WorldWideScience

Sample records for replication bir occurs

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

    Science.gov (United States)

    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

  2. Global profiling of DNA replication timing and efficiency reveals that efficient replication/firing occurs late during S-phase in S. pombe.

    Directory of Open Access Journals (Sweden)

    Majid Eshaghi

    Full Text Available BACKGROUND: During S. pombe S-phase, initiation of DNA replication occurs at multiple sites (origins that are enriched with AT-rich sequences, at various times. Current studies of genome-wide DNA replication profiles have focused on the DNA replication timing and origin location. However, the replication and/or firing efficiency of the individual origins on the genomic scale remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-wide ORF-specific DNA microarray analysis, we show that in S. pombe, individual origins fire with varying efficiencies and at different times during S-phase. The increase in DNA copy number plotted as a function of time is approximated to the near-sigmoidal model, when considering the replication start and end timings at individual loci in cells released from HU-arrest. Replication efficiencies differ from origin to origin, depending on the origin's firing efficiency. We have found that DNA replication is inefficient early in S-phase, due to inefficient firing at origins. Efficient replication occurs later, attributed to efficient but late-firing origins. Furthermore, profiles of replication timing in cds1Delta cells are abnormal, due to the failure in resuming replication at the collapsed forks. The majority of the inefficient origins, but not the efficient ones, are found to fire in cds1Delta cells after HU removal, owing to the firing at the remaining unused (inefficient origins during HU treatment. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that efficient DNA replication/firing occurs late in S-phase progression in cells after HU removal, due to efficient late-firing origins. Additionally, checkpoint kinase Cds1p is required for maintaining the efficient replication/firing late in S-phase. We further propose that efficient late-firing origins are essential for ensuring completion of DNA duplication by the end of S-phase.

  3. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

    DEFF Research Database (Denmark)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia

    2016-01-01

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells....

  4. Intermolecular RNA Recombination Occurs at Different Frequencies in Alternate Forms of Brome Mosaic Virus RNA Replication Compartments

    Directory of Open Access Journals (Sweden)

    Hernan Garcia-Ruiz

    2018-03-01

    Full Text Available Positive-strand RNA viruses replicate their genomes in membrane-bound replication compartments. Brome mosaic virus (BMV replicates in vesicular invaginations of the endoplasmic reticulum membrane. BMV has served as a productive model system to study processes like virus-host interactions, RNA replication and recombination. Here we present multiple lines of evidence showing that the structure of the viral RNA replication compartments plays a fundamental role and that recruitment of parental RNAs to a common replication compartment is a limiting step in intermolecular RNA recombination. We show that a previously defined requirement for an RNA recruitment element on both parental RNAs is not to function as a preferred crossover site, but in order for individual RNAs to be recruited into the replication compartments. Moreover, modulating the form of the replication compartments from spherular vesicles (spherules to more expansive membrane layers increased intermolecular RNA recombination frequency by 200- to 1000-fold. We propose that intermolecular RNA recombination requires parental RNAs to be recruited into replication compartments as monomers, and that recruitment of multiple RNAs into a contiguous space is much more common for layers than for spherules. These results could explain differences in recombination frequencies between viruses that replicate in association with smaller spherules versus larger double-membrane vesicles and convoluted membranes.

  5. Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and Requires Okazaki Fragment Ligation

    Directory of Open Access Journals (Sweden)

    Takashi Kubota

    2015-08-01

    Full Text Available The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely PCNA loading and unloading are central for genome integrity and must be strictly coordinated with other DNA processing steps during replication. Here, we show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to PCNA accumulation on chromatin, similar to the accumulation caused by lack of Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1-RLC acts as a general PCNA unloader and is dependent upon DNA ligation during chromosome replication.

  6. Spontaneous Chloroplast Mutants Mostly Occur by Replication Slippage and Show a Biased Pattern in the Plastome of Oenothera.

    Science.gov (United States)

    Massouh, Amid; Schubert, Julia; Yaneva-Roder, Liliya; Ulbricht-Jones, Elena S; Zupok, Arkadiusz; Johnson, Marc T J; Wright, Stephen I; Pellizzer, Tommaso; Sobanski, Johanna; Bock, Ralph; Greiner, Stephan

    2016-04-01

    Spontaneous plastome mutants have been used as a research tool since the beginning of genetics. However, technical restrictions have severely limited their contributions to research in physiology and molecular biology. Here, we used full plastome sequencing to systematically characterize a collection of 51 spontaneous chloroplast mutants in Oenothera (evening primrose). Most mutants carry only a single mutation. Unexpectedly, the vast majority of mutations do not represent single nucleotide polymorphisms but are insertions/deletions originating from DNA replication slippage events. Only very few mutations appear to be caused by imprecise double-strand break repair, nucleotide misincorporation during replication, or incorrect nucleotide excision repair following oxidative damage. U-turn inversions were not detected. Replication slippage is induced at repetitive sequences that can be very small and tend to have high A/T content. Interestingly, the mutations are not distributed randomly in the genome. The underrepresentation of mutations caused by faulty double-strand break repair might explain the high structural conservation of seed plant plastomes throughout evolution. In addition to providing a fully characterized mutant collection for future research on plastid genetics, gene expression, and photosynthesis, our work identified the spectrum of spontaneous mutations in plastids and reveals that this spectrum is very different from that in the nucleus. © 2016 American Society of Plant Biologists. All rights reserved.

  7. Spontaneous Chloroplast Mutants Mostly Occur by Replication Slippage and Show a Biased Pattern in the Plastome of Oenothera[OPEN

    Science.gov (United States)

    Massouh, Amid; Schubert, Julia; Yaneva-Roder, Liliya; Ulbricht-Jones, Elena S.; Johnson, Marc T.J.; Wright, Stephen I.; Pellizzer, Tommaso; Sobanski, Johanna; Greiner, Stephan

    2016-01-01

    Spontaneous plastome mutants have been used as a research tool since the beginning of genetics. However, technical restrictions have severely limited their contributions to research in physiology and molecular biology. Here, we used full plastome sequencing to systematically characterize a collection of 51 spontaneous chloroplast mutants in Oenothera (evening primrose). Most mutants carry only a single mutation. Unexpectedly, the vast majority of mutations do not represent single nucleotide polymorphisms but are insertions/deletions originating from DNA replication slippage events. Only very few mutations appear to be caused by imprecise double-strand break repair, nucleotide misincorporation during replication, or incorrect nucleotide excision repair following oxidative damage. U-turn inversions were not detected. Replication slippage is induced at repetitive sequences that can be very small and tend to have high A/T content. Interestingly, the mutations are not distributed randomly in the genome. The underrepresentation of mutations caused by faulty double-strand break repair might explain the high structural conservation of seed plant plastomes throughout evolution. In addition to providing a fully characterized mutant collection for future research on plastid genetics, gene expression, and photosynthesis, our work identified the spectrum of spontaneous mutations in plastids and reveals that this spectrum is very different from that in the nucleus. PMID:27053421

  8. Prion replication occurs in endogenous adult neural stem cells and alters their neuronal fate: involvement of endogenous neural stem cells in prion diseases.

    Directory of Open Access Journals (Sweden)

    Aroa Relaño-Ginès

    Full Text Available Prion diseases are irreversible progressive neurodegenerative diseases, leading to severe incapacity and death. They are characterized in the brain by prion amyloid deposits, vacuolisation, astrocytosis, neuronal degeneration, and by cognitive, behavioural and physical impairments. There is no treatment for these disorders and stem cell therapy therefore represents an interesting new approach. Gains could not only result from the cell transplantation, but also from the stimulation of endogenous neural stem cells (NSC or by the combination of both approaches. However, the development of such strategies requires a detailed knowledge of the pathology, particularly concerning the status of the adult neurogenesis and endogenous NSC during the development of the disease. During the past decade, several studies have consistently shown that NSC reside in the adult mammalian central nervous system (CNS and that adult neurogenesis occurs throughout the adulthood in the subventricular zone of the lateral ventricle or the Dentate Gyrus of the hippocampus. Adult NSC are believed to constitute a reservoir for neuronal replacement during normal cell turnover or after brain injury. However, the activation of this system does not fully compensate the neuronal loss that occurs during neurodegenerative diseases and could even contribute to the disease progression. We investigated here the status of these cells during the development of prion disorders. We were able to show that NSC accumulate and replicate prions. Importantly, this resulted in the alteration of their neuronal fate which then represents a new pathologic event that might underlie the rapid progression of the disease.

  9. The structure of XIAP BIR2: understanding the selectivity of the BIR domains

    Energy Technology Data Exchange (ETDEWEB)

    Lukacs, Christine, E-mail: cmlukacs230@gmail.com; Belunis, Charles; Crowther, Robert; Danho, Waleed; Gao, Lin; Goggin, Barry; Janson, Cheryl A.; Li, Shirley; Remiszewski, Stacy; Schutt, Andrew [Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States); Thakur, Manish K.; Singh, Saroj K.; Swaminathan, Srinivasan; Pandey, Rajat; Tyagi, Rajiv; Gosu, Ramachandraiah; Kamath, Ajith V. [Jubilant Biosys Ltd, Bangalore (India); Kuglstatter, Andreas, E-mail: cmlukacs230@gmail.com [Hoffmann-La Roche, 340 Kingsland Street, Nutley, NJ 07110 (United States)

    2013-09-01

    The high-resolution crystal structures of apo and peptide-bound XIAP BIR2 are presented and compared with BIR3 structures to understand their selectivity. This crystal system can be used to determine the structures of BIR2–inhibitor complexes. XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain–caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3–caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2–caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2–tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

  10. Evidence of systematic bias in sexual over- and underperception of naturally occurring events: a direct replication of Haselton (2003) in a more gender-equal culture.

    Science.gov (United States)

    Bendixen, Mons

    2014-11-17

    Error Management Theory (Haselton and Buss, 2000; Haselton and Nettle, 2006) maintains that natural selection has engineered adaptations for judgment under uncertainty to minimize the overall cost of making errors, leading to universal biases in judgments of sexual interest in men and women. This study, using a sample of het erosexual Norwegian students (n = 308), was carried out as a direct replication of Haselton's (2003) original study of naturally occurring events of sexual misperception. The results strongly supported the main hypotheses in the original study, showing that women reported being subject to opposite-sex sexual overperception far more often relative to underperception, and that this difference was small for men. In support of Error Management Theory, and in contrast to Social Role / Structure Theory expectations, the pattern of misperception for women and men was largely invariant across studies and across demographic groups within a culture. The findings suggest that cross-national differences in the level of gender inequality do not influence reports of sexual over- and underperception in women and men. Beyond sex, factors associated with more sexual overperception relative to underperception were being single, young, and having attitudes condoning casual sex.

  11. Evidence of Systematic Bias in Sexual Over- and Underperception of Naturally Occurring Events: A Direct Replication of Haselton (2003 in a more Gender-Equal Culture

    Directory of Open Access Journals (Sweden)

    Mons Bendixen

    2014-04-01

    Full Text Available Error Management Theory (Haselton and Buss, 2000; Haselton and Nettle, 2006 maintains that natural selection has engineered adaptations for judgment under uncertainty to minimize the overall cost of making errors, leading to universal biases in judgments of sexual interest in men and women. This study, using a sample of heterosexual Norwegian students (n = 308, was carried out as a direct replication of Haselton's (2003 original study of naturally occurring events of sexual misperception. The results strongly supported the main hypotheses in the original study, showing that women reported being subject to opposite-sex sexual overperception far more often relative to underperception, and that this difference was small for men. In support of Error Management Theory, and in contrast to Social Role / Structure Theory expectations, the pattern of misperception for women and men was largely invariant across studies and across demographic groups within a culture. The findings suggest that cross-national differences in the level of gender inequality do not influence reports of sexual over- and underperception in women and men. Beyond sex, factors associated with more sexual overperception relative to underperception were being single, young, and having attitudes condoning casual sex.

  12. Yeni Bir Global Viral Etken: Zika virus

    OpenAIRE

    Ece, Gülfem; Aslan, Ferhat G; Altındiş, Mustafa

    2016-01-01

    Zika virus ateşi bir flavirus'un neden olduğu sivrisineklerle bulaşan bir hastalıktır. Klinik tablo asemptomatik vakalardan ateş, başağrısı, yorgunluk, ve kutanöz döküntü ile ilişkili bir influanza benzeri sendroma kadar değişmektedir. Zika virus ilk kez Nisan 1947’de Uganda ormanlarından izole edilmiştir. Ek olarak, 2007’ye kadar Afrika ve Asya’dan bazı Zika virus vakaları bildirilmiş olmasına rağmen, 2007 yılında Mikronezyada bir epidemi meydana gelmiştir. Son zamanlarda, özellikle de ...

  13. BIRS - Bioterrorism Information Retrieval System.

    Science.gov (United States)

    Tewari, Ashish Kumar; Rashi; Wadhwa, Gulshan; Sharma, Sanjeev Kumar; Jain, Chakresh Kumar

    2013-01-01

    Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system. The database is freely available at http://www.bioterrorism.biowaves.org.

  14. Structures of BIR domains from human NAIP and cIAP2

    International Nuclear Information System (INIS)

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-01-01

    The crystal structures of the human NAIP BIR2 and cIAP2 BIR3 domains have been determined. Both BIR domains harbors an amino-terminal tetrapeptide in its peptide-binding groove. The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1′–P4′ side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3′ position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2′ and P4′ pockets make similar interactions to those seen in other BIR domain–peptide complexes. The structures also reveal how a serine in the P1′ position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins

  15. Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center.

    Directory of Open Access Journals (Sweden)

    Gabriela N Condezo

    2017-04-01

    Full Text Available Adenovirus (AdV morphogenesis is a complex process, many aspects of which remain unclear. In particular, it is not settled where in the nucleus assembly and packaging occur, and whether these processes occur in a sequential or a concerted manner. Here we use immunofluorescence and immunoelectron microscopy (immunoEM to trace packaging factors and structural proteins at late times post infection by either wildtype virus or a delayed packaging mutant. We show that representatives of all assembly factors are present in the previously recognized peripheral replicative zone, which therefore is the AdV assembly factory. Assembly intermediates and abortive products observed in this region favor a concurrent assembly and packaging model comprising two pathways, one for capsid proteins and another one for core components. Only when both pathways are coupled by correct interaction between packaging proteins and the genome is the viral particle produced. Decoupling generates accumulation of empty capsids and unpackaged cores.

  16. Gorlin Goltz sendromu: Bir olgu sunumu

    OpenAIRE

    Kestane, Recep; Yurttutan, Mehmet; Şentürk, Mehmet; Koçer, Atilla; Keskin, Ahmet

    2015-01-01

    Gorlin Goltz sendromu esas olarak kutanöz bazal hücreli karsinom, çoklu keratokistik odontojenik tümörler ve iskeletsel anomaliler ile karakterize otozomal dominant bir rahatsızlıktır. Gorlin ve Goltz tarafından tanımlanan bu klasik triada ek olarak diğer nörolojik, oftalmolojik, endokrin ve genital bulgular da sendromun özellikleri arasında yer almaktadır. Bu raporda 12 yaşındaki Gorlin Goltz sendromlu erkek hastanın tedavisi ve 1,5 yıllık takibi sunulmuştur. Bu olgu deride herhangi bir lezy...

  17. Structures of BIR domains from human NAIP and cIAP2.

    Science.gov (United States)

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-11-01

    The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

  18. Distributional Replication

    OpenAIRE

    Beare, Brendan K.

    2009-01-01

    Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...

  19. BIR 2014 - Bibliometric-enhanced Information Retrieval

    DEFF Research Database (Denmark)

    This first “Bibliometric-enhanced Information Retrieval” (BIR 2014) workshop1 aims to engage with the IR community about possible links to bibliometrics and scholarly communication. Bibliometric techniques are not yet widely used to enhance retrieval processes in digital libraries, although...... analysis of co-authorship network, can improve retrieval services for specific communities, as well as for large, cross-domain collections. This workshop aims to raise awareness of the missing link between information retrieval (IR) and bibliometrics / scientometrics and to create a common ground...... for the incorporation of bibliometric-enhanced services into retrieval at the digital library interface. Our interests include information retrieval, information seeking, science modelling, network analysis, and digital libraries. The goal is to apply insights from bibliometrics, scientometrics, and informetrics...

  20. Replication Catastrophe

    DEFF Research Database (Denmark)

    Toledo, Luis; Neelsen, Kai John; Lukas, Jiri

    2017-01-01

    Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...

  1. A microhomology-mediated break-induced replication model for the origin of human copy number variation.

    Directory of Open Access Journals (Sweden)

    P J Hastings

    2009-01-01

    Full Text Available Chromosome structural changes with nonrecurrent endpoints associated with genomic disorders offer windows into the mechanism of origin of copy number variation (CNV. A recent report of nonrecurrent duplications associated with Pelizaeus-Merzbacher disease identified three distinctive characteristics. First, the majority of events can be seen to be complex, showing discontinuous duplications mixed with deletions, inverted duplications, and triplications. Second, junctions at endpoints show microhomology of 2-5 base pairs (bp. Third, endpoints occur near pre-existing low copy repeats (LCRs. Using these observations and evidence from DNA repair in other organisms, we derive a model of microhomology-mediated break-induced replication (MMBIR for the origin of CNV and, ultimately, of LCRs. We propose that breakage of replication forks in stressed cells that are deficient in homologous recombination induces an aberrant repair process with features of break-induced replication (BIR. Under these circumstances, single-strand 3' tails from broken replication forks will anneal with microhomology on any single-stranded DNA nearby, priming low-processivity polymerization with multiple template switches generating complex rearrangements, and eventual re-establishment of processive replication.

  2. Drought occurence

    Science.gov (United States)

    John W. Coulston

    2007-01-01

    Why Is Drought Important? Drought is an important forest disturbance that occurs regularly in the Western United States and irregularly in the Eastern United States (Dale and others 2001). Moderate drought stress tends to slow plant growth while severedrought stress can also reduce photosynthesis (Kareiva and others 1993). Drought can also interact with...

  3. BIRS – Bioterrorism Information Retrieval System

    Science.gov (United States)

    Tewari, Ashish Kumar; Rashi; Wadhwa, Gulshan; Sharma, Sanjeev Kumar; Jain, Chakresh Kumar

    2013-01-01

    Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system. Availability The database is freely available at http://www.bioterrorism.biowaves.org PMID:23390356

  4. Database Replication

    CERN Document Server

    Kemme, Bettina

    2010-01-01

    Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

  5. Non‐Canonical Replication Initiation: You’re Fired!

    Directory of Open Access Journals (Sweden)

    Bazilė Ravoitytė

    2017-01-01

    Full Text Available The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis‐acting DNA sequences, the so‐called origins of replication (ori, with trans‐acting factors involved in the onset of DNA synthesis. The interplay of cis‐acting elements and trans‐acting factors ensures that cells initiate replication at sequence‐specific sites only once, and in a timely order, to avoid chromosomal endoreplication. However, chromosome breakage and excessive RNA:DNA hybrid formation can cause breakinduced (BIR or transcription‐initiated replication (TIR, respectively. These non‐canonical replication events are expected to affect eukaryotic genome function and maintenance, and could be important for genome evolution and disease development. In this review, we describe the difference between canonical and non‐canonical DNA replication, and focus on mechanistic differences and common features between BIR and TIR. Finally, we discuss open issues on the factors and molecular mechanisms involved in TIR.

  6. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

    Science.gov (United States)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

    2016-12-15

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Kearns-Sayre Sendromlu Bir Hastada Anestezi Yöntemi,

    OpenAIRE

    , A.Yektaş; Şinikoğlu, S. N.; Erol, M.; , M.Çömlekçi; Erkalp, K.

    2012-01-01

    Kearns-Sayre sendromu; Kronik-progresif, eksternal oftalmopleji ve pigmenter retina dejenerasyonu ile karakterize, 20 yaşından önce bulgu veren, mitokondriyal bir hastalıktır. Kearns-Sayre sendromlu hastalarda; potansiyel aspirasyon riski, zayıf faringeal kas kontrolü ve oral sekresyonlara bağlı hava yolu komplikasyonları nedeniyle, genel anestezi uygulaması dikkatli bir şekilde yürütülmelidir. Kalp iletim defektleri de hastalığın sık görülen ve önlenebilen ölümcül komplikasyonlarındandır. Bu...

  8. Turkiye’de Vergi Gelirlerinin Oynakligina Dair Bir Analiz

    OpenAIRE

    Tuba Ozsevinc; Erdal Yilmaz

    2014-01-01

    [TR] Vergi gelirlerinin oynakliginin dusuk olmasi, butce planlarini kolaylastirici bir role sahiptir. Bu calismada, degisim katsayisi ve vergi geliri istikrar katsayisi kullanilarak, Turkiye’de vergi gelirlerinin istikrarli olup olmadigi ortaya koyulmaya calisilmistir. Bu nedenle, 2007-2013 yillarina ait vergi gelirleri ele alinmistir. Calismanin sonuclari, Turkiye’de goreli en istikrarli vergi gelirinin, dolaysiz vergilerin en onemli bileseni olan gelir ve kazanc uzerinden alinan vergiler ol...

  9. Kaybolmuş bir İçecek Kefir

    OpenAIRE

    Zekâi Varnacı

    2015-01-01

    Kafkasya’da bir parça dana veya koyun şirdeni keçi tulumlarında inek sütüyle maserasyona bırakılarak hazırlanır. Süt çabuk ve spontan olarak koagüle olur. Bundan sonra tulum yeniden doldurularak yeni bir işleme geçilir. Birkaç hafta sonra tulumun iç cidarlarında yavaş yavaş süngerimsi bir kabuk tabakası oluşur. İşte bu kabuk tabakası bölünüp veya kasılıp, sonra kurutularak kefir daneleri meydana getirilir. Danelerin görünüşü sarımsı, küçük, tomurcuğumsudur. Bu daneler kefirin hazırlanmasında ...

  10. Kaybolmuş bir İçecek Kefir

    OpenAIRE

    Varnacı, Zekai

    1980-01-01

    Kafkasya’da bir parça dana veya koyun şirdeni keçi tulumlarında inek sütüyle maserasyona bırakılarak hazırlanır. Süt çabuk ve spontan olarak koagüle olur. Bundan sonra tulum yeniden doldurularak yeni bir işleme geçilir. Birkaç hafta sonra tulumun iç cidarlarında yavaş yavaş süngerimsi bir kabuk tabakası oluşur. İşte bu kabuk tabakası bölünüp veya kasılıp, sonra kurutularak kefir daneleri meydana getirilir. Danelerin görünüşü sarımsı, küçük, tomurcuğumsudur. Bu daneler kefirin hazırlanmasınd...

  11. Kaybolmuş bir İçecek Kefir

    Directory of Open Access Journals (Sweden)

    Zekâi Varnacı

    2015-02-01

    Full Text Available Kafkasya’da bir parça dana veya koyun şirdeni keçi tulumlarında inek sütüyle maserasyona bırakılarak hazırlanır. Süt çabuk ve spontan olarak koagüle olur. Bundan sonra tulum yeniden doldurularak yeni bir işleme geçilir. Birkaç hafta sonra tulumun iç cidarlarında yavaş yavaş süngerimsi bir kabuk tabakası oluşur. İşte bu kabuk tabakası bölünüp veya kasılıp, sonra kurutularak kefir daneleri meydana getirilir. Danelerin görünüşü sarımsı, küçük, tomurcuğumsudur. Bu daneler kefirin hazırlanmasında maya olarak kullanılmak üzere ticarete arzedilir.

  12. Çevre sorunlarına etik bir yaklaşım: felsefi bir sorgulama

    OpenAIRE

    Ağbuğa, Fatma

    2016-01-01

    Çevre olmadan yaşamdan bahsetmenin mümkün olmayacağının bilincinde olan filozoflar doğal dengeyi bozucu, yok edici faaliyetlerin tek sorumlusunun insan olduğunu görmüşler ve çözüm olarak etiğin uygulamalı bir alanı olan “çevre etiği” kavramını ortaya koymuşlardır. Ancak çevre etiği 1970’lere kadar felsefenin bir disiplin alanı olarak tanınmadı. Uluslararası bilimsel alanda çevre sorunlarına felsefi bir bakış açısıyla bakan çok sayıda araştırmalar yapılmaya devam edilmesine rağmen, ülkemizde b...

  13. Mechanisms of bacterial DNA replication restart

    Science.gov (United States)

    Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

    2018-01-01

    Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

  14. Database Replication Prototype

    OpenAIRE

    Vandewall, R.

    2000-01-01

    This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....

  15. SlBIR3 Negatively Regulates PAMP Responses and Cell Death in Tomato

    Directory of Open Access Journals (Sweden)

    Shuhua Huang

    2017-09-01

    Full Text Available Bri1-associated kinase 1 (BAK1-interacting receptor-like kinase (BIR proteins have been shown to play important roles in regulating growth and development, pathogen associated molecular pattern (PAMP-triggered immunity (PTI responses, and cell death in the model plant, Arabidopsis thaliana. We identified four BIR family members in tomato (Solanum lycopersicum, including SlBIR3, an ortholog of AtBIR3 from A. thaliana. SlBIR3 is predicted to encode a membrane localized non-arginine-aspartate (non-RD kinase that, based on protein sequence, does not have autophosphorylation activity but that can be phosphorylated in vivo. We established that SlBIR3 interacts with SlBAK1 and AtBAK1 using yeast two-hybrid assays and co-immunoprecipitation and maltose-binding protein pull down assays. We observed that SlBIR3 overexpression in tomato (cv. micro-tom and A. thaliana has weak effect on growth and development through brassinosteroid (BR signaling. SlBIR3 overexpression in A. thaliana suppressed flg22-induced defense responses, but did not affect infection with the bacterial pathogen Pseudomonas syringae (PstDC3000. This result was confirmed using virus-induced gene silencing (VIGS in tomato in conjunction with PstDC3000 infection. Overexpression of SlBIR3 in tomato (cv. micro-tom and A. thaliana resulted in enhanced susceptibility to the necrotrophic fungus Botrytis cinerea. In addition, co-silencing SlBIR3 with SlSERK3A or SlSERK3B using VIGS and the tobacco rattle virus (TRV-RNA2 vector containing fragments of both the SlSERK3 and SlBIR3 genes induced spontaneous cell death, indicating a cooperation between the two proteins in this process. In conclusion, our study revealed that SlBIR3 is the ortholog of AtBIR3 and that it participates in BR, PTI, and cell death signaling pathways.

  16. Postpartum dönemde nadir bir non-anevrizmal subaraknoid kanama nedeni: Postpartum serebral anjiyopati

    OpenAIRE

    Güler, A; Deveci, E; Çiftçi, Ş; Toprak, Gökçay F; Şirin, H

    2014-01-01

    Serebral vazokonstrüksiyon sendromu serebral arterlerin reversibl multifokal vazokonstrüksiyonu ile karakterize bir tablodur. Postpartum serebral anjiyopati (PSA) eklampsisi olmayan kadınlarda sıklıkla doğumdan 1-4 hafta sonra görülen serebrovasküler hastalıktır. PSA komplikasyonu olarak daha çok intraserebral hemoraji ve serebral infarkt bildirilmiştir. Bu yazıda, PSA'nın nadir bir komplikasyonu olan non-anevrizmal subaraknoid hemoraji saptanan bir olgu bildirilmektedir.

  17. Altered Regulation of Escherichia coli Biotin Biosynthesis in BirA Superrepressor Mutant Strains

    Science.gov (United States)

    Chakravartty, Vandana

    2012-01-01

    Transcription of the Escherichia coli biotin (bio) operon is directly regulated by the biotin protein ligase BirA, the enzyme that covalently attaches biotin to its cognate acceptor proteins. Binding of BirA to the bio operator requires dimerization of the protein, which is triggered by BirA-catalyzed synthesis of biotinoyl-adenylate (biotinoyl-5′-AMP), the obligatory intermediate of the ligation reaction. Although several aspects of this regulatory system are well understood, no BirA superrepressor mutant strains had been isolated. Such superrepressor BirA proteins would repress the biotin operon transcription in vivo at biotin concentrations well below those needed for repression by wild-type BirA. We isolated mutant strains having this phenotype by a combined selection-screening approach and resolved multiple mutations to give several birA superrepressor alleles, each having a single mutation, all of which showed repression dominant over that of the wild-type allele. All of these mutant strains repressed bio operon transcription in vivo at biotin concentrations that gave derepression of the wild-type strain and retained sufficient ligation activity for growth when overexpressed. All of the strains except that encoding G154D BirA showed derepression of bio operon transcription upon overproduction of a biotin-accepting protein. In BirA, G154D was a lethal mutation in single copy, and the purified protein was unable to transfer biotin from enzyme-bound biotinoyl-adenylate either to the natural acceptor protein or to a biotin-accepting peptide sequence. Consistent with the transcriptional repression data, each of the purified mutant proteins showed increased affinity for the biotin operator DNA in electrophoretic mobility shift assays. Surprisingly, although most of the mutations were located in the catalytic domain, all of those tested, except G154D BirA, had normal ligase activity. Most of the mutations that gave superrepressor phenotypes altered residues

  18. Prelife catalysts and replicators

    OpenAIRE

    Ohtsuki, Hisashi; Nowak, Martin A.

    2009-01-01

    Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...

  19. Lithospheric mantle evolution in the Afro-Arabian domain: Insights from Bir Ali mantle xenoliths (Yemen)

    Science.gov (United States)

    Sgualdo, P.; Aviado, K.; Beccaluva, L.; Bianchini, G.; Blichert-Toft, J.; Bryce, J. G.; Graham, D. W.; Natali, C.; Siena, F.

    2015-05-01

    Detailed petrological and geochemical investigations of an extensive sampling of mantle xenoliths from the Neogene-Quaternary Bir Ali diatreme (southern Yemen) indicate that the underlying lithospheric mantle consists predominantly of medium- to fine-grained (often foliated) spinel-peridotites (85-90%) and spinel-pyroxenites (10-15%) showing thermobarometric estimates in the P-T range of 0.9-2.0 GPa and 900-1150 °C. Peridotites, including lherzolites, harzburgites and dunites delineate continuous chemical, modal and mineralogical variations compatible with large extractions of basic melts occurring since the late Proterozoic (~ 2 Ga, according to Lu-Hf model ages). Pyroxenites may represent intrusions of subalkaline basic melts interacting and equilibrated with the host peridotite. Subsequent metasomatism has led to modal changes, with evidence of reaction patches and clinopyroxene and spinel destabilization, as well as formation of new phases (glass, amphibole and feldspar). These changes are accompanied by enrichment of the most incompatible elements and isotopic compositions. 143Nd/144Nd ranges from 0.51419 to 0.51209 (εNd from + 30.3 to - 10.5), 176Hf/177Hf from 0.28459 to 0.28239 (εHf from + 64.4 to - 13.6), and 208Pb/204Pb from 36.85 to 41.56, thus extending from the depleted mantle (DM) towards the enriched OIB mantle (EM and HIMU) components. 3He/4He (R/RA) ratios vary from 7.2 to 7.9 with He concentrations co-varying with the most incompatible element enrichment, in parallel with metasomatic effects. These metasomatic events, particularly effective in harzburgites and dunites, are attributable to the variable interaction with alkaline basic melts related to the general extensional and rifting regime affecting the East Africa-Arabian domain during the Cenozoic. In this respect, Bir Ali mantle xenoliths resemble those occurring along the Arabian margins and the East Africa Rift system, similarly affected by alkaline metasomatism, whereas they are

  20. Tıpta işbirliği ve hukuksal sorunlar

    OpenAIRE

    Rosenau, Henning

    2010-01-01

    Tıpta işbirliği ve hukuksal sorunlar : tarih: 16-17 nisan 2010, Kurupelit Yerleskesi, Samsun = Delegation und Kooperation im Gesundheitswesen / ed.: Henning Rosenau ... - Samsun : Adalet, 2010. - XII, 331 S.

  1. Bir1 Deletion Causes Malfunction of the Spindle Assembly Checkpoint and Apoptosis in Yeast

    International Nuclear Information System (INIS)

    Ren, Qun; Liou, Liang-Chun; Gao, Qiuqiang; Bao, Xiaoming; Zhang, Zhaojie

    2012-01-01

    Cell division in yeast is a highly regulated and well studied event. Various checkpoints are placed throughout the cell cycle to ensure faithful segregation of sister chromatids. Unexpected events, such as DNA damage or oxidative stress, cause the activation of checkpoint(s) and cell cycle arrest. Malfunction of the checkpoints may induce cell death. We previously showed that under oxidative stress, the budding yeast cohesin Mcd1, a homolog of human Rad21, was cleaved by the caspase-like protease Esp1. The cleaved Mcd1 C-terminal fragment was then translocated to mitochondria, causing apoptotic cell death. In the present study, we demonstrated that Bir1 plays an important role in spindle assembly checkpoint and cell death. Similar to H 2 O 2 treatment, deletion of BIR1 using a BIR1-degron strain caused degradation of the securin Pds1, which binds and inactivates Esp1 until metaphase-anaphase transition in a normal cell cycle. BIR1 deletion caused an increase level of ROS and mis-location of Bub1, a major protein for spindle assembly checkpoint. In wild type, Bub1 was located at the kinetochores, but was primarily in the cytoplasm in bir1 deletion strain. When BIR1 was deleted, addition of nocodazole was unable to retain the Bub1 localization on kinetochores, further suggesting that Bir1 is required to activate and maintain the spindle assembly checkpoint. Our study suggests that the BIR1 function in cell cycle regulation works in concert with its anti-apoptosis function.

  2. Three Conceptual Replication Studies in Group Theory

    Science.gov (United States)

    Melhuish, Kathleen

    2018-01-01

    Many studies in mathematics education research occur with a nonrepresentative sample and are never replicated. To challenge this paradigm, I designed a large-scale study evaluating student conceptions in group theory that surveyed a national, representative sample of students. By replicating questions previously used to build theory around student…

  3. Topology of a Membrane Associated Regulator of Prokaryotic DNA Replication

    National Research Council Canada - National Science Library

    Firshein, William

    1998-01-01

    This proposal has focused on a broad host range plasmid, RK2, as a model system to study how a pair of initiation proteins encoded by the plasmid for DNA replication function when replication occurs...

  4. RPA Stabilization of Single-Stranded DNA Is Critical for Break-Induced Replication.

    Science.gov (United States)

    Ruff, Patrick; Donnianni, Roberto A; Glancy, Eleanor; Oh, Julyun; Symington, Lorraine S

    2016-12-20

    DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to maintain genome stability. Replication protein A (RPA) plays an important role in homology-dependent repair of DSBs by protecting the single-stranded DNA (ssDNA) intermediates formed by end resection and by facilitating Rad51 loading. We found that hypomorphic mutants of RFA1 that support intra-chromosomal homologous recombination are profoundly defective for repair processes involving long tracts of DNA synthesis, in particular break-induced replication (BIR). The BIR defects of the rfa1 mutants could be partially suppressed by eliminating the Sgs1-Dna2 resection pathway, suggesting that Dna2 nuclease attacks the ssDNA formed during end resection when not fully protected by RPA. Overexpression of Rad51 was also found to suppress the rfa1 BIR defects. We suggest that Rad51 binding to the ssDNA formed by excessive end resection and during D-loop migration can partially compensate for dysfunctional RPA. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Elucidating respective functions of two domains BIR and C-helix of human IAP survivin for precise targeted regulating mitotic cycle, apoptosis and autophagy of cancer cells.

    Science.gov (United States)

    Hu, Fabiao; Pan, Daxia; Zheng, Wenyun; Yan, Ting; He, Xiujuan; Ren, Fuzheng; Lu, Yiming; Ma, Xingyuan

    2017-12-26

    Survivin was the smallest member of the IAP family, which was over expressed in many different cancers, and considered to be a promising hot target for cancer therapy, and our previous study demonstrated that multiple dominant negative mutants from full-length survivin could have many complex effects on cancer cells, such as cell cycle, apoptosis, and autophagy. But it was not yet known what role the two main domains played in those functions, which would be very important for the design of targeted anticancer drugs and for the interpretation of their molecular mechanisms. In this study, based on preparation the two parts (BIR domain and CC domain) of survivin by genetic engineering and cell characterization assay, we discovered that BIR (T34A)-domain peptide could inhibit Bcap-37 cells growth in a dose- and time-dependent manner, increase the proportion of G2/M phase, and induce caspase-dependent apoptosis via the mitochondrial pathway. While CC (T117A)-domain peptide increased the proportion of S-phase cells and increased the level of the autophagy marker protein LC3B significantly. These further experiments confirmed that TAT-BIR (T34A) peptide could be used to inhibit cell proliferation, promote apoptosis, and block mitosis, and TAT-CC (T117A) peptide showed mainly to promote autophagy, process of DNA replication, and mitosis to breast cancer cells. This research will lay the foundation for interpreting the multifunction mechanism of survivin in cell fates, further make senses in developing the anticancer drugs targeting it precisely and efficiently.

  6. In vitro replication of poliovirus

    International Nuclear Information System (INIS)

    Lubinski, J.M.

    1986-01-01

    Poliovirus is a member of the Picornaviridae whose genome is a single stranded RNA molecule of positive polarity surrounded by a proteinaceous capsid. Replication of poliovirus occurs via negative strand intermediates in infected cells using a virally encoded RNA-dependent RNA polymerase and host cell proteins. The authors have exploited the fact that complete cDNA copies of the viral genome when transfected onto susceptible cells generate virus. Utilizing the bacteriophage SP6 DNA dependent RNA polymerase system to synthesize negative strands in vitro and using these in an in vitro reaction the authors have generated full length infectious plus strands. Mutagenesis of the 5' and 3' ends of the negative and positive strands demonstrated that replication could occur either de novo or be extensions of the templates from their 3' ends or from nicks occurring during replication. The appearance of dimeric RNA molecules generated in these reactions was not dependent upon the same protein required for de novo initiation. Full length dimeric RNA molecules using a 5' 32 P end-labelled oligo uridylic acid primer and positive strand template were demonstrated in vitro containing only the 35,000 Mr host protein and the viral RNA-dependent RNA polymerase. A model for generating positive strands without protein priming by cleavage of dimeric RNA molecules was proposed

  7. Co-Occurring Disorders

    Science.gov (United States)

    ... the mental health field. Alcohol and Drug Abuse, Addiction and Co-occurring Disorders: Co-occurring Disorders and ... 500 Montgomery Street, Suite 820 Alexandria, VA 22314 Phone (703) 684.7722 Toll Free (800) 969.6642 ...

  8. Percieved functions of naturally occurring autobiographical memories

    DEFF Research Database (Denmark)

    Treebak, L. S.; Henriksen, J. R.; Lundhus, S.

    2005-01-01

    The main empirical reference on functions of autobiographical memories is still Hyman & Faries (1992) who used the cue-word-method and retrospective judgements. We used diaries to sample naturally occurring autobiographical memories and participants? perceived use of these. Results partly replicate...

  9. DNA replication and cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... 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....

  10. pHis 317 Pro Mutasyonu Saptanmış Bir Mody Tip 2 Olgusu

    OpenAIRE

    BİNİCİ, Doğan Nasır; TİMUR, Özge; TURHAN, Aykut; ŞENYİĞİT2, Abdülhalim; FİLİZ, Murat; KİPER, Tuğba

    2017-01-01

    Genç yaşta ortaya çıkan erişkin tip diyabet [Maturity- onset Diabetes of the Young (MODY)], otozomal dominant kalıtılan nadir bir diyabet türüdür. Tüm diyabet olgularının %1-2’sini oluşturur. MODY tip diyabet olgularının çoğunluğu yanlışlıkla tip 1 veya tip 2 diyabet tanısı almaktadır. Birçok tipi tanımlanmasına rağmen glukokinaz mutasyonu ile meydana gelen MODY tip 2 daha sık görülmektedir. Bu vaka sunumunda daha önce rastlanmamış bir mutasyon, pHis 317 Pro mutasyonu saptanmış MODY tip 2 olg...

  11. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

    DEFF Research Database (Denmark)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine

    2014-01-01

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus...... as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications....

  12. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  13. Who Needs Replication?

    Science.gov (United States)

    Porte, Graeme

    2013-01-01

    In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…

  14. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chro......Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division......, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple......-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive...

  15. Avrupa Birliği hukukunun önceliği ilkesi kapsamında Avrupa Birliğinde temel hak koruması

    OpenAIRE

    BİLGİN, Azime Aslı

    2011-01-01

    TEZ ÖZETİBirlik için bir çok açıdan önemi haiz bir konu olan temel hak korumasının Avrupa Birliğinin (Birlik) oluşumundan bugüne geçirdiği evreleri ve temel hak koruması konusundaki gelişmelerin Birlik hukukunun vazgeçilmezi öncelik ilkesi ile olan ilişkisini ele aldığımız çalışmamız üç ana bölümden oluşmaktadır.İlk bölümde temel hak korumasını Divan ve ulusal mahkelemeler arasındaki tartışmanın merkezine yerleştiren ve oluşumdan itibaren temel hak ile olan ilişkis...

  16. Registered Replication Report

    DEFF Research Database (Denmark)

    Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.

    2017-01-01

    and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...

  17. The replication recipe : What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  18. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  19. ESR analyses for herbivore teeth and molluscs from Kharga, Dakhleh, and Bir Tarfawi Oases: Constraining water availability and hominin paleolithic activity in the Western Desert, Egypt

    Science.gov (United States)

    Blackwell, B. A. B.; Skinner, A. R.; Smith, J. R.; Hill, C. L.; Churcher, C. S.; Kieniewicz, J. M.; Adelsberger, K. A.; Blickstein, J. I. B.; Florentin, J. A.; Deely, A. E.; Spillar, K. V.

    2017-12-01

    Today, Bir Tarfawi, Kharga and Dakhleh Oases all sit in Egypt's hyperarid Western Desert. A dearth of naturally occurring surface water coupled with ≤ 0.1 mm/y of precipitation, and evaporation rates > 2 m/y make Bir Tarfawi uninhabitable today, while Dakhleh and Kharga depend on borehole water to support human inhabitation. Yet in scattered locations dotting the Quaternary surfaces and deposits near each oasis, Paleolithic artefacts, fossil ungulate teeth, and snails record times when surface water did exist in wetlands, small ponds, and even large lakes. At Bir Tarfawi in Marine Isotope Stages (MIS) 5, 7, and 13, wetlands or small lakes supported freshwater snails, large herbivores, and hominins. Dakhleh Oasis hosted a large lake in MIS 6 that provided a deep reliable water supply for many millennia subsequently. ESR dates on fossils and tufa dates show thriving lacustrine and terrestrial ecosystems at Dakhleh during MIS 5, 7, 9, 11, and 17, and in shorter episodes in MIS 1, 2, 3, 6, and 12. At Kharga Oasis, springs discharged along the Libyan Escarpment edge, but the water was ponded in small basins dammed within tufa deposits. These dated deposits and fossils attest that water existed there in MIS 2-11, and one spot dating to ∼ 2.3 Ma. This proxy evidence suggest that, thanks to higher rainfall and/or groundwater tables, sufficient water persisted for much of the Pleistocene, supporting food resources, like large herbivores and molluscs, to thrive and enabling hominin habitation. and activity in the Western Desert.

  20. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

    This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

  1. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  2. Chromatin Immunoprecipitation of Replication Factors Moving with the Replication Fork

    OpenAIRE

    Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi

    2009-01-01

    Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...

  3. birääkijate viis lemmikviga / Max H. Bazerman, Don A Moore

    Index Scriptorium Estoniae

    Bazerman, Max H.

    2008-01-01

    Harvardi Ärikooli professorid annavad nõu, mida teha siis, kui jäädakse läbirääkimistel liigselt pidama esimese pakkumise külge, ollakse jäärapäine, minnakse liiale enesekindlusega või keskendutakse liiga kitsale eesmärgile

  4. Põhja-Korea lahkus tuumaläbirääkimistelt / Jüri Piirisild

    Index Scriptorium Estoniae

    Piirisild, Jüri

    2005-01-01

    Põhja-Korea teatas tuumaprogrammi alaste läbirääkimiste tähtajatust katkestamisest. Analüütikute arvates peaks USA pehmendama oma jäika hoiakut Põhja-Korea suhtes ning püüdma senisest aktiivsemalt leida kriisile lahendust

  5. Kas sugu on läbirääkimistel tähtis

    Index Scriptorium Estoniae

    2006-01-01

    Ülevaade Harvard Business Schooli uudiskirja Working Knowledge 2006. aasta veebruari numbris ilmunud Dina W. Pradel'i, Hannah Riley Bowles'i ja Kathleen L. McGinn'i artiklist inimese soo mõjust läbirääkimistele

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

    Science.gov (United States)

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

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

  7. The Inherent Asymmetry of DNA Replication.

    Science.gov (United States)

    Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

    2017-10-06

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

  8. Pengaruh Lama Perendaman dan Jenis Minuman Beralkohol Bir dan Tuak terhadap Kekerasan Email Gigi Manusia (In Vitro)

    OpenAIRE

    Magista, Malida; Nuryanti, Archadian; Wahyudi, Ivan Arie

    2014-01-01

    Erosi gigi merupakan hilangnya lapisan email gigi karena asam. Jenis asam, pH rendah, serta kandungan kalsium, fosfat, dan fluoride pada bir dan tuak diduga merupakan faktor kimiawi penyebab erosi gigi. Tujuan penelitian ini untuk mengetahui pengaruh lama perendaman dan jenis minuman beralkohol bir dan tuak terhadap kekerasan email gigi manusia (in vitro). Penelitian ini menggunakan 14 sampel gigi premolar pertama atas. Setiap gigi dibagi menjadi 2 bagian, bukal dan palatal. kemudian dibagi m...

  9. Pengaruh Lama Perendaman Dan Jenis Minuman Beralkohol Bir Dan Tuak Terhadap Kekerasan Email Gigi Manusia (in Vitro)

    OpenAIRE

    Magista, Malida; Nuryanti, Archadian; Wahyudi, Ivan Arie

    2014-01-01

    Erosi gigi merupakan hilangnya lapisan email gigi karena asam. Jenis asam, pH rendah, serta kandungan kalsium, fosfat, dan fluoride pada bir dan tuak diduga merupakan faktor kimiawi penyebab erosi gigi. Tujuan penelitian ini untuk mengetahui pengaruh lama perendaman dan jenis minuman beralkohol bir dan tuak terhadap kekerasan email gigi manusia (in vitro). Penelitian ini menggunakan 14 sampel gigi premolar pertama atas. Setiap gigi dibagi menjadi 2 bagian, bukal dan palatal. kemudian dibagi m...

