to achieve satisfactory performance in difficult environments, such as open-pit mines, urban canyons and indoors. Pseudolites have the potential to extend GNSS usage and significantly improve receiver performance in such environments by providing additional navigation signals. This also applies to asynchronous pseudolite systems, where different pseudolites operate in an independent way. Asynchronous pseudolite systems require, however, dedicated strategies in order to properly integrate GNSS and pseudolite measurements. In this paper, several asynchronous pseudolite/GNSS integration strategies are considered: loosely- and tightly-coupled approaches are developed and combined with pseudolite proximity and receiver signal strength (RSS)-based positioning. The performance of the approaches proposed has been tested in different scenarios, including static and kinematic conditions. The tests performed demonstrate that the methods developed are effective techniques for integrating heterogeneous measurements from different sources, such as asynchronous pseudolites and GNSS. PMID:25609041

Distributed Consensus of Stochastic Delayed Multi-agent Systems Under Asynchronous Switching.

PubMed

Wu, Xiaotai; Tang, Yang; Cao, Jinde; Zhang, Wenbing

2016-08-01

In this paper, the distributed exponential consensus of stochastic delayed multi-agent systems with nonlinear dynamics is investigated under asynchronous switching. The asynchronous switching considered here is to account for the time of identifying the active modes of multi-agent systems. After receipt of confirmation of mode's switching, the matched controller can be applied, which means that the switching time of the matched controller in each node usually lags behind that of system switching. In order to handle the coexistence of switched signals and stochastic disturbances, a comparison principle of stochastic switched delayed systems is first proved. By means of this extended comparison principle, several easy to verified conditions for the existence of an asynchronously switched distributed controller are derived such that stochastic delayed multi-agent systems with asynchronous switching and nonlinear dynamics can achieve global exponential consensus. Two examples are given to illustrate the effectiveness of the proposed method.

Hydrodynamic advantages of swimming by salp chains.

PubMed

Sutherland, Kelly R; Weihs, Daniel

2017-08-01

Salps are marine invertebrates comprising multiple jet-propelled swimming units during a colonial life-cycle stage. Using theory, we show that asynchronous swimming with multiple pulsed jets yields substantial hydrodynamic benefit due to the production of steady swimming velocities, which limit drag. Laboratory comparisons of swimming kinematics of aggregate salps ( Salpa fusiformis and Weelia cylindrica ) using high-speed video supported that asynchronous swimming by aggregates results in a smoother velocity profile and showed that this smoother velocity profile is the result of uncoordinated, asynchronous swimming by individual zooids. In situ flow visualizations of W. cylindrica swimming wakes revealed that another consequence of asynchronous swimming is that fluid interactions between jet wakes are minimized. Although the advantages of multi-jet propulsion have been mentioned elsewhere, this is the first time that the theory has been quantified and the role of asynchronous swimming verified using experimental data from the laboratory and the field. © 2017 The Author(s).

The pitfalls of platform comparison: DNA copy number array technologies assessed

PubMed Central

2009-01-01

Background The accurate and high resolution mapping of DNA copy number aberrations has become an important tool by which to gain insight into the mechanisms of tumourigenesis. There are various commercially available platforms for such studies, but there remains no general consensus as to the optimal platform. There have been several previous platform comparison studies, but they have either described older technologies, used less-complex samples, or have not addressed the issue of the inherent biases in such comparisons. Here we describe a systematic comparison of data from four leading microarray technologies (the Affymetrix Genome-wide SNP 5.0 array, Agilent High-Density CGH Human 244A array, Illumina HumanCNV370-Duo DNA Analysis BeadChip, and the Nimblegen 385 K oligonucleotide array). We compare samples derived from primary breast tumours and their corresponding matched normals, well-established cancer cell lines, and HapMap individuals. By careful consideration and avoidance of potential sources of bias, we aim to provide a fair assessment of platform performance. Results By performing a theoretical assessment of the reproducibility, noise, and sensitivity of each platform, notable differences were revealed. Nimblegen exhibited between-replicate array variances an order of magnitude greater than the other three platforms, with Agilent slightly outperforming the others, and a comparison of self-self hybridizations revealed similar patterns. An assessment of the single probe power revealed that Agilent exhibits the highest sensitivity. Additionally, we performed an in-depth visual assessment of the ability of each platform to detect aberrations of varying sizes. As expected, all platforms were able to identify large aberrations in a robust manner. However, some focal amplifications and deletions were only detected in a subset of the platforms. Conclusion Although there are substantial differences in the design, density, and number of replicate probes, the comparison indicates a generally high level of concordance between platforms, despite differences in the reproducibility, noise, and sensitivity. In general, Agilent tended to be the best aCGH platform and Affymetrix, the superior SNP-CGH platform, but for specific decisions the results described herein provide a guide for platform selection and study design, and the dataset a resource for more tailored comparisons. PMID:19995423

Aberrant functioning of the putamen links delusions, antipsychotic drug dose, and compromised connectivity in first episode psychosis--Preliminary fMRI findings.

PubMed

Raij, Tuukka T; Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana

2015-08-30

The dopamine theory proposes the relationship of delusions to aberrant signaling in striatal circuitries that can be normalized with dopamine D2 receptor-blocking drugs. Localization of such circuitries, as well as their upstream and downstream signaling, remains poorly known. We collected functional magnetic resonance images from first-episode psychosis patients and controls during an audiovisual movie. Final analyses included 20 patients and 20 controls; another sample of 10 patients and 10 controls was used to calculate a comparison signal-time course. We identified putamen circuitry in which the signal aberrance (poor correlation with the comparison signal time course) was predicted by the dopamine theory, being greater in patients than controls; correlating positively with delusion scores; and correlating negatively with antipsychotic-equivalent dosage. In Granger causality analysis, patients showed a compromised contribution of the cortical salience network to the putamen and compromised contribution of the putamen to the default mode network. Results were corrected for multiple comparisons at the cluster level with primary voxel-wise threshold p < 0.005 for the salience network contribution, but liberal primary threshold p < 0.05 was used in other group comparisons. If replicated in larger studies, these findings may help unify and extend current hypotheses on dopaminergic dysfunction, salience processing and pathogenesis of delusions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Merging the Forces of Asynchronous Tutoring and Synchronous Conferencing: A Qualitative Study of Arab ESL Academic Writers Using E-Tutoring

ERIC Educational Resources Information Center

Alqadoumi, Omar Mohamed

2012-01-01

Previous studies in the field of e-tutoring dealt either with asynchronous tutoring or synchronous conferencing as modes for providing e-tutoring services to English learners. This qualitative research study reports the experiences of Arab ESL tutees with both asynchronous tutoring and synchronous conferencing. It also reports the experiences of…

Differences in Electronic Exchanges in Synchronous and Asynchronous Computer-Mediated Communication: The Effect of Culture as a Mediating Variable

ERIC Educational Resources Information Center

Angeli, Charoula; Schwartz, Neil H.

2016-01-01

Two hundred and eighty undergraduates from universities in two countries were asked to read didactic material, and then think and write about potential solutions to an ill-defined problem. The writing was conducted within a synchronous or asynchronous computer-mediated communication (CMC) environment. Asynchronous CMC took the form of email…

Localized radio frequency communication using asynchronous transfer mode protocol

DOEpatents

Witzke, Edward L [Edgewood, NM; Robertson, Perry J [Albuquerque, NM; Pierson, Lyndon G [Albuquerque, NM

2007-08-14

A localized wireless communication system for communication between a plurality of circuit boards, and between electronic components on the circuit boards. Transceivers are located on each circuit board and electronic component. The transceivers communicate with one another over spread spectrum radio frequencies. An asynchronous transfer mode protocol controls communication flow with asynchronous transfer mode switches located on the circuit boards.

Features of the Asynchronous Correlation between the China Coal Price Index and Coal Mining Accidental Deaths.

PubMed

Huang, Yuecheng; Cheng, Wuyi; Luo, Sida; Luo, Yun; Ma, Chengchen; He, Tailin

2016-01-01

The features of the asynchronous correlation between accident indices and the factors that influence accidents can provide an effective reference for warnings of coal mining accidents. However, what are the features of this correlation? To answer this question, data from the China coal price index and the number of deaths from coal mining accidents were selected as the sample data. The fluctuation modes of the asynchronous correlation between the two data sets were defined according to the asynchronous correlation coefficients, symbolization, and sliding windows. We then built several directed and weighted network models, within which the fluctuation modes and the transformations between modes were represented by nodes and edges. Then, the features of the asynchronous correlation between these two variables could be studied from a perspective of network topology. We found that the correlation between the price index and the accidental deaths was asynchronous and fluctuating. Certain aspects, such as the key fluctuation modes, the subgroups characteristics, the transmission medium, the periodicity and transmission path length in the network, were analyzed by using complex network theory, analytical methods and spectral analysis method. These results provide a scientific reference for generating warnings for coal mining accidents based on economic indices.

Chlamydia trachomatis Intercepts Golgi-Derived Sphingolipids through a Rab14-Mediated Transport Required for Bacterial Development and Replication

PubMed Central

Capmany, Anahí; Damiani, María Teresa

2010-01-01

Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation. PMID:21124879

Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

PubMed

Capmany, Anahí; Damiani, María Teresa

2010-11-22

Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

The NEIL1 G83D germline DNA glycosylase variant induces genomic instability and cellular transformation

PubMed Central

Galick, Heather A.; Marsden, Carolyn G.; Kathe, Scott; Dragon, Julie A.; Volk, Lindsay; Nemec, Antonia A.; Wallace, Susan S.; Prakash, Aishwarya; Doublié, Sylvie; Sweasy, Joann B.

2017-01-01

Base excision repair (BER) is a key genome maintenance pathway. The NEIL1 DNA glycosylase recognizes oxidized bases, and likely removes damage in advance of the replication fork. The rs5745906 SNP of the NEIL1 gene is a rare human germline variant that encodes the NEIL1 G83D protein, which is devoid of DNA glycosylase activity. Here we show that expression of G83D NEIL1 in MCF10A immortalized but non-transformed mammary epithelial cells leads to replication fork stress. Upon treatment with hydrogen peroxide, we observe increased levels of stalled replication forks in cells expressing G83D NEIL1 versus cells expressing the wild-type (WT) protein. Double-strand breaks (DSBs) arise in G83D-expressing cells during the S and G2/M phases of the cell cycle. Interestingly, these breaks result in genomic instability in the form of high levels of chromosomal aberrations and micronuclei. Cells expressing G83D also grow in an anchorage independent manner, suggesting that the genomic instability results in a carcinogenic phenotype. Our results are consistent with the idea that an inability to remove oxidative damage in an efficient manner at the replication fork leads to genomic instability and mutagenesis. We suggest that individuals who harbor the G83D NEIL1 variant face an increased risk for human cancer. PMID:29156764

DNA-PKcs phosphorylates hnRNP-A1 to facilitate the RPA-to-POT1 switch and telomere capping after replication.

PubMed

Sui, Jiangdong; Lin, Yu-Fen; Xu, Kangling; Lee, Kyung-Jong; Wang, Dong; Chen, Benjamin P C

2015-07-13

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP-A1) has been implicated in telomere protection and telomerase activation. Recent evidence has further demonstrated that hnRNP-A1 plays a crucial role in maintaining newly replicated telomeric 3' overhangs and facilitating the switch from replication protein A (RPA) to protection of telomeres 1 (POT1). The role of hnRNP-A1 in telomere protection also involves DNA-dependent protein kinase catalytic subunit (DNA-PKcs), although the detailed regulation mechanism has not been clear. Here we report that hnRNP-A1 is phosphorylated by DNA-PKcs during the G2 and M phases and that DNA-PK-dependent hnRNP-A1 phosphorylation promotes the RPA-to-POT1 switch on telomeric single-stranded 3' overhangs. Consequently, in cells lacking hnRNP-A1 or DNA-PKcs-dependent hnRNP-A1 phosphorylation, impairment of the RPA-to-POT1 switch results in DNA damage response at telomeres during mitosis as well as induction of fragile telomeres. Taken together, our results indicate that DNA-PKcs-dependent hnRNP-A1 phosphorylation is critical for capping of the newly replicated telomeres and prevention of telomeric aberrations. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP

PubMed Central

Mimmler, Maximilian; Peter, Simon; Kraus, Alexander; Stroh, Svenja; Nikolova, Teodora; Seiwert, Nina; Hasselwander, Solveig; Neitzel, Carina; Haub, Jessica; Monien, Bernhard H.; Nicken, Petra; Steinberg, Pablo; Shay, Jerry W.; Kaina, Bernd; Fahrer, Jörg

2016-01-01

PhIP is an abundant heterocyclic aromatic amine (HCA) and important dietary carcinogen. Following metabolic activation, PhIP causes bulky DNA lesions at the C8-position of guanine. Although C8-PhIP-dG adducts are mutagenic, their interference with the DNA replication machinery and the elicited DNA damage response (DDR) have not yet been studied. Here, we analyzed PhIP-triggered replicative stress and elucidated the role of the apical DDR kinases ATR, ATM and DNA-PKcs in the cellular defense response. First, we demonstrate that PhIP induced C8-PhIP-dG adducts and DNA strand breaks. This stimulated ATR-CHK1 signaling, phosphorylation of histone 2AX and the formation of RPA foci. In proliferating cells, PhIP treatment increased the frequency of stalled replication forks and reduced fork speed. Inhibition of ATR in the presence of PhIP-induced DNA damage strongly promoted the formation of DNA double-strand breaks, activation of the ATM-CHK2 pathway and hyperphosphorylation of RPA. The abrogation of ATR signaling potentiated the cell death response and enhanced chromosomal aberrations after PhIP treatment, while ATM and DNA-PK inhibition had only marginal effects. These results strongly support the notion that ATR plays a key role in the defense against cancer formation induced by PhIP and related HCAs. PMID:27599846

Fanconi anemia proteins in telomere maintenance.

PubMed

Sarkar, Jaya; Liu, Yie

2016-07-01

Mammalian chromosome ends are protected by nucleoprotein structures called telomeres. Telomeres ensure genome stability by preventing chromosome termini from being recognized as DNA damage. Telomere length homeostasis is inevitable for telomere maintenance because critical shortening or over-lengthening of telomeres may lead to DNA damage response or delay in DNA replication, and hence genome instability. Due to their repetitive DNA sequence, unique architecture, bound shelterin proteins, and high propensity to form alternate/secondary DNA structures, telomeres are like common fragile sites and pose an inherent challenge to the progression of DNA replication, repair, and recombination apparatus. It is conceivable that longer the telomeres are, greater is the severity of such challenges. Recent studies have linked excessively long telomeres with increased tumorigenesis. Here we discuss telomere abnormalities in a rare recessive chromosomal instability disorder called Fanconi Anemia and the role of the Fanconi Anemia pathway in telomere biology. Reports suggest that Fanconi Anemia proteins play a role in maintaining long telomeres, including processing telomeric joint molecule intermediates. We speculate that ablation of the Fanconi Anemia pathway would lead to inadequate aberrant structural barrier resolution at excessively long telomeres, thereby causing replicative burden on the cell. Published by Elsevier B.V.

Secret Forwarding of Events over Distributed Publish/Subscribe Overlay Network.

PubMed

Yoon, Young; Kim, Beom Heyn

2016-01-01

Publish/subscribe is a communication paradigm where loosely-coupled clients communicate in an asynchronous fashion. Publish/subscribe supports the flexible development of large-scale, event-driven and ubiquitous systems. Publish/subscribe is prevalent in a number of application domains such as social networking, distributed business processes and real-time mission-critical systems. Many publish/subscribe applications are sensitive to message loss and violation of privacy. To overcome such issues, we propose a novel method of using secret sharing and replication techniques. This is to reliably and confidentially deliver decryption keys along with encrypted publications even under the presence of several Byzantine brokers across publish/subscribe overlay networks. We also propose a framework for dynamically and strategically allocating broker replicas based on flexibly definable criteria for reliability and performance. Moreover, a thorough evaluation is done through a case study on social networks using the real trace of interactions among Facebook users.

Secret Forwarding of Events over Distributed Publish/Subscribe Overlay Network

PubMed Central

Kim, Beom Heyn

2016-01-01

Publish/subscribe is a communication paradigm where loosely-coupled clients communicate in an asynchronous fashion. Publish/subscribe supports the flexible development of large-scale, event-driven and ubiquitous systems. Publish/subscribe is prevalent in a number of application domains such as social networking, distributed business processes and real-time mission-critical systems. Many publish/subscribe applications are sensitive to message loss and violation of privacy. To overcome such issues, we propose a novel method of using secret sharing and replication techniques. This is to reliably and confidentially deliver decryption keys along with encrypted publications even under the presence of several Byzantine brokers across publish/subscribe overlay networks. We also propose a framework for dynamically and strategically allocating broker replicas based on flexibly definable criteria for reliability and performance. Moreover, a thorough evaluation is done through a case study on social networks using the real trace of interactions among Facebook users. PMID:27367610

The Effects on Health Behavior and Health Outcomes of Internet-Based Asynchronous Communication Between Health Providers and Patients With a Chronic Condition: A Systematic Review

PubMed Central

Ros, Wynand JG; Schrijvers, Guus

2014-01-01

Background In support of professional practice, asynchronous communication between the patient and the provider is implemented separately or in combination with Internet-based self-management interventions. This interaction occurs primarily through electronic messaging or discussion boards. There is little evidence as to whether it is a useful tool for chronically ill patients to support their self-management and increase the effectiveness of interventions. Objective The aim of our study was to review the use and usability of patient-provider asynchronous communication for chronically ill patients and the effects of such communication on health behavior, health outcomes, and patient satisfaction. Methods A literature search was performed using PubMed and Embase. The quality of the articles was appraised according to the National Institute for Health and Clinical Excellence (NICE) criteria. The use and usability of the asynchronous communication was analyzed by examining the frequency of use and the number of users of the interventions with asynchronous communication, as well as of separate electronic messaging. The effectiveness of asynchronous communication was analyzed by examining effects on health behavior, health outcomes, and patient satisfaction. Results Patients’ knowledge concerning their chronic condition increased and they seemed to appreciate being able to communicate asynchronously with their providers. They not only had specific questions but also wanted to communicate about feeling ill. A decrease in visits to the physician was shown in two studies (P=.07, P=.07). Increases in self-management/self-efficacy for patients with back pain, dyspnea, and heart failure were found. Positive health outcomes were shown in 12 studies, where the clinical outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced expiratory volume [FEV]) improved. Physical symptoms improved in five studies. Five studies generated a variety of positive psychosocial outcomes. Conclusions The effect of asynchronous communication is not shown unequivocally in these studies. Patients seem to be interested in using email. Patients are willing to participate and are taking the initiative to discuss health issues with their providers. Additional testing of the effects of asynchronous communication on self-management in chronically ill patients is needed. PMID:24434570

The effects on health behavior and health outcomes of Internet-based asynchronous communication between health providers and patients with a chronic condition: a systematic review.

PubMed

de Jong, Catharina Carolina; Ros, Wynand Jg; Schrijvers, Guus

2014-01-16

In support of professional practice, asynchronous communication between the patient and the provider is implemented separately or in combination with Internet-based self-management interventions. This interaction occurs primarily through electronic messaging or discussion boards. There is little evidence as to whether it is a useful tool for chronically ill patients to support their self-management and increase the effectiveness of interventions. The aim of our study was to review the use and usability of patient-provider asynchronous communication for chronically ill patients and the effects of such communication on health behavior, health outcomes, and patient satisfaction. A literature search was performed using PubMed and Embase. The quality of the articles was appraised according to the National Institute for Health and Clinical Excellence (NICE) criteria. The use and usability of the asynchronous communication was analyzed by examining the frequency of use and the number of users of the interventions with asynchronous communication, as well as of separate electronic messaging. The effectiveness of asynchronous communication was analyzed by examining effects on health behavior, health outcomes, and patient satisfaction. Patients' knowledge concerning their chronic condition increased and they seemed to appreciate being able to communicate asynchronously with their providers. They not only had specific questions but also wanted to communicate about feeling ill. A decrease in visits to the physician was shown in two studies (P=.07, P=.07). Increases in self-management/self-efficacy for patients with back pain, dyspnea, and heart failure were found. Positive health outcomes were shown in 12 studies, where the clinical outcomes for diabetic patients (HbA1c level) and for asthmatic patients (forced expiratory volume [FEV]) improved. Physical symptoms improved in five studies. Five studies generated a variety of positive psychosocial outcomes. The effect of asynchronous communication is not shown unequivocally in these studies. Patients seem to be interested in using email. Patients are willing to participate and are taking the initiative to discuss health issues with their providers. Additional testing of the effects of asynchronous communication on self-management in chronically ill patients is needed.

Asynchronous vibration problem of centrifugal compressor

NASA Technical Reports Server (NTRS)

Fujikawa, T.; Ishiguro, N.; Ito, M.

1980-01-01

An unstable asynchronous vibration problem in a high pressure centrifugal compressor and the remedial actions against it are described. Asynchronous vibration of the compressor took place when the discharge pressure (Pd) was increased, after the rotor was already at full speed. The typical spectral data of the shaft vibration indicate that as the pressure Pd increases, pre-unstable vibration appears and becomes larger, and large unstable asynchronous vibration occurs suddenly (Pd = 5.49MPa). A computer program was used which calculated the logarithmic decrement and the damped natural frequency of the rotor bearing systems. The analysis of the log-decrement is concluded to be effective in preventing unstable vibration in both the design stage and remedial actions.

Optimization of parameters of special asynchronous electric drives

NASA Astrophysics Data System (ADS)

Karandey, V. Yu; Popov, B. K.; Popova, O. B.; Afanasyev, V. L.

2018-03-01

The article considers the solution of the problem of parameters optimization of special asynchronous electric drives. The solution of the problem will allow one to project and create special asynchronous electric drives for various industries. The created types of electric drives will have optimum mass-dimensional and power parameters. It will allow one to realize and fulfill the set characteristics of management of technological processes with optimum level of expenses of electric energy, time of completing the process or other set parameters. The received decision allows one not only to solve a certain optimizing problem, but also to construct dependences between the optimized parameters of special asynchronous electric drives, for example, with the change of power, current in a winding of the stator or rotor, induction in a gap or steel of magnetic conductors and other parameters. On the constructed dependences, it is possible to choose necessary optimum values of parameters of special asynchronous electric drives and their components without carrying out repeated calculations.

Asynchronous Communication of TLNS3DMB Boundary Exchange

NASA Technical Reports Server (NTRS)

Hammond, Dana P.

1997-01-01

This paper describes the recognition of implicit serialization due to coarse-grain, synchronous communication and demonstrates the conversion to asynchronous communication for the exchange of boundary condition information in the Thin-Layer Navier Stokes 3-Dimensional Multi Block (TLNS3DMB) code. The implementation details of using asynchronous communication is provided including buffer allocation, message identification, and barrier control. The IBM SP2 was used for the tests presented.

[Cost-effectiveness of Synchronous vs. Asynchronous Telepsychiatry in Prison Inmates With Depression].

PubMed

Barrera-Valencia, Camilo; Benito-Devia, Alexis Vladimir; Vélez-Álvarez, Consuelo; Figueroa-Barrera, Mario; Franco-Idárraga, Sandra Milena

Telepsychiatry is defined as the use of information and communication technology (ICT) in providing remote psychiatric services. Telepsychiatry is applied using two types of communication: synchronous (real time) and asynchronous (store and forward). To determine the cost-effectiveness of a synchronous and an asynchronous telepsychiatric model in prison inmate patients with symptoms of depression. A cost-effectiveness study was performed on a population consisting of 157 patients from the Establecimiento Penitenciario y Carcelario de Mediana Seguridad de Manizales, Colombia. The sample was determined by applying Zung self-administered surveys for depression (1965) and the Hamilton Depression Rating Scale (HDRS), the latter being the tool used for the comparison. Initial Hamilton score, arrival time, duration of system downtime, and clinical effectiveness variables had normal distributions (P>.05). There were significant differences (P<.001) between care costs for the different models, showing that the mean cost of the asynchronous model is less than synchronous model, and making the asynchronous model more cost-effective. The asynchronous model is the most cost-effective model of telepsychiatry care for patients with depression admitted to a detention centre, according to the results of clinical effectiveness, cost measurement, and patient satisfaction. Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Features of the Asynchronous Correlation between the China Coal Price Index and Coal Mining Accidental Deaths

PubMed Central

Huang, Yuecheng; Cheng, Wuyi; Luo, Sida; Luo, Yun; Ma, Chengchen; He, Tailin

2016-01-01

The features of the asynchronous correlation between accident indices and the factors that influence accidents can provide an effective reference for warnings of coal mining accidents. However, what are the features of this correlation? To answer this question, data from the China coal price index and the number of deaths from coal mining accidents were selected as the sample data. The fluctuation modes of the asynchronous correlation between the two data sets were defined according to the asynchronous correlation coefficients, symbolization, and sliding windows. We then built several directed and weighted network models, within which the fluctuation modes and the transformations between modes were represented by nodes and edges. Then, the features of the asynchronous correlation between these two variables could be studied from a perspective of network topology. We found that the correlation between the price index and the accidental deaths was asynchronous and fluctuating. Certain aspects, such as the key fluctuation modes, the subgroups characteristics, the transmission medium, the periodicity and transmission path length in the network, were analyzed by using complex network theory, analytical methods and spectral analysis method. These results provide a scientific reference for generating warnings for coal mining accidents based on economic indices. PMID:27902748

Efficacy of an asynchronous electronic curriculum in emergency medicine education in the United States.

PubMed

Wray, Alisa; Bennett, Kathryn; Boysen-Osborn, Megan; Wiechmann, Warren; Toohey, Shannon

2017-01-01

The aim of this study was to measure the effect of an iPad-based asynchronous curriculum on emergency medicine resident performance on the in-training exam (ITE). We hypothesized that the implementation of an asynchronous curriculum (replacing 1 hour of weekly didactic time) would result in non-inferior ITE scores compared to the historical scores of residents who had participated in the traditional 5-hour weekly didactic curriculum. The study was a retrospective, non-inferiority study. conducted at the University of California, Irvine Emergency Medicine Residency Program. We compared ITE scores from 2012 and 2013, when there were 5 weekly hours of didactic content, with scores from 2014 and 2015, when 1 hour of conference was replaced with asynchro-nous content. Examination results were compared using a non-inferiority data analysis with a 10% margin of difference. Using a non-inferiority test with a 95% confidence interval, there was no difference between the 2 groups (before and after implementation of asynchronous learning), as the confidence interval for the change of the ITE was -3.5 to 2.3 points, whereas the 10% non-inferiority margin was 7.8 points. Replacing 1 hour of didactic conference with asynchronous learning showed no negative impact on resident ITE scores.

ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes

PubMed Central

Voon, Hsiao P.J.; Hughes, Jim R.; Rode, Christina; De La Rosa-Velázquez, Inti A.; Jenuwein, Thomas; Feil, Robert; Higgs, Douglas R.; Gibbons, Richard J.

2015-01-01

Summary Histone H3.3 is a replication-independent histone variant, which replaces histones that are turned over throughout the entire cell cycle. H3.3 deposition at euchromatin is dependent on HIRA, whereas ATRX/Daxx deposits H3.3 at pericentric heterochromatin and telomeres. The role of H3.3 at heterochromatic regions is unknown, but mutations in the ATRX/Daxx/H3.3 pathway are linked to aberrant telomere lengthening in certain cancers. In this study, we show that ATRX-dependent deposition of H3.3 is not limited to pericentric heterochromatin and telomeres but also occurs at heterochromatic sites throughout the genome. Notably, ATRX/H3.3 specifically localizes to silenced imprinted alleles in mouse ESCs. ATRX KO cells failed to deposit H3.3 at these sites, leading to loss of the H3K9me3 heterochromatin modification, loss of repression, and aberrant allelic expression. We propose a model whereby ATRX-dependent deposition of H3.3 into heterochromatin is normally required to maintain the memory of silencing at imprinted loci. PMID:25865896

Chromatic-aberration-corrected diffractive lenses for ultra-broadband focusing

DOE PAGES

Wang, Peng; Mohammad, Nabil; Menon, Rajesh

2016-02-12

We exploit the inherent dispersion in diffractive optics to demonstrate planar chromatic-aberration-corrected lenses. Specifically, we designed, fabricated and characterized cylindrical diffractive lenses that efficiently focus the entire visible band (450 nm to 700 nm) onto a single line. These devices are essentially pixelated, multi-level microstructures. Experiments confirm an average optical efficiency of 25% for a three-wavelength apochromatic lens whose chromatic focus shift is only 1.3 μm and 25 μm in the lateral and axial directions, respectively. Super-achromatic performance over the continuous visible band is also demonstrated with averaged lateral and axial focus shifts of only 1.65 μm and 73.6 μm,more » respectively. These lenses are easy to fabricate using single-step grayscale lithography and can be inexpensively replicated. Furthermore, these devices are thin (<3 μm), error tolerant, has low aspect ratio (<1:1) and offer polarization-insensitive focusing, all significant advantages compared to alternatives that rely on metasurfaces. Lastly, our design methodology offers high design flexibility in numerical aperture and focal length, and is readily extended to 2D.« less

Asynchronous networks: modularization of dynamics theorem

NASA Astrophysics Data System (ADS)

Bick, Christian; Field, Michael

2017-02-01

Building on the first part of this paper, we develop the theory of functional asynchronous networks. We show that a large class of functional asynchronous networks can be (uniquely) represented as feedforward networks connecting events or dynamical modules. For these networks we can give a complete description of the network function in terms of the function of the events comprising the network: the modularization of dynamics theorem. We give examples to illustrate the main results.

Distributed Data-aggregation Consensus for Sensor Networks: Relaxation of Consensus Concept and Convergence Property

DTIC Science & Technology

2014-08-01

consensus algorithm called randomized gossip is more suitable [7, 8]. In asynchronous randomized gossip algorithms, pairs of neighboring nodes exchange...messages and perform updates in an asynchronous and unattended manner, and they also 1 The class of broadcast gossip algorithms [9, 10, 11, 12] are...dynamics [2] and asynchronous pairwise randomized gossip [7, 8], broadcast gossip algorithms do not require that nodes know the identities of their

Asynchronous Video Interviewing as a New Technology in Personnel Selection: The Applicant’s Point of View

PubMed Central

Brenner, Falko S.; Ortner, Tuulia M.; Fay, Doris

2016-01-01

The present study aimed to integrate findings from technology acceptance research with research on applicant reactions to new technology for the emerging selection procedure of asynchronous video interviewing. One hundred six volunteers experienced asynchronous video interviewing and filled out several questionnaires including one on the applicants’ personalities. In line with previous technology acceptance research, the data revealed that perceived usefulness and perceived ease of use predicted attitudes toward asynchronous video interviewing. Furthermore, openness revealed to moderate the relation between perceived usefulness and attitudes toward this particular selection technology. No significant effects emerged for computer self-efficacy, job interview self-efficacy, extraversion, neuroticism, and conscientiousness. Theoretical and practical implications are discussed. PMID:27378969

Phosphorylation of the NFAR proteins by the dsRNA-dependent protein kinase PKR constitutes a novel mechanism of translational regulation and cellular defense.

PubMed

Harashima, Ai; Guettouche, Toumy; Barber, Glen N

2010-12-01

Here, we describe a new mechanism of host defense that involves the nuclear factors associated with dsRNA (NFAR1 [90 kDa] and NFAR2 [110 kDa]), which constitute part of the shuttling ribonuclear protein (RNP) complex. Activation of the dsRNA-activated protein kinase PKR by viral RNA enabled phosphorylation of NFAR1 and NFAR2 on Thr 188 and Thr 315, an event found to be evolutionarily conserved in Xenopus. Phosphorylated NFAR1 and NFAR2 became dissociated from nuclear factor 45 (NF45), which was requisite for NFAR reshuttling, causing the NFARs to be retained on ribosomes, associate with viral transcripts, and impede viral replication. Cre-loxP animals with depletion of the NFARs in the thymus were exquisitely sensitive to the cytoplasmic replicating virus VSV (vesicular stomatitis virus). Thus, the NFARs constitute a novel, conserved mechanism of host defense used by the cell to detect and impede aberrant translation events.

Effects of Homology Length in the Repeat Region on Minus-Strand DNA Transfer and Retroviral Replication

PubMed Central

Dang, Que; Hu, Wei-Shau

2001-01-01

Homology between the two repeat (R) regions in the retroviral genome mediates minus-strand DNA transfer during reverse transcription. We sought to define the effects of R homology lengths on minus-strand DNA transfer. We generated five murine leukemia virus (MLV)-based vectors that contained identical sequences but different lengths of the 3′ R (3, 6, 12, 24 and 69 nucleotides [nt]); 69 nt is the full-length MLV R. After one round of replication, viral titers from the vector with a full-length downstream R were compared with viral titers generated from the other four vectors with reduced R lengths. Viral titers generated from vectors with R lengths reduced to one-third (24 nt) or one-sixth (12 nt) that of the wild type were not significantly affected; however, viral titers generated from vectors with only 3- or 6-nt homology in the R region were significantly lower. Because expression and packaging of the RNA were similar among all the vectors, the differences in the viral titers most likely reflected the impact of the homology lengths on the efficiency of minus-strand DNA transfer. The molecular nature of minus-strand DNA transfer was characterized in 63 proviruses. Precise R-to-R transfer was observed in most proviruses generated from vectors with 12-, 24-, or 69-nt homology in R, whereas aberrant transfers were predominantly used to generate proviruses from vectors with 3- or 6-nt homology. Reverse transcription using RNA transcribed from an upstream promoter, termed read-in RNA transcripts, resulted in most of the aberrant transfers. These data demonstrate that minus-strand DNA transfer is homology driven and a minimum homology length is required for accurate and efficient minus-strand DNA transfer. PMID:11134294

Links between nucleolar activity, rDNA stability, aneuploidy and chronological aging in the yeast Saccharomyces cerevisiae.

PubMed

Lewinska, Anna; Miedziak, Beata; Kulak, Klaudia; Molon, Mateusz; Wnuk, Maciej

2014-06-01

The nucleolus is speculated to be a regulator of cellular senescence in numerous biological systems (Guarente, Genes Dev 11(19):2449-2455, 1997; Johnson et al., Curr Opin Cell Biol 10(3):332-338, 1998). In the budding yeast Saccharomyces cerevisiae, alterations in nucleolar architecture, the redistribution of nucleolar protein and the accumulation of extrachromosomal ribosomal DNA circles (ERCs) during replicative aging have been reported. However, little is known regarding rDNA stability and changes in nucleolar activity during chronological aging (CA), which is another yeast aging model used. In the present study, the impact of aberrant cell cycle checkpoint control (knock-out of BUB1, BUB2, MAD1 and TEL1 genes in haploid and diploid hemizygous states) on CA-mediated changes in the nucleolus was studied. Nucleolus fragmentation, changes in the nucleolus size and the nucleolus/nucleus ratio, ERC accumulation, expression pattern changes and the relocation of protein involved in transcriptional silencing during CA were revealed. All strains examined were affected by oxidative stress, aneuploidy (numerical rather than structural aberrations) and DNA damage. However, the bub1 cells were the most prone to aneuploidy events, which may contribute to observed decrease in chronological lifespan. We postulate that chronological aging may be affected by redox imbalance-mediated chromosome XII instability leading to both rDNA instability and whole chromosome aneuploidy. CA-mediated nucleolus fragmentation may be a consequence of nucleolus enlargement and/or Nop2p upregulation. Moreover, the rDNA content of chronologically aging cells may be a factor determining the subsequent replicative lifespan. Taken together, we demonstrated that the nucleolus state is also affected during CA in yeast.

Novel Approaches Reveal that Toxoplasma gondii Bradyzoites within Tissue Cysts Are Dynamic and Replicating Entities In Vivo.

PubMed

Watts, Elizabeth; Zhao, Yihua; Dhara, Animesh; Eller, Becca; Patwardhan, Abhijit; Sinai, Anthony P

2015-09-08

Despite their critical role in chronic toxoplasmosis, the biology of Toxoplasma gondii bradyzoites is poorly understood. In an attempt to address this gap, we optimized approaches to purify tissue cysts and analyzed the replicative potential of bradyzoites within these cysts. In order to quantify individual bradyzoites within tissue cysts, we have developed imaging software, BradyCount 1.0, that allows the rapid establishment of bradyzoite burdens within imaged optical sections of purified tissue cysts. While in general larger tissue cysts contain more bradyzoites, their relative "occupancy" was typically lower than that of smaller cysts, resulting in a lower packing density. The packing density permits a direct measure of how bradyzoites develop within cysts, allowing for comparisons across progression of the chronic phase. In order to capture bradyzoite endodyogeny, we exploited the differential intensity of TgIMC3, an inner membrane complex protein that intensely labels newly formed/forming daughters within bradyzoites and decays over time in the absence of further division. To our surprise, we were able to capture not only sporadic and asynchronous division but also synchronous replication of all bradyzoites within mature tissue cysts. Furthermore, the time-dependent decay of TgIMC3 intensity was exploited to gain insights into the temporal patterns of bradyzoite replication in vivo. Despite the fact that bradyzoites are considered replicatively dormant, we find evidence for cyclical, episodic bradyzoite growth within tissue cysts in vivo. These findings directly challenge the prevailing notion of bradyzoites as dormant nonreplicative entities in chronic toxoplasmosis and have implications on our understanding of this enigmatic and clinically important life cycle stage. The protozoan Toxoplasma gondii establishes a lifelong chronic infection mediated by the bradyzoite form of the parasite within tissue cysts. Technical challenges have limited even the most basic studies on bradyzoites and the tissue cysts in vivo. Bradyzoites, which are viewed as dormant, poorly replicating or nonreplicating entities, were found to be surprisingly active, exhibiting not only the capacity for growth but also previously unrecognized patterns of replication that point to their being considerably more dynamic than previously imagined. These newly revealed properties force us to reexamine the most basic questions regarding bradyzoite biology and the progression of the chronic phase of toxoplasmosis. By developing new tools and approaches to study the chronic phase at the level of bradyzoites, we expose new avenues to tackle both drug development and a better understanding of events that may lead to reactivated symptomatic disease. Copyright © 2015 Watts et al.

Network evolution induced by asynchronous stimuli through spike-timing-dependent plasticity.

PubMed

Yuan, Wu-Jie; Zhou, Jian-Fang; Zhou, Changsong

2013-01-01

In sensory neural system, external asynchronous stimuli play an important role in perceptual learning, associative memory and map development. However, the organization of structure and dynamics of neural networks induced by external asynchronous stimuli are not well understood. Spike-timing-dependent plasticity (STDP) is a typical synaptic plasticity that has been extensively found in the sensory systems and that has received much theoretical attention. This synaptic plasticity is highly sensitive to correlations between pre- and postsynaptic firings. Thus, STDP is expected to play an important role in response to external asynchronous stimuli, which can induce segregative pre- and postsynaptic firings. In this paper, we study the impact of external asynchronous stimuli on the organization of structure and dynamics of neural networks through STDP. We construct a two-dimensional spatial neural network model with local connectivity and sparseness, and use external currents to stimulate alternately on different spatial layers. The adopted external currents imposed alternately on spatial layers can be here regarded as external asynchronous stimuli. Through extensive numerical simulations, we focus on the effects of stimulus number and inter-stimulus timing on synaptic connecting weights and the property of propagation dynamics in the resulting network structure. Interestingly, the resulting feedforward structure induced by stimulus-dependent asynchronous firings and its propagation dynamics reflect both the underlying property of STDP. The results imply a possible important role of STDP in generating feedforward structure and collective propagation activity required for experience-dependent map plasticity in developing in vivo sensory pathways and cortices. The relevance of the results to cue-triggered recall of learned temporal sequences, an important cognitive function, is briefly discussed as well. Furthermore, this finding suggests a potential application for examining STDP by measuring neural population activity in a cultured neural network.

FAST: A fully asynchronous and status-tracking pattern for geoprocessing services orchestration

NASA Astrophysics Data System (ADS)

Wu, Huayi; You, Lan; Gui, Zhipeng; Gao, Shuang; Li, Zhenqiang; Yu, Jingmin

2014-09-01

Geoprocessing service orchestration (GSO) provides a unified and flexible way to implement cross-application, long-lived, and multi-step geoprocessing service workflows by coordinating geoprocessing services collaboratively. Usually, geoprocessing services and geoprocessing service workflows are data and/or computing intensive. The intensity feature may make the execution process of a workflow time-consuming. Since it initials an execution request without blocking other interactions on the client side, an asynchronous mechanism is especially appropriate for GSO workflows. Many critical problems remain to be solved in existing asynchronous patterns for GSO including difficulties in improving performance, status tracking, and clarifying the workflow structure. These problems are a challenge when orchestrating performance efficiency, making statuses instantly available, and constructing clearly structured GSO workflows. A Fully Asynchronous and Status-Tracking (FAST) pattern that adopts asynchronous interactions throughout the whole communication tier of a workflow is proposed for GSO. The proposed FAST pattern includes a mechanism that actively pushes the latest status to clients instantly and economically. An independent proxy was designed to isolate the status tracking logic from the geoprocessing business logic, which assists the formation of a clear GSO workflow structure. A workflow was implemented in the FAST pattern to simulate the flooding process in the Poyang Lake region. Experimental results show that the proposed FAST pattern can efficiently tackle data/computing intensive geoprocessing tasks. The performance of all collaborative partners was improved due to the asynchronous mechanism throughout communication tier. A status-tracking mechanism helps users retrieve the latest running status of a GSO workflow in an efficient and instant way. The clear structure of the GSO workflow lowers the barriers for geospatial domain experts and model designers to compose asynchronous GSO workflows. Most importantly, it provides better support for locating and diagnosing potential exceptions.

Asynchronous collision integrators: Explicit treatment of unilateral contact with friction and nodal restraints

PubMed Central

Wolff, Sebastian; Bucher, Christian

2013-01-01

This article presents asynchronous collision integrators and a simple asynchronous method treating nodal restraints. Asynchronous discretizations allow individual time step sizes for each spatial region, improving the efficiency of explicit time stepping for finite element meshes with heterogeneous element sizes. The article first introduces asynchronous variational integration being expressed by drift and kick operators. Linear nodal restraint conditions are solved by a simple projection of the forces that is shown to be equivalent to RATTLE. Unilateral contact is solved by an asynchronous variant of decomposition contact response. Therein, velocities are modified avoiding penetrations. Although decomposition contact response is solving a large system of linear equations (being critical for the numerical efficiency of explicit time stepping schemes) and is needing special treatment regarding overconstraint and linear dependency of the contact constraints (for example from double-sided node-to-surface contact or self-contact), the asynchronous strategy handles these situations efficiently and robust. Only a single constraint involving a very small number of degrees of freedom is considered at once leading to a very efficient solution. The treatment of friction is exemplified for the Coulomb model. Special care needs the contact of nodes that are subject to restraints. Together with the aforementioned projection for restraints, a novel efficient solution scheme can be presented. The collision integrator does not influence the critical time step. Hence, the time step can be chosen independently from the underlying time-stepping scheme. The time step may be fixed or time-adaptive. New demands on global collision detection are discussed exemplified by position codes and node-to-segment integration. Numerical examples illustrate convergence and efficiency of the new contact algorithm. Copyright © 2013 The Authors. International Journal for Numerical Methods in Engineering published by John Wiley & Sons, Ltd. PMID:23970806

Within-female plasticity in sex allocation is associated with a behavioural polyphenism in house wrens.

PubMed

Bowers, E K; Thompson, C F; Sakaluk, S K

2016-03-01

Sex allocation theory assumes individual plasticity in maternal strategies, but few studies have investigated within-individual changes across environments. In house wrens, differences between nests in the degree of hatching synchrony of eggs represent a behavioural polyphenism in females, and its expression varies with seasonal changes in the environment. Between-nest differences in hatching asynchrony also create different environments for offspring, and sons are more strongly affected than daughters by sibling competition when hatching occurs asynchronously over several days. Here, we examined variation in hatching asynchrony and sex allocation, and its consequences for offspring fitness. The number and condition of fledglings declined seasonally, and the frequency of asynchronous hatching increased. In broods hatched asynchronously, sons, which are over-represented in the earlier-laid eggs, were in better condition than daughters, which are over-represented in the later-laid eggs. Nonetheless, asynchronous broods were more productive later within seasons. The proportion of sons in asynchronous broods increased seasonally, whereas there was a seasonal increase in the production of daughters by mothers hatching their eggs synchronously, which was characterized by within-female changes in offspring sex and not by sex-biased mortality. As adults, sons from asynchronous broods were in better condition and produced more broods of their own than males from synchronous broods, and both males and females from asynchronous broods had higher lifetime reproductive success than those from synchronous broods. In conclusion, hatching patterns are under maternal control, representing distinct strategies for allocating offspring within broods, and are associated with offspring sex ratios and differences in offspring reproductive success. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Asynchronous P300-based brain-computer interface to control a virtual environment: initial tests on end users.

PubMed

Aloise, Fabio; Schettini, Francesca; Aricò, Pietro; Salinari, Serenella; Guger, Christoph; Rinsma, Johanna; Aiello, Marco; Mattia, Donatella; Cincotti, Febo

2011-10-01

Motor disability and/or ageing can prevent individuals from fully enjoying home facilities, thus worsening their quality of life. Advances in the field of accessible user interfaces for domotic appliances can represent a valuable way to improve the independence of these persons. An asynchronous P300-based Brain-Computer Interface (BCI) system was recently validated with the participation of healthy young volunteers for environmental control. In this study, the asynchronous P300-based BCI for the interaction with a virtual home environment was tested with the participation of potential end-users (clients of a Frisian home care organization) with limited autonomy due to ageing and/or motor disabilities. System testing revealed that the minimum number of stimulation sequences needed to achieve correct classification had a higher intra-subject variability in potential end-users with respect to what was previously observed in young controls. Here we show that the asynchronous modality performed significantly better as compared to the synchronous mode in continuously adapting its speed to the users' state. Furthermore, the asynchronous system modality confirmed its reliability in avoiding misclassifications and false positives, as previously shown in young healthy subjects. The asynchronous modality may contribute to filling the usability gap between BCI systems and traditional input devices, representing an important step towards their use in the activities of daily living.

Synchronous contextual irregularities affect early scene processing: replication and extension.

PubMed

Mudrik, Liad; Shalgi, Shani; Lamy, Dominique; Deouell, Leon Y

2014-04-01

Whether contextual regularities facilitate perceptual stages of scene processing is widely debated, and empirical evidence is still inconclusive. Specifically, it was recently suggested that contextual violations affect early processing of a scene only when the incongruent object and the scene are presented a-synchronously, creating expectations. We compared event-related potentials (ERPs) evoked by scenes that depicted a person performing an action using either a congruent or an incongruent object (e.g., a man shaving with a razor or with a fork) when scene and object were presented simultaneously. We also explored the role of attention in contextual processing by using a pre-cue to direct subjects׳ attention towards or away from the congruent/incongruent object. Subjects׳ task was to determine how many hands the person in the picture used in order to perform the action. We replicated our previous findings of frontocentral negativity for incongruent scenes that started ~ 210 ms post stimulus presentation, even earlier than previously found. Surprisingly, this incongruency ERP effect was negatively correlated with the reaction times cost on incongruent scenes. The results did not allow us to draw conclusions about the role of attention in detecting the regularity, due to a weak attention manipulation. By replicating the 200-300 ms incongruity effect with a new group of subjects at even earlier latencies than previously reported, the results strengthen the evidence for contextual processing during this time window even when simultaneous presentation of the scene and object prevent the formation of prior expectations. We discuss possible methodological limitations that may account for previous failures to find this an effect, and conclude that contextual information affects object model selection processes prior to full object identification, with semantic knowledge activation stages unfolding only later on. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-05-07

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

The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time

PubMed Central

Josefsson, Lina; von Stockenstrom, Susanne; Faria, Nuno R.; Sinclair, Elizabeth; Bacchetti, Peter; Killian, Maudi; Epling, Lorrie; Tan, Alice; Ho, Terence; Lemey, Philippe; Shao, Wei; Hunt, Peter W.; Somsouk, Ma; Wylie, Will; Douek, Daniel C.; Loeb, Lisa; Custer, Jeff; Hoh, Rebecca; Poole, Lauren; Deeks, Steven G.; Hecht, Frederick; Palmer, Sarah

2013-01-01

The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from naïve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4–12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4+ T cells [CD45RO+/CD27(+/−)]. The HIV-1 infection frequency of CD4+ T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4–12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4–12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes. PMID:24277811

DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9.

PubMed

Ohouo, Patrice Y; Bastos de Oliveira, Francisco M; Liu, Yi; Ma, Chu Jian; Smolka, Marcus B

2013-01-03

In response to genotoxic stress, a transient arrest in cell-cycle progression enforced by the DNA-damage checkpoint (DDC) signalling pathway positively contributes to genome maintenance. Because hyperactivated DDC signalling can lead to a persistent and detrimental cell-cycle arrest, cells must tightly regulate the activity of the kinases involved in this pathway. Despite their importance, the mechanisms for monitoring and modulating DDC signalling are not fully understood. Here we show that the DNA-repair scaffolding proteins Slx4 and Rtt107 prevent the aberrant hyperactivation of DDC signalling by lesions that are generated during DNA replication in Saccharomyces cerevisiae. On replication stress, cells lacking Slx4 or Rtt107 show hyperactivation of the downstream DDC kinase Rad53, whereas activation of the upstream DDC kinase Mec1 remains normal. An Slx4-Rtt107 complex counteracts the checkpoint adaptor Rad9 by physically interacting with Dpb11 and phosphorylated histone H2A, two positive regulators of Rad9-dependent Rad53 activation. A decrease in DDC signalling results from hypomorphic mutations in RAD53 and H2A and rescues the hypersensitivity to replication stress of cells lacking Slx4 or Rtt107. We propose that the Slx4-Rtt107 complex modulates Rad53 activation by a competition-based mechanism that balances the engagement of Rad9 at replication-induced lesions. Our findings show that DDC signalling is monitored and modulated through the direct action of DNA-repair factors.

Universal filtered multi-carrier system for asynchronous uplink transmission in optical access network

NASA Astrophysics Data System (ADS)

Kang, Soo-Min; Kim, Chang-Hun; Han, Sang-Kook

2016-02-01

In passive optical network (PON), orthogonal frequency division multiplexing (OFDM) has been studied actively due to its advantages such as high spectra efficiency (SE), dynamic resource allocation in time or frequency domain, and dispersion robustness. However, orthogonal frequency division multiple access (OFDMA)-PON requires tight synchronization among multiple access signals. If not, frequency orthogonality could not be maintained. Also its sidelobe causes inter-channel interference (ICI) to adjacent channel. To prevent ICI caused by high sidelobes, guard band (GB) is usually used which degrades SE. Thus, OFDMA-PON is not suitable for asynchronous uplink transmission in optical access network. In this paper, we propose intensity modulation/direct detection (IM/DD) based universal filtered multi-carrier (UFMC) PON for asynchronous multiple access. The UFMC uses subband filtering to subsets of subcarriers. Since it reduces sidelobe of each subband by applying subband filtering, it could achieve better performance compared to OFDM. For the experimental demonstration, different sample delay was applied to subbands to implement asynchronous transmission condition. As a result, time synchronization robustness of UFMC was verified in asynchronous multiple access system.

A Binary Array Asynchronous Sorting Algorithm with Using Petri Nets

NASA Astrophysics Data System (ADS)

Voevoda, A. A.; Romannikov, D. O.

2017-01-01

Nowadays the tasks of computations speed-up and/or their optimization are actual. Among the approaches on how to solve these tasks, a method applying approaches of parallelization and asynchronization to a sorting algorithm is considered in the paper. The sorting methods are ones of elementary methods and they are used in a huge amount of different applications. In the paper, we offer a method of an array sorting that based on a division into a set of independent adjacent pairs of numbers and their parallel and asynchronous comparison. And this one distinguishes the offered method from the traditional sorting algorithms (like quick sorting, merge sorting, insertion sorting and others). The algorithm is implemented with the use of Petri nets, like the most suitable tool for an asynchronous systems description.

An ATR-dependent function for the Ddx19 RNA helicase in nuclear R-loop metabolism.

PubMed

Hodroj, Dana; Recolin, Bénédicte; Serhal, Kamar; Martinez, Susan; Tsanov, Nikolay; Abou Merhi, Raghida; Maiorano, Domenico

2017-05-02

Coordination between transcription and replication is crucial in the maintenance of genome integrity. Disturbance of these processes leads to accumulation of aberrant DNA:RNA hybrids (R-loops) that, if unresolved, generate DNA damage and genomic instability. Here we report a novel, unexpected role for the nucleopore-associated mRNA export factor Ddx19 in removing nuclear R-loops formed upon replication stress or DNA damage. We show, in live cells, that Ddx19 transiently relocalizes from the nucleopore to the nucleus upon DNA damage, in an ATR/Chk1-dependent manner, and that Ddx19 nuclear relocalization is required to clear R-loops. Ddx19 depletion induces R-loop accumulation, proliferation-dependent DNA damage and defects in replication fork progression. Further, we show that Ddx19 resolves R-loops in vitro via its helicase activity. Furthermore, mutation of a residue phosphorylated by Chk1 in Ddx19 disrupts its interaction with Nup214 and allows its nuclear relocalization. Finally, we show that Ddx19 operates in resolving R-loops independently of the RNA helicase senataxin. Altogether these observations put forward a novel, ATR-dependent function for Ddx19 in R-loop metabolism to preserve genome integrity in mammalian cells. © 2017 The Authors.

Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight into Virus Life Cycle▿

PubMed Central

Bourne, Christina; Lee, Sejin; Venkataiah, Bollu; Lee, Angela; Korba, Brent; Finn, M. G.; Zlotnick, Adam

2008-01-01

The relationship between the physical chemistry and biology of self-assembly is poorly understood, but it will be critical to quantitatively understand infection and for the design of antivirals that target virus genesis. Here we take advantage of heteroaryldihydropyrimidines (HAPs), which affect hepatitis B virus (HBV) assembly, to gain insight and correlate in vitro assembly with HBV replication in culture. Based on a low-resolution crystal structure of a capsid-HAP complex, a closely related series of HAPs were designed and synthesized. These differentially strengthen the association between neighboring capsid proteins, alter the kinetics of assembly, and give rise to aberrant structures incompatible with a functional capsid. The chemical nature of the HAP variants correlated well with the structure of the HAP binding pocket. The thermodynamics and kinetics of in vitro assembly had strong and predictable effects on product morphology. However, only the kinetics of in vitro assembly had a strong correlation with inhibition of HBV replication in HepG2.2.15 cells; there was at best a weak correlation between assembly thermodynamics and replication. The correlation between assembly kinetics and virus suppression implies a competition between successful assembly and misassembly, small molecule induced or otherwise. This is a predictive and testable model for the mechanism of action of assembly effectors. PMID:18684823

High content image based analysis identifies cell cycle inhibitors as regulators of Ebola virus infection.

PubMed

Kota, Krishna P; Benko, Jacqueline G; Mudhasani, Rajini; Retterer, Cary; Tran, Julie P; Bavari, Sina; Panchal, Rekha G

2012-09-25

Viruses modulate a number of host biological responses including the cell cycle to favor their replication. In this study, we developed a high-content imaging (HCI) assay to measure DNA content and identify different phases of the cell cycle. We then investigated the potential effects of cell cycle arrest on Ebola virus (EBOV) infection. Cells arrested in G1 phase by serum starvation or G1/S phase using aphidicolin or G2/M phase using nocodazole showed much reduced EBOV infection compared to the untreated control. Release of cells from serum starvation or aphidicolin block resulted in a time-dependent increase in the percentage of EBOV infected cells. The effect of EBOV infection on cell cycle progression was found to be cell-type dependent. Infection of asynchronous MCF-10A cells with EBOV resulted in a reduced number of cells in G2/M phase with concomitant increase of cells in G1 phase. However, these effects were not observed in HeLa or A549 cells. Together, our studies suggest that EBOV requires actively proliferating cells for efficient replication. Furthermore, multiplexing of HCI based assays to detect viral infection, cell cycle status and other phenotypic changes in a single cell population will provide useful information during screening campaigns using siRNA and small molecule therapeutics.

Interpolation algorithm for asynchronous ADC-data

NASA Astrophysics Data System (ADS)

Bramburger, Stefan; Zinke, Benny; Killat, Dirk

2017-09-01

This paper presents a modified interpolation algorithm for signals with variable data rate from asynchronous ADCs. The Adaptive weights Conjugate gradient Toeplitz matrix (ACT) algorithm is extended to operate with a continuous data stream. An additional preprocessing of data with constant and linear sections and a weighted overlap of step-by-step into spectral domain transformed signals improve the reconstruction of the asycnhronous ADC signal. The interpolation method can be used if asynchronous ADC data is fed into synchronous digital signal processing.

Application of intelligent soft start in asynchronous motor

NASA Astrophysics Data System (ADS)

Du, Xue; Ye, Ying; Wang, Yuelong; Peng, Lei; Zhang, Suying

2018-05-01

The starting way of three phase asynchronous motor has full voltage start and step-down start. Direct starting brings large current impact, causing excessive local temperature to the power grid and larger starting torque will also impact the motor equipment and affect the service life of the motor. Aim at the problem of large current and torque caused by start-up, an intelligent soft starter is proposed. Through the application of intelligent soft start on asynchronous motor, highlights its application advantage in motor control.

Does affective touch influence the virtual reality full body illusion?

PubMed

de Jong, Jutta R; Keizer, Anouk; Engel, Manja M; Dijkerman, H Chris

2017-06-01

The sense of how we experience our physical body as our own represents a fundamental component of human self-awareness. Body ownership can be studied with bodily illusions which are generated by inducing a visuo-tactile conflict where individuals experience illusionary ownership over a fake body or body part, such as a rubber hand. Previous studies showed that different types of touch modulate the strength of experienced ownership over a rubber hand. Specifically, participants experienced more ownership after the rubber hand illusion was induced through affective touch vs non-affective touch. It is, however, unclear whether this effect would also occur for an entire fake body. The aim of this study was, therefore, to investigate whether affective touch modulates the strength of ownership in a virtual reality full body illusion. To elicit this illusion, we used slow (3 cm/s; affective touch) and fast (30 cm/s; non-affective touch) stroking velocities on the participants' abdomen. Both stroking velocities were performed either synchronous or asynchronous (control condition), while participants viewed a virtual body from a first-person-perspective. In our first study, we found that participants experienced more subjective ownership over a virtual body in the affective touch condition, compared to the non-affective touch condition. In our second study, we found higher levels of subjective ownership for synchronous stimulation, compared to asynchronous, for both touch conditions, but failed to replicate the findings from study 1 that show a difference between affective and non-affective touch. We, therefore, cannot conclude unequivocally that affective touch enhances the full-body illusion. Future research is required to study the effects of affective touch on body ownership.

Aberrant localization of lamin B receptor (LBR) in cellular senescence in human cells

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

Arai, Rumi; En, Atsuki; Ukekawa, Ryo

2016-05-13

5-Bromodeoxyuridine (BrdU), a thymidine analogue, induces cellular senescence in mammalian cells. BrdU induces cellular senescence probably through the regulation of chromatin because BrdU destabilizes or disrupts nucleosome positioning and decondenses heterochromatin. Since heterochromatin is tethered to the nuclear periphery through the interaction with the nuclear envelope proteins, we examined the localization of the several nuclear envelope proteins such as lamins, lamin-interacting proteins, nuclear pore complex proteins, and nuclear transport proteins in senescent cells. We have shown here that lamin B receptor (LBR) showed a change in localization in both BrdU-induced and replicative senescent cells.

Determination of power and moment on shaft of special asynchronous electric drives

NASA Astrophysics Data System (ADS)

Karandey, V. Yu; Popov, B. K.; Popova, O. B.; Afanasyev, V. L.

2018-03-01

In the article, questions and tasks of determination of power and the moment on a shaft of special asynchronous electric drives are considered. Use of special asynchronous electric drives in mechanical engineering and other industries is relevant. The considered types of electric drives possess the improved mass-dimensional indicators in comparison with singleengine systems. Also these types of electric drives have constructive advantages; the improved characteristics allow one to realize the technological process. But creation and design of new electric drives demands adjustment of existing or development of new methods and approaches of calculation of parameters. Determination of power and the moment on a shaft of special asynchronous electric drives is the main objective during design of electric drives. This task has been solved based on a method of electromechanical transformation of energy.

Distributed asynchronous microprocessor architectures in fault tolerant integrated flight systems

NASA Technical Reports Server (NTRS)

Dunn, W. R.

1983-01-01

The paper discusses the implementation of fault tolerant digital flight control and navigation systems for rotorcraft application. It is shown that in implementing fault tolerance at the systems level using advanced LSI/VLSI technology, aircraft physical layout and flight systems requirements tend to define a system architecture of distributed, asynchronous microprocessors in which fault tolerance can be achieved locally through hardware redundancy and/or globally through application of analytical redundancy. The effects of asynchronism on the execution of dynamic flight software is discussed. It is shown that if the asynchronous microprocessors have knowledge of time, these errors can be significantly reduced through appropiate modifications of the flight software. Finally, the papear extends previous work to show that through the combined use of time referencing and stable flight algorithms, individual microprocessors can be configured to autonomously tolerate intermittent faults.

Why the tautomerization of the G·C Watson-Crick base pair via the DPT does not cause point mutations during DNA replication? QM and QTAIM comprehensive analysis.

PubMed

Brovarets', Ol'ha O; Hovorun, Dmytro M

2014-01-01

The ground-state tautomerization of the G·C Watson-Crick base pair by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (ϵ = 4), corresponding to a hydrophobic interface of protein-nucleic acid interactions, using DFT and MP2 levels of quantum-mechanical (QM) theory and quantum theory "Atoms in molecules" (QTAIM). Based on the sweeps of the electron-topological, geometric, polar, and energetic parameters, which describe the course of the G·C ↔ G*·C* tautomerization (mutagenic tautomers of the G and C bases are marked with an asterisk) through the DPT along the intrinsic reaction coordinate (IRC), it was proved that it is, strictly speaking, a concerted asynchronous process both at the DFT and MP2 levels of theory, in which protons move with a small time gap in vacuum, while this time delay noticeably increases in the continuum with ϵ = 4. It was demonstrated using the conductor-like polarizable continuum model (CPCM) that the continuum with ϵ = 4 does not qualitatively affect the course of the tautomerization reaction. The DPT in the G·C Watson-Crick base pair occurs without any intermediates both in vacuum and in the continuum with ϵ = 4 at the DFT/MP2 levels of theory. The nine key points along the IRC of the G·C base pair tautomerization, which could be considered as electron-topological "fingerprints" of a concerted asynchronous process of the tautomerization via the DPT, have been identified and fully characterized. These key points have been used to define the reactant, transition state, and product regions of the DPT reaction in the G·C base pair. Analysis of the energetic characteristics of the H-bonds allows us to arrive at a definite conclusion that the middle N1H⋯N3/N3H⋯N1 and the lower N2H⋯O2/N2H⋯O2 parallel H-bonds in the G·C/G*·C* base pairs, respectively, are anticooperative, that is, the strengthening of the middle H-bond is accompanied by the weakening of the lower H-bond. At that point, the upper N4H⋯O6 and O6H⋯N4 H-bonds in the G·C and G*·C* base pairs, respectively, remain constant at the changes of the middle and the lower H-bonds at the beginning and at the ending of the G·C ↔ G*·C* tautomerization. Aiming to answer the question posed in the title of the article, we established that the G*·C* Löwdin's base pair satisfies all the requirements necessary to cause point mutations in DNA except its lifetime, which is much less than the period of time required for the replication machinery to forcibly dissociate a base pair into the monomers (several ns) during DNA replication. So, from the physicochemical point of view, the G*·C* Löwdin's base pair cannot be considered as a source of point mutations arising during DNA replication.

Digital Self-Interference Cancellation for Asynchronous In-Band Full-Duplex Underwater Acoustic Communication.

PubMed

Qiao, Gang; Gan, Shuwei; Liu, Songzuo; Ma, Lu; Sun, Zongxin

2018-05-24

To improve the throughput of underwater acoustic (UWA) networking, the In-band full-duplex (IBFD) communication is one of the most vital pieces of research. The major drawback of IBFD-UWA communication is Self-Interference (SI). This paper presents a digital SI cancellation algorithm for asynchronous IBFD-UWA communication system. We focus on two issues: one is asynchronous communication dissimilar to IBFD radio communication, the other is nonlinear distortion caused by power amplifier (PA). First, we discuss asynchronous IBFD-UWA signal model with the nonlinear distortion of PA. Then, we design a scheme for asynchronous IBFD-UWA communication utilizing the non-overlapping region between SI and intended signal to estimate the nonlinear SI channel. To cancel the nonlinear distortion caused by PA, we propose an Over-Parameterization based Recursive Least Squares (RLS) algorithm (OPRLS) to estimate the nonlinear SI channel. Furthermore, we present the OPRLS with a sparse constraint to estimate the SI channel, which reduces the requirement of the length of the non-overlapping region. Finally, we verify our concept through simulation and the pool experiment. Results demonstrate that the proposed digital SI cancellation scheme can cancel SI efficiently.

A massively asynchronous, parallel brain.

PubMed

Zeki, Semir

2015-05-19

Whether the visual brain uses a parallel or a serial, hierarchical, strategy to process visual signals, the end result appears to be that different attributes of the visual scene are perceived asynchronously--with colour leading form (orientation) by 40 ms and direction of motion by about 80 ms. Whatever the neural root of this asynchrony, it creates a problem that has not been properly addressed, namely how visual attributes that are perceived asynchronously over brief time windows after stimulus onset are bound together in the longer term to give us a unified experience of the visual world, in which all attributes are apparently seen in perfect registration. In this review, I suggest that there is no central neural clock in the (visual) brain that synchronizes the activity of different processing systems. More likely, activity in each of the parallel processing-perceptual systems of the visual brain is reset independently, making of the brain a massively asynchronous organ, just like the new generation of more efficient computers promise to be. Given the asynchronous operations of the brain, it is likely that the results of activities in the different processing-perceptual systems are not bound by physiological interactions between cells in the specialized visual areas, but post-perceptually, outside the visual brain.