  10. Evolution of Replication Machines

    Science.gov (United States)

    Yao, Nina Y.; O'Donnell, Mike E.

    2016-01-01

    The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

  11. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  12. Duchenne Musküler Distrofili Bir Olguda Anestezi Yönetimi

    OpenAIRE

    KARAHAN, N.; AKSUN, M.; KOROĞLU, L.; GİRGİN, S.; ARAN, G.; AKHAN, G.; GÜRBÜZ, A.

    2014-01-01

    Duchenne Musküler Distrofi (DMD); X’e bağlı resesif olarak geçiş gösteren ilerleyici kas zayıflığı ve kas kontraktürleri ile karakterize kalıtımsal bir hastalıktır. En sık çocukluk yaşlarında ve 3.500 erkek doğumda 1 görülmektedir. Bu hastalarda anestezi yönetimi özellik göstermektedir. Çünkü inhalasyon anestezikleri ve süksinilkolin gibi ajanlar, hipermetabolik bir klinik tablo ile seyreden malign hipertermi gibi ölümcül komplikasyonlara yol açabilir. Biz ventriküler septal defekt (VSD) nede...

  13. Bir Buzağıda Notomeli (Notomelia) ve Pakomeli (Phocomelia) Olgusu

    OpenAIRE

    HAYAT, Ali

    2013-01-01

    Bu vaka takdiminde, 15 günlük dişi melez bir buzağıda notomeli ve pakomeli anomalisi klinik ve radyolojik olarak değerlendirildi. Notomelie ve pakomeli olgusunun buzağılarda çok nadir görülmesi ve ilginç olmasından dolayı bu vaka rapor edilmiştir.

  14. Dialoogsüsteem ja läbirääkimiste struktuur

    Directory of Open Access Journals (Sweden)

    Mare Koit

    2017-05-01

    Full Text Available "Dialogue systems and the structure of negotiation" We are studying the negotiations in the Estonian dialogue corpus, with the aim of identifying the typical dialogue acts and communicative strategies used in the dialogues. Three sub-corpora have been analysed: 1 conversations between a travel agent and a customer who is planning a trip; 2 telemarketing calls where a sales clerk for an educational company argues that a customer should take a training course, and 3 everyday conversations where the initiator attempts to persuade the communication partner to perform an action. The structure of the different types of dialogues is represented as a sequence of dialogue acts and communicative strategies. The general structure of human-human negotiation is identified and described. This structure is compared with the structure of the negotiations carried out by an experimental dialogue system. The results can help to develop the dialogue system in order to make conversations with the system more human-like. Artiklis uuritakse eesti dialoogikorpuses leiduvaid inimestevahelisi läbirääkimisi, et välja selgitada sellistes dialoogides tüüpiliselt kasutatavad dialoogiaktid ja suhtlusstrateegiad. Analüüsitakse kolme alamkorpust: 1 dialooge reisibüroo agendi ja kliendi vahel, 2 müügiläbirääkimisi, kus koolitusfirma ametnik pakub võimalikule kliendile firma kursusi, ning 3 argivestlusi, kus kaks omavahel tuttavat osalejat püüavad saavutada kokkulepet teatava tegevuse tegemise suhtes. Erinevat tüüpi dialoogide struktuur esitatakse nii dialoogiaktide kui ka suhtlusstrateegiate järjendina ning nende andmete põhjal leitakse ka läbirääkimiste üldine struktuur. Seda struktuuri võrreldakse olemasoleva eksperimentaalse dialoogsüsteemiga peetavate läbirääkimiste struktuuriga. Tulemused võimaldavad dialoogsüsteemi edasi arendada, et muuta sellega suhtlemist inimlähedasemaks.

  15. Experimental toxicology: Issues of statistics, experimental design, and replication.

    Science.gov (United States)

    Briner, Wayne; Kirwan, Jeral

    2017-01-01

    The difficulty of replicating experiments has drawn considerable attention. Issues with replication occur for a variety of reasons ranging from experimental design to laboratory errors to inappropriate statistical analysis. Here we review a variety of guidelines for statistical analysis, design, and execution of experiments in toxicology. In general, replication can be improved by using hypothesis driven experiments with adequate sample sizes, randomization, and blind data collection techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Tespiti Güç Bir İmza Sahteciliği Yöntemi “Serbest Taklit”: Bir Olgu Sunumu

    Directory of Open Access Journals (Sweden)

    Güven Seçkin Kırcı

    2017-06-01

    Full Text Available Giriş ve Amaç: İmza; atan kişiyi kesin bir şekilde belirleyen ve atıldığı belgeyi onaylama iradesini belirten, kişiye ait el yazısı yanında her çeşit işarete verilen isim olarak tanımlanmaktadır. Kişinin kendisi tarafından atılmayan yani kendi eli ürünü olmayan sahte imzalar çeşitli yöntemler kullanılarak elde edilmektedirler. Bunlar, üstten kopyalama, bakarak taklit, serbest taklit yöntemi ile atılan imzalar, üzerinde imza ihtiva eden pulların sökülerek başka belgelere nakli, bilgisayar ve fotokopi teknolojileriyle atılan imzalar ve hayali kişiler adına atılmış uydurma imzalar olarak sıralanabilmektedir. Buna son zamanlarda icat edilerek giderek artan sıklıkla karşılaştığımız imza makineleriyle atılanlar eklenebilir. Sıraladığımız bu yöntemler içerisinde “Serbest Taklit Yöntemi” ile yapılan imza sahteciliği belirli yönleriyle diğer yöntemlerden ayrılmaktadır. Serbest Taklit Yöntemi ile atılan imzalarda sahteci, günlerce atacağı imzaya özen içinde çalışıp denemeler yaparak, imzayı tüm yönleriyle hafızasına alır ve taklidini oluşturabileceğine kanaat getirdiğinde bir bütün olarak atar. Sahtecinin birçok kez deneme yapma şansı olması nedeniyle de orjinaline oldukça benzeyen, tespiti güç bir imza modeli ortaya çıkması hiç te uzak bir ihtimal değildir. Bu nedenlerden ötürü, farklılıklar detaylarda gizli kalabilmektedir. Birçok özelliğiyle bu yöntem, incelemeciler açısından ortaya çıkarılması en güç olan sahtecilik tipidir . Olgu: Olgumuza konu olan inceleme konusu imzaya ve karşılaştırma imzalarına baktığımızda, hız, işleklik, istif, eğim, kalem bası dereceleri de dahil olmak üzere birçok tanı unsuru yönünden birbirine benzer özellikler içerdiklerini görmekteyiz. Ancak imzalar daha ayrıntılı incelendiğinde; özellikle başlangıç ve bitiş noktalarında, ara grama yapıları ve sayılarında, imzalar

  17. iç Göçler: Teorik Bir Analiz

    OpenAIRE

    ÇELİK, Fatih

    2013-01-01

    An indicator of changing in the social structure is migration Migration that has economic social and political reasons and consequences is an event that occurs internal and external country This study aims to explain economic reasons of internal migration In the literature the principal approches about migration are those: Returns costs approach push pull approach and selective approach Key Words: Migration Internal Migration Theory Migration Approaches

  18. Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates.

    Science.gov (United States)

    Kurat, Christoph F; Yeeles, Joseph T P; Patel, Harshil; Early, Anne; Diffley, John F X

    2017-01-05

    The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription). The FACT-associated Nhp6 protein, the nucleosome remodelers INO80 or ISW1A, and the lysine acetyltransferases Gcn5 and Esa1 each contribute separately to maximum DNA synthesis rates. Chromatin promotes the regular priming of lagging-strand DNA synthesis by facilitating DNA polymerase α function at replication forks. Finally, nucleosomes disrupted during replication are efficiently re-assembled into regular arrays on nascent DNA. Our work defines the minimum requirements for chromatin replication in vitro and shows how multiple chromatin factors might modulate replication fork rates in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Mechanisms of DNA replication termination.

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2017-08-01

    Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

  20. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  1. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  2. Yerel Dokusunu Yitirmekte Olan Bir Kent: Malatya A City Losing Its Local Texture: Malatya

    Directory of Open Access Journals (Sweden)

    Zaliha İnci KARABACAK

    2013-07-01

    Full Text Available Turkey is a country that was built on Anatolia’s rich heritage in respect to historical, social, cultural and economical. This study approaches the changing face of Malatya which is one of the new big cities of Turkey. Change is one of the realities that can not be ignored. In social life, cities have emerged as spaces which are exposed to changes. Cities are being transformed for various reasons such as population growth, modern urbanization policies, economic interests. In some cases, the change is damaging the essence of the city. Today, the change shows its effect in this aspect on many cities. This situation causes many cities to lose the local texture of its’. Malatya distinguishes itself as an city with some characteristics of economic, geographic, social and cultural. But a significant portion of these distinctive values are being succumbed in the face of change. In this context in the study it’s elaborated on fall of; especially greenbelt which -Malatya’s the worldwide economic value-apricotes are grown on and Malatya’s traditional houses because of construction of boulevard, junction, multiplex housing to create a modern city. The values which are being lost in Malatya are expressed visually by nearby dated photos. In this study similar changes, which are often internalized by most of us in everyday city life, are bringing forward once again with the example of Malatya. So, it’s tried to wake up the consciousness of being more sensitive to these changes as an individual and a citizen. Bu çalışmada; tarihi, sosyal, kültürel ve ekonomik bakımdan zengin bir mirasa ev sahipliği yapan Anadolu topraklarında kurulu Türkiye’nin yeni büyükşehirlerinden biri olan Malatya’nın bir süredir değişen çehresi ele alınmaktadır. Değişim, yaşamın gözardı edilemeyecek gerçeklerinden biridir. Toplumsal yaşamda kentler değişime maruz kalan mekanlar olarak karşımıza çıkmaktadırlar. Kentler; nüfus art

  3. KRONİK HİPERPLASTÎK PULPİTİS (PULPA POLİPİ) - Bir Olgu Nedeni İle CHRONIC HYPERPLASTIC PULPITIS (PULP POLYP) -A Case Report-

    OpenAIRE

    Ulukapı, Işın; Stich, Herrmann

    2012-01-01

    ÖZETKronik hipcrpiasük pulpitis (pulpa polipi) kronikBu çalışmada bir pulpa polipi plgusu histolojik olarak incelenmiştir.Anahtar sözcükler: Kronik pulpa hastalıkları, kronik hiperplastik pulpitis, pulpa polipi.ABTRACTChronic hyperplastic pulpitis (pulp polyp) is a quite uncommon form of chronic pulp disease. It occurs almost exclusively in children and young adults and involves teeth with large open carious lesions. The hyperplastic tissue is basically granulation tissue and inflammatory cel...

  4. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to ada......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.......Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...

  5. Induction of UV-resistant DNA replication in Escherichia coli: Induced stable DNA replication as an SOS function

    International Nuclear Information System (INIS)

    Kogoma, T.; Torrey, T.A.; Connaughton, M.J.

    1979-01-01

    The striking similarity between the treatments that induce SOS functions and those that result in stable DNA replication (continuous DNA replication in the absence of protein synthesis) prompted us to examine the possibility of stable DNA replication being a recA + lexA + -dependent SOS function. In addition to the treatments previously reported, ultraviolet (UV) irradiation or treatment with mitomycin C was also found to induce stable DNA replication. The thermal treatment of tif-1 strains did not result in detectable levels of stable DNA replication, but nalidixic acid readily induced the activity in these strains. The induction of stable DNA replication with nalidixic acid was severely suppressed in tif-1 lex A mutant strains. The inhibitory activity of lexA3 was negated by the presence of the spr-5l mutation, an intragenic suppressor of lexA3. Induced stable DNA replication was found to be considerably more resistant to UV irradiation than normal replication both in a uvr A6 strain and a uvr + strain. The UV-resistant replication occurred mostly in the semiconservative manner. The possible roles of stable DNA replication in repair of damaged DNA are discussed. (orig.)

  6. Modeling inhomogeneous DNA replication kinetics.

    Directory of Open Access Journals (Sweden)

    Michel G Gauthier

    Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.

  7. Hüzün Turizmi Üzerine Bir Derleme

    Directory of Open Access Journals (Sweden)

    Ahmet ÇELİK

    2017-09-01

    Full Text Available Gün geçtikçe değişen özel ilgi turları, kitle turizminin bölgelere vermiş olduğu fiziksel ve kültürel etkilerini azaltarak, yeni çekim merkezleri ve daha sürdürülebilir bir turizmi amaç edinmektedir. Hüzün turizmi, kişilerde geçmişe yönelik acı, keder, üzüntü, hüzün, empati, sempati, korku, nefret ve intikam gibi içsel duyguların yönlendirilmesi ile alternatif bir turizm hareketi olarak gerçekleştirilmektedir. Son on yılda başlayan hüzün turizminin akademik çalışmaları genel olarak destinasyon pazarlamasını ele almaktadır. Ölümün sadece turizm açısından değil, kültür ve sosyal olarak incelenmesi gerekmektedir. Bu çalışmada, ulusal yayınlarda yer alan çalışmaların derlemesi yapılıp, isimlendirme konusunda yaşanan problemlere çözüm aranmaktadır. Ayrıca çalışmanın yürütüldüğü zamana kadar belirlenen ve potansiyeli olan bölgeler incelenip bir araya getirilerek, literatüre tek çalışmada kazandırılması hedeflenmektedir

  8. Paleohydrology and paleoenvironments at Bir Sahara: Pleistocene lithostratigraphy and sedimentology in the southern Egyptian Sahara

    Science.gov (United States)

    Hill, Christopher L.; Schild, Romuald

    2017-12-01

    The Bir Sahara area contains a remarkable record of Middle and Late Pleistocene hydrologic and environmental conditions for Saharan North Africa, based on lithostratigraphic and sedimentologic evidence from basin-fill deposits. Some of the deposits contain Lower Paleolithic (Acheulean) or Middle Paleolithic artifacts that help to constrain their age, since Acheulian artifacts are assigned to the Middle Pleistocene, while Middle Paleolithic artifacts are limited to either the Middle or Late Pleistocene. Locality BS-14 is in the southern part of Bir Sahara, while localities E-88-15, E-88-2, BS-13, and BS-16 are situated in the south-central part of the deflational basin, closer to the present-day water-hole. Lowered groundwater conditions during arid intervals resulted in erosional topographic basins. These deflational basins were later filled with sediments associated with wetter hydrologic conditions. The oldest studied sedimentary sequence in the Bir Sahara depression (BS-14) contains in situ Acheulian artifacts. Acheulian handaxes are found in sands underlying carbonates that are interpreted as evidence of spring-fed pond and marsh environments during a Middle Pleistocene wet interval. At the E-88-15 locality, the stratigraphic sequence documents deposition in a possible perennial pond or small lake that varied in extent and depth and is associated with Middle Paleolithic artifacts. At E-88-12 and BS-13, lateral and vertical variations in the lithofacies of the basin-fill sediments provide additional records of changing hydrologic conditions during the Late Pleistocene. These hydrologic conditions appear to reflect variations in water-table levels related to groundwater recharge and, at times, local rains.

  9. SCADA Sistemi ile Bir İşletmenin Dış Saha Otomasyonu

    OpenAIRE

    Kılıç, Murat; Özdemir, Şule

    2010-01-01

    Bu çalışmada, PLC (Programmable Logic Controller: Programlanabilir Mantık Denetleyici) ve SCADA (Supervising Control and Data Acquisition: Veri Tabanlı Kontrol ve Gözetleme) sistemleriyle bir MDF (Medium Density Fiberboard) presi dış saha besleme hattının otomasyonu gerçekleştirilmiştir. Tüm sistem SCADA sayesinde bilgisayar ekranından izlenebilmekte ve kontrol edilebilmektedir. MDF presi dış saha besleme hattı tam otomasyon ile çalışmaktadır. Otomasyon sisteminde PLC yazılımı olarak Siemens ...

  10. Bir köpekte Lucilia sericata (Diptera: Calliphoridae)’dan kaynaklanan travmatik myiasis olgusu

    OpenAIRE

    Işık, Nermin; Dik, Bilal

    2015-01-01

    Selçuk Üniversitesi, Veteriner Fakültesi Kliniğine yaralanmaşikâyeti ile getirilen bir erkek köpeğin muayenesinde, solkulağında ve çevresinde yüzlerce sayıda sinek larvalarınarastlandı. Toplanan larvalar, anterior ve posterior stigmalarave sefalo-faringeal iskeletin morfolojik özelliklerine göreteşhis edildi. Mikroskobik muayene sonucu larvaların Luciliasericata’nın üçüncü dönem larvası olduğu tespit edildi.

  11. SUMO and KSHV Replication

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

    2014-09-29

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

  12. DNA Replication Profiling Using Deep Sequencing.

    Science.gov (United States)

    Saayman, Xanita; Ramos-Pérez, Cristina; Brown, Grant W

    2018-01-01

    Profiling of DNA replication during progression through S phase allows a quantitative snap-shot of replication origin usage and DNA replication fork progression. We present a method for using deep sequencing data to profile DNA replication in S. cerevisiae.

  13. Hydroxyurea-Induced Replication Stress

    Directory of Open Access Journals (Sweden)

    Kenza Lahkim Bennani-Belhaj

    2010-01-01

    Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

  14. Mechanisms and regulation of DNA replication initiation in eukaryotes.

    Science.gov (United States)

    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.

  15. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    OpenAIRE

    Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

    2014-01-01

    The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MyS...

  16. Tatil Kararı Verme Tarzına Dayalı Bir Tipoloji

    OpenAIRE

    DECROP, Alain; ZIDDA, Pietro

    2008-01-01

    Bu çalışmada, geleneksel sosyodemografik ve psikografik ölçütlerden ziyade, karar verme tarzı değişkenlerine dayalı, yeni bir turist tipolojisi sunulmaktadır. Çalışmada altı turist tipi tanımlanmaktadır: alışılmış turist, akılcı turist, hedonik turist, fırsatçı turist, kısıtlı turist ve uyumlu turist. Bu tipoloji, Belçikalı turistlerle yürütülen niteliksel bir çalışmanın sonuçlarının yorumlanması neticesinde ortaya çıkmıştır. Çalışmada, tipolojinin niceliksel olarak da geçerli kılınmasını sağ...

  17. İran Halk Kütüphaneleri: Niceliksel Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    Jahangir Gholipour

    2013-06-01

    Full Text Available Halk kütüphaneleri dijital uçurumun azaltılmasında önemli roller üstlenen toplumsal kuruluşlardır. On­ların, bu rollerini gerçekleştirebilmeleri için niceliksel açıdan yeterli durumda olmaları gerekmektedir. Ayrıca, halk kütüphanelerine ilişkin niceliksel göstergeler niteliklerini ve nitelikli hizmet vermelerini doğrudan belirler. İran, 30 ilde yaşayan 71 milyon nüfusa sahip bir Ortadoğu ülkesidir. Bu çalışmada, İran’daki halk kütüphanelerine ilişkin niceliksel durum kütüphane sayısı, kullanıcı, derme ve personel unsurları açısından ortaya konulmaya çalışılmıştır. Elde edilen sonuçlara göre, İran’da ele alınan söz konusu unsurlar açısından genelde bir yetersizlik olduğu anlaşılmıştır. Çalışma sonunda bazı önerilerde bulunulmuştur.

  18. Fermente bir Soya Ürünü “Miso”

    Directory of Open Access Journals (Sweden)

    Kamuran Ayhan

    2015-02-01

    Full Text Available Miso, Uzakdoğu’da üretilen ve insanlarca fazla miktarda tüketilen fermente bir soya ürünüdür. Miso üretiminde hammadde olarak soya fasulyesi, pirinç veya arpa, tuz ve mikroorganizma kültürü (Aspergillus oryzae kullanılmaktadır. Miso’nun rengi koyu kahverenginden açık sarıya kadar değişim göstermektedir. Fermentasyon sırasında soya fasulyesinde bulunan protein, karbonhidrat ve yağlar daha basit bileşim unsurlarına parçalanmaktadır. Miso, %12.5-19.0 protein, %1.4-6.9 yağ, %5.5-13 oranında tuz içermekte, lezzet verici bir gıda maddesi özelliği taşımaktadır. Miso özellikle esansiyel amino asitlerce zengindir. Protein kalitesini belirleyen NPU (Net protein kullanımı değeri misoda %72’dir. Protein kalitesi açısından bilinen protein kaynaklı gıdalar içinde ilk sırayı almaktadır.

  19. Replication of bacteriophage lambda DNA

    International Nuclear Information System (INIS)

    Tsurimoto, T.; Matsubara, K.

    1983-01-01

    In this paper results of studies on the mechanism of bacteriophage lambda replication using molecular biological and biochemical approaches are reported. The purification of the initiator proteins, O and P, and the role of the O and P proteins in the initiation of lambda DNA replication through interactions with specific DNA sequences are described. 47 references, 15 figures

  20. Pattern replication by confined dewetting

    NARCIS (Netherlands)

    Harkema, S.; Schäffer, E.; Morariu, M.D.; Steiner, U

    2003-01-01

    The dewetting of a polymer film in a confined geometry was employed in a pattern-replication process. The instability of dewetting films is pinned by a structured confining surface, thereby replicating its topographic pattern. Depending on the surface energy of the confining surface, two different

  1. Charter School Replication. Policy Guide

    Science.gov (United States)

    Rhim, Lauren Morando

    2009-01-01

    "Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

  2. LHCb experience with LFC replication

    International Nuclear Information System (INIS)

    Bonifazi, F; Carbone, A; D'Apice, A; Dell'Agnello, L; Re, G L; Martelli, B; Ricci, P P; Sapunenko, V; Vitlacil, D; Perez, E D; Duellmann, D; Girone, M; Peco, G; Vagnoni, V

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements

  3. LHCb experience with LFC replication

    CERN Document Server

    Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  4. Dünya Denizcilik Eğitim Faaliyetleriyle İlgili Genel Bir Kıyaslama

    Directory of Open Access Journals (Sweden)

    Feramuz AŞKIN

    2015-12-01

    Full Text Available Deniz taşımacılığındaki artan profesyonelleşme gereksinimleri bu alanda hizmet veren personel ve mürettebatın aynı düzeyde eğitim alması ile cevap bulacaktır. Bu da eğitim veren kurum ve üniversitelerin belirli bir standartta eğitim vermesi ile mümkün olacaktır. Burada üzerinde durulması gereken konu eğitim veren kurumların eğitim düzeylerinin alt ve üst noktası arasındaki farkın mümkün mertebede birbirine yakın olması ile belirli bir kalite düzeyinde tutulabilecek olmasıdır. Bunun için eğitim veren kurumların uyması gereken başta STCW Manila kararları gibi uluslararası standartlar olmak üzere, iç mevzuatlar, çeşitli idarelerin önerileri ve kararları, EMSA gibi denetleyici birimlerin üzerinde durmuş olduğu çeşitli standartlar bir dayanak noktası oluşturacaktır. Bu çalışmada yazarlar, farklı düzeylerde eğitim veren örnek eğitim sistemlerinin karşılaştırılması yolu ile bu standartların uygulanması hususunu göz önüne sermeyi hedeflemektedir. Böylece bu bildirinin yazım amacı olan ve standartlarla genel kaideleri belirlenmiş daha kaliteli ve profesyonel eğitim sistemine geçişe katkıda bulunulabilecektir.

  5. Klasifikasi Ilmu Pengetahuan Dalam Perspektif Jābir Bin Ḥayyān

    Directory of Open Access Journals (Sweden)

    Asep N. Musadad

    2015-12-01

    Full Text Available Abstract : The central purpose of this article is to provide a preliminary exploration on epistemological background of the classical Islamic sciences through the investigation on the classification of knowledge. One of the earliest exponent to turn to this problem is Jābir bin Ḥayyān (Geber (721 - 815 AD, known as the Father of Arabic and – indirectly – Latin Alchemy. Start on describing  Jābir’s  profile  and  his  significance  in  Islamic  philosophy,  this  article  discusses the  classification  of  knowledge  according  to  him  in  his  book  “Kitāb  al-Ḥudūd”  (Book  of Limits, in which he make his own classification of various knowledge. It finally deals with the philosophical basis of the classification and the intellectual perspective of its author. Keywords : Jabir bin Hayyan, classification of knowledge, Islamic philosophy, natural sciences.   Abstrak : Artikel ini bertujuan untuk melakukan eksplorasi singkat terkait latar epistemologis dalam pengetahuan  Islam  klasik  melalui  analisis  terhadap  konsep  klasifikasi  ilmu  pengetahuan. Salah satu eksponen awal yang berbicara hal tersebut adalah Jābir bin Ḥayyān (Geber (721 - 815 M, dikenal sebagai Bapak Ilmu Kimia Arab dan – secara tidak langsung – Eropa-Latin. Diawali  dengan  penjelasan  tentang  signifikansi  Jābir  bin  Ḥayyān  dalam  wacana  filsafat Islam,  artikel  ini  mendiskusikan  klasifikasi  ilmu  pengetahuan  dalam  perspektifnya  yang terdapat  dalam  karyanya,  “Kitāb  al-Ḥudūd”  (Buku  tentang  Batas-Batas,  yang  membuat klasifikasi versinya sendiri dari berbagai macam ilmu pengetahuan. Pada akhirnya, tulisan ini juga akan menjelaskan basis filosofis dari klasifikasi tersebut dan perspektif intelektual pembuatnya. Kata-Kata Kunci : Jabir bin Hayyan, klasifikasi pengetahuan, filsafat Islam, ilmu-ilmu alam.

  6. The hunt for origins of DNA replication in multicellular eukaryotes

    DEFF Research Database (Denmark)

    Urban, J. M.; Foulk, M. S.; Casella, Cinzia

    2015-01-01

    Origins of DNA replication (ORIs) occur at defined regions in the genome. Although DNA sequence defines the position of ORIs in budding yeast, the factors for ORI specification remain elusive in metazoa. Several methods have been used recently to map ORIs in metazoan genomes with the hope...... that features for ORI specification might emerge. These methods are reviewed here with analysis of their advantages and shortcomings. The various factors that may influence ORI selection for initiation of DNA replication are discussed....

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

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

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

  8. ULUSLARIN REKABET ÜSTÜNLÜĞÜ VE ELMAS MODELI ÜZERINE BIR DEĞERLENDIRME

    Directory of Open Access Journals (Sweden)

    Murat KOC

    2014-07-01

    Full Text Available Günümüzde, rekabet kavramı daha çok firma düzeyinde bir kavram olmakla beraber, artık ulusal düzeyde de ele alınmaya başlanmıştır. Rekabet şartlarının değişken bir yapı içerisinde olması ve yaşanan küreselleşme, bir ulusun rekabet üstünlüğünün analiz edilebilmesi açısından yeni yöntemlerin uygulanması gerekliliğini ortaya koymuştur. Bu kapsamda Michael E. Porter, kapsamlı bir araştırma niteliği taşımakta olan, Elmas Modeli (Diamond Model’ni ortaya koymuştur. “Bazı ulusların neden diğerlerine göre belirli sektörlerde daha rekabetçi olduğu” sorusuna yanıt vermeye çalışılan model, belirli bir sektörde ulusal rekabet gücünü belirleyen bazı unsurların birbirleriyle ilişkili olarak incelenmesini öngörmektedir. Bu çalışmanın amacı, ulusların rekabet üstünlüğü sağlamasında Porter’ın literatüre kazandırdığı “Elmas Modeli” yaklaşımının değerlendirilmesi ve modele yönelik eleştirilerin ortaya konulmasıdır.

  9. DNA replication in ultraviolet light irradiated Chinese hamster cells: the nature of replicon inhibition and post-replication repair

    International Nuclear Information System (INIS)

    Doniger, J.

    1978-01-01

    DNA replication in ultraviolet light irradiated Chinese hamster cells was studied using techniques of DNA fiber autoradiography and alkaline sucrose sedimentation. Bidirectionally growing replicons were observed in the autoradiograms independent of the irradiation conditions. After a dose of 5 J/m 2 at 254 nm the rate of fork progression was the same as in unirradiated cells, while the rate of replication was reduced by 50%. After a dose of 10J/m 2 the rate of fork progression was reduced 40%, while the replication rate was only 25% of normal. Therefore, at low doses of ultraviolet light irradiation, the inhibition of DNA replication is due to reduction in the number of functioning replicons, while at higher doses the rate of fork progression is also slowed. Those replicons which no longer function after irradiation are blocked in fork movement rather than replicon initiation. After irradiation, pulse label was first incorporated into short nascent strands, the average size of which was approximately equal to the distance between pyrimidine dimers. Under conditions where post-replication repair occurs these short strands were eventually joined into larger pieces. Finally, the data show that slowing post-replication repair with caffeine does not slow fork movement. The results presented here support the post-replication repair model of 'gapped synthesis' and rule out a major role for 'replicative bypass'. (author)

  10. Atipik Özellikler Gösteren Akut Enflamatuvar Polinöropatili Bir Olgu

    Directory of Open Access Journals (Sweden)

    Sule Aydin Turkoglu

    2016-01-01

    Full Text Available Bilateral fasiyal paralizi, ilerleyici kas güçsüzlüğü ve elektrofizyolojik değerlendirmede akut motor aksonal polinöropati bulguları gösteren bir olgu sunulmaktadır. Öncesinde karın ağrısı, ishal ve grip benzeri şikayetlere sonrasında otonom anormallikler, görsel halüsinasyon epizotları, konuşma bozukluğu eklendi. Campylobacter jejuni enfeksiyonu, Lyme hastalığı ve porfiri ayırıcı tanısı yapıldı. Western-blot testi Lyme hastalığı birlikteliğini doğruladı. Ek olarak porfirine spesifik testler pozitif bulundu.

  11. Hepatit A Enfeksiyonu Sonrası Gelişen Bir Guillian-Barre Sendromu Olgusu+

    OpenAIRE

    Özışık, Handan Işın; Kızkın, Sibel; Çalışkan, Özden; Özcan, Cemal

    2002-01-01

    Guillian-Barre Sendromu ile enfeksiyon hastalıkları arasındaki ilişki iyi bilinmektedir. Hepatit A enfeksiyonu sırasında GBS gelişimi ender görülen bir tablodur. Hepatit A enfeksiyonuna bağlı olarak gelişen GBS'lu olgular gözden geçirildiğinde bazı ortak klinik özellikleri saptanmıştır. Bunlar: 1- Erkeklerde daha sık olması 2- Hepatit A enfeksiyonundan ortalama 14 gün sonra gelişmesi 3- Fasiyal sinir ve bulbar tutulumun sık olması 4- Yüzeyel duyu bozukluklarına ek olarak p...

  12. Replication stress-induced chromosome breakage is correlated with replication fork progression and is preceded by single-stranded DNA formation.

    Science.gov (United States)

    Feng, Wenyi; Di Rienzi, Sara C; Raghuraman, M K; Brewer, Bonita J

    2011-10-01

    Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or "collapsed" replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.

  13. Pengaruh Lama Perendaman dan Jenis Minuman Beralkohol Bir dan Tuak terhadap Kekerasan Email Gigi Manusia (In Vitro

    Directory of Open Access Journals (Sweden)

    Malida Magista

    2014-06-01

    Full Text Available Erosi gigi merupakan hilangnya lapisan email gigi karena asam. Jenis asam, pH rendah, serta kandungan kalsium, fosfat, dan fluoride pada bir dan tuak diduga merupakan faktor kimiawi penyebab erosi gigi. Tujuan penelitian ini untuk mengetahui pengaruh lama perendaman dan jenis minuman beralkohol bir dan tuak terhadap kekerasan email gigi manusia (in vitro. Penelitian ini menggunakan 14 sampel gigi premolar pertama atas. Setiap gigi dibagi menjadi 2 bagian, bukal dan palatal. kemudian dibagi menjadi 7 kelompok perlakuan, yaitu kelompok (A1 perendaman dalam bir (ringan; (A2 kelompok perendaman dalam bir sedang; kelompok (A3 perendaman dalam bir berat, kelompok (B1: perendaman dalam tuak ringan, (B2: perendaman dalam tuak sedang, (B3: perendaman dalam tuak berat dan kelompok kontrol (C. Uji kekerasan email gigi dilakukan menggunakan Micro Vickers Hardness Tester. Pengujian kekerasan awal email gigi dilakukan sebelum perendaman gigi. Perendaman gigi premolar pertama atas pada bir dan tuak dilakukan selama 10 detik, 50 detik, dan 250 detik perhari dengan penyimpanan subjek penelitian pada saliva buatan. Uji kekerasan akhir email gigi dilakukan setelah perlakuan selama 30 hari. Nilai perubahan kekerasan email gigi merupakan selisih nilai kekerasan akhir dan nilai kekerasan awal email gigi. Sebagai tambahan data, pada bir dan tuak juga diukur kandungan pH, kalsium, dan fosfor. Data dianalisis menggunakan uji ANAVA dua jalur dilanjutkan dengan uji LSD. Hasil analisis ANAVA dua jalur menujukkan bahwa jenis minuman dan lama perendaman berpengaruh bermakna terhadap kekerasan email gigi (p<0,05. Hasil uji LSD menunjukkan adanya perbedaan rerata yang signifikan (p<0,05 antar kelompok uji bir dan tuak. Kesimpulan dari penelitian ini adalah terdapat pengaruh jenis minuman beralkohol bir dan tuak dan lama perendaman terhadap kekerasan email gigi manusia (in vitro. The Effect Of Contact Time And Alcohol Beverages Beer And Tuak On Human Dental Enamel Hardness (In

  14. Lattice gas simulations of replicating domains

    International Nuclear Information System (INIS)

    Dawson, S.P.; Hasslacher, B.; Pearson, J.E.

    1993-01-01

    We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting

  15. Lattice gas simulations of replicating domains

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, S.P.; Hasslacher, B.; Pearson, J.E.

    1993-12-31

    We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting.

  16. Oxidation mechanisms occurring in wines

    OpenAIRE

    Oliveira, Carla Maria; Ferreira, António César Silva; Freitas, Victor De; Silva, Artur M. S.

    2011-01-01

    The present review aims to show the state of the art on the oxidation mechanisms occurring in wines, as well as the methods to monitor, classify and diagnose wine oxidation. Wine oxidation can be divided in enzymatic oxidation and non-enzymatic oxidation. Enzymatic oxidation almost entirely occurs in grape must and is largely correlated with the content of hydroxycinnamates, such as caffeoyltartaric acid and paracoumaroyltartaric acid, and flavan-3-ols. Non-enzymatic oxidation, al...

  17. The use of multifrequency and polarimetric SIR-C/X-SAR data in geologic studies of Bir Safsaf, Egypt

    Science.gov (United States)

    Schaber, G.G.; McCauley, J.F.; Breed, C.S.

    1997-01-01

    Bir Safsaf, within the hyperarid 'core' of the Sahara in the Western Desert of Egypt, was recognized following the SIR-A and SIR-B missions in the 1980s as one of the key localities in northeast Africa, where penetration of dry sand by radar signals delineates previously unknown, sand-buried paleodrainage valleys ('radar-rivers') of middle Tertiary to Quaternary age. The Bir Safsaf area was targeted as a focal point for further research in sand penetration and geologic mapping using the multifrequency and polarimetric SIR-C/X-SAR sensors. Analysis of the SIR-C/X-SAR data from Bir Safsaf provides important new information on the roles of multiple SAR frequency and polarimetry in portraying specific types of geologic units, materials, and structures mostly hidden from view on the ground and on Landsat TM images by a relatively thin, but extensive blanket of blow sand. Basement rock units (granitoids and gneisses) and the fractures associated with them at Bir Safsaf are shown here for the first time to be clearly delineated using C- and L-band SAR images. The detectability of most geologic features is dependent primarily on radar frequency, as shown for wind erosion patterns in bedrock at X-band (3 cm wavelength), and for geologic units and sand and clay-filled fractures in weathered crystal-line basement rocks at C-band (6 cm) and L-band (24 cm). By contrast, Quaternary paleodrainage channels are detectable at all three radar frequencies owing, among other things, to an usually thin cover of blow sand. The SIR-C/X-SAR data investigated to date enable us to make specific recommendations about the utility of certain radar sensor configurations for geologic and paleoenvironmental reconnaissance in desert regions.Analysis of the shuttle imaging radar-C/X-synthetic aperture radar (SIR-C/X-SAR) data from Bir Safsaf provides important new information on the roles of multiple SAR frequency and polarimetry in portraying specific types of geologic units, materials, and

  18. Türkiye’de Sosyal Demokratların Avrupa Birliği’ne Yaklaşımları

    OpenAIRE

    ERDEM, Seçil

    2008-01-01

    Türkiye ve Avrupa Birliği arasındaki ilişkiler ve bu süreci ilgilendiren güncel gelişmeler Türkiye’deki ekonomik, siyasal ve toplumsal dinamikler üzerinde doğrudan ve dolaylı etkileri olan önemli konulardır. Bu bağlamda Avrupa Birliği, Türkiye’deki politik tartışmaların da önemli bir konusu haline gelmiştir. Bu çalışma, Türk Sosyal Demokrasi Hareketi çerçevesi içindeki çeşitli politik unsurların Türkiye-Avrupa Birliği ilişkilerinin belirlenmesi sürecindeki rolleri ve yaklaşımlarını analiz etm...

  19. DNA replication after mutagenic treatment in Hordeum vulgare.

    Science.gov (United States)

    Kwasniewska, Jolanta; Kus, Arita; Swoboda, Monika; Braszewska-Zalewska, Agnieszka

    2016-12-01

    The temporal and spatial properties of DNA replication in plants related to DNA damage and mutagenesis is poorly understood. Experiments were carried out to explore the relationships between DNA replication, chromatin structure and DNA damage in nuclei from barley root tips. We quantitavely analysed the topological organisation of replication foci using pulse EdU labelling during the S phase and its relationship with the DNA damage induced by mutagenic treatment with maleic hydrazide (MH), nitroso-N-methyl-urea (MNU) and gamma ray. Treatment with mutagens did not change the characteristic S-phase patterns in the nuclei; however, the frequencies of the S-phase-labelled cells after treatment differed from those observed in the control cells. The analyses of DNA replication in barley nuclei were extended to the micronuclei induced by mutagens. Replication in the chromatin of the micronuclei was rare. The results of simultanous TUNEL reaction to identify cells with DNA strand breaks and the labelling of the S-phase cells with EdU revealed the possibility of DNA replication occurring in damaged nuclei. For the first time, the intensity of EdU fluorescence to study the rate of DNA replication was analysed. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Dynamics of picornavirus RNA replication within infected cells

    DEFF Research Database (Denmark)

    Belsham, Graham; Normann, Preben

    2008-01-01

    Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks the initiat......Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks...... the initiation of negative-strand synthesis. We have now examined the dynamics of RNA replication, measured by quantitative RT-PCR, within cells infected with either swine vesicular disease virus (an enterovirus) or foot-and-mouth disease virus as regulated by the presence or absence of guanidine. Following...... the removal of guanidine from the infected cells, RNA replication occurs after a significant lag phase. This restoration of RNA synthesis requires de novo protein synthesis. Viral RNA can be maintained for at least 72 h within cells in the absence of apparent replication but guanidine-resistant virus can...

  1. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

  2. FBH1 Catalyzes Regression of Stalled Replication Forks

    Directory of Open Access Journals (Sweden)

    Kasper Fugger

    2015-03-01

    Full Text Available DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA double-strand break formation. Furthermore, FBH1-dependent signaling promotes checkpoint control and preserves genome integrity. We propose a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks.

  3. Tüketim kültüründe etkili bir araç olarak reklamın işlevlerine dair genel bir değerlendirme

    OpenAIRE

    Elmasoğlu, Kamile

    2017-01-01

    Betimsel analiz yönteminin kullanıldığı bu çalışmada, tüketim kültürünün yayılmasında etkili bir araç olarak görülen reklamın rolüne dair genel bir değerlendirme sunmak hedeflenmektedir. Bu hedef dâhilinde, tüketim toplumu, tüketim kültürü ve reklamın tüketim kültürü içindeki işlevleri; çeşitli düşünürlerin görüşlerinden istifade edilerek tartışılmıştır. Tüketim kültürünün hakim olduğu bir toplumda reklama ilişkin çeşitli fikirlerin benimsendiği görülmektedir. Çalışma genel olarak değerlendir...

  4. Yoğun Bakımda Hafif Şiddetli Bir Propofol İnfüzyon Sendromu

    OpenAIRE

    Tezcan, Aysu Hayriye; Oterkus, Mesut; Donmez, Ilksen; Ozturk, Omur; Yavuzekinci, Zeynep

    2018-01-01

    Propofol infüzyon sendromu (PRİS) nadir ama ölümcül bir hastalıktır. Bu sendrom çoğunlukla ilacın yüksek dozda uzun süreli infüzyonundan sonra oluşur. Metabolik asidoz, hipotansiyon, miyoglobinüri, artmış karaciğer ve kas enzimleri, kardiyak aritmiler ve kalp durması sendromun genel özellikleridir. Bu olgu sunumunda uzun süreli düşük doz (25–50 mcg/kg/dk) ilaç infüzyonundan sonra ortaya çıkan hafif tipte bir PRİS tartışılmıştır. Bu olguda ilaç infüzyonu esnasında ciddi metabolik asidoz, hipot...

  5. Hepatit A'ya Bağlı Guillain-Barre Sendromu: Nadir Bir Birliktelik

    OpenAIRE

    Canpolat, Mehmet; Ceylan, Özgür; Çelik, İlknur; Bayram, Ayşe Kaçar; Per, Hüseyin; Doğanay, Selim; Gümüş, Hakan; Aslan, Duran; Kumandaş, Sefer

    2015-01-01

    Guillain Barre Sendromu (GBS), çocukluktan ileri yaşlara kadar her yaş grubunda rastlanabilen, akut başlangıçlı, simetrik ve jeneralize kas güçsüzlüğü, arefleksi ve periferik sinirlerin inflamatuvar demyelinizasyonu ile karakterize bir hastalıktır. GBS 'un patogenezi net olarak bilinmemekle birlikte otoimmun bir hastalık olduğu düşünülmektedir. Guillian-Barre Sendromu(GBS) ile enfeksiyon hastalıkları arasındaki ilişki iyi bilinmektedir. Hepatit A enfeksiyonu sırasında GBS gelişimi nadir ...

  6. Türkiye İçin Gümrük Birliği’ne Alternatif Bir Pazar: İslam İşbirliği Teşkilatı / An Alternative Market to European Union for Turkey: The Organization of Islamic Cooperation

    Directory of Open Access Journals (Sweden)

    Hayrettin Kesgingöz

    2018-03-01

    Full Text Available Abstract Increasing competition in the world by the help of globalization has directed countries to cooperation with other countries and interregional organizations. Nowadays competition in foreign trade is becoming more and more challenging due to globalization process and countries use the most important alternatives, economic integrations to export and import. The new idea of creating new regional alternatives to increase foreign trade for Turkey is becoming more important day by day. Organization of Islamic Cooperation (OIC which is being created under the leadership of Turkey has an important share on Turkish foreign trade after G20, OECD and Customs Union. Though OIC has occupied an important place in Turkish foreign trade it is least known and this study searches whether OIC can become an alternative in future. In order to answer this question, the performance analysis of foreign trade was conducted with the help of macroeconomic indicators while the analysis of foreign trade compliance was held with the help of international foreign trade indices. As a result of foreign trade compliance analysis it is concluded that importance of Organization of Islamic Cooperation is increasing every day. Though foreign trade between Turkey and Customs Union reduced, foreign trade between Turkey and OIC increased and that result shows that Turkey turns his face to markets of OIC. However foreign trade between Turkey and OIC can just be alternative to Custom union in further years.   Öz Küreselleşmeyle birlikte dünyada artan rekabet ortamı 2008 küresel ekonomik krizinden sonra dünya ülkelerini ülkeler ve bölgeler arası işbirliğine doğru yöneltmiştir. Küreselleşme sürecinde dış ticarette rekabetin her geçen gün zorlaştığı bir dönemde bugün ülkeler, dış ticareti gerçekleştirmek için en önemli seçenekleri olan ülkeler ve bölgesel arası ekonomik bütünleşmeleri kullanmaktadırlar. Yeni yeni bölgesel ekonomik b

  7. Kayseri İlinin Gastronomi Turizmine Yönelik Bir SWOT Analizi Çalışması

    Directory of Open Access Journals (Sweden)

    Doç. Dr. Taşkın DENİZ

    2017-09-01

    Full Text Available Kayseri ili tarihi, kültürel ve doğal güzellikleri ile yüksek bir turizm potansiyeline sahiptir. Binlerce yıllık geçmişe sahip bir yerleşim merkezi olan Kayseri, farklı özelliklere sahip çok sayıda kültüre ev sahipliği yapması sebebi ile adeta bir kültür beşiği durumundadır. Söz konusu kültürel zenginliğin yansıması Kayseri mutfağında ve geleneksel lezzetlerinde de kendisini göstermektedir. Bu araştırmada literatür araştırması kapsamında Kayseri ilinin SWOT analizi ve Kayseri mutfağının gastronomi ürünleri açısından bir değerlendirilmesi yapılmış, Kayseri ilin gastronomi turizmi potansiyeli hakkında görüşler ortaya konmuştur. Elde edilen sonuçlara göre, Kayserinin rakipleri arasında rekabet avantajı kazanmak, marka haline gelmek ve yerel ekonomiye katkıda bulunmak için gastronomi turizminden elde ettiği payı arttırması gerektiği tespit edilmiştir.

  8. Kosovo albaanlaste imelootus hääbub läbirääkimiste kiuste / Triin Oppi

    Index Scriptorium Estoniae

    Oppi, Triin

    2007-01-01

    Serbia ja Kosovo provintsi esindajate läbirääkimistest Viinis ning ÜRO esindaja Martti Ahtisaari ettepanekust Kosovo suhtes, kus välditakse sõna "iseseisvus". Euroopa Liit üritab Kosovot juhtida iseseisvuse teele, pakkudes Serbiale võimalust mitte anda välja Haagi sõjatribunalile Ratko Mladicit. Vt. samas: Kosovo äärmuslased õhkisid kolm ÜRO sõidukit. Kaart

  9. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  10. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  11. Hz. Peygamber Dönemi Eğitimine Genel Bir Bakış

    Directory of Open Access Journals (Sweden)

    Yasin Yılmaz

    2015-11-01

    Full Text Available Allah'a inanan güzel ahlakla teçhiz edilen erdemli bir toplum oluşturmayı amaçlayan Hz. Peygamber için bunu gerçekleştirmede, ilim, eğitim ve öğretim bir hayat felsefesi olmuştur. Buna paralel olarak onun çalışmalarında ve sözlerinde bilgi, öğrenme, öğretme, öğrenci ve öğretmene büyük önem verildiği görülmektedir. İnsanIarın karanlıktan aydınlığa çıkması için bütün imkanları kullanmıştır. Ancak Hz. Peygamber'in yaptığı eğitim ve öğretimi kendi döneminin sosyal ve fiziki şartları, ihtiyaçları ve metotları çerçevesinde gerçekleştirdiğini unutmamak gerekir. Dönemin şartlarının, imkanlarının ve olumsuzluklarının çok fazla olmasına rağmen, Hz.Peygamber'in eğitim ve öğretim konusunda bugün dahi geçerliliğini koruyan evrensel nitelikteki uygulamaları bizim için çok önemlidir. Modem çağların insanlarının olan günümüz insanlarının onun eğitim ve öğretim sisteminden istifade edeceği çok yönlerin olduğu kanaatindeyim

  12. Turist Rehberlerinin Liderlik Yönelimlerinin Belirlenmesine Yönelik Bir

    Directory of Open Access Journals (Sweden)

    Mehmet Teoman TÜRKMEN

    2017-07-01

    Full Text Available Turist rehberlerinin, turistlerin yabancı oldukları kültürle temasları sürecinde bilgi verici, yorumcu, tercüman, danışman ve aracı gibi çok sayıda rolleri bulunmaktadır. Bu rolleri ile rehberler, turistik deneyimin olumlu ya da olumsuz neticelenmesinde doğrudan etkilidirler. Rehberlerin tüm rollerinin başarılı bir şekilde ifa edilmesinde kilit öneme sahip rol ise, gruba hâkimiyet süreçlerini içeren liderlik rolüdür. Bu noktada, turist rehberlerinin liderlik rollerinin, turistin kaliteli hizmet almasında ve en nihai sonuç olarak turizmin hedeflenen amaçlarına ulaşmasında önemli bir etken olduğunu söylemek mümkündür. Çalışmada turist rehberlerinin liderlik yönelimleri ve liderlik yönelimleri ile demografik özellikleri arasındaki ilişki incelenmiştir. Turist rehberlerine uygulanan anketlerle elde edilen veriler istatiksel analizler aracılığıyla değerlendirilmiştir. Araştırma sonucunda turist rehberlerinin genel olarak göreve yönelik liderlik davranışlarını benimsediği ortaya çıkmıştır. Ayrıca koşulların gerekliliğine göre görevi ya da ilişkileri ön planda tutmayı gerektiren değişim davranışı, rehberlerin en az tercih ettikleri liderlik davranışı olduğu tespit edilmiştir.

  13. Personality and Academic Motivation: Replication, Extension, and Replication

    Science.gov (United States)

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  14. Naturally Occurring Radioactive Materials (NORM)

    International Nuclear Information System (INIS)

    Gray, P.

    1997-01-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training)

  15. Naturally Occurring Radioactive Materials (NORM)

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P. [ed.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  16. Naturally occurring radionuclides in food

    International Nuclear Information System (INIS)

    Djujic, I.

    1995-01-01

    The naturally occurring radionuclides are the major source of radiation exposure to humans. The principal way of natural radiation exposure is the inhalation of 222 Rn decay products (about 85% of the total). The remainder is equally divided between internally deposited radionuclides, cosmic and terrestrial sources. In the present study, the content of 40 K, 210 Pb, 226 Ra, 230 Th, 232 Th and 238 U in representative food samples (milk, pork, beef, potatoes, wheat and corn flour) and samples of different food items that do not represent entire national production but provide interesting additional data for approximative calculation of naturally occurring radionuclide intake is presented. Daily weight of food eaten, participation of food groups, as well as daily intake by food of mentioned naturally occurring radionuclides in the Serbian diet was obtained on the base of house hold budget surveys. The result obtained for daily intake estimates in mBq for Serbian population are 78.1 ( 40 K), 38.2( 210 Pb), 52.3( 226 Ra), 2.0( 230 Th) and 12.5( 238 U). (author)

  17. An Evaluation on Library Cooperation in Turkey Türkiye'de Kütüphanelerarası İşbirliği Üzerine Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    Mehmet Emin Küçük

    2004-06-01

    Full Text Available No library in the world has the sufficient budget, space, and professionals to acquire all existing information sources, and to organise and serve the acquired materials. For this reason, libraries cooperate in collection development, cata loguing, providing access to the others' collections and document delivery. Aiming at evaluating the co-operation efforts during the Republican era from the perspective of the historical, organisational and practicable fields of implementation, this paper examines the library co-operation in Turkey. To determine the present situation, the Turkish National Library, General Directorate of Libraries and Publications, National Academic Network and Information Centr, and some special and school libraries in Ankara, Ministry of National Education, university libraries, consortia, and professional associations are examined, and the data gathered from literature and interviews are evaluated. In conclusion, it has been observed that in recent years, co-operation effort has gained momentum, two consortia have emerged to provide access to the electronic information sources, document delivery projects between university libraries have been started, but efforts in some practicable fields of co-operation, such as preparing union catalogues, sharing bibliographic data, and developing authority files have been unsuccessful. It has also been observed that there is lack of co-operation except among university libraries, and that institutions have failed in establishing a "common wisdom" and consequently in developing the skills of planning and organisation. Inadequacy of resources, legislation, and infrastructure, and most importantly the lack of dedication resulted in discontinuity of the ongoing projects and the production of the new ones. Dünyadaki hiç bir kütüphane varolan tüm bilgi kaynaklarını sağlama, düzenleme ve hizmete sunmada yeterli bütçe, bina ve profesyonele sahip değildir. Bu nedenle k

  18. Chameleon Chasing II: A Replication.

    Science.gov (United States)

    Newsom, Doug A.; And Others

    1993-01-01

    Replicates a 1972 survey of students, educators, and Public Relations Society of America members regarding who the public relations counselor really serves. Finds that, in 1992, most respondents thought primary responsibility was to the client, then to the client's relevant publics, then to self, then to society, and finally to media. Compares…

  19. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  20. Adressing Replication and Model Uncertainty

    DEFF Research Database (Denmark)

    Ebersberger, Bernd; Galia, Fabrice; Laursen, Keld

    innovation survey data for France, Germany and the UK, we conduct a ‘large-scale’ replication using the Bayesian averaging approach of classical estimators. Our method tests a wide range of determinants of innovation suggested in the prior literature, and establishes a robust set of findings on the variables...

  1. Replication of kinetoplast minicircle DNA

    International Nuclear Information System (INIS)

    Sheline, C.T.

    1989-01-01

    These studies describe the isolation and characterization of early minicircle replication intermediates from Crithidia fasciculata, and Leishmania tarentolae, the mitochondrial localization of a type II topoisomerase (TIImt) in C. fasciculata, and the implication of the aforementioned TIImt in minicircle replication in L. tarentolae. Early minicircle replication intermediates from C. fasciculata were identified and characterized using isolated kinetoplasts to incorporate radiolabeled nucleotides into its DNA. The pulse-label in an apparent theta-type intermediate chase into two daughter molecules. A uniquely gapped, ribonucleotide primed, knotted molecule represents the leading strand in the model proposed, and a highly gapped molecule represents the lagging strand. This theta intermediate is repaired in vitro to a doubly nicked catenated dimer which was shown to result from the replication of a single parental molecule. Very similar intermediates were found in the heterogeneous population of minicircles of L. tarentolae. The sites of the Leishmania specific discontinuities were mapped and shown to lie within the universally conserved sequence blocks in identical positions as compared to C. fasciculata and Trypanosoma equiperdum

  2. Manual of Cupule Replication Technology

    Directory of Open Access Journals (Sweden)

    Giriraj Kumar

    2015-09-01

    Full Text Available Throughout the world, iconic rock art is preceded by non-iconic rock art. Cupules (manmade, roughly semi-hemispherical depressions on rocks form the major bulk of the early non-iconic rock art globally. The antiquity of cupules extends back to the Lower Paleolithic in Asia and Africa, hundreds of thousand years ago. When one observes these cupules, the inquisitive mind poses so many questions with regard to understanding their technology, reasons for selecting the site, which rocks were used to make the hammer stones used, the skill and cognitive abilities employed to create the different types of cupules, the objective of their creation, their age, and so on. Replication of the cupules can provide satisfactory answers to some of these questions. Comparison of the hammer stones and cupules produced by the replication process with those obtained from excavation can provide support to observations. This paper presents a manual of cupule replication technology based on our experience of cupule replication on hard quartzite rock near Daraki-Chattan in the Chambal Basin, India.

  3. Bir Felaketin Anatomisi Bazar de La Charite Yangını

    Directory of Open Access Journals (Sweden)

    Anıl Özgüç

    2011-12-01

    Full Text Available Bazar de la Charite, 1885 yılında Katolik Fransız Aristokratlan tarafından yardım ve hayır amacıyla Paris'de kurulmuştur. 1897 yılında yangına kadar yıllık bir organizasyon olarak varlığını sürdürmüştür. Yangında çoğu aristokrat 126 kişi hayatmı kaybetmiştir. Yangının ardından 30 ceset yakınlan tarafından teşhis edilememiş, kimliklendirme amacıyla diş hekimlerine başvurulmuştur. Dr. Oscar Amoedo'nun yürüttüğü çalışmalann sonucunda teşhis edilemeyen cesetler kimliklendirilmiştir. Dr. Oscar Amoedo, yangın sonrası kimliklendirmede diş hekimlerinin rolünü anlatan makalesi ve ardından yayınladığı “L'Art dentaire en Medecine Legale” adlı kitabıyla adli odontolojinin temellerini kurmuştur. Anahtar kelimeler: Bazar de la Charite, adli odontoloji, yangın, Paris

  4. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  5. Replicative intermediates in UV-irradiated Simian virus 40

    International Nuclear Information System (INIS)

    Clark, J.M.; Hanawalt, P.C.

    1984-01-01

    The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)

  6. Early occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.

    1985-01-01

    This chapter deals with health-risk estimates for early and continuing effects of exposure to ionizing radiations that could be associated with light water nuclear power plants accidents. Early and continuing effects considered are nonneoplastic diseases and symptoms that normally occur soon after radiation exposure, but may also occur after years have passed. They are generally associated with relatively high (greater than 1 Gy) doses. For most of the effects considered, there is a practical dose threshold. Organs of primary interest, because of their high sensitivity or the likelihood of receiving a large radiation dose, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. In utero exposure of the fetus is also considered. New data and modeling techniques available since publication of the Reactor Safety Study (WASH 1400, 1975) were used along with data cited in the Study to develop improved health-risk models for morbidity and mortality. The new models are applicable to a broader range of accident scenarios, provide a more detailed treatment of dose protraction effects, and include morbidity effects not considered in the Reactor Safety Study. 115 references, 20 figures, 19 tables

  7. Naturally-occurring alpha activity

    Energy Technology Data Exchange (ETDEWEB)

    Mayneord, W V

    1960-12-01

    In view of the difficulties of assessing the significance of man-made radioactivity it is important to study for comparison the background of natural radioactivity against which the human race has evolved and lives. It is also important to define the present levels of activity so that it will be possible to detect and study as quickly as possible any changes which may occur owing to the release into the environment of new radioactive materials. Moreover, by the study of the behaviour of natural radioactivity light may be shed upon that of the artificially produced isotopes and a number of analogies traced between the two groups. These concepts have led to studies of naturally-occurring radioactive materials alongside a programme of research into fission products in food, water and air, as well as studies of the metabolism of both sets of materials in the human body. Since the last report there has been a useful increase in our knowledge of natural radioactivity in the biosphere, and its levels relative to the new man-made activities. These studies have necessitated technical developments, particularly in the methods of measuring and identifying alpha-ray emitters, to which group many of the more important natural radioactive materials belong.

  8. XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell

    Directory of Open Access Journals (Sweden)

    Chao Huang

    2017-01-01

    Full Text Available Abstract Background The X-linked inhibitor of apoptosis protein (XIAP is a well-known potent apoptosis suppressor and also participates in cancer cell biological behaviors, therefore attracting great attentions as a potential antineoplastic therapeutic target for past years. Anti-IAP therapy is reported to be closely related to epidermal growth factor receptor (EGFR expression level. However, whether and how XIAP modulates EGFR expression remains largely unknown. Methods Human XIAP was knockdown with short-hairpin RNA in two different bladder cancer cell lines, T24T and UMUC3. Two XIAP mutants, XIAP ∆BIR (deletion of N-terminal three BIR domains and XIAP ∆RING (deletion of C-terminal RING domain and keeping the function of BIR domains, were generated to determine which domain is involved in regulating EGFR. Results We found here that lacking of XIAP expression resulted in a remarkable suppression of EGFR expression, consequently leading to the deficiency of anchorage-independent cell growth. Further study demonstrated that BIR domain of XIAP was crucial for regulating the EGFR translation by suppressing the transcription and expression of miR-200a. Mechanistic studies indicated that BIR domain activated the protein phosphatase 2 (PP2A activity by decreasing the phosphorylation of PP2A at Tyr307 in its catalytic subunit, PP2A-C. Such activated PP2A prevented the deviant phosphorylation and activation of MAPK kinases/MAPKs, their downstream effector c-Jun, and in turn inhibiting transcription of c-Jun-regulated the miR-200a. Conclusions Our study uncovered a novel function of BIR domain of XIAP in regulating the EGFR translation, providing significant insight into the understanding of the XIAP overexpression in the cancer development and progression, further offering a new theoretical support for using XIAP BIR domain and EGFR as targets for cancer therapy.

  9. Naturally occurring methyl salicylate glycosides.

    Science.gov (United States)

    Mao, Ping; Liu, Zizhen; Xie, Meng; Jiang, Rui; Liu, Weirui; Wang, Xiaohong; Meng, Shen; She, Gaimei

    2014-01-01

    As an important part of non steroids anti-inflammation drug (NSAIDs), salicylate has developed from natural substance salicylic acid to natrium salicylicum, to aspirin. Now, methyl salicylate glycoside, a new derivative of salicylic acid, is modified with a -COOH group integrated one methyl radical into formic ether, and a -OH linked with a monosaccharide, a disaccharide or a trisaccharide unit by glycosidic linkage. It has the similar pharmacological activities, anti-inflammatory, analgesic, antipyretic and antithrombotic as the previous salicylates' without resulting in serious side effects, particularly the gastrointestinal toxicity. Owing to the superiority of those significant bioactivities, methyl salicylate glycosides have became a hot research area in NSAIDs for several years. This paper compiles all 9 naturally occurring methyl salicylate glycosides, their distribution of the resource and pharmacological mechanism, which could contribute to the new drug discovery.

  10. Once Upon A Time There Was Ana Mendieta / Bir Ana Mendieta Varmış, Bir Ana Mendieta Yokmuş

    Directory of Open Access Journals (Sweden)

    Nur BALKIR

    2018-04-01

    search of her physical and spiritual presence. Mendieta’s questioning and dissecting of such presence and her raced and gendered self requires an existential exploration. This paper will examine Mendieta’s approach through concepts of phenomenologists Heidegger’s existential space and Merleau Ponty’s ‘lived body’, which describes the roles of sensation in perception. Furthermore, Mendieta’s works will be compared to the works of Marcel Duchamp, Frida Kahlo and Rachel Whiteread on the basis of shared concepts. [TR: 8 Eylül 1985’te New York’taki Soho polis departmanı bir acil durum çağrısı aldı. Ünlü minimalist sanatçı Carl Andre, karısı Ana’nın, yaşadıkları apartmanın 34’üncü kat penceresinden düştüğünü söyleyerek yardım istiyordu. Yardım ekipleri ulaştığında Ana Mendieta’nın cansız bedenini New York Performans Sanatları Okulu’nun çaprazında buldu. Komşuları kısa süre önce onların dairesinden kavga sesleri duyduklarını söylüyorlardı. Mendieta’nın vücudundaki izlerden ve pencerenin konumundan yola çıkan polis, cinayetten şüphelenerek Andre’yi zanlı olarak gözaltına aldı. Davada, Andre’nin avukatları, sanatı ve hayat hikayesinden yola çıkarak Mendieta’nın intihara meyilli bir kişilik yapısı sergilediğini iddia ettiler. Mahkeme, Mendieta’nın intihar ettiğine, sanatına bakarak karar verdi. İronik biçimde, Mendieta’nın toprağı kazarak varlığa dönüştürdüğü “kendi”nden kalan boşluğu “intihara meyilli beden” ile doldurup kapattı. Sanatçının ölümü ve fiziki yokluğu, sanatının temel soruları olan zaman, mekan, beden, kimlik gibi kavramlar etrafından yorumlanarak ünlü “Silueta” serisinin altına, tabiri caizse serinin son işi olarak eklendi. Küba kökenli Amerikalı performans sanatçısı, heykeltraş, ressam ve video sanatçısı Ana Mendieta’nın yarattığı imgeler yeryüzü ve ruh arasında ilişkileri sorgularken, sevgi,

  11. Naturally occurring Vpr inhibitors from medicinal plants of Myanmar.

    Science.gov (United States)

    Win, Nwet Nwet; Ngwe, Hla; Abe, Ikuro; Morita, Hiroyuki

    2017-10-01

    Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.

  12. What occurred in the reactors

    International Nuclear Information System (INIS)

    Kudo, Kazuhiko

    2013-01-01

    Described is what occurred in the reactors of Fukushima Daiichi Nuclear Power Plant at the Tohoku earthquake and tsunami (Mar. 11, 2011) from the aspect of engineering science. The tsunami attacked the Plant 1 hr after the quake. The Plant had reactors in buildings no.1-4 at 10 m height from the normal sea level which was flooded by 1.5-5.5 m high wave. All reactors in no.1-6 in the Plant were the boiling water type, and their core nuclear reactions were stopped within 3 sec due to the first quake by control rods inserted automatically. Reactors in no.1-5 lost their external AC power sources by the breakdown and subsequent submergence (no.1-4) of various equipments and in no.1, 2 and 4, the secondary DC power was then lost by the battery death. Although the isolation condenser started to cool the reactor in no.1 after DC cut, its valve was then kept closed to heat up the reactor, leading to the reaction of heated Zr in the fuel tube and water to yield H 2 which was accumulated in the building: the cause of hydrogen explosion on 12th. The reactor in no.2 had the reactor core isolation cooling system (RCIC) which operated normally for few hrs, then probably stopped to heat up the reactor, resulting in meltdown of the core but no explosion occurred because of the opened door of the blowout panel on the wall by the blast of no.1 explosion. The reactor in no.3 had RCIC and high pressure coolant injection system, but their works stopped to result in the core damage and H 2 accumulation leading to the explosion on 14th. The reactor in no.4 had not been operated because of its periodical annual examination, but was explored on 15th, of which cause was thought to be due to backward flow of H 2 from no.3. Finally, the author discusses about this accident from the industrial aspect of the design of safety level (defense in depth) on international views, and problems and tasks given. (T.T.)

  13. The yeast replicative aging model.

    Science.gov (United States)

    He, Chong; Zhou, Chuankai; Kennedy, Brian K

    2018-03-08

    It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

  14. Replicator dynamics in value chains

    DEFF Research Database (Denmark)

    Cantner, Uwe; Savin, Ivan; Vannuccini, Simone

    2016-01-01

    The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...

  15. Replication confers β cell immaturity.

    Science.gov (United States)

    Puri, Sapna; Roy, Nilotpal; Russ, Holger A; Leonhardt, Laura; French, Esra K; Roy, Ritu; Bengtsson, Henrik; Scott, Donald K; Stewart, Andrew F; Hebrok, Matthias

    2018-02-02

    Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues.

  16. Chromatin replication and histone dynamics

    DEFF Research Database (Denmark)

    Alabert, Constance; Jasencakova, Zuzana; Groth, Anja

    2017-01-01

    Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate...... choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper...... organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure...

  17. DNA Copy-Number Control through Inhibition of Replication Fork Progression

    Directory of Open Access Journals (Sweden)

    Jared T. Nordman

    2014-11-01

    Full Text Available Proper control of DNA replication is essential to ensure faithful transmission of genetic material and prevent chromosomal aberrations that can drive cancer progression and developmental disorders. DNA replication is regulated primarily at the level of initiation and is under strict cell-cycle regulation. Importantly, DNA replication is highly influenced by developmental cues. In Drosophila, specific regions of the genome are repressed for DNA replication during differentiation by the SNF2 domain-containing protein SUUR through an unknown mechanism. We demonstrate that SUUR is recruited to active replication forks and mediates the repression of DNA replication by directly inhibiting replication fork progression instead of functioning as a replication fork barrier. Mass spectrometry identification of SUUR-associated proteins identified the replicative helicase member CDC45 as a SUUR-associated protein, supporting a role for SUUR directly at replication forks. Our results reveal that control of eukaryotic DNA copy number can occur through the inhibition of replication fork progression.

  18. Live Replication of Paravirtual Machines

    OpenAIRE

    Stodden, Daniel

    2009-01-01

    Virtual machines offer a fair degree of system state encapsulation, which promotes practical advances in fault tolerance, system debugging, profiling and security applications. This work investigates deterministic replay and semi-active replication for system paravirtualization, a software discipline trading guest kernel binar compatibility for reduced dependency on costly trap-and-emulate techniques. A primary contribution is evidence that trace capturing under a piecewise deterministic exec...

  19. Earl occurring and continuing effects

    International Nuclear Information System (INIS)

    Scott, B.R.; Hahn, F.F.

    1989-01-01

    This chapter develops health-risk models for early and continuing effects of exposure to beta or gamma radiation that could be associated with light water nuclear power plant accidents. The main purpose of the chapter is to provide details on each health-risk model and on the data used. Early and continuing effects considered are prodromal symptoms and nonneoplastic diseases that usually occur soon after a brief radiation exposure. These effects are generally associated with relatively high (greater than 1 Gy) absorbed organ doses. For most of the effects considered, there is an absorbed organ dose threshold below which no effects are seen. Some information is provided on health effects observed in victims of the Chernobyl power plant accident. Organs of primary interest, because of their high sensitivity or their potential for receiving large doses, are bone marrow, gastrointestinal tract, thyroid glands, lungs, skin, gonads, and eyes. Exposure of the fetus is also considered. Additional data and modeling techniques available since publication of the Reactor Safety Study were used to obtain models for morbidity and mortality

  20. Does overtraining occur in triathletes?

    Directory of Open Access Journals (Sweden)

    I Margaritis

    2003-06-01

    Full Text Available 1. Objective: Long distance triathlon training is characterized by considerably high volume training loads. This volume can provoke an overtraining state. The aim of the study was to determine whether overtraining occurs in well-trained male triathletes in relation with their volume training loads. 2. Experimental design: A questionnaire investigation was completed two days before the Nice long-distance triathlon (October 1995: 4-km swim, 120-km bike ride and 30-km run. 3. Participants: Ninety-three well-trained male triathletes who took part in the triathlon race. 4. Measures: A questionnaire to relate clinical symptoms, which are known to appear in case of overtraining, was collected. 5. Results: 39.8% of the questioned triathletes reported a decrease in triathlon performances within the last month preceding the race. Moreover, these triathletes exhibited significantly more overtraining-relied symptoms than the others (5.9±3.8 vs 3.4±2.6, P<0.05. Surprisingly, the occurrence of overtraining in triathletes appears not to depend on the volume training loads. 6. Conclusions: These results suggest that overtraining has to be considered in the case of triathletes. This preliminary study evidences the need for further investigation in order to monitor triathletes training respond and prevent overtraining.

  1. Christopher Nolan’ın ‘Batman Üçlemesi’ Üzerine İdeolojik Bir İnceleme

    OpenAIRE

    BÖLÜKBAŞI, Mustafa

    2013-01-01

    Bu makalede bir süperkahraman anlatısı olarak Batman’in nasıl bir ideolojik anlamı olduğu sorgulanmaktadır. Bu amaçlaChristopher Nolan’ın çekmiş olduğu Batman Başlıyor (2005), Kara Şövalye (2008) ve Kara Şövalye Yükseliyor (2012) filmleri,altında yatan ideolojiyi ortaya serecek bir içerik analizine tabi tutulmaktadır. Bu incelemede, “kötülük” ile mücadeleetmek için neden bir Batman yaratıldığı, bunun nasıl bir amacının olabileceği, Batman’e kimin ihtiyaç duyduğu, kısacasıNolan’ın Batman üçlem...

  2. Kamu Yönetiminde Bir Yönetişim Hedefi Olarak Kaynak Optimizasyonu: Kalkınma Ajanslarında COBIT-5 Çerçevesinde Bir Analiz

    Directory of Open Access Journals (Sweden)

    Ahmet Efe

    2016-01-01

    Full Text Available Kurumsal kaynak planlaması (ERP ve insan kaynakları yönetimi (HRM sistemleri sayesinde fiziki, beşeri, fikri ve mali kaynakların yönetimi gibi kavramlar, standartlar ve gerektirdikleri uygulamalar işletmecilik ve kamu yönetimi alanına girmiştir. Ancak kaynak optimizasyonu yaklaşımı ise ilk defa bir yönetişim hedefi ve süreci olarak yapılandırılması olarak COBİT-5 ile ortaya atılmıştır. Bu çalışmada kaynak optimizasyonu ile ilgili olarak Türkiye’de kalkınma ajansları (KA ve bölgesel gelişme dinamiklerinde yapılandırılmış bir yaklaşımın mevcut olmadığından dolayı Devlet Denetleme Kurulu (DDK tarafından belirlenmiş olan kurumsal sorunların çekirdek nedenleri araştırma problemi olarak ele alınmaktadır. COBIT-5 kaynak optimizasyonu ile ilgili modellemesinin KA dinamiklerine uyabilecek ve ilişkili kurumsal sorunları çözebilecek bir modellemenin olanaklı olduğu araştırmamızda iddia edilmektedir. Bu çerçevede yapılan analizler sonucunda kaynak optimizasyonu sürecinin KA dinamiklerinde nasıl işletilebileceği, kilit performans göstergeleri, kriter faaliyetler ile süreçlerde sorumlu, mesul, danışılan ve bilgilendirilen rollerin neler olduğu tespit edilmeye çalışılmaktadır.

  3. Naturally occurring flavonoids against human norovirus surrogates.

    Science.gov (United States)

    Su, Xiaowei; D'Souza, Doris H

    2013-06-01

    Naturally occurring plant-derived flavonoids are reported to have antibacterial, antiviral, and pharmacological activities. The objectives of this study were to determine the antiviral effects of four flavonoids (myricetin, L-epicatechin, tangeretin, and naringenin) on the infectivity of food borne norovirus surrogates after 2 h at 37 °C. The lab-culturable surrogates, feline calicivirus (FCV-F9) at titers of ~7 log₁₀ PFU/ml (high titer) or ~5 log₁₀ PFU/ml (low titer) and murine norovirus (MNV-1) at ~5 log₁₀ PFU/ml, were mixed with equal volumes of myricetin, L-epicatechin, tangeretin, or naringenin at concentrations of 0.5 or 1 mM, and incubated for 2 h at 37 °C. Treatments of viruses were neutralized in cell culture medium containing 10 % heat-inactivated fetal bovine serum, serially diluted, and plaque assayed. Each treatment was replicated thrice and assayed in duplicate. FCV-F9 (low titer) was not found to be reduced by tangeretin or naringenin, but was reduced to undetectable levels by myricetin at both concentrations. Low titer FCV-F9 was also decreased by 1.40 log₁₀ PFU/ml with L-epicatechin at 0.5 mM. FCV-F9 at high titers was decreased by 3.17 and 0.72 log₁₀ PFU/ml with myricetin and L-epicatechin at 0.5 mM, and 1.73 log10 PFU/ml with myricetin at 0.25 mM, respectively. However, MNV-1 showed no significant inactivation by the four tested treatments. The antiviral effects of the tested flavonoids are dependent on the virus type, titer, and dose. Further research will focus on understanding the antiviral mechanism of myricetin and L-epicatechin.

  4. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido

    2011-01-01

    The paper describes the state-of-the-art in replication of surface texture and topography at micro and nano scale. The description includes replication of surfaces in polymers, metals and glass. Three different main technological areas enabled by surface replication processes are presented......: manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

  5. Çelik Bir Bacanın Dinamik Davranışının Analizi

    OpenAIRE

    GÜRSOY, Gökhan; YERLİ, Hüseyin R.; KAÇIN, Selçuk

    2015-01-01

    Giderek artan endüstriyel tesislerin (termik ve nükleer santraller, demir çelik fabrikaları, değişik imalata yönelik fabrikalar) ihtiyacı olan endüstriyel bacalar için ülkemizde henüz bir standart bulunmamaktadır. Yine bu yapıların modellenmesi için paket programlar kullanılmakta ancak gerçek davranışı hakkında saha çalışmalarına gerek duyulmaktadır

  6. Monitoring Voltage-Dependent Charge Displacement of Shaker B-IR K+ Ion Channels Using Radio Frequency Interrogation

    OpenAIRE

    Dharia, Sameera; Rabbitt, Richard D.

    2011-01-01

    Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K(+) ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential a...

  7. Adenovirus sequences required for replication in vivo.

    OpenAIRE

    Wang, K; Pearson, G D

    1985-01-01

    We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...

  8. Parametrised Constants and Replication for Spatial Mobility

    DEFF Research Database (Denmark)

    Hüttel, Hans; Haagensen, Bjørn

    2009-01-01

    Parametrised replication and replication are common ways of expressing infinite computation in process calculi. While parametrised constants can be encoded using replication in the π-calculus, this changes in the presence of spatial mobility as found in e.g. the distributed π- calculus...... of the distributed π-calculus with parametrised constants and replication are incomparable. On the other hand, we shall see that there exists a simple encoding of recursion in mobile ambients....

  9. 36 CFR 910.64 - Replication.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.64 Replication. Replication means the process of using modern methods...

  10. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

  11. Variance Swap Replication: Discrete or Continuous?

    Directory of Open Access Journals (Sweden)

    Fabien Le Floc’h

    2018-02-01

    Full Text Available The popular replication formula to price variance swaps assumes continuity of traded option strikes. In practice, however, there is only a discrete set of option strikes traded on the market. We present here different discrete replication strategies and explain why the continuous replication price is more relevant.

  12. Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells.

    Science.gov (United States)

    Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

    2017-07-15

    Parvovirus B19 (B19V) infection is restricted to erythroid progenitor cells (EPCs) of the human bone marrow, leading to transient arrest of erythropoiesis and severe complications mainly in subjects with underlying hematological disorders or with immune system deficits. Currently, there are no specific antiviral drugs for B19V treatment, but identification of compounds inhibiting B19V replication can be pursued by a drug repositioning strategy. In this frame, the present study investigates the activity of hydroxyurea (HU), the only disease-modifying therapy approved for sickle cell disease (SCD), towards B19V replication in the two relevant cellular systems, the UT7/EpoS1 cell line and EPCs. Results demonstrate that HU inhibits B19V replication with EC 50 values of 96.2µM and 147.1µM in UT7/EpoS1 and EPCs, respectively, providing experimental evidence of the antiviral activity of HU towards B19V replication, and confirming the efficacy of a drug discovery process by drug repositioning strategy. The antiviral activity occurs in vitro at concentrations lower than those affecting cellular DNA replication and viability, and at levels measured in plasma samples of SCD patients undergoing HU therapy. HU might determine a dual beneficial effect on SCD patients, not only for the treatment of the disease but also towards a virus responsible for severe complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Dengue virus replicates and accumulates in Aedes aegypti salivary glands

    Energy Technology Data Exchange (ETDEWEB)

    Raquin, Vincent, E-mail: vincent.raquin@univ-lyon1.fr [Insect-Virus Interactions Group, Department of Genomes and Genetics, Institut Pasteur, 75015 Paris (France); Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris (France); Lambrechts, Louis, E-mail: louis.lambrechts@pasteur.fr [Insect-Virus Interactions Group, Department of Genomes and Genetics, Institut Pasteur, 75015 Paris (France); Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, 75015 Paris (France)

    2017-07-15

    Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors, mainly Aedes aegypti. DENV transmission requires viral dissemination from the mosquito midgut to the salivary glands. During this process the virus undergoes several population bottlenecks, which are stochastic reductions in population size that restrict intra-host viral genetic diversity and limit the efficiency of natural selection. Despite the implications for virus transmission and evolution, DENV replication in salivary glands has not been directly demonstrated. Here, we used a strand-specific quantitative RT-PCR assay to demonstrate that negative-strand DENV RNA is produced in Ae. aegypti salivary glands, providing conclusive evidence that viral replication occurs in this tissue. Furthermore, we showed that the concentration of DENV genomic RNA in salivary glands increases significantly over time, indicating that active replication likely replenishes DENV genetic diversity prior to transmission. These findings improve our understanding of the biological determinants of DENV fitness and evolution. - Highlights: •Strand-specific RT-qPCR allows accurate quantification of DENV (-) RNA in mosquito tissues. •Detection of DENV (-) RNA in salivary glands provides evidence of viral replication in this tissue. •Viral replication in salivary glands likely replenishes DENV genetic diversity prior to transmission.

  14. Dengue virus replicates and accumulates in Aedes aegypti salivary glands

    International Nuclear Information System (INIS)

    Raquin, Vincent; Lambrechts, Louis

    2017-01-01

    Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors, mainly Aedes aegypti. DENV transmission requires viral dissemination from the mosquito midgut to the salivary glands. During this process the virus undergoes several population bottlenecks, which are stochastic reductions in population size that restrict intra-host viral genetic diversity and limit the efficiency of natural selection. Despite the implications for virus transmission and evolution, DENV replication in salivary glands has not been directly demonstrated. Here, we used a strand-specific quantitative RT-PCR assay to demonstrate that negative-strand DENV RNA is produced in Ae. aegypti salivary glands, providing conclusive evidence that viral replication occurs in this tissue. Furthermore, we showed that the concentration of DENV genomic RNA in salivary glands increases significantly over time, indicating that active replication likely replenishes DENV genetic diversity prior to transmission. These findings improve our understanding of the biological determinants of DENV fitness and evolution. - Highlights: •Strand-specific RT-qPCR allows accurate quantification of DENV (-) RNA in mosquito tissues. •Detection of DENV (-) RNA in salivary glands provides evidence of viral replication in this tissue. •Viral replication in salivary glands likely replenishes DENV genetic diversity prior to transmission.

  15. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    KAUST Repository

    Knodel, Markus; Reiter, Sebastian; Targett-Adams, Paul; Grillo, Alfio; Herrmann, Eva; Wittum, Gabriel

    2017-01-01

    virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural

  16. Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication.

    Science.gov (United States)

    Morrow, Carl A; Nguyen, Michael O; Fower, Andrew; Wong, Io Nam; Osman, Fekret; Bryer, Claire; Whitby, Matthew C

    2017-06-06

    Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. Collapsed forks can be rescued by homologous recombination, which restarts replication. However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. Based on our findings, we propose that IFSA is a potential threat to genomic stability in eukaryotes.

  17. Managing Single-Stranded DNA during Replication Stress in Fission Yeast

    Directory of Open Access Journals (Sweden)

    Sarah A. Sabatinos

    2015-09-01

    Full Text Available Replication fork stalling generates a variety of responses, most of which cause an increase in single-stranded DNA. ssDNA is a primary signal of replication distress that activates cellular checkpoints. It is also a potential source of genome instability and a substrate for mutation and recombination. Therefore, managing ssDNA levels is crucial to chromosome integrity. Limited ssDNA accumulation occurs in wild-type cells under stress. In contrast, cells lacking the replication checkpoint cannot arrest forks properly and accumulate large amounts of ssDNA. This likely occurs when the replication fork polymerase and helicase units are uncoupled. Some cells with mutations in the replication helicase (mcm-ts mimic checkpoint-deficient cells, and accumulate extensive areas of ssDNA to trigger the G2-checkpoint. Another category of helicase mutant (mcm4-degron causes fork stalling in early S-phase due to immediate loss of helicase function. Intriguingly, cells realize that ssDNA is present, but fail to detect that they accumulate ssDNA, and continue to divide. Thus, the cellular response to replication stalling depends on checkpoint activity and the time that replication stress occurs in S-phase. In this review we describe the signs, signals, and symptoms of replication arrest from an ssDNA perspective. We explore the possible mechanisms for these effects. We also advise the need for caution when detecting and interpreting data related to the accumulation of ssDNA.

  18. FOTOVOLTAiK SiSTEMLERiN DENETLENMESi iÇiN YENi BiR KONTROL KARTI VE BiLGiSAYAR YAZILIMI

    Directory of Open Access Journals (Sweden)

    Mustafa Berkant SELEK

    2008-02-01

    Full Text Available Bu çalısmada, İzmir ili Bornova ilçesindeki Ege Üniversitesi Günes Enerjisi Enstitüsü bünyesinde kurulan bir yenilenebilir enerji sisteminin elektrik akısını kontrol eden bir mikroislemci kartı tasarlanmıs ve bilgisayar yazılımı gelistirilmistir. Bu amaçla, anahtarlama görevi yapan güç elektronigi devre elemanlarının bulundugu ayrı bir elektronik kartın kontrol islemini üstlenen PIC18F452 mikrodenetleyicisi kullanan bir elektronik devre gerçeklestirilmistir. Piyasadaki standart kontrol kartları tek seviyeli eviricilerin anahtarlanmasına olanak saglamaktadır. Gelistirilen kontrol kartı ise çok seviyeli eviricilerle çalısmak üzere tasarlanmıstır. Bunun yanı sıra, günes enerjisi panellerinin verimleri oldukça düsük oldugundan, günes panellerinin maksimum güç noktasında (MPP çalıstırmak çok önemlidir. Bu yüzden, tasarlanan kontrol kartı üzerinde MPP algoritması da bulunmaktadır. Ayrıca, tasarlanan kontrol kartının üzerinde RS232 seri haberlesme arabirimi mevcuttur. Böylece, kontrol kartı üzerinde gerçeklestirilen tüm fonksiyonların kullanıcının istegine göre bir bilgisayar yazılımı aracılıgı ile seçilebilmesine ve istenirse kullanıcıya rapor olarak verilebilmesine olanak tanınmıstır. Son olarak, gelistirilen kontrol kartının, gelistirdigimiz yazılım ile haberlesebilmesi için bir komut seti olusturulmustur. Böylece, kendi kontrol kartını gelistirmek isteyen veya daha görsel bir yazılım gelistirmek isteyen diger arastırmacılar için ortak bir taban olusturulması hedeflenmistir.

  19. Replication dynamics of the yeast genome.

    Science.gov (United States)

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

    2001-10-05

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

  20. Chromosomal DNA replication of Vicia faba cells

    International Nuclear Information System (INIS)

    Ikushima, Takaji

    1976-01-01

    The chromosomal DNA replication of higher plant cells has been investigated by DNA fiber autoradiography. The nuclear DNA fibers of Vicia root meristematic cells are organized into many tandem arrays of replication units or replicons which exist as clusters with respect to replication. DNA is replicated bidirectionally from the initiation points at the average rate of 0.15 μm/min at 20 0 C, and the average interinitiation interval is about 16 μm. The manner of chromosomal DNA replication in this higher plant is similar to that found in other eukaryotic cells at a subchromosomal level. (auth.)

  1. Inferential misconceptions and replication crisis

    Directory of Open Access Journals (Sweden)

    Norbert Hirschauer

    2016-12-01

    Full Text Available Misinterpretations of the p value and the introduction of bias through arbitrary analytical choices have been discussed in the literature for decades. Nonetheless, they seem to have persisted in empirical research, and criticisms of p value misuses have increased in the recent past due to the non-replicability of many studies. Unfortunately, the critical concerns that have been raised in the literature are scattered over many disciplines, often linguistically confusing, and differing in their main reasons for criticisms. Misuses and misinterpretations of the p value are currently being discussed intensely under the label “replication crisis” in many academic disciplines and journals, ranging from specialized scientific journals to Nature and Science. In a drastic response to the crisis, the editors of the journal Basic and Applied Social Psychology even decided to ban the use of p values from future publications at the beginning of 2015, a fact that has certainly added fuel to the discussions in the relevant scientific forums. Finally, in early March, the American Statistical Association released a brief formal statement on p values that explicitly addresses misuses and misinterpretations. In this context, we systematize the most serious flaws related to the p value and discuss suggestions of how to prevent them and reduce the rate of false discoveries in the future.

  2. Repair replication in replicating and nonreplicating DNA after irradiation with uv light

    Energy Technology Data Exchange (ETDEWEB)

    Slor, H.; Cleaver, J.E.

    1978-06-01

    Ultraviolet light induces more pyrimidine dimers and more repair replication in DNA that replicates within 2 to 3 h of irradiation than in DNA that does not replicate during this period. This difference may be due to special conformational changes in DNA and chromatin that might be associated with semiconservative DNA replication.

  3. Nef’î Hakkında Bir Bibliyografya Denemesi An Essay Of Bibliography About Nef’i

    Directory of Open Access Journals (Sweden)

    Halil Sercan KOŞİK

    2013-03-01

    Full Text Available Nef’î who lived in the first half of 17th century was born in Hasankale one of districts of Erzurum. The poet whose real name was Ömer had a life full of struggles but he managed to produce some important works through his life. Nef’î, one of the leading poets of divan poetry was celebrated much at his age and after his death. Such a reputation is originated from the sharpness of his pen, his talent as well as his wit. Nef’î whose usage of praise and satire is extreme is known forhis mastership in using rhythm and rhyme in his poems. While attaching importance to meaning and utterance he tried to use a new language and accomplished that to a great degree. His knowledge of Persian Language and Literature played a considerable role.A lot has been written so far about Nef’î and a great many research exists about his works too. However it is obvious that there will be many works about Nef’î, a productive poet. In this study a classification of Nef’î’s works and scientific studies about him and his works will be presented. Our research focuses to illustrate which part of his works is the center of modern researches and which parts are not. In addition, it is expected that our research will provided useful information to researchers studying Nef’î as a guide for sources regarding him. On yedinci yüzyılın ilk yarısında yaşamış olan Nef’î, Erzurum’un Hasankale ilçesinde doğmuştur. Asıl adı Ömer olan şair, oldukça mücadele dolu bir hayat geçirmiş ve bu hayata aynı zamanda önemli denilebilecek eserler de sığdırabilmeyi başarmıştır. Divan şiirinin önde gelen şairlerden biri olan Nef’î, adından hem yaşadığı dönemde hem de sonrasında çokça söz ettirmiştir. Nef’î’nin böyle bir şöhrete kavuşması onun edebi yeteneği ve kıvrak zekası yanında kaleminin keskin olmasından kaynaklanmaktadır. Övdüğünü çok iyi öven, yerdiğini de çok kötü bir şekilde yeren Nef

  4. Türkiye’de entomofagi hakkında bir kamuoyu araştırması

    OpenAIRE

    CANHİLAL, Ramazan; YÜKSEL, Ebubekir

    2018-01-01

    Yenilebilir böcekler, gelecekte dünyanın gıda kıtlığını gidermek içiniyi bir potansiyele sahiptir ve küresel açlığı ve yetersiz beslenmeyi azaltmayayardımcı olabilirler. Entomofagi dünyanın bazı kesiminde oldukçayaygın olmasına rağmen batı ülkelerinde hala kabul görmemiştir. Türkiye’dekigenç neslin entomofagiyekarşı tutumlarını ve entomofagiyi reddetme nedenlerini belirlemek için, 2017yılında Erciyes Üniversitesi kampüsünde 610 katılımcı üzerinde bir anketçalışması yapılmıştır. Erciyes Üniver...

  5. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  6. Initiation of DNA replication: functional and evolutionary aspects

    Science.gov (United States)

    Bryant, John A.; Aves, Stephen J.