Scenario Decomposition for 0-1 Stochastic Programs: Improvements and Asynchronous Implementation

DOE PAGES

Ryan, Kevin; Rajan, Deepak; Ahmed, Shabbir

2016-05-01

We recently proposed scenario decomposition algorithm for stochastic 0-1 programs finds an optimal solution by evaluating and removing individual solutions that are discovered by solving scenario subproblems. In our work, we develop an asynchronous, distributed implementation of the algorithm which has computational advantages over existing synchronous implementations of the algorithm. Improvements to both the synchronous and asynchronous algorithm are proposed. We also test the results on well known stochastic 0-1 programs from the SIPLIB test library and is able to solve one previously unsolved instance from the test set.

Finite-time synchronization of uncertain coupled switched neural networks under asynchronous switching.

PubMed

Wu, Yuanyuan; Cao, Jinde; Li, Qingbo; Alsaedi, Ahmed; Alsaadi, Fuad E

2017-01-01

This paper deals with the finite-time synchronization problem for a class of uncertain coupled switched neural networks under asynchronous switching. By constructing appropriate Lyapunov-like functionals and using the average dwell time technique, some sufficient criteria are derived to guarantee the finite-time synchronization of considered uncertain coupled switched neural networks. Meanwhile, the asynchronous switching feedback controller is designed to finite-time synchronize the concerned networks. Finally, two numerical examples are introduced to show the validity of the main results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.

PubMed

Amaya, Ronny; Cancel, Limary M; Tarbell, John M

2016-01-01

Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle-SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease.

Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression

PubMed Central

Amaya, Ronny; Cancel, Limary M.; Tarbell, John M.

2016-01-01

Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle–SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA as well as reversal flow (OSI) are important parameters characterizing arterial susceptibility to disease. PMID:27846267

Electrical engineering unit for the reactive power control of the load bus at the voltage instability

NASA Astrophysics Data System (ADS)

Kotenev, A. V.; Kotenev, V. I.; Kochetkov, V. V.; Elkin, D. A.

2018-01-01

For the purpose of reactive power control error reduction and decrease of the voltage sags in the electric power system caused by the asynchronous motors started the mathematical model of the load bus was developed. The model was built up of the sub-models of the following elements: a transformer, a transmission line, a synchronous and an asynchronous loads and a capacitor bank load, and represents the automatic reactive power control system taking into account electromagnetic processes of the asynchronous motors started and reactive power changing of the electric power system elements caused by the voltage fluctuation. The active power/time and reactive power/time characteristics based on the recommended procedure of the equivalent electric circuit parameters calculation were obtained. The derived automatic reactive power control system was shown to eliminate the voltage sags in the electric power system caused by the asynchronous motors started.

PsychVACS: a system for asynchronous telepsychiatry.

PubMed

Odor, Alberto; Yellowlees, Peter; Hilty, Donald; Parish, Michelle Burke; Nafiz, Najia; Iosif, Ana-Maria

2011-05-01

To describe the technical development of an asynchronous telepsychiatry application, the Psychiatric Video Archiving and Communication System. A client-server application was developed in Visual Basic.Net with Microsoft(®) SQL database as the backend. It includes the capability of storing video-recorded psychiatric interviews and manages the workflow of the system with automated messaging. Psychiatric Video Archiving and Communication System has been used to conduct the first ever series of asynchronous telepsychiatry consultations worldwide. A review of the software application and the process as part of this project has led to a number of improvements that are being implemented in the next version, which is being written in Java. This is the first description of the use of video recorded data in an asynchronous telemedicine application. Primary care providers and consulting psychiatrists have found it easy to work with and a valuable resource to increase the availability of psychiatric consultation in remote rural locations.

An improved asynchronous brain interface: making use of the temporal history of the LF-ASD feature vectors

NASA Astrophysics Data System (ADS)

Bashashati, Ali; Mason, Steve; Ward, Rabab K.; Birch, Gary E.

2006-06-01

The low-frequency asynchronous switch design (LF-ASD) has been introduced as a direct brain interface (BI) for asynchronous control applications. Asynchronous interfaces, as opposed to synchronous interfaces, have the advantage of being operational at all times and not only at specific system-defined periods. This paper modifies the LF-ASD design by incorporating into the system more knowledge about the attempted movements. Specifically, the history of feature values extracted from the EEG signal is used to detect a right index finger movement attempt. Using data collected from individuals with high-level spinal cord injuries and able-bodied subjects, it is shown that the error characteristics of the modified design are significantly better than the previous LF-ASD design. The true positive rate percentage increased by up to 15 which corresponds to 50% improvement when the system is operating with false positive rates in the 1-2% range.

Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

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

Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators.more » We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM binding to mtDNA. • Replicating nucleoids are less prone to DNA intercalator and preserve more TFAM. • Nucleoid clusters mostly contain nucleoids with newly replicated mtDNA. • Recently replicated nucleoids are protected in clusters by increased TFAM and p53.« less

A Communication Perspective on Sexual Harassment: Affiliative Nonverbal Behaviors in Asynchronous Relationships.

ERIC Educational Resources Information Center

Hickson, Mark, III; And Others

1991-01-01

Develops a communication perspective on sexual harassment in asynchronous relationships. Presents a six-step process model to predict private harassing behavior among faculty members in higher education. Makes suggestions for prevention of sexual harassment. (SR)

DNA replication events during larval silk gland development in the silkworm, Bombyx mori.

PubMed

Zhang, Chun-Dong; Li, Fang-Fang; Chen, Xiang-Yun; Huang, Mao-Hua; Zhang, Jun; Cui, Hongjuan; Pan, Min-Hui; Lu, Cheng

2012-07-01

The silk gland is an important organ in silkworm as it synthesizes silk proteins and is critical to spinning. The genomic DNA content of silk gland cells dramatically increases 200-400 thousand times for the larval life span through the process of endomitosis. Using in vitro culture, DNA synthesis was measured using BrdU labeling during the larval molt and intermolt periods. We found that the cell cycle of endomitosis was activated during the intermolt and was inhibited during the molt phase. The anterior silk gland, middle silk gland, and posterior silk gland cells asynchronously exit the endomitotic cycle after day 6 in 5th instar larvae, which correlated with the reduced expression of the cell cycle-related cdt1, pcna, cyclin E, cdk2 and cdk1 mRNAs in the wandering phase. Additional starvation had no effect on the initiation of silk gland DNA synthesis of the freshly ecdysed larvae. Copyright © 2012 Elsevier Ltd. All rights reserved.

Student Satisfaction with Asynchronous Learning

ERIC Educational Resources Information Center

Dziuban, Charles; Moskal, Patsy; Brophy, Jay; Shea, Peter

2007-01-01

The authors discuss elements that potentially impact student satisfaction with asynchronous learning: the media culture, digital, personal and mobile technologies, student learning preferences, pedagogy, complexities of measurement, and the digital generation. They describe a pilot study to identify the underlying dimensions of student…

Software and hardware complex for research and management of the separation process

NASA Astrophysics Data System (ADS)

Borisov, A. P.

2018-01-01

The article is devoted to the development of a program for studying the operation of an asynchronous electric drive using vector-algorithmic switching of windings, as well as the development of a hardware-software complex for controlling parameters and controlling the speed of rotation of an asynchronous electric drive for investigating the operation of a cyclone. To study the operation of an asynchronous electric drive, a method was used in which the average value of flux linkage is found and a method for vector-algorithmic calculation of the power and electromagnetic moment of an asynchronous electric drive feeding from a single-phase network is developed, with vector-algorithmic commutation, and software for calculating parameters. The software part of the complex allows to regulate the speed of rotation of the motor by vector-algorithmic switching of transistors or, using pulse-width modulation (PWM), set any engine speed. Also sensors are connected to the hardware-software complex at the inlet and outlet of the cyclone. The developed cyclone with an inserted complex allows to receive high efficiency of product separation at various entrance speeds. At an inlet air speed of 18 m / s, the cyclone’s maximum efficiency is achieved. For this, it is necessary to provide the rotational speed of an asynchronous electric drive with a frequency of 45 Hz.

An exploration of teaching presence in online interprofessional education facilitation.

PubMed

Evans, Sherryn Maree; Ward, Catherine; Reeves, Scott

2017-07-01

Although the prevalence of online asynchronous interprofessional education (IPE) has increased in the last decade, little is known about the processes of facilitation in this environment. The teaching presence element of the Community of Inquiry Framework offers an approach to analyze the contributions of online facilitators, however, to date it has only been used on a limited basis in health professions education literature. Using an exploratory case study design, we explored the types of contributions made by IPE facilitators to asynchronous interprofessional team discussions by applying the notion of teaching presence. Using a purposeful sampling approach, we analyzed 14 facilitators' contributions to asynchronous team discussion boards in an online IPE course. We analyzed data using directed content analysis based on the key indicators of teaching presence. The online IPE facilitators undertook the three critical pedagogical functions identified in teaching presence: facilitating discourse, direct instruction, and instructional design and organization. While our data fitted well with a number of key activities embedded in these three functions, further modification of the teaching presence concept was needed to describe our facilitators' teaching presence. This study provides an initial insight into the key elements of online asynchronous IPE facilitation. Further research is required to continue to illuminate the complexity of online asynchronous IPE facilitation.

Asynchronous P300 classification in a reactive brain-computer interface during an outlier detection task

NASA Astrophysics Data System (ADS)

Krumpe, Tanja; Walter, Carina; Rosenstiel, Wolfgang; Spüler, Martin

2016-08-01

Objective. In this study, the feasibility of detecting a P300 via an asynchronous classification mode in a reactive EEG-based brain-computer interface (BCI) was evaluated. The P300 is one of the most popular BCI control signals and therefore used in many applications, mostly for active communication purposes (e.g. P300 speller). As the majority of all systems work with a stimulus-locked mode of classification (synchronous), the field of applications is limited. A new approach needs to be applied in a setting in which a stimulus-locked classification cannot be used due to the fact that the presented stimuli cannot be controlled or predicted by the system. Approach. A continuous observation task requiring the detection of outliers was implemented to test such an approach. The study was divided into an offline and an online part. Main results. Both parts of the study revealed that an asynchronous detection of the P300 can successfully be used to detect single events with high specificity. It also revealed that no significant difference in performance was found between the synchronous and the asynchronous approach. Significance. The results encourage the use of an asynchronous classification approach in suitable applications without a potential loss in performance.

Influence of homologous recombinational repair on cell survival and chromosomal aberration induction during the cell cycle in γ-irradiated CHO cells

PubMed Central

Wilson, Paul F.; Hinz, John M.; Urbin, Salustra S.; Nham, Peter B.; Thompson, Larry H.

2010-01-01

The repair of DNA double-strand breaks (DSB) by homologous recombinational repair (HRR) underlies the high radioresistance and low mutability observed in S-phase mammalian cells. To evaluate the contributions of HRR and nonhomologous end-joining (NHEJ) to overall DSB repair capacity throughout the cell cycle after γ-irradiation, we compared HRR-deficient RAD51D-knockout 51D1 to CgRAD51D-complemented 51D1 (51D1.3) CHO cells for survival and chromosomal aberrations (CAs). Asynchronous cultures were irradiated with 150 or 300 cGy and separated by cell size using centrifugal elutriation. Cell survival of each synchronous fraction (~20 fractions total from early G1 to late G2/M) was measured by colony formation. 51D1.3 cells were most resistant in S, while 51D1 cells were most resistant in early G1 (with survival and chromosome-type CA levels similar to 51D1.3) and became progressively more sensitive throughout S and G2. Both cell lines experienced significantly reduced survival from late S into G2. Metaphases were collected from every third elutriation fraction at the first post-irradiation mitosis and scored for CAs. 51D1 cells irradiated in S and G2 had ~2-fold higher chromatid-type CAs and a remarkable ~25-fold higher level of complex chromatid-type exchanges compared to 51D1.3 cells. Complex exchanges in 51D1.3 cells were only observed in G2. These results show an essential role for HRR in preventing gross chromosomal rearrangements in proliferating cells and, with our previous report of reduced survival of G2-phase NHEJ-deficient prkdc CHO cells [Hinz et al. DNA Repair 4, 782–792, 2005], imply reduced activity/efficiency of both HRR and NHEJ as cells transition from S to G2. PMID:20434408

The human intra-S checkpoint response to UVC-induced DNA damage.

PubMed

Kaufmann, William K

2010-05-01

The intra-S checkpoint response to 254 nm light (UVC)-induced DNA damage appears to have dual functions to slow the rate of DNA synthesis and stabilize replication forks that become stalled at sites of UVC-induced photoproducts in DNA. These functions should provide more time for repair of damaged DNA before its replication and thereby reduce the frequencies of mutations and chromosomal aberrations in surviving cells. This review tries to summarize the history of discovery of the checkpoint, the current state of understanding of the biological features of intra-S checkpoint signaling and its mechanisms of action with a focus primarily on intra-S checkpoint responses in human cells. The differences in the intra-S checkpoint responses to UVC and ionizing radiation-induced DNA damage are emphasized. Evidence that [6-4]pyrimidine-pyrimidone photoproducts in DNA trigger the response is discussed and the relationships between cellular responses to UVC and the molecular dose of UVC-induced DNA damage are briefly summarized. The role of the intra-S checkpoint response in protecting against solar radiation carcinogenesis remains to be determined.

Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites.

PubMed

Dey, Abhishek; Chakrabarti, Kausik

2018-01-24

Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma , etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases.

Can tautomerization of the A·T Watson-Crick base pair via double proton transfer provoke point mutations during DNA replication? A comprehensive QM and QTAIM analysis.

PubMed

Brovarets, Ol'ha O; Hovorun, Dmytro M

2014-01-01

Trying to answer the question posed in the title, we have carried out a detailed theoretical investigation of the biologically important mechanism of the tautomerization of the A·T Watson-Crick DNA base pair, information that is hard to establish experimentally. By combining theoretical investigations at the MP2 and density functional theory levels of QM theory with quantum theory of atoms in molecules analysis, the tautomerization of the A·T Watson-Crick base pair by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (ϵ = 4) corresponding to a hydrophobic interfaces of protein-nucleic acid interactions. Based on the sweeps of the electron-topological, geometric, and energetic parameters, which describe the course of the tautomerization along its intrinsic reaction coordinate (IRC), it was proved that the A·T → A(∗)·T(∗) tautomerization through the DPT is a concerted (i.e. the pathway without an intermediate) and asynchronous (i.e. protons move with a time gap) process. The limiting stage of this phenomenon is the final PT along the N6H⋯O4 hydrogen bond (H-bond). The continuum with ϵ = 4 does not affect qualitatively the course of the tautomerization reaction: similar to that observed in vacuo, it proceeds via a concerted asynchronous process with the same structure of the transition state (TS). For the first time, the nine key points along the IRC of the A·T base pair tautomerization, which could be considered as electron-topological "fingerprints" of a concerted asynchronous process of the tautomerization via the DPT, have been identified and fully characterized. These nine key points have been used to define the reactant, TS, and product regions of the DPT in the A·T base pair. Considering the energy dependence of each of the three H-bonds, which stabilize the Watson-Crick and Löwdin's base pairs, along the IRC of the tautomerization, it was found that all these H-bonds in the А·Т base pair are cooperative, reinforcing each other, whereas the C2H⋯O2 H-bond in the А(∗)·Т(∗) base pair behaves anticooperatively, in other words it gets weakened while two others get strengthened. From a quantum-mechanical point of view, the A(∗)·T(∗) Löwdin's base pair appeared to be dynamically unstable because the electronic energy of the back-reaction barrier of the A·T → A(∗)·T(∗) tautomerization does not exceed zero-point vibrational energy associated with the mode for which vibrational frequency becomes imaginary in the TS of tautomerization. Additionally, it was demonstrated using the conductor-like polarizable continuum model that the effects of biomolecular environment (ϵ = 4) cannot ensure dynamic stabilization of the A(∗)·T(∗) Löwdin's base pair. These findings, together with data available from the literature, indicate that the tautomerization of the A·T Watson-Crick base pair to the A(∗)·T(∗) Löwdin's base pair through the DPT cannot be a source of spontaneous point errors that occur during DNA replication.

Learning Objects and Gerontology

ERIC Educational Resources Information Center

Weinreich, Donna M.; Tompkins, Catherine J.

2006-01-01

Virtual AGE (vAGE) is an asynchronous educational environment that utilizes learning objects focused on gerontology and a learning anytime/anywhere philosophy. This paper discusses the benefits of asynchronous instruction and the process of creating learning objects. Learning objects are "small, reusable chunks of instructional media" Wiley…

Redundant Asynchronous Microprocessor System

NASA Technical Reports Server (NTRS)

Meyer, G.; Johnston, J. O.; Dunn, W. R.

1985-01-01

Fault-tolerant computer structure called RAMPS (for redundant asynchronous microprocessor system) has simplicity of static redundancy but offers intermittent-fault handling ability of complex, dynamically redundant systems. New structure useful wherever several microprocessors are employed for control - in aircraft, industrial processes, robotics, and automatic machining, for example.

A comparison of classroom and online asynchronous problem-based learning for students undertaking statistics training as part of a Public Health Masters degree.

PubMed

de Jong, N; Verstegen, D M L; Tan, F E S; O'Connor, S J

2013-05-01

This case-study compared traditional, face-to-face classroom-based teaching with asynchronous online learning and teaching methods in two sets of students undertaking a problem-based learning module in the multilevel and exploratory factor analysis of longitudinal data as part of a Masters degree in Public Health at Maastricht University. Students were allocated to one of the two study variants on the basis of their enrolment status as full-time or part-time students. Full-time students (n = 11) followed the classroom-based variant and part-time students (n = 12) followed the online asynchronous variant which included video recorded lectures and a series of asynchronous online group or individual SPSS activities with synchronous tutor feedback. A validated student motivation questionnaire was administered to both groups of students at the start of the study and a second questionnaire was administered at the end of the module. This elicited data about student satisfaction with the module content, teaching and learning methods, and tutor feedback. The module coordinator and problem-based learning tutor were also interviewed about their experience of delivering the experimental online variant and asked to evaluate its success in relation to student attainment of the module's learning outcomes. Student examination results were also compared between the two groups. Asynchronous online teaching and learning methods proved to be an acceptable alternative to classroom-based teaching for both students and staff. Educational outcomes were similar for both groups, but importantly, there was no evidence that the asynchronous online delivery of module content disadvantaged part-time students in comparison to their full-time counterparts.

Innovative Methods for Providing Instruction to Distance Students Using Technology.

ERIC Educational Resources Information Center

Pival, Paul R.; Tunon, Johanna

2001-01-01

Examines three innovative methods tried at Nova Southeastern University for providing quality bibliographic instruction to distance students: one synchronous, one asynchronous, and one that combined features from both synchronous and asynchronous methods of delivering instruction. Topics include compressed video, collaborative groupware, streaming…

Miscellany of Students' Satisfaction in an Asynchronous Learning Environment

ERIC Educational Resources Information Center

Larbi-Siaw, Otu; Owusu-Agyeman, Yaw

2017-01-01

This study investigates the determinants of students' satisfaction in an asynchronous learning environment using seven key considerations: the e-learning environment, student-content interaction, student and student interaction, student-teacher interaction, group cohesion and timely participation, knowledge of Internet usage, and satisfaction. The…

Developing asynchronous online interprofessional education.

PubMed

Sanborn, Heidi

2016-09-01

For many health programmes, developing interprofessional education (IPE) has been a challenge. Evidence on the best method for design and implementation of IPE has been slow to emerge, with little research on how to best incorporate IPE in the asynchronous online learning environment. This leaves online programmes with no clear guidance when embarking upon an initiative to integrate IPE into the curriculum. One tool that can be effective at guiding the incorporation of IPE across all learning platforms is the Interprofessional Education Collaborative (IPEC) competencies. A project was designed to integrate the nationally defined IPEC competencies throughout an asynchronous, online baccalaureate nursing completion programme. A programme-wide review led to targeted revision of course and unit-level objectives, learning experiences, and assessments based on the IPEC framework. As a result of this effort, the programme curriculum now provides interprofessional learning activities across all courses. This report provides a method for using the IPEC competencies to incorporate IPE within various asynchronous learning assessments, assuring students learn about, with, and from other professions.

AP-IO: asynchronous pipeline I/O for hiding periodic output cost in CFD simulation.

PubMed

Xiaoguang, Ren; Xinhai, Xu

2014-01-01

Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%.

Asynchronous Cholinergic Drive Correlates with Excitation-Inhibition Imbalance via a Neuronal Ca2+ Sensor Protein.

PubMed

Zhou, Keming; Cherra, Salvatore J; Goncharov, Alexandr; Jin, Yishi

2017-05-09

Excitation-inhibition imbalance in neural networks is widely linked to neurological and neuropsychiatric disorders. However, how genetic factors alter neuronal activity, leading to excitation-inhibition imbalance, remains unclear. Here, using the C. elegans locomotor circuit, we examine how altering neuronal activity for varying time periods affects synaptic release pattern and animal behavior. We show that while short-duration activation of excitatory cholinergic neurons elicits a reversible enhancement of presynaptic strength, persistent activation results to asynchronous and reduced cholinergic drive, inducing imbalance between endogenous excitation and inhibition. We find that the neuronal calcium sensor protein NCS-2 is required for asynchronous cholinergic release in an activity-dependent manner and dampens excitability of inhibitory neurons non-cell autonomously. The function of NCS-2 requires its Ca 2+ binding and membrane association domains. These results reveal a synaptic mechanism implicating asynchronous release in regulation of excitation-inhibition balance. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

High-Throughput Bit-Serial LDPC Decoder LSI Based on Multiple-Valued Asynchronous Interleaving

NASA Astrophysics Data System (ADS)

Onizawa, Naoya; Hanyu, Takahiro; Gaudet, Vincent C.

This paper presents a high-throughput bit-serial low-density parity-check (LDPC) decoder that uses an asynchronous interleaver. Since consecutive log-likelihood message values on the interleaver are similar, node computations are continuously performed by using the most recently arrived messages without significantly affecting bit-error rate (BER) performance. In the asynchronous interleaver, each message's arrival rate is based on the delay due to the wire length, so that the decoding throughput is not restricted by the worst-case latency, which results in a higher average rate of computation. Moreover, the use of a multiple-valued data representation makes it possible to multiplex control signals and data from mutual nodes, thus minimizing the number of handshaking steps in the asynchronous interleaver and eliminating the clock signal entirely. As a result, the decoding throughput becomes 1.3 times faster than that of a bit-serial synchronous decoder under a 90nm CMOS technology, at a comparable BER.

AP-IO: Asynchronous Pipeline I/O for Hiding Periodic Output Cost in CFD Simulation

PubMed Central

Xiaoguang, Ren; Xinhai, Xu

2014-01-01

Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%. PMID:24955390

Asynchronous and synchronous dual-wavelength pulse generation in a passively mode-locked fiber laser with a mode-locker.

PubMed

Hu, Guoqing; Pan, Yingling; Zhao, Xin; Yin, Siyao; Zhang, Meng; Zheng, Zheng

2017-12-01

The evolution from asynchronous to synchronous dual-wavelength pulse generation in a passively mode-locked fiber laser is experimentally investigated by tailoring the intracavity dispersion. Through tuning the intracavity-loss-dependent gain profile and the birefringence-induced filter effect, asynchronous dual-wavelength soliton pulses can be generated until the intracavity anomalous dispersion is reduced to ∼8  fs/nm. The transition from asynchronous to synchronous pulse generation is then observed at an elevated pump power in the presence of residual anomalous dispersion, and it is shown that pulses are temporally synchronized at the mode-locker in the cavity. Spectral sidelobes are observed and could be attributed to the four-wave-mixing effect between dual-wavelength pulses at the carbon nanotube mode-locker. These results could provide further insight into the design and realization of such dual-wavelength ultrafast lasers for different applications such as dual-comb metrology as well as better understanding of the inter-pulse interactions in such dual-comb lasers.

Asynchronous updates can promote the evolution of cooperation on multiplex networks

NASA Astrophysics Data System (ADS)

Allen, James M.; Hoyle, Rebecca B.

2017-04-01

We study the importance to the frequency of cooperation of the choice of updating strategies in a game played asynchronously or synchronously across layers in a multiplex network. Updating asynchronously in the public goods game leads to higher frequencies of cooperation compared to synchronous updates. How large this effect is depends on the sensitivity of the game dynamics to changes in the number of cooperators surrounding a player, with the largest effect observed when players payoffs are small. The discovery of this effect enhances understanding of cooperation on multiplex networks, and demonstrates a new way to maintain cooperation in these systems.

Control strategy for a variable-speed wind energy conversion system

NASA Technical Reports Server (NTRS)

Jacob, A.; Veillette, D.; Rajagopalan, V.

1979-01-01

A control concept for a variable-speed wind energy conversion system is proposed, for which a self-exited asynchronous cage generator is used along with a system of thyristor converters. The control loops are the following: (1) regulation of the entrainment speed as function of available mechanical energy by acting on the resistance couple of the asynchronous generator; (2) control of electric power delivered to the asynchronous machine, functioning as a motor, for start-up of the vertical axis wind converter; and (3) limitation of the slip value, and by consequence, of the induction currents in the presence of sudden variations of input parameters.

Asynchronous versus Synchronous Learning in Pharmacy Education

ERIC Educational Resources Information Center

Motycka, Carol A.; St. Onge, Erin L.; Williams, Jennifer

2013-01-01

Objective: To better understand the technology being used today in pharmacy education through a review of the current methodologies being employed at various institutions. Also, to discuss the benefits and difficulties of asynchronous and synchronous methodologies, which are being utilized at both traditional and distance education campuses.…

Knowledge Building in Asynchronous Discussion Groups: Going Beyond Quantitative Analysis

ERIC Educational Resources Information Center

Schrire, Sarah

2006-01-01

This contribution examines the methodological challenges involved in defining the collaborative knowledge-building processes occurring in asynchronous discussion and proposes an approach that could advance understanding of these processes. The written protocols that are available to the analyst provide an exact record of the instructional…

Creating and Nurturing Distributed Asynchronous Learning Environments.

ERIC Educational Resources Information Center

Kochtanek, Thomas R.; Hein, Karen K.

2000-01-01

Describes the evolution of a university course from a face-to-face experience to a Web-based asynchronous learning environment. Topics include cognition and learning; distance learning and distributed learning; student learning communities and the traditional classroom; the future as it relates to education and technology; collaborative student…

Learning about the Literacy Development of English Language Learners in Asynchronous Online Discussions

ERIC Educational Resources Information Center

De Oliveira, Luciana C.; Olesova, Larisa

2013-01-01

This study examined asynchronous online discussions in the online course "English Language Development" to identify themes related to participants' learning about the language and literacy development of English Language Learners when they facilitated online discussions to determine whether the participants developed sufficient…

Creating Asynchronous Online Learning Communities

ERIC Educational Resources Information Center

Kerr, Crystal

2009-01-01

This research project examined how to develop and sustain online, asynchronous learning communities in continuous intake, distance education environments for learners in grades 7 through 10. The study is an action research project that is based upon in-depth, qualitative data. Interviews were conducted with distance education teachers,…

E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution.

PubMed

Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

2015-10-01

Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53(-/-) mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy.

E2F1 and E2F2 prevent replicative stress and subsequent p53-dependent organ involution

PubMed Central

Iglesias-Ara, A; Zenarruzabeitia, O; Buelta, L; Merino, J; Zubiaga, A M

2015-01-01

Tissue homeostasis requires tight regulation of cellular proliferation, differentiation and apoptosis. E2F1 and E2F2 transcription factors share a critical role in tissue homeostasis, since their combined inactivation results in overall organ involution, specially affecting the pancreatic gland, which subsequently triggers diabetes. We have examined the mechanism by which these E2Fs regulate tissue homeostasis. We show that pancreas atrophy in E2F1/E2F2 double-knockout (DKO) mice is associated with mitochondrial apoptosis and activation of the p53 pathway in young animals, before the development of diabetes. A deregulated expression of E2F target genes was detected in pancreatic cells of young DKO animals, along with unscheduled DNA replication and activation of a DNA damage response. Importantly, suppression of DNA replication in vivo with aphidicolin led to a significant inhibition of the p53 pathway in DKO pancreas, implying a causal link between DNA replication stress and p53 activation in this model. We further show that activation of the p53 pathway has a key role in the aberrant phenotype of DKO mice, since targeted inactivation of p53 gene abrogated cellular apoptosis and prevented organ involution and insulin-dependent diabetes in mice lacking E2F1/E2F2. Unexpectedly, p53 inactivation unmasked oncogenic features of E2F1/E2F2-depleted cells, as evidenced by an accelerated tumor development in triple-knockout mice compared with p53−/− mice. Collectively, our data reveal a role for E2F1 and E2F2 as suppressors of replicative stress in differentiating cells, and uncover the existence of a robust E2F-p53 regulatory axis to enable tissue homeostasis and prevent tumorigenesis. These findings have implications in the design of approaches targeting E2F for cancer therapy. PMID:25656653

Defining the steps that lead to cancer: replicative telomere erosion, aneuploidy and an epigenetic maturation arrest of tissue stem cells.

PubMed

Stindl, Reinhard

2008-01-01

Recently, an influential sequencing study found that more than 1700 genes had non-silent mutations in either a breast or colorectal cancer, out of just 11 breast and 11 colorectal tumor samples. This is not surprising given the fact that genomic instability is the hallmark of cancer cells. The plethora of genomic alterations found in every carcinoma does not obey the 'law of genotype-phenotype correlation', since the same histological subtype of cancer harbors different gene mutations and chromosomal aberrations in every patient. In an attempt to make sense out of the observed genetic and chromosomal chaos in cancer, I propose a cascade model. According to this model, tissue regeneration depends on the proliferation and serial activation of stem cells. Replicative telomere erosion limits the proliferative life span of adult stem cells and results in the Hayflick limit (M1). However, local tissue exhaustion or old age might promote the activation of M1-deficient tissue stem cells. Extended proliferation of these cells leads to telomere-driven chromosomal instability and aneuploidy (abnormal balance of chromosomes and/or chromosome material). Several of the aforementioned steps have been already described in the literature. However, in contrast to common theories, it is proposed here that the genomic damage blocks the epigenetic differentiation switch. As a result of aneuploidy, differentiation-specific genes cannot be activated by modification of methylation patterns. Consequently, the phenotype of cancer tissue is largely determined by the epigenetic maturation arrest of tissue stem cells, which in addition enables a fraction of cancer cells to proliferate, invade and metastasize, as normal adult stem cells do. The new model combines genetic and epigenetic alterations of cancer cells in one causative cascade and offers an explanation for why identical histologic cancer types harbor a confusing variety of chromosomal and gene aberrations. The Viennese Cascade, as presented here, may end the debate on if and how 'tumor-unspecific' aneuploidy leads to cancer.

Multistage carcinogenesis in cell culture.

PubMed

Rubin, H

2001-01-01

Rodent fibroblasts explanted from embryos to culture undergo a period of declining growth rate in serial passages leading to crisis, followed by the appearance of variants which can multiply indefinitely. If the "immortal" cell line was established by low density passage, i.e., 3T3 cells, it has a low saturation density and is non-tumorigenic. If it was established by high density passage, it has a high saturation density and is tumorigenic. The establishment of cells goes through successive stages, including increased capacity to multiply in low serum concentration, growth to high saturation density, growth in suspension, assisted tumour formation in susceptible hosts and unassisted tumour formation. Chromosome aberrations and aneuploidy occur long before the capacity to produce tumours appears. Contrary to conventional belief, human fibroblast populations also undergo a continuous loss of capacity to multiply from the time of explantation, with only the longest surviving clone reaching the Hayflick limit. Neoplastic transformation of rodent cells is strongly favoured by maintaining them in a quiescent state at confluence for prolonged periods, which results in genetic damage to the cells. It also produces a large variety of chromosomal aberrations in human cells and extends their replicative lifespan. Individual clones are more susceptible to spontaneous transformation than their heterogeneous parental cultures. The implications of these results for tumour development in vivo are that oncogenic genetic changes may be common under stressful conditions which restrict replication, and that such changes are maximized when a rogue clone reaches a critical size that reduces stabilizing interactions with neighbouring clones. An alternative explanation, described in the Addendum, which we retrospectively favor is that the easily transformed clones are a minority in the uncloned parental population. The reason they transform before the parental population is that when they are expanded, they have more transformable cells available under the selective condition of confluence than the uncloned parental population from which they are derived.

The Necessity of Real-Time: Fact and Fiction in Digital Reference Systems.