    2011-01-01

    Background The initiation of DNA replication is a very important and highly regulated step in the cell division cycle. It is of interest to compare different groups of eukaryotic organisms (a) to identify the essential molecular events that occur in all eukaryotes, (b) to start to identify higher-level regulatory mechanisms that are specific to particular groups and (c) to gain insights into the evolution of initiation mechanisms. Scope This review features a wide-ranging literature survey covering replication origins, origin recognition and usage, modification of origin usage (especially in response to plant hormones), assembly of the pre-replication complex, loading of the replisome, genomics, and the likely origin of these mechanisms and proteins in Archaea. Conclusions In all eukaryotes, chromatin is organized for DNA replication as multiple replicons. In each replicon, replication is initiated at an origin. With the exception of those in budding yeast, replication origins, including the only one to be isolated so far from a plant, do not appear to embody a specific sequence; rather, they are AT-rich, with short tracts of locally bent DNA. The proteins involved in initiation are remarkably similar across the range of eukaryotes. Nevertheless, their activity may be modified by plant-specific mechanisms, including regulation by plant hormones. The molecular features of initiation are seen in a much simpler form in the Archaea. In particular, where eukaryotes possess a number of closely related proteins that form ‘hetero-complexes’ (such as the origin recognition complex and the MCM complex), archaeans typically possess one type of protein (e.g. one MCM) that forms a homo-complex. This suggests that several eukaryotic initiation proteins have evolved from archaeal ancestors by gene duplication and divergence. PMID:21508040

  7. Complex Dynamic Development of Poliovirus Membranous Replication Complexes

    Science.gov (United States)

    Nair, Vinod; Hansen, Bryan T.; Hoyt, Forrest H.; Fischer, Elizabeth R.; Ehrenfeld, Ellie

    2012-01-01

    Replication of all positive-strand RNA viruses is intimately associated with membranes. Here we utilize electron tomography and other methods to investigate the remodeling of membranes in poliovirus-infected cells. We found that the viral replication structures previously described as “vesicles” are in fact convoluted, branching chambers with complex and dynamic morphology. They are likely to originate from cis-Golgi membranes and are represented during the early stages of infection by single-walled connecting and branching tubular compartments. These early viral organelles gradually transform into double-membrane structures by extension of membranous walls and/or collapsing of the luminal cavity of the single-membrane structures. As the double-membrane regions develop, they enclose cytoplasmic material. At this stage, a continuous membranous structure may have double- and single-walled membrane morphology at adjacent cross-sections. In the late stages of the replication cycle, the structures are represented mostly by double-membrane vesicles. Viral replication proteins, double-stranded RNA species, and actively replicating RNA are associated with both double- and single-membrane structures. However, the exponential phase of viral RNA synthesis occurs when single-membrane formations are predominant in the cell. It has been shown previously that replication complexes of some other positive-strand RNA viruses form on membrane invaginations, which result from negative membrane curvature. Our data show that the remodeling of cellular membranes in poliovirus-infected cells produces structures with positive curvature of membranes. Thus, it is likely that there is a fundamental divergence in the requirements for the supporting cellular membrane-shaping machinery among different groups of positive-strand RNA viruses. PMID:22072780

  8. Hili Inhibits HIV Replication in Activated T Cells.

    Science.gov (United States)

    Peterlin, B Matija; Liu, Pingyang; Wang, Xiaoyun; Cary, Daniele; Shao, Wei; Leoz, Marie; Hong, Tian; Pan, Tao; Fujinaga, Koh

    2017-06-01

    P-element-induced wimpy-like (Piwil) proteins restrict the replication of mobile genetic elements in the germ line. They are also expressed in many transformed cell lines. In this study, we discovered that the human Piwil 2 (Hili) protein can also inhibit HIV replication, especially in activated CD4 + T cells that are the preferred target cells for this virus in the infected host. Although resting cells did not express Hili, its expression was rapidly induced following T cell activation. In these cells and transformed cell lines, depletion of Hili increased levels of viral proteins and new viral particles. Further studies revealed that Hili binds to tRNA. Some of the tRNAs represent rare tRNA species, whose codons are overrepresented in the viral genome. Targeting tRNA Arg (UCU) with an antisense oligonucleotide replicated effects of Hili and also inhibited HIV replication. Finally, Hili also inhibited the retrotransposition of the endogenous intracysternal A particle (IAP) by a similar mechanism. Thus, Hili joins a list of host proteins that inhibit the replication of HIV and other mobile genetic elements. IMPORTANCE Piwil proteins inhibit the movement of mobile genetic elements in the germ line. In their absence, sperm does not form and male mice are sterile. This inhibition is thought to occur via small Piwi-interacting RNAs (piRNAs). However, in some species and in human somatic cells, Piwil proteins bind primarily to tRNA. In this report, we demonstrate that human Piwil proteins, especially Hili, not only bind to select tRNA species, including rare tRNAs, but also inhibit HIV replication. Importantly, T cell activation induces the expression of Hili in CD4 + T cells. Since Hili also inhibited the movement of an endogenous retrovirus (IAP), our finding shed new light on this intracellular resistance to exogenous and endogenous retroviruses as well as other mobile genetic elements. Copyright © 2017 American Society for Microbiology.

  9. Ankara Üniversitesi Kriz Merkezine başvuran yas olguları üzerine bir çalışma

    OpenAIRE

    ŞENELMİŞ, Halil

    2006-01-01

    Ankara Üniversitesi Kriz Merkezi'ne BaşvuranYas Olguları Üzerine Bir ÇalışmaSosyal bir varlık olan insan yaşam süreci içerisinde zorlayıcı, yıpratıcı, tehdit edicibirçok olay ve sorunla karşılaşır. Her zaman sorunlar karşısında kullandığı çözüm yollarınınişe yaramadığını gören kişi, kendisini çaresiz hisseder. Bu yaşanan bir kriz durumudur. Krizçeşitli duygusal zorlanmalar sonunda meydana gelen akut ve süresi sınırlı bir dengebozukluğudur.Kişinin yaşamı boyunca karşılaştı...

  10. Partiklid jah, jaa ning jajaa naaberpaari järelliikmena müügiläbirääkimistes / Riina Kasterpalu

    Index Scriptorium Estoniae

    Kasterpalu, Riina

    2005-01-01

    Vastavate partiklite funktsionaalsetest ülesannetest, kasutamisest ja tähendustest müügivestlustes telefoni teel peetud müügiläbirääkimisi analüüsides. Järgneb: Keel ja Kirjandus, 2005, nr. 12

  11. Bir Doğu Liderliğinin Batı Liderlik Yaklaşımları Perspektifinden Değerlendirilmesi: Konosuke Matsushita

    OpenAIRE

    Danışman, Sümeyra Alpaslan

    2013-01-01

    Bu çalışmanın amacı, yeni liderlik yaklaşımları açısından Japon bir lider ve yönetici olanKonosuke MATSUSHITA’nın liderlik davranışlarının incelenmesidir. Japonya’nın günümüzdekihaline gelmesinde büyük katkısı olan Matsushita’nın seçilmesinin nedeni;Matsushita’nın liderlik davranışlarının John P. Kotter tarafından Matsushita Liderliği adlıbir yaklaşım olarak öne sürülmesidir. Yani bir doğu liderinden ziyade, bir doğu liderliği,batı liderlik yaklaşımlarınca analiz edilmiştir. Günümüzün modern ...

  12. Zamanın Bir Başlangıcı Olmalı mıdır?

    Directory of Open Access Journals (Sweden)

    Zikri Yavuz

    2015-12-01

    Full Text Available Bu makalede, zamanın bir başlangıcı olup olmadığını tartışacağım. Büyük patlama modeline göre, evrenimiz sonsuz bir şekilde geçmişe sahip değildir. Bu, muhtemelen modern kozmolojinin en görkemli keşiflerinden birisidir. Buna rağmen bazı filozoflar zamanın zorunlu olarak bir başlangıcının olmadığını iddia etmektedirler. Büyük patlamanın âlemin zamansal bir başlangıcı olduğu görüşünü desteklediğini ileri süreceğim. Aynı zamanda zamanın başlangıcı olmadığına dair a priori argümanların da başarılı olmadığını göstermeyi deneyeceğim.

  13. Sr and Pb isotopic composition of five USGS glasses (BHVO-2G, BIR-1G, BCR-2G, TB-1G, NKT-1G)

    NARCIS (Netherlands)

    Elburg, M.A.; Vroon, P.Z.; van der Wagt, R.A.C.A.; Tchalikian, A.

    2005-01-01

    Sr isotopic compositions and Rb/Sr ratios of three USGS glasses (BHVO-2G, BIR-1G, BCR-2G) are identical to those of the original USGS reference materials. NKT-1G and TB-1G give values of 0.70351 and 0.70558, respectively. Pb isotopic ratios were measured by the standard-sample bracketing technique

  14. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    Thermoplastic injection moulding is a widely used industrial process that involves surface generation by replication. The surface topography of injection moulded plastic parts can be important for aesthetical or technical reasons. With the emergence of microengineering and nanotechnology additional...... importance of surface topography follows. In general the replication is not perfect and the topography of the plastic part differs from the inverse topography of the mould cavity. It is desirable to be able to control the degree of replication perfection or replication quality. This requires an understanding...... of the physical mechanisms of replication. Such understanding can lead to improved process design and facilitate in-line process quality control with respect to surface properties. The purpose of the project is to identify critical factors that affect topography replication quality and to obtain an understanding...

  15. Host ESCRT proteins are required for bromovirus RNA replication compartment assembly and function.

    Directory of Open Access Journals (Sweden)

    Arturo Diaz

    2015-03-01

    Full Text Available Positive-strand RNA viruses genome replication invariably is associated with vesicles or other rearranged cellular membranes. Brome mosaic virus (BMV RNA replication occurs on perinuclear endoplasmic reticulum (ER membranes in ~70 nm vesicular invaginations (spherules. BMV RNA replication vesicles show multiple parallels with membrane-enveloped, budding retrovirus virions, whose envelopment and release depend on the host ESCRT (endosomal sorting complexes required for transport membrane-remodeling machinery. We now find that deleting components of the ESCRT pathway results in at least two distinct BMV phenotypes. One group of genes regulate RNA replication and the frequency of viral replication complex formation, but had no effect on spherule size, while a second group of genes regulate RNA replication in a way or ways independent of spherule formation. In particular, deleting SNF7 inhibits BMV RNA replication > 25-fold and abolishes detectable BMV spherule formation, even though the BMV RNA replication proteins accumulate and localize normally on perinuclear ER membranes. Moreover, BMV ESCRT recruitment and spherule assembly depend on different sets of protein-protein interactions from those used by multivesicular body vesicles, HIV-1 virion budding, or tomato bushy stunt virus (TBSV spherule formation. These and other data demonstrate that BMV requires cellular ESCRT components for proper formation and function of its vesicular RNA replication compartments. The results highlight growing but diverse interactions of ESCRT factors with many viruses and viral processes, and potential value of the ESCRT pathway as a target for broad-spectrum antiviral resistance.

  16. Parasites Sustain and Enhance RNA-Like Replicators through Spatial Self-Organisation.

    Directory of Open Access Journals (Sweden)

    Enrico Sandro Colizzi

    2016-04-01

    Full Text Available In a prebiotic RNA world, parasitic behaviour may be favoured because template dependent replication happens in trans, thus being altruistic. Spatially extended systems are known to reduce harmful effects of parasites. Here we present a spatial system to show that evolution of replication is (indirectly enhanced by strong parasites, and we characterise the phase transition that leads to this mode of evolution. Building on the insights of this analysis, we identify two scenarios, namely periodic disruptions and longer replication time-span, in which speciation occurs and an evolved parasite-like lineage enables the evolutionary increase of replication rates in replicators. Finally, we show that parasites co-evolving with replicators are selected to become weaker, i.e. worse templates for replication when the duration of replication is increased. We conclude that parasites may not be considered a problem for evolution in a prebiotic system, but a degree of freedom that can be exploited by evolution to enhance the evolvability of replicators, by means of emergent levels of selection.

  17. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

    Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...

  18. Kablosuz Ağlarda Yeni Bir Anahtar Dağıtım Yöntemi

    Directory of Open Access Journals (Sweden)

    Çağatay Ay

    2017-01-01

    Full Text Available Ağ teknolojilerinin gelişimi ve dijital cihazların artışı multimedya iletimini hızlı ve kolay kılmıştır. Bununla birlikte açık haberleşme kanalları üzerinden yapılan dijital veri iletimi, telif hakkı ihlalleri, dolandırıcılık vb. birçok güvenlik açığını beraberinde getirmiştir. Bu sebepten dolayı güvenli veri iletimi için geliştirilen yöntem ve teknikler oldukça önem kazanmaktadır. Bu tekniklerden biri olan steganografi, gizli iletişim için zararsız görünen bir taşıyıcıya veri eklemesi yapan bilgi gizlemenin alt dallarından biri olarak tanımlanabilir. Veri gizlenirken kullanılan yöntem ve tekniğin sistem dışı kişiler tarafından bilinmesi güvenli veri iletişimini olumsuz yönde etkileyecektir. Steganografinin güvenlik konusunda yetersiz olması, beraberinde şifrelemeyi gündeme getirmektedir. Açık haberleşme kanalları ile yapılmak istenilen gizli iletişimin, çeşitli steganografik metotlar ve şifreleme algoritmaları ile desteklenmesi gerekmektedir. Bu çalışmada, ağ kanalları üzerinden güvenli anahtar dağıtımı için ağ steganografisinden yararlanan bir yöntem geliştirilmiştir. Deneysel sonuçlar, yapılan çalışmanın sağlamlık ve algılanamazlık koşullarında uygulanabilir olduğunu göstermiştir.

  19. Bir Sinema Filminde Sınıfların Temsili Ve Politik Duruş: Kış Uykusu

    Directory of Open Access Journals (Sweden)

    Defne Özonur

    2016-12-01

    Full Text Available Bir yansıtma aracı olarak sinema filmleri, ele aldığı toplumsal çatışmalı konuları ele alışına bağlı olarak, gizli veya açık, bilinçli veya bilinçsiz belli bir dünya görüşünün taşıyıcısıdır. Bir sanat eserini felsefenin ışığında eleştirmek, belli dünya görüşleri üzerinden sanatçının kafasından geçen süreci aydınlatmaktır. Yönetmen Nuri Bilge Ceylan’ın Kış Uykusu (2014 filmi, pek çok film eleştirmeni tarafından yönetmenin toplumdaki sınıfsal yapıları ve iktidarı eleştirdiği en politik filmi olarak nitelendirilmiştir. Bu çalışmanın temel iddiaları; filmde Marksist anlamda sınıf, sınıf bilinci ve sınıf çatışmasının gösterilmeyip Weberci anlamda sınıf ve statü grupları olarak sosyal katmanların temsil edildiği; filmin idealist dünya görüşünü yansıttığı ve politik olarak da statükocu olduğu ve egemen düzeni yeniden ürettiğidir. Filmde sınıflar “kendi için sınıf” olmaktan ziyade “kendinde sınıf” olarak ve salt zengin/yoksul; mülk sahibi mülksüz gibi ekonomik yapılar üzerinden temsil edilirken, sosyal alanda daha çok statü gruplarının yaşam tarzı yansıtılmaktadır.

  20. Distribution of DNA replication proteins in Drosophila cells

    Science.gov (United States)

    Easwaran, Hariharan P; Leonhardt, Heinrich; Cardoso, M Cristina

    2007-01-01

    Background DNA replication in higher eukaryotic cells is organized in discrete subnuclear sites called replication foci (RF). During the S phase, most replication proteins assemble at the RF by interacting with PCNA via a PCNA binding domain (PBD). This has been shown to occur for many mammalian replication proteins, but it is not known whether this mechanism is conserved in evolution. Results Fluorescent fusions of mammalian replication proteins, Dnmt1, HsDNA Lig I and HsPCNA were analyzed for their ability to target to RF in Drosophila cells. Except for HsPCNA, none of the other proteins and their deletions showed any accumulation at RF in Drosophila cells. We hypothesized that in Drosophila cells there might be some other peptide sequence responsible for targeting proteins to RF. To test this, we identified the DmDNA Lig I and compared the protein sequence with HsDNA Lig I. The two orthologs shared the PBD suggesting a functionally conserved role for this domain in the Drosophila counterpart. A series of deletions of DmDNA Lig I were analyzed for their ability to accumulate at RF in Drosophila and mammalian cells. Surprisingly, no accumulation at RF was observed in Drosophila cells, while in mammalian cells DmDNA Lig I accumulated at RF via its PBD. Further, GFP fusions with the PBD domains from Dnmt1, HsDNA Lig I and DmDNA Lig I, were able to target to RF only in mammalian cells but not in Drosophila cells. Conclusion We show that S phase in Drosophila cells is characterized by formation of RF marked by PCNA like in mammalian cells. However, other than PCNA none of the replication proteins and their deletions tested here showed accumulation at RF in Drosophila cells while the same proteins and deletions are capable of accumulating at RF in mammalian cells. We hypothesize that unlike mammalian cells, in Drosophila cells, replication proteins do not form long-lasting interactions with the replication machinery, and rather perform their functions via very

  1. Enzymatic recognition of DNA replication origins

    International Nuclear Information System (INIS)

    Stayton, M.M.; Bertsch, L.; Biswas, S.

    1983-01-01

    In this paper we discuss the process of recognition of the complementary-strand origin with emphasis on RNA polymerase action in priming M13 DNA replication, the role of primase in G4 DNA replication, and the function of protein n, a priming protein, during primosome assembly. These phage systems do not require several of the bacterial DNA replication enzymes, particularly those involved in the regulation of chromosome copy number of the initiatiion of replication of duplex DNA. 51 references, 13 figures, 1 table

  2. Sakyamuni Buda'nın Tarihsel Kişiliği Ve Öğretisinin Yeni Bir Din Haline Geliş Süreci

    Directory of Open Access Journals (Sweden)

    Hüsamettin Karataş

    2013-06-01

    Full Text Available Sakyamuni Buda, Hindu kast sistemindeki yönetici sınıfa mensup bir prenstir. O, yaşadığı bir takım hayat tecrübelerinden hareketle, var olan anlayışların yetersiz olduğunu düşünerek kendi gerçeğinin peşine düşmüş tarihsel bir şahsiyettir. Sakyamuni Buda, çeşitli yollar deneyerek sonunda mutlak kurtuluşa erdiğini, yani aydınlandığını iddia eden bir din kurucusudur. Onun kurduğu dinî ve felsefi sistemin adı Budizm'dir. Budizm, ortaya çıktığı dönemdeki politeist yapıya, aşırı çileci veya hazcı ahlak ilkelerine, kurtuluş yolunun formalitelerine ve kast sistemine tepki göstermiştir. Bunun yanı sıra var olmaya çalıştığı bölgedeki dinlerin en belirgin özelliklerini de bünyesinde barındırmış, bazı öğreti ve uygulamaları aynen sürdürmüş, kültürel ve toplumsal hayata dair konularda ise devamlı surette esnek bir yol takip etmiştir. Budizm uzun tarihsel süreç içerisinde dünyanın çok farklı bölgelerine yayılmış ve günümüzün en çok taraftara sahip dinlerden biri haline gelmiştir

  3. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  4. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

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

    2013-10-01

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

  5. Duchenne Müsküler Distrofi ve Gilbert"s Sendromu Birlikteliği: Bir Olgu Sunumu

    OpenAIRE

    İncecik, Faruk; Hergüner, Özlem M.; Mert, Gülen; Horoz, Özden; Altunbaşak, Şakir

    2014-01-01

    Gilbert"s sendromu konjuge olmayan hiperbilirubinemi ile karekterize bir hastalıktır. 5 yaşında erkek çocuğu hafif sarılık ile hastanemize getirildi. Hastanın karaciğer enzimleri ve kreatin fosfokinaz yüksekliği ile beraber ısrarcı unkonjuge hiperbilirubinemisi vardı. Normal hemoglobin ve retikülosit değerleri ile hemoliz dışlandı ve Gilbert"s sendromu tanısı konuldu. Kreatin kinaz değeri 15600 U/l idi ve distrofin geninde delesyon mevcuttu. Sonuç olarak hastaya Gilbert"s sendr...

  6. Bir Yeşil İguana'da {İguana iguana) Saptanan Peritonitle Beraber Seyreden Oxyurid Enfestasyonu

    OpenAIRE

    KOENHEMSİ, Lora; ULUTAŞ ESATGİL, Meltem; BAYRAKAL, Alper; ERDOĞAN, Özge; GÖNÜL, Remzi

    2013-01-01

    ÖZETBu olgunun materyalini halsizlik ve iştahsızlık şikayeti ile kliniğimize getirilen 18 aylık bir iguana oluşturdu. Yapılan klinik muayene ve radyolojik incelemeler sonucunda toraks ve sölomda sıvı toplanması saptandı. Hastada yapılan aspirasyon biyopsisi sonucunda yapılan sitolojik incelemede peritonit olduğu tespit edildi. Diğer taraftan dışkısında mukus görülmesi şikayeti nedeniyle yapılan parazitolojik incelemede Pharyngodonidae ailesinden: Alaeuris sp. veya Ozolamius sp. cinslerinden h...

  7. Orta Ölçekli Bir İşletmenin Enerji İzleme Sisteminin Tasarlanması

    Directory of Open Access Journals (Sweden)

    Erdal Irmak

    2012-02-01

    Full Text Available Bu uygulamada, orta ölçekli bir işletmenin gerçek zamanlı ve geçmişe yönelik enerji takibinin bilgisayar ara yüzünden izlenmesi gerçekleştirilmiştir. Enerjinin ölçülmesi için akım ve gerilim bilgilerini Programlanabilir Lojik Kontrolörün ( PLC algılayacağı seviyeye getiren bir kart tasarlanmıştır. Bu karttan alınan akım ve gerilim bilgileri, PLC'nin analog kanalları ile okunmaktadır. Sistemin güç katsayısının algılanması için, bir sıfır geçiş detektörü tasarlanmıştır. Sıfır geçiş detektöründen elde edilen sinyaller arasındaki zaman farkı FM 350-1 sayıcı modül kullanılarak ölçülmüştür. Alınan bilgiler, PLC tarafından RS485/RS232 dönüştürme protokolü kullanarak, bilgisayarın seri iletişim kanalı aracılığı ile veritabanına aktarılmaktadır. Elde edilen veriler, C# programlama dili kullanılarak tasarlanan bir arayüz ile anlık takip edilebilmektedir. Elde edilen veriler sürekli olarak kaydedilerek geçmişe yönelik enerji analizleri yapma olanağı sağlanmıştır. Böylece, istenildiğinde belirlenen zaman aralığında kullanılan aktif, reaktif ve görünür güçler gözlemlenebilmektedir. Geçmişe yönelik enerji izleme sistemi kullanılarak işletmelerin fazla enerji harcadığı zamanlar tespit edilebilmektedir. Böylece, yoğun çalışma saatleri enerjinin ucuz olduğu zamanlara kaydırılarak kullanılan enerjinin işletmeye olan maliyetinin azaltılması gibi olanaklar sağlanmaktadır.

  8. Pratique de l’extranéité dans l’écriture d’Abdelkébir Khatibi

    Directory of Open Access Journals (Sweden)

    Hassan Moustir

    2013-11-01

    Full Text Available Promoted to the rank of operational concept in writing, the notion of "foreign professional" means in both fictional and critical work of Abdelkébir Khatibi (1938-2009 this cosmopolitan otherness that reduces identity disparities and cultural differences. Late Khatibi’s fictions, including Un été à Stockholm (1990 and Féerie d’un mutant (2005 represent an ontological extraneous out with all cultural and identity anchors and discourse representations. Op-erating in a global space, and private of a fixed identity and separated cultural roots, the characters of these two fictions embody the thought of foreignness and border crossing practice, at the linguistic and the cultural levels. This fact grows to reflect on what would be writing and deterritorialized identity.

  9. Topraktan Pestisitlerin Arındırılmasında Önemli Bir Araç: Fitoremediasyon

    OpenAIRE

    TİRYAKİ, Osman; POTUR, Tayfun

    2018-01-01

    Pestisitler bitki koruma önlemleri arasındaen fazla uygulananıdır.Ancak, pestisitlerin tarımsal alanlarda bilinçsiz ve yoğun bir şekilde kullanımı bazı ekosistem problemlerine neden olur.Pestisitlerin sınıflandırma şekillerinden biri de topraktaki yarılanma sürelerine göre yapılanıdır. Bu sınıflandırmada pestisitler kalıcı değil, orta derece kalıcı, kalıcı ve devamlı kalıcı olarak 4 gruba ayrılırlar. Kullanılan pestisitler arasında toprakta çok çabuk parçalananları olduğu gi...

  10. RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks.

    Science.gov (United States)

    Elia, Andrew E H; Wang, David C; Willis, Nicholas A; Boardman, Alexander P; Hajdu, Ildiko; Adeyemi, Richard O; Lowry, Elizabeth; Gygi, Steven P; Scully, Ralph; Elledge, Stephen J

    2015-10-15

    We have used quantitative proteomics to profile ubiquitination in the DNA damage response (DDR). We demonstrate that RPA, which functions as a protein scaffold in the replication stress response, is multiply ubiquitinated upon replication fork stalling. Ubiquitination of RPA occurs on chromatin, involves sites outside its DNA binding channel, does not cause proteasomal degradation, and increases under conditions of fork collapse, suggesting a role in repair at stalled forks. We demonstrate that the E3 ligase RFWD3 mediates RPA ubiquitination. RFWD3 is necessary for replication fork restart, normal repair kinetics during replication stress, and homologous recombination (HR) at stalled replication forks. Mutational analysis suggests that multisite ubiquitination of the entire RPA complex is responsible for repair at stalled forks. Multisite protein group sumoylation is known to promote HR in yeast. Our findings reveal a similar requirement for multisite protein group ubiquitination during HR at stalled forks in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

  12. Sezai Karakoç'un Bir Sorusu Üzerine On A Question Of Sezai Karakoç

    Directory of Open Access Journals (Sweden)

    Fırat CANER

    2013-07-01

    Full Text Available The voice in Sezai Karakoç’s Hızırla Kırk Saat says that he learned how to break the idols made of rocks from Abraham, but he doesn’t know how to destroy the idols made of words. This voice constitutes a typical 20th century philosopher concerned with pornography. Those philosophers who live in the age of images, and whose minds areblurred by the excessive bombardment of images, generally act as ifthey were iconaclasts in the age of Byzantium. Philosophers and literarywriters of our age are hopeless because of the pornographic patternswhich determine our lives. This hopelessness is driven by volontarismwhen they speak about the future, and/but by determinism when theyspeak about the past. But we should take the historical necessities intoaccount when what’s at stake is a consideration of the future. Thencewe can foresee that pornography will lose its effect on our lives becauseof the historical necessities. As a result of the coexistence of thousandsof images, no image can sufficiently satisfy or provoke the eye. That’swhy iconaclasts are not different from romantic revolutionists whohopefully dream that they can change the world in a moment.Consequently we can say that satisfying the eye is a stage within theprocess of images’ losing their effect on out minds. Sezai Karakoç’un Hızırla Kırk Saat adlı eserindeki ses, mermer putları nasıl devireceğini Hz. İbrahim’den öğrendiğini, buna karşılık, nesnesi olmayan putları, örneğin sözlerle, yani zihinlerde inşa edilen putları nasıl devireceğini bilmediğini, bunu kimsenin öğretmediğini söyler. Sözlerle inşa edilen putların nasıl kırılacağını bilmediğini söyleyen ses, pornografi hakkında yazan tipik bir 20. yüzyıl düşünürü sesidir. İmaj çağının imaj bombardımanı altında zihni bulanan bu düşünürler, genel olarak, Bizans tarihindeki put kırıcıların tavrını benimsemişlerdir. Günümüz felsefe ve edebiyatının günlük ya

  13. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  14. Using Replication Projects in Teaching Research Methods

    Science.gov (United States)

    Standing, Lionel G.; Grenier, Manuel; Lane, Erica A.; Roberts, Meigan S.; Sykes, Sarah J.

    2014-01-01

    It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well-known experiments, yielding…

  15. Dynamic behavior of DNA replication domains

    NARCIS (Netherlands)

    Manders, E. M.; Stap, J.; Strackee, J.; van Driel, R.; Aten, J. A.

    1996-01-01

    Like many nuclear processes, DNA replication takes place in distinct domains that are scattered throughout the S-phase nucleus. Recently we have developed a fluorescent double-labeling procedure that allows us to visualize nascent DNA simultaneously with "newborn" DNA that had replicated earlier in

  16. A Replication by Any Other Name: A Systematic Review of Replicative Intervention Studies

    Science.gov (United States)

    Cook, Bryan G.; Collins, Lauren W.; Cook, Sara C.; Cook, Lysandra

    2016-01-01

    Replication research is essential to scientific knowledge. Reviews of replication studies often electronically search for "replicat*" as a textword, which does not identify studies that replicate previous research but do not self-identify as such. We examined whether the 83 intervention studies published in six non-categorical research…

  17. Recommendations for Replication Research in Special Education: A Framework of Systematic, Conceptual Replications

    Science.gov (United States)

    Coyne, Michael D.; Cook, Bryan G.; Therrien, William J.

    2016-01-01

    Special education researchers conduct studies that can be considered replications. However, they do not often refer to them as replication studies. The purpose of this article is to consider the potential benefits of conceptualizing special education intervention research within a framework of systematic, conceptual replication. Specifically, we…

  18. Surface Microstructure Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Arlø, Uffe Rolf

    2005-01-01

    topography is transcribed onto the plastic part through complex mechanisms. This replication however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... moulding of surface microstructures. Emphasis is put on the ability to replicate surface microstructures under normal injection moulding conditions, notably with low cost materials at low mould temperatures. The replication of surface microstructures in injection moulding has been explored...... for Polypropylene at low mould temperatures. The process conditions were varied over the recommended process window for the material. The geometry of the obtained structures was analyzed. Evidence suggests that step height replication quality depends linearly on structure width in a certain range. Further...

  19. Surface microstructure replication in injection molding

    DEFF Research Database (Denmark)

    Theilade, Uffe Arlø; Hansen, Hans Nørgaard

    2006-01-01

    topography is transcribed onto the plastic part through complex mechanisms. This replication, however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... molding of surface microstructures. The fundamental problem of surface microstructure replication has been studied. The research is based on specific microstructures as found in lab-on-a-chip products and on rough surfaces generated from EDM (electro discharge machining) mold cavities. Emphasis is put...... on the ability to replicate surface microstructures under normal injection-molding conditions, i.e., with commodity materials within typical process windows. It was found that within typical process windows the replication quality depends significantly on several process parameters, and especially the mold...

  20. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  1. Suppression of Poxvirus Replication by Resveratrol.

    Science.gov (United States)

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

    2017-01-01

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

  2. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

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

  3. A New Replication Norm for Psychology

    Directory of Open Access Journals (Sweden)

    Etienne P LeBel

    2015-10-01

    Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.

  4. Hepatitis A Virus Genome Organization and Replication Strategy.

    Science.gov (United States)

    McKnight, Kevin L; Lemon, Stanley M

    2018-04-02

    Hepatitis A virus (HAV) is a positive-strand RNA virus classified in the genus Hepatovirus of the family Picornaviridae It is an ancient virus with a long evolutionary history and multiple features of its capsid structure, genome organization, and replication cycle that distinguish it from other mammalian picornaviruses. HAV proteins are produced by cap-independent translation of a single, long open reading frame under direction of an inefficient, upstream internal ribosome entry site (IRES). Genome replication occurs slowly and is noncytopathic, with transcription likely primed by a uridylated protein primer as in other picornaviruses. Newly produced quasi-enveloped virions (eHAV) are released from cells in a nonlytic fashion in a unique process mediated by interactions of capsid proteins with components of the host cell endosomal sorting complexes required for transport (ESCRT) system. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. Investigation of radiation enhanced reactivation of cytoplasmic replicating human virus

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Haynes, K.F.; Stafford, J.E.

    1976-01-01

    When monolayers of CV-1 monkey kidney cells were exposed to ultraviolet (uv) radiation (0 to 200 erg/nm 2 ) or x rays (0 to 10 krads) before infection with uv-irradiated herpes simplex virus, an increase in the infectivity of this nuclear replicating virus occurred as measured by plaque formation. These phenomena are known as uv (Weigle) reactivation (WR) and x-ray reactivation (x-ray R). In this study the presence of WR and x-ray R was examined in CV-1 cells infected with uv-irradiated vaccinia virus or poliovirus, both cytoplasmic replicating viruses. Little or no WR or x-ray R was observed for either of these viruses. These results suggest that WR and x-ray R in mammalian cells may be restricted to viruses which are synthesized in the cell nucleus

  6. Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

    Science.gov (United States)

    Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

    2015-11-01

    Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

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

    Science.gov (United States)

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

    2006-02-01

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

  8. DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in Haloferax volcanii.

    Science.gov (United States)

    Lestini, Roxane; Delpech, Floriane; Myllykallio, Hannu

    2015-11-01

    Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication

    Science.gov (United States)

    Trask, Shane D.; McDonald, Sarah M.; Patton, John T.

    2013-01-01

    Preface Viral replication is rapid and robust, but it is far from a chaotic process. Instead, successful production of infectious progeny requires that events occur in the correct place and at the correct time. Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, seems to govern its replication through ordered disassembly and assembly of a triple-layered icosahedral capsid. In recent years, high-resolution structural data have provided unprecedented insight into these events. In this Review, we explore the current understanding of rotavirus replication and how it compares to other Reoviridae family members. PMID:22266782

  11. Hepatitis C virus translation preferentially depends on active RNA replication.

    Directory of Open Access Journals (Sweden)

    Helene Minyi Liu

    Full Text Available Hepatitis C virus (HCV RNA initiates its replication on a detergent-resistant membrane structure derived from the endoplasmic reticulum (ER in the HCV replicon cells. By performing a pulse-chase study of BrU-labeled HCV RNA, we found that the newly-synthesized HCV RNA traveled along the anterograde-membrane traffic and moved away from the ER. Presumably, the RNA moved to the site of translation or virion assembly in the later steps of viral life cycle. In this study, we further addressed how HCV RNA translation was regulated by HCV RNA trafficking. When the movement of HCV RNA from the site of RNA synthesis to the Golgi complex was blocked by nocodazole, an inhibitor of ER-Golgi transport, HCV protein translation was surprisingly enhanced, suggesting that the translation of viral proteins occurred near the site of RNA synthesis. We also found that the translation of HCV proteins was dependent on active RNA synthesis: inhibition of viral RNA synthesis by an NS5B inhibitor resulted in decreased HCV viral protein synthesis even when the total amount of intracellular HCV RNA remained unchanged. Furthermore, the translation activity of the replication-defective HCV replicons or viral RNA with an NS5B mutation was greatly reduced as compared to that of the corresponding wildtype RNA. By performing live cell labeling of newly synthesized HCV RNA and proteins, we further showed that the newly synthesized HCV proteins colocalized with the newly synthesized viral RNA, suggesting that HCV RNA replication and protein translation take place at or near the same site. Our findings together indicate that the translation of HCV RNA is coupled to RNA replication and that the both processes may occur at the same subcellular membrane compartments, which we term the replicasome.

  12. Transcription and replication result in distinct epigenetic marks following repression of early gene expression

    OpenAIRE

    Kallestad, Les; Woods, Emily; Christensen, Kendra; Gefroh, Amanda; Balakrishnan, Lata; Milavetz, Barry

    2013-01-01

    Simian Virus 40 (SV40) early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. Because SV40 minichromosomes undergo replication and transcription potentially repression could occur during active transcription or during DNA replication. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized th...

  13. Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Tobey, R.A.

    1989-01-01

    Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 μg mL -1 aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression

  14. Data from Investigating Variation in Replicability: A “Many Labs” Replication Project

    Directory of Open Access Journals (Sweden)

    Richard A. Klein

    2014-04-01

    Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.

  15. Endüstriyel İşletmelerde Franchising Model Önerisi: Hazır Beton Sektöründe Bir Uygulama

    Directory of Open Access Journals (Sweden)

    İpek Kazançoğlu

    2016-12-01

    Full Text Available Endüstriyel pazarda faaliyet gösteren firmaların daha hızlı büyüyerek, yeni pazarlara açılmasında franchising sistemi bir yeni bir satış, dağıtım kanalı olarak değerlendirilmektedir. Bu araştırmada amaç,  hazır beton sektöründe faaliyet gösteren bir firmanın franchising sistemini bir iş modeli olarak benimseme kararında dikkat etmesi gereken unsurları ve karşılaşılan zorlukları incelemektedir. Örnek olay çalışması olarak ele alınan çalışmada,  BATIBETON A.Ş. firmasının yedi yöneticiyle BATIBETON markasının franchising uygulamalarına ilişkin görüşlerini öğrenmek amacıyla derinlemesine görüşmeler yapılmıştır. Bu görüşmeler sonucunda, franchising sisteminin hazır beton sektöründe bir model önerisi olarak uygulanıp/uygulanmayacağı değerlendirilmiştir. Yapılan görüşmelerden elde edilen bulguların diğer endüstriyel işletmeler içinde geliştirilebilecek bir franchising iş modeli kararında etkili olabilecek faktörlerin anlaşılması yönünden uygulamaya katkı sağlayacağı düşünülmektedir.

  16. Orta Asya ve Kafkasya’da Nükleer Enerji Açısından Türkiye’nin Mali Beklenti ve Riskleri: Praksiyolojik Bir İnceleme

    OpenAIRE

    Bahçe, Abdullah; Gümüş, Öner

    2016-01-01

     ÖzNükleer enerji birçok ülkenin birbirine karşı üstünlük sağlamada kullanabildikleri bir araçtır. Bunun temel sebebi de nükleer enerjinin ekonomik ve mali getiri sağlayarak ülkelerin kalkınmalarını etkileyebilecek bir potansiyele sahip olmasıdır. Bu yönüyle nükleer enerji, verginin doğmasına neden olacak bir etkiye de sahiptir. Türkiye’de ise nükleer enerji üretilememektedir. Bununla birlikte diğer enerji çeşitlerinin üretimi söz konusudur ve bu enerji çeşitlerinden üretilen mal ve hizmetler...

  17. İbn Haldun'un mukaddimequot123sinde toplumun yasalarını keşfeden bir düşünce etkinliği olarak tarih

    OpenAIRE

    KARACA, Çağlar

    2011-01-01

    ÖZET Bu çalıĢmada, Ġbn Haldun‟un tarih anlayıĢı ve toplumun yasalarını keĢfeden bir tarih bilimine katkısı incelenmiĢtir. Ġbn Haldun, kendinden sonraki birçok tarih görüĢüne esin kaynağı olmuĢtur. Ancak onun ününün yanında, Mukaddime‟deki fikirlerin ve tarihsel etkinliğin kuramsal bir değerlendirmesi sönük kalmıĢtır. Ġbn Haldun, kurucusu olduğu umran biliminde tarihsel zorunlulukları, toplumun hal ve tavırlarını keĢfetmeyi amaçlamaktadır. Bir Ġslam bilgini olarak, Aristoteles‟ten et...

  18. PHP, SOL ve AJAX teknolojileri kullanarak Hacettepe Üniversitesi biyoloji bölümü herbaryumu için bir sorgulama yazılımının geliştirilmesi

    OpenAIRE

    Enginer, Erman

    2009-01-01

    Bu çalısmada Hacettepe Üniversitesi Biyoloji Bölümü Herbaryumu’ndaki (HUB) veriler kullanılarak PHP, SQL ve AJAX teknoljileri ile bir herbaryum sorgulama programı gelistirilmistir. Herbaryumlar özellikle botanik, ekolojik ve eczacılık çalısmaları için bir bilgi kaynagı olusturmaktadır. Bu kaynagın sistemli bir sekilde bilgisayar ortamındaki bir veritabanına aktarımı ile veritabanlarının bize sagladıgı hızlı sorgulama ve düzenli kayıt tutma imkanlarından faydalanabiliriz. ...

  19. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  20. Factors influencing microinjection molding replication quality

    Science.gov (United States)

    Vera, Julie; Brulez, Anne-Catherine; Contraires, Elise; Larochette, Mathieu; Trannoy-Orban, Nathalie; Pignon, Maxime; Mauclair, Cyril; Valette, Stéphane; Benayoun, Stéphane

    2018-01-01

    In recent years, there has been increased interest in producing and providing high-precision plastic parts that can be manufactured by microinjection molding: gears, pumps, optical grating elements, and so on. For all of these applications, the replication quality is essential. This study has two goals: (1) fabrication of high-precision parts using the conventional injection molding machine; (2) identification of robust parameters that ensure production quality. Thus, different technological solutions have been used: cavity vacuuming and the use of a mold coated with DLC or CrN deposits. AFM and SEM analyses were carried out to characterize the replication profile. The replication quality was studied in terms of the process parameters, coated and uncoated molds and crystallinity of the polymer. Specific studies were processed to quantify the replicability of injection molded parts (ABS, PC and PP). Analysis of the Taguchi experimental designs permits prioritization of the impact of each parameter on the replication quality. A discussion taking into account these new parameters and the thermal and spreading properties on the coatings is proposed. It appeared that, in general, increasing the mold temperature improves the molten polymer fill in submicron features except for the steel insert (for which the presence of a vacuum is the most important factor). Moreover, the DLC coating was the best coating to increase the quality of the replication. This result could be explained by the lower thermal diffusivity of this coating. We noted that the viscosity of the polymers is not a primordial factor of the replication quality.

  1. Ultrastructural Characterization of Zika Virus Replication Factories

    Directory of Open Access Journals (Sweden)

    Mirko Cortese

    2017-02-01

    Full Text Available Summary: A global concern has emerged with the pandemic spread of Zika virus (ZIKV infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs. Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton. : Cortese et al. show that ZIKV infection in both human hepatoma and neuronal progenitor cells induces drastic structural modification of the cellular architecture. Microtubules and intermediate filaments surround the viral replication factory composed of vesicles corresponding to ER membrane invagination toward the ER lumen. Importantly, alteration of microtubule flexibility impairs ZIKV replication. Keywords: Zika virus, flavivirus, human neural progenitor cells, replication factories, replication organelles, microtubules, intermediate filaments, electron microscopy, electron tomography, live-cell imaging

  2. MYC and the Control of DNA Replication

    Science.gov (United States)

    Dominguez-Sola, David; Gautier, Jean

    2014-01-01

    The MYC oncogene is a multifunctional protein that is aberrantly expressed in a significant fraction of tumors from diverse tissue origins. Because of its multifunctional nature, it has been difficult to delineate the exact contributions of MYC’s diverse roles to tumorigenesis. Here, we review the normal role of MYC in regulating DNA replication as well as its ability to generate DNA replication stress when overexpressed. Finally, we discuss the possible mechanisms by which replication stress induced by aberrant MYC expression could contribute to genomic instability and cancer. PMID:24890833

  3. Replicated Data Management for Mobile Computing

    CERN Document Server

    Douglas, Terry

    2008-01-01

    Managing data in a mobile computing environment invariably involves caching or replication. In many cases, a mobile device has access only to data that is stored locally, and much of that data arrives via replication from other devices, PCs, and services. Given portable devices with limited resources, weak or intermittent connectivity, and security vulnerabilities, data replication serves to increase availability, reduce communication costs, foster sharing, and enhance survivability of critical information. Mobile systems have employed a variety of distributed architectures from client-server

  4. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  5. Geleneksel ve Elektronik Ağızdan Ağıza İletişim Yöntemlerine Genel Bir Bakış

    OpenAIRE

    Demirbaş, Esra

    2018-01-01

    Ağızdan ağıza iletişim (WOM-word of mouth); tüketicilerin, bir ürün, hizmet veya kurumlailgili çoğunlukla memnun kalmadıkları veya beğendikleri hususları diğer kişilere iletmek üzerekullandıkları resmi olmayan bir iletişim yoludur.Bazı özel ürün kategorilerinde ve özellikle de hizmet sektöründe, müşterilerin satın alım öncesiWOM’dan etkilenip karar verdikleri düşünülmektedir. Globalleşen ve gelişen iletişim teknolojilerineticesinde WOM’un gittikçe artan önemi ve kurumların performansını etkil...

  6. Sanat Yapıtı Sergileme ve Sunum Çeşitlerine Örnekler Eşliğinde Bir Bakış

    OpenAIRE

    AYAN ERGEN, Burcu

    2014-01-01

    Sergi, sahip olunanları gerek göstermek gerekse ticaret amacıyla başkalarına sunmak için oluşturulan bir düzendir. Sergilemek eski kullanımıyla teşhir etmek anlamına gelir. Sergileme ve sunum yöntemleri, gereksinimlerin ve teknolojinin zaman içinde geçirdiği evrime bağlı olarak sürekli değişen ve yenilenen bir biçim alır. Günümüzde müze ve galerilerde sergileme çeşitleri üzerinde durulacak ve sergilerin oluşturulma düşüncesi ile nasıl oluşturulduğunun inceleneceği bu bildiride, örnekler üzeri...

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

    Science.gov (United States)

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

    2016-07-01

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

  8. Mapping replication origins in yeast chromosomes.

    Science.gov (United States)

    Brewer, B J; Fangman, W L

    1991-07-01

    The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.

  9. Advancing Polymerase Ribozymes Towards Self-Replication

    Science.gov (United States)

    Tjhung, K. F.; Joyce, G. F.

    2017-07-01

    Autocatalytic replication and evolution in vitro by (i) a cross-chiral RNA polymerase catalyzing polymerization of mononucleotides of the opposite handedness; (ii) non-covalent assembly of component fragments of an existing RNA polymerase ribozyme.

  10. Initiation of Replication in Escherichia coli

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob

    The circular chromosome of Escherichia coli is replicated by two replisomes assembled at the unique origin and moving in the opposite direction until they meet in the less well defined terminus. The key protein in initiation of replication, DnaA, facilitates the unwinding of double-stranded DNA...... to single-stranded DNA in oriC. Although DnaA is able to bind both ADP and ATP, DnaA is only active in initiation when bound to ATP. Although initiation of replication, and the regulation of this, is thoroughly investigated it is still not fully understood. The overall aim of the thesis was to investigate...... the regulation of initiation, the effect on the cell when regulation fails, and if regulation was interlinked to chromosomal organization. This thesis uncovers that there exists a subtle balance between chromosome replication and reactive oxygen species (ROS) inflicted DNA damage. Thus, failure in regulation...

  11. LHCb Data Replication During SC3

    CERN Multimedia

    Smith, A

    2006-01-01

    LHCb's participation in LCG's Service Challenge 3 involves testing the bulk data transfer infrastructure developed to allow high bandwidth distribution of data across the grid in accordance with the computing model. To enable reliable bulk replication of data, LHCb's DIRAC system has been integrated with gLite's File Transfer Service middleware component to make use of dedicated network links between LHCb computing centres. DIRAC's Data Management tools previously allowed the replication, registration and deletion of files on the grid. For SC3 supplementary functionality has been added to allow bulk replication of data (using FTS) and efficient mass registration to the LFC replica catalog.Provisional performance results have shown that the system developed can meet the expected data replication rate required by the computing model in 2007. This paper details the experience and results of integration and utilisation of DIRAC with the SC3 transfer machinery.

  12. Molecular Mechanisms of DNA Replication Checkpoint Activation

    Directory of Open Access Journals (Sweden)

    Bénédicte Recolin

    2014-03-01

    Full Text Available The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.

  13. Locating Nearby Copies of Replicated Internet Servers

    National Research Council Canada - National Science Library

    Guyton, James D; Schwartz, Michael F

    1995-01-01

    In this paper we consider the problem of choosing among a collection of replicated servers focusing on the question of how to make choices that segregate client/server traffic according to network topology...

  14. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf; Hansen, Hans Nørgaard; Kjær, Erik Michael

    2005-01-01

    The surface micro topography of injection moulded plastic parts can be important for aesthetical and technical reasons. The quality of replication of mould surface topography onto the plastic surface depends among other factors on the process conditions. A study of this relationship has been...... carried out with rough EDM (electrical discharge machining) mould surfaces, a PS grade, and by applying established three-dimensional topography parameters. Significant quantitative relationships between process parameters and topography parameters were established. It further appeared that replication...

  15. The Legal Road To Replicating Silicon Valley

    OpenAIRE

    John Armour; Douglas Cumming

    2004-01-01

    Must policymakers seeking to replicate the success of Silicon Valley’s venture capital market first replicate other US institutions, such as deep and liquid stock markets? Or can legal reforms alone make a significant difference? In this paper, we compare the economic and legal determinants of venture capital investment, fundraising and exits. We introduce a cross-sectional and time series empirical analysis across 15 countries and 13 years of data spanning an entire business cycle. We show t...

  16. Evolution of Database Replication Technologies for WLCG

    OpenAIRE

    Baranowski, Zbigniew; Pardavila, Lorena Lobato; Blaszczyk, Marcin; Dimitrov, Gancho; Canali, Luca

    2015-01-01

    In this article we summarize several years of experience on database replication technologies used at WLCG and we provide a short review of the available Oracle technologies and their key characteristics. One of the notable changes and improvement in this area in recent past has been the introduction of Oracle GoldenGate as a replacement of Oracle Streams. We report in this article on the preparation and later upgrades for remote replication done in collaboration with ATLAS and Tier 1 databas...

  17. Radiation enhanced reactivation of nuclear replicating mammalian viruses

    International Nuclear Information System (INIS)

    Bockstahler, L.E.; Lytle, C.D.

    1977-01-01

    When CV-1 monkey kidney cells were UV-irradiated (0 to 18 J/m 2 ) or X-irradiated (0 to 10 krads) before infection with UV-irradiated simian adenovirus 7 (SA7) or simian virus 40 (SV40), increases in the infectivity of these nuclear replicating viruses as measured by plaque formation were observed. These radiation enhanced reactivations, UV enhanced reactivation (UVER) and X-ray enhanced reactivation (X-ray ER), occurred both when virus infection immediately followed irradiation of the cells (except for X-ray ER with SA7) and when virus infection was delayed until 3 to 5 days after cell irradiation. While there was little difference in the levels of reactivation of UV-irradiated SV40 between immediate and delayed infection, delayed infection resulted in higher levels of reactivation of SA7. X-ray enhanced reactivation of UV-irradiated Herpes simplex virus persisted for several days but did not increase. Thus, X-ray enhanced and UV enhanced reactivations of these mammalian viruses were relatively long-lived effects. Essentially no UVER or X-ray ER was found in CV-1 cells for either immediate or delayed infection with UV-irradiated vaccinia virus or poliovirus, both of which replicate in the cell cytoplasm. These results suggest UVER and X-ray ER in mammalian cells may be restricted to viruses which are replicated in the cell nucleus. (author)

  18. Modes of DNA repair and replication

    International Nuclear Information System (INIS)

    Hanawalt, P.; Kondo, S.

    1979-01-01

    Modes of DNA repair and replication require close coordination as well as some overlap of enzyme functions. Some classes of recovery deficient mutants may have defects in replication rather than repair modes. Lesions such as the pyrimidine dimers produced by ultraviolet light irradiation are the blocks to normal DNA replication in vivo and in vitro. The DNA synthesis by the DNA polymerase 1 of E. coli is blocked at one nucleotide away from the dimerized pyrimidines in template strands. Thus, some DNA polymerases seem to be unable to incorporate nucleotides opposite to the non-pairing lesions in template DNA strands. The lesions in template DNA strands may block the sequential addition of nucleotides in the synthesis of daughter strands. Normal replication utilizes a constitutive ''error-free'' mode that copies DNA templates with high fidelity, but which may be totally blocked at a lesion that obscures the appropriate base pairing specificity. It might be expected that modified replication system exhibits generally high error frequency. The error rate of DNA polymerases may be controlled by the degree of phosphorylation of the enzyme. Inducible SOS system is controlled by recA genes that also control the pathways for recombination. It is possible that SOS system involves some process other than the modification of a blocked replication apparatus to permit error-prone transdimer synthesis. (Yamashita, S.)

  19. Replication and robustness in developmental research.

    Science.gov (United States)

    Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J

    2014-11-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  20. Nonequilibrium Entropic Bounds for Darwinian Replicators

    Directory of Open Access Journals (Sweden)

    Jordi Piñero

    2018-01-01

    Full Text Available Life evolved on our planet by means of a combination of Darwinian selection and innovations leading to higher levels of complexity. The emergence and selection of replicating entities is a central problem in prebiotic evolution. Theoretical models have shown how populations of different types of replicating entities exclude or coexist with other classes of replicators. Models are typically kinetic, based on standard replicator equations. On the other hand, the presence of thermodynamical constraints for these systems remain an open question. This is largely due to the lack of a general theory of statistical methods for systems far from equilibrium. Nonetheless, a first approach to this problem has been put forward in a series of novel developements falling under the rubric of the extended second law of thermodynamics. The work presented here is twofold: firstly, we review this theoretical framework and provide a brief description of the three fundamental replicator types in prebiotic evolution: parabolic, malthusian and hyperbolic. Secondly, we employ these previously mentioned techinques to explore how replicators are constrained by thermodynamics. Finally, we comment and discuss where further research should be focused on.

  1. Commercial Building Partnerships Replication and Diffusion

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-16

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

  2. Bir Ortaokul Matematik Öğretmeninin WebQuestin Uygulamasına Yönelik Görüşü

    OpenAIRE

    Kurtuluş, Aytaç; Ada, Tuba; Yanık, H. Bahadır

    2014-01-01

    t. Bu çalışmada bir WebQuest etkinliğini sınıfında ilk defa uygulayan bir ortaokul matematik öğretmeninin WebQuestin uygulama sürecine ve öğrencileri üzerinde bıraktığı etkisine yönelik görüşü incelenmiştir. Çalışmaya katılan öğretmen histogram konusuna yönelik hazırlamış olduğu bir WebQuest etkinliğini 8. sınıf öğrencilerine proje ödevi olarak uygulamıştır. Bu çalışma olgubilim araştırması olarak tasarlanmış olup, veriler öğretmenle uygulama sırasında ve sonunda yapılan görüşm...

  3. Hayvan Islahında Güncel Bir Yaklaşım: CRISPR/Cas9 Genom Modifikasyon Sistemi

    Directory of Open Access Journals (Sweden)

    Fatih Bilgi

    2016-12-01

    Full Text Available Genom modifikasyonları, verimin arttırılmasında ve hastalıklara karşı direncin kazandırılması konusunda önemli avantajlar sağlama potansiyeli içermektedir. Bireyin zaten sahip olduğu bir genin susturulmasını ya da ifade edilmesini sağlayan gen düzenlenmesi yöntemleri (gene editing çevreyi en az etkileyerek genetik yapının geliştirilmesi konusunda önemli olanaklar sağlamaktadır. Son zamanlarda yeni genetik düzenleme yöntemleri geliştirilmiştir. Bunlar ZFN (Zinc Finger Nuclease’ler, TALEN (Transcription Activator-like Effector Nuclease’ler ve CRISPR/Cas nükleaz sistemleridir. CRISPR/Cas sistemi yabancı genetik materyalleri yok etmek için RNA güdümlü nükleazları kullanan bir mikrobiyal immün sistem olup, bu sistemin günümüzde hayvanlarda basit ve etkili bir gen düzenleme mekanizması olarak kullanılabilme potansiyeli değerlendirilmektedir. Bu derlemede CRISPR/Cas9 sistemi ve hayvan ıslahında kullanılabilirliği özetlenmiştir.

  4. Sistem Yaklaşımına Dayalı Bir Metodoloji: Yumuşak Sistemler Metodolojisi

    Directory of Open Access Journals (Sweden)

    S. Serap Kurbanoğlu

    1993-06-01

    Full Text Available Bu yazıda Checkland tarafından geliştirilen sistem yaklaşımına dayalı bir metodoloji olan Yumuşak Sistemler Metodolojisi (YSM tanıtılmaktadır. YSM "problemi yaratan nedir" ? veya yaşanan zorlukların üstesinden gelmek için yapılması gereken nedir?" gibi konuların açık olmadığı belirsiz ve karmaşık problem durumlarında kullanılmak üzere geliştirilmiştir. Bu tür problemlerle (karmaşık, belirsiz "katı" olarak tanımlanan problemler arasındaki en temel farklılık ikincisinde sonucun veya başarılmak istenen şeyin önceden bilinmesidir. YSM kavramsal model geliştirmeye dayanır. Geliştirilen kavramsal model gerçek dünyadaki mevcut durumla karşılaştırılır. Ve bu ikisi arasındaki farklılıklar, çözümleri problem durumundaki insanlarla tartışabilecek problem alanlarını aydınlatmaya yardımcı olur. YSM yöneticilerin varsayılan bir problem hakkındaki önyargılı fikirler üzerinde geliştirilmiş zayıf ve hazır çözümlere yönelmelerine engel olur. Bu yazıda önyargılı çözümlerden kaçınmanın ve gerçek problemlere ulaşmanın önemi de ayrıca vurgulanmaktadır.

  5. Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

    Science.gov (United States)

    Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

    2018-03-01

    Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

  6. Organization of Replication of Ribosomal DNA in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Linskens, Maarten H.K.; Huberman, Joel A.

    1988-01-01

    Using recently developed replicon mapping techniques, we have analyzed the replication of the ribosomal DNA in Saccharomyces cerevisiae. The results show that (i) the functional origin of replication colocalizes with an autonomously replicating sequence element previously mapped to the

  7. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  8. How many bootstrap replicates are necessary?

    Science.gov (United States)

    Pattengale, Nicholas D; Alipour, Masoud; Bininda-Emonds, Olaf R P; Moret, Bernard M E; Stamatakis, Alexandros

    2010-03-01

    Phylogenetic bootstrapping (BS) is a standard technique for inferring confidence values on phylogenetic trees that is based on reconstructing many trees from minor variations of the input data, trees called replicates. BS is used with all phylogenetic reconstruction approaches, but we focus here on one of the most popular, maximum likelihood (ML). Because ML inference is so computationally demanding, it has proved too expensive to date to assess the impact of the number of replicates used in BS on the relative accuracy of the support values. For the same reason, a rather small number (typically 100) of BS replicates are computed in real-world studies. Stamatakis et al. recently introduced a BS algorithm that is 1 to 2 orders of magnitude faster than previous techniques, while yielding qualitatively comparable support values, making an experimental study possible. In this article, we propose stopping criteria--that is, thresholds computed at runtime to determine when enough replicates have been generated--and we report on the first large-scale experimental study to assess the effect of the number of replicates on the quality of support values, including the performance of our proposed criteria. We run our tests on 17 diverse real-world DNA--single-gene as well as multi-gene--datasets, which include 125-2,554 taxa. We find that our stopping criteria typically stop computations after 100-500 replicates (although the most conservative criterion may continue for several thousand replicates) while producing support values that correlate at better than 99.5% with the reference values on the best ML trees. Significantly, we also find that the stopping criteria can recommend very different numbers of replicates for different datasets of comparable sizes. Our results are thus twofold: (i) they give the first experimental assessment of the effect of the number of BS replicates on the quality of support values returned through BS, and (ii) they validate our proposals for

  9. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast.

    Science.gov (United States)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine; Mankouri, Hocine W; Hickson, Ian D

    2014-04-07

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

  10. MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.

    Science.gov (United States)

    Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K

    2018-03-15

    The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response. Copyright © 2018 American Society for Microbiology.

  11. Sterol Binding by the Tombusviral Replication Proteins Is Essential for Replication in Yeast and Plants.

    Science.gov (United States)

    Xu, Kai; Nagy, Peter D

    2017-04-01

    Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication have been gaining full attention only recently. Previous work with Tomato bushy stunt tombusvirus (TBSV) in model host yeast has revealed essential roles for phosphatidylethanolamine and sterols in viral replication. To further our understanding of the role of sterols in tombusvirus replication, in this work we showed that the TBSV p33 and p92 replication proteins could bind to sterols in vitro The sterol binding by p33 is supported by cholesterol recognition/interaction amino acid consensus (CRAC) and CARC-like sequences within the two transmembrane domains of p33. Mutagenesis of the critical Y amino acids within the CRAC and CARC sequences blocked TBSV replication in yeast and plant cells. We also showed the enrichment of sterols in the detergent-resistant membrane (DRM) fractions obtained from yeast and plant cells replicating TBSV. The DRMs could support viral RNA synthesis on both the endogenous and exogenous templates. A lipidomic approach showed the lack of enhancement of sterol levels in yeast and plant cells replicating TBSV. The data support the notion that the TBSV replication proteins are associated with sterol-rich detergent-resistant membranes in yeast and plant cells. Together, the results obtained in this study and the previously published results support the local enrichment of sterols around the viral replication proteins that is critical for TBSV replication. IMPORTANCE One intriguing aspect of viral infections is their dependence on efficient subcellular assembly platforms serving replication, virion assembly, or virus egress via budding out of infected cells. These assembly platforms might involve sterol-rich membrane microdomains, which are

  12. X-irradiation affects all DNA replication intermediates when inhibiting replication initiation

    International Nuclear Information System (INIS)

    Loenn, U.; Karolinska Hospital, Stockholm

    1982-01-01

    When a human melanoma line was irradiated with 10 Gy, there was, after 30 to 60 min, a gradual reduction in the DNA replication rate. Ten to twelve hours after the irradiation, the DNA replication had returned to near normal rate. The results showed tht low dose-rate X-irradiation inhibits preferentially the formation of small DNA replication intermediates. There is no difference between the inhibition of these replication intermediates formed only in the irradiated cells and those formed also in untreated cells. (U.K.)

  13. Enhanced replication of damaged SV40 DNA in carcinogen-treated monkey cells

    International Nuclear Information System (INIS)

    Maga, J.A.; Dixon, K.

    1984-01-01

    Treatment of mammalian cells with certain chemical or physical carcinogens prior to infection with ultraviolet-irradiated virus results in enhanced survival or reactivation of the damaged virus. To investigate the molecular basis of this enhanced reactivation (ER), Simian virus 40 DNA replication in carcinogen-treated cells was examined. Treatment of monkey kidney cells with N-acetoxy-2-acetylamino-fluorene or UV radiation 24 h prior to infection with ultraviolet-irradiated Simian virus 40 leads to enhancement of viral DNA replication measured at 36 h after infection by [ 3 H]thymidine incorporation or hybridization. The enhancement of DNA replication is observed when cells are treated from 1 to 60 h before infection or 1 to 16 h after infection. The fact that enhancement is observed also when cells are treated after infection rules out the possiblity that enhancement occurs at the level of adsorption or penetration of the virus. Measurements of the time course of viral DNA replication indicate that pretreatment of cells does not alter the time of onset of viral DNA replication. It is concluded that ER of Simain virus 40 occurs at the level of viral DNA replication. (author)

  14. Realistic Vascular Replicator for TAVR Procedures.

    Science.gov (United States)

    Rotman, Oren M; Kovarovic, Brandon; Sadasivan, Chander; Gruberg, Luis; Lieber, Baruch B; Bluestein, Danny

    2018-04-13

    Transcatheter aortic valve replacement (TAVR) is an over-the-wire procedure for treatment of severe aortic stenosis (AS). TAVR valves are conventionally tested using simplified left heart simulators (LHS). While those provide baseline performance reliably, their aortic root geometries are far from the anatomical in situ configuration, often overestimating the valves' performance. We report on a novel benchtop patient-specific arterial replicator designed for testing TAVR and training interventional cardiologists in the procedure. The Replicator is an accurate model of the human upper body vasculature for training physicians in percutaneous interventions. It comprises of fully-automated Windkessel mechanism to recreate physiological flow conditions. Calcified aortic valve models were fabricated and incorporated into the Replicator, then tested for performing TAVR procedure by an experienced cardiologist using the Inovare valve. EOA, pressures, and angiograms were monitored pre- and post-TAVR. A St. Jude mechanical valve was tested as a reference that is less affected by the AS anatomy. Results in the Replicator of both valves were compared to the performance in a commercial ISO-compliant LHS. The AS anatomy in the Replicator resulted in a significant decrease of the TAVR valve performance relative to the simplified LHS, with EOA and transvalvular pressures comparable to clinical data. Minor change was seen in the mechanical valve performance. The Replicator showed to be an effective platform for TAVR testing. Unlike a simplified geometric anatomy LHS, it conservatively provides clinically-relevant outcomes and complement it. The Replicator can be most valuable for testing new valves under challenging patient anatomies, physicians training, and procedural planning.

  15. Huzursuzlukla Yuvaya Dönüş: Fatih-Harbiye Ve Bir Tereddüdün Romanı’nda Aşılamayan Kriz

    Directory of Open Access Journals (Sweden)

    Jale Özata Dirlikyapan

    2017-12-01

    Full Text Available Döneminin en önemli romancı ve düşünce adamlarından biri olan Peyami Safa (1899-1961, hemen her devride romanları üzerine düşünülen ve söz söylenen bir yazar olmuştur. Özellikle ilk dönem romanlarının şematik yapısından sıkça söz edilmiş ve bu romanlar çoğunlukla “ulusal alegori” düşüncesi etrafında değerlendirilmişlerdir. Fatih-Harbiye ve Bir Tereddüdün Romanı kitaplarındaki kadın-erkek ilişkileri çoğunlukla bir medeniyet krizinin görünümleri olarak ele alınmış, romanlardaki bazı önemli detaylar görmezden gelinebilmiştir. Her iki romanın sonunda da Batıyı temsil eden değerler savuşturulmuş gibi görünse de, aslında romanlar bir tür bezginlik, boşvermişlik ve huzursuzlukla son bulur. Peyami Safa genelde söylendiği gibi dişil, irrasyonel, kozmopolit unsurları bünyesinden kovmayı arzular görünse de, tam da dişil, irrasyonel veya “vahşi ölçüde samimi” olanın alanındayken kısmen daha özgür bir bilinçle nitelikli edebiyat yapıyordur. Birbirine sıkı sıkıya bağlı olan bu unsurlar, yazarın “milli ideal” etrafında ördüğü kürsü konuşmaları tarafından gizlenmeye, baskılanmaya çalışılsa da, bunları ele alışı sayesinde Peyami Safa’daki “büyük romancı” kendini gösterebilmiştir

  16. Correlation of fine needle aspiration cytology with histopathology findings in cases of thyroid lesions in Bir Hospital

    Directory of Open Access Journals (Sweden)

    PB Thapa

    2014-01-01

    Full Text Available Aims: To correlate the findings of fine needle aspiration cytology (FNAC with the histopathology( HPE of the excised nodule or specimen and to assess the accuracy and efficacy of FNAC in the diagnosis of the thyroid nodules. Materials and methods: This is a prospective study conducted at the Department of Ear Nose Throat (ENT & Head & NecK Surgery( HNS, National Academy of Medical Sciences, Bir Hospital, Kathmandu from 2nd January 2009 to 29th December 2011. One hundred patients with thyroid nodule were included in the study. Results: Out of 100 patients 77 were females and 23 males. The age ranged from 11-60 years. Statistical analysis of results for Benign Thyroid lesion showed 98.6% sensitivity, 75 % specificity. Likewise, results for Malignant thyroid lesions showed 75 % sensitivity, 98.6 % specificity . Conclusion: FNAC has high accuracy in the diagnostic evaluation of thyroid lesions. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 23-29 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9670

  17. Bir Üniversitenin Ebelik Bölümü Öğrencilerinde Premenstrual Sendrom

    OpenAIRE

    DOĞAN YÜKSEKOL, Özlem

    2018-01-01

    Premenstruel sendrom en sık ergenlik döneminde görülen, genç kızların yaşamını, derslere devam etme durumunu, okul başarısını ve sosyal yaşamını olumsuz etkileyen bir sağlık sorunudur. Bu çalışma Elazığ Sağlık Yüksekokulu Ebelik bölümünde öğrenim gören öğrencilerin premenstruel semptomlarını belirlemek amacıyla yapılmıştır. Tanımlayıcı ve ilişki arayıcı nitelikteki çalışmanın evrenini 2010-2011 eğitim öğretim yılında Fırat Üniversitesi Elazığ Sağlık Yüksekokulu Ebelik bölümü 1., 2. ve 3.sınıf...

  18. Raspberry Pi Kullanılarak bir Akıllı Ev Uygulaması Geliştirilmesi

    OpenAIRE

    YÜZGEÇ, Uğur; ABA, Ömer

    2018-01-01

    Bu çalışmada Raspberry Pi mikrodenetleyici tabanlı bir akıllı ev uygulaması gerçekleştirilmiştir. Çalışmakapsamında 64 Bit BCM2837 Chip, 1.2 GHz ARM Cortex A53 dört çekirdekli işlemci özelliklerine sahip RaspberryPi 3 mikrodenetleyici ile ultrasonik, hareket algılayıcı, sıcaklık/nem, titreşim modülü, servo motoru, buzzer (sesmodülü), kamera, ateş algılayıcı, DC motor, LDR, RGB led, tuş takımı, su tespit, RFID kit sensörleri kullanılmıştır.Uygulama kısmında çeşitli senaryo durumları için yapıl...

  19. GENÇ PARTİ'Yİ ANLAMAK (Parti, Lider ve Kitle Üzerine Bir Çalısma)

    OpenAIRE

    TÜRK, Hasan Bahadır

    2007-01-01

    Türk, Hasan Bahadır, Genç Parti’yi Anlamak: Parti, Lider ve Kitle Üzerine BirÇalısma, Doktora Tezi, Danısman: Doç.Dr. Aykut Çelebi, 399 s.ÖZETBu çalısmanın amacı; Genç Parti’nin temel yapısal özelliklerine ısık tutmaktır. Çalısma;Genç Parti’yi lider, kadro, parti tipolojisi, ideoloji ve söylem gibi parçalarındanhareketle analiz etmeye ve kitleyle kurdugu iliskiyi tartısmaya odaklanacaktır. Çalısma,üç ana bölümden olusmaktadır. lk iki bölümde Uzanlar’ın genel yapısı, yükselis veçöküs süreci Ge...

  20. Permanent Magnet Senkron Bir Motorun Tasarımının Optimizasyonunda Genetik Algoritma Uygulaması

    OpenAIRE

    Mutluer, Mümtaz; Bilgin, Osman

    2012-01-01

    Kalıcı mıknatıslı senkron motorlar, yüksek moment/hacim oranları ve özellikle yüksek verimlerinden dolayı, 1985 yılından itibaren endüstriyel uyuglmarda tercih edilmektedir. Kalıcı mıknatıslı senkron motorların verimini belirleyen temel faktör rotor sargılarının olmaması olsa da, tasarım parametrelerinin ve kalıcı mıknatıslı senkron motor tasarım modelinin etkin seçimi de verimi etkilemektedir. Bu çalışma konsantre-sargılı yüzey-mıknatıslı bir kalıcı mıknatıslı senkron motorun tasarım op...

  1. Macaristan Türkolojisi Üzerine Bir Biyo-Biyografi Denemesi An Attempt At A Bioagrapy of Hungarian Turkology

    Directory of Open Access Journals (Sweden)

    Mehmet GÜMÜŞKILIÇ

    2012-12-01

    Full Text Available Hungary is the place where Turcology studies started in modern terms. For many years Hungarian scientists have been engaged in Turkish studies- as a part of their research of their own roots -. Theyhad great contribution to Turkish language, history, literature,geography, ethnography and music. It may also be supposed thatTurkish Hungarian relations were better than now. However, todayTurkish Hungarian relations have been enjoying a revival again.Considering the closeness of Hungarians and Turks, it is obvious thatthe two nations share some responsibilities in improving their relations.In this article, after organizing the names of all the HungarianTurcologs who have conducted studies on Turks after the foundation ofmodern Turcology in alphabetical order, their articles on Turcologyfromoldest to newest will be presented as well as their career lives.Also the lists of some of the studies on some of the Turcologs will begiven. The Hungarian scientists and their studies mentioned in thisarticle do not encompass all of them. If we include other articles, books,presentations, credits, reviews and the studies of other scientists thatwe haven’t been able to mention here, the number will swell and gobeyond the limits of this article. In the future, we hope that furtherdetailed studies will be conducted on Hungarian Turcology. Through anattempt at biyo biography, we have tried to touch briefly on theimportance Hungarians give to Turks.Undoubtedly in the future, Turkish Hungarian relations andfriendship will further improve with the help of further detailed studies.This article will serve its purpose if we have a tiny contribution. Modern anlamda Türkoloji çalışmalarının başladığı yer Macaristan’dır. Macar bilim adamları yıllar boyu -bir bakıma kendi köklerini de arama çabaları sebebiyle- Türklük bilimiyle uğraştılar. Türk diline, tarihine, kültürüne, edebiyatına, coğrafyasına, etnoğrafyasına, musikîsine b

  2. Bir destan kahramanı olarak Alpamış'ın sosyal statüsü

    OpenAIRE

    Çetin, Nagihan

    2016-01-01

    Bu makalede Vadim V. Trepavlov tarafından hazırlanmış olan “Yakut Destan Kahramanının Sosyal Statüsü” isimli makale esas alınarak Alpamış Destanının Kazak varyantı üzerinden Alpamış’ın sosyal statüsü belirlenmeye çalışılmıştır.Alpamış Destanı “Altay, Kazak, Karakalpak, Özbek, Başkurt Türkleri tarafından bilinen bir destandır. Bu destanın Türk kültüründeki önemini göstermesi bakımından yayılmış olduğu coğrafya önemlidir. Destanda epik Türk destanlarının pek çoğunda görülen çocuksuzluk ve bunun...

  3. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  4. İletişim Çalışmalarında Yeni Bir Mecra: Finansal İletişim

    Directory of Open Access Journals (Sweden)

    Gökhan Gökgöz

    2013-09-01

    Full Text Available 1970’li yıllar toplumsal ve politik tarih açısından önemli bir uğrağı temsil eder. Bu yılların başında yaşanan kriz, ekonominin işleyiş süreçlerini, devletin yapısını ve toplumsal alanın tasavvur edilme biçimini büyük ölçüde değiştirmiştir. Bu dönemde, finansal sermaye, kapitalizm içerisinde bir hegemonik lider olarak ön plana çıkmış; devlet, bir yandan üretimin çekirdeğinden uzak bir yerde konumlandırılırken diğer yandan paranın dolaşım kanallarının rehabilitasyonu işine odaklanmış; insana ilişkin değerler, kültürel mefhumlar ve toplumsal pratikler ise birer değişken olarak ekonomi-politikanın merkezine taşınmıştır. Kültür ile ekonomi arasındaki geleneksel ilişki bozulmuş; bir ekonomi-politikanın başarısı, toplumsal aktörlere temas etme kabiliyeti ile paralel hale gelmiştir. Finansallaşma sürecinde bu temas, iletişim politikaları vasıtasıyla sağlanır; ekonomi-politika ve bundan sorumlu merkezi kurumlarla toplumsal alan arasındaki bağ, iletişim stratejileri üzerinden kurulur; ekonomik alan ile kültürel alan arasındaki boşluk, iletişim kanalları içerisinden taşınan enformasyon marifetiyle doldurulur; insana ilişkin öngörülemezlikler, iletişim süreçleri vasıtasıyla öngörülebilir kılınır. Bu çalışmada, iletişim çalışmaları içerisinde yeni bir mecra olarak çağrılan “finansal iletişim”in farklı temas noktalarına işaret edilecek ve her bir uğrağın finansal iletişim alanına bağlandığı nokta, modeller üzerinden gösterilecektir. 

  5. Drill machine guidance using natural occurring radiation

    International Nuclear Information System (INIS)

    Dahl, H.D.; Schroeder, R.L.; Williams, B.J.

    1980-01-01

    A drilling machine guidance system is described which uses only the naturally occuring radiation within the seam or stratum of interest. The apparatus can be used for guiding horizontal drilling machines through coal seams and the like. (U.K.)

  6. Multiple Primary Cancers: Simultaneously Occurring Prostate ...

    African Journals Online (AJOL)

    2016-05-20

    May 20, 2016 ... occurring prostate cancer and other primary tumors-our experience and literature ..... thyroid cancers, pancreatic tumors, renal cancers, and melanoma. ... Hsing AW, Yeboah E, Biritwum R, Tettey Y, De Marzo AM,. Adjei A, et ...

  7. Spacetime replication of continuous variable quantum information

    International Nuclear Information System (INIS)

    Hayden, Patrick; Nezami, Sepehr; Salton, Grant; Sanders, Barry C

    2016-01-01

    The theory of relativity requires that no information travel faster than light, whereas the unitarity of quantum mechanics ensures that quantum information cannot be cloned. These conditions provide the basic constraints that appear in information replication tasks, which formalize aspects of the behavior of information in relativistic quantum mechanics. In this article, we provide continuous variable (CV) strategies for spacetime quantum information replication that are directly amenable to optical or mechanical implementation. We use a new class of homologically constructed CV quantum error correcting codes to provide efficient solutions for the general case of information replication. As compared to schemes encoding qubits, our CV solution requires half as many shares per encoded system. We also provide an optimized five-mode strategy for replicating quantum information in a particular configuration of four spacetime regions designed not to be reducible to previously performed experiments. For this optimized strategy, we provide detailed encoding and decoding procedures using standard optical apparatus and calculate the recovery fidelity when finite squeezing is used. As such we provide a scheme for experimentally realizing quantum information replication using quantum optics. (paper)

  8. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  9. Extremal dynamics in random replicator ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Kärenlampi, Petri P., E-mail: petri.karenlampi@uef.fi

    2015-10-02

    The seminal numerical experiment by Bak and Sneppen (BS) is repeated, along with computations with replicator models, including a greater amount of features. Both types of models do self-organize, and do obey power-law scaling for the size distribution of activity cycles. However species extinction within the replicator models interferes with the BS self-organized critical (SOC) activity. Speciation–extinction dynamics ruins any stationary state which might contain a steady size distribution of activity cycles. The BS-type activity appears as a dissimilar phenomenon in comparison to speciation–extinction dynamics in the replicator system. No criticality is found from the speciation–extinction dynamics. Neither are speciations and extinctions in real biological macroevolution known to contain any diverging distributions, or self-organization towards any critical state. Consequently, biological macroevolution probably is not a self-organized critical phenomenon. - Highlights: • Extremal Dynamics organizes random replicator ecosystems to two phases in fitness space. • Replicator systems show power-law scaling of activity. • Species extinction interferes with Bak–Sneppen type mutation activity. • Speciation–extinction dynamics does not show any critical phase transition. • Biological macroevolution probably is not a self-organized critical phenomenon.

  10. Replication of cultured lung epithelial cells

    International Nuclear Information System (INIS)

    Guzowski, D.; Bienkowski, R.

    1986-01-01

    The authors have investigated the conditions necessary to support replication of lung type 2 epithelial cells in culture. Cells were isolated from mature fetal rabbit lungs (29d gestation) and cultured on feeder layers of mitotically inactivated 3T3 fibroblasts. The epithelial nature of the cells was demonstrated by indirect immunofluorescent staining for keratin and by polyacid dichrome stain. Ultrastructural examination during the first week showed that the cells contained myofilaments, microvilli and lamellar bodies (markers for type 2 cells). The following changes were observed after the first week: increase in cell size; loss of lamellar bodies and appearance of multivesicular bodies; increase in rough endoplasmic reticulum and golgi; increase in tonafilaments and well-defined junctions. General cell morphology was good for up to 10 wk. Cells cultured on plastic surface degenerated after 1 wk. Cell replication was assayed by autoradiography of cultures exposed to ( 3 H)-thymidine and by direct cell counts. The cells did not replicate during the first week; however, between 2-10 wk the cells incorporated the label and went through approximately 6 population doublings. They have demonstrated that lung alveolar epithelial cells can replicate in culture if they are maintained on an appropriate substrate. The coincidence of ability to replicate and loss of markers for differentiation may reflect the dichotomy between growth and differentiation commonly observed in developing systems

  11. The evolutionary ecology of molecular replicators.

    Science.gov (United States)

    Nee, Sean

    2016-08-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

  12. Yalın üretim için değer akış haritalandırma ve simülasyon: Mobilya sektöründe bir uygulama

    Directory of Open Access Journals (Sweden)

    Hacer Güner Gören

    2017-08-01

    Full Text Available Pazarda yoğun rekabetin artması sonucu, yalın prensipler birçok işletme tarafından takip edilmektedir. Bu prensipler, israfları azaltarak ve yok ederek operasyonların etkinliğini artırmaya odaklanmaktadır. Yalın olabilmek için ise birçok değişik teknik ve yöntem uygulanmaktadır. Bu tekniklerden biri de kolaylıkla farklı sektörlere uygulanabilen Değer Akış Haritalandırmadır (DAH. Fakat, DAH sadece bir organizasyonun mevcut durumunu gösteren statik bir araçtır. Bu eksikliği giderebilmek adına, önerilen iyileştirmelerin değerlendirilmesini kolayca yapabilen simülasyon yardımcı teknik olarak yaygın olarak kullanılmaktadır. Bu çalışma, israfın çok olduğu mobilya sektörüne yönelik DAH ve simülasyonu birleştiren bir endüstriyel uygulama örneği sunmaktadır. Belirlenen bir ürün ailesine yönelik iyileştirme önerileri ile birlikte mevcut ve gelecek durum haritaları DAH kullanılarak açıklanmıştır. Bir simülasyon modeli oluşturularak “önce” ve “sonra” senaryoları detaylı olarak analiz edilmiştir.

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

    Science.gov (United States)

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

    2013-01-01

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

  14. The progression of replication forks at natural replication barriers in live bacteria

    NARCIS (Netherlands)

    Moolman, M.C.; Tiruvadi Krishnan, S; Kerssemakers, J.W.J.; de Leeuw, R.; Lorent, V.J.F.; Sherratt, David J.; Dekker, N.H.

    2016-01-01

    Protein-DNA complexes are one of the principal barriers the replisome encounters during replication. One such barrier is the Tus-ter complex, which is a direction dependent barrier for replication fork progression. The details concerning the dynamics of the replisome when encountering these

  15. Using Replicates in Information Retrieval Evaluation.

    Science.gov (United States)

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

    2017-09-01

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

  16. DNA replication stress and cancer chemotherapy.

    Science.gov (United States)

    Kitao, Hiroyuki; Iimori, Makoto; Kataoka, Yuki; Wakasa, Takeshi; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

    2018-02-01

    DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Evolution of Database Replication Technologies for WLCG

    CERN Document Server

    Baranowski, Zbigniew; Blaszczyk, Marcin; Dimitrov, Gancho; Canali, Luca

    2015-01-01

    In this article we summarize several years of experience on database replication technologies used at WLCG and we provide a short review of the available Oracle technologies and their key characteristics. One of the notable changes and improvement in this area in recent past has been the introduction of Oracle GoldenGate as a replacement of Oracle Streams. We report in this article on the preparation and later upgrades for remote replication done in collaboration with ATLAS and Tier 1 database administrators, including the experience from running Oracle GoldenGate in production. Moreover, we report on another key technology in this area: Oracle Active Data Guard which has been adopted in several of the mission critical use cases for database replication between online and offline databases for the LHC experiments.

  18. Synchronization of DNA array replication kinetics

    Science.gov (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.

    2016-04-01

    In the present work we discuss the features of the DNA replication kinetics at the case of multiplicity of simultaneously elongated DNA fragments. The interaction between replicated DNA fragments is carried out by free protons that appears at the every nucleotide attachment at the free end of elongated DNA fragment. So there is feedback between free protons concentration and DNA-polymerase activity that appears as elongation rate dependence. We develop the numerical model based on a cellular automaton, which can simulate the elongation stage (growth of DNA strands) for DNA elongation process with conditions pointed above and we study the possibility of the DNA polymerases movement synchronization. The results obtained numerically can be useful for DNA polymerase movement detection and visualization of the elongation process in the case of massive DNA replication, eg, under PCR condition or for DNA "sequencing by synthesis" sequencing devices evaluation.

  19. Psoriatik Artritli Bir Hastada Ižnfliksimab Tedavisi Sirasinda Gelisen Guillain-Barre Sendromu: Olgu Sunumu

    Directory of Open Access Journals (Sweden)

    Osman Tufekci

    2014-12-01

    Full Text Available Tumor necrosis factor (TNF-α plays an important role in many aspects of immune system development, immune-response regulation, and T-cell–mediated tissue injury. The evidence that TNF-α, released by auto reactive T cells and macrophages, may contribute to the pathogenesis of immune-mediated demyelinating neuropathies is reviewed. Demyelinating neuropathies are rare adverse events of anti–TNF-α therapy. Improvement usually occurs after drug interruption and/or in association with conventional treatments for demyelinating neuropathies. We aimed to report a patient with demyelinating neuropathy occurring after TNF blocker (infliximab treatment. The development of Guillain-Barre syndrome in this report may have been secondary to anti-TNF-α treatment.  The influence of anti-TNF-α treatment continuation on the long-term course of neuropathy is variable, suggesting that anti-TNF-α treatment withdrawal is not always necessary for neuropathy control. But such as the report, anti-TNF-α treatment may be stopped.

  20. Signal replication in a DNA nanostructure

    Science.gov (United States)

    Mendoza, Oscar; Houmadi, Said; Aimé, Jean-Pierre; Elezgaray, Juan

    2017-01-01

    Logic circuits based on DNA strand displacement reaction are the basic building blocks of future nanorobotic systems. The circuits tethered to DNA origami platforms present several advantages over solution-phase versions where couplings are always diffusion-limited. Here we consider a possible implementation of one of the basic operations needed in the design of these circuits, namely, signal replication. We show that with an appropriate preparation of the initial state, signal replication performs in a reproducible way. We also show the existence of side effects concomitant to the high effective concentrations in tethered circuits, such as slow leaky reactions and cross-activation.

  1. Temporal organization of cellular self-replication

    Science.gov (United States)

    Alexandrov, Victor; Pugatch, Rami

    Recent experiments demonstrate that single cells grow exponentially in time. A coarse grained model of cellular self-replication is presented based on a novel concept - the cell is viewed as a self-replicating queue. This allows to have a more fundamental look into various temporal organizations and, importantly, the inherent non-Markovianity of noise distributions. As an example, the distribution of doubling times can be inferred and compared to single cell experiments in bacteria. We observe data collapse upon scaling by the average doubling time for different environments and present an inherent task allocation trade-off. Support from the Simons Center for Systems Biology, IAS, Princeon.

  2. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

    Inheritance and maintenance of the DNA sequence and its organization into chromatin are central for eukaryotic life. To orchestrate DNA-replication and -repair processes in the context of chromatin is a challenge, both in terms of accessibility and maintenance of chromatin organization. To meet...... the challenge of maintenance, cells have evolved efficient nucleosome-assembly pathways and chromatin-maturation mechanisms that reproduce chromatin organization in the wake of DNA replication and repair. The aim of this Review is to describe how these pathways operate and to highlight how the epigenetic...... landscape may be stably maintained even in the face of dramatic changes in chromatin structure....

  3. Iterated function systems for DNA replication

    Science.gov (United States)

    Gaspard, Pierre

    2017-10-01

    The kinetic equations of DNA replication are shown to be exactly solved in terms of iterated function systems, running along the template sequence and giving the statistical properties of the copy sequences, as well as the kinetic and thermodynamic properties of the replication process. With this method, different effects due to sequence heterogeneity can be studied, in particular, a transition between linear and sublinear growths in time of the copies, and a transition between continuous and fractal distributions of the local velocities of the DNA polymerase along the template. The method is applied to the human mitochondrial DNA polymerase γ without and with exonuclease proofreading.

  4. Involvement of Autophagy in Coronavirus Replication

    Directory of Open Access Journals (Sweden)

    Paul Britton

    2012-11-01

    Full Text Available Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3 in coronavirus replication.

  5. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

    Wæhrens, Brian Vejrum; Yang, Cheng; Madsen, Erik Skov

    2012-01-01

    Purpose – With the aim to support offshore production line replication, this paper specifically aims to explore the use of templates and principles to transfer expansive productive knowledge embedded in a production line and understand the contingencies that influence the mix of these approaches......; and (2) rather than being viewed as alternative approaches, templates and principles should be seen as complementary once the transfer motive moves beyond pure replication. Research limitations – The concepts introduced in this paper were derived from two Danish cases. While acceptable for theory...

  6. In vivo dynamics of EBNA1-oriP interaction during latent and lytic replication of Epstein-Barr virus.

    Science.gov (United States)

    Daikoku, Tohru; Kudoh, Ayumi; Fujita, Masatoshi; Sugaya, Yutaka; Isomura, Hiroki; Tsurumi, Tatsuya

    2004-12-24

    The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is required for maintenance of the viral genome DNA during the latent phase of EBV replication but continues to be synthesized after the induction of viral productive replication. An EBV genome-wide chromatin immunoprecipitation assay revealed that EBNA1 constantly binds to oriP of the EBV genome during not only latent but also lytic infection. Although the total levels of EBNA1 proved constant throughout the latter, the levels of the oriP-bound form were increased as lytic infection proceeded. EBV productive DNA replication occurs at discrete sites in nuclei, called replication compartments, where viral replication proteins are clustered. Confocal laser microscopic analyses revealed that whereas EBNA1 was distributed broadly in nuclei as fine punctate dots during the latent phase of infection, the protein became redistributed to the viral replication compartments and localized as distinct spots within and/or nearby the compartments after the induction of lytic replication. Taking these findings into consideration, oriP regions of the EBV genome might be organized by EBNA1 into replication domains that may set up scaffolding for lytic replication and transcription.

  7. Three-Dimensional Architecture and Biogenesis of Membrane Structures Associated with Plant Virus Replication

    Directory of Open Access Journals (Sweden)

    Xuejiao Jin

    2018-01-01

    Full Text Available Positive-sense (+ RNA viruses represent the most abundant group of viruses and are dependent on the host cell machinery to replicate. One remarkable feature that occurs after (+ RNA virus entry into cells is the remodeling of host endomembranes, leading to the formation of viral replication factories. Recently, rapid progress in three-dimensional (3D imaging technologies, such as electron tomography (ET and focused ion beam-scanning electron microscopy (FIB-SEM, has enabled researchers to visualize the novel membrane structures induced by viruses at high resolution. These 3D imaging technologies provide new mechanistic insights into the viral infection cycle. In this review, we summarize the latest reports on the cellular remodeling that occurs during plant virus infection; in particular, we focus on studies that provide 3D architectural information on viral replication factories. We also outline the mechanisms underlying the formation of these membranous structures and discuss possible future research directions.

  8. The Genomic Replication of the Crenarchaeal Virus SIRV2

    DEFF Research Database (Denmark)

    Martinez Alvarez, Laura

    reinitiation events may partially explain the branched topology of the viral replication intermediates. We also analyzed the intracellular location of viral replication, showing the formation of viral peripheral replication centers in SIRV2-infected cells, where viral DNA synthesis and replication...

  9. Bayesian tests to quantify the result of a replication attempt

    NARCIS (Netherlands)

    Verhagen, J.; Wagenmakers, E.-J.

    2014-01-01

    Replication attempts are essential to the empirical sciences. Successful replication attempts increase researchers’ confidence in the presence of an effect, whereas failed replication attempts induce skepticism and doubt. However, it is often unclear to what extent a replication attempt results in

  10. Determination of natural occurring radionuclides concentrations

    International Nuclear Information System (INIS)

    Stajic, J.; Markovic, V.; Krstic, D.; Nikezic, D.

    2011-01-01

    Tobacco smoke contains certain concentrations of naturally occurring radionuclides from radioactive chains of uranium and thorium - 214 Pb, 214 Bi, 228 Ac, 208 Tl, 226 Ra, 232 Th and 40 K. Inhaling of tobacco smoke leads to internal exposure of man. In order to estimate absorbed dose of irradiation it is necessary to determine concentrations of radionuclides present in the tobacco leaves. In this paper specific activities of naturally occurring radionuclides were measured in tobacco samples from cigarettes which are used in Serbia. [sr

  11. Detection of Harmonic Occurring using Kalman Filtering

    DEFF Research Database (Denmark)

    Hussain, Dil Muhammad Akbar; Shoro, Ghulam Mustafa; Imran, Raja Muhammed

    2014-01-01

    /current characteristic. These harmonics are not to be allowed to grow beyond a certain limit to avoid any grave consequence to the customer’s main supply. Filters can be implemented at the power source or utility location to eliminate these harmonics. In this paper we detect the instance at which these harmonics occur...

  12. Formal synthesis of naturally occurring norephedrine

    Indian Academy of Sciences (India)

    A concise and simple synthesis of 1-hydroxy-phenethylamine derivatives has been achieved following classical organic transformations using commercially available chiral pools. The said derivatives were explored for the synthesis of naturally occurring bio-active small molecules. Formal synthesis of norephedrine, virolin ...

  13. A naturally occurring trap for antiprotons

    International Nuclear Information System (INIS)

    Eades, J.; Morita, N.; Ito, T.M.