ERIC Educational Resources Information Center

Lankes, R. David; Shostack, Pauline

2002-01-01

Discussion of digital reference services and the use of real-time versus asynchronous services such as email focuses on data from the AskERIC digital reference service to demonstrate that asynchronous services are not only useful but may have greater utility than real-time systems. (Author/LRW)

Positioning (Mis)Aligned: The (Un)Making of Intercultural Asynchronous Computer-Mediated Communication

ERIC Educational Resources Information Center

Wu, Zhiwei

2018-01-01

Framed from positioning theory and dynamic systems theory, the paper reports on a naturalistic study involving four Chinese participants and their American peers in an intercultural asynchronous computer-mediated communication (ACMC) activity. Based on the moment-by-moment analysis and triangulation of forum posts, reflective essays, and…

Automated Feedback as a Convergence Tool

ERIC Educational Resources Information Center

Chenoweth, Tim; Corral, Karen; Scott, Kit

2016-01-01

This study evaluates two content delivery options for teaching a programming language to determine whether an asynchronous format can achieve the same learning efficacy as a traditional lecture (face-to-face) format. We use media synchronicity theory as a guide to choose media capabilities to incorporate into an asynchronous tutorial used…

Designing a Web-Based Asynchronous Innovation/Entrepreneurism Course

ERIC Educational Resources Information Center

Ghandforoush, Parviz

2017-01-01

Teaching an online fully asynchronous information technology course that requires students to ideate, build an e-commerce website, and develop an effective business plan involves a well-developed and highly engaging course design. This paper describes the design, development, and implementation of such a course and presents information on…

Asynchronous Assessment in a Large Lecture Marketing Course

ERIC Educational Resources Information Center

Downey, W. Scott; Schetzsle, Stacey

2012-01-01

Asynchronous assessment, which includes quizzes or exams online or outside class, offers marketing educators an opportunity to make more efficient use of class time and to enhance students' learning experiences by giving them more flexibility and choice in their assessment environment. In this paper, we examine the performance difference between…

Principles for Effective Asynchronous Online Instruction in Religious Studies

ERIC Educational Resources Information Center

McGuire, Beverley

2017-01-01

Asynchronous online instruction has become increasingly popular in the field of religious studies. However, despite voluminous research on online learning in general and numerous articles on online theological instruction, there has been little discussion of how to effectively design and deliver online undergraduate courses in religious studies.…

Investigating Asynchronous Online Communication: A Connected Stance Revealed

ERIC Educational Resources Information Center

Wegmann, Susan J.; McCauley, Joyce K.

2014-01-01

This research project explores the effects of altering the structure of discussion board formats to increase students' engagement and participation. This paper will present the findings of a two-university, two-class research project in which asynchronous discussion board entries were analyzed for substance. By using oral discourse analysis…

Theoretically Based Pedagogical Strategies Leading to Deep Learning in Asynchronous Online Gerontology Courses

ERIC Educational Resources Information Center

Majeski, Robin; Stover, Merrily

2007-01-01

Online learning has enjoyed increasing popularity in gerontology. This paper presents instructional strategies grounded in Fink's (2003) theory of significant learning designed for the completely asynchronous online gerontology classroom. It links these components with the development of mastery learning goals and provides specific guidelines for…

Developing a Successful Asynchronous Online Extension Program for Forest Landowners

ERIC Educational Resources Information Center

Zobrist, Kevin W.

2014-01-01

Asynchronous online Extension classes can reach a wide audience, is convenient for the learner, and minimizes ongoing demands on instructor time. However, producing such classes takes significant effort up front. Advance planning and good communication with contributors are essential to success. Considerations include delivery platforms, content…

Cultural Influences on Chinese Students' Asynchronous Online Learning in a Canadian University

ERIC Educational Resources Information Center

Zhao, Naxin; McDougall, Douglas

2008-01-01

This study explored six Chinese graduate students' asynchronous online learning in a large urban Canadian university. Individual interviews in Mandarin elicited their perceptions of online learning, their participation in it, and the cultural factors that influenced their experiences. In general, the participants had a positive attitude towards…

Language Use in Asynchronous Computer-Mediated Communication in Taiwan

ERIC Educational Resources Information Center

Huang, Daphne Li-jung

2009-01-01

This paper describes how Chinese-English bilinguals in Taiwan use their languages in asynchronous computer-mediated communication, specifically, via Bulletin Board System (BBS) and email. The main data includes two types: emails collected from a social network and postings collected from two BBS websites. By examining patterns of language choice…

Students' Use of Asynchronous Discussions for Academic Discourse Socialization

ERIC Educational Resources Information Center

Beckett, Gulbahar H.; Amaro-Jimenez, Carla; Beckett, Kelvin S.

2010-01-01

Our universities are becoming increasingly diverse at the same time as online asynchronous discussions (OADs) are emerging as the most important forum for computer mediated communication (CMC) in distance education. But there is shortage of studies that explore how graduate students from different ethnic, linguistic and cultural backgrounds use…

Effects of Belongingness and Synchronicity on Face-to-Face and Computer-Mediated Online Cooperative Pedagogy

ERIC Educational Resources Information Center

Saltarelli, Andrew John

2012-01-01

Previous research suggests asynchronous online computer-mediated communication (CMC) has deleterious effects on certain cooperative learning pedagogies (e.g., constructive controversy), but the processes underlying this effect and how it may be ameliorated remain unclear. This study tests whether asynchronous CMC thwarts belongingness needs…

Synchronous versus Asynchronous CMC and Transfer to Japanese Oral Performance

ERIC Educational Resources Information Center

Hirotani, Maki

2009-01-01

This study investigated the effects of synchronous and asynchronous CMC (computer-mediated communication)on the development of linguistic features of learners' speech in Japanese. Using learners from fourth-semester Japanese classes, the following research questions were examined: (a) Does CMC have positive effects on the development of oral…

A Group Intelligence-Based Asynchronous Argumentation Learning-Assistance Platform

ERIC Educational Resources Information Center

Huang, Chenn-Jung; Chang, Shun-Chih; Chen, Heng-Ming; Tseng, Jhe-Hao; Chien, Sheng-Yuan

2016-01-01

Structured argumentation support environments have been built and used in scientific discourse in the literature. However, to the best our knowledge, there is no research work in the literature examining whether student's knowledge has grown during learning activities with asynchronous argumentation. In this work, an intelligent computer-supported…

Participation, Interaction and Social Presence: An Exploratory Study of Collaboration in Online Peer Review Groups

ERIC Educational Resources Information Center

Zhao, Huahui; Sullivan, Kirk P. H.; Mellenius, Ingmarie

2014-01-01

A key reason for using asynchronous computer conferencing in instruction is its potential for supporting collaborative learning. However, few studies have examined collaboration in computer conferencing. This study examined collaboration in six peer review groups within an asynchronous computer conferencing. Eighteen tertiary students participated…

Asynchronous Group Review of EFL Writing: Interactions and Text Revisions

ERIC Educational Resources Information Center

Saeed, Murad Abdu; Ghazali, Kamila

2017-01-01

The current paper reports an empirical study of asynchronous online group review of argumentative essays among nine English as foreign language (EFL) Arab university learners joining English in their first, second, and third years at the institution. In investigating online interactions, commenting patterns, and how the students facilitate text…

The Role of Beliefs and Motivation in Asynchronous Online Learning in College-Level Classes

ERIC Educational Resources Information Center

Xie, Kui; Huang, Kun

2014-01-01

Epistemic and learning beliefs were found to affect college students' cognitive engagement and study strategies, as well as motivation in classroom settings. However, the relationships between epistemic and learning beliefs, motivation, learning perception, and students' actual learning participation in asynchronous online settings have been…

A Coding Scheme to Analyse the Online Asynchronous Discussion Forums of University Students

ERIC Educational Resources Information Center

Biasutti, Michele

2017-01-01

The current study describes the development of a content analysis coding scheme to examine transcripts of online asynchronous discussion groups in higher education. The theoretical framework comprises the theories regarding knowledge construction in computer-supported collaborative learning (CSCL) based on a sociocultural perspective. The coding…

Relationship of Metacognitive Monitoring with Interaction in an Asynchronous Online Discussion Forum

ERIC Educational Resources Information Center

Topcu, Abdullah

2010-01-01

Monitoring one's own performance accurately is essential for information-processing and self-regulation, which are indispensable in an online learning environment. In this article, the effect of metacognitive monitoring (MM) on interaction in an asynchronous online discussion forum was investigated. Transcripts of this forum, which was integrated…

Using Computer-Mediated Communication to Establish Social and Supportive Environments in Teacher Education

ERIC Educational Resources Information Center

Arnold, Nike; Ducate, Lara; Lomicka, Lara; Lord, Gillian

2005-01-01

This article examines social presence in virtual asynchronous learning communities among foreign language teachers. We present the findings of two studies investigating cross-institutional asynchronous forums created to engage participants in online dialogues regarding their foreign language teacher preparation experiences in and out of the…

The Effect of Synchronous and Asynchronous Participation on Students' Performance in Online Accounting Courses

ERIC Educational Resources Information Center

Duncan, Keith; Kenworthy, Amy; McNamara, Ray

2012-01-01

This article examines the relationship between MBA students' performance and participation in two online environments: a synchronous forum (chat room) and an asynchronous forum (discussion board) at an Australian university. The "quality" and "quantity" of students' participation is used to predict their final examination and…

Adding the Human Touch to Asynchronous Online Learning

ERIC Educational Resources Information Center

Glenn, Cynthia Wheatley

2018-01-01

For learners to actively accept responsibility in a virtual classroom platform, it is necessary to provide special motivation extending across the traditional classroom setting into asynchronous online learning. This article explores specific ways to do this that bridge the gap between ground and online students' learning experiences, and how…

Increasing Student Engagement Using Asynchronous Learning

ERIC Educational Resources Information Center

Northey, Gavin; Bucic, Tania; Chylinski, Mathew; Govind, Rahul

2015-01-01

Student engagement is an ongoing concern for educators because of its positive association with deep learning and educational outcomes. This article tests the use of a social networking site (Facebook) as a tool to facilitate asynchronous learning opportunities that complement face-to-face interactions and thereby enable a stronger learning…

Resistance to pyridine-based inhibitor KF116 reveals an unexpected role of integrase in HIV-1 Gag-Pol polyprotein proteolytic processing.

PubMed

Hoyte, Ashley C; Jamin, Augusta V; Koneru, Pratibha C; Kobe, Matthew J; Larue, Ross C; Fuchs, James R; Engelman, Alan N; Kvaratskhelia, Mamuka

2017-12-01

The pyridine-based multimerization selective HIV-1 integrase (IN) inhibitors (MINIs) are a distinct subclass of allosteric IN inhibitors. MINIs potently inhibit HIV-1 replication during virion maturation by inducing hyper- or aberrant IN multimerization but are largely ineffective during the early steps of viral replication. Here, we investigated the mechanism for the evolution of a triple IN substitution (T124N/V165I/T174I) that emerges in cell culture with a representative MINI, KF116. We show that HIV-1 NL4-3(IN T124N/V165I/T174I) confers marked (>2000-fold) resistance to KF116. Two IN substitutions (T124N/T174I) directly weaken inhibitor binding at the dimer interface of the catalytic core domain but at the same time markedly impair HIV-1 replication capacity. Unexpectedly, T124N/T174I IN substitutions inhibited proteolytic processing of HIV-1 polyproteins Gag and Gag-Pol, resulting in immature virions. Strikingly, the addition of the third IN substitution (V165I) restored polyprotein processing, virus particle maturation, and significant levels of replication capacity. These results reveal an unanticipated role of IN for polyprotein proteolytic processing during virion morphogenesis. The complex evolutionary pathway for the emergence of resistant viruses, which includes the need for the compensatory V165I IN substitution, highlights a relatively high genetic barrier exerted by MINI KF116. Additionally, we have solved the X-ray structure of the drug-resistant catalytic core domain protein, which provides means for rational development of second-generation MINIs. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

PubMed

Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

2017-08-22

The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts.

PubMed

Ray, F A; Peabody, D S; Cooper, J L; Cram, L S; Kraemer, P M

1990-01-01

To define the role of SV40 large T antigen in the transformation and immortalization of human cells, we have constructed a plasmid lacking most of the unique coding sequences of small t antigen as well as the SV40 origin of replication. The promoter for T antigen, which lies within the origin of replication, was deleted and replaced by the Rous sarcoma virus promoter. This minimal construct was co-electroporated into normal human fibroblasts of neonatal origin along with a plasmid containing the neomycin resistance gene (neo). Three G418-resistant, T antigen-positive clones were expanded and compared to three T antigen-positive clones that received the pSV3neo plasmid (capable of expressing large and small T proteins and having two origins of replication). Autonomous replication of plasmid DNA was observed in all three clones that received pSV3neo but not in any of the three origin minus clones. Immediately after clonal expansion, several parameters of neoplastic transformation were assayed. Low percentages of cells in T antigen-positive populations were anchorage independent or capable of forming colonies in 1% fetal bovine serum. The T antigen-positive clones generally exhibited an extended lifespan in culture but rarely became immortalized. Large numbers of dead cells were continually generated in all T antigen-positive, pre-crisis populations. Ninety-nine percent of all T antigen-positive cells had numerical or structural chromosome aberrations. Control cells that received the neo gene did not have an extended life span, did not have noticeable numbers of dead cells, and did not exhibit karyotype instability. We suggest that the role of T antigen protein in the transformation process is to generate genetic hypervariability, leading to various consequences including neoplastic transformation and cell death.

High-speed asynchronous optical sampling for high-sensitivity detection of coherent phonons

NASA Astrophysics Data System (ADS)

Dekorsy, T.; Taubert, R.; Hudert, F.; Schrenk, G.; Bartels, A.; Cerna, R.; Kotaidis, V.; Plech, A.; Köhler, K.; Schmitz, J.; Wagner, J.

2007-12-01

A new optical pump-probe technique is implemented for the investigation of coherent acoustic phonon dynamics in the GHz to THz frequency range which is based on two asynchronously linked femtosecond lasers. Asynchronous optical sampling (ASOPS) provides the performance of on all-optical oscilloscope and allows us to record optically induced lattice dynamics over nanosecond times with femtosecond resolution at scan rates of 10 kHz without any moving part in the set-up. Within 1 minute of data acquisition time signal-to-noise ratios better than 107 are achieved. We present examples of the high-sensitivity detection of coherent phonons in superlattices and of the coherent acoustic vibration of metallic nanoparticles.

Dual stator winding variable speed asynchronous generator: optimal design and experiments

NASA Astrophysics Data System (ADS)

Tutelea, L. N.; Deaconu, S. I.; Popa, G. N.

2015-06-01

In the present paper is carried out a theoretical and experimental study of dual stator winding squirrel cage asynchronous generator (DSWA) behavior in the presence of saturation regime (non-sinusoidal) due to the variable speed operation. The main aims are the determination of the relations of calculating the equivalent parameters of the machine windings to optimal design using a Matlab code. Issue is limited to three phase range of double stator winding cage-induction generator of small sized powers, the most currently used in the small adjustable speed wind or hydro power plants. The tests were carried out using three-phase asynchronous generator having rated power of 6 [kVA].

Emotional first aid for a suicide crisis: comparison between Telephonic hotline and internet.

PubMed

Gilat, Itzhak; Shahar, Golan

2007-01-01

The telephone and the internet have become popular sources of psychological help in various types of distress, including a suicide crisis. To gain more insight into the unique features of these media, we compared characteristics of calls to three technologically mediated sources of help that are part of the volunteer-based Israeli Association for Emotional First Aid (ERAN): Telephonic hotline (n = 4426), personal chat (n = 373) and an asynchronous online support group (n = 954). Threats of suicide were much more frequent among participants in the asynchronous support group than the telephone and personal chat. These findings encourage further research into suicide-related interpersonal exchanges in asynchronous online support groups.

Asynchronous emergence by loggerhead turtle (Caretta caretta) hatchlings

NASA Astrophysics Data System (ADS)

Houghton, J. D. R.; Hays, G. C.

2001-03-01

For many decades it has been accepted that marine turtle hatchlings from the same nest generally emerge from the sand together. However, for loggerhead turtles (Caretta caretta) nesting on the Greek Island of Kefalonia, a more asynchronous pattern of emergence has been documented. By placing temperature loggers at the top and bottom of nests laid on Kefalonia during 1998, we examined whether this asynchronous emergence was related to the thermal conditions within nests. Pronounced thermal variation existed not only between, but also within, individual nests. These within-nest temperature differences were related to the patterns of hatchling emergence, with hatchlings from nests displaying large thermal ranges emerging over a longer time-scale than those characterised by more uniform temperatures.

Asynchronous, macrotasked relaxation strategies for the solution of viscous, hypersonic flows

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.

1991-01-01

A point-implicit, asynchronous macrotasked relaxation of the steady, thin-layer, Navier-Stokes equations is presented. The method employs multidirectional, single-level storage Gauss-Seidel relaxation sweeps, which effectively communicate perturbations across the entire domain in 2n sweeps, where n is the dimension of the domain. In order to enhance convergence the application of relaxation factors to specific components of the Jacobian is examined using a stability analysis of the advection and diffusion equations. Attention is also given to the complications associated with asynchronous multitasking. Solutions are generated for hypersonic flows over blunt bodies in two and three dimensions with chemical reactions, utilizing single-tasked and multitasked relaxation strategies.

Student Outcomes Associated with Use of Asynchronous Online Discussion Forums in Gross Anatomy Teaching

ERIC Educational Resources Information Center

Green, Rodney A.; Hughes, Diane L.

2013-01-01

Asynchronous online discussion forums are increasingly common in blended learning environments but the relationship to student learning outcomes has not been reported for anatomy teaching. Forums were monitored in two multicampus anatomy courses; an introductory first year course and a second year physiotherapy-specific course. The forums are…

At a Distance: A Comparative Study of Distance Delivery Modalities for PhD Nursing Students

ERIC Educational Resources Information Center

Black, Andrew G.

2010-01-01

This study sought to ascertain and compare the attitudes and perceptions of PhD nursing students attending their coursework through synchronous and asynchronous means at two different universities. Many studies have been performed comparing both synchronous videoconferencing and asynchronous online education with the traditional classroom, but no…

Students' Desired and Experienced Levels of Connectivity to an Asynchronous, Online, Distance Degree Program

ERIC Educational Resources Information Center

Schroeder, Shawnda; Baker, Mary; Terras, Katherine; Mahar, Patti; Chiasson, Kari

2016-01-01

This study examined graduate students' desired and experienced levels of connectivity in an online, asynchronous distance degree program. Connectivity was conceptualized as the students' feelings of community and involvement, not their level of access to the Internet. Graduate students enrolled in a distance degree program were surveyed on both…

Three Interaction Patterns on Asynchronous Online Discussion Behaviours: A Methodological Comparison

ERIC Educational Resources Information Center

Jo, I.; Park, Y.; Lee, H.

2017-01-01

An asynchronous online discussion (AOD) is one format of instructional methods that facilitate student-centered learning. In the wealth of AOD research, this study evaluated how students' behavior on AOD influences their academic outcomes. This case study compared the differential analytic methods including web log mining, social network analysis…

Microbial infection affects egg viability and incubation behavior in a tropical passerine.

Treesearch

Mark I. Cook; Steven R. Beissinger; Gary A. Toranzos; Roberto A. Arendt Rodriguez

2004-01-01

Many avian species initiate incubation before clutch completion, which causes eggs to hatch asynchronously. This influences brood competitive dynamics and often results in nestling mortality. The prevailing hypotheses contend that parents incubate early because asynchronous hatching provides fitness benefits to parents or surviving offspring. An alternative idea is...

FIFO Buffer for Asynchronous Data Streams

NASA Technical Reports Server (NTRS)

Bascle, K. P.

1985-01-01

Variable-rate, asynchronous data signals from up to four measuring instruments or other sources combined in first-in/first-out (FIFO) buffer for transmission on single channel. Constructed in complementary metal-oxide-semiconductor (CMOS) logic, buffer consumes low power (only 125 mW at 5V) and conforms to aerospace standards of reliability and maintainability.

Critical Thinking in Asynchronous Online Discussion: An Investigation of Student Facilitation Techniques

ERIC Educational Resources Information Center

Lim, Sze Chung Raymond; Cheung, Wing Sum; Hew, Khe Foon

2011-01-01

Background: In the last decade, asynchronous online discussion forums have become a primary focus of many educational researchers. Some advocates believed that the process of typing out messages in itself can promote in-depth critical thinking skills. Nevertheless, empirical research has not provided much support for this claim in natural…

Interaction and Cognition in Asynchronous Computer Conferencing

ERIC Educational Resources Information Center

Schrire, Sarah

2004-01-01

This paper is based on a multiple-case study of the learning process in three asynchronous computer conferences. The conferences were part of the distance learning component in doctoral degree courses in computing technology in education offered at an American university. The conferences were analyzed from a number of perspectives, the emphasis in…

Socially Shared Metacognitive Regulation in Asynchronous CSCL in Science: Functions, Evolution and Participation

ERIC Educational Resources Information Center

Iiskala, Tuike; Volet, Simone; Lehtinen, Erno; Vauras, Marja

2015-01-01

The significance of socially shared metacognitive regulation (SSMR) in collaborative learning is gaining momentum. To date, however, there is still a paucity of research of how SSMR is manifested in asynchronous computer-supported collaborative learning (CSCL), and hardly any systematic investigation of SSMR's functions and evolution across…

The Effects of Self-Generated Synchronous and Asynchronous Visual Speech Feedback on Overt Stuttering Frequency

ERIC Educational Resources Information Center

Snyder, Gregory J.; Hough, Monica Strauss; Blanchet, Paul; Ivy, Lennette J.; Waddell, Dwight

2009-01-01

Purpose: Relatively recent research documents that visual choral speech, which represents an externally generated form of synchronous visual speech feedback, significantly enhanced fluency in those who stutter. As a consequence, it was hypothesized that self-generated synchronous and asynchronous visual speech feedback would likewise enhance…

Cooperative Learning in Graduate Student Projects: Comparing Synchronous versus Asynchronous Collaboration

ERIC Educational Resources Information Center

Strang, Kenneth

2013-01-01

Cooperative learning was applied in a graduate project management course to compare the effectiveness of asynchronous versus synchronous online team meetings. An experiment was constructed to allocate students to project teams while ensuring there was a balance of requisite skills, namely systems analysis and design along with HTML/Javascript…

Asynchronous Education: A Blueprint for the Future of Adult Learning.

ERIC Educational Resources Information Center

Krueger, Lyle L.; Porter, Cyndi Wilson; Burke, Daniel

While the distance learning curriculum at Lakeland College (Wisconsin) began 20 years ago, the idea for Lakeland Online was conceived about two and one-half years ago. A variety of delivery modes were considered before discovering Convene software. Since the communication process enabled by the Convene software is asynchronous and requires only a…

Synchronous and Asynchronous Communication in Distance Learning: A Review of the Literature

ERIC Educational Resources Information Center

Watts, Lynette

2016-01-01

Distance learning is commonplace in higher education, with increasing numbers of students enjoying the flexibility e-learning provides. Keeping students connected with peers and instructors has been a challenge with e-learning, but as technology has advanced, the methods by which educators keep students engaged, synchronously and asynchronously,…

Evaluating the Quality of Interaction in Asynchronous Discussion Forums in Fully Online Courses

ERIC Educational Resources Information Center

Nandi, Dip; Hamilton, Margaret; Harland, James

2012-01-01

Fully online courses are becoming progressively more popular because of their "anytime anywhere" learning flexibility. One of the ways students interact with each other and with the instructors within fully online learning environments is via asynchronous discussion forums. However, student engagement in online discussion forums does not…

Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

DTIC Science & Technology

2007-06-01

Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

Reflections of Students in Their Use of Asynchronous Online Seminars

ERIC Educational Resources Information Center

Groves, Mark; O'Donoghue, John

2009-01-01

This paper reports on research that has been carried out into the use, process, and effectiveness of an asynchronous online seminar within an undergraduate sports studies degree programme. Contemporary sources are used to justify the use of technology supported learning (TSL) in higher education and to inform a reflective and critical account of…

Using Asynchronous Electronic Surveys to Help In-Class Revision: A Case Study

ERIC Educational Resources Information Center

Tong, Vincent C. H.

2012-01-01

Synchronous e-voting systems (commonly known as "clickers") have become increasingly popular as they can be used to enhance interactivity in lectures. Asynchronous electronic surveys (AESs), unlike these voting system, usually serve as a method of gathering feedback before or after teaching sessions. This paper describes and evaluates a project…

Argumentation in a Multi Party Asynchronous Computer Mediated Conference: A Generic Analysis

ERIC Educational Resources Information Center

Coffin, Caroline; Painter, Clare; Hewings, Ann

2005-01-01

This paper draws on systemic functional linguistic genre analysis to illuminate the way in which post graduate applied linguistics students structure their argumentation within a multi party asynchronous computer mediated conference. Two conference discussions within the same postgraduate course are compared in order to reveal the way in which…

The Socratic Dialogue in Asynchronous Online Discussions: Is Constructivism Redundant?

ERIC Educational Resources Information Center

Kingsley, Paul

2011-01-01

Purpose: This paper aims to examine Socratic dialogue in asynchronous online discussions in relation to constructivism. The links between theory and practice in teaching are to be discussed whilst tracing the origins of Socratic dialogue and recent trends and use of seminar in research based institutions. Design/methodology/approach: Many online…

Asynchronous Online Peer Assistance: Telephone Messages of Encouragement in Post Licensure Nursing Programs

ERIC Educational Resources Information Center

Melrose, Sherri; Swettenham, Steve

2012-01-01

Peer assistance activities can strengthen online learning environments. And yet, like other professional adult learners, working post licensure nurses attending university part time to upgrade their credentials may have limited interest in student-to-student interaction. Some intentionally choose asynchronous self-paced courses so they can work on…

Thematic Analysis of the "Games" Students Play in Asynchronous Learning Environments

ERIC Educational Resources Information Center

MacMillan, Thalia; Forte, Michele; Grant, Cynthia

2014-01-01

The dynamics of the student-student relationship within the asynchronous online classroom, as evidenced by conversations in an online discussion board, is a balancing act potentially more complex than those occurring in real-time. In order for learning to truly be considered effective, a collaborative, safe environment needs to exist among…

Scaffolding Collaborative Argumentation in Asynchronous Discussions with Message Constraints and Message Labels

ERIC Educational Resources Information Center

Jeong, Allan; Joung, Sunyoung

2007-01-01

This study examined the effects of message constraints and labels on collaborative argumentation in asynchronous online discussions. Thirty-eight undergraduate students in an introductory educational technology course were assigned to one of three groups. In one group, students posted specific types of messages using a prescribed set of message…

Flipping the Online Classroom with Web 2.0: The Asynchronous Workshop

ERIC Educational Resources Information Center

Cummings, Lance

2016-01-01

This article examines how Web 2.0 technologies can be used to "flip" the online classroom by creating asynchronous workshops in social environments where immediacy and social presence can be maximized. Using experience teaching several communication and writing classes in Google Apps (Google+, Google Hangouts, Google Drive, etc.), I…

Peer Moderation of Asynchronous Online Discussions: An Exploratory Study of Peer E-Moderating Behaviour

ERIC Educational Resources Information Center

Ghadirian, Hajar; Ayub, Ahmad Fauzi Mohd

2017-01-01

This study explored patterns of e-moderating behaviour students performed when they were assigned as peer moderators of asynchronous online discussions in a reciprocal manner. Eighty-four students from an undergraduate blended course were observed during a 7-week-long online discussions. Using quantitative content analysis peer moderators'…

Asynchronous CMC, Collaboration and the Development of Critical Thinking in a Graduate Seminar in Applied Linguistics

ERIC Educational Resources Information Center

Abrams, Zsuzsanna I.

2005-01-01

A primary objective of graduate education, and often promoted by peer collaboration tasks, is the development of critical thinking skills. The present study compares how graduate students enrolled in a qualitative research design course in applied linguistics utilized asynchronous computer-mediated communication (ACMC) and face-to-face…

Asynchronous Computer-Mediated Corrective Feedback and the Correct Use of Prepositions: Is It Really Effective?

ERIC Educational Resources Information Center

Hosseini, Seyyed Behrooz

2012-01-01

An area that has recently attracted increasing attention is providing feedback on learners' writing accuracy through the Internet. However, research in this area has largely focused on synchronous communication, i.e., chatting, with fewer studies assessing asynchronous technologies, i.e., e-mailing. Therefore, this study investigates the…

The Role of Technology-Based Scaffolding in Problem-Based Online Asynchronous Discussion

ERIC Educational Resources Information Center

Ak, Serife

2016-01-01

This study examined the effects of technology-based scaffolds that were composed through the use of the seven-stage, problem-based learning strategy on knowledge construction in a problem-based online asynchronous discussion. In a quasi-experimental setting, 60 students in an undergraduate Instructional Technology and Material Design course were…

Superconducting magnetic energy storage for asynchronous electrical systems

DOEpatents

Boenig, H.J.

1984-05-16

It is an object of the present invention to provide superconducting magnetic energy storage for a plurality of asynchronous electrical systems. It is a further object of the present invention to provide load leveling and stability improvement in a plurality of independent ac systems using a single superconducting magnetic energy storage coil.

Factors Affecting Pre-Service Teachers' Participation in Asynchronous Discussion: The Case of Iran

ERIC Educational Resources Information Center

Ebrahimi, Alice; Faghih, Esmail; Marandi, Seyyedeh Susan

2016-01-01

This study reports on a qualitative small-scale exploratory study which examined the factors influencing 32 Iranian pre-service language teachers' participation in online asynchronous text-based discussion forums. By adopting a multiple case study design and analysing data gathered through semi-structured interviews and participants' online…

A Dynamic Analysis of the Interplay between Asynchronous and Synchronous Communication in Online Learning: The Impact of Motivation

ERIC Educational Resources Information Center

Giesbers, B.; Rienties, B.; Tempelaar, D.; Gijselaers, W.

2014-01-01

With the increased affordances of synchronous communication tools, more opportunities for online learning to resemble face-to-face settings have recently become available. However, synchronous communication does not afford as much time for reflection as asynchronous communication. Therefore, a combination of synchronous and asynchronous…

An Investigation of Assessment and Feedback Practices in Fully Asynchronous Online Undergraduate Mathematics Courses

ERIC Educational Resources Information Center

Trenholm, Sven; Alcock, Lara; Robinson, Carol

2015-01-01

Research suggests it is difficult to learn mathematics in the fully asynchronous online (FAO) instructional modality, yet little is known about associated teaching and assessment practices. In this study, we investigate FAO mathematics assessment and feedback practices in particular consideration of both claims and findings that these practices…

An Integrated Approach to Preempt Cheating on Asynchronous, Objective, Online Assessments in Graduate Business Classes

ERIC Educational Resources Information Center

Sullivan, Daniel P.

2016-01-01

Cheating, left untended, erodes the validity of evaluation and, ultimately, corrupts the legitimacy of a course. We profile an approach to manage, with an eye toward preempting, cheating on asynchronous, objective, online quizzes. This approach taps various technological and social solutions to academic dishonesty, integrating them into a…

An Examination of Computer Engineering Students' Perceptions about Asynchronous Discussion Forums

ERIC Educational Resources Information Center

Ozyurt, Ozcan; Ozyurt, Hacer

2013-01-01

This study was conducted in order to reveal the usage profiles and perceptions of Asynchronous Discussion Forums (ADFs) of 126 computer engineering students from the Computer Engineering Department in a university in Turkey. By using a mixed methods research design both quantitative and qualitative data were collected and analyzed. Research…

Students' Learning in Asynchronous Discussion Forums: A Meta-Analysis

ERIC Educational Resources Information Center

Martono, Fkipuntan; Salam, Urai

2017-01-01

Asynchronous discussion forums are among the most preferred tools chosen to foster learning opportunities and knowledge construction. To reveal the cognitive engagement evidenced in the transcripts of the discussion forums, this study presents 51 papers. 17 papers reported research on students' attitude toward the use of ICT for learning, 16…

Student Moderators in Asynchronous Online Discussion: A Question of Questions

ERIC Educational Resources Information Center

Zingaro, Daniel

2012-01-01

Much current research exalts the benefits of having students facilitate weekly discussions in asynchronous online courses. This study seeks to add to what is known about student moderation through an analysis of the types of questions students use to spur each discussion. Prior experimental work has demonstrated that the types of questions posed…

Content Analysis Coding Schemes for Online Asynchronous Discussion

ERIC Educational Resources Information Center

Weltzer-Ward, Lisa

2011-01-01

Purpose: Researchers commonly utilize coding-based analysis of classroom asynchronous discussion contributions as part of studies of online learning and instruction. However, this analysis is inconsistent from study to study with over 50 coding schemes and procedures applied in the last eight years. The aim of this article is to provide a basis…

Does the Medium Dictate the Message? Cultivating E-Communication in an Asynchronous Environment.

ERIC Educational Resources Information Center

Kiernan, Mary; Thomas, Pete; Woodroffe, Mark

Virtual learning environments (VLEs) are often perceived by education establishments as an opportunity to widen access without traditional overheads. An integral part of most VLEs is asynchronous computer conferencing and on-line moderators must help students migrate quickly to the new virtual environment to minimize learning disruption. This…

An Investigation of Student Practices in Asynchronous Computer Conferencing Courses

ERIC Educational Resources Information Center

Peters, Vanessa L.; Hewitt, Jim

2010-01-01

This study investigated the online practices of students enrolled in graduate-level distance education courses. Using interviews and a questionnaire as data sources, the study sought to: (a) identify common practices that students adopt in asynchronous discussions, and (b) gain an understanding of why students adopt them. An analysis of the data…

Air Temperature Distribution Measurement Using Asynchronous-Type Sound Probe

NASA Astrophysics Data System (ADS)

Katano, Yosuke; Wakatsuki, Naoto; Mizutani, Koichi

2009-07-01

In conventional temperature measurement using a sound probe, the operation beginnings of two acoustic sensors must be completely synchronized to measure time of flight (TOF), tf, because the precision of synchronization determines TOF measurement accuracy. A wireless local area network (LAN) is convenient for constructing a sensing grid; however, it causes a fluctuation in the delay of millisecond order. Therefore, it cannot provide sufficient precision for synchronizing acoustic sensors. In previous studies, synchronization was achieved by a trigger line using a coaxial cable; however, the cable reduces the flexibility of a wireless sensing grid especially in larger-scale measurement. In this study, an asynchronous-type sound probe is devised to compensate for the effect of the delay of millisecond order caused by the network. The validity of the probe was examined, and the air temperature distribution was measured using this means. A matrix method is employed to obtain the distribution. Similar results were observed using both asynchronous-type sound probes and thermocouples. This shows the validity of the use of a sensing grid with an asynchronous-type sound probe for temperature distribution measurement even if the trigger line is omitted.

Research on navigation of satellite constellation based on an asynchronous observation model using X-ray pulsar

NASA Astrophysics Data System (ADS)

Guo, Pengbin; Sun, Jian; Hu, Shuling; Xue, Ju

2018-02-01

Pulsar navigation is a promising navigation method for high-altitude orbit space tasks or deep space exploration. At present, an important reason for restricting the development of pulsar navigation is that navigation accuracy is not high due to the slow update of the measurements. In order to improve the accuracy of pulsar navigation, an asynchronous observation model which can improve the update rate of the measurements is proposed on the basis of satellite constellation which has a broad space for development because of its visibility and reliability. The simulation results show that the asynchronous observation model improves the positioning accuracy by 31.48% and velocity accuracy by 24.75% than that of the synchronous observation model. With the new Doppler effects compensation method in the asynchronous observation model proposed in this paper, the positioning accuracy is improved by 32.27%, and the velocity accuracy is improved by 34.07% than that of the traditional method. The simulation results show that without considering the clock error will result in a filtering divergence.

Asynchronous hatching and food limitation: A test of Lack's hypothesis

USGS Publications Warehouse

Skagen, Susan Knight

1988-01-01

Lack's (1954, 1968) hypothesis that asynchronous hatching of altricial birds is an adaptive response to unpredictable food shortages during the breeding season was examined in the highly granivorous Zebra Finch (Poephila guttata). I compared growth and survival of nestlings in asynchronous and artificially created synchronous broods reared under food-limited and food-abundant conditions in an aviary. I also examined the role of parental experience on survival and growth of nestlings.There was no differential mortality of Zebra Finch nestlings due to either asynchrony or food abundance. Young in abundant food treatments grew more rapidly, however, than those in food-restricted treatments. Heaviest Zebra Finch nestlings in a brood grew more quickly than their lightest siblings when food was limited, supporting Lack's hypothesis. Further, differential survival of light and heavy siblings occurred when food was abundant, suggesting that asynchronous hatching can be maladaptive under some ecological conditions. Nestlings reared by inexperienced parents suffered greater mortality and slower growth when food was abundant than nestlings raised by experienced parents. Prefledging mass was correlated with size at adulthood

Neighbor Discovery Algorithm in Wireless Local Area Networks Using Multi-beam Directional Antennas

NASA Astrophysics Data System (ADS)

Wang, Jin; Peng, Wei; Liu, Song

2017-10-01

Neighbor discovery is an important step for Wireless Local Area Networks (WLAN) and the use of multi-beam directional antennas can greatly improve the network performance. However, most neighbor discovery algorithms in WLAN, based on multi-beam directional antennas, can only work effectively in synchronous system but not in asynchro-nous system. And collisions at AP remain a bottleneck for neighbor discovery. In this paper, we propose two asynchrono-us neighbor discovery algorithms: asynchronous hierarchical scanning (AHS) and asynchronous directional scanning (ADS) algorithm. Both of them are based on three-way handshaking mechanism. AHS and ADS reduce collisions at AP to have a good performance in a hierarchical way and directional way respectively. In the end, the performance of the AHS and ADS are tested on OMNeT++. Moreover, it is analyzed that different application scenarios and the factors how to affect the performance of these algorithms. The simulation results show that AHS is suitable for the densely populated scenes around AP while ADS is suitable for that most of the neighborhood nodes are far from AP.

A formal model of asynchronous communication and its use in mechanically verifying a biphase mark protocol

NASA Technical Reports Server (NTRS)

Moore, J. Strother

1992-01-01

In this paper we present a formal model of asynchronous communication as a function in the Boyer-Moore logic. The function transforms the signal stream generated by one processor into the signal stream consumed by an independently clocked processor. This transformation 'blurs' edges and 'dilates' time due to differences in the phases and rates of the two clocks and the communications delay. The model can be used quantitatively to derive concrete performance bounds on asynchronous communications at ISO protocol level 1 (physical level). We develop part of the reusable formal theory that permits the convenient application of the model. We use the theory to show that a biphase mark protocol can be used to send messages of arbitrary length between two asynchronous processors. We study two versions of the protocol, a conventional one which uses cells of size 32 cycles and an unconventional one which uses cells of size 18. We conjecture that the protocol can be proved to work under our model for smaller cell sizes and more divergent clock rates but the proofs would be harder.

Quasi-perfect FIFO: Synchronous or asynchronous with application in controller design for the UNICON laser memory. [digital memory and buffer storage

NASA Technical Reports Server (NTRS)

Lim, R. S.

1974-01-01

The first-in-first-out memory buffer (FIFO), is an elastic digital memory whose main application is in data buffering between devices operating at different rates. Data written into the top is moved autonomously down toward the bottom of the FIFO to the lowest unoccupied location, and data read from the bottom of the FIFO will cause data from the top to move autonomously down toward the bottom. The FIFO is available in MOS LSI asynchronous form with data rate in the 1 MHz region. The FIFO described yields a simple high-speed iterative implementation, either synchronous of asynchronous. Because of this simple iterative structure, the FIFO is expandable in both number of words and bits per word, and it is attractive from the viewpoint of integrated-circuit production. For the synchronous FIFO, a model was built and successfully used in the controller for the UNICON laser memory. For the asynchronous FIFO, a model was built and also successfully used in a high-performance magnetic tape controller.

Exploring Online Asynchronous Counseling With Tobacco Treatment Specialists in the QUIT-PRIMO and National Dental PBRN HI-QUIT Studies: Who Uses It and What Do They Say?

PubMed

Williams, Jessica H; DeLaughter, Kathryn; Volkman, Julie E; Sadasivam, Rajani S; Ray, Midge N; Gilbert, Gregg H; Houston, Thomas K

2018-06-01

To describe the content of messages sent by smokers through asynchronous counseling within a Web-based smoking cessation intervention. Qualitative. National community-based setting of patients who had been engaged by the medical or dental practices at which they attended or via Google advertisements. Adults older than 19 years who were current smokers and interested in quitting. Participants throughout the United States referred to a Web-based cessation intervention by their medical or dental provider or by clicking on a Google advertisement. We conducted a qualitative review of 742 asynchronous counseling messages sent by 270 Web site users. Messages were reviewed, analyzed, and organized into qualitative themes by the investigative team. The asynchronous counseling feature of the intervention was used most frequently by smokers who were white (87%), female (67%), aged 45 to 54 (32%), and who had at least some college-level education (70%). Qualitative analysis yielded 7 basic themes-Talk about the Process of Quitting, Barriers to Quitting, Reasons to Quit, Quit History, Support and Strategies for Quitting, Quitting with Medication, and Quit Progress. The most common theme was Support and Strategies for Quitting with 255 references among all messages. We found rich communication across the spectrum of the quit process, from persons preparing to quit to those who had successfully quit. Asynchronous smoking cessation counseling provides a promising means of social support for smokers during the quit process.

Hatching behavior of eastern long-necked turtles (Chelodina longicollis): The influence of asynchronous environments on embryonic heart rate and phenotype.

PubMed

McGlashan, Jessica K; Loudon, Fiona K; Thompson, Michael B; Spencer, Ricky-John

2015-10-01

Variable temperatures within a nest cause asynchronous development within clutches of freshwater turtle embryos, yet synchronous hatching occurs and is thought to be an important survival strategy for hatchlings. Metabolic compensation and circadian rhythms in heart rates of embryonic turtles indicate the potential of communication between embryos in a nest. Heart rates were used to identify metabolic circadian rhythms in clutches of an Australian freshwater turtle (Chelodina longicollis) and determine whether embryos metabolically compensate and hatch synchronously when incubated in asynchronous environments. The effects of a group environment during incubation on egg development and incubation period were also investigated during the final 3 weeks of development. Chelodina longicollis hatch synchronously and metabolically compensate so that less advanced embryos catch up to more advanced clutch-mates. Heart rates of embryos remained stable from week 4-7 in asynchronous (M=89 bpm) and synchronous (M=92 bpm) groups and declined in the final 2 weeks of incubation (M=72 and 77 bpm). Circadian rhythms were present throughout development and diel heart rates of embryos in asynchronous groups showed less deviation from the mean (M=-0.5 bpm) than synchronous groups (M=-4 bpm). Eggs incubated in groups had a significantly shorter incubation period than eggs incubated individually. Phenotypic traits including size, performance, and growth of all hatchlings were not affected. Egg position within a turtle nest is important for coordinating development throughout incubation and facilitating synchronous hatching. Copyright © 2015 Elsevier Inc. All rights reserved.

Telemedicine for children with developmental disabilities: a more effective clinical process than office-based care.

PubMed

Langkamp, Diane L; McManus, Mark D; Blakemore, Susan D

2015-02-01

The literature on the use of telemedicine for children with developmental disabilities (DD) is limited and mostly describes telemedicine being used to link patients with distant subspecialty multidisciplinary care. Parents generally have reported satisfaction with such care and have perceived it to be equally effective as in-person care. Here we report on the use of school-based asynchronous telemedicine to connect children with DD with primary care providers. We developed Tele-Health-Kids, a school-based program using asynchronous telemedicine to connect children with DD with their primary care physician for the care of minor illnesses. We surveyed parents at enrollment and after the child's first telemedicine visit to assess satisfaction. We describe 4 cases that illustrate benefits, particularly for children with DD and challenging behaviors, suggesting that asynchronous telemedicine may actually be superior to traditional in-office visits in some circumstances. Most parents expressed a high level of satisfaction with the program. Benefits identified include decreased stress to the child and the parents as well as increasing the likelihood of a successful medical examination due to greater cooperation by the child. Visits using asynchronous or "store and forward" telemedicine technology may be superior in some situations by allowing the visit to be performed at a pace that can be adjusted to the needs of the child with DD. More research in the use of asynchronous telemedicine for children and youth with DD, particularly for children with DD and challenging behaviors, is needed.

Emerging roles of microRNAs as molecular switches in the integrated circuit of the cancer cell

PubMed Central

Sotiropoulou, Georgia; Pampalakis, Georgios; Lianidou, Evi; Mourelatos, Zissimos

2009-01-01

Transformation of normal cells into malignant tumors requires the acquisition of six hallmark traits, e.g., self-sufficiency in growth signals, insensitivity to antigrowth signals and self-renewal, evasion of apoptosis, limitless replication potential, angiogenesis, invasion, and metastasis, which are common to all cancers (Hanahan and Weinberg 2000). These new cellular traits evolve from defects in major regulatory microcircuits that are fundamental for normal homeostasis. The discovery of microRNAs (miRNAs) as a new class of small non-protein-coding RNAs that control gene expression post-transcriptionally by binding to various mRNA targets suggests that these tiny RNA molecules likely act as molecular switches in the extensive regulatory web that involves thousands of transcripts. Most importantly, accumulating evidence suggests that numerous microRNAs are aberrantly expressed in human cancers. In this review, we discuss the emergent roles of microRNAs as switches that function to turn on/off known cellular microcircuits. We outline recent compelling evidence that deregulated microRNA-mediated control of cellular microcircuits cooperates with other well-established regulatory mechanisms to confer the hallmark traits of the cancer cell. Furthermore, these exciting insights into aberrant microRNA control in cancer-associated circuits may be exploited for cancer therapies that will target deregulated miRNA switches. PMID:19561119

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing

PubMed Central

Ning, Baitang; Su, Zhenqiang; Mei, Nan; Hong, Huixiao; Deng, Helen; Shi, Leming; Fuscoe, James C.; Tolleson, William H.

2017-01-01

The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual’s susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy. PMID:24875441

Suboptimal Doses of Raltegravir Cause Aberrant HIV Integrations | Center for Cancer Research

Cancer.gov

When a cell is infected with HIV, a DNA copy of the HIV genome is inserted into that cell’s chromosomal DNA. This insertion reaction is carried out by the viral enzyme integrase (IN) and involves two distinct steps: removal of two nucleotides from each 3’ end of the viral DNA, followed by the strand transfer reaction, in which the viral DNA ends are inserted into the host chromosomal DNA. Integration is essential for viral replication, making it an important target for antiviral therapy. Raltegravir, and the other approved integrase inhibitor, Elvitegravir, are called integrase strand transfer inhibitors (INSTIs), because they bind to the active site of IN and block the strand transfer reaction.      

Area/latency optimized early output asynchronous full adders and relative-timed ripple carry adders.

PubMed

Balasubramanian, P; Yamashita, S

2016-01-01

This article presents two area/latency optimized gate level asynchronous full adder designs which correspond to early output logic. The proposed full adders are constructed using the delay-insensitive dual-rail code and adhere to the four-phase return-to-zero handshaking. For an asynchronous ripple carry adder (RCA) constructed using the proposed early output full adders, the relative-timing assumption becomes necessary and the inherent advantages of the relative-timed RCA are: (1) computation with valid inputs, i.e., forward latency is data-dependent, and (2) computation with spacer inputs involves a bare minimum constant reverse latency of just one full adder delay, thus resulting in the optimal cycle time. With respect to different 32-bit RCA implementations, and in comparison with the optimized strong-indication, weak-indication, and early output full adder designs, one of the proposed early output full adders achieves respective reductions in latency by 67.8, 12.3 and 6.1 %, while the other proposed early output full adder achieves corresponding reductions in area by 32.6, 24.6 and 6.9 %, with practically no power penalty. Further, the proposed early output full adders based asynchronous RCAs enable minimum reductions in cycle time by 83.4, 15, and 8.8 % when considering carry-propagation over the entire RCA width of 32-bits, and maximum reductions in cycle time by 97.5, 27.4, and 22.4 % for the consideration of a typical carry chain length of 4 full adder stages, when compared to the least of the cycle time estimates of various strong-indication, weak-indication, and early output asynchronous RCAs of similar size. All the asynchronous full adders and RCAs were realized using standard cells in a semi-custom design fashion based on a 32/28 nm CMOS process technology.

Refining an Asynchronous Telerehabilitation Platform for Speech-Language Pathology: Engaging End-Users in the Process

PubMed Central

Hill, Annie J.; Breslin, Hugh M.

2016-01-01

Asynchronous telerehabilitation in which computer-based interventions are remotely monitored and adapted offline is an emerging service delivery model in the rehabilitation of communication disorders. The asynchronous nature of this model may hold a benefit over its synchronous counterpart by eliminating scheduling issues and thus improving efficiency in a healthcare landscape of constrained resource allocation. The design of asynchronous telerehabilitation platforms should therefore ensure efficiency and flexibility. The authors have been engaged in a program of research to develop and evaluate an asynchronous telerehabilitation platform for use in speech-language pathology. eSALT is a novel asynchronous telerehabilitation platform in which clinicians design and individualize therapy tasks for transfer to a client's mobile device. An inbuilt telerehabilitation module allows for remote monitoring and updating of tasks. This paper introduces eSALT and reports outcomes from an usability study that considered the needs of two end-user groups, people with aphasia and clinicians, in the on-going refinement of eSALT. In the study participants with aphasia were paired with clinicians who used eSALT to design and customize therapy tasks. After training on the mobile device the participants engaged in therapy at home for a period of 3 weeks, while clinicians remotely monitored and updated tasks. Following the home trial, participants, and clinicians engaged in semi-structured interviews and completed surveys on the usability of eSALT and their satisfaction with the platform. Content analysis of data involving five participants and three clinicians revealed a number of usability themes including ease of use, user support, satisfaction, limitations, and potential improvements. These findings were translated into a number of refinements of the eSALT platform including the development of a client interface for use on the Apple iPad®, greater variety in feedback options to both the participant and clinician, automatic transfer of results to the clinician, and expansion of the task template list. This research highlights the importance of including end-users in the process of technology refinement, in order to ensure effective and efficient use of the technology. Future directions for research are discussed including clinical trials in which the effectiveness of and adherence to intervention protocols using asynchronous telerehabilitation are examined. PMID:28066211

Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

PubMed Central

Burton, Shawn D.

2015-01-01

Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE STATEMENT Inhibitory granule cells are involved critically in shaping odor-evoked principal neuron activity in the mammalian olfactory bulb, yet little is known about how sensory input activates granule cells. Here, we show that sensory input to the olfactory bulb evokes a barrage of asynchronous synaptic excitation and highly reliable, short-latency synaptic inhibition onto granule cells via a disynaptic feedforward inhibitory circuit involving deep short-axon cells. Feedforward inhibition attenuates local depolarization within granule cell dendritic branches, interacts with asynchronous excitation to suppress granule cell spike-timing precision, and scales in strength with excitation across different levels of sensory input to normalize granule cell firing rates. PMID:26490853

Replication Stress and Mitotic Dysfunction in Cells Expressing Simian Virus 40 Large T Antigen

PubMed Central

Hu, Liang; Filippakis, Harilaos; Huang, Haomin; Yen, Timothy J.

2013-01-01

We previously demonstrated that simian virus 40 (SV40) large T antigen (LT) binds to the Bub1 kinase, a key regulator of the spindle checkpoint and chromosome segregation. Bub1 mutations or altered expression patterns are linked to chromosome missegregation and are considered to be a driving force in some human cancers. Here we report that LT, dependent on Bub1 binding, causes micronuclei, lagging chromatin, and anaphase bridges, which are hallmarks of chromosomal instability (CIN) and Bub1 insufficiency. Using time-lapse microscopy, we demonstrate that LT imposes a Bub1 binding-dependent delay in the metaphase-to-anaphase transition. Kinetochore fibers reveal that LT, via Bub1 binding, causes aberrant kinetochore (KT)-microtubule (MT) attachments and a shortened interkinetochore distance, consistent with a lack of tension. Previously, we showed that LT also induces the DNA damage response (DDR) via Bub1 binding. Using inducible LT cell lines, we show that an activated DDR was observed before the appearance of anaphase bridges and micronuclei. Furthermore, LT induction in serum-starved cells demonstrated γ-H2AX accumulation in cells that had not yet entered mitosis. Thus, DDR activation can occur independently of chromosome segregation defects. Replication stress pathways may be responsible, because signatures of replication stress were observed, which were attenuated by exogenous supplementation with nucleosides. Our observations allow us to propose a model that explains and integrates the diverse manifestations of genomic instability induced by LT. PMID:24067972

Participation in Asynchronous Online Discussion Forums Does Improve Student Learning of Gross Anatomy

ERIC Educational Resources Information Center

Green, Rodney A.; Farchione, Davide; Hughes, Diane L.; Chan, Siew-Pang

2014-01-01

Asynchronous online discussion forums are common in blended learning models and are popular with students. A previous report has suggested that participation in these forums may assist student learning in a gross anatomy subject but it was unclear as to whether more academically able students post more often or whether participation led to…

Online-BSEE (Online Bachelor of Science in Electrical Engineering): An Asynchronous Online Electrical Engineering Degree Program with Laboratory

ERIC Educational Resources Information Center

Tang, Wendy; Westgate, Charles; Liu, Pao-Lo; Gouzman, Michael

2014-01-01

The Online Bachelor of Science in Electrical Engineering is a collaborative effort among three University Centers at SUNY (State University of New York), namely Stony Brook, Binghamton, and Buffalo. The program delivers the complete electrical engineering curriculum at the bachelor level to students online and asynchronously. Students, however,…

Reversible logic gates on Physarum Polycephalum

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

Schumann, Andrew

2015-03-10

In this paper, we consider possibilities how to implement asynchronous sequential logic gates and quantum-style reversible logic gates on Physarum polycephalum motions. We show that in asynchronous sequential logic gates we can erase information because of uncertainty in the direction of plasmodium propagation. Therefore quantum-style reversible logic gates are more preferable for designing logic circuits on Physarum polycephalum.

Use of Podcasting as an Innovative Asynchronous E-Learning Tool for Students

ERIC Educational Resources Information Center

Jalali, Alireza; Leddy, John; Gauthier, Martin; Sun, Rong; Hincke, Maxwell; Carnegie, Jacqueline

2011-01-01

Podcasting is an innovative, asynchronous communication tool. A pilot study was conducted to assess the utility of podcasting as an educational tool for undergraduate medical students. A paper-and-pencil questionnaire was developed and distributed to the 40 first-year students enrolled in the francophone stream of the medical curriculum at the…

A Comparison of Asynchronous Online Text-Based Lectures and Synchronous Interactive Web Conferencing Lectures

ERIC Educational Resources Information Center

Skylar, Ashley Ann

2009-01-01

Online learning environments are more prevalent in teacher education than ever before. In 2009, many instructors are attempting to emulate traditional instructional methods in the online learning environment as much as possible. Online courses are separated into two categories, (1) asynchronous; and (2) synchronous, depending on the nature of the…

Educational Outcomes of Synchronous and Asynchronous High School Students: A Quantitative Causal-Comparative Study of Online Algebra 1

ERIC Educational Resources Information Center

Berry, Sharon

2017-01-01

This study used a quantitative, causal-comparative design. It compared educational outcome data from online Algebra 1 courses to determine if a significant difference existed between synchronous and asynchronous students for end-of-course grades, state assessments scores, and student perceptions of their course. The study found that synchronous…

The Effectiveness of Synchronous and Asynchronous Written Corrective Feedback on Grammatical Accuracy in a Computer-Mediated Environment

ERIC Educational Resources Information Center

Shintani, Natsuko; Aubrey, Scott

2016-01-01

This study extends research on written corrective feedback (CF) by investigating how timing of CF affects grammar acquisition. Specifically, it examined the relative effects of synchronous and asynchronous CF on the accurate use of the hypothetical conditional structure. Participants were 68 intermediate-level students of English at a university…

Microanalytic Case studies of Individual Participation Patterns in an Asynchronous Online Discussion in an Undergraduate Blended Course

ERIC Educational Resources Information Center

Wise, Alyssa Friend; Perera, Nishan; Hsiao, Ying-Ting; Speer, Jennifer; Marbouti, Farshid

2012-01-01

This study presents three case studies of students' participation patterns in an online discussion to address the gap in our current understanding of how "individuals" experience asynchronous learning environments. Cases were constructed via microanalysis of log-file data, post contents, and the evolving discussion structure. The first student was…

Collaborative Learning Processes in an Asynchronous Environment: An Analysis through Discourse and Social Networks

ERIC Educational Resources Information Center

Tirado, Ramon; Aguaded, Ignacio; Hernando, Angel

2011-01-01

This article analyses an experience in collaborative learning in an asynchronous writing environment through discussion forums on a WebCt platform of the University of Huelva's virtual campus, and was part of an innovative teaching project in 2007-08. The main objectives are to describe the processes of collaborative knowledge construction and the…

Asynchronous Online Access as an Accommodation on Students with Learning Disabilities and/or Attention-Deficit Hyperactivity Disorders in Postsecondary STEM Courses

ERIC Educational Resources Information Center

Graves, Laura; Asunda, Paul A.; Plant, Stacey J.; Goad, Chester

2011-01-01

The purpose of this study was to investigate whether asynchronous online access of course recordings was beneficial to students with learning disabilities (LD) and/or Attention Deficit/Hyperactivity Disorder (ADHD) enrolled in science, technology, engineering, and mathematics (STEM) courses. Data were collected through semi-structured interviews…

Digging beneath the Surface: Analyzing the Complexity of Instructors' Participation in Asynchronous Discussion

ERIC Educational Resources Information Center

Clarke, Lane Whitney; Bartholomew, Audrey

2014-01-01

The purpose of this study was to investigate instructor participation in asynchronous discussions through an in-depth content analysis of instructors' postings and comments through the Community of Inquiry (COI) framework (Garrison et. al, 2001). We developed an analytical tool based on this framework in order to better understand what instructors…

Writer L1/L2 Status and Asynchronous Online Writing Center Feedback: Consultant Response Patterns

ERIC Educational Resources Information Center

Weirick, Joshua; Davis, Tracy; Lawson, Daniel

2017-01-01

This case study examines the differences in comments offered by asynchronous online writing center consultants to L1 and L2 speakers and examines the potential disconnects in consultant perceptions of their practice. The researchers collected and coded sample papers and interviewed participants to contextualize data from the quantitative portion…

Reconceptualising Moderation in Asynchronous Online Discussions Using Grounded Theory

ERIC Educational Resources Information Center

Vlachopoulos, Panos; Cowan, John

2010-01-01

This article reports a grounded theory study of the moderation of asynchronous online discussions, to explore the processes by which tutors in higher education decide when and how to moderate. It aims to construct a theory of e-moderation based on some key factors which appear to influence e-moderation. It discusses previous research on the…

Exploring Singapore Primary School Students' Perceptions of Chinese Asynchronous Online Discussions

ERIC Educational Resources Information Center

Chin, Wong Wan; Sum, Cheung Wing; Foon, Hew Khe

2008-01-01

Background: Asynchronous online discussion (AOD) has found widespread use in tertiary education and adult learning environment; however, there has been little research on its use in elementary school, especially in the context of the teaching of the Chinese Language. This study explores the use of AOD in a Chinese Language class in a primary…

Synchronous and Asynchronous Text-Based CMC in Educational Contexts: A Review of Recent Research

ERIC Educational Resources Information Center

Johnson, Genevieve, Marie

2006-01-01

This paper presents a review of recent research that examines the relative instructional utility of text-based synchronous and asynchronous computer-mediated communication (CMC). As a mechanism for limiting the number of studies reviewed as well as controlling for emergent technologies, only research published since 2000 was reviewed. The goal was…

Asynchronous Knowledge Sharing and Conversation Interaction Impact on Grade in an Online Business Course

ERIC Educational Resources Information Center

Strang, Kenneth David

2011-01-01

Student knowledge sharing and conversation theory interactions were coded from asynchronous discussion forums to measure the effect of learning-oriented utterances on academic performance. The sample was 3 terms of an online business course (in an accredited MBA program) at a U.S.-based university. Correlation, stepwise regression, and multiple…

A Study of Synchronous versus Asynchronous Collaboration in an Online Business Writing Class

ERIC Educational Resources Information Center

Mabrito, Mark

2006-01-01

A case study examined the collaborative experiences of students in an online business writing classroom. The purpose was to examine the same groups of students working on collaborative writing assignments in both a synchronous (real-time) and an asynchronous (non-real-time) discussion forum. This study focused on examining the amount, pattern, and…

Distributed Training for the Reserve Component: Remote Delivery Using Asynchronous Computer Conferencing.

ERIC Educational Resources Information Center

Hahn, H. A.; And Others

The purposes of this research were to evaluate the cost effectiveness of using Asynchronous Computer Conferencing (ACC) and to develop guidelines for effectively conducting high quality military training using ACC. The evaluation used a portion of the Engineer Officer Advanced Course (EOAC) as a test bed. Course materials which taught the same…

Interaction and Critical Inquiry in Asynchronous Computer-Mediated Conferencing: A Research Agenda

ERIC Educational Resources Information Center

Hopkins, Joseph; Gibson, Will; Ros i. Sole, Cristina; Savvides, Nicola; Starkey, Hugh

2008-01-01

This paper reviews research on learner and tutor interaction in asynchronous computer-mediated (ACM) conferences used in distance learning. The authors note claims made for the potential of ACM conferences to promote higher-order critical inquiry and the social construction of knowledge, and argue that there is a general lack of evidence regarding…

Analysis of an Asynchronous Online Discussion as a Supportive Model for Peer Collaboration and Reflection in Teacher Education

ERIC Educational Resources Information Center

Plešec Gasparic, Romina; Pecar, Mojca

2016-01-01

Professional development of future teachers is based on connecting theory and practice with the aim of supporting and developing critical, independent, responsible decision-making and active teaching. With this aim we designed a blended learning environment with an asynchronous online discussion, enabling collaboration and reflection even when…

Comparing Face-To-Face and Asynchronous Online Communication as Mechanisms for Critical Reflective Dialogue

ERIC Educational Resources Information Center

Salter, Susan; Douglas, Tracy; Kember, David

2017-01-01

Two mechanisms for engaging in critical reflective dialogue are discussed and compared: face-to-face meetings and asynchronous online discussion. The context is an umbrella action research project, with over 20 participants, which aimed to improve practices in online teaching and contribute to the development of graduate attributes. The article…

Using Asynchronous Video to Achieve Instructor Immediacy and Closeness in Online Classes: Experiences from Three Cases

ERIC Educational Resources Information Center

Griffiths, Michael; Graham, Charles

2010-01-01

This research sought to understand the experiences of students and instructors with asynchronous video (video-mail) using webcams in three online sections of teacher education classes at Brigham Young University. We examined the experiences of students through scores and comments posted in student ratings surveys, and the experiences of…

Toward Personal and Emotional Connectivity in Mobile Higher Education through Asynchronous Formative Audio Feedback

ERIC Educational Resources Information Center

Rasi, Päivi; Vuojärvi, Hanna

2018-01-01

This study aims to develop asynchronous formative audio feedback practices for mobile learning in higher education settings. The development was conducted in keeping with the principles of design-based research. The research activities focused on an inter-university online course, within which the use of instructor audio feedback was tested,…

Asynchronous online foresight panels: the case of wildfire management

Treesearch

David N. Bengston; Robert L. Olson

2015-01-01

Text-based asynchronous online conferencing involves structured online discussion and deliberation among multiple participants from multiple sites in which there is a delay in interaction between contributors. This method has been widely used for a variety of purposes in higher education and other settings, but has not been commonly used in futures research. This paper...

Effects of Synchronous and Asynchronous Computer-Mediated Communication (CMC) Oral Conversations on English Language Learners' Discourse Functions

ERIC Educational Resources Information Center

AbuSeileek, Ali Farhan; Qatawneh, Khaleel

2013-01-01

This study aimed to explore the effects of synchronous and asynchronous computer mediated communication (CMC) oral discussions on question types and strategies used by English as a Foreign Language (EFL) learners. The participants were randomly assigned to two treatment conditions/groups; the first group used synchronous CMC, while the second…

Introducing Group-Based Asynchronous Learning to Business Education. Reflections on Effective Course Design and Delivery

ERIC Educational Resources Information Center

Walker, Richard; Arnold, Ivo

2004-01-01

This paper explores the contribution of virtual tools to student learning within full-time management programmes. More specifically, the paper focuses on asynchronous communication tools, considering the scope they offer for group-based collaborative learning outside the classroom. We report on the effectiveness of this approach for an economics…

Student Perceptions of Asynchronous Multimodal Instructor Feedback: A Multiple Case Study

ERIC Educational Resources Information Center

Lenards, Nishele Dyan

2017-01-01

Student dissatisfaction has been a problem in higher education with regard to the provision of assessment-related feedback. Due to the distant nature of online learning, instructors are faced with many challenges in delivering quality feedback because the communication is asynchronous and lacks social cues that are present in a F2F environment.…

Students' Perceptions of Online Discussions, Participation and E-Moderation Behaviours in Peer-Moderated Asynchronous Online Discussions

ERIC Educational Resources Information Center

Ghadirian, Hajar; Fauzi Mohd Ayub, Ahmad; Salehi, Keyvan

2018-01-01

The aim of this study was to investigate the relationships between students' perceptions of online discussions, participation and e-moderation behaviours in peer-moderated asynchronous online discussions. Using survey data, the learning system's activity log and discussion transcripts, the authors analysed how 84 learners' perceptions of online…

Three-Dimensional Temperature Field Simulation for the Rotor of an Asynchronous Motor

ERIC Educational Resources Information Center

Wang, Yanwu; Fan, Chunli; Yang, Li; Sun, Fengrui

2010-01-01

A three-dimensional heat transfer model is built according to the rotor structure of an asynchronous motor, and three-dimensional temperature fields of the rotor under different working conditions, such as the unloaded, rated loaded and that with broken rotor bars, are studied based on the finite element numerical method and experiments. The…

Bully Proofing Your Twice-Exceptional Child

ERIC Educational Resources Information Center

Mohammed, Amra

2018-01-01

Twice-exceptional (2E) students are those who demonstrate a gift or talent in one or more areas and have a disability in another area. One identifying characteristic of 2E children is asynchronous development, or the display of unusual talent or maturity in one or more areas alongside a struggle to develop in other areas. Asynchronous development…

The Effect of Asynchronous/Synchronous Approaches on English Vocabulary Achievement: A Study of Iranian EFL Learners

ERIC Educational Resources Information Center

Khodaparast, Fatemeh; Ghafournia, Narjes

2015-01-01

The contribution of computer-assisted instructional programs to language learning process has been the focus of researchers for about two decades. However, the effect of synchronous and asynchronous computer-assisted approaches of language teaching on improving L2 vocabulary has been scarcely investigated. This study explored whether synchronous,…

Effects of Asynchronous Music on Students' Lesson Satisfaction and Motivation at the Situational Level

ERIC Educational Resources Information Center

Digelidis, Nikolaos; Karageorghis, Costas I.; Papapavlou, Anastasia; Papaioannou, Athanasios G.