    1993-05-01

    The phenomenon of delayed annihilation of antiprotons in helium is the first instance of a naturally occurring trap for antimatter in ordinary matter. Recent studies of this effect at CERN are summarized, and plans are described for laser excitation experiments to test its interpretation in terms of metastable exotic helium atom formation. (author)

  14. Jerky periods: myoclonus occurring solely during menses

    NARCIS (Netherlands)

    Buijink, Arthur W. G.; Gelauff, Jeannette M.; van der Salm, Sandra M. A.; Tijssen, Marina A. J.; van Rootselaar, Anne-Fleur

    2013-01-01

    In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic

  15. Sesli Okuma ve Konuşma Prozodisi: İlişkisel Bir Çalışma

    Directory of Open Access Journals (Sweden)

    Hasan Keskin

    2013-02-01

    Full Text Available Bu araştırma,  ilköğretim dördüncü sınıf öğrencilerinin sesli okuma ve konuşma prozodileri arasındaki ilişkiyi incelemek amacıyla ilişkisel tarama modelinde yapılmıştır. Araştırmaya,  Konya ve Afyonkarahisar’da ilköğretim dördüncü sınıfa devam eden 50 öğrenci katılmıştır.  Öğrencilerin sesli okumaları ve konuşmaları video ile kayıt altına alınmış, daha sonra bu kayıtlar üzerinde ölçekler aracılığıyla puanlamalar yapılmıştır. Sesli okuma ve konuşma prozodisi arasındaki ilişkiyi belirlemeye yönelik, Pearson Momentler Çarpım Korelasyon Tekniği kullanılmıştır. Analiz sonuçlarına göre, öğrencilerin sesli okuma ve konuşma prozodileri arasında, pozitif yönlü orta düzeyde bir ilişki çıkmıştır. Öğrencilerin sesli okumaları ve konuşma prozodi puanları cinsiyet açısından ayrı ayrı incelenmiş; kız ve erkek öğrencilerin ortalamaları arasında anlamlı bir farklılık çıkmamıştır. Ayrıca, öğrencilerin sesli okuma ve konuşmalarındaki prozodik düzeyi belirlemeye yönelik ölçümler yapılmıştır. Bu ölçüm sonuçlarına göre, araştırmaya katılan öğrencilerin %52’sinin sesli okuma prozodilerinin,  %48’inin ise konuşma prozodilerinin düşük düzeyde olduğu görülmüştür.

  16. The International Framework of Information Policies Enformasyon Politikalarına Küresel Bir Bakış

    Directory of Open Access Journals (Sweden)

    Nick Moore

    2000-03-01

    Full Text Available The emergence of information societies is one of the defining characteristics of the last decade of the twentieth century. Countries all over the world are repositioning themselves to take advantage of the opportunities offered by the information age. They share common objectives although there are significant differences in the motivations underlying the re-positioning and in the mechanisms chosen to implement information society developments. Formal frameworks of policy are being established to steer the development of information societies. There can be few other examples of technological change stimulating formal policy creation in order to bring about social change. This paper surveys the approaches to information policy in various countries all over the world and forecasts future progress with views as to how to ensure that the information society will work for the good of every one. 20. yüzyılın son on yılının belirleyici karakteristiklerinden biri enformasyon toplumlarının ortaya çıkması olmuştur. Dünyanın dört bir yanında ülkeler, enformasyon çağının yarattığı olanaklardan yararlanabilmek için konumlarını gözden geçirmektedirler. Bu ülkelerin hedefleri aynı olmakla birlikte, yönelimlerinin ardındaki motivasyonlar her zaman aynı değildir ve enformasyon toplumu gelişmelerini uygulamaya sokmak için seçtikleri mekanizmalar önemli farklılıklar göstermektedir. Enformasyon toplumuna geçişi harekete geçirmek için resmi politikalar saptanmaktadır. Bunun dışında, teknolojik değişimin, bağlantılı bir toplumsal değişimi sağlamak için resmi politikalar belirlenmesini zorladığı çok ender görülmüştür. Bu bildiride dünyanın çeşitli ülkelerinde enformasyon politikalarına yaklaşımların neler olduğu gözden geçirilmekte, geleceğe yönelik görüşler sunulmakta ve enformasyon toplumunun herkesin yararına gelişmesi için neler yapılması gerektiği konusu işlenmektedir.

  17. Optical replication techniques for image slicers

    Czech Academy of Sciences Publication Activity Database

    Schmoll, J.; Robertson, D.J.; Dubbeldam, C.M.; Bortoletto, F.; Pína, L.; Hudec, René; Prieto, E.; Norrie, C.; Ramsay- Howat, S.

    2006-01-01

    Roč. 50, 4-5 (2006), s. 263-266 ISSN 1387-6473 Institutional research plan: CEZ:AV0Z10030501 Keywords : smart focal planes * image slicers * replication Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 1.914, year: 2006

  18. Inhibition of DNA replication by ultraviolet light

    International Nuclear Information System (INIS)

    Edenberg, H.J.

    1976-01-01

    DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10 J/m 2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers

  19. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-08-01

    Full Text Available The Enterovirus (EV and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV. They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.

  20. Chaotic interactions of self-replicating RNA.

    Science.gov (United States)

    Forst, C V

    1996-03-01

    A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.

  1. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  2. Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

    2017-08-01

    Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Preferential flow occurs in unsaturated conditions

    Science.gov (United States)

    Nimmo, John R.

    2012-01-01

    Because it commonly generates high-speed, high-volume flow with minimal exposure to solid earth materials, preferential flow in the unsaturated zone is a dominant influence in many problems of infiltration, recharge, contaminant transport, and ecohydrology. By definition, preferential flow occurs in a portion of a medium – that is, a preferred part, whether a pathway, pore, or macroscopic subvolume. There are many possible classification schemes, but usual consideration of preferential flow includes macropore or fracture flow, funneled flow determined by macroscale heterogeneities, and fingered flow determined by hydraulic instability rather than intrinsic heterogeneity. That preferential flow is spatially concentrated associates it with other characteristics that are typical, although not defining: it tends to be unusually fast, to transport high fluxes, and to occur with hydraulic disequilibrium within the medium. It also has a tendency to occur in association with large conduits and high water content, although these are less universal than is commonly assumed. Predictive unsaturated-zone flow models in common use employ several different criteria for when and where preferential flow occurs, almost always requiring a nearly saturated medium. A threshold to be exceeded may be specified in terms of the following (i) water content; (ii) matric potential, typically a value high enough to cause capillary filling in a macropore of minimum size; (iii) infiltration capacity or other indication of incipient surface ponding; or (iv) other conditions related to total filling of certain pores. Yet preferential flow does occur without meeting these criteria. My purpose in this commentary is to point out important exceptions and implications of ignoring them. Some of these pertain mainly to macropore flow, others to fingered or funneled flow, and others to combined or undifferentiated flow modes.

  4. Biržoje prekiaujamų fondų (ETF bendrojo išlaidų rodiklio tyrimas

    Directory of Open Access Journals (Sweden)

    Lukas Macijauskas

    2011-07-01

    Full Text Available Diskusijai, kuris – pasyvus ar aktyvus – investicijų valdymas yra efektyvesnis, ryškėjant, biržoje prekiaujami fondai (Exchange Traded Funds – ETF sulaukia vis didesnio investuotojų dėmesio, o tai skatina detalesnius šių priemonių tyrinėjimus. Pagrindinis šio straipsnio tikslas – įvairiais aspektais analizuoti šių finansinių priemonių bendrąjį išlaidų rodiklį (Total Expense Ratio (TER. Naudodami duomenų bazę, kurią sudaro 1020 ETF, apskaičiavome, kad paprastųjų, t. y. nenaudojančių sverto ir ne atvirkštinių ETF, svertinis bendrojo išlaidų rodiklio vidurkis (įvertinant kapitalizaciją yra lygus 0,32 proc. Analizė rodo, kad atvirkštiniai ir svertiniai ETF vidutiniškai apie 3 kartus brangesni nei paprastieji ETF. Atlikę skaičiavimus nustatėme, kad bendrasis išlaidų rodiklis yra gerokai mažesnis nei vidutinių investicinių fondų. Tai leidžia daryti išvadą, kad vertinant per išlaidų koeficiento prizmę, ETF yra daug efektyvesnė investavimo priemonė nei įprasti investiciniai fondai.Straipsnis lietuvių kalba

  5. Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

    Directory of Open Access Journals (Sweden)

    Sameera Dharia

    2011-02-01

    Full Text Available Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR K(+ ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+ addition to the external bath. Cu(2+ is known to bind to the ShB-IR ion channel and inhibit Shaker K(+ conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

  6. Monitoring voltage-dependent charge displacement of Shaker B-IR K+ ion channels using radio frequency interrogation.

    Science.gov (United States)

    Dharia, Sameera; Rabbitt, Richard D

    2011-02-28

    Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K(+) ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu(2+) addition to the external bath. Cu(2+) is known to bind to the ShB-IR ion channel and inhibit Shaker K(+) conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu(2+)-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains--capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug-protein interactions.

  7. /ı/ Türkçede Bir Anasesbirim midir? Is The Letter of /ı/ Archiphoneme In Turkish?

    Directory of Open Access Journals (Sweden)

    Fatih ÖZEK

    2013-03-01

    Full Text Available We can mention two letters of /ı/ in world languages. One ofthem is /ı/ (ы vowel called "yeri" in Russian language and the other is/ı/ vowel that is designated with [ï] in alphabet of internationaltranscription and that almost belongs to the Turkish language. The /ı/vowel of the Turkish language is a velarized, narrow, flat velum vowel interms of its characteristic features. It has normal duration. /a/, /i/ and/u/ vowels are generally deemed as cardinal vowels of the Turkishlanguage. According to this common view, eight vowels in the Turkishlanguage derived from these vowels. However, A.N. Baskakov thinksthat /ı/ is an archiphoneme and [i,u,ü] vowels are variants of the /ı/phoneme. This different view has had an influence on issuance of thispaper. It is possible to define the archiphoneme as main voicecontaining characteristics of more than one voice or first known voicesof a language. The archiphonemes are strong voices. They usually retaintheir existences. However, such characteristics are not seen in /ı/phoneme. Following determinations can be considered as evidenceshereof:1. qlıç (~ qılıç [cliç, cliz/kiliç] writings in Codex Cumanicus,2. Front palatalization of the /ı/ vowel in the first syllable (Uigur biş- ~ bış-‘mature, age out ’; Khorezm biş-; Kipchak biş- ~ piş-; Chagatai piş-; ETT piş-; Bashkir,Tatar, Turkmen, Azerbaijani biş-; Kazakh pis-; Uzbek, New Uigur, Gagauz, Trk. piş- Dünya dillerinde iki tane /ı/’dan bahsedilebilir. Bunlardan bir tanesi Rusça “yeri” adı verilen /ı/ (ы ünlüsü, diğeri ise uluslar arası transkripsiyon alfabesinde [ï] işaretiyle gösterilen ve neredeyse tamamen Türkçeye ait olan /ı/ ünlüsüdür. Türkçeye has /ı/ ünlüsü nitelik özellikleri bakımından kalın, dar, düz bir art damak ünlüsüdür. Nicelik bakımından ise normal sürelidir. /a/, /i/ ve /u/ ünlüleri genel olarak Türkçenin temel ünlüleri olarak kabul edilir. Bu yaygın görüşe g

  8. Studies on the mechanism of replication of adenovirus DNA. IV. Discontinuous DNA chain propagation

    NARCIS (Netherlands)

    Vlak, J.M.; Rozijn, Th.H.; Sussenbach, J.S.

    The replication of adenovirus type 5 DNA occurs by discontinuous chain propagation via short pieces of DNA. These pieces accumulate if the infected cells are treated with hydroxyurea. They have a sedimentation coefficient of 11 S corresponding to a molecular weight of about 700,000, and they contain

  9. Therapist-Aided Exposure for Women with Lifelong Vaginismus: A Replicated Single-Case Design

    Science.gov (United States)

    ter Kuile, Moniek M.; Bulte, Isis; Weijenborg, Philomeen T. M.; Beekman, Aart; Melles, Reinhilde; Onghena, Patrick

    2009-01-01

    Vaginismus is commonly described as a persistent difficulty in allowing vaginal entry of a penis or other object. Lifelong vaginismus occurs when a woman has never been able to have intercourse. A replicated single-case A-B-phase design was used to investigate the effectiveness of therapist-aided exposure for lifelong vaginismus. A baseline period…

  10. Schadenfreude as a mate-value-tracking mechanism. Replication and extension of Colyn and Gordon .

    NARCIS (Netherlands)

    van Dijk, W.W.; Ouwerkerk, J.W.; Smith, R.H.

    2015-01-01

    The present research provides a replication and extension of L. A. Colyn and A. K. Gordon's (2013) study on gender differences in schadenfreude. An experiment-in which both the gender of the unfortunate other and the dimension on which the misfortune occurred were manipulated-showed that female

  11. Vizier And Alim Giving Political Advice: Ethical Argumentation In Asafname And Usul Al-Hikam Bir Vezir ile Bir Alimin Siyasetle İlgili Tavsiyelerinin Karşılaştırılması: Asafname ve Usulü’l-Hikem’de Kullanılan Ahlaki Gerekçeler

    Directory of Open Access Journals (Sweden)

    Salih BAYRAM

    2013-03-01

    Full Text Available This article provides a parallel reading of Lutfi Paşa’s Asafname and Hasan Kafi’s Usul al-Hikam, both 16th century Ottoman siyasetnames. These books, the former penned by a prominent member of the bureaucracy and the latter by a middle ranking scholar, were compared in terms of the religious references they make, and the justifications they provide for specific recommendations. It was found, as was expected, that Usul uses religious references and religious justification more frequently than Asafname does. However, formal/rule-based justification, a larger ethical category encompassing the religious as well as traditional and legal justification and defined in opposition to utilitarian/consequentialist justification, was used more frequently by Asafname. Despite its heavily religious language and the religious background of its author, Usul used utilitarian arguments more frequently than formal ones when making recommendations. Bu makalede 16. yy. Osmanlı siyasetnamelerinden Lütfi Paşa’nınAsafname’si ile Hasan Kafi Akhisari’nin Usulü’l Hikem’ikarşılaştırılacaktır. Birincisi sadrazamlık da dahil olmak üzere birçoküst düzey görevde bulunmuş bir devlet adamı tarafından, diğeri iseçeşitli vilayetlerde kadılık ve müderrislik görevlerinde bulunmuş bir dinadamı tarafından kaleme alınmış olan bu iki eser, kullandıkları dinireferansların içeriği ve siyasetle ilgili tavsiyelerinin ne şekildegerekçelendirildiği bakımlarından paralel bir okumaya tabi tutulmuştur. Beklendiği üzere dini referansların ve dini içerikligerekçelerin Usulül’l Hikem’de Asafname’den daha fazla kullanıldığıgörülmüştür. Bununla beraber, daha geniş bir kategori olan ve hemdini, hem geleneksel, hem de yasal gerekçelendirmeyi içeren kuraladayalı/formel argümanların Asafname’de daha fazla kullanıldığıgörülmüştür. Dini bir eğitim alan ve dini referansları metin içinde s

  12. Malezya’da Din-Devlet İlişkisine Kısa Bir Bakış

    Directory of Open Access Journals (Sweden)

    Mehmet Özay

    2013-03-01

    Full Text Available AbstractStarting from the second half of the 1960s onwards, socio-religious youth movements, which are regarded as the initial element of civil expressions on university campuses, were constructively influential on the perception of the political elites’ understanding of Islam and political evolution of the Islamisation policies in the process in Malaysia. There are opinions that this effect encompassed the efforts of Islamisation particularly in the 1980s. In this process, the task of the state apparatus, as a political power, which managed the religious domain mostly considered belonging to the civil sector, deserves to be scrutinized in relation with at least some influential factors in the near and distant past of the Muslim Malay community. And, it cannot be overseen that the functions of the traditional Malay rulers, say, Sultans, were transferred, to some or larger extent, to the Federal government after the independence. With regard to this, in this article, the present writer will focus on some aspects of the policies of Dr. Mahathir Mohamad, who has molded majorily the history of modern Malaysia, regarding his Islamisation policy aligned with the state-religion relationship.ÖzetMalezya’da 1960’lı yılların ikinci yarısından itibaren üniversite kampüslerinde başlayan ve sivilleşmenin bir unsuru olarak telâkki edilen dini-toplumsal hareketlerin İslam’ın ülke siyasi elitince algılanmasında ve pratikte İslamlaştırma adıyla anılabilecek politikalara evrilmesinde önemli etkisi olmuştur. Bu etkinin, özellikle 1980’li yıllarda devlet eliyle İslamlaştırma çabalarına yol açtığı konusunda görüşler bulunmaktadır. Bu süreçte, yani devletin siyasi bir güç olarak sivil alana dahil olan dini çekip çevirme işini üstlenmesinde, özellikle Müslüman Malay toplumunun yakın ve uzak geçmişindeki kimi faktörler dikkate alınmayı hak etmektedir. Bu bağlamda, geleneksel Malay devletlerinde Sultanlar

  13. Asynchronous replication and autosome-pair non-equivalence in human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Devkanya Dutta

    Full Text Available A number of mammalian genes exhibit the unusual properties of random monoallelic expression and random asynchronous replication. Such exceptional genes include genes subject to X inactivation and autosomal genes including odorant receptors, immunoglobulins, interleukins, pheromone receptors, and p120 catenin. In differentiated cells, random asynchronous replication of interspersed autosomal genes is coordinated at the whole chromosome level, indicative of chromosome-pair non-equivalence. Here we have investigated the replication pattern of the random asynchronously replicating genes in undifferentiated human embryonic stem cells, using fluorescence in situ hybridization based assay. We show that allele-specific replication of X-linked genes and random monoallelic autosomal genes occur in human embryonic stem cells. The direction of replication is coordinated at the whole chromosome level and can cross the centromere, indicating the existence of autosome-pair non-equivalence in human embryonic stem cells. These results suggest that epigenetic mechanism(s that randomly distinguish between two parental alleles are emerging in the cells of the inner cell mass, the source of human embryonic stem cells.

  14. DNA moves sequentially towards the nuclear matrix during DNA replication in vivo

    Directory of Open Access Journals (Sweden)

    Aranda-Anzaldo Armando

    2011-01-01

    Full Text Available Abstract Background In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM. There is varied evidence indicating that DNA replication occurs in replication factories organized upon the NM and that DNA loops may correspond to the actual replicons in vivo. In normal rat liver the hepatocytes are arrested in G0 but they synchronously re-enter the cell cycle after partial-hepatectomy leading to liver regeneration in vivo. We have previously determined in quiescent rat hepatocytes that a 162 kbp genomic region containing members of the albumin gene family is organized into five structural DNA loops. Results In the present work we tracked down the movement relative to the NM of DNA sequences located at different points within such five structural DNA loops during the S phase and after the return to cellular quiescence during liver regeneration. Our results indicate that looped DNA moves sequentially towards the NM during replication and then returns to its original position in newly quiescent cells, once the liver regeneration has been achieved. Conclusions Looped DNA moves in a sequential fashion, as if reeled in, towards the NM during DNA replication in vivo thus supporting the notion that the DNA template is pulled progressively towards the replication factories on the NM so as to be replicated. These results provide further evidence that the structural DNA loops correspond to the actual replicons in vivo.

  15. Variety of DNA Replication Activity Among Cyanobacteria Correlates with Distinct Respiration Activity in the Dark.

    Science.gov (United States)

    Ohbayashi, Ryudo; Yamamoto, Jun-Ya; Watanabe, Satoru; Kanesaki, Yu; Chibazakura, Taku; Miyagishima, Shin-Ya; Yoshikawa, Hirofumi

    2017-02-01

    Cyanobacteria exhibit light-dependent cell growth since most of their cellular energy is obtained by photosynthesis. In Synechococcus elongatus PCC 7942, one of the model cyanobacteria, DNA replication depends on photosynthetic electron transport. However, the critical signal for the regulatory mechanism of DNA replication has not been identified. In addition, conservation of this regulatory mechanism has not been investigated among cyanobacteria. To understand this regulatory signal and its dependence on light, we examined the regulation of DNA replication under both light and dark conditions among three model cyanobacteria, S. elongatus PCC 7942, Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120. Interestingly, DNA replication activity in Synechocystis and Anabaena was retained when cells were transferred to the dark, although it was drastically decreased in S. elongatus. Glycogen metabolism and respiration were higher in Synechocystis and Anabaena than in S. elongatus in the dark. Moreover, DNA replication activity in Synechocystis and Anabaena was reduced to the same level as that in S. elongatus by inhibition of respiratory electron transport after transfer to the dark. These results demonstrate that there is disparity in DNA replication occurring in the dark among cyanobacteria, which is caused by the difference in activity of respiratory electron transport. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication.

    Science.gov (United States)

    Camara, Johanna E; Breier, Adam M; Brendler, Therese; Austin, Stuart; Cozzarelli, Nicholas R; Crooke, Elliott

    2005-08-01

    Initiation of DNA replication from the Escherichia coli chromosomal origin is highly regulated, assuring that replication occurs precisely once per cell cycle. Three mechanisms for regulation of replication initiation have been proposed: titration of free DnaA initiator protein by the datA locus, sequestration of newly replicated origins by SeqA protein and regulatory inactivation of DnaA (RIDA), in which active ATP-DnaA is converted to the inactive ADP-bound form. DNA microarray analyses showed that the level of initiation in rapidly growing cells that lack datA was indistinguishable from that in wild-type cells, and that the absence of SeqA protein caused only a modest increase in initiation, in agreement with flow-cytometry data. In contrast, cells lacking Hda overinitiated replication twofold, implicating RIDA as the predominant mechanism preventing extra initiation events in a cell cycle.

  17. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

    KAUST Repository

    Elshenawy, Mohamed; Jergic, Slobodan; Xu, Zhi Qiang; Sobhy, Mohamed Abdelmaboud; Takahashi, Masateru; Oakley, Aaron J.; Dixon, Nicholas E.; Hamdan, Samir

    2015-01-01

    In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a 'replication fork trap' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. ©2015 Macmillan Publishers Limited. All rights reserved.

  18. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier

    KAUST Repository

    Elshenawy, Mohamed

    2015-08-31

    In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a \\'replication fork trap\\' that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus-Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus-Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes. ©2015 Macmillan Publishers Limited. All rights reserved.

  19. Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability.

    Science.gov (United States)

    Schalbetter, Stephanie A; Mansoubi, Sahar; Chambers, Anna L; Downs, Jessica A; Baxter, Jonathan

    2015-08-18

    Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein-DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein-DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin.

  20. Natural occurring radioactive substances. Vol. 1

    Energy Technology Data Exchange (ETDEWEB)

    Emara, A E [National Center for radiation Research and Technology Atomic Energy Authority, Cairo (Egypt)

    1996-03-01

    Naturally occurring radioactive substances produced by cosmic rays of those of terrestrial origin are surveyed. The different radioactive decay series are discussed. Special emphasis is given to the element radium as regards its properties and distribution in different environmental samples. The properties of naturally occurring k-40 and its distribution in different natural media are also outlined. Induced radionuclides which are formed as a result of the interaction of cosmic rays with the constituents of the atmosphere are mentioned. In this respect the intensity of natural background radiation and the dose at different locations and levels is surveyed. Some regions of exceptionally high radioactivity which result in high exposure rates are mentioned. Monazite deposits and water springs are mentioned in some detail. The Oklo phenomenon as a natural reactor is also discussed. 8 tabs.

  1. Natural occurring radioactive substances. Vol. 1

    International Nuclear Information System (INIS)

    Emara, A.E.

    1996-01-01

    Naturally occurring radioactive substances produced by cosmic rays of those of terrestrial origin are surveyed. The different radioactive decay series are discussed. Special emphasis is given to the element radium as regards its properties and distribution in different environmental samples. The properties of naturally occurring k-40 and its distribution in different natural media are also outlined. Induced radionuclides which are formed as a result of the interaction of cosmic rays with the constituents of the atmosphere are mentioned. In this respect the intensity of natural background radiation and the dose at different locations and levels is surveyed. Some regions of exceptionally high radioactivity which result in high exposure rates are mentioned. Monazite deposits and water springs are mentioned in some detail. The Oklo phenomenon as a natural reactor is also discussed. 8 tabs

  2. Bir Ortaokul Matematik Öğretmeninin WebQuestin Uygulamasına Yönelik Görüşü

    Directory of Open Access Journals (Sweden)

    Aytaç Kurtuluş

    2014-03-01

    Full Text Available t. Bu çalışmada bir WebQuest etkinliğini sınıfında ilk defa uygulayan bir ortaokul matematik öğretmeninin WebQuestin uygulama sürecine ve öğrencileri üzerinde bıraktığı etkisine yönelik görüşü incelenmiştir. Çalışmaya katılan öğretmen histogram konusuna yönelik hazırlamış olduğu bir WebQuest etkinliğini 8. sınıf öğrencilerine proje ödevi olarak uygulamıştır. Bu çalışma olgubilim araştırması olarak tasarlanmış olup, veriler öğretmenle uygulama sırasında ve sonunda yapılan görüşmelerden ve uygulama sonunda öğrencilerle yapılan görüşmeler ve öğrenci sunumlarının gözlemlenmesi yoluyla toplanmıştır. Çalışma bulguları, WebQuest uygulamasının öğrencilerin motivasyonuna, özgüvenlerine olumlu katkıda bulunduğunu göstermiştir. Elde edilen öğretmen görüşleri, WebQuestlerin proje ve performans ödevi olarak uygulanabileceğini ve ortaokul matematik öğretim programını desteklediğini ortaya koymuşt

  3. Portföy Yönetiminde Sistematik Olmayan Riski Azaltacak Bir Doğrusal Programlama Model Önerisi

    Directory of Open Access Journals (Sweden)

    Murat UĞURLU

    2016-04-01

    Full Text Available Geleneksel portföy teorisi portföy riskini azaltmak için çeşitlendirmeye önem verirken modern portföy teorisi geçmiş nicel bilgileri kullanarak matematiksel ve istatistiksel yöntemlerle yatırımcıya etkin sınır üzerinde bir portföy oluşturma seçeneğini sunmaktadır. Modern portföy teorisinin öncülerinden Markowitz risk olarak standart sapmayı dikkate almıştır. Seçim yapılacak hisse senetlerinin sayısının çokluğu standart sapma hesaplamalarını zorlaştırmaktadır. Konno ve Yamazaki risk olarak standart sapma yerine mutlak sapmayı kullanmış, böylelikle portföy seçimi doğrusal programlama modeli olarak ifade edilebilmiştir. Her iki model portföye girecek hisse senetlerinin sayısına ve endüstri kollarına dağıtılmasına müdahale edemez. Bu ise oluşacak portföyün, teorik olarak bir tek hisse senedinden oluşmasını mümkün kılabilir. Bu çalışmada, bahsedilen olumsuzluğu gidermek amacıyla Konno ve Yamazaki modeli ilave kısıtlarla genişletilerek yatırımcıya en yüksek beklenen getiriyi sağlayan yeni bir doğrusal programlama modeli önerisi yapılmaktadır.

  4. Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Nunya Chotiwan

    2018-02-01

    Full Text Available We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several

  5. Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

    Science.gov (United States)

    Chotiwan, Nunya; Andre, Barbara G; Sanchez-Vargas, Irma; Islam, M Nurul; Grabowski, Jeffrey M; Hopf-Jannasch, Amber; Gough, Erik; Nakayasu, Ernesto; Blair, Carol D; Belisle, John T; Hill, Catherine A; Kuhn, Richard J; Perera, Rushika

    2018-02-01

    We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several flaviviruses transmitted

  6. Inclusion bodies are a site of ebolavirus replication.

    Science.gov (United States)

    Hoenen, Thomas; Shabman, Reed S; Groseth, Allison; Herwig, Astrid; Weber, Michaela; Schudt, Gordian; Dolnik, Olga; Basler, Christopher F; Becker, Stephan; Feldmann, Heinz

    2012-11-01

    Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.

  7. Interferon lambda inhibits dengue virus replication in epithelial cells.

    Science.gov (United States)

    Palma-Ocampo, Helen K; Flores-Alonso, Juan C; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Flores-Mendoza, Lilian; Herrera-Camacho, Irma; Rosas-Murrieta, Nora H; Santos-López, Gerardo

    2015-09-28

    In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

  8. Jerky Periods - Myoclonus Occurring Solely During Menses

    OpenAIRE

    Arthur W. Buijink; Jeannette M. Gelauff; Sandra M. van der Salm; Marina A. Tijssen; Anne-Fleur van Rootselaar

    2013-01-01

    Background: In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. Case Report: A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. Discussion: This appears to be the first descr...

  9. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Science.gov (United States)

    Ke, Po-Yuan; Chen, Steve S-L

    2013-01-01

    So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  10. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Directory of Open Access Journals (Sweden)

    Po-Yuan Ke

    Full Text Available So far how hepatitis C virus (HCV replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp infection and downregulated cell surface level of CD81, a critical HCV entry (coreceptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  11. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. The Problem of Anonymity in Archives: A Literature Review=Arşivlerde Anonimlik Sorunu: Bir Literatür Değerlendirmesi

    Directory of Open Access Journals (Sweden)

    Emily Ross

    2013-12-01

    Full Text Available Archivists processing documents rely on factors such as authorship and provenance to contextualize their materials and render them searchable. But in my past experience as an archives user, I repeatedly came across instances of anonymity: letters and diaries by unnamed authors or to unknown recipients, photographs of unknown subjects. In some cases this anonymity is a loss of information that was once there, but in other case it enabled the material to come into existence in the first place: such as in the case of satirical political poetry, for which a writer might face legal censure. In this literature review, the issue of anonymity in the archives is explored, both in a pragmatic sense (recommended strategies for managing it, and a philosophical sense (according anonymous documents the same status as documents with known authors./Arşivcilikte belgelerin işlenmesi, materyallerin kavramsallaştırılması ve aranabilir hale gelmesinde önemli olan yazarlık ve kaynak (menşe gibi faktörlere dayanmaktadır. Ancak bir arşiv kullanıcısı olarak deneyimlerimizde defalarca isimsiz yazarlar tarafından bilinmeyen kişilere atfedilmiş mektuplar ve günlükler, bilinmeyen konuların fotoğrafları gibi anonim eserlerle karşılaşmaktayız. Bir zamanlar bu anonimlik bazen bir bilgi kaybı olarak görülürken bazen de belgenin yazarının yasal kınamaya maruz kalabildiği hicivli siyasi bir şiir örneğinde olduğu gibi eserin ilk etapta ortaya çıkmasını sağlamaktaydı. Bu literatür taramasında arşivlerde anonimlik sorunu hem pragmatik anlamda (konunun yönetimi için önerilen stratejiler hem de felsefi anlamda (anonim belgelere uygun olarak bilinen yazarlı belgelerle aynı statüde ele alınmaktadır.

  13. Mahalli Fıkra Tipine Bir Örnek: Erzurumlu Naim Hoca One Type of Anecdote of Local Example: Hoca Erzurumlu Naim

    Directory of Open Access Journals (Sweden)

    Yusuf KOTAN

    2012-09-01

    Full Text Available One of the important types of folk literature satire, in a large geographical area consisting of many thousands of years, products of oral tradition of folk literaturen. These products, although oral edebiyatımız as a kind of took its place in the literature long ago, particularly after the Tanzimat era has gained vitality. This vitality,though no doubt in some quarters that the jokes have suffered tab, inalmost every nation acquires an important social and cultural life.Feeling and thinking, of a nation, intelligence, humor, and mostimportantly the power of judgment to reflect the common opinion is ofgreat importance in terms of paragraphs. One of the important elementsin the formation of these clauses in the clause types. These types, asdescribed in the paragraph is the hero, as well as to express thecommon characteristics of living is important for society. These typeswith almost every region of Anatolia, and they faced a yararlanmaktayızthis narrative. Who live in this very important region in terms ofreflecting the properties of typecasting, giving expressions to represent aparticular feature of the local stage.Erzurum folklore, is a rich resource for Turkish folklore. Althoughthis has been a rich source folklorumuzun on the part of many researchstudies conducted on jokes is almost negligible. Based on theseapproaches, we also provide a contribution to the folklore of Erzurum inboth types of clause in Erzurum, an important place in the memory ofour people who had said Naim Hodja jokes we introduce this valuableanecdotes of people will try to share with you. Halk edebiyatımızın önemli türlerinden biri olan fıkralar, çok geniş bir coğrafi alan içinde oluşan binlerce yıldan beri sözlü gelenekte yaşayan halk edebiyatı ürünleridir. Bu ürünler, sözlü edebiyatımız içerisinde yerini çok öncelerden almış olsa da bir tür olarak edebiyatımızda bilhassa Tanzimat döneminden sonra canlılık kazanmıştır. Bu canl

  14. Gezgin satıcı problemi için yeni bir meta-sezgisel: kör fare algoritması

    Directory of Open Access Journals (Sweden)

    Tevfik YILDIRIM

    2016-02-01

    Full Text Available Gezgin Satıcı Problemi (GSP, başlangıç ve bitiş şehirleri aynı olan ve her şehrin sadece bir kez ziyaret edildiği minimum mesafeli turu bulma problemidir. Şehir sayısı arttıkça, kesin yöntemler ile kabul edilebilir sürelerde bir optimum çözüm bulunması zordur. Bu nedenle, son elli yılda GSP’nin çözümü için doğadan ve biyolojiden esinlenen birçok meta-sezgisel yöntem geliştirilmiştir. Bu çalışmada, toprak altındaki bireysel tünel sistemlerinde yaşayan kör farelerin toprak altındaki engelleri geçme stratejisinden esinlenilerek GSP’nin çözümü için yeni bir meta-sezgisel tasarlanmıştır. Geliştirilen yönteme Kör Fare Algoritması adı verilmiştir. Bu yeni sezgisel ile farklı boyutlardaki simetrik test veri setleri için deneyler yapılmış ve sonuçları bilinen en iyi sonuçlar ile kıyaslanmıştır. Önerilen meta-sezgisel henüz literatürdeki diğer algoritmalarla yarışabilecek düzeyde olmamasına rağmen, başlangıç test çözümlerinin umut verici olduğu söylenebilir.Anahtar Kelimeler: Gezgin satıcı problemi, Kombinatoryel eniyileme, Meta-Sezgisel, Kör fare algoritması

  15. High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins

    2013-11-01

    Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

  16. DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells

    International Nuclear Information System (INIS)

    Lavin, M.F.; McCombe, P.; Kidson, C.

    1976-01-01

    Mouse neuroblastoma cells differentiated when grown in the absence of serum; differentiation was reversed on the addition of serum. Differentiated cells were more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally resulted in immediate, synchronous entry into S phase, irradiation just before the addition of serum resulted in a long delay in the onset of DNA replication. During this lag period, incorporated 3 H-thymidine appeared in the light density region of CsCl gradients, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may have been due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold. (author)

  17. The Role of the Transcriptional Response to DNA Replication Stress.

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

  18. The Role of the Transcriptional Response to DNA Replication Stress

    Science.gov (United States)

    Herlihy, Anna E.; de Bruin, Robertus A.M.

    2017-01-01

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

  19. Host phylogeny determines viral persistence and replication in novel hosts.

    Directory of Open Access Journals (Sweden)

    Ben Longdon

    2011-09-01

    Full Text Available Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts.

  20. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  1. Replication Protein A (RPA) Phosphorylation Prevents RPA Association with Replication Centers

    OpenAIRE

    Vassin, Vitaly M.; Wold, Marc S.; Borowiec, James A.

    2004-01-01

    Mammalian replication protein A (RPA) undergoes DNA damage-dependent phosphorylation at numerous sites on the N terminus of the RPA2 subunit. To understand the functional significance of RPA phosphorylation, we expressed RPA2 variants in which the phosphorylation sites were converted to aspartate (RPA2D) or alanine (RPA2A). Although RPA2D was incorporated into RPA heterotrimers and supported simian virus 40 DNA replication in vitro, the RPA2D mutant was selectively unable to associate with re...

  2. Functions of Ubiquitin and SUMO in DNA Replication and Replication Stress

    Science.gov (United States)

    García-Rodríguez, Néstor; Wong, Ronald P.; Ulrich, Helle D.

    2016-01-01

    Complete and faithful duplication of its entire genetic material is one of the essential prerequisites for a proliferating cell to maintain genome stability. Yet, during replication DNA is particularly vulnerable to insults. On the one hand, lesions in replicating DNA frequently cause a stalling of the replication machinery, as most DNA polymerases cannot cope with defective templates. This situation is aggravated by the fact that strand separation in preparation for DNA synthesis prevents common repair mechanisms relying on strand complementarity, such as base and nucleotide excision repair, from working properly. On the other hand, the replication process itself subjects the DNA to a series of hazardous transformations, ranging from the exposure of single-stranded DNA to topological contortions and the generation of nicks and fragments, which all bear the risk of inducing genomic instability. Dealing with these problems requires rapid and flexible responses, for which posttranslational protein modifications that act independently of protein synthesis are particularly well suited. Hence, it is not surprising that members of the ubiquitin family, particularly ubiquitin itself and SUMO, feature prominently in controlling many of the defensive and restorative measures involved in the protection of DNA during replication. In this review we will discuss the contributions of ubiquitin and SUMO to genome maintenance specifically as they relate to DNA replication. We will consider cases where the modifiers act during regular, i.e., unperturbed stages of replication, such as initiation, fork progression, and termination, but also give an account of their functions in dealing with lesions, replication stalling and fork collapse. PMID:27242895

  3. DNA Replication in Engineered Escherichia coli Genomes with Extra Replication Origins.

    Science.gov (United States)

    Milbredt, Sarah; Farmani, Neda; Sobetzko, Patrick; Waldminghaus, Torsten

    2016-10-21

    The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects.

  4. Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase.

    Science.gov (United States)

    Lõoke, Marko; Maloney, Michael F; Bell, Stephen P

    2017-02-01

    Activation of the Mcm2-7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2-7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2-7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2-7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication. © 2017 Lõoke et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Jerky periods: myoclonus occurring solely during menses.

    Science.gov (United States)

    Buijink, Arthur W G; Gelauff, Jeannette M; van der Salm, Sandra M A; Tijssen, Marina A J; van Rootselaar, Anne-Fleur

    2013-01-01

    In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus.

  6. Jerky Periods - Myoclonus Occurring Solely During Menses

    Directory of Open Access Journals (Sweden)

    Arthur W. Buijink

    2013-05-01

    Full Text Available Background: In this case report, we describe an unusual case of a patient with myoclonus only occurring during menses. Case Report: A 41-year-old female, known to have neurological sequelae after a car accident 1 year earlier, presented with myoclonic movements of the right arm and hand only during menses. Brain magnetic resonance imaging is compatible with head trauma. Electromyography shows brief irregular bursts with a duration of about 20 ms. Discussion: This appears to be the first description of myoclonus appearing only during menses. We suggest a cortical origin for myoclonus.

  7. DNA replication and repair in Tilapia cells

    International Nuclear Information System (INIS)

    Yew, F.H.; Chang, L.M.

    1984-01-01

    The effect of ultraviolet radiation on a cell line established from the warm water fish Tilapia has been assessed by measuring the rate of DNA synthesis, excision repair, post-replication repair and cell survival. The cells tolerate ultraviolet radiation better than mammalian cells with respect to DNA synthesis, post-replication repair and cell survival. They are also efficient in excision repair, which in other fish cell lines has been found to be at a low level or absent. Their response to the inhibitors hydroxyurea and 1-β-D-arabinofuranosylcytosine is less sensitive than that of other cell lines, yet the cells seem to have very small pools of DNA precursor. (author)

  8. Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand.

    Science.gov (United States)

    Yasukawa, Takehiro; Reyes, Aurelio; Cluett, Tricia J; Yang, Ming-Yao; Bowmaker, Mark; Jacobs, Howard T; Holt, Ian J

    2006-11-15

    Using two-dimensional agarose gel electrophoresis, we show that mitochondrial DNA (mtDNA) replication of birds and mammals frequently entails ribonucleotide incorporation throughout the lagging strand (RITOLS). Based on a combination of two-dimensional agarose gel electrophoretic analysis and mapping of 5' ends of DNA, initiation of RITOLS replication occurs in the major non-coding region of vertebrate mtDNA and is effectively unidirectional. In some cases, conversion of nascent RNA strands to DNA starts at defined loci, the most prominent of which maps, in mammalian mtDNA, in the vicinity of the site known as the light-strand origin.

  9. Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing

    OpenAIRE

    Kim, Jin S.; Nanfara, Michael T.; Chodavarapu, Sundari; Jin, Kyeong S.; Babu, Vignesh?M.?P.; Ghazy, Mohamed A.; Chung, Scisung; Kaguni, Jon M.; Sutton, Mark D.; Cho, Yunje

    2017-01-01

    Abstract Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda?sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda?? clam...

  10. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.

    Science.gov (United States)

    Hilton, Benjamin A; Liu, Ji; Cartwright, Brian M; Liu, Yiyong; Breitman, Maya; Wang, Youjie; Jones, Rowdy; Tang, Hui; Rusinol, Antonio; Musich, Phillip R; Zou, Yue

    2017-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene, resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA sequestration likely exposed ds-ssDNA junctions at replication forks for XPA binding. Depletion of XPA or progerin each significantly restored PCNA at replication forks. Our results suggest that although PCNA is much more competitive than XPA in binding replication forks, PCNA sequestration by progerin may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that progerin-induced apoptosis could be rescued by XPA, suggesting that XPA-replication fork binding may prevent apoptosis in HGPS cells. Our results propose a mechanism for progerin-induced genome instability and accelerated replicative senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman, M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes. © FASEB.

  11. Circus: A Replicated Procedure Call Facility

    Science.gov (United States)

    1984-08-01

    298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 client client stubs ...... ...... ..... ..... runtime libary stub compiler binding agent...runtime libary Figure 1: Structure of the Circus system replicated procedure call paired message protocol unreliable datagrams Figure 2: Circus...114-121. [11) Digit &! Equipment Corporation, Intel Corporation, a.nd Xerox Corporation. The Ethernet: A Local Area Networlc. September 1080. [12

  12. Nonequilibrium Phase Transitions Associated with DNA Replication

    Science.gov (United States)

    2011-02-11

    polymerases) catalyzing the growth of a DNA primer strand (the nascent chain of nucleotides complementary to the template strand) based on the Watson ...the fraction (error rate) of monomers for which y, where y is the correct Watson - Crick complementary base of , can be obtained by ¼ X...Nonequilibrium Phase Transitions Associated with DNA Replication Hyung-June Woo* and Anders Wallqvist Biotechnology High Performance Computing

  13. Recursion vs. Replication in Simple Cryptographic Protocols

    DEFF Research Database (Denmark)

    Huttel, Hans; Srba, Jiri

    2005-01-01

    We use some recent techniques from process algebra to draw several conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbeek's spect...... of messages in the sense of Amadio, Lugiez and Vanackere. We conclude by showing that reachability analysis for a replicative variant of the protocol becomes decidable....

  14. Nipah virus entry can occur by macropinocytosis

    International Nuclear Information System (INIS)

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    2009-01-01

    Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.

  15. Leachability of naturally occurring radioactive materials

    International Nuclear Information System (INIS)

    Desideri, D.; Feduzi, L.; Meli, M.A.; Roselli, C.

    2006-01-01

    Naturally occurring radioactive materials (NORM) are present in the environment and can be concentrated by technical activities, particularly those involving natural resources. These NORM deposits are highly stable and very insoluble under environmental conditions at the earth's surface. However, reducing or oxidant conditions or pH changes may enable a fraction of naturally occurring radionuclides to eventually be released to the environment. Leachability of 210 Pb and 210 Po was determined in three samples coming from a refractories production plant (dust, sludge, finished product), in one dust sample from a steelwork and in one ash sample coming from an electric power station. A sequential extraction method consisting of five operationally-defined fractions was used. The average leaching potential observed in the samples from the refractory industry is very low (mean values: 5.8% for 210 Pb and 1.7% for 210 Po). The 210 Pb and 210 Po leachability increases for the ash sample coming from an electric power plant using carbon (17.8% for 210 Pb and 10.0% for 210 Po); for the dust sample coming from a steelwork, the percent soluble fraction is 41.1% for 210 Pb and 8.5% for 210 Po. For all samples the results obtained show that 210 Pb is slightly more soluble than 210 Po. (author)

  16. Registered Replication Report: Strack, Martin, & Stepper (1988).

    Science.gov (United States)

    Acosta, Alberto; Adams, Reginald B; Albohn, Daniel N; Allard, Eric S; Beek, Titia; Benning, Stephen D; Blouin- Hudon, Eve-Marie; Bulnes, Luis Carlo; Caldwell, Tracy L; Calin-Jageman, Robert J; Capaldi, Colin A; Carfagno, Nicholas S; Chasten, Kelsie T; Cleeremans, Axel; Connell, Louise; DeCicco, Jennifer M.; Dijkhoff, Laura; Dijkstra, Katinka; Fischer, Agneta H; Foroni, Francesco; Gronau, Quentin F; Hess, Ursula; Holmes, Kevin J; Jones, Jacob L H; Klein, Olivier; Koch, Christopher; Korb, Sebastian; Lewinski, Peter; Liao, Julia D; Lund, Sophie; Lupiáñez, Juan; Lynott, Dermot; Nance, Christin N; Oosterwijk, Suzanne; Özdog˘ru, Asil Ali; Pacheco-Unguetti, Antonia Pilar; Pearson, Bethany; Powis, Christina; Riding, Sarah; Roberts, Tomi-Ann; Rumiati, Raffaella I; Senden, Morgane; Shea-Shumsky, Noah B; Sobocko, Karin; Soto, Jose A; Steiner, Troy G; Talarico, Jennifer M; vanAllen, Zack M; Wagenmakers, E-J; Vandekerckhove, Marie; Wainwright, Bethany; Wayand, Joseph F; Zeelenberg, Rene; Zetzer, Emily E; Zwaan, Rolf A

    2016-11-01

    According to the facial feedback hypothesis, people's affective responses can be influenced by their own facial expression (e.g., smiling, pouting), even when their expression did not result from their emotional experiences. For example, Strack, Martin, and Stepper (1988) instructed participants to rate the funniness of cartoons using a pen that they held in their mouth. In line with the facial feedback hypothesis, when participants held the pen with their teeth (inducing a "smile"), they rated the cartoons as funnier than when they held the pen with their lips (inducing a "pout"). This seminal study of the facial feedback hypothesis has not been replicated directly. This Registered Replication Report describes the results of 17 independent direct replications of Study 1 from Strack et al. (1988), all of which followed the same vetted protocol. A meta-analysis of these studies examined the difference in funniness ratings between the "smile" and "pout" conditions. The original Strack et al. (1988) study reported a rating difference of 0.82 units on a 10-point Likert scale. Our meta-analysis revealed a rating difference of 0.03 units with a 95% confidence interval ranging from -0.11 to 0.16. © The Author(s) 2016.