2014-01-01

The aim of this study was to examine the effects of asynchronous (background) music on senior students' motivation and lesson satisfaction at the situational level. A counterbalanced mixed-model design was employed with two factors comprising condition (three levels) and gender (two levels). Two hundred students (82 boys, 118 girls; M [subscript…

Synchronous and Asynchronous E-Language Learning: A Case Study of Virtual University of Pakistan

ERIC Educational Resources Information Center

Perveen, Ayesha

2016-01-01

This case study evaluated the impact of synchronous and asynchronous E-Language Learning activities (ELL-ivities) in an E-Language Learning Environment (ELLE) at Virtual University of Pakistan. The purpose of the study was to assess e-language learning analytics based on the constructivist approach of collaborative construction of knowledge. The…

Computer-Mediated Synchronous and Asynchronous Corrective Feedback Provided by Trainee Teachers to Learners of French: A Preliminary Study

ERIC Educational Resources Information Center

Vidal, Julie; Thouësny, Sylvie

2015-01-01

In this paper, we investigate whether trainee teachers' practices, with respect to multimodal feedback, differ from current research, and to what extent it may affect students' language development. More specifically, the goal of the present study is threefold: (1) it observes how trainee teachers responded, whether synchronously, asynchronously,…

Beyond Social Presence: Facelessness and the Ethics of Asynchronous Online Education

ERIC Educational Resources Information Center

Rose, Ellen

2017-01-01

In this position paper, I argue that a focus on achieving and increasing social presence in online courses tends to derail a consideration of the ethical implications and dimensions of the essential facelessness of asynchronous education. Drawing upon the work of Emmanuel Levinas and Nel Noddings, who contended that the face is the basis of…

Exploring Change in Graduate Students' Perceptions of Web-Based Education throughout an Asynchronous Course

ERIC Educational Resources Information Center

Timotheou, Maria Mama

2017-01-01

This paper presents the main findings of a UK study exploring graduate students' perceptions of web-based education, with a specific focus on their change over time, throughout an asynchronous course. Data were collected through online messages and interviews, and analyzed qualitatively, following content and thematic analyses. Participant pre-…

Distributed Teaching Presence and Communicative Patterns in Asynchronous Learning: Name versus Reply Networks

ERIC Educational Resources Information Center

Engel, Anna; Coll, Cesar; Bustos, Alfonso

2013-01-01

This work explores some methodological challenges in the application of Social Network Analysis (SNA) to the study of "Asynchronous Learning Networks" (ALN). Our interest in the SNA is situated within the framework of the study of Distributed Teaching Presence (DTP), understood as the exercise of educational influence, through a multi-method…

Cyber Asynchronous versus Blended Cyber Approach in Distance English Learning

ERIC Educational Resources Information Center

Ge, Zi-Gang

2012-01-01

This study aims to compare the single cyber asynchronous learning approach with the blended cyber learning approach in distance English education. Two classes of 70 students participated in this study, which lasted one semester of about four months, with one class using the blended approach for their English study and the other only using the…

Using the Community of Inquiry Model to Investigate Students' Knowledge Construction in Asynchronous Online Discussions

ERIC Educational Resources Information Center

Liu, Chien-Jen; Yang, Shu Ching

2014-01-01

This study used the Community of Inquiry (CoI) model proposed by Garrison to investigate students' level of knowledge construction in asynchronous discussions. The participants included 36 senior students (27 males) majoring in information management. The students attended 18 weeks of an online information ethics course. In this study, four types…

Comparing the Social Knowledge Construction Behavioral Patterns of Problem-Based Online Asynchronous Discussion in E/M-Learning Environments

ERIC Educational Resources Information Center

Lan, Yu-Feng; Tsai, Pei-Wei; Yang, Shih-Hsien; Hung, Chun-Ling

2012-01-01

In recent years, researchers have conducted various studies on applying wireless networking technology and mobile devices in education settings. However, research on behavioral patterns in learners' online asynchronous discussions with mobile devices is limited. The purposes of this study are to develop a mobile learning system, mobile interactive…

A Survey of Factors Contributing to Learners' "Listening" Behaviors in Asynchronous Online Discussions

ERIC Educational Resources Information Center

Wise, Alyssa Friend; Marbouti, Farshid; Hsiao, Ying-Ting; Hausknecht, Simone

2012-01-01

Sixty-seven undergraduates taking either a Blended Business Course (BBC) or an Online Education Course (OEC) were surveyed about factors influencing their "listening" behaviors in asynchronous online course discussions. These are the ways they attend to the posts made by others: which posts they open, how they engage with open posts, and…

Reflective Outcomes of Convergent and Divergent Group Tasking in the Online Learning Environment

ERIC Educational Resources Information Center

Hawkes, Mark

2007-01-01

Using collaborative critical reflection as an index, this study examines the asynchronous and face-to-face discourse of 28 suburban Chicago elementary teachers developing problem based learning (PBL) curriculum. Statistical analysis of the corpus produced by the 2 mediums shows that the asynchronous online network emerges as the medium of choice…

The Effects of Computer-Mediated Synchronous and Asynchronous Direct Corrective Feedback on Writing: A Case Study

ERIC Educational Resources Information Center

Shintani, Natsuko

2016-01-01

This case study investigated the characteristics of computer-mediated synchronous corrective feedback (SCF, provided while students wrote) and asynchronous corrective feedback (ACF, provided after students had finished writing) in an EFL writing task. The task, designed to elicit the use of the hypothetical conditional, was completed by two…

Live Synchronous Web Meetings in Asynchronous Online Courses: Reconceptualizing Virtual Office Hours

ERIC Educational Resources Information Center

Lowenthal, Patrick R.; Snelson, Chareen; Dunlap, Joanna C.

2017-01-01

Most online courses rely solely on asynchronous text-based online communication. This type of communication can foster anytime, anywhere reflection, critical thinking, and deep learning. However, it can also frustrate participants because of the lack of spontaneity and visual cues and the time it takes for conversations to develop and feedback to…

Use of a Post-Asynchronous Online Discussion Assessment to Enhance Student Critical Thinking

ERIC Educational Resources Information Center

Klisc, Chris; McGill, Tanya; Hobbs, Valerie

2017-01-01

Asynchronous online discussion (AOD) is used in many tertiary education courses, and assessing it has been shown to enhance critical thinking outcomes. There has, however, been debate on what should be assessed and how the assessment should be implemented. The most common form of assessment involves grading the individual discussion contributions,…

Asynchronous Cooperative e-Learning System and Its Evaluation

NASA Astrophysics Data System (ADS)

Eto, Kazuhiro; Miyoshi, Takumi

Much attention has been attracted to collaborative learning on an e-learning system. However, it is difficult to implement the collaborative environment to an asynchronous e-learning system since collaboration would be realized only when learners join the system at the same time. On the other hand, cooperative learning has been proposed. In this method, learners can study on their own pace without making mutual agreement but with receiving cognitive information from others. In this paper, the authors have developed the asynchronous cooperative e-learning system that provides learners' attendance and studying progress as the cognitive information. The subjective evaluation experiments show that our system is slightly inferior to the synchronous collaborative e-learning system, but it can motivate the learners more than the conventional system.

Performance evaluation of an asynchronous multisensor track fusion filter

NASA Astrophysics Data System (ADS)

Alouani, Ali T.; Gray, John E.; McCabe, D. H.

2003-08-01

Recently the authors developed a new filter that uses data generated by asynchronous sensors to produce a state estimate that is optimal in the minimum mean square sense. The solution accounts for communications delay between sensors platform and fusion center. It also deals with out of sequence data as well as latent data by processing the information in a batch-like manner. This paper compares, using simulated targets and Monte Carlo simulations, the performance of the filter to the optimal sequential processing approach. It was found that the new asynchronous Multisensor track fusion filter (AMSTFF) performance is identical to that of the extended sequential Kalman filter (SEKF), while the new filter updates its track at a much lower rate than the SEKF.

Asynchronous communication in spectral-element and discontinuous Galerkin methods for atmospheric dynamics - a case study using the High-Order Methods Modeling Environment (HOMME-homme_dg_branch)

NASA Astrophysics Data System (ADS)

Jamroz, Benjamin F.; Klöfkorn, Robert

2016-08-01

The scalability of computational applications on current and next-generation supercomputers is increasingly limited by the cost of inter-process communication. We implement non-blocking asynchronous communication in the High-Order Methods Modeling Environment for the time integration of the hydrostatic fluid equations using both the spectral-element and discontinuous Galerkin methods. This allows the overlap of computation with communication, effectively hiding some of the costs of communication. A novel detail about our approach is that it provides some data movement to be performed during the asynchronous communication even in the absence of other computations. This method produces significant performance and scalability gains in large-scale simulations.

Bloom’s Syndrome: Why Not Premature Aging? A comparison of the BLM and WRN helicases

PubMed Central

de Renty, Christelle; Ellis, Nathan A.

2016-01-01

Genomic instability is a hallmark of cancer and aging. Premature aging (progeroid) syndromes are often caused by mutations in genes whose function is to ensure genomic integrity. The RecQ family of DNA helicases is highly conserved and plays crucial roles as genome caretakers. In human, mutations in three RecQ genes — BLM, WRN, and RECQL4 — give rise to Bloom’s syndrome (BS), Werner syndrome (WS), and Rothmund-Thomson’s syndrome (RTS), respectively. WS is a prototypic premature aging disorder; however, the clinical features present in BS and RTS do not indicate accelerated aging. The BLM helicase has pivotal functions at the crossroads of DNA replication, recombination, and repair. BS cells exhibit a characteristic form of genomic instability that includes excessive recombination. The excessive homologous recombination drives the development of the many types of cancers that affect persons in the normal population. Replication delay and slower cell turnover rates have been proposed to explain many features of Bloom’s syndrome, such as short stature. More recently, aberrant transcriptional regulation of growth and survival genes has been proposed as a hypothesis. PMID:27238185

Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase.

PubMed

van Overbeek, Megan; de Lange, Titia

2006-07-11

Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.

The timing of UV mutagenesis in yeast: a pedigree analysis of induced recessive mutation.

PubMed

James, A P; Kilbey, B J

1977-10-01

The mechanism of UV-induced mutation in eukaryotes was studied in individual yeast cells by a procedure that combined pedigree analysis and tetrad analysis. The technique involved the induction of recessive lethals and semilethals in G1 diploid cells. Induced frequencies were 25 and 61 percent at survival levels of 90 and 77 percent, respectively. No evidence of gross chromosome aberrations was detected. Recessive mutations that affect only one strand or that affect both strands of the DNA molecule are induced much at random among a population of cells, and both types can occur within the same cell. However, the data confirm that two-strand mutations are in the majority after a low level of irradiation. The simplest explanation involves a mechanism whereby most mutations are fixed in both strands prior to the first round of post-irradiation DNA replication. The recessive mutational consequences of irradiation are exhausted at the conclusion of the first post-irradiation cell division, although dominant-lethal sectoring continues at a high level through the second post-irradiation division. It is concluded that pyrimidine dimers that persist to the second round of DNA replication are rare or ineffective.

Induced maturation of human immunodeficiency virus.

PubMed

Mattei, Simone; Anders, Maria; Konvalinka, Jan; Kräusslich, Hans-Georg; Briggs, John A G; Müller, Barbara

2014-12-01

HIV-1 assembles at the plasma membrane of virus-producing cells as an immature, noninfectious particle. Processing of the Gag and Gag-Pol polyproteins by the viral protease (PR) activates the viral enzymes and results in dramatic structural rearrangements within the virion--termed maturation--that are a prerequisite for infectivity. Despite its fundamental importance for viral replication, little is currently known about the regulation of proteolysis and about the dynamics and structural intermediates of maturation. This is due mainly to the fact that HIV-1 release and maturation occur asynchronously both at the level of individual cells and at the level of particle release from a single cell. Here, we report a method to synchronize HIV-1 proteolysis in vitro based on protease inhibitor (PI) washout from purified immature virions, thereby temporally uncoupling virus assembly and maturation. Drug washout resulted in the induction of proteolysis with cleavage efficiencies correlating with the off-rate of the respective PR-PI complex. Proteolysis of Gag was nearly complete and yielded the correct products with an optimal half-life (t(1/2)) of ~5 h, but viral infectivity was not recovered. Failure to gain infectivity following PI washout may be explained by the observed formation of aberrant viral capsids and/or by pronounced defects in processing of the reverse transcriptase (RT) heterodimer associated with a lack of RT activity. Based on our results, we hypothesize that both the polyprotein processing dynamics and the tight temporal coupling of immature particle assembly and PR activation are essential for correct polyprotein processing and morphological maturation and thus for HIV-1 infectivity. Cleavage of the Gag and Gag-Pol HIV-1 polyproteins into their functional subunits by the viral protease activates the viral enzymes and causes major structural rearrangements essential for HIV-1 infectivity. This proteolytic maturation occurs concomitant with virus release, and investigation of its dynamics is hampered by the fact that virus populations in tissue culture contain particles at all stages of assembly and maturation. Here, we developed an inhibitor washout strategy to synchronize activation of protease in wild-type virus. We demonstrated that nearly complete Gag processing and resolution of the immature virus architecture are accomplished under optimized conditions. Nevertheless, most of the resulting particles displayed irregular morphologies, Gag-Pol processing was not faithfully reconstituted, and infectivity was not recovered. These data show that HIV-1 maturation is sensitive to the dynamics of processing and also that a tight temporal link between virus assembly and PR activation is required for correct polyprotein processing. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Infrared spectroscopic studies of myeloid leukemia (ML-1) cells at different phases of the cell cycle

NASA Astrophysics Data System (ADS)

Boydston-White, Susie; Diem, Max

1999-06-01

Advances in infrared spectroscopic methodology permit excellent infrared spectra to be collected from objects as small as single human cells. These advances have lead to an increased interest of the use of infrared spectroscopy as a medical diagnostic tool. Infrared spectra of myeloid leukemia (ML-1) cells are reported for cells derived from an asynchronous, exponentially-growing culture, as well as for cells that were fractionated according to their stage within the cell division cycle. The observed results suggest that the cells' DNA is detectable by infrared spectroscopy mainly when the cell is in the S phase, during the replication of DNA. In the G1 and G2 phases, the DNA is so tightly packed in the nucleus that it appears opaque to infrared radiation. Consequently, the nucleic acid spectral contributions in the G1 and G2 phases would be mostly that of cytoplasmic RNA. These results suggest that infrared spectral changes observed earlier between normal and abnormal cells may have been due to different distributions of cells within the stages of the cell division cycle.

Psychophysiological effects of synchronous versus asynchronous music during cycling.

PubMed

Lim, Harry B T; Karageorghis, Costas I; Romer, Lee M; Bishop, Daniel T

2014-02-01

Synchronizing movement to a musical beat may reduce the metabolic cost of exercise, but findings to date have been equivocal. Our aim was to examine the degree to which the synchronous application of music moderates the metabolic demands of a cycle ergometer task. Twenty-three recreationally active men made two laboratory visits. During the first visit, participants completed a maximal incremental ramp test on a cycle ergometer. At the second visit, they completed four randomized 6-min cycling bouts at 90% of ventilatory threshold (control, metronome, synchronous music, and asynchronous music). Main outcome variables were oxygen uptake, HR, ratings of dyspnea and limb discomfort, affective valence, and arousal. No significant differences were evident for oxygen uptake. HR was lower under the metronome condition (122 ± 15 bpm) compared to asynchronous music (124 ± 17 bpm) and control (125 ± 16 bpm). Limb discomfort was lower while listening to the metronome (2.5 ± 1.2) and synchronous music (2.3 ± 1.1) compared to control (3.0 ± 1.5). Both music conditions, synchronous (1.9 ± 1.2) and asynchronous (2.1 ± 1.3), elicited more positive affective valence compared to metronome (1.2 ± 1.4) and control (1.2 ± 1.2), while arousal was higher with synchronous music (3.4 ± 0.9) compared to metronome (2.8 ± 1.0) and control (2.8 ± 0.9). Synchronizing movement to a rhythmic stimulus does not reduce metabolic cost but may lower limb discomfort. Moreover, synchronous music has a stronger effect on limb discomfort and arousal when compared to asynchronous music.

Benefits and Limitations of Online Instruction in Natural Science Undergraduate Liberal Arts Courses

NASA Astrophysics Data System (ADS)

Liddicoat, Joseph; Roberts, Godfrey; Liddicoat, Kendra; Porzecanski, Ana Luz; Mendez, Martin; McMullen, David

2013-04-01

Online courses in the Natural Sciences are taught three ways at New York University to undergraduate students majoring in the liberal arts and professional programs - synchronous courses in which students communicate online with the instructor and classmates in real time, asynchronous courses when faculty present course material for students to access and learn at their leisure, and hybrid or blended courses when part is taught asynchronously and part is taught face-to-face in a classroom with all students present. We have done online courses each way - Global Ecology (synchronous); Stars, Planets, and Life (synchronous and asynchronous); Darwin to DNA: An Overview of Evolution (asynchronous); Biodiversity Conservation (asynchronous); and Biology of Hunger and Population (blended). We will present the advantages and challenges we experienced teaching courses online in this fashion. Besides the advantages listed in the description for this session, another can be programmed learning that allows a set of sequential steps or a more complex branching of steps that allows students to repeat lessons multiple times to master the material. And from an academic standpoint, course content and assessment can be standardized, making it possible for each student to learn the same material. Challenges include resistance to online learning by a host of stakeholders who might be educators, students, parents, and the community. Equally challenging might be the readiness of instructors and students to teach and learn online. Student integrity issues such as plagiarism and cheating are a concern in a course taught online (Thormann and Zimmerman, 2012), so we will discuss our strategies to mitigate them.

Student Perceptions of Peer versus Instructor Facilitation of Asynchronous Online Discussions: Further Findings from Three Cases

ERIC Educational Resources Information Center

Hew, Khe Foon

2015-01-01

This study aims to extend a previous work on the role of peer facilitation of asynchronous online discussions. Specifically, in this paper I report three cases that examine students' preference for peer or instructor facilitation of online discussion forums, as well as their respective reasons for it. These three cases involved the following…

Credit Hours with No Set Time: A Study of Credit Policies in Asynchronous Online Education

ERIC Educational Resources Information Center

Prasuhn, Frederick Carl

2014-01-01

U.S. public university system policies were examined to learn how credit hours were determined for asynchronous online education. Findings indicated that (a) credit hour meaning and use are not consistent, (b) primary responsibility for credit hour decisions was at the local level, and (c) no policies exist to guide credit hour application for…

Student Voices on the Roles of Instructors in Asynchronous Learning Environments in the 21st Century

ERIC Educational Resources Information Center

Gómez-Rey, Pilar; Barbera, Elena; Fernández-Navarro, Francisco

2017-01-01

This paper determines which instructional roles and outputs are important in the 21st century from the perspective of students in asynchronous learning environments. This research work uses a literature review, in-depth interviews with experts, and a pilot study with students to define the instructors' outputs. Following this, roles are determined…

Analysis of the Relevance of Posts in Asynchronous Discussions

ERIC Educational Resources Information Center

Azevedo, Breno T.; Reategui, Eliseo; Behar, Patrícia A.

2014-01-01

This paper presents ForumMiner, a tool for the automatic analysis of students' posts in asynchronous discussions. ForumMiner uses a text mining system to extract graphs from texts that are given to students as a basis for their discussion. These graphs contain the most relevant terms found in the texts, as well as the relationships between them.…

Questions as Indicators of Ocean Literacy: Students' Online Asynchronous Discussion with a Marine Scientist

ERIC Educational Resources Information Center

Fauville, Géraldine

2017-01-01

In this article, 61 high-school students learned about ocean acidification through a virtual laboratory followed by a virtual lecture and an asynchronous discussion with a marine scientist on an online platform: VoiceThread. This study focuses on the students' development of ocean literacy when prompted to ask questions to the scientist. The…

Facing Off: Comparing an In-Person Library Orientation Lecture with an Asynchronous Online Library Orientation

ERIC Educational Resources Information Center

Gall, Dan

2014-01-01

A study to compare the effectiveness of an in-person library orientation with an online asynchronous orientation was conducted with three sections of Social Work Research Methods, a required course in the University of Iowa's Master of Social Work program. Two sections of the course received an online orientation involving short videos, text and…

Self-Efficacy for Learning Mathematics Asynchronously: Instrument Refinement and the Relationship to Mathematics Achievement

ERIC Educational Resources Information Center

Hodges, Charles; Jones, R. Caroline; Prater, Alyssa

2014-01-01

The purpose of this paper is to report the results of a two-part study. Study 1 was conducted to refine and validate a survey instrument, SELMA (Hodges, 2008), used to measure learners' self-efficacy toward learning mathematics in online or technology-intensive, asynchronous learning environments. Study 2 was conducted to investigate the…

Arguing as an Academic Purpose: The Role of Asynchronous Conferencing in Supporting Argumentative Dialogue in School and University

ERIC Educational Resources Information Center

Coffin, Caroline; Hewings, Ann; North, Sarah

2012-01-01

Learning to argue is a key academic purpose for both first and second language students. It has been claimed that computer mediated asynchronous text-based conferencing is a useful medium for developing argumentation skills (Andriessen, Baker, & Suthers, 2003). This paper reports on two research studies which explore this claim. One study focused…

Missed Opportunities for Science Learning: Unacknowledged Unscientific Arguments in Asynchronous Online and Face-To-Face Discussions

ERIC Educational Resources Information Center

Callis-Duehl, Kristine; Idsardi, Robert; Humphrey, Eve A.; Gougis, Rebekka Darner

2018-01-01

We explored the scientific argumentation that occurs among university biology students during an argumentation task implemented in two environments: face-to-face in a classroom and online in an asynchronous discussion. We observed 10 student groups, each composed of three students. Our analysis focused on how students respond to their peers'…

Effects of Synchronous Lessons on Students in an Asynchronous Online Art Course

ERIC Educational Resources Information Center

Werner, Polly D.

2011-01-01

The purpose of this study was to determine what effects synchronous instruction has on students in an asynchronous online art course. Action research was selected as the research method as it allows the researcher to study his or her own classroom in order to improve their own instruction. Data was collected for a period of one month from five…

Factor Validity of the Motivated Strategies for Learning Questionnaire (MSLQ) in Asynchronous Online Learning Environments (AOLE)

ERIC Educational Resources Information Center

Cho, Moon-Heum; Summers, Jessica

2012-01-01

The purpose of this study was to investigate the factor validity of the Motivated Strategies for Learning Questionnaire (MSLQ) in asynchronous online learning environments. In order to check the factor validity, confirmatory factor analysis (CFA) was conducted with 193 cases. Using CFA, it was found that the original measurement model fit for…

A Quantitative Study of Faculty Perceptions and Attitudes on Asynchronous Virtual Teamwork Using the Technology Acceptance Model

ERIC Educational Resources Information Center

Wolusky, G. Anthony

2016-01-01

This quantitative study used a web-based questionnaire to assess the attitudes and perceptions of online and hybrid faculty towards student-centered asynchronous virtual teamwork (AVT) using the technology acceptance model (TAM) of Davis (1989). AVT is online student participation in a team approach to problem-solving culminating in a written…

Instructional Design and Facilitation Approaches That Promote Critical Thinking in Asynchronous Online Discussions: A Review of the Literature

ERIC Educational Resources Information Center

Schindler, Laura A.; Burkholder, Gary J.

2014-01-01

Asynchronous online discussions (AODs) are often used to promote critical thinking in online courses; however, recent research suggests that levels of critical thinking in discussions remain low. Furthermore, there is a lack of consensus in the literature about the definition of critical thinking and many of the existing studies focus on one…

Growth Patterns and E-Moderating Supports in Asynchronous Online Discussions in an Undergraduate Blended Course

ERIC Educational Resources Information Center

Ghadirian, Hajar; Ayub, Ahmad Fauzi Mohd; Bakar, Kamariah Binti Abu; Hassanzadeh, Maryam

2016-01-01

This study presents a case study of asynchronous online discussions' (AOD) growth patterns in an undergraduate blended course to address the gap in our current understanding of how threads are developed in peer-moderated AODs. Building on a taxonomy of thread pattern proposed by Chan, Hew and Cheung (2009), growth patterns of thirty-six forums…

An Analysis of Peer-Submitted and Peer-Reviewed Answer Rationales, in an Asynchronous Peer Instruction Based Learning Environment

ERIC Educational Resources Information Center

Bhatnagar, Sameer; Lasry, Nathaniel; Desmarais, Michel; Dugdale, Michael; Whittaker, Chris; Charles, Elizabeth S.

2015-01-01

This paper reports on an analyis of data from a novel "Peer Instruction" application, named DALITE. The Peer Instruction paradigm is well suited to take advantage of peer-input in web-based learning environments. DALITE implements an asynchronous instantiation of peer instruction: after submitting their answer to a multiple-choice…

Shifting from Obligatory Discourse to Rich Dialogue: Promoting Student Interaction in Asynchronous Threaded Discussion Postings

ERIC Educational Resources Information Center

Mooney, Mara; Southard, Sheryne; Burton, Christie H.

2014-01-01

Asynchronous online threaded discussions are widely recognized as a tool to enhance learning in the virtual classroom. While they can serve as a mechanism for reinforcing material and promoting a deeper understanding of course content, discussion boards often lack rich and dynamic dialogue, and instead serve as a field of obligatory discourse,…

How People Learn in an Asynchronous Online Learning Environment: The Relationships between Graduate Students' Learning Strategies and Learning Satisfaction

ERIC Educational Resources Information Center

Choi, Beomkyu

2016-01-01

The purpose of this study was to examine the relationships between learners' learning strategies and learning satisfaction in an asynchronous online learning environment. In an attempt to shed some light on how people learn in an online learning environment, one hundred and sixteen graduate students who were taking online learning courses…

An Investigation of Native and Nonnative English Speakers' Levels of Written Syntactic Complexity in Asynchronous Online Discussions

ERIC Educational Resources Information Center

Mancilla, Rae L.; Polat, Nihat; Akcay, Ahmet O.

2017-01-01

This manuscript reports on a corpus-based comparison of native and nonnative graduate students' language production in an asynchronous learning environment. Using 486 discussion board postings from a five-year period (2009-2013), we analyzed the extent to which native and nonnative university students' writing differed in 10 measures of syntactic…

An Exploratory, Descriptive Study of the Attitudes of Instructors and Students toward the Use of Asynchronous Online Discussion at a Female University in Saudi Arabia

ERIC Educational Resources Information Center

Alshahrani, Hamed A.; Walker, David A.

2016-01-01

This exploratory, descriptive study examined instructor and female student attitudes toward asynchronous online discussion (AOD) in Saudi Arabia. Preliminary results, derived from an attitudinal-based survey, indicated that, in aggregate, instructors and students had positive attitudes toward using AOD at a female institution of higher education…

The Influence of Collective Asynchronous Discourse Elaborated Online by Pre-Service Teachers on Their Educational Interventions in the Classroom

ERIC Educational Resources Information Center

Allaire, Stéphane

2015-01-01

Networked learning communities are growing and they offer new opportunities for reflection on practice in education. Many authors have studied the processes followed and the contents produced by such communities. On the other hand, few have observed how collective asynchronous discourse can be enacted in the classroom. This objective was pursued…

Blending Asynchronous Discussion Groups and Peer Tutoring in Higher Education: An Exploratory Study of Online Peer Tutoring Behaviour

ERIC Educational Resources Information Center

De Smet, Marijke; Van Keer, Hilde; Valcke, Martin

2008-01-01

In the present study cross-age peer tutoring was implemented in a higher education context. Fourth-year students (N=39) operated as online tutors to support freshmen in discussing cases and solving authentic problems. This study contributes to a better understanding of the supportive interventions of tutors in asynchronous discussion groups. Peer…

An Examination of Undergraduates' Metacognitive Strategies in Pre-Class Asynchronous Activity in a Flipped Classroom

ERIC Educational Resources Information Center

Yilmaz, Rabia M.; Baydas, Ozlem

2017-01-01

The aim of the study is to examine undergraduate students' awareness of metacognition, the metacognitive strategies they use in their learning and their learning performance in pre-class asynchronous activity in a flipped classroom. The sample consisted of 47 undergraduate students. Eleven students were not included in this study since they did…

Case Study Discussion Experiences of Computer Education and Instructional Technologies Students about Instructional Design on an Asynchronous Environment

ERIC Educational Resources Information Center

Baran, Bahar; Keles, Esra

2011-01-01

The aim of this study is to reveal opinions and experiences of two Computer Education and Instructional Technologies Departments' students about case study discussion method after they discussed in online asynchronous environment about Instructional Design (ID). Totally, 80 second year students, 40 from Dokuz Eylul University and 40 from Karadeniz…

Global interrupt and barrier networks

DOEpatents

Blumrich, Matthias A.; Chen, Dong; Coteus, Paul W.; Gara, Alan G.; Giampapa, Mark E; Heidelberger, Philip; Kopcsay, Gerard V.; Steinmacher-Burow, Burkhard D.; Takken, Todd E.

2008-10-28

A system and method for generating global asynchronous signals in a computing structure. Particularly, a global interrupt and barrier network is implemented that implements logic for generating global interrupt and barrier signals for controlling global asynchronous operations performed by processing elements at selected processing nodes of a computing structure in accordance with a processing algorithm; and includes the physical interconnecting of the processing nodes for communicating the global interrupt and barrier signals to the elements via low-latency paths. The global asynchronous signals respectively initiate interrupt and barrier operations at the processing nodes at times selected for optimizing performance of the processing algorithms. In one embodiment, the global interrupt and barrier network is implemented in a scalable, massively parallel supercomputing device structure comprising a plurality of processing nodes interconnected by multiple independent networks, with each node including one or more processing elements for performing computation or communication activity as required when performing parallel algorithm operations. One multiple independent network includes a global tree network for enabling high-speed global tree communications among global tree network nodes or sub-trees thereof. The global interrupt and barrier network may operate in parallel with the global tree network for providing global asynchronous sideband signals.

A Scalable Multicore Architecture With Heterogeneous Memory Structures for Dynamic Neuromorphic Asynchronous Processors (DYNAPs).

PubMed

Moradi, Saber; Qiao, Ning; Stefanini, Fabio; Indiveri, Giacomo

2018-02-01

Neuromorphic computing systems comprise networks of neurons that use asynchronous events for both computation and communication. This type of representation offers several advantages in terms of bandwidth and power consumption in neuromorphic electronic systems. However, managing the traffic of asynchronous events in large scale systems is a daunting task, both in terms of circuit complexity and memory requirements. Here, we present a novel routing methodology that employs both hierarchical and mesh routing strategies and combines heterogeneous memory structures for minimizing both memory requirements and latency, while maximizing programming flexibility to support a wide range of event-based neural network architectures, through parameter configuration. We validated the proposed scheme in a prototype multicore neuromorphic processor chip that employs hybrid analog/digital circuits for emulating synapse and neuron dynamics together with asynchronous digital circuits for managing the address-event traffic. We present a theoretical analysis of the proposed connectivity scheme, describe the methods and circuits used to implement such scheme, and characterize the prototype chip. Finally, we demonstrate the use of the neuromorphic processor with a convolutional neural network for the real-time classification of visual symbols being flashed to a dynamic vision sensor (DVS) at high speed.

Data Collection for Mobile Group Consumption: An Asynchronous Distributed Approach.

PubMed

Zhu, Weiping; Chen, Weiran; Hu, Zhejie; Li, Zuoyou; Liang, Yue; Chen, Jiaojiao

2016-04-06

Mobile group consumption refers to consumption by a group of people, such as a couple, a family, colleagues and friends, based on mobile communications. It differs from consumption only involving individuals, because of the complex relations among group members. Existing data collection systems for mobile group consumption are centralized, which has the disadvantages of being a performance bottleneck, having single-point failure and increasing business and security risks. Moreover, these data collection systems are based on a synchronized clock, which is often unrealistic because of hardware constraints, privacy concerns or synchronization cost. In this paper, we propose the first asynchronous distributed approach to collecting data generated by mobile group consumption. We formally built a system model thereof based on asynchronous distributed communication. We then designed a simulation system for the model for which we propose a three-layer solution framework. After that, we describe how to detect the causality relation of two/three gathering events that happened in the system based on the collected data. Various definitions of causality relations based on asynchronous distributed communication are supported. Extensive simulation results show that the proposed approach is effective for data collection relating to mobile group consumption.

Data Collection for Mobile Group Consumption: An Asynchronous Distributed Approach †

PubMed Central

Zhu, Weiping; Chen, Weiran; Hu, Zhejie; Li, Zuoyou; Liang, Yue; Chen, Jiaojiao

2016-01-01

Mobile group consumption refers to consumption by a group of people, such as a couple, a family, colleagues and friends, based on mobile communications. It differs from consumption only involving individuals, because of the complex relations among group members. Existing data collection systems for mobile group consumption are centralized, which has the disadvantages of being a performance bottleneck, having single-point failure and increasing business and security risks. Moreover, these data collection systems are based on a synchronized clock, which is often unrealistic because of hardware constraints, privacy concerns or synchronization cost. In this paper, we propose the first asynchronous distributed approach to collecting data generated by mobile group consumption. We formally built a system model thereof based on asynchronous distributed communication. We then designed a simulation system for the model for which we propose a three-layer solution framework. After that, we describe how to detect the causality relation of two/three gathering events that happened in the system based on the collected data. Various definitions of causality relations based on asynchronous distributed communication are supported. Extensive simulation results show that the proposed approach is effective for data collection relating to mobile group consumption. PMID:27058544

Asynchronous communication in spectral-element and discontinuous Galerkin methods for atmospheric dynamics – a case study using the High-Order Methods Modeling Environment (HOMME-homme_dg_branch)

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

Jamroz, Benjamin F.; Klofkorn, Robert

The scalability of computational applications on current and next-generation supercomputers is increasingly limited by the cost of inter-process communication. We implement non-blocking asynchronous communication in the High-Order Methods Modeling Environment for the time integration of the hydrostatic fluid equations using both the spectral-element and discontinuous Galerkin methods. This allows the overlap of computation with communication, effectively hiding some of the costs of communication. A novel detail about our approach is that it provides some data movement to be performed during the asynchronous communication even in the absence of other computations. This method produces significant performance and scalability gains in large-scalemore » simulations.« less

Asynchronous communication in spectral-element and discontinuous Galerkin methods for atmospheric dynamics – a case study using the High-Order Methods Modeling Environment (HOMME-homme_dg_branch)

DOE PAGES

Jamroz, Benjamin F.; Klofkorn, Robert

2016-08-26

The scalability of computational applications on current and next-generation supercomputers is increasingly limited by the cost of inter-process communication. We implement non-blocking asynchronous communication in the High-Order Methods Modeling Environment for the time integration of the hydrostatic fluid equations using both the spectral-element and discontinuous Galerkin methods. This allows the overlap of computation with communication, effectively hiding some of the costs of communication. A novel detail about our approach is that it provides some data movement to be performed during the asynchronous communication even in the absence of other computations. This method produces significant performance and scalability gains in large-scalemore » simulations.« less

Taming the Wild: A Unified Analysis of Hogwild!-Style Algorithms.

PubMed

De Sa, Christopher; Zhang, Ce; Olukotun, Kunle; Ré, Christopher

2015-12-01

Stochastic gradient descent (SGD) is a ubiquitous algorithm for a variety of machine learning problems. Researchers and industry have developed several techniques to optimize SGD's runtime performance, including asynchronous execution and reduced precision. Our main result is a martingale-based analysis that enables us to capture the rich noise models that may arise from such techniques. Specifically, we use our new analysis in three ways: (1) we derive convergence rates for the convex case (Hogwild!) with relaxed assumptions on the sparsity of the problem; (2) we analyze asynchronous SGD algorithms for non-convex matrix problems including matrix completion; and (3) we design and analyze an asynchronous SGD algorithm, called Buckwild!, that uses lower-precision arithmetic. We show experimentally that our algorithms run efficiently for a variety of problems on modern hardware.

Dynamic modelling and estimation of the error due to asynchronism in a redundant asynchronous multiprocessor system

NASA Technical Reports Server (NTRS)

Huynh, Loc C.; Duval, R. W.

1986-01-01

The use of Redundant Asynchronous Multiprocessor System to achieve ultrareliable Fault Tolerant Control Systems shows great promise. The development has been hampered by the inability to determine whether differences in the outputs of redundant CPU's are due to failures or to accrued error built up by slight differences in CPU clock intervals. This study derives an analytical dynamic model of the difference between redundant CPU's due to differences in their clock intervals and uses this model with on-line parameter identification to idenitify the differences in the clock intervals. The ability of this methodology to accurately track errors due to asynchronisity generate an error signal with the effect of asynchronisity removed and this signal may be used to detect and isolate actual system failures.

Network Security Guideline

DTIC Science & Technology

1993-06-01

3.2.15.3 ISDN Services over the Telephone Network 3 Integrated Services Digital Network (ISDN) services are subject to the same restrictions as router...to be audited: [SYS$SYSTEM]SYS.EXE, LOGINOUT.EXE, STARTUP.COM, RIGHTSLIST.DAT [SYS$ LIBARY ] I SECURESHR.EXE [SYS$ROOT] SYSEXE.DIR, SYSLIB.DIR...quantification) of the encoded value; ASCII is normally used for asynchronous transmission. compare with digital . ASYNCHRONOUS-Data transmission that is

When Groups Decide to Use Asynchronous Online Discussions: Collaborative Learning and Social Presence under a Voluntary Participation Structure

ERIC Educational Resources Information Center

So, H.-J.

2009-01-01

The purpose of this study is to explore how groups decide to use asynchronous online discussion forums in a non-mandatory setting, and, after the group decision is made, how group members use online discussion forums to complete a collaborative learning project requiring complex data gathering and research processes. While a large body of research…

A Qualitative Analysis of African American Female High School Graduates' Perceptions of Participating in an Asynchronous Credit Recovery Program

ERIC Educational Resources Information Center

Waters, Eric L.

2010-01-01

Asynchronous online credit recovery programs have been implemented in public schools across the United States for a variety of reasons. In this case, African American female students who are deficient in course credits towards high school graduation have taken advantage of this relatively new e-programming mechanism as a means to capture course…

Effectiveness of an Asynchronous Online Module on University Students' Understanding of the Bohr Model of the Hydrogen Atom

ERIC Educational Resources Information Center

Farina, William J., Jr.; Bodzin, Alec M.

2018-01-01

Web-based learning is a growing field in education, yet empirical research into the design of high quality Web-based university science instruction is scarce. A one-week asynchronous online module on the Bohr Model of the atom was developed and implemented guided by the knowledge integration framework. The unit design aligned with three identified…

A Simple Analytical Model for Asynchronous Dense WDM/OOK Systems

DTIC Science & Technology

1994-06-01

asynchronous dense WDM systems employing an external OOK modulator. Our model is based upon a close approximation of the optical Fabry - Perot filter in the...receiver as a single-pole RC filter for signals that are bandlimitr i, & -equency band approximately equal to one sixtieth of the Fabry - Perot filter’s...4 A. INPUT SIGNAL ............................................................................................... 4 B. FABRY - PEROT FILTERED OUTPUT

Teaching Writing within the Common European Framework of Reference (CEFR): A Supplement Asynchronous Blended Learning Approach in an EFL Undergraduate Course in Egypt

ERIC Educational Resources Information Center

Shaarawy, Hanaa Youssef; Lotfy, Nohayer Esmat

2013-01-01

Based on the Common European Framework of Reference (CEFR) and following a blended learning approach (a supplement model), this article reports on a quasi-experiment where writing was taught evenly with other language skills in everyday language contexts and where asynchronous online activities were required from students to extend learning beyond…

Practical applications of digital integrated circuits. Part 2: Minimization techniques, code conversion, flip-flops, and asynchronous circuits

NASA Technical Reports Server (NTRS)

1972-01-01

Here, the 7400 line of transistor to transistor logic (TTL) devices is emphasized almost exclusively where hardware is concerned. However, it should be pointed out that the logic theory contained herein applies to all hardware. Binary numbers, simplification of logic circuits, code conversion circuits, basic flip-flop theory, details about series 54/7400, and asynchronous circuits are discussed.

Asynchronous inputs and flip-flop metastability in the CLAS trigger at CEBAF

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

Doughty, D.C. Jr.; Lemon, S.; Bonneau, P.

1993-08-01

The impact of flip-flop metastability on the pipelined trigger for the CLAS detector at CEBAF has been studied. The authors find that the newest ECL flip-flops (ECLinPS) are much faster than older families (10H) at resolving the metastable condition. This will allow their use in systems with asynchronous inputs without an extra stage of synchronizing flip-flops.

A Comparison of Classroom and Online Asynchronous Problem-Based Learning for Students Undertaking Statistics Training as Part of a Public Health Masters Degree

ERIC Educational Resources Information Center

de Jong, N.; Verstegen, D. M. L.; Tan, F. E. S.; O'Connor, S. J.

2013-01-01

This case-study compared traditional, face-to-face classroom-based teaching with asynchronous online learning and teaching methods in two sets of students undertaking a problem-based learning module in the multilevel and exploratory factor analysis of longitudinal data as part of a Masters degree in Public Health at Maastricht University. Students…

"Picturing Them Right in Front of Me": Guidelines for Implementing Video Communication in Online and Blended Learning

ERIC Educational Resources Information Center

West, Richard E.; Jay, Jason; Armstrong, Matt; Borup, Jered

2017-01-01

We provide actionable strategies that teachers can follow when implementing asynchronous video communication and feedback in their own courses. These strategies are based on our own research over many years in the use of asynchronous video in online teaching, as well as our review of the literature, and are provided to foster greater discussion on…

An asynchronous traversal engine for graph-based rich metadata management

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

Dai, Dong; Carns, Philip; Ross, Robert B.

Rich metadata in high-performance computing (HPC) systems contains extended information about users, jobs, data files, and their relationships. Property graphs are a promising data model to represent heterogeneous rich metadata flexibly. Specifically, a property graph can use vertices to represent different entities and edges to record the relationships between vertices with unique annotations. The high-volume HPC use case, with millions of entities and relationships, naturally requires an out-of-core distributed property graph database, which must support live updates (to ingest production information in real time), low-latency point queries (for frequent metadata operations such as permission checking), and large-scale traversals (for provenancemore » data mining). Among these needs, large-scale property graph traversals are particularly challenging for distributed graph storage systems. Most existing graph systems implement a "level synchronous" breadth-first search algorithm that relies on global synchronization in each traversal step. This performs well in many problem domains; but a rich metadata management system is characterized by imbalanced graphs, long traversal lengths, and concurrent workloads, each of which has the potential to introduce or exacerbate stragglers (i.e., abnormally slow steps or servers in a graph traversal) that lead to low overall throughput for synchronous traversal algorithms. Previous research indicated that the straggler problem can be mitigated by using asynchronous traversal algorithms, and many graph-processing frameworks have successfully demonstrated this approach. Such systems require the graph to be loaded into a separate batch-processing framework instead of being iteratively accessed, however. In this work, we investigate a general asynchronous graph traversal engine that can operate atop a rich metadata graph in its native format. We outline a traversal-aware query language and key optimizations (traversal-affiliate caching and execution merging) necessary for efficient performance. We further explore the effect of different graph partitioning strategies on the traversal performance for both synchronous and asynchronous traversal engines. Our experiments show that the asynchronous graph traversal engine is more efficient than its synchronous counterpart in the case of HPC rich metadata processing, where more servers are involved and larger traversals are needed. Furthermore, the asynchronous traversal engine is more adaptive to different graph partitioning strategies.« less

An asynchronous traversal engine for graph-based rich metadata management

DOE PAGES

Dai, Dong; Carns, Philip; Ross, Robert B.; ...

2016-06-23

Rich metadata in high-performance computing (HPC) systems contains extended information about users, jobs, data files, and their relationships. Property graphs are a promising data model to represent heterogeneous rich metadata flexibly. Specifically, a property graph can use vertices to represent different entities and edges to record the relationships between vertices with unique annotations. The high-volume HPC use case, with millions of entities and relationships, naturally requires an out-of-core distributed property graph database, which must support live updates (to ingest production information in real time), low-latency point queries (for frequent metadata operations such as permission checking), and large-scale traversals (for provenancemore » data mining). Among these needs, large-scale property graph traversals are particularly challenging for distributed graph storage systems. Most existing graph systems implement a "level synchronous" breadth-first search algorithm that relies on global synchronization in each traversal step. This performs well in many problem domains; but a rich metadata management system is characterized by imbalanced graphs, long traversal lengths, and concurrent workloads, each of which has the potential to introduce or exacerbate stragglers (i.e., abnormally slow steps or servers in a graph traversal) that lead to low overall throughput for synchronous traversal algorithms. Previous research indicated that the straggler problem can be mitigated by using asynchronous traversal algorithms, and many graph-processing frameworks have successfully demonstrated this approach. Such systems require the graph to be loaded into a separate batch-processing framework instead of being iteratively accessed, however. In this work, we investigate a general asynchronous graph traversal engine that can operate atop a rich metadata graph in its native format. We outline a traversal-aware query language and key optimizations (traversal-affiliate caching and execution merging) necessary for efficient performance. We further explore the effect of different graph partitioning strategies on the traversal performance for both synchronous and asynchronous traversal engines. Our experiments show that the asynchronous graph traversal engine is more efficient than its synchronous counterpart in the case of HPC rich metadata processing, where more servers are involved and larger traversals are needed. Furthermore, the asynchronous traversal engine is more adaptive to different graph partitioning strategies.« less

SAChES: Scalable Adaptive Chain-Ensemble Sampling.

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

Swiler, Laura Painton; Ray, Jaideep; Ebeida, Mohamed Salah

We present the development of a parallel Markov Chain Monte Carlo (MCMC) method called SAChES, Scalable Adaptive Chain-Ensemble Sampling. This capability is targed to Bayesian calibration of com- putationally expensive simulation models. SAChES involves a hybrid of two methods: Differential Evo- lution Monte Carlo followed by Adaptive Metropolis. Both methods involve parallel chains. Differential evolution allows one to explore high-dimensional parameter spaces using loosely coupled (i.e., largely asynchronous) chains. Loose coupling allows the use of large chain ensembles, with far more chains than the number of parameters to explore. This reduces per-chain sampling burden, enables high-dimensional inversions and the usemore » of computationally expensive forward models. The large number of chains can also ameliorate the impact of silent-errors, which may affect only a few chains. The chain ensemble can also be sampled to provide an initial condition when an aberrant chain is re-spawned. Adaptive Metropolis takes the best points from the differential evolution and efficiently hones in on the poste- rior density. The multitude of chains in SAChES is leveraged to (1) enable efficient exploration of the parameter space; and (2) ensure robustness to silent errors which may be unavoidable in extreme-scale computational platforms of the future. This report outlines SAChES, describes four papers that are the result of the project, and discusses some additional results.« less

Analysis of compaction initiation in human embryos by using time-lapse cinematography.

PubMed

Iwata, Kyoko; Yumoto, Keitaro; Sugishima, Minako; Mizoguchi, Chizuru; Kai, Yoshiteru; Iba, Yumiko; Mio, Yasuyuki

2014-04-01

To analyze the initiation of compaction in human embryos in vitro by using time-lapse cinematography (TLC), with the goal of determining the precise timing of compaction and clarifying the morphological changes underlying the compaction process. One hundred and fifteen embryos donated by couples with no further need for embryo-transfer were used in this study. Donated embryos were thawed and processed, and then their morphological behavior during the initiation of compaction was dynamically observed via time-lapse cinematography (TLC) for 5 days. Although the initiation of compaction occurred throughout the period from the 4-cell to 16-cell stage, 99 (86.1 %) embryos initiated compaction at the 8-cell stage or later, with initiation at the 8-cell stage being most frequent (22.6 %). Of these 99 embryos, 49.5 % developed into good-quality blastocysts. In contrast, of the 16 (13.9 %) embryos that initiated compaction prior to the 8-cell stage, only 18.8 % developed into good-quality blastocysts. Embryos that initiated compaction before the 8-cell stage showed significantly higher numbers of multinucleated blastomeres, due to asynchronism in nuclear division at the third mitotic division resulting from cytokinetic failure. The initiation of compaction primarily occurs at the third mitotic division or later in human embryos. Embryos that initiate compaction before the 8-cell stage are usually associated with aberrant embryonic development (i.e., cytokinetic failure accompanied by karyokinesis).

Two-dimensional correlation spectroscopic studies on coordination between organic ligands and Ni2 + ions

NASA Astrophysics Data System (ADS)

Bao, Ya-nan; Zeng, Yi-wei; Guo, Ran; Ablikim, Mesude; Shi, Hai-fang; Yang, Li-min; Yang, Zhan-lan; Xu, Yi-zhuang; Noda, Isao; Wu, Jin-guang

2018-05-01

3A2g → 3T1g(P) transition band of Ni2 + is used to probe the coordination of Ni2 +. Two-dimensional asynchronous spectra (2DCOS) are generated using the Double Asynchronous Orthogonal Sample Design (DAOSD), Asynchronous Spectrum with Auxiliary Peaks (ASAP) and Two-Trace Two-Dimensional (2T2D) approaches. Cross peaks relevant to the 3A2g → 3T1g(P) transition band of Ni2 + are utilized to probe coordination between Ni2 + and various ligands. We studied the spectral behavior of the 3A2g → 3T1g(P) transition band when Ni2 + is coordinated with ethylenediaminetetraacetic acid disodium salt (EDTA). The pattern of cross peaks in 2D asynchronous spectrum demonstrates that coordination brings about significant blue shift of the band. In addition, the absorptivity of the band increases remarkably. The interaction between Ni2 + and galactitol is also investigated. Although no clearly observable change is found on the 3A2g → 3T1g(P) transition band when galactitol is introduced, the appearance of cross peak in 2D asynchronous spectrum demonstrates that coordination indeed occurs between Ni2 + and galactitol. Furthermore, the pattern of cross peak indicates that peak position, bandwidth and absorptivity of the 3A2g → 3T1g(P) transition band of Ni(galactitol)x2 + is considerably different from those of Ni(H2O)62 +. Thus, 2DCOS is helpful to reveal subtle spectral variation, which might be helpful in shedding light on the physical-chemical nature of coordination.

Achieving Precision Death with Cell-Cycle Inhibitors that Target DNA Replication and Repair.

PubMed

Lin, Aimee Bence; McNeely, Samuel C; Beckmann, Richard P

2017-07-01

All cancers are characterized by defects in the systems that ensure strict control of the cell cycle in normal tissues. The consequent excess tissue growth can be countered by drugs that halt cell division, and, indeed, the majority of chemotherapeutics developed during the last century work by disrupting processes essential for the cell cycle, particularly DNA synthesis, DNA replication, and chromatid segregation. In certain contexts, the efficacy of these classes of drugs can be impressive, but because they indiscriminately block the cell cycle of all actively dividing cells, their side effects severely constrain the dose and duration with which they can be administered, allowing both normal and malignant cells to escape complete growth arrest. Recent progress in understanding how cancers lose control of the cell cycle, coupled with comprehensive genomic profiling of human tumor biopsies, has shown that many cancers have mutations affecting various regulators and checkpoints that impinge on the core cell-cycle machinery. These defects introduce unique vulnerabilities that can be exploited by a next generation of drugs that promise improved therapeutic windows in patients whose tumors bear particular genomic aberrations, permitting increased dose intensity and efficacy. These developments, coupled with the success of new drugs targeting cell-cycle regulators, have led to a resurgence of interest in cell-cycle inhibitors. This review in particular focuses on the newer strategies that may facilitate better therapeutic targeting of drugs that inhibit the various components that safeguard the fidelity of the fundamental processes of DNA replication and repair. Clin Cancer Res; 23(13); 3232-40. ©2017 AACR . ©2017 American Association for Cancer Research.

Therapeutic targeting of replicative immortality

PubMed Central

Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

2015-01-01

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

Asynchronous decision making in a memorized paddle pressing task

NASA Astrophysics Data System (ADS)

Dankert, James R.; Olson, Byron; Si, Jennie

2008-12-01

This paper presents a method for asynchronous decision making using recorded neural data in a binary decision task. This is a demonstration of a technique for developing motor cortical neural prosthetics that do not rely on external cued timing information. The system presented in this paper uses support vector machines and leaky integrate-and-fire elements to predict directional paddle presses. In addition to the traditional metrics of accuracy, asynchronous systems must also optimize the time needed to make a decision. The system presented is able to predict paddle presses with a median accuracy of 88% and all decisions are made before the time of the actual paddle press. An alternative bit rate measure of performance is defined to show that the system proposed here is able to perform the task with the same efficiency as the rats.

Asynchronous Gossip for Averaging and Spectral Ranking

NASA Astrophysics Data System (ADS)

Borkar, Vivek S.; Makhijani, Rahul; Sundaresan, Rajesh

2014-08-01

We consider two variants of the classical gossip algorithm. The first variant is a version of asynchronous stochastic approximation. We highlight a fundamental difficulty associated with the classical asynchronous gossip scheme, viz., that it may not converge to a desired average, and suggest an alternative scheme based on reinforcement learning that has guaranteed convergence to the desired average. We then discuss a potential application to a wireless network setting with simultaneous link activation constraints. The second variant is a gossip algorithm for distributed computation of the Perron-Frobenius eigenvector of a nonnegative matrix. While the first variant draws upon a reinforcement learning algorithm for an average cost controlled Markov decision problem, the second variant draws upon a reinforcement learning algorithm for risk-sensitive control. We then discuss potential applications of the second variant to ranking schemes, reputation networks, and principal component analysis.

Asynchronous State Estimation for Discrete-Time Switched Complex Networks With Communication Constraints.

PubMed

Zhang, Dan; Wang, Qing-Guo; Srinivasan, Dipti; Li, Hongyi; Yu, Li

2018-05-01

This paper is concerned with the asynchronous state estimation for a class of discrete-time switched complex networks with communication constraints. An asynchronous estimator is designed to overcome the difficulty that each node cannot access to the topology/coupling information. Also, the event-based communication, signal quantization, and the random packet dropout problems are studied due to the limited communication resource. With the help of switched system theory and by resorting to some stochastic system analysis method, a sufficient condition is proposed to guarantee the exponential stability of estimation error system in the mean-square sense and a prescribed performance level is also ensured. The characterization of the desired estimator gains is derived in terms of the solution to a convex optimization problem. Finally, the effectiveness of the proposed design approach is demonstrated by a simulation example.

The use of online discussions for post-clinical conference.

PubMed

Berkstresser, Kristie

2016-01-01

Nurse educators, at every level of pre-licensure nursing education, are charged with developing critical thinking skills within their students. Post-clinical conference is one teaching strategy that nurse educators can employ to help promote the development of critical thinking skills in pre-licensure nursing students. However, traditional face-to-face post-clinical conference is marred with issues and concerns, as identified in the nursing education literature. An alternative to face-to-face post-clinical conference, asynchronous online learning environment, mitigates the issues and concerns associated with traditional post-clinical conference. Adult learning theory supports the use of asynchronous online learning environment because the asynchronous online learning environment promotes student-centered teaching strategy in place of teacher-centered learning, which by its nature traditional face-to-face post-clinical conference tends to support. Copyright © 2015 Elsevier Ltd. All rights reserved.

Event-Based Tone Mapping for Asynchronous Time-Based Image Sensor

PubMed Central

Simon Chane, Camille; Ieng, Sio-Hoi; Posch, Christoph; Benosman, Ryad B.

2016-01-01

The asynchronous time-based neuromorphic image sensor ATIS is an array of autonomously operating pixels able to encode luminance information with an exceptionally high dynamic range (>143 dB). This paper introduces an event-based methodology to display data from this type of event-based imagers, taking into account the large dynamic range and high temporal accuracy that go beyond available mainstream display technologies. We introduce an event-based tone mapping methodology for asynchronously acquired time encoded gray-level data. A global and a local tone mapping operator are proposed. Both are designed to operate on a stream of incoming events rather than on time frame windows. Experimental results on real outdoor scenes are presented to evaluate the performance of the tone mapping operators in terms of quality, temporal stability, adaptation capability, and computational time. PMID:27642275

Bayesian operational modal analysis with asynchronous data, part I: Most probable value

NASA Astrophysics Data System (ADS)

Zhu, Yi-Chen; Au, Siu-Kui

2018-01-01

In vibration tests, multiple sensors are used to obtain detailed mode shape information about the tested structure. Time synchronisation among data channels is required in conventional modal identification approaches. Modal identification can be more flexibly conducted if this is not required. Motivated by the potential gain in feasibility and economy, this work proposes a Bayesian frequency domain method for modal identification using asynchronous 'output-only' ambient data, i.e. 'operational modal analysis'. It provides a rigorous means for identifying the global mode shape taking into account the quality of the measured data and their asynchronous nature. This paper (Part I) proposes an efficient algorithm for determining the most probable values of modal properties. The method is validated using synthetic and laboratory data. The companion paper (Part II) investigates identification uncertainty and challenges in applications to field vibration data.

Investigation on intermolecular interaction between berberine and β-cyclodextrin by 2D UV-Vis asynchronous spectra

NASA Astrophysics Data System (ADS)

He, Anqi; Kang, Xiaoyan; Xu, Yizhuang; Noda, Isao; Ozaki, Yukihiro; Wu, Jinguang

2017-10-01

The interaction between berberine chloride and β-cyclodextrin (β-CyD) is investigated via 2D asynchronous UV-Vis spectrum. The occurrence of cross peaks around (420 nm, 420 nm) in 2D asynchronous spectrum reveals that specific intermolecular interaction indeed exists between berberine chloride and β-CyD. In spite of the difficulty caused by overlapping of cross peaks, we manage to confirm that the 420 nm band of berberine undergoes a red-shift, and its bandwidth decreases under the interaction with β-CyD. The red-shift of the 420 nm band that can be assigned to n-π* transition indicates the environment of berberine becomes more hydrophobic. The above spectral behavior is helpful in understanding why the solubility of berberine is enhanced by β-CyD.

Genomic instability in cancer: Teetering on the limit of tolerance

PubMed Central

Andor, Noemi; Maley, Carlo C.; Ji, Hanlee P.

2017-01-01

Cancer genomic instability contributes to the phenomenon of intratumoral genetic heterogeneity, provides the genetic diversity required for natural selection and enables the extensive phenotypic diversity that is frequently observed among patients. Genomic instability has previously been associated with poor prognosis. However, we have evidence that for solid tumors of epithelial origin, extreme levels of genomic instability, where more than 75% of the genome is subject to somatic copy number alterations, are associated with a potentially better prognosis compared to intermediate levels under this threshold. This has been observed in clonal subpopulations of larger size, especially when genomic instability is shared among a limited number of clones. We hypothesize that cancers with extreme levels of genomic instability may be teetering on the brink of a threshold where so much of their genome is adversely altered that cells rarely replicate successfully. Another possibility is that tumors with high levels of genomic instability are more immunogenic than other cancers with a less extensive burden of genetic aberrations. Regardless of the exact mechanism, but hinging on our ability to quantify how a tumor’s burden of genetic aberrations is distributed among coexisting clones – genomic instability has important therapeutic implications. Herein, we explore the possibility that a high genomic instability could be the basis for a tumor’s sensitivity to DNA damaging therapies. We primarily focus on studies of epithelial-derived solid tumors. PMID:28432052

The histone variant H2A.Bbd is enriched at sites of DNA synthesis

PubMed Central

Sansoni, Viola; Casas-Delucchi, Corella S.; Rajan, Malini; Schmidt, Andreas; Bönisch, Clemens; Thomae, Andreas W.; Staege, Martin S.; Hake, Sandra B.; Cardoso, M. Cristina; Imhof, Axel

2014-01-01

Histone variants play an important role in shaping the mammalian epigenome and their aberrant expression is frequently observed in several types of cancer. However, the mechanisms that mediate their function and the composition of the variant-containing chromatin are still largely unknown. A proteomic interrogation of chromatin containing the different H2A variants macroH2A.1.2, H2A.Bbd and H2A revealed a strikingly different protein composition. Gene ontology analysis reveals a strong enrichment of splicing factors as well as components of the mammalian replisome in H2A.Bbd-containing chromatin. We find H2A.Bbd localizing transiently to sites of DNA synthesis during S-phase and during DNA repair. Cells that express H2A.Bbd have a shortened S-phase and are more susceptible to DNA damage, two phenotypes that are also observed in human Hodgkin's lymphoma cells that aberrantly express this variant. Based on our experiments we conclude that H2A.Bbd is targeted to newly synthesized DNA during replication and DNA repair. The transient incorporation of H2A.Bbd may be due to the intrinsic instability of nucleosomes carrying this variant or a faster chromatin loading. This potentially leads to a disturbance of the existing chromatin structure, which may have effects on cell cycle regulation and DNA damage sensitivity. PMID:24753410

Technologies That Assist in Online Group Work: A Comparison of Synchronous and Asynchronous Computer Mediated Communication Technologies on Students' Learning and Community

ERIC Educational Resources Information Center

Rockinson-Szapkiw, Amanda; Wendt, Jillian

2015-01-01

While the benefits of online group work completed using asynchronous CMC technology is documented, researchers have identified a number of challenges that result in ineffective and unsuccessful online group work. Fewer channels of communication and lack of immediacy when compared to face-to-face group work are a few of the noted limitations. Thus,…

Overview of AMS (CCSDS Asynchronous Message Service)

NASA Technical Reports Server (NTRS)

Burleigh, Scott

2006-01-01

This viewgraph presentation gives an overview of the Consultative Committee for Space Data Systems (CCSDS) Asynchronous Message Service (AMS). The topics include: 1) Key Features; 2) A single AMS continuum; 3) The AMS Protocol Suite; 4) A multi-continuum venture; 5) Constraining transmissions; 6) Security; 7) Fault Tolerance; 8) Performance of Reference Implementation; 9) AMS vs Multicast (1); 10) AMS vs Multicast (2); 11) RAMS testing exercise; and 12) Results.

A Study on Run Time Assurance for Complex Cyber Physical Systems

DTIC Science & Technology

2013-04-18

safety verification approach was applied to synchronization of distributed local clocks of the nodes on a CAN bus by Jiang et al. [36]. The class of...mode of interaction between the instrumented system and the checker, we distin- guish between synchronous and asynchronous monitoring. In synchronous ...occurred. Synchronous monitoring may deliver a higher degree of assurance than the asynchronous one, because it can block a dangerous action. However

Asynchronous inputs and flip-flop metastability in the CLAS trigger at CEBAF

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

Dave Doughty; S. Lemon; P. Bonneau

1992-10-01

The impact of flip-flop metastability on the pipelined trigger for the CLAS detector at CEBAF (Continuous Electron Beam Accelerator Facility) has been studied. It is found that the newest ECL (emitter coupled logic) flip-flops (ECLinPS) are much faster than older families at resolving the metastable condition. This will allow their use in systems with asynchronous inputs without an extra stage of synchronizing flip-flops.

TACS Central Control Facility.

DTIC Science & Technology

1981-02-12

PULSE RTC REAL TIME CLOCK -{> I . SIGNAL INVERSION UASC UNIVERSAL ASYNCHRONOUS SERIAL - ---- 4w SPECIAL INTERFACE CONTROLLER Fiq. 2-1. MAC hardware...34 Universal Asynchronous Serial Controller" (UASC) cards. The cards implement an RS-232 standard interface. All controllers are set to operate at a data...Bridwell and I. Richer, "A Preliminary Design of a TDMA System for FLEETSAT," Technical Note 1975-5, Lincoln Laboratory, M.I.T. (12 March 1975), DDC

Friend or foe? An exploratory study of Australian parents' use of asynchronous discussion boards in childhood obesity.

PubMed

Appleton, Jessica; Fowler, Cathrine; Brown, Nicola

2014-01-01

The use of Internet and social media is increasing in every area of life. Parents are increasingly using online mediums to seek information about their children's health. Therefore, this is becoming an increasingly important topic area for health professionals to acknowledge. Developing an understanding about the dissemination of child health information through these online mediums will assist health professional to continue to engage and support parents to seek and share accurate and safe child health information. To explore parents' use of asynchronous online discussion boards for child health information seeking, advice and social support. A qualitative descriptive approach using an a priori template analysis was used to explore 34 discussions threads sampled from two Australian based online parenting discussion forums. To contain the scope of this study the threads chosen focused on childhood obesity in the Australian context. Four major themes related to parents' use of asynchronous online discussion boards were found. These were seeking advice, sharing advice, social support and making judgement. This final theme of making judgements included parents' perceptions of health professionals' advice. Asynchronous online discussion boards are online mediums being utilised for seeking and sharing child health related information and support between parents. The notion

Pseudo Asynchronous Level Crossing adc for ecg Signal Acquisition.

PubMed

Marisa, T; Niederhauser, T; Haeberlin, A; Wildhaber, R A; Vogel, R; Goette, J; Jacomet, M

2017-02-07

A new pseudo asynchronous level crossing analogue-to-digital converter (adc) architecture targeted for low-power, implantable, long-term biomedical sensing applications is presented. In contrast to most of the existing asynchronous level crossing adc designs, the proposed design has no digital-to-analogue converter (dac) and no continuous time comparators. Instead, the proposed architecture uses an analogue memory cell and dynamic comparators. The architecture retains the signal activity dependent sampling operation by generating events only when the input signal is changing. The architecture offers the advantages of smaller chip area, energy saving and fewer analogue system components. Beside lower energy consumption the use of dynamic comparators results in a more robust performance in noise conditions. Moreover, dynamic comparators make interfacing the asynchronous level crossing system to synchronous processing blocks simpler. The proposed adc was implemented in [Formula: see text] complementary metal-oxide-semiconductor (cmos) technology, the hardware occupies a chip area of 0.0372 mm 2 and operates from a supply voltage of [Formula: see text] to [Formula: see text]. The adc's power consumption is as low as 0.6 μW with signal bandwidth from [Formula: see text] to [Formula: see text] and achieves an equivalent number of bits (enob) of up to 8 bits.

Chick Development and Asynchroneous Hatching in the Zebra Finch (Taeniopygia guttata castanotis).

PubMed

Ikebuchi, Maki; Okanoya, Kazuo; Hasegawa, Toshikazu; Bischof, Hans-Joachim

2017-10-01

The mode of hatching in birds has important impacts on both parents and chicks, including the costs and risks of breeding for parents, and sibling competition in a clutch. Birds with multiple eggs in a single clutch often begin incubating when most eggs are laid, thereby reducing time of incubation, nursing burden, and sibling competition. In some songbirds and some other species, however, incubation starts immediately after the first egg is laid, and the chicks thus hatch asynchronously. This may result in differences in parental care and in sibling competition based on body size differences among older and younger chicks, which in turn might produce asynchronous development among siblings favoring the first hatchling, and further affect the development and fitness of the chicks after fledging. To determine whether such processes in fact occur in the zebra finch, we observed chick development in 18 clutches of zebra finches. We found that there were effects of asynchronous hatching, but these were smaller than expected and mostly not significant. Our observations suggest that the amount of care given to each chick may be equated with such factors as a camouflage effect of the down feathers, and that the low illumination within the nest also complicates the determination of the hatching order by the parents.