  17. The Anisotropy of Replicated Aluminum Foams

    Directory of Open Access Journals (Sweden)

    Eugeny L. Furman

    2014-01-01

    Full Text Available The replication casting process gives the open-cell aluminum foams that can be used in many industrial applications as well as in filtering technology. The essential requirement for filters is the uniformity of filtering degree which is defined by the minimal pore size. However the structure of replication castings is often inhomogeneous and the minimal pore radius is decreasing in the direction of melt infiltration. The objective of this investigation is to study the dynamics of melt impregnation of the porous medium by vacuum suction to identify the possibility of reducing the anisotropy. Theoretical data illustrate the processes at the boundary between melt and gas medium. The experiments were carried out using the replication aluminum samples produced according to commercial technology. It was found that the permeability coefficient varies throughout the height of castings. A method for estimation of pressure on the line of melt movement was proposed. The resistance of NaCl layer and circular vents of the mold causes the inhomogeneity of castings. Finally the ways of minimizing the anisotropy were offered.

  18. The molecular biology of Bluetongue virus replication.

    Science.gov (United States)

    Patel, Avnish; Roy, Polly

    2014-03-01

    The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

  20. Wegener's granulomatosis occurring de novo during pregnancy.

    Science.gov (United States)

    Alfhaily, F; Watts, R; Leather, A

    2009-01-01

    Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients.

  1. Ayran Üretim Metotları Üzerine Karşılaştırmalı Bir Çalışma

    Directory of Open Access Journals (Sweden)

    Celalettin Koçak

    2015-02-01

    Full Text Available Ayran, yoğurt, tuz ve sudan oluşan, geleneksel bir Türk içeceğidir. Ticari olarak Ayran iki şekilde üretilmektedir. Bu iki üretim şekli arasındaki başlıca fark, inkübasyondan önce Ayran sütüne su ilave edilmesi veya inkübasyondan sonra yoğurda suyun ilave edilmesidir. Bu nedenle bu araştırma, bu iki üretim metodunun Ayranın kimyasal, mikrobiyolojik ve duyusal özellikleri üzerindeki etkilerini araştırmayı amaçlamaktadır. Elde edilen sonuçlar, üretim metotlarının Ayranın genel bileşimi ve tüketici beğenisi üzerinde herhangi bir etkilerinin bulunmadığını göstermiştir (P >0.05. Ancak, yoğurda su katılarak üretilen ayranların asetaldehit içeriklerinde 7. gün depolamada, S. thermophilus içeriğinde ise 1. gün depolamada diğer metoda göre daha düşük değerler elde edilmiştir (P < 0.05.

  2. Mode de mise en place des corps salifères dans l'Atlas septentrional de Tunisie. Exemple de l'appareil de Bir Afou

    Science.gov (United States)

    Ben Chelbi, Mohamed; Melki, Fetheddine; Zargouni, Fouad

    2006-05-01

    30 km southwest of Tunis, two thin flaky 'Triassic' intrusions underline the two flanks of the Atlasic anticline of Bir Afou. These evaporites are interbedded within the Clansayesian shales, and are under and overlain by glauconitic conglomeratic contacts. The 'Triassic' flakes, topic of our study, are sourced from the Bir Afou Triassic mass after a rapid pouring out during Late Aptian extensional tectonics. This structure corresponds, for us, to a 'salt glacier', similar to that one described at Ben Gasseur by Vila and al. [J.M. Vila, M. Ben Youssef, M. Chikhaoui, M. Ghanmi, Bull. Soc. géol. France 167 (1996) 235-246], which was subsequently folded during Lower Eocene times. Middle and Upper Eocene transgressive formations unconformably deposited on top of the Aptian anticlinal hinge. The major Late Miocene compressive phase is responsible for the present structures and that are superimposed onto the pre-existing 'salt glacier'. This salifereous system extends the 'salt glacier' domain towards the eastern part of the Tunisian Atlas. To cite this article: M. Ben Chelbi et al., C. R. Geoscience 338 (2006).

  3. Konaklama İşletmeleri Yöneticilerinin Stres Nedenlerinin Belirlenmesinde Cinsiyet Faktörü: Adana’da Ampirik Bir Araştırma

    OpenAIRE

    Sökmen, Alptekin

    2005-01-01

    Stres, son yıllarda sıkça duyulan ve kullanılan bir kelime olmakla birlikte, stres kavramı literatürde uzun yıllardır hem nedenleri, hem de sonuçları açısından çeşitli araştırmalara konu olmuştur. Sektörün kendine özgü yapısı nedeniyle, günlük iş hayatları kapsamında çeşitli kritik kararlar verme durumunda kalan otel yöneticileri açısından da stres, önemli bir problem olarak kabul edilmektedir. Bu çalışmada, Adana ilinde faaliyet gösteren dört ve beş yıldızlı otel işletmelerinde görev yapan o...

  4. John Brown as an Independent Character from Warburton Circle / Warburton Camiası’ndan Bağımsız Bir Karakter Olarak John Brown

    Directory of Open Access Journals (Sweden)

    Pervin Yigit

    2017-09-01

    Full Text Available Abstract John Brown (1715-1766 and William Warburton (1698-1779 were two leading characters of the English Enlightenment. The enlightenment associated with their works could provide a political, social and intellectual situation of eighteenth century Britain. Therefore, they are worthy of attention. Britain became a trans-oceanic commercial and colonial power in the first half of the century and thus the growth of commercial society and empire changed the character of the nation. Warburton’s works were presenting a complicated programme for reform. Warburton and also his party (Warburton circle aimed to preserve the Great Britain from the effects of intolerance, superstition, religious enthusiasm and religious division. They aimed to maintain the Anglican establishment. Brown who was considered as a loyal member of Warburton circle, regardless their fall out later, introduced reform strategies for the eighteenth century Britain like other members. In this paper it is indicated that Brown was developing a different reform agenda to that of William Warburton. I argue that the Brown’s main work “An Estimate of the Manners and Principles of The Times” (1757 can actually be read as a refutation of Warburton’s thoughts and of the reform strategies developed by members of his circle and thus Brown need to be considered as a self-directed political reformist.   Öz John Brown (1715-1766 ve William Warburton (1698-1779 İngiliz Aydınlaması’nın en önemli karakterlerindendir. Her ikisinin de yapıtları 18. yüzyıl İngilteresi’nin siyasi, sosyal ve entellektüel durumunu ve dolayısı ile İngiliz Aydınlanması’nı bize gösterdikleri için, çalışmaya değerdir. Britanya 18. yüzyılın ilk yarısında okyanus aşırı ticari bir güç ve bir sömürge imparatorluğu olduğu için, ulusun karakteri değişikliğe uğramıştır. Bu sebepten Warburton, eserleri aracılığı ile İngiltere için ulusal bir reform program sunar. O

  5. Gezi’nin Dili: Göstergebilimsel Bir İnceleme / The Language of Taksim Gezi Park Protests: A Semiotic Review

    Directory of Open Access Journals (Sweden)

    Ahmet GÜVEN

    2014-09-01

    Full Text Available Türkiye’nin yakın tarihinde meydana gelmiş olan ve birçok açıdan ilkleri barındıran Gezi Parkı Olayları, göstericilerin kullandıkları dil açısından da dikkat çekicidir. Özellikle sloganlar ve duvar yazıları şeklinde karşımıza çıkan bu farklı dil, olaylar esnasında da sıkça dile getirilmiş, pek çok köşe yazısına ve mizah dergisine de konu olmuştur. Önceki dönemlerdeki gösteri ve protestoların dillerine kıyasla Gezi’nin dili belirgin bir farklılık arz etmektedir. Dildeki bu değişim/dönüşüm toplumsal olayları okumak açısından anahtar niteliğindedir. Kültürün ve dolayısıyla toplumsal olayların dil gibi yapılandığı kabul edildiğinde doğrudan göstergebilimsel bir incelemenin alanına girilmiş olur. Bu çalışmada Gezi Parkı Olaylarındaki söylem göstergebilim kavramlarından olan metaforik ve metonimik bağlamlarda incelenecektir. Bunu yaparken Gezi Parkı Olayları sürecinde kullanılan sloganlar ve duvar yazıları temel alınacaktır. Bu slogan ve duvar yazılarının yapılarında metaforik düzlemden metonimik düzleme doğru bir dönüşüm olduğunu varsayıyoruz. Metonimik düzleme doğru meydana gelen dönüşümü ise toplumsal dönüşümün okunabilmesi için uygun bir anahtar olarak değerlendiriyoruz. / The protesters’ language used in Taksim Gezi Park Protests which has included many initials in many aspects in Turkey is remarkable. That this different language has been manifested especially in the form of slogans and graffitis has been subjected to many column and humor magazines during the protests. In comparison to older protests Gezi has many distinct differences. This transformation in language has played a key role to understand social movements. When we accept the culture and accordingly social movements are structured as language we enter the field of semiotics directly. The aim of this study is to examine the discourse of Gezi Park Protests in the

  6. Radiation-induced inhibition of human endothelial cells replicating in culture

    International Nuclear Information System (INIS)

    DeGowin, R.L.; Lewis, L.J.; Mason, R.E.; Borke, M.K.; Hoak, J.C.

    1976-01-01

    The radiosensitivity of some tumors may depend upon the sensitivity of their microvasculature to radiation. Heretofore, the dose-response of human endothelial cells replicating in tissue culture has not been published. In studies reported here, we exposed flasks containing 4 to 7 x 10 4 genetically identical human endothelial cells to doses of x irradiation from 125 to 1000 rad. During the phase of logarithmic growth, cell counts were compared to those of an unirradiated control to construct a dose--response curve. Similar studies were performed with normal fibroblasts. We found that 160 rad suppressed endothelial cell replication by 37 percent. Although recovery was evident with doses of 500 rad, no net increase in cell number occurred in 3 weeks in flasks of endothelial cells that received 750 or 1000 rad. Fibroblasts were slightly less sensitive under these conditions. To our knowledge, this is the first report of a radiation dose--response curve for human endothelial cells replicating in culture

  7. Restoring chromatin after replication: How new and old histone marks come together

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    In dividing cells genome stability and function rely on faithful transmission of both DNA sequence and its organization into chromatin. In the course of DNA replication chromatin undergoes transient genome-wide disruption followed by restoration on new DNA. This involves tight coordination of DNA...... replication and chromatin assembly processes in time and space. Dynamic recycling and de novo deposition of histones are fundamental for chromatin restoration. Histone post-translational modifications (PTMs) are thought to have a causal role in establishing distinct chromatin structures. Here we discuss PTMs...... present on new and parental histones and how they influence genome stability and restoration of epigenetically defined domains. Newly deposited histones must change their signature in the process of chromatin restoration, this may occur in a step-wise fashion involving replication-coupled processes...

  8. Darwinian Evolution of Mutualistic RNA Replicators with Different Genes

    Science.gov (United States)

    Mizuuchi, R.; Ichihashi, N.

    2017-07-01

    We report a sustainable long-term replication and evolution of two distinct cooperative RNA replicators encoding different genes. One of the RNAs evolved to maintain or increase the cooperativity, despite selective advantage of selfish mutations.

  9. Replication assessment of surface texture at sub-micrometre scale

    DEFF Research Database (Denmark)

    Quagliotti, Danilo; Tosello, Guido; Hansen, Hans Nørgaard

    2017-01-01

    [2]. A replication process requires reproducing a master geometry by conveying it to a substrate material. It is typically induced by means of different energy sources (usually heat and force) and a direct physical contact between the master and the substrate. Furthermore, concepts of advanced......, because of the replication nature of molding processes, the required specifications for the manufacture of micro molded components must be ensured by means of a metrological approach to surface replication and dimensional control of both master geometry and replicated substrate [3]-[4]. Therefore...... replication was assessed by the replication fidelity, i.e., comparing the produced parts with the tool used to replicate the geometry. Furthermore, the uncertainty of the replication fidelity was achieved by propagating the uncertainties evaluated for both masters and replicas. Finally, despite the specimens...

  10. The Design of Finite State Machine for Asynchronous Replication Protocol

    Science.gov (United States)

    Wang, Yanlong; Li, Zhanhuai; Lin, Wei; Hei, Minglei; Hao, Jianhua

    Data replication is a key way to design a disaster tolerance system and to achieve reliability and availability. It is difficult for a replication protocol to deal with the diverse and complex environment. This means that data is less well replicated than it ought to be. To reduce data loss and to optimize replication protocols, we (1) present a finite state machine, (2) run it to manage an asynchronous replication protocol and (3) report a simple evaluation of the asynchronous replication protocol based on our state machine. It's proved that our state machine is applicable to guarantee the asynchronous replication protocol running in the proper state to the largest extent in the event of various possible events. It also can helpful to build up replication-based disaster tolerance systems to ensure the business continuity.

  11. Chromosome biology: conflict management for replication and transcription.

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2013-03-04

    A recent study has uncovered a new mechanism that attenuates DNA replication during periods of heightened gene expression to avoid collisions between replication and transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Introduction to naturally occurring radioactive material

    International Nuclear Information System (INIS)

    Egidi, P.

    1997-01-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. Some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose-based standards. So when is TENORM a problem? Where is it a problem? That depends on when, where, and whom you talk to exclamation point We will start by reviewing background radioactivity, then we will proceed to the geology, mobility, and variability of these

  13. Introduction to naturally occurring radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

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

    Science.gov (United States)

    Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

    2012-09-01

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

  15. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

    Science.gov (United States)

    Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

    2016-10-01

    DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  16. The progression of replication forks at natural replication barriers in live bacteria.

    Science.gov (United States)

    Moolman, M Charl; Tiruvadi Krishnan, Sriram; Kerssemakers, Jacob W J; de Leeuw, Roy; Lorent, Vincent; Sherratt, David J; Dekker, Nynke H

    2016-07-27

    Protein-DNA complexes are one of the principal barriers the replisome encounters during replication. One such barrier is the Tus-ter complex, which is a direction dependent barrier for replication fork progression. The details concerning the dynamics of the replisome when encountering these Tus-ter barriers in the cell are poorly understood. By performing quantitative fluorescence microscopy with microfuidics, we investigate the effect on the replisome when encountering these barriers in live Escherichia coli cells. We make use of an E. coli variant that includes only an ectopic origin of replication that is positioned such that one of the two replisomes encounters a Tus-ter barrier before the other replisome. This enables us to single out the effect of encountering a Tus-ter roadblock on an individual replisome. We demonstrate that the replisome remains stably bound after encountering a Tus-ter complex from the non-permissive direction. Furthermore, the replisome is only transiently blocked, and continues replication beyond the barrier. Additionally, we demonstrate that these barriers affect sister chromosome segregation by visualizing specific chromosomal loci in the presence and absence of the Tus protein. These observations demonstrate the resilience of the replication fork to natural barriers and the sensitivity of chromosome alignment to fork progression. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Science.gov (United States)

    Anderson, Samantha F; Maxwell, Scott E

    2017-01-01

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

  18. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Pol{kappa}). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development.

  19. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    International Nuclear Information System (INIS)

    Kai, Mihoko; Wang, Teresa S.-F.

    2003-01-01

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Polκ). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development

  20. Checkpoint independence of most DNA replication origins in fission yeast

    OpenAIRE

    Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

    2007-01-01

    Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleo...

  1. Fungi of genus Alternaria occurring on tomato

    Directory of Open Access Journals (Sweden)

    Joanna Marcinkowska

    2013-12-01

    Full Text Available Tomato early blight in central Poland was caused by Alternaria solani (A. porri f. sp., solani and A. alernata (A. tenuis. A. alternata was isolated more often than A. solani. All isolates of A. solani in controlled conditions killed tomato seedlings, while pathogenic isolates of A. alternata caused only slight seedling blight. In greenhouse tests A. solani proved to be strongly pathogenic for leaves and stems of tomato but A. alternata was weakly pathogenic. The latter species attacked only injured fruits while, A. solanicould penetrate through undamaged peel of fruits. Both of these species caused the same type of symptoms; the differences consisted only in intensification of disease symptoms. During 1974 and 1975 field tomatoes were moderately attacked by early blight. Thebest development of this disease occurred by the turn of August and September. Determinate variety 'New Yorker' was distinguished by more severe infection of stem parts of tomato whereas the fruits of a stock variety 'Apollo' were more strongly attacked.

  2. Uranium occurence in California near Bucaramanga (Columbia)

    International Nuclear Information System (INIS)

    Heider Polania, J.

    1980-01-01

    The mining district of California, Bucaramanga, is on the west side of the Cordillera Oriental in the Santander massif region. The oldest rocks of the area form a complex of metamorphites and migmatites of the predevonic age. Amphibolite various types of paragneiss and orthogneiss are represented. Several stages of metamorphism can be documented in some rocks, as well as double anatexis. Triassic to jurassic quarz diorites and leukogranites show wide distribution. Porphyric rocks of granodioritic to granitic composition, to which the uranium mineralization is mainly bonded, intruded into the sediments of the lower cretaceous. Atomic absorption spectral analyses were carried out for the elements Cu, Zn and Li, as well as the uranium contents of some samples using fluorimetry. Uranium is primarily bonded to pitch blende and coffinite. The latter mostly occur in fine distribution grown in quarz and belong to the most recent mineralization phase. Autunite, meta-autunite, torbernite, meta-torbernite, zeunerite, meta-zeunerite and meta uranocircite detected as secondary uranium minerals. (orig./HP) [de

  3. Bioassay of naturally occurring allelochemicals for phytotoxicity.

    Science.gov (United States)

    Leather, G R; Einhellig, F A

    1988-10-01

    The bioassay has been one of the most widely used tests to demonstrate allelopathic activity. Often, claims that a particular plant species inhibits the growth of another are based entirely on the seed germination response to solvent extracts of the suspected allelopathic plant; few of these tests are of value in demonstrating allelopathy under natural conditions. The veracity of the bioassay for evaluating naturally occurring compounds for phytotoxicity depends upon the physiological and biochemical response capacity of the bioassay organism and the mechanism(s) of action of the allelochemicals. The possibility that more than one allelochemical, acting in concert at very low concentrations, may be responsible for an observed allelopathic effect makes it imperative that bioassays be extremely sensitive to chemical growth perturbation agents. Among the many measures of phytotoxicity of allelochemicals, the inhibition (or stimulation) of seed germination, radicle elongation, and/or seedling growth have been the parameters of choice for most investigations. Few of these assays have been selected with the view towards the possible mechanism of the allelopathic effect.

  4. Laying a Solid Foundation: Strategies for Effective Program Replication

    Science.gov (United States)

    Summerville, Geri

    2009-01-01

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

  5. Geminin: a major DNA replication safeguard in higher eukaryotes

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

    Eukaryotes have evolved multiple mechanisms to restrict DNA replication to once per cell cycle. These mechanisms prevent relicensing of origins of replication after initiation of DNA replication in S phase until the end of mitosis. Most of our knowledge of mechanisms controlling prereplication...

  6. Anaphase onset before complete DNA replication with intact checkpoint responses

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; De Piccoli, Giacomo; Cordon-Preciado, Violeta

    2007-01-01

    Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most...

  7. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes.

  8. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van

    2009-01-01

    We describe a simple fluorescence microscopy-based real-time method for observing DNA replication at the single-molecule level. A circular, forked DNA template is attached to a functionalized glass coverslip and replicated extensively after introduction of replication proteins and nucleotides. The

  9. Mapping autonomously replicating sequence elements in a 73-kb ...

    Indian Academy of Sciences (India)

    Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards identifying all potential replication origins in a 73-kb region of the long arm ...

  10. Test of models for replication of SV40 DNA following UV irradiation

    International Nuclear Information System (INIS)

    Barnett, S.W.

    1983-01-01

    The replication of SV40 DNA immediately after irradiation of infected monkey cells has been examined. SV40 DNA synthesis is inhibited in a UV fluence-dependent fashion, and the synthesis of completely replicated (Form I) SV40 molecules is more severely inhibited than is total SV40 DNA synthesis. Two models for DNA replication-inhibition have been tested. Experimental results have been compared to those predicted by mathematical models derived to describe two possible molecular mechanisms of replication inhibition. No effect of UV irradiation on the uptake and phosphorylation of 3 H-thymidine nor on the size of the intracellular deoxythymidine triphosphate pool of SV40-infected cells have been observed, validating the use of 3 H-thymidine incorporation as a measure of DNA synthesis in this system. In vitro studies have been performed to further investigate the mechanism of dimer-specific inhibition of completion of SV40 DNA synthesis observed in in vivo. The results of these studies are consistent with a mechanism of discontinuous synthesis past dimer sites, but it is equally possible that the mechanism of DNA replication of UV-damaged DNA in the in vitro system is different from that which occurs in vivo

  11. Gambling, Risk-Taking, and Antisocial Behavior: A Replication Study Supporting the Generality of Deviance.

    Science.gov (United States)

    Mishra, Sandeep; Lalumière, Martin L; Williams, Robert J

    2017-03-01

    Research suggests that high frequency gambling is a component of the "generality of deviance", which describes the observation that various forms of risky and antisocial behavior tend to co-occur among individuals. Furthermore, risky and antisocial behaviors have been associated with such personality traits as low self-control, and impulsivity, and sensation-seeking. We conducted a replication (and extension) of two previous studies examining whether high frequency gambling is part of the generality of deviance using a large and diverse community sample (n = 328). This study was conducted as a response to calls for more replication studies in the behavioral and psychological sciences (recent systematic efforts suggest that a significant proportion of psychology studies do not replicate). The results of the present study largely replicate those previously found, and in many cases, we observed stronger associations among measures of gambling, risk-taking, and antisocial behavior in this diverse sample. Together, this study provides evidence for the generality of deviance inclusive of gambling (and, some evidence for the replicability of research relating to gambling and individual differences).

  12. Replication slippage of the thermophilic DNA polymerases B and D from the Euryarchaeota Pyrococcus abyssi

    Directory of Open Access Journals (Sweden)

    Melissa G. eCastillo-Lizardo

    2014-08-01

    Full Text Available Replication slippage or slipped-strand mispairing involves the misalignment of DNA strands during the replication of repeated DNA sequences, and can lead to genetic rearrangements such as microsatellite instability. Here, we show that PolB and PolD replicative DNA polymerases from the archaeal model Pyrococcus abyssi (Pab slip in vitro during replication of a single-stranded DNA template carrying a hairpin structure and short direct repeats. We find that this occurs in both their wild-type (exo+ and exonuclease deficient (exo- forms. The slippage behavior of PabPolB and PabPolD, probably due to limited strand displacement activity, resembles that observed for the high fidelity Pyrococcus furiosus (Pfu DNA polymerase. The presence of PabPCNA inhibited PabPolB and PabPolD slippage. We propose a model whereby PabPCNA stimulates strand displacement activity and polymerase progression through the hairpin, thus permitting the error-free replication of repetitive sequences.

  13. R-loops and initiation of DNA replication in human cells: a missing link?

    Directory of Open Access Journals (Sweden)

    Rodrigo eLombraña

    2015-04-01

    Full Text Available The unanticipated widespread occurrence of stable hybrid DNA/RNA structures (R-loops in human cells and the increasing evidence of their involvement in several human malignancies have invigorated the research on R-loop biology in recent years. Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. Quite likely, this occurs by the strand-displacement reaction activating the formation of G-quadruplex structures that target the Origin Recognition Complex (ORC in the single-stranded conformation. In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells.

  14. Error threshold ghosts in a simple hypercycle with error prone self-replication

    International Nuclear Information System (INIS)

    Sardanyes, Josep

    2008-01-01

    A delayed transition because of mutation processes is shown to happen in a simple hypercycle composed by two indistinguishable molecular species with error prone self-replication. The appearance of a ghost near the hypercycle error threshold causes a delay in the extinction and thus in the loss of information of the mutually catalytic replicators, in a kind of information memory. The extinction time, τ, scales near bifurcation threshold according to the universal square-root scaling law i.e. τ ∼ (Q hc - Q) -1/2 , typical of dynamical systems close to a saddle-node bifurcation. Here, Q hc represents the bifurcation point named hypercycle error threshold, involved in the change among the asymptotic stability phase and the so-called Random Replication State (RRS) of the hypercycle; and the parameter Q is the replication quality factor. The ghost involves a longer transient towards extinction once the saddle-node bifurcation has occurred, being extremely long near the bifurcation threshold. The role of this dynamical effect is expected to be relevant in fluctuating environments. Such a phenomenon should also be found in larger hypercycles when considering the hypercycle species in competition with their error tail. The implications of the ghost in the survival and evolution of error prone self-replicating molecules with hypercyclic organization are discussed

  15. Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli.

    Science.gov (United States)

    Kato , J; Katayama, T

    2001-08-01

    The bacterial DnaA protein binds to the chromosomal origin of replication to trigger a series of initiation reactions, which leads to the loading of DNA polymerase III. In Escherichia coli, once this polymerase initiates DNA synthesis, ATP bound to DnaA is efficiently hydrolyzed to yield the ADP-bound inactivated form. This negative regulation of DnaA, which occurs through interaction with the beta-subunit sliding clamp configuration of the polymerase, functions in the temporal blocking of re-initiation. Here we show that the novel DnaA-related protein, Hda, from E.coli is essential for this regulatory inactivation of DnaA in vitro and in vivo. Our results indicate that the hda gene is required to prevent over-initiation of chromosomal replication and for cell viability. Hda belongs to the chaperone-like ATPase family, AAA(+), as do DnaA and certain eukaryotic proteins essential for the initiation of DNA replication. We propose that the once-per-cell-cycle rule of replication depends on the timely interaction of AAA(+) proteins that comprise the apparatus regulating the activity of the initiator of replication.

  16. The fork and the kinase: a DNA replication tale from a CHK1 perspective.

    Science.gov (United States)

    González Besteiro, Marina A; Gottifredi, Vanesa

    2015-01-01

    Replication fork progression is being continuously hampered by exogenously introduced and naturally occurring DNA lesions and other physical obstacles. Checkpoint kinase 1 (Chk1) is activated at replication forks that encounter damaged DNA. Subsequently, Chk1 inhibits the initiation of new replication factories and stimulates the firing of dormant origins (those in the vicinity of stalled forks). Chk1 also avoids fork collapse into DSBs (double strand breaks) and promotes fork elongation. At the molecular level, the current model considers stalled forks as the site of Chk1 activation and the nucleoplasm as the location where Chk1 phosphorylates target proteins. This model certainly serves to explain how Chk1 modulates origin firing, but how Chk1 controls the fate of stalled forks is less clear. Interestingly, recent reports demonstrating that Chk1 phosphorylates chromatin-bound proteins and even holds kinase-independent functions might shed light on how Chk1 contributes to the elongation of damaged DNA. Indeed, such findings have unveiled a puzzling connection between Chk1 and DNA lesion bypass, which might be central to promoting fork elongation and checkpoint attenuation. In summary, Chk1 is a multifaceted and versatile signaling factor that acts at ongoing forks and replication origins to determine the extent and quality of the cellular response to replication stress. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Speculations on the initiation of chromosome replication in Escherichia coli: the dualism hypothesis.

    Science.gov (United States)

    Norris, Vic

    2011-05-01

    The exact nature of the mechanism that triggers initiation of chromosome replication in the best understood of all organisms, Escherichia coli, remains mysterious. Here, I suggest that this mechanism evolved in response to the problems that arise if chromosome replication does not occur. E. coli is now known to be highly structured. This leads me to propose a mechanism for initiation of replication based on the dynamics of large assemblies of molecules and macromolecules termed hyperstructures. In this proposal, hyperstructures and their constituents are put into two classes, non-equilibrium and equilibrium, that spontaneously separate and that are appropriate for life in either good or bad conditions. Maintaining the right ratio(s) of non-equilibrium to equilibrium hyperstructures is therefore a major challenge for cells. I propose that this maintenance entails a major transfer of material from equilibrium to non-equilibrium hyperstructures once per cell and I further propose that this transfer times the cell cycle. More specifically, I speculate that the dialogue between hyperstructures involves the structuring of water and the condensation of cations and that one of the outcomes of ion condensation on ribosomal hyperstructures and decondensation from the origin hyperstructure is the separation of strands at oriC responsible for triggering initiation of replication. The dualism hypothesis that comes out of these speculations may help integrate models for initiation of replication, chromosome segregation and cell division with the 'prebiotic ecology' scenario of the origins of life. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    KAUST Repository

    Knodel, Markus

    2017-10-02

    Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

  19. Plasticity of DNA replication initiation in Epstein-Barr virus episomes.

    Directory of Open Access Journals (Sweden)

    Paolo Norio

    2004-06-01

    Full Text Available In mammalian cells, the activity of the sites of initiation of DNA replication appears to be influenced epigenetically, but this regulation is not fully understood. Most studies of DNA replication have focused on the activity of individual initiation sites, making it difficult to evaluate the impact of changes in initiation activity on the replication of entire genomic loci. Here, we used single molecule analysis of replicated DNA (SMARD to study the latent duplication of Epstein-Barr virus (EBV episomes in human cell lines. We found that initiation sites are present throughout the EBV genome and that their utilization is not conserved in different EBV strains. In addition, SMARD shows that modifications in the utilization of multiple initiation sites occur across large genomic regions (tens of kilobases in size. These observations indicate that individual initiation sites play a limited role in determining the replication dynamics of the EBV genome. Long-range mechanisms and the genomic context appear to play much more important roles, affecting the frequency of utilization and the order of activation of multiple initiation sites. Finally, these results confirm that initiation sites are extremely redundant elements of the EBV genome. We propose that these conclusions also apply to mammalian chromosomes.

  20. Inhibition of Poliovirus-Induced Cleavage of Cellular Protein PCBP2 Reduces the Levels of Viral RNA Replication

    Science.gov (United States)

    Chase, Amanda J.; Daijogo, Sarah

    2014-01-01

    ABSTRACT Due to their small genome size, picornaviruses must utilize host proteins to mediate cap-independent translation and viral RNA replication. The host RNA-binding protein poly(rC) binding protein 2 (PCBP2) is involved in both processes in poliovirus infected cells. It has been shown that the viral proteinase 3CD cleaves PCBP2 and contributes to viral translation inhibition. However, cleaved PCBP2 remains active in viral RNA replication. This would suggest that both cleaved and intact forms of PCBP2 have a role in the viral RNA replication cycle. The picornavirus genome must act as a template for both translation and RNA replication. However, a template that is actively being translated cannot function as a template for RNA replication, suggesting that there is a switch in template usage from translation to RNA replication. We demonstrate that the cleavage of PCBP2 by the poliovirus 3CD proteinase is a necessary step for efficient viral RNA replication and, as such, may be important for mediating a switch in template usage from translation to RNA replication. IMPORTANCE Poliovirus, like all positive-strand RNA viruses that replicate in the cytoplasm of eukaryotic cells, uses its genomic RNA as a template for both viral protein synthesis and RNA replication. Given that these processes cannot occur simultaneously on the same template, poliovirus has evolved a mechanism(s) to facilitate the switch from using templates for translation to using them for RNA synthesis. This study explores one possible scenario for how the virus alters the functions of a host cell RNA binding protein to mediate, in part, this important transition. PMID:24371074

  1. Differential dormancy of co-occurring copepods

    Science.gov (United States)

    Ohman, Mark D.; Drits, Aleksandr V.; Elizabeth Clarke, M.; Plourde, Stéphane

    1998-08-01

    Four species of planktonic calanoid copepods that co-occur in the California Current System ( Eucalanus californicus Johnson, Rhincalanus nasutus Giesbrecht, Calanus pacificus californicus Brodsky, and Metridia pacifica Brodsky) were investigated for evidence of seasonal dormancy in the San Diego Trough. Indices used to differentiate actively growing from dormant animals included developmental stage structure and vertical distribution; activity of aerobic metabolic enzymes (Citrate Synthase and the Electron Transfer System complex); investment in depot lipids (wax esters and triacylglycerols); in situ grazing activity from gut fluorescence; and egg production rates in simulated in situ conditions. None of the 4 species exhibited a canonical calanoid pattern of winter dormancy - i.e., synchronous developmental arrest as copepodid stage V, descent into deep waters, reduced metabolism, and lack of winter reproduction. Instead, Calanus pacificus californicus has a biphasic life history in this region, with an actively reproducing segment of the population in surface waters overlying a deep dormant segment in winter. Eucalanus californicus is dormant as both adult females and copepodid V's, although winter females respond relatively rapidly to elevated food and temperature conditions; they begin feeding and producing eggs within 2-3 days. Rhincalanus nasutus appears to enter dormancy as adult females, although the evidence is equivocal. Metridia pacifica shows no evidence of dormancy, with sustained active feeding, diel vertical migration behavior, and elevated activity of metabolic enzymes in December as well as in June. The four species also differ markedly in water content, classes of storage lipids, and specific activity of Citrate Synthase. These results suggest that copepod dormancy traits and structural composition reflect diverse adaptations to regional environmental conditions rather than a uniform, canonical series of traits that remain invariant among taxa

  2. Physically Embedded Minimal Self-Replicating Systems

    DEFF Research Database (Denmark)

    Fellermann, Harold

    Self-replication is a fundamental property of all living organisms, yet has only been accomplished to limited extend in manmade systems. This thesis is part of the ongoing research endeavor to bridge the two sides of this gap. In particular, we present simulation results of a minimal life...... for any model above the atomistic scale. This is achieved by deriving an alternative scaling procedure for interaction parameters in the model. We perform system-level simulations of the design which attempt to account for theoretical, and experimental knowledge, as well as results from other...

  3. Replication of DNA during barley endosperm development

    DEFF Research Database (Denmark)

    Giese, H.

    1992-01-01

    The incorporation of [6-H-3]-thymidine into DNA of developing barley end sperm was examined by autoradiography of cross sections of seeds and DNA analysis. The majority of nuclear divisions took place in the very young endosperm, but as late as 25 days after anthesis there was evidence for DNA...... replication. The DNA content of the endosperm increases during development and in response to nitrogen application in parallel to the storage protein synthesis profile. The hordein genes were hypersensitive to DNase I treatment throughout development....

  4. The Nature of Stability in Replicating Systems

    Directory of Open Access Journals (Sweden)

    Addy Pross

    2011-02-01

    Full Text Available We review the concept of dynamic kinetic stability, a type of stability associated specifically with replicating entities, and show how it differs from the well-known and established (static kinetic and thermodynamic stabilities associated with regular chemical systems. In the process we demonstrate how the concept can help bridge the conceptual chasm that continues to separate the physical and biological sciences by relating the nature of stability in the animate and inanimate worlds, and by providing additional insights into the physicochemical nature of abiogenesis.

  5. Dynamic and nucleolin-dependent localization of human cytomegalovirus UL84 to the periphery of viral replication compartments and nucleoli.

    Science.gov (United States)

    Bender, Brian J; Coen, Donald M; Strang, Blair L

    2014-10-01

    proteins required for HCMV genome replication and replicating viral DNA. We found that UL84 localizes with viral proteins, viral DNA, and the cellular nucleolar protein nucleolin in the subnuclear replication compartments in which viral DNA replication occurs. Unexpectedly, we also found localization of UL84 with nucleolin in nucleoli and showed that the presence of nucleolin is involved in localization of UL84 to the nucleus. These results add to previous work showing the importance of nucleolin in replication compartment architecture and viral DNA synthesis and are relevant to understanding UL84 function. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Râzî’nin, Kur’an’daki Yeryüzü (Arz Âyetleriyle İlgili Tefsir-i Kebir’deki Yorumları: Modern Jeoloji Biliminin Verileriyle Kısa Bir Mukayese

    Directory of Open Access Journals (Sweden)

    Enver BAYRAM

    2012-03-01

    Full Text Available Batı dünyasında bilimsel buluş ve keşiflerin yeni başladığı bir dönemde, İslam dünyasında birçok bilimsel buluş ve keşif Müslüman bilim adamları tarafından ortaya konulmuştur. Bu buluş ve keşiflerin yapıldığı alanlardan biri de Jeoloji (yer ilmidir. Bu konuyu tefsirinde etraflıca ele alan Râzî (ö. 606/1210, yer ile ilgili âyetleri kendi döneminin ilmi verileri doğrultusunda ayrıntılı bir şekilde tefsir etmiştir. Bu yüzden onun bazı açıklamaları, zaman zaman modern Jeoloji ilminin verilerine ters düşebilmektedir. Onun, bu âyetleri tefsir ederken en temel amacı, bunları Allah’ın varlığına ve birliğine delil getirmesi olmuştur.

  7. Önlenebilir Bir Halk Sağlığı Sorunu: İşyerlerinde Mobbing ve Sonuçları (The Preventable Public Health Problem:Mobbing and results At Workplaces )

    OpenAIRE

    ÇEVİRME, Ayşe

    2017-01-01

     ÖZETMobbing(psikolojik taciz) veya yıldırma, iş sağlığı alanında sıkça dile getirilen bir konu olup, akademi ve iş çevrelerinin dikkatini gittikçe daha fazla çektiği görülmektedir. Mobbing önlenebilir bir halk sağlığı sorunudur. Birey ve işyeri bağlamında önemli olumsuz sonuçları olan mobbing ile ilgili çalışmalar 1990’larda başlamıştır. Mobbing kavramı bir veya daha fazla kişi tarafından bir kişiye uygulanan etik olmayan ve muhalif davranış varlığı olarak tanımlanır. Bu yazıda mobbingin tan...

  8. Ekolojik Sistem Yaklaşımı Üzerine Bir Olgu Sunumu: Suça Sürüklenen Çocuk ve Ailesiyle Çalışma

    Directory of Open Access Journals (Sweden)

    Uzman Deniz YILMAZ

    2017-06-01

    Full Text Available Ekolojik sistem yaklaşımı, bireyi, çevresi içerisinde yaşayan bir varlık olarak ele alır ve bireyin davranışını değerlendirirken bu çevreyi de göz önünde bulundurur ve sorunun çözümüne bu noktadan hareketle başlar. Bu çalışmada, bir bakkal dükkanından hırsızlık yaptığı gerekçesiyle ilgili mahkemece hakkında Danışmanlık Tedbiri kararı verilen 16 yaşında bir erkek çocuğu ile yapılan mesleki çalışmada Ekolojik Sistem yaklaşımı kullanılmıştır. Buna göre, çocuk, içinde bulunduğu sistem içerisinde değerlendirilmiş ve her bir sistemin değiştirilmesi yoluna gidilerek çocuğun sorunlu davranışlarının düzeltilmesi sağlanmıştır.

  9. Ahlaki sıkıntı: Türkiye’de sağlık alanında gündeme gelmeyen bir boyut

    OpenAIRE

    Gülay Yıldırım; Dilek Özden; Şerife Karagözoğlu

    2013-01-01

    Özet Ahlaki sıkıntı (moral distres) sağlık bakım alanlarında çalışan profesyoneller ve yöneticilerde yaygın olarak yaşanan bir problemdir. Ahlaki sıkıntı, bir profesyonelin yapılacak doğru eylemi bildiği halde engeller nedeniyle doğru eylemi gerçekleştirememesi durumunda yaşadığı bir sıkıntıdır. Bireysel ve kurumsal birçok durumun neden olduğu ahlaki sıkıntı, sağlık profesyonellerinde öfke ve engellenme duygusundan iş doyumunda azalmaya, tükenmişlik ve meslekten ayrılmaya kadar önemli sonuçla...

  10. Information Needs While A Disaster Is Occurring

    Science.gov (United States)

    Perry, S. C.

    2010-12-01

    that rainfall intensity at their homes might be less than the intensity up in the mountains where the debris flows would start. Nor did they know that debris flows travel too quickly to be outrun. These and many other examples indicate need for social and natural scientists to increase awareness of what to expect when the disaster strikes. This information must be solidly understood before the event occurs - while a disaster is unfolding there are no teachable moments. Case studies indicate that even those who come into a disaster well educated about the phenomenon can struggle to apply what they know when the real situation is at hand. In addition, psychological studies confirm diminished ability to comprehend information at times of stress.

  11. Seyyid Vehbi'nin Divanında Yer Almayan Bir Kasidesi The Kaside That Doesn’t Take Place In Divan Of Seyyid Vehbi

    Directory of Open Access Journals (Sweden)

    Haluk GÖKALP

    2013-03-01

    Full Text Available Perodicals include kinds of poems. In addition they comprise artistic and cultural accumulation when they were written. Pastiche collections give knowledge abaut pastiche tradition and interactions between poets. Poem notebooks which can collect diffrent subjects contribute to history of literatüre. So, pastiche collections or other collections are one of the main source of classical poetry. Contributions of periodicals to classical school of poetry investigating, may be collected with three groups. Firsh of all, periodicals reflect the plcasure of poem when they were written and poems which were approued can be determined. Second one, they contribute to recognition of poets who weren’t mentioned in history of literature. Third one, investigetors can benefit from periodicals for poems which weren’t mentioned in poet’s divan which include their poems. By this way, investigators can collect all poems of poet. İn this study, we evalvated the contributions of periodicals to classical poetry investigators. And than we are going to publish Seyyid Vehbi’s kaside in “Sıhhatname ve Sur-ı Hıtana Müteallik Kasaid” which was found from Topkapı Palace Library. With this study, Seyyid Vehbi’s poem which weren’t mentioned in other 31 copy is going to be presented to investigator’s advantage. Şiir mecmuaları çeşitli şiirleri derlemekle birlikte yazıldığı devrin sanat ve kültür birikimini de bir araya getirirler. Nazire mecmuaları nazire geleneğini ve şairler arası etkileşimi örnekleriyle gözler önüne sererken, farklı konular etrafında toplanan ya da -tamamen okuyucunun zevkine göre gelişigüzel toplanan- şiir defterleri edebiyat tarihini bir bütünlük içinde görmemize olumlu katkılar sağlar. Bu nedenle nazire mecmuaları ya da diğer şiir mecmuaları, divan şiiri araştırmalarının başlıca kaynaklarındandır. Genel olarak baktığımızda mecmuaların divan edebiyatı araştırmalarına katk

  12. 2. Bölgesel TIAFT (Uluslararası Adli Toksikologlar Birliği Toplantısı Sonuç Bildirgesi

    Directory of Open Access Journals (Sweden)

    Halis Dokgöz

    2016-12-01

    Full Text Available Adli ve Klinik Toksikoloji Derneği (AKTOD tarafından, Adli Tıp Kurumu, Adli Tıp Uzmanları Derneği, TUBİM, Jandarma Kriminal Daire Başkanlığı, Türk Farmakoloji Derneği, Türkiye Acil Tıp Derneği destekleri ile, 30 Ekim 2 Kasım 2016 tarihleri arasında 2. Bölgesel TIAFT (The International Association of Forensic Toxicologists-http://www.tiaftturkey2016.org Toplantısı, Antalya WOW Topkapı Palace Oteli’nde düzenlenmiştir. Kongreye The International Association of Forensic Toxicologists (TIAFT, European Workplace Drug Testing Society, Regional Anti-Doping Center of Turin,  National Institute on Drug Abuse (NIDA, UCSF School of Medicine, Society of Forensic Toxicologists (USA, National Institute of Toxicology and Forensic Sciences, Ministery of Justice (Spain Driving Under the Influence Drugs – ROSITA projesi gibi birçok alanda bilim adamları çalışmalarını paylaşmışlardır. Ülkemiz ulusal uyuşturucu politika ve stratejisi kapsamında, “Uyuşturucu Maddelerle Mücadele” Üst Kurulundan (Adalet Bakanlığı Müsteşar Yardımcısı, Sağlık Bakanlığı Müsteşar Yardımcısı, Adalet Bakanlığı Ceza İşleri Müdürlüğü hâkimleri ve AB Devletlerinden bu alanda aktif olarak çalışmış yöneticiler tarafından sunulan faaliyet raporları, güncel gelişmeler ve yeni eylem planları “Uyuşturucu ile Mücadele” oturumunda; sunulmuştur. Bu oturumda; arz ve taleple mücadelede, suçun delillendirilmesi ve Denetimli Serbestlik hakkından yararlanılması aşamasında laboratuvar sonucunun bilimsel kanıt/somut veri olması nedeniyle bu analizden sorumlu “Referans adli toksikoloji laboratuvarları” nın önemi ve özellikleri, bu laboratuvarlarda çalışacak kişilerin ilgili bilimsel kurul tarafından onaylanması konuları tartışılmıştır ve yurtdışı örnekleri incelenmiştir. Bu açıklamalar kapsamında; madde bağımlılığında madde testinin birçok amaçla yapılabildiği, klinik

  13. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus.

    Science.gov (United States)

    Lin, Chia-Chi; Yang, Zhi-Wei; Iang, Shan-Bei; Chao, Mei

    2015-01-02

    Hepatitis delta virus (HDV) replication is carried out by host RNA polymerases. Since homologous inter-genotypic RNA recombination is known to occur in HDV, possibly via a replication-dependent process, we hypothesized that the degree of sequence homology and the replication level should be related to the recombination frequency in cells co-expressing two HDV sequences. To confirm this, we separately co-transfected cells with three different pairs of HDV genomic RNAs and analyzed the obtained recombinants by RT-PCR followed by restriction fragment length polymorphism and sequencing analyses. The sequence divergence between the clones ranged from 24% to less than 0.1%, and the difference in replication levels was as high as 100-fold. As expected, significant differences were observed in the recombination frequencies, which ranged from 0.5% to 47.5%. Furthermore, varying the relative amounts of parental RNA altered the dominant recombinant species produced, suggesting that template switching occurs frequently during the synthesis of genomic HDV RNA. Taken together, these data suggest that during the host RNA polymerase-driven RNA recombination of HDV, both inter- and intra-genotypic recombination events are important in shaping the genetic diversity of HDV. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Molecular analysis of the replication program in unicellular model organisms.

    Science.gov (United States)

    Raghuraman, M K; Brewer, Bonita J

    2010-01-01

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

  15. Materials Chemistry and Performance of Silicone-Based Replicating Compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin

    2014-11-01

    Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.