The impact of asynchronous online course design for professional development on science-teacher self-efficacy

NASA Astrophysics Data System (ADS)

Long, Caryn L. Smith

This dissertation examines how various designs of asynchronous online courses for teacher professional development may impact science-teacher self-efficacy. Mayer's studies, providing the cognitive theory of multimedia learning, targeted designs of asynchronous online learning and the point where contributions of written, auditory, and visual information on these sites could cause cognitive overload (Mayer, 2005). With increasing usage of online resources for educators to gain teaching credits, understanding how to construct these professional development offerings is critical. Teacher self-efficacy can affect how well information from these courses relays to students in their classroom. This research explored the connection between online asynchronous professional development design and teacher self-efficacy through analysis of a physics-based course in three distinct course-design offerings, while collecting content-acquisition data and self-efficacy effects before and after participation. Results from this research showed teacher self-efficacy had improved in all online treatments which included a text-only, text and audio and text, audio and animation version of the same physics content. Content knowledge was most effected by the text-only and text and audio treatments with significan growth occurring in the remember, apply, and analyze levels of bloom's taxonomy. Due to the small number of participants, it cannot be said that these results are conclusive.

A Methodology for the Design and Verification of Globally Asynchronous/Locally Synchronous Architectures

NASA Technical Reports Server (NTRS)

Miller, Steven P.; Whalen, Mike W.; O'Brien, Dan; Heimdahl, Mats P.; Joshi, Anjali

2005-01-01

Recent advanced in model-checking have made it practical to formally verify the correctness of many complex synchronous systems (i.e., systems driven by a single clock). However, many computer systems are implemented by asynchronously composing several synchronous components, where each component has its own clock and these clocks are not synchronized. Formal verification of such Globally Asynchronous/Locally Synchronous (GA/LS) architectures is a much more difficult task. In this report, we describe a methodology for developing and reasoning about such systems. This approach allows a developer to start from an ideal system specification and refine it along two axes. Along one axis, the system can be refined one component at a time towards an implementation. Along the other axis, the behavior of the system can be relaxed to produce a more cost effective but still acceptable solution. We illustrate this process by applying it to the synchronization logic of a Dual Fight Guidance System, evolving the system from an ideal case in which the components do not fail and communicate synchronously to one in which the components can fail and communicate asynchronously. For each step, we show how the system requirements have to change if the system is to be implemented and prove that each implementation meets the revised system requirements through modelchecking.

Effect of music-movement synchrony on exercise oxygen consumption.

PubMed

Bacon, C J; Myers, T R; Karageorghis, C I

2012-08-01

Past research indicates that endurance is improved when exercise movements are synchronised with a musical beat, however it is unclear whether such benefits are associated with reduced metabolic cost. We compared oxygen consumption (.VO2) and related physiological effects of exercise conducted synchronously and asynchronously with music. Three music tracks, each recorded at three different tempi (123, 130, and 137 beats.min-1), accompanied cycle ergometry at 65 pedal revolutions.min-1. Thus three randomly-assigned experimental conditions were administered: slow tempo asynchronous, synchronous, and fast tempo asynchronous. Exercise response of .VO2, HR, and ratings of perceived exertion (RPE), to each condition was monitored in 10 untrained male participants aged 21.7±0.8 years (mean±SD) who cycled for 12 min at 70% maximal heart rate (HR). Mean .VO2 differed among conditions (P=0.008), being lower in the synchronous (1.80±0.22 L.min-1) compared to the slow tempo asynchronous condition (1.94±0.21 L.min-1; P<0.05). There was no difference in HR or RPE among conditions, although HR showed a similar trend to .VO2. The present results indicate that exercise is more efficient when performed synchronously with music than when musical tempo is slightly slower than the rate of cyclical movement.

A massively asynchronous, parallel brain

PubMed Central

Zeki, Semir

2015-01-01

Whether the visual brain uses a parallel or a serial, hierarchical, strategy to process visual signals, the end result appears to be that different attributes of the visual scene are perceived asynchronously—with colour leading form (orientation) by 40 ms and direction of motion by about 80 ms. Whatever the neural root of this asynchrony, it creates a problem that has not been properly addressed, namely how visual attributes that are perceived asynchronously over brief time windows after stimulus onset are bound together in the longer term to give us a unified experience of the visual world, in which all attributes are apparently seen in perfect registration. In this review, I suggest that there is no central neural clock in the (visual) brain that synchronizes the activity of different processing systems. More likely, activity in each of the parallel processing-perceptual systems of the visual brain is reset independently, making of the brain a massively asynchronous organ, just like the new generation of more efficient computers promise to be. Given the asynchronous operations of the brain, it is likely that the results of activities in the different processing-perceptual systems are not bound by physiological interactions between cells in the specialized visual areas, but post-perceptually, outside the visual brain. PMID:25823871

Design Improvements and Analysis of Innovative High-Level Waste Pipeline Unplugging Technologies - 12171

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

Pribanic, Tomas; Awwad, Amer; Crespo, Jairo

2012-07-01

Transferring high-level waste (HLW) between storage tanks or to treatment facilities is a common practice performed at the Department of Energy (DoE) sites. Changes in the chemical and/or physical properties of the HLW slurry during the transfer process may lead to the formation of blockages inside the pipelines resulting in schedule delays and increased costs. To improve DoE's capabilities in the event of a pipeline plugging incident, FIU has continued to develop two novel unplugging technologies: an asynchronous pulsing system and a peristaltic crawler. The asynchronous pulsing system uses a hydraulic pulse generator to create pressure disturbances at two oppositemore » inlet locations of the pipeline to dislodge blockages by attacking the plug from both sides remotely. The peristaltic crawler is a pneumatic/hydraulic operated crawler that propels itself by a sequence of pressurization/depressurization of cavities (inner tubes). The crawler includes a frontal attachment that has a hydraulically powered unplugging tool. In this paper, details of the asynchronous pulsing system's ability to unplug a pipeline on a small-scale test-bed and results from the experimental testing of the second generation peristaltic crawler are provided. The paper concludes with future improvements for the third generation crawler and a recommended path forward for the asynchronous pulsing testing. (authors)« less

Tissue Culture as a Source of Replicates in Nonmodel Plants: Variation in Cold Response in Arabidopsis lyrata ssp. petraea.

PubMed

Kenta, Tanaka; Edwards, Jessica E M; Butlin, Roger K; Burke, Terry; Quick, W Paul; Urwin, Peter; Davey, Matthew P

2016-12-07

While genotype-environment interaction is increasingly receiving attention by ecologists and evolutionary biologists, such studies need genetically homogeneous replicates-a challenging hurdle in outcrossing plants. This could be potentially overcome by using tissue culture techniques. However, plants regenerated from tissue culture may show aberrant phenotypes and "somaclonal" variation. Here, we examined somaclonal variation due to tissue culturing using the response to cold treatment of photosynthetic efficiency (chlorophyll fluorescence measurements for F v /F m , F v '/F m ', and Φ PSII , representing maximum efficiency of photosynthesis for dark- and light-adapted leaves, and the actual electron transport operating efficiency, respectively, which are reliable indicators of photoinhibition and damage to the photosynthetic electron transport system). We compared this to variation among half-sibling seedlings from three different families of Arabidopsis lyrata ssp. petraea Somaclonal variation was limited, and we could detect within-family variation in change in chlorophyll fluorescence due to cold shock successfully with the help of tissue-culture derived replicates. Icelandic and Norwegian families exhibited higher chlorophyll fluorescence, suggesting higher performance after cold shock, than a Swedish family. Although the main effect of tissue culture on F v /F m , F v '/F m ', and Φ PSII was small, there were significant interactions between tissue culture and family, suggesting that the effect of tissue culture is genotype-specific. Tissue-cultured plantlets were less affected by cold treatment than seedlings, but to a different extent in each family. These interactive effects, however, were comparable to, or much smaller than the single effect of family. These results suggest that tissue culture is a useful method for obtaining genetically homogenous replicates for studying genotype-environment interaction related to adaptively-relevant phenotypes, such as cold response, in nonmodel outcrossing plants. Copyright © 2016 Kenta et al.

Determination of aberration center of Ronchigram for automated aberration correctors in scanning transmission electron microscopy.

PubMed

Sannomiya, Takumi; Sawada, Hidetaka; Nakamichi, Tomohiro; Hosokawa, Fumio; Nakamura, Yoshio; Tanishiro, Yasumasa; Takayanagi, Kunio

2013-12-01

A generic method to determine the aberration center is established, which can be utilized for aberration calculation and axis alignment for aberration corrected electron microscopes. In this method, decentering induced secondary aberrations from inherent primary aberrations are minimized to find the appropriate axis center. The fitness function to find the optimal decentering vector for the axis was defined as a sum of decentering induced secondary aberrations with properly distributed weight values according to the aberration order. Since the appropriate decentering vector is determined from the aberration values calculated at an arbitrary center axis, only one aberration measurement is in principle required to find the center, resulting in /very fast center search. This approach was tested for the Ronchigram based aberration calculation method for aberration corrected scanning transmission electron microscopy. Both in simulation and in experiments, the center search was confirmed to work well although the convergence to find the best axis becomes slower with larger primary aberrations. Such aberration center determination is expected to fully automatize the aberration correction procedures, which used to require pre-alignment of experienced users. This approach is also applicable to automated aperture positioning. Copyright © 2013 Elsevier B.V. All rights reserved.

Transcranial phase aberration correction using beam simulations and MR-ARFI

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

Vyas, Urvi, E-mail: urvi.vyas@gmail.com; Kaye, Elena; Pauly, Kim Butts

2014-03-15

Purpose: Transcranial magnetic resonance-guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation-MR-ARFI technique to achieve aberration correction for transcranial MR-guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR-ARFI) to correct skull-caused phase aberrations. Methods: Skull-based numerical aberrations were obtained from a MR-guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focusedmore » ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR-ARFI images were used in the hybrid simulation-MR-ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16-aberration and 1024-aberration) was repeated three times. Results: The corrected MR-ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation-MR-ARFI technique resulted in an average increase in focal MR-ARFI phase of 44% for the 16-aberration case and 52% for the 1024-aberration case, and recovered 83% and 39% of the ideal MR-ARFI phase for the 16-aberrations and 1024-aberration case, respectively. Conclusions: Using one MR-ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation-MR-ARFI technique improved the maximum MR-ARFI phase of the beam's focus.« less

Regional brain activation/deactivation during word generation in schizophrenia: fMRI study.

PubMed

John, John P; Halahalli, Harsha N; Vasudev, Mandapati K; Jayakumar, Peruvumba N; Jain, Sanjeev

2011-03-01

Examination of the brain regions that show aberrant activations and/or deactivations during semantic word generation could pave the way for a better understanding of the neurobiology of cognitive dysfunction in schizophrenia. To examine the pattern of functional magnetic resonance imaging blood oxygen level dependent activations and deactivations during semantic word generation in schizophrenia. Functional magnetic resonance imaging was performed on 24 participants with schizophrenia and 24 matched healthy controls during an overt, paced, 'semantic category word generation' condition and a baseline 'word repetition' condition that modelled all the lead-in/associated processes involved in the performance of the generation task. The brain regions activated during word generation in healthy individuals were replicated with minimal redundancies in participants with schizophrenia. The individuals with schizophrenia showed additional activations of temporo-parieto-occipital cortical regions as well as subcortical regions, despite significantly poorer behavioural performance than the healthy participants. Importantly, the extensive deactivations in other brain regions during word generation in healthy individuals could not be replicated in those with schizophrenia. More widespread activations and deficient deactivations in the poorly performing participants with schizophrenia may reflect an inability to inhibit competing cognitive processes, which in turn could constitute the core information-processing deficit underlying impaired word generation in schizophrenia.

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

PubMed

Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

2015-05-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts

PubMed Central

Bernstein, Diana L.; Le Lay, John E.; Ruano, Elena G.; Kaestner, Klaus H.

2015-01-01

Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator–like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics. PMID:25866970

Asynchronous Communication Scheme For Hypercube Computer

NASA Technical Reports Server (NTRS)

Madan, Herb S.

1988-01-01

Scheme devised for asynchronous-message communication system for Mark III hypercube concurrent-processor network. Network consists of up to 1,024 processing elements connected electrically as though were at corners of 10-dimensional cube. Each node contains two Motorola 68020 processors along with Motorola 68881 floating-point processor utilizing up to 4 megabytes of shared dynamic random-access memory. Scheme intended to support applications requiring passage of both polled or solicited and unsolicited messages.

Process membership in asynchronous environments

NASA Technical Reports Server (NTRS)

Ricciardi, Aleta M.; Birman, Kenneth P.

1993-01-01

The development of reliable distributed software is simplified by the ability to assume a fail-stop failure model. The emulation of such a model in an asynchronous distributed environment is discussed. The solution proposed, called Strong-GMP, can be supported through a highly efficient protocol, and was implemented as part of a distributed systems software project at Cornell University. The precise definition of the problem, the protocol, correctness proofs, and an analysis of costs are addressed.

A Motion-Based Feature for Event-Based Pattern Recognition

PubMed Central

Clady, Xavier; Maro, Jean-Matthieu; Barré, Sébastien; Benosman, Ryad B.

2017-01-01

This paper introduces an event-based luminance-free feature from the output of asynchronous event-based neuromorphic retinas. The feature consists in mapping the distribution of the optical flow along the contours of the moving objects in the visual scene into a matrix. Asynchronous event-based neuromorphic retinas are composed of autonomous pixels, each of them asynchronously generating “spiking” events that encode relative changes in pixels' illumination at high temporal resolutions. The optical flow is computed at each event, and is integrated locally or globally in a speed and direction coordinate frame based grid, using speed-tuned temporal kernels. The latter ensures that the resulting feature equitably represents the distribution of the normal motion along the current moving edges, whatever their respective dynamics. The usefulness and the generality of the proposed feature are demonstrated in pattern recognition applications: local corner detection and global gesture recognition. PMID:28101001

Implementing asyncronous collective operations in a multi-node processing system

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

Chen, Dong; Eisley, Noel A.; Heidelberger, Philip

A method, system, and computer program product are disclosed for implementing an asynchronous collective operation in a multi-node data processing system. In one embodiment, the method comprises sending data to a plurality of nodes in the data processing system, broadcasting a remote get to the plurality of nodes, and using this remote get to implement asynchronous collective operations on the data by the plurality of nodes. In one embodiment, each of the nodes performs only one task in the asynchronous operations, and each nodes sets up a base address table with an entry for a base address of a memorymore » buffer associated with said each node. In another embodiment, each of the nodes performs a plurality of tasks in said collective operations, and each task of each node sets up a base address table with an entry for a base address of a memory buffer associated with the task.« less

[Asynchronous asymmetry (sexual and lateral differentiation--a consequence of asynchronous evolution)].

PubMed

Geodakian, V A

1993-01-01

In the paper is presented a unified interpretation of sex differentiation and lateral asymmetry as asynchronous evolution. The operative subsystems, i.e. the male and the left hemisphere of the brain evolutionize earlier than the conservative ones, i.e. the female and the right hemisphere. New functions appear at first in males and after many generations they are transferred to females. The leading centers of their control are at first originated in the left hemisphere, then they are translocated to the right one. The criterion for functions localization in the hemisphere is their evolutionary age: new functions are controlled by the left hemisphere, old functions by the right one. Therefore the left hemisphere is socio-cultural, ethnic, the right one is biological, special. The theory explains from a single standpoint the phenomena of sex, handedness, nervous crossover, as well as many know facts, and predicts the new ones.

Parallel, Asynchronous Executive (PAX): System concepts, facilities, and architecture

NASA Technical Reports Server (NTRS)

Jones, W. H.

1983-01-01

The Parallel, Asynchronous Executive (PAX) is a software operating system simulation that allows many computers to work on a single problem at the same time. PAX is currently implemented on a UNIVAC 1100/42 computer system. Independent UNIVAC runstreams are used to simulate independent computers. Data are shared among independent UNIVAC runstreams through shared mass-storage files. PAX has achieved the following: (1) applied several computing processes simultaneously to a single, logically unified problem; (2) resolved most parallel processor conflicts by careful work assignment; (3) resolved by means of worker requests to PAX all conflicts not resolved by work assignment; (4) provided fault isolation and recovery mechanisms to meet the problems of an actual parallel, asynchronous processing machine. Additionally, one real-life problem has been constructed for the PAX environment. This is CASPER, a collection of aerodynamic and structural dynamic problem simulation routines. CASPER is not discussed in this report except to provide examples of parallel-processing techniques.

Surface-distributed low-frequency asynchronous stimulation delays fatigue of stimulated muscles.

PubMed

Maneski, Lana Z Popović; Malešević, Nebojša M; Savić, Andrej M; Keller, Thierry; Popović, Dejan B

2013-12-01

One important reason why functional electrical stimulation (FES) has not gained widespread clinical use is the limitation imposed by rapid muscle fatigue due to non-physiological activation of the stimulated muscles. We aimed to show that asynchronous low-pulse-rate (LPR) electrical stimulation applied by multipad surface electrodes greatly postpones the occurrence of muscle fatigue compared with conventional stimulation (high pulse rate, HPR). We compared the produced force vs. time of the forearm muscles responsible for finger flexion in 2 stimulation protocols, LPR (fL = 10 Hz) and HPR (fH = 40 Hz). Surface-distributed low-frequency asynchronous stimulation (sDLFAS) doubles the time interval before the onset of fatigue (104 ± 80%) compared with conventional synchronous stimulation. Combining the performance of multipad electrodes (increased selectivity and facilitated positioning) with sDLFAS (decreased fatigue) can improve many FES applications in both the lower and upper extremities. Copyright © 2013 Wiley Periodicals, Inc.

Investigation on intermolecular interaction between berberine and β-cyclodextrin by 2D UV-Vis asynchronous spectra.

PubMed

He, Anqi; Kang, Xiaoyan; Xu, Yizhuang; Noda, Isao; Ozaki, Yukihiro; Wu, Jinguang

2017-10-05

The interaction between berberine chloride and β-cyclodextrin (β-CyD) is investigated via 2D asynchronous UV-Vis spectrum. The occurrence of cross peaks around (420nm, 420nm) in 2D asynchronous spectrum reveals that specific intermolecular interaction indeed exists between berberine chloride and β-CyD. In spite of the difficulty caused by overlapping of cross peaks, we manage to confirm that the 420nm band of berberine undergoes a red-shift, and its bandwidth decreases under the interaction with β-CyD. The red-shift of the 420nm band that can be assigned to n-π* transition indicates the environment of berberine becomes more hydrophobic. The above spectral behavior is helpful in understanding why the solubility of berberine is enhanced by β-CyD. Copyright © 2017. Published by Elsevier B.V.

Privacy Preservation in Distributed Subgradient Optimization Algorithms.

PubMed

Lou, Youcheng; Yu, Lean; Wang, Shouyang; Yi, Peng

2017-07-31

In this paper, some privacy-preserving features for distributed subgradient optimization algorithms are considered. Most of the existing distributed algorithms focus mainly on the algorithm design and convergence analysis, but not the protection of agents' privacy. Privacy is becoming an increasingly important issue in applications involving sensitive information. In this paper, we first show that the distributed subgradient synchronous homogeneous-stepsize algorithm is not privacy preserving in the sense that the malicious agent can asymptotically discover other agents' subgradients by transmitting untrue estimates to its neighbors. Then a distributed subgradient asynchronous heterogeneous-stepsize projection algorithm is proposed and accordingly its convergence and optimality is established. In contrast to the synchronous homogeneous-stepsize algorithm, in the new algorithm agents make their optimization updates asynchronously with heterogeneous stepsizes. The introduced two mechanisms of projection operation and asynchronous heterogeneous-stepsize optimization can guarantee that agents' privacy can be effectively protected.

Asynchronous Transfer Mode Quality-of-Service Testing

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1998-01-01

In support of satellite-ATM interoperability, researchers at the NASA Lewis Research Center performed asynchronous transfer mode (ATM) quality-of-service experiments using MPEG-2 (ATM application layer 5, AAL5) over ATM over an emulated satellite link. The purpose of these experiments was to determine the free-space link quality necessary to use the ATM protocol to transmit high-quality multimedia information. The experimental results have been submitted to various International Telecommunications Union (ITU) study groups in order to improve and modify current standards and recommendations for the telecommunications industry. Quality-of-service parameters for Class I, stringent class requirements for ITU-T I.356 are currently being debated. The experimental results presented will help to establish these quality-of-service thresholds. This material will also be useful in the development of the ITU-R WP-4B's Draft Preliminary New Recommendation on the Transmission of Asynchronous Transfer Mode Traffic via Satellite (Rec. S.atm).

The queueing perspective of asynchronous network coding in two-way relay network

NASA Astrophysics Data System (ADS)

Liang, Yaping; Chang, Qing; Li, Xianxu

2018-04-01

Asynchronous network coding (NC) has potential to improve the wireless network performance compared with a routing or the synchronous network coding. Recent researches concentrate on the optimization between throughput/energy consuming and delay with a couple of independent input flow. However, the implementation of NC requires a thorough investigation of its impact on relevant queueing systems where few work focuses on. Moreover, few works study the probability density function (pdf) in network coding scenario. In this paper, the scenario with two independent Poisson input flows and one output flow is considered. The asynchronous NC-based strategy is that a new arrival evicts a head packet holding in its queue when waiting for another packet from the other flow to encode. The pdf for the output flow which contains both coded and uncoded packets is derived. Besides, the statistic characteristics of this strategy are analyzed. These results are verified by numerical simulations.

Supporting Handoff in Asynchronous Collaborative Sensemaking Using Knowledge-Transfer Graphs.

PubMed

Zhao, Jian; Glueck, Michael; Isenberg, Petra; Chevalier, Fanny; Khan, Azam

2018-01-01

During asynchronous collaborative analysis, handoff of partial findings is challenging because externalizations produced by analysts may not adequately communicate their investigative process. To address this challenge, we developed techniques to automatically capture and help encode tacit aspects of the investigative process based on an analyst's interactions, and streamline explicit authoring of handoff annotations. We designed our techniques to mediate awareness of analysis coverage, support explicit communication of progress and uncertainty with annotation, and implicit communication through playback of investigation histories. To evaluate our techniques, we developed an interactive visual analysis system, KTGraph, that supports an asynchronous investigative document analysis task. We conducted a two-phase user study to characterize a set of handoff strategies and to compare investigative performance with and without our techniques. The results suggest that our techniques promote the use of more effective handoff strategies, help increase an awareness of prior investigative process and insights, as well as improve final investigative outcomes.

Regression analysis of sparse asynchronous longitudinal data.

PubMed

Cao, Hongyuan; Zeng, Donglin; Fine, Jason P

2015-09-01

We consider estimation of regression models for sparse asynchronous longitudinal observations, where time-dependent responses and covariates are observed intermittently within subjects. Unlike with synchronous data, where the response and covariates are observed at the same time point, with asynchronous data, the observation times are mismatched. Simple kernel-weighted estimating equations are proposed for generalized linear models with either time invariant or time-dependent coefficients under smoothness assumptions for the covariate processes which are similar to those for synchronous data. For models with either time invariant or time-dependent coefficients, the estimators are consistent and asymptotically normal but converge at slower rates than those achieved with synchronous data. Simulation studies evidence that the methods perform well with realistic sample sizes and may be superior to a naive application of methods for synchronous data based on an ad hoc last value carried forward approach. The practical utility of the methods is illustrated on data from a study on human immunodeficiency virus.

Exoplanet dynamics. Asynchronous rotation of Earth-mass planets in the habitable zone of lower-mass stars.

PubMed

Leconte, Jérémy; Wu, Hanbo; Menou, Kristen; Murray, Norman

2015-02-06

Planets in the habitable zone of lower-mass stars are often assumed to be in a state of tidally synchronized rotation, which would considerably affect their putative habitability. Although thermal tides cause Venus to rotate retrogradely, simple scaling arguments tend to attribute this peculiarity to the massive Venusian atmosphere. Using a global climate model, we show that even a relatively thin atmosphere can drive terrestrial planets' rotation away from synchronicity. We derive a more realistic atmospheric tide model that predicts four asynchronous equilibrium spin states, two being stable, when the amplitude of the thermal tide exceeds a threshold that is met for habitable Earth-like planets with a 1-bar atmosphere around stars more massive than ~0.5 to 0.7 solar mass. Thus, many recently discovered terrestrial planets could exhibit asynchronous spin-orbit rotation, even with a thin atmosphere. Copyright © 2015, American Association for the Advancement of Science.

Adaptive Optics Analysis of Visual Benefit with Higher-order Aberrations Correction of Human Eye - Poster Paper

NASA Astrophysics Data System (ADS)

Xue, Lixia; Dai, Yun; Rao, Xuejun; Wang, Cheng; Hu, Yiyun; Liu, Qian; Jiang, Wenhan

2008-01-01

Higher-order aberrations correction can improve visual performance of human eye to some extent. To evaluate how much visual benefit can be obtained with higher-order aberrations correction we developed an adaptive optics vision simulator (AOVS). Dynamic real time optimized modal compensation was used to implement various customized higher-order ocular aberrations correction strategies. The experimental results indicate that higher-order aberrations correction can improve visual performance of human eye comparing with only lower-order aberration correction but the improvement degree and higher-order aberration correction strategy are different from each individual. Some subjects can acquire great visual benefit when higher-order aberrations were corrected but some subjects acquire little visual benefit even though all higher-order aberrations were corrected. Therefore, relative to general lower-order aberrations correction strategy, customized higher-order aberrations correction strategy is needed to obtain optimal visual improvement for each individual. AOVS provides an effective tool for higher-order ocular aberrations optometry for customized ocular aberrations correction.

The Design of Data Disaster Recovery of National Fundamental Geographic Information System

NASA Astrophysics Data System (ADS)

Zhai, Y.; Chen, J.; Liu, L.; Liu, J.

2014-04-01

With the development of information technology, data security of information system is facing more and more challenges. The geographic information of surveying and mapping is fundamental and strategic resource, which is applied in all areas of national economic, defence and social development. It is especially vital to national and social interests when such classified geographic information is directly concerning Chinese sovereignty. Several urgent problems that needs to be resolved for surveying and mapping are how to do well in mass data storage and backup, establishing and improving the disaster backup system especially after sudden natural calamity accident, and ensuring all sectors rapidly restored on information system will operate correctly. For overcoming various disaster risks, protect the security of data and reduce the impact of the disaster, it's no doubt the effective way is to analysis and research on the features of storage and management and security requirements, as well as to ensure that the design of data disaster recovery system suitable for the surveying and mapping. This article analyses the features of fundamental geographic information data and the requirements of storage management, three site disaster recovery system of DBMS plan based on the popular network, storage and backup, data replication and remote switch of application technologies. In LAN that synchronous replication between database management servers and the local storage of backup management systems, simultaneously, remote asynchronous data replication between local storage backup management systems and remote database management servers. The core of the system is resolving local disaster in the remote site, ensuring data security and business continuity of local site. This article focuses on the following points: background, the necessity of disaster recovery system, the analysis of the data achievements and data disaster recovery plan. Features of this program is to use a hardware-based data hot backup, and remote online disaster recovery support for Oracle database system. The achievement of this paper is in summarizing and analysing the common characteristics of disaster of surveying and mapping business system requirements, while based on the actual situation of the industry, designed the basic GIS disaster recovery solutions, and we also give the conclusions about key technologies of RTO and RPO.

Asynchronous interaction, online technologies self-efficacy and self-regulated learning as predictors of academic achievement in an online class

NASA Astrophysics Data System (ADS)

McGhee, Rosie M. Hector

This research is a correlational study of the relationship among the independent variables: asynchronous interaction, online technologies self-efficacy, and self-regulated learning, and the dependent variable; academic achievement. This study involves an online computer literacy course at a local community college. Very little research exists on the relationship among asynchronous interaction, online technologies self-efficacy and self-regulated learning on predicting academic achievement in an online class. Liu (2008), in his study on student interaction in online courses, concluded that student interaction is a complex issue that needs more research to increase our understanding as it relates to distance education. The purpose of this study was to examine the relationships between asynchronous interaction, online technologies self-efficacy, self-regulated learning and academic achievement in an online computer literacy class at a community college. The researcher used quantitative methods to obtain and analyze data on the relationships among the variables during the summer 2010 semester. Forty-five community college students completed three web-based self-reporting instruments: (a) the GVU 10th WWW User Survey Questionnaire, (b) the Online Technologies Self-Efficacy Survey, and (c) selected items from the Motivated Strategies for Learning Questionnaire. Additional data was obtained from asynchronous discussions posted on Blackboard(TM) Learning Management System. The results of this study found that there were statistically significant relationships between asynchronous interaction and academic achievement (r = .55, p < .05) and between online technologies self-efficacy and academic achievement (r = .50, p < .05). However, there were low correlations between self-regulated learning and academic achievement ( r = -.02, p < .05). The results of this study reflect the constructivist tenants that the student is at the center of the learning experience. Driscoll (2005) said constructivist pedagogy sees the learner as an active participant in their learning experience rather than a passive vessel to be filled with information. This study is beneficial to theorists, administrators, leaders, online instructors, online course designers, faculty, students and others who are concerned about predictors for online students' success. Also, it serves as a foundation for future research and provides valuable information for educators interested in taking online teaching and learning to the next level.

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

Chen Min; Mikecz, Anna von

Despite of their exponentially growing use, little is known about cell biological effects of nanoparticles. Here, we report uptake of silica (SiO{sub 2}) nanoparticles to the cell nucleus where they induce aberrant clusters of topoisomerase I (topo I) in the nucleoplasm that additionally contain signature proteins of nuclear domains, and protein aggregation such as ubiquitin, proteasomes, cellular glutamine repeat (polyQ) proteins, and huntingtin. Formation of intranuclear protein aggregates (1) inhibits replication, transcription, and cell proliferation; (2) does not significantly alter proteasomal activity or cell viability; and (3) is reversible by Congo red and trehalose. Since SiO{sub 2} nanoparticles trigger amore » subnuclear pathology resembling the one occurring in expanded polyglutamine neurodegenerative disorders, we suggest that integrity of the functional architecture of the cell nucleus should be used as a read out for cytotoxicity and considered in the development of safe nanotechnology.« less

WES (Waterways Experiment Station) Communications Plan for Voice and Data

DTIC Science & Technology

1989-01-01

modem on a leased line, and two wideband HDLC 56K connections not used on the Honeywell. 30. Honeywell DPS-8 configuration, as of October 1987, is as...based voice system to support additional asynchronous dial-up modem traffic. In June 1987, Dr. N. Radhakhrishnan of the WES Information Technology...voice system (PBX) and very low-speed data communications by the laboratories using 1,200/2,400-baud asynchronous modems over analog phone lines, and

Asynchronous data change notification between database server and accelerator controls system

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

Fu, W.; Morris, J.; Nemesure, S.

2011-10-10

Database data change notification (DCN) is a commonly used feature. Not all database management systems (DBMS) provide an explicit DCN mechanism. Even for those DBMS's which support DCN (such as Oracle and MS SQL server), some server side and/or client side programming may be required to make the DCN system work. This makes the setup of DCN between database server and interested clients tedious and time consuming. In accelerator control systems, there are many well established software client/server architectures (such as CDEV, EPICS, and ADO) that can be used to implement data reflection servers that transfer data asynchronously to anymore » client using the standard SET/GET API. This paper describes a method for using such a data reflection server to set up asynchronous DCN (ADCN) between a DBMS and clients. This method works well for all DBMS systems which provide database trigger functionality. Asynchronous data change notification (ADCN) between database server and clients can be realized by combining the use of a database trigger mechanism, which is supported by major DBMS systems, with server processes that use client/server software architectures that are familiar in the accelerator controls community (such as EPICS, CDEV or ADO). This approach makes the ADCN system easy to set up and integrate into an accelerator controls system. Several ADCN systems have been set up and used in the RHIC-AGS controls system.« less

Analysis Tools for Interconnected Boolean Networks With Biological Applications.

PubMed

Chaves, Madalena; Tournier, Laurent

2018-01-01

Boolean networks with asynchronous updates are a class of logical models particularly well adapted to describe the dynamics of biological networks with uncertain measures. The state space of these models can be described by an asynchronous state transition graph, which represents all the possible exits from every single state, and gives a global image of all the possible trajectories of the system. In addition, the asynchronous state transition graph can be associated with an absorbing Markov chain, further providing a semi-quantitative framework where it becomes possible to compute probabilities for the different trajectories. For large networks, however, such direct analyses become computationally untractable, given the exponential dimension of the graph. Exploiting the general modularity of biological systems, we have introduced the novel concept of asymptotic graph , computed as an interconnection of several asynchronous transition graphs and recovering all asymptotic behaviors of a large interconnected system from the behavior of its smaller modules. From a modeling point of view, the interconnection of networks is very useful to address for instance the interplay between known biological modules and to test different hypotheses on the nature of their mutual regulatory links. This paper develops two new features of this general methodology: a quantitative dimension is added to the asymptotic graph, through the computation of relative probabilities for each final attractor and a companion cross-graph is introduced to complement the method on a theoretical point of view.