  16. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone c...... progression and histone supply and demand.......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  17. From structure to mechanism—understanding initiation of DNA replication

    Science.gov (United States)

    Riera, Alberto; Barbon, Marta; Noguchi, Yasunori; Reuter, L. Maximilian; Schneider, Sarah; Speck, Christian

    2017-01-01

    DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2–7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability. PMID:28717046

  18. Bir Su Ürünleri İşleme Tesisinde İş Sağlığı ve Güvenliği Risk Analizi Uygulaması

    Directory of Open Access Journals (Sweden)

    Servet Atayeter

    2015-02-01

    Full Text Available Bu çalışmada, Bodrum’da bulunan bir su ürünleri işleme ve paketleme tesisinde TS 18001 İş Sağlığı ve Güvenliği Sistemi çerçevesinde pilot bir risk analizi uygulaması gerçekleştirilerek sonuçları değerlendirilmiştir. Çalışanların kendilerini güvende hissetme gereksinimi ile doğrudan ilgili olan iş sağlığı ve güvenliği konusu, günümüzde tüm sektörlerde olduğu gibi su ürünleri işletmeleri için de rekabet edilebilirlik, verimlilik, sosyal sorumluluk ve ülke ekonomisi açılarından üzerinde önemle durulması gereken bir konu haline gelmiştir. TS 18001 İş Sağlığı ve Güvenliği Sistemi bir işletmede insan sağlığı ve güvenliğini sağlamaya, can ve mal kayıplarını önlemeye, bu konudaki riskleri azaltmaya odaklı dinamik ve esnek bir sistemin kurulmasını amaçlar. Sistemin amaç ve hedeflerine ulaşılması ve etkinliğinin sürekli iyileştirilebilmesi ise gerçekçi bir risk analizinin yapılmasına bağlıdır. Risk analizinin sonuçları değerlendirilerek, işletmede can güvenliği ve maddi kayıpların önlenmesine yönelik önleyici tedbirlerin alınması yönünde önemli bir adım atılmış olmakta, böylelikle faaliyetlerle ilgili risklerin azaltılması ve ortadan kaldırılması olanaklı hale gelmektedir.

  19. Replicative DNA polymerase mutations in cancer☆

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-01-01

    Three DNA polymerases — Pol α, Pol δ and Pol ɛ — are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson–Crick base pairing and 3′exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to ‘polymerase proofreading associated polyposis’ (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an ‘ultramutator’ phenotype, with a dramatic increase in base substitutions. PMID:24583393

  20. Replicative DNA polymerase mutations in cancer.

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-02-01

    Three DNA polymerases - Pol α, Pol δ and Pol ɛ - are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson-Crick base pairing and 3'exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to 'polymerase proofreading associated polyposis' (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an 'ultramutator' phenotype, with a dramatic increase in base substitutions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Education: DNA replication using microscale natural convection.

    Science.gov (United States)

    Priye, Aashish; Hassan, Yassin A; Ugaz, Victor M

    2012-12-07

    There is a need for innovative educational experiences that unify and reinforce fundamental principles at the interface between the physical, chemical, and life sciences. These experiences empower and excite students by helping them recognize how interdisciplinary knowledge can be applied to develop new products and technologies that benefit society. Microfluidics offers an incredibly versatile tool to address this need. Here we describe our efforts to create innovative hands-on activities that introduce chemical engineering students to molecular biology by challenging them to harness microscale natural convection phenomena to perform DNA replication via the polymerase chain reaction (PCR). Experimentally, we have constructed convective PCR stations incorporating a simple design for loading and mounting cylindrical microfluidic reactors between independently controlled thermal plates. A portable motion analysis microscope enables flow patterns inside the convective reactors to be directly visualized using fluorescent bead tracers. We have also developed a hands-on computational fluid dynamics (CFD) exercise based on modeling microscale thermal convection to identify optimal geometries for DNA replication. A cognitive assessment reveals that these activities strongly impact student learning in a positive way.

  2. Le Chatelier's principle in replicator dynamics

    Science.gov (United States)

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-10-01

    The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

  3. Why threefold-replication of families?

    Science.gov (United States)

    Fitzpatrick, Gerald L.

    1998-04-01

    In spite of the many successes of the standard model of particle physics, the observed proliferation of matter-fields, in the form of ``replicated'' generations or families, is a major unsolved problem. In this paper, I explore some of the algebraic, geometric and physical consequences of a new organizing principle for fundamental fermions (quarks and leptons)(Gerald L. Fitzpatrick, phThe Family Problem--New Internal Algebraic and Geometric Regularities), Nova Scientific Press, Issaquah, Washington, 1997. Read more about this book (ISBN 0--9655695--0--0) and its subject matter at: http://www.tp.umu.se/TIPTOP and/or amazon.com>http://www.amazon.com.. The essence of the new organizing principle is the idea that the standard-model concept of scalar fermion numbers f can be generalized. In particular, a ``generalized fermion number,'' which consists of a 2× 2 matrix F that ``acts'' on an internal 2-space, instead of spacetime, is taken to describe certain internal properties of fundamental fermions. This generalization automatically introduces internal degrees of freedom that ``explain,'' among other things, family replication and the number (three) of families observed in nature.

  4. Endoplasmic reticulum stress causes EBV lytic replication.

    Science.gov (United States)

    Taylor, Gwen Marie; Raghuwanshi, Sandeep K; Rowe, David T; Wadowsky, Robert M; Rosendorff, Adam

    2011-11-17

    Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)-specific phosphatase inhibitor Salubrinal (SAL) synergized with TG to induce EBV lytic genes; however, TG treatment alone was sufficient to activate EBV lytic replication. SAL showed ER-stress-dependent and -independent antiviral effects, preventing virus release in human LCLs and abrogating gp350 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B95-8 cells. TG resulted in sustained BCL6 but not BLIMP1 or CD138 expression, which is consistent with maintenance of a germinal center B-cell, rather than plasma-cell, phenotype. Microarray analysis identified candidate genes governing lytic replication in LCLs undergoing ER stress.

  5. How to securely replicate services (preliminary version)

    Science.gov (United States)

    Reiter, Michael; Birman, Kenneth

    1992-01-01

    A method is presented for constructing replicated services that retain their availability and integrity despite several servers and clients being corrupted by an intruder, in addition to others failing benignly. More precisely, a service is replicated by 'n' servers in such a way that a correct client will accept a correct server's response if, for some prespecified parameter, k, at least k servers are correct and fewer than k servers are correct. The issue of maintaining causality among client requests is also addressed. A security breach resulting from an intruder's ability to effect a violation of causality in the sequence of requests processed by the service is illustrated. An approach to counter this problem is proposed that requires that fewer than k servers are corrupt and, to ensure liveness, that k is less than or = n - 2t, where t is the assumed maximum total number of both corruptions and benign failures suffered by servers in any system run. An important and novel feature of these schemes is that the client need not be able to identify or authenticate even a single server. Instead, the client is required only to possess at most two public keys for the service.

  6. Examining a DNA Replication Requirement for Bacteriophage λ Red- and Rac Prophage RecET-Promoted Recombination in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Lynn C. Thomason

    2016-09-01

    Full Text Available Recombineering, in vivo genetic engineering with bacteriophage homologous recombination systems, is a powerful technique for making genetic modifications in bacteria. Two systems widely used in Escherichia coli are the Red system from phage λ and RecET from the defective Rac prophage. We investigated the in vivo dependence of recombineering on DNA replication of the recombining substrate using plasmid targets. For λ Red recombination, when DNA replication of a circular target plasmid is prevented, recombination with single-stranded DNA oligonucleotides is greatly reduced compared to that under replicating conditions. For RecET recombination, when DNA replication of the targeted plasmid is prevented, the recombination frequency is also reduced, to a level identical to that seen for the Red system in the absence of replication. The very low level of oligonucleotide recombination observed in the absence of any phage recombination functions is the same in the presence or absence of DNA replication. In contrast, both the Red and RecET systems recombine a nonreplicating linear dimer plasmid with high efficiency to yield a circular monomer. Therefore, the DNA replication requirement is substrate dependent. Our data are consistent with recombination by both the Red and RecET systems occurring predominately by single-strand annealing rather than by strand invasion.

  7. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  8. İki Spor Kulübünün Hisse Senedi Getirileri Üzerine Bir İnceleme

    Directory of Open Access Journals (Sweden)

    Deniz PARLAK

    2014-12-01

    Full Text Available Futbol, günümüz dünyasında bir eğlence unsuru olmaktan çıkarak endüstri kolu haline gelmiştir. Bu sporun Türkiye’deki en önemli temsilcileri olan Fenerbahçe ve Galatasaray’ın arasındaki rekabet hem takım düzeyinde sahada hem de şirket düzeyinde borsada yaşanmaktadır. Çalışmanın amacı bu iki futbol takımının yaptıkları karşılaşmalarda aldıkları sonuçların borsada işlem gören hisselerine ait fiyatlara etkisini incelemektir. Takımların kendi sonuçlarının yanı sıra rakibinin aldığı sonuçların da şirketin hisse senedi getirisine etki edip etmediği araştırılmıştır. Kullanılan üç günlük olay etüdü analizi ile maç sonuçlarına ait beklentilerin maçtan bir gün önce, maç sonuçlarının ise maçtan bir gün sonra kümülatif anormal getiri yarattığını göstermiştir. Kümülatif anormal getirinin rakibin elde ettiği sonuçlara göre farklılık göstermediği saptanmıştır.

  9. Akıllı Telefon Seçiminin Belirleyicileri: Üniversite Öğrencileri Üzerine Bir Uygulama

    Directory of Open Access Journals (Sweden)

    Halim TATLI

    2015-09-01

    Full Text Available Bu çalışmada, üniversite öğrencilerinin akıllı telefon seçimi üzerinde etkili olan faktörlerin tespit edilmesi amaçlanmıştır. Bu kapsamda, Bingöl Üniversitesinde okuyan öğrencilere uygulanan bir anketten elde edilen veriler kullanılmıştır. Bu anket, Ekim-Kasım 2014 tarihlerinde 400 öğrenciye uygulanmıştır. Öğrencilerin akıllı telefon seçimi cevap değişkeni, yaşın logaritması, aylık gelirin logaritması ve öğrencilerin akıllı telefona ilişkin bakış açılarının puanın logaritması açıklayıcı değişken olarak alınmıştır. Analizlerde lojistik regresyon kullanılmıştır. Tahmin edilen lojistik regresyon analizi sonucunda; öğrencilerin akıllı telefona ilişkin bakış açılarının puanın logaritması ve aylık gelirin logaritması anlamlı bir şekilde akıllı telefonu seçme olasılığını artırdığı tespit edilmiştir. Yaşın logaritması ile öğrencilerin akıllı telefon seçimi arasında anlamlı bir ilişki bulunamamıştır. Araştırmanın sonuçları, aylık gelir ve öğrencilerin akıllı telefona ilişkin bakış açıları, akıllı telefon seçiminin önemli belirleyicileri olduğunu göstermiştir.

  10. A new MCM modification cycle regulates DNA replication initiation.

    Science.gov (United States)

    Wei, Lei; Zhao, Xiaolan

    2016-03-01

    The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation.

  11. Replication, falsification, and the crisis of confidence in social psychology.

    Science.gov (United States)

    Earp, Brian D; Trafimow, David

    2015-01-01

    The (latest) crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how it should be carried out as well as interpreted by scholars in the field. For example, what does it mean if a replication attempt "fails"-does it mean that the original results, or the theory that predicted them, have been falsified? And how should "failed" replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we highlight the importance of auxiliary assumptions (for both testing theories and attempting replications), and introduce a Bayesian framework for assessing "failed" replications in terms of how they should affect our confidence in original findings.

  12. Replication, falsification, and the crisis of confidence in social psychology

    Science.gov (United States)

    Earp, Brian D.; Trafimow, David

    2015-01-01

    The (latest) crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how it should be carried out as well as interpreted by scholars in the field. For example, what does it mean if a replication attempt “fails”—does it mean that the original results, or the theory that predicted them, have been falsified? And how should “failed” replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we highlight the importance of auxiliary assumptions (for both testing theories and attempting replications), and introduce a Bayesian framework for assessing “failed” replications in terms of how they should affect our confidence in original findings. PMID:26042061

  13. The Staphylococcus aureus group II biotin protein ligase BirA is an effective regulator of biotin operon transcription and requires the DNA binding domain for full enzymatic activity.

    Science.gov (United States)

    Henke, Sarah K; Cronan, John E

    2016-11-01

    Group II biotin protein ligases (BPLs) are characterized by the presence of an N-terminal DNA binding domain that functions in transcriptional regulation of the genes of biotin biosynthesis and transport. The Staphylococcus aureus Group II BPL which is called BirA has been reported to bind an imperfect inverted repeat located upstream of the biotin synthesis operon. DNA binding by other Group II BPLs requires dimerization of the protein which is triggered by synthesis of biotinoyl-AMP (biotinoyl-adenylate), the intermediate in the ligation of biotin to its cognate target proteins. However, the S. aureus BirA was reported to dimerize and bind DNA in the absence of biotin or biotinoyl-AMP (Soares da Costa et al. (2014) Mol Microbiol 91: 110-120). These in vitro results argued that the protein would be unable to respond to the levels of biotin or acceptor proteins and thus would lack the regulatory properties of the other characterized BirA proteins. We tested the regulatory function of the protein using an in vivo model system and examined its DNA binding properties in vitro using electrophoretic mobility shift and fluorescence anisotropy analyses. We report that the S. aureus BirA is an effective regulator of biotin operon transcription and that the prior data can be attributed to artifacts of mobility shift analyses. We also report that deletion of the DNA binding domain of the S. aureus BirA results in loss of virtually all of its ligation activity. © 2016 John Wiley & Sons Ltd.

  14. Yüzde tabanlı String Eşleme Problemi için yeni bir donanım modülü tasarımı

    Directory of Open Access Journals (Sweden)

    İbrahim Şahin

    2016-12-01

    Full Text Available Bir verinin bir dizgi içerisinde veya bir gen yapısının bir DNA gen dizilimi içerisinde arama işleminin gerçekleştirilmesi için çeşitli algoritmalar kullanılmaktadır. Kullanılan bu algoritmalardan bazıları bize mutlak eşleşme olmadığı durumlarda olumsuz dönüt vermekte, bazıları ise “bunu mu arıyorsunuz” diye alternatifler sunmaktadır. Her iki algoritma da genel amaçlı PC’lerde saniyeler süren işlemler sonucunda bize dönüt verebilmektedir. Bu çalışmada bize hem mutlak eşleşmeyi hem de hedef dizgi içinde yüzdelik eşleşme oranlarının gerçekleştiği konumu veren FPGA çiplerine yönelik yüksek performanslı bir donanım modülü tasarlanmıştır. Geliştirilen modülün veri işleme hızı farklı PC’lerle karşılaştırılmış ve 2300 kata kadar daha hızlı arama gerçekleştirdiği karşılaştırma sonuçlarından elde edilen veriler ile doğrulanmıştır.

  15. Ücret Teorileri ve Türkiye İşgücü Piyasaları İçin Uygulanabilir Bir Ücret Modeli Önerisi

    Directory of Open Access Journals (Sweden)

    M. Veysel KAYA

    2016-04-01

    Full Text Available Uluslararası emek piyasalarının genel olarak iki blok halinde kutuplaştığı kabul edilirse; ücretlerin iktisadi ve sosyal boyutlarının ele alınması isabetli olacaktır. Çalışanlarla işverenler arasında adeta bir mücadele haline bürünen bu ayrım, ücretlerin adil bir şekilde düzenlenmesi konusunda pek çok iktisatçıyı yeni formüller geliştirmeye itmiştir. Ne var ki, çalışma ekonomisi literatüründe tali aktörler olarak emek piyasalarında çalışan ve işverenler dışında devlet ve sendikaların varlığını kabul etmek gerekir. Bu tali aktörlerin emek piyasalarından paylarını almaları, ekonominin dengesini dörtlü bir saç ayağına oturtmaktadır. Bugüne kadar ortaya konulmuş olan doktriner açıklamalar ışığında, oluşabilecek çok boyutlu ve çok fonksiyonlu bir ücret modeli, emek piyasalarındaki bu dört aktör bazında ulaşılabilecek bir dengeye katkıda bulunacaktır.

  16. DNA replication error-induced extinction of diploid yeast.

    Science.gov (United States)

    Herr, Alan J; Kennedy, Scott R; Knowels, Gary M; Schultz, Eric M; Preston, Bradley D

    2014-03-01

    Genetic defects in DNA polymerase accuracy, proofreading, or mismatch repair (MMR) induce mutator phenotypes that accelerate adaptation of microbes and tumor cells. Certain combinations of mutator alleles synergistically increase mutation rates to levels that drive extinction of haploid cells. The maximum tolerated mutation rate of diploid cells is unknown. Here, we define the threshold for replication error-induced extinction (EEX) of diploid Saccharomyces cerevisiae. Double-mutant pol3 alleles that carry mutations for defective DNA polymerase-δ proofreading (pol3-01) and accuracy (pol3-L612M or pol3-L612G) induce strong mutator phenotypes in heterozygous diploids (POL3/pol3-01,L612M or POL3/pol3-01,L612G). Both pol3-01,L612M and pol3-01,L612G alleles are lethal in the homozygous state; cells with pol3-01,L612M divide up to 10 times before arresting at random stages in the cell cycle. Antimutator eex mutations in the pol3 alleles suppress this lethality (pol3-01,L612M,eex or pol3-01,L612G,eex). MMR defects synergize with pol3-01,L612M,eex and pol3-01,L612G,eex alleles, increasing mutation rates and impairing growth. Conversely, inactivation of the Dun1 S-phase checkpoint kinase suppresses strong pol3-01,L612M,eex and pol3-01,L612G,eex mutator phenotypes as well as the lethal pol3-01,L612M phenotype. Our results reveal that the lethal error threshold in diploids is 10 times higher than in haploids and likely determined by homozygous inactivation of essential genes. Pronounced loss of fitness occurs at mutation rates well below the lethal threshold, suggesting that mutator-driven cancers may be susceptible to drugs that exacerbate replication errors.

  17. Studies on the mechanism of replication of adenovirus DNA. III. Electron microscopy of replicating DNA

    NARCIS (Netherlands)

    Ellens, D.J.; Sussenbach, J.S.; Jansz, H.S.

    1974-01-01

    Replicating Ad5 DNA was isolated from nuclei of infected KB cells and studied by electron microscopy. Branched as well as unbranched linear intermediates were observed containing extended regions of single-stranded DNA. The relationship between the branched and unbranched structures was studied

  18. Late-replicating X-chromosome: replication patterns in mammalian females

    Directory of Open Access Journals (Sweden)

    Tunin Karen

    2002-01-01

    Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.

  19. A CI-Independent Form of Replicative Inhibition: Turn Off of Early Replication of Bacteriophage Lambda

    Science.gov (United States)

    Hayes, Sidney; Horbay, Monique A.; Hayes, Connie

    2012-01-01

    Several earlier studies have described an unusual exclusion phenotype exhibited by cells with plasmids carrying a portion of the replication region of phage lambda. Cells exhibiting this inhibition phenotype (IP) prevent the plating of homo-immune and hybrid hetero-immune lambdoid phages. We have attempted to define aspects of IP, and show that it is directed to repλ phages. IP was observed in cells with plasmids containing a λ DNA fragment including oop, encoding a short OOP micro RNA, and part of the lambda origin of replication, oriλ, defined by iteron sequences ITN1-4 and an adjacent high AT-rich sequence. Transcription of the intact oop sequence from its promoter, pO is required for IP, as are iterons ITN3–4, but not the high AT-rich portion of oriλ. The results suggest that IP silencing is directed to theta mode replication initiation from an infecting repλ genome, or an induced repλ prophage. Phage mutations suppressing IP, i.e., Sip, map within, or adjacent to cro or in O, or both. Our results for plasmid based IP suggest the hypothesis that there is a natural mechanism for silencing early theta-mode replication initiation, i.e. the buildup of λ genomes with oop + oriλ+ sequence. PMID:22590552

  20. Uranium occurence in nature: Geophysical prospecting, and its occurence in Syria

    International Nuclear Information System (INIS)

    Al-Haj Rasheed, Zaki

    1985-01-01

    A general idea about naturaly occured uranium minerals such as uranite, pechblende, carnotite, coffinit, and bronnerit is given. At the same time, different geophysical methods and detecting devices applied for uranium exploration have been demonstrated. Investigations and studies carried out in Syria point to a uranium content of 100 ppm in the exploited Syrian phosphorite. 1 fig., 1 tab

  1. Cumhuriyet Tarihi Üzerine Kısa Bir Dönemlendirme Denemesi / A Short Essay on Periodization of History of Republic

    Directory of Open Access Journals (Sweden)

    Cengiz SUNAY

    2016-01-01

    Full Text Available Türkiye Cumhuriyeti tarihi, bir asra yaklaşan geçmişiyle oldukça keskin dönüşümlerin gözlendiği bir süreci ifade ediyor. Bu dönüşümlerin içeride ve dışarıdaki hangi değişimler ekseninde meydana geldiği konusunda, nesnel araştırmaların yapıldığı bilinmekle birlikte; son tahlilde, cumhuriyet tarihinde olan bitenleri ileri-geri; devrimci-karşı devrimci şeklindeki öznel değerlendirmelerin belirlediği de söylenebilir. Geçmişte, nelerin olup bittiğine dair çoğu anlatımın, örtülü de olsa bu zaafla malul olduğu söylenebilir; bu çerçevede, tarihin bilimden ziyade, ideoloji olduğuna ilişkin tezler üzerinde düşünmek gerekiyor. Tarihin bilim olduğu kabul edilse bile, güçlünün kaleminden okunduğu, bu nedenle bilimlerin en Darwinist’i olduğu tezi, ihmal edilebilir gibi gözükmüyor. Bu çalışmada, Türkiye Cumhuriyeti tarihinin ana hatları üzerinden kuşbakışı bir gözlem deneniyor; ek okumalar öneriliyor. Son doksan beş yılda nelerin olup, nelerin bittiğine ilişkin kimi zaman alternatif bir perspektiften bakılmaya çalışılıyor. / History of the Turkish Republic expresses a period with considerably sharp transformations with its past which almost reaches one century. It is known that objective studies have been made on the axises on which these transformations took place at home and abroad; nevertheless, in the last analysis, it can be claimed that the occurrences in republican history are determined by subjective evaluations such as forward-backward, revolutionary-counter revolutionary etc. It can be said that most narrations as to what happened in the past suffer from this weakness albeit implicitly; within this framework, the thesis that history is more an ideology than a science should be contemplated. Even if it is accepted that history is science, it is hardly negligible that it is read from the pen of the mighty, for which reason it is the most Darwinist of all sciences

  2. Duygusal ve Rasyonel Sosyal Reklam Mesajlarının Etkililiği Üzerine Bir Araştırma

    OpenAIRE

    AYTEKİN, Pınar; YAKIN, Volkan

    2015-01-01

    Çalışmada, sosyal pazarlamanın tanımına ve uygulama alanlarına değinilmiş, sosyal pazarlamada kullanılan duygusal ve rasyonel çekiciliklerin ve hedef kitle üzerindeki etkilerinin belirlenmesi üzerine nitel ve nicel olmak üzere iki aşamalı bir araştırma gerçekleştirilmiştir. Araştırmada Türk Kızılay’ına ait iki reklam afişinden faydalanılmıştır. İlk aşamada reklamların mesaj içerikleri göstergebilimsel analiz yardımıyla analiz edilerek rasyonel/duygusal çekiciliklerden hangisine sahip olduklar...

  3. Parametrik Olmayan Çok Değişkenli Varyans Analizi ve Sağlık Alanında Bir Uygulaması

    OpenAIRE

    PASİN, Özge; ANKARALI, Handan; CANGÜR, Şengül; SUNGUR, Mehmet Ali

    2016-01-01

    Sağlık araştırmalarında, etkenlerin genellikle birbirleriyle ilişkili birden fazla sonucu olabilir. Bu ilişkili sonuçları ayrı analiz etmek 1.Tip hatanın artmasına neden olur. Ancak pratik uygulamalarda veri analizinde sıklıkla bu hata yapılmakta, daha basit, kolay yorumlanabilen tek değişkenli analiz yöntemlerinden yararlanılmaktadır.  Ayrıca sağlık araştırmalarındaki özelliklerin önemli bir bölümü tek değişkenli parametrik modellerin varsayımlarından olan normal dağılım ve varyansların homo...

  4. Türkiye’de Denizcilik Eğitiminin Geleceğine Yönelik Nicel Bir Çalışma Örneği

    Directory of Open Access Journals (Sweden)

    Ünal ÖZDEMİR

    2017-07-01

    Full Text Available Bu çalışma ile ülkemizde yükseköğretim kurumuna (YÖK bağlı denizcilik eğitimi veren lisans düzeyindeki bölümlerde yer alan öğretim üyelerine yönelik kantitatif bir araştırma yapılması amaçlanmıştır. Lisans düzeyinde denizcilik eğitimi veren deniz ulaştırma işletme ve gemi makinaları işletme mühendisliği bölümleri kapsamında yer alan öğretim üyeleri çalışmanın ana kapsamını oluşturmaktadır. Bu bölümlerin eğitim-öğretim faaliyetlerini yerine getirebilmeleri için gerekliliklerini sağlama konusunda yaşanan sorunların, yeni kurulan fakülte ve yüksekokul sayılarının artması ile birlikte daha da çarpıcı boyuta geleceği tahmin edilmektedir. Çalışmada probleme neden olan etkenler kantitatif teknikler yardımı ile incelenmiş ve soruna yönelik çözüm önerileri sunulmaya çalışılmıştır. Probleme neden olan çeşitli etkenler bir araya getirilerek, bu etkenlerin birbirleri ile olan ilişkileri ve önem dereceleri bulanık AHP (Fuzzy Analytic Hierarchy Process ve soruna çözüm sunabilecek çözüm önerileri arasında da bir değerlendirme yapabilmesi adına bulanık TOPSIS (Fuzzy Technique for Order Performance by Similarity to Ideal Solution yönteminin ele alındığı bir model yaklaşımı kullanılmıştır. Çalışma sonuçlarına göre öğretim üyesi sayısının yeterli sayıda olmayışının temel nedenlerinden bazıları sırasıyla; “akademisyen ücretlerinin düşüklüğü”, “denizde çalışanlar için yüksek ücret imkânı”, “üniversiteler tarafından yeteri sayıda akademik kadronun açılmaması” olarak tespit edilmiştir. Bu soruna çözüm getirebilecek en önemli alternatiflerden bazıları ise; “akademisyenlik mesleğine olan ilginin arttırılması, özendirilmesi ve öğrencilerin bu alana yönlendirilmesi”, “YÖK’ün istemiş olduğu gerekliliklerin denizcilik eğitimi veren kurumlar için farklı kategoride d

  5. Bir Katı Atık Bertaraf Tesisi için Otomasyon Sistem Tasarımı ve Uygulaması

    Directory of Open Access Journals (Sweden)

    Murat AYAZ

    2014-09-01

    Full Text Available Kontrolsüz atık sahalarında çöp depolanması sonucu koku oluşması, haşere üremesi, başıboş hayvanların beslenme ortamının oluşması, çöplerin etrafa yayılması ve yangın riski gibi sebepler bu tür çöp döküm alanlarının kontrol altına alınmasını gerektirmektedir. Bu durum kontrolsüz depolama sahalarının yerine düzenli (kontrollü depolama sahalarının kullanımını zorunlu kılmaktadır. Gerek ülkemizde gerekse de diğer ülkelerde düzenli depolama sahalarının sayısı gün geçtikçe artış göstermektedir. Düzenli depolama sahaları yapısal olarak geniş bir alan üzerine tesis edilmektedir. Geniş yüzey alanına sahip bu tür tesislerde birimler arası iletişim ve kontrol SCADA (Supervisory Control and Data Acquisition sistemi ile gerçekleştirildiğinde, gerçek zamanlı izleme – kontrol, güvenli çalışma, düşük işletme maliyeti, insan iş gücü gereksiniminin azaltılması ve esneklik gibi birçok avantaj sağlamaktadır. Bu çalışmada yaklaşık 225000 m2 üzerine kurulmuş bir katı atık bertaraf tesisinin tüm ünitelerinin kontrolü ve izlenmesi SCADA otomasyonu kullanılarak gerçekleştirilmiştir. Katı atık bertaraf tesisi trafo ve jeneratörün yer aldığı enerji dağıtım noktası, toplanan katı atıkların miktarının ölçüldüğü kantar noktası, atık suyun biriktirildiği atık su havuzu ve pompa istasyonu, çevre aydınlatması kontrol noktası ve tesis içerisinde yer alan bütün bileşenlerin izlendiği idari bina olmak üzere beş ayrı noktadan oluşmaktadır. Tesisin belirtilen bu beş ayrı noktasında PLC (Programmable Logic Controller kontrol panelleri yer almaktadır. Bu noktalar arası haberleşme 1500 metrelik bir profibus hattı ile gerçekleştirilmektedir. İdari bina ile kantar bölgelerinde sistemin izleme ve kontrolünün gerçekleştirilebileceği SCADA merkezi oluşturulmuştur. Bu endüstriyel tesisin otomasyon sisteminin tasarımı ve

  6. SMS Reklamları ve Mobil Bilgi Servislerine Yönelik Tüketici Tutumunu Belirleyen Bir Araştırma

    OpenAIRE

    DURUCASU, R. Reha; AKSOY, N. Figen

    2018-01-01

    Akıllı telefonların gelişmesiyle MMS, Wap, Mobil Uygulamalar, IVR vb. mobil pazarlama mecralarının kullanımında artış meydana gelmiştir. Türkiye’de akıllı telefon kullanım oranı her geçen sene artmaktadır. Buna rağmen işletmeler yaygın bir tüketici kitlesine ulaşmak için halen en çok kullanılan mobil pazarlama mecralarından birisi olan SMS reklamlarını kullanmaya devam etmektedir. Mobil bilgi servisleri ise, kullanıcılar için fayda sağlayan bilgilerin; cep telefonu aracılığıyla kullanıcılara ...

  7. THE VILLAGE UTOPIS AS THE PRESENTATION OF THE IDEAL PLACE ON THE MODERN NATION-STATE PROJECT MODERN ULUS DEVLET PROJESİNDE BIR İDEAL MEKÂN TEMSILI OLARAK KÖY ÜTOPYASI

    Directory of Open Access Journals (Sweden)

    Esra DİCLE

    2012-01-01

    Full Text Available Foucault says that space is an area of power warfare, conflict between organizing and disciplinizing authority and the people who live there. He emphasizes that the politics of town planning of power has a direct relationship with the ideology of power. In this respect, power, organizes the space and also disciplines the individual by separating the areas of power to parts, making individuals visible, normalizing the behaviors, Space is a stage on which ideological transfers occur. It is an instrument that forwards the power’s being to subjects and legitimizes and normalizes this power. After the eighteenth century, town planning and the organization of public sphere have an important role in almost all political debates. As Foucault says power is dispersed to all social places and can be seen every part of the city as a stage and sign. Power’s being is transferred to the conscious of individual by means of signs and passwords that are positioned on all around the city. Turkish Republic’s ekonomic, cultural and political projects are based on the village politics of Kemalizm, after the 1930’s. Kemalizm thinks that the ekonomic independence and the modernization of the country should start from the villages. In this period, they determine the problems of the village where the ideology will be produced. Kemalism has two main aims about the village modernization project: To supply the development of the village and to educate peasents. It is possible to encounter with the Kemalist village discourse on the plays which are written to be staged on People’s Houses. These plays represent peasants as the origin of Turkish identity, express the importance of statepeasant unification, education of the villagers and the industrilazion of village. Foucault, mekânın iktidar mücadelesinin de bir alanı olduğunu söyler. Mekân, düzenleyen ve disipline edenle, yaşayan ve kendiliğinden olanın çatışma alanıdır. Bu noktada iktidarların

  8. Replicability and generalizability of PTSD networks

    DEFF Research Database (Denmark)

    Eiko I., Fried; Eidhof, Marloes B.; Palic, Sabina

    2018-01-01

    The growing literature conceptualizing mental disorders like Posttraumatic Stress Disorder (PTSD) as networks of interacting symptoms faces three key challenges. Prior studies predominantly used (a) small samples with low power for precise estimation, (b) non-clinical samples, and (c) single...... samples. This renders network structures in clinical data, and the extent to which networks replicate across datasets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four datasets...... of traumatized patients receiving treatment for PTSD (total N=2,782). Despite differences in culture, trauma-type and severity of the samples, considerable similarities emerged, with moderate to high correlations between symptom profiles (0.43-0.82), network structures (0.62-0.74), and centrality estimates (0...

  9. Archaeal Viruses: Diversity, Replication, and Structure.

    Science.gov (United States)

    Dellas, Nikki; Snyder, Jamie C; Bolduc, Benjamin; Young, Mark J

    2014-11-01

    The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.

  10. Data Service: Distributed Data Capture and Replication

    Science.gov (United States)

    Warner, P. B.; Pietrowicz, S. R.

    2007-10-01

    Data Service is a critical component of the NOAO Data Management and Science Support (DMaSS) Solutions Platform, which is based on a service-oriented architecture, and is to replace the current NOAO Data Transport System. Its responsibilities include capturing data from NOAO and partner telescopes and instruments and replicating the data across multiple (currently six) storage sites. Java 5 was chosen as the implementation language, and Java EE as the underlying enterprise framework. Application metadata persistence is performed using EJB and Hibernate on the JBoss Application Server, with PostgreSQL as the persistence back-end. Although potentially any underlying mass storage system may be used as the Data Service file persistence technology, DTS deployments and Data Service test deployments currently use the Storage Resource Broker from SDSC. This paper presents an overview and high-level design of the Data Service, including aspects of deployment, e.g., for the LSST Data Challenge at the NCSA computing facilities.

  11. Security in a Replicated Metadata Catalogue

    CERN Document Server

    Koblitz, B

    2007-01-01

    The gLite-AMGA metadata has been developed by NA4 to provide simple relational metadata access for the EGEE user community. As advanced features, which will be the focus of this presentation, AMGA provides very fine-grained security also in connection with the built-in support for replication and federation of metadata. AMGA is extensively used by the biomedical community to store medical images metadata, digital libraries, in HEP for logging and bookkeeping data and in the climate community. The biomedical community intends to deploy a distributed metadata system for medical images consisting of various sites, which range from hospitals to computing centres. Only safe sharing of the highly sensitive metadata as provided in AMGA makes such a scenario possible. Other scenarios are digital libraries, which federate copyright protected (meta-) data into a common catalogue. The biomedical and digital libraries have been deployed using a centralized structure already for some time. They now intend to decentralize ...

  12. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  13. Experimenter gender and replicability in science.

    Science.gov (United States)

    Chapman, Colin D; Benedict, Christian; Schiöth, Helgi B

    2018-01-01

    There is a replication crisis spreading through the annals of scientific inquiry. Although some work has been carried out to uncover the roots of this issue, much remains unanswered. With this in mind, this paper investigates how the gender of the experimenter may affect experimental findings. Clinical trials are regularly carried out without any report of the experimenter's gender and with dubious knowledge of its influence. Consequently, significant biases caused by the experimenter's gender may lead researchers to conclude that therapeutics or other interventions are either overtreating or undertreating a variety of conditions. Bearing this in mind, this policy paper emphasizes the importance of reporting and controlling for experimenter gender in future research. As backdrop, it explores what we know about the role of experimenter gender in influencing laboratory results, suggests possible mechanisms, and suggests future areas of inquiry.

  14. Mindlessly Polite: A Conceptual Replication of the Emotional Seesaw Effect on Compliance and Information Processing

    OpenAIRE

    Kaczmarek, Magdalena C.; Steffens, Melanie C.

    2017-01-01

    Recent studies demonstrated that the sequential induction of contrasting negative and positive emotions can be used as a social influence technique. The original field experiments found that whenever a sudden change in the emotional dynamic occurs – from negative to positive or vice versa – an increase in compliant behavior and an impairment in cognitive functioning can be observed. The goal of the present experiments was a conceptual replication and extension of the results in a more control...

  15. Inhibition of Zika Virus Replication by Silvestrol

    Directory of Open Access Journals (Sweden)

    Fabian Elgner

    2018-03-01

    Full Text Available The Zika virus (ZIKV outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A which is required to unwind structured 5´-untranslated regions (5′-UTRs of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.

  16. Direct Visualization of DNA Replication Dynamics in Zebrafish Cells.

    Science.gov (United States)

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2015-12-01

    Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.

  17. Assembly of Slx4 signaling complexes behind DNA replication forks.

    Science.gov (United States)

    Balint, Attila; Kim, TaeHyung; Gallo, David; Cussiol, Jose Renato; Bastos de Oliveira, Francisco M; Yimit, Askar; Ou, Jiongwen; Nakato, Ryuichiro; Gurevich, Alexey; Shirahige, Katsuhiko; Smolka, Marcus B; Zhang, Zhaolei; Brown, Grant W

    2015-08-13

    Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. © 2015 The Authors.

  18. Maqâshid al-Qur’ân dalam Ayat Kebebasan Beragama Menurut Thahâ Jâbir al-‘Alwânî

    Directory of Open Access Journals (Sweden)

    Ah. Fawaid

    2017-12-01

    Full Text Available Maqâshid al-Qur’ân in the Verses of Religious Freedom in Interpretation of Thahâ Jâbir al-’Alwânî. This article is aimed at describing Thahâ Jâbir al-‘Alwânî’s interpretation on various verses dealing with the issues of religious freedom. Adapting an approach of maqâshid al-Qur’ân, the present paper comes to answer two main issues on the true of Alwânî’s maqâshid al-Qur’ân perception and the theoretical application of Alwânî’s maqâshid al-Qur’ân in interpreting verses of religious freedom. According to ‘Alwânî, it was concluded that there are three main segments that he called al-maqâshid al-Qur’âniyyah al-hâkimah: (1 al-tawhîd, (2 al-tazkiyah, and (3 al-‘umrân. ‘Alwânî stated that freedom of interfaith religion is important goal of sharia meaning. Freedom of interfaith religion, on the other hand, is one of the important embodiments in believing the God and tauhid. Seeing this pattern, the later purpose of the Quran is tazkiyah. This term is a value that enables people apply the message, fulfill the promise, and can perform the tasks of the caliphate. When such principles are implemented, something appears that Alwânî called ‘umrân as the next purpose of the Quran can be manifested well. ‘Umrân or ‘prosperity’ in which human being performs as a khalifah actually can create baldatun thayyibatun wa rabbun ghafûr as the real welfare.

  19. Biyodizel ve Karışımlarının Kullanıldığı bir Dizel Motorda Performans ve Emisyon Analizi

    Directory of Open Access Journals (Sweden)

    Ahmet Necati ÖZSEZEN

    2009-02-01

    Full Text Available Bu çalışmada, atık palmiye yağı kökenli biyodizel ve petrol kökenli dizel yakıtı (PKDY ile karışımlarının, bir dizel motordaki performans ve emisyon karakteristikleri üç boyutlu haritalar üzerinden analiz edilmiştir. Biyodizel ve karışımlarının performans ve emisyon karakterlerini belirlemek amacıyla, motor tam yük ve değişik devir testlerine tabi tutulmuştur. Analiz sonucunda, karışımdaki biyodizel oranı arttıkça PKDY'a göre özgül yakıt tüketiminde artış olduğu, motorun döndürme momentinde ise azalma meydana geldiği tespit edilmiştir. Emisyon analizi sonucunda ise, karışımdaki biyodizel oranı ile ilişkili olarak PKDY'a kıyasla yanmamış hidrokarbon (HC, karbon monoksit (CO ve duman koyuluğu emisyonlarında iyileşmeler olduğu, bununla birlikte karbon dioksit (CO2 ve azot oksit (NOx emisyonlarının motor devrine göre kararlı bir yapı sergilemediği belirlenmiştir.

  20. ULUSLARARASI PORTFÖY YÖNETIMINDE REJIM GEÇIŞKEN KARAR DESTEK MODELLERI: GELIŞMEKTE OLAN MENKUL KIYMET PIYASALARI ÜZERINE BIR UYGULAMA

    Directory of Open Access Journals (Sweden)

    Kadir TUNA

    2014-04-01

    Full Text Available Bu makale, portföy yatırımlarında bir karar destek sistemi olarak rejim geçişken modellerin ne şekilde kullanılabileceğini gelişmekte olan hisse senedi piyasalarına ait zaman serilerini ve Gauss yazılım programını kullanarak incelemektedir. Yönetim bilişim sistemlerinde, model riskinin minimize edilmesi, karar destek siteminin uygulanacağı problemin net olarak tanımlanması ve bu problemin çözümünde kullanılacak modelin doğru seçilmesi ile mümkündür. Ekonometrik testlerin sonuçları, Ukrayna hariç, gelişmekte olan ekonomilerde hisse senetleri piyasalarında 09/01/2004-13/09/2007 tarihleri arasında, ABD hisse senedi piyasaları ile karşılaştırıldığında kalıcı bir volatilitenin gözlemlendiğini ortaya koymaktadır. Bu kapsamda, Türkiye, Rusya, Ukrayna, Brezilya, Lübnan, ABD (Dow Jones Industrial Average ve MSCI (Morgan Stanley Composite Index hisse senedi piyasalarında rejim geçişkenliği ekonometrik olarak karşılaştırmalı incelenmiştir.

  1. Küresel Bir Modele Doğru Çin Medyası / Chinese Media: Towards a Global Model

    Directory of Open Access Journals (Sweden)

    Emre Tansu KETEN

    2015-04-01

    Full Text Available Çin, 1991 sonrası “tek kutuplu” dünya sahnesine ABD’ye alternatif bir siyasi güç olarak çıkmasıyla ve 2008 krizinin ardından dünyanın en büyük ikinci ekonomisi haline gelmesiyle dikkatleri üzerine çekmektedir. Maoist bir işçi devletinden, yüzlerce milyarderi olan ve “dünyanın imalathanesi” olarak anılan günümüz Çin’ine uzanan yolda birçok ekonomik reform hayata geçirilmiş, ancak siyaset alanında aynı cüretle bir dönüşüm tercih edilmemiştir. Bu ekonomik reformların sonucu olarak, tek partili iktidar yapısı değişmeden kalsa da, “parti medyası” yerini “medya sektörü”ne bırakmıştır. Devrimin başından 1970’lerin sonuna kadar tamamen parti denetiminde olan Çin medyası, 1980’lerle birlikte özel sektöre açılmış, 2000’lerden itibaren ise özel sektörün ağırlığına geçmiştir. Ancak, sahiplik yapısı itibariyle çoğunluğu özel sektörün elinde olan Çin medyasında, Çin Komünist Partisi, söz sahipliğini elden bırakmamış, sansür, oto-sansür ve manipülasyon araçlarını kullandığı, kendine has bir kontrol sistemi geliştirmiştir. Bu çalışmada, Çin medya sisteminin yapısı, işleyişi ve dinamikleri incelenerek, bu yapının temel dayanağının işçi devleti geçmişinden kalan politik miras mı, yoksa neoliberal ekonomik yönelimin otoriter düzenlemeleri mi olduğu ve Çin medya sisteminin “neoliberal otoriterleşme” rotasına giren ülkeler için bir medya kontrol modeli sunup sunamadığı tartışılacaktır. / China has been drawing attention both by having emerged after 1991 as an alternative political power in the “uni-polar” world supervised by the U.S and by having become the second largest economy after the crisis of 2008. Despite the economics reforms aimed at transition to the market economy that have transformed China into the “workshop of the world” and created hundreds of multibilionaires, the political sphere has

  2. Hadoop ve Mapreduce Teknolojisi aracılığıyla Gıda-tabanlı Mobil Uygulamaları için bir Arama Hizmeti

    Directory of Open Access Journals (Sweden)

    Mehmet Akif ÇİFÇİ

    2017-02-01

    Full Text Available Özet. Son zamanlarda güvenli gıda tüketimi ve e-sağlık üzerine birçok mobil uygulama geliştirilmiştir. Sağlık bilinciyle hareket eden kullanıcılar, özellikle zararlı gıda ve katkı maddelerinden kaçınarak, güvenli gıda tüketimi için bu alana yönelik uygulamaları son derece önemsemektedir. Günümüzde bu tür uygulamaları destekleyen yapılandırılmış veya yapılandırılmamış verileri içeren kapsamlı bir veritabanı eksikliği bulunmaktadır. Bu makalede mobil uygulamalar için sağlıklı bir gıda tüketimi arama hizmeti sunan Hadoop ve Mapreduce (MR yaklaşımından yararlanan Mobile Apps Search Sevice (MSS önerilmektedir. MSS, gıda ve gıda katkı maddeleri alanına yönelik hizmet vermekte ve mobil kullanıcıların sorgularını ele alarak bilgi sunma hizmetini kapsamaktadır. MSS herhangi bir mobil uygulamanın arkasındaki işlem olarak çalışabilir. Çünkü MSS, bir arama motoru ile aynı mantıkla çalışır; mobil uygulamalarda tıklamalarla oluşan kullanıcı sorgularına yanıt aramak ve kullanıcıya bilgi sunmak için bağlantılı bilgileri kataloglar ve web kaynakları üzerinde tarama yapar. MSS’in tasarımı ve geliştirilmesi, sistem mimarisi, sorgu anlayışı, Hadoop-MR ortamında ve Action Script kullanımı ile vurgulanmaktadır. Makalenin içinde, bir örnek olay incelemesi ile MSS'in genel özellikleri, işleyişi ve mevcut faydaları ortaya konulmuştur.Anahtar Kelimeler: Mobil Sağlık Sistemleri, Gıda-Tabanlı Mobil Uygulamalar, Hadoop ve MR, Mobil Sistemler İçin Büyük Veri, Mobil Bilgi Servisi Abstract. Many mobile applications on safe food consumption and e-health have been developed recently. Health conscious users highly regard such applications for safe food consumption, especially avoiding offending foods and additives. However, there is the lack of a comprehensive database containing structured or unstructured data to support such applications. In this paper we

  3. Mehmed Enisî Yalkı’nın Alman Ruhu Adlı Seyahatnamesine İmgebilimsel Bir Yaklaşım An Imagologist Approach To Mehmet Enisi Yalkı's Travelbook

    Directory of Open Access Journals (Sweden)

    Yılmaz DAŞCIOĞLU

    2012-12-01

    Full Text Available The period of second constitutional is very important in terms of providing transition between Reorganization and Republic period. Besides this, it is a pioneer period in that it encloses determinants which play an important role in bulding a new national identity. It is a clear fact that literary works take a crucial assignment in creation of a new national identity. In this respect, to asses that some literary works published during second contitutional had very important functions to build up western-type turkish identity which was systematized later by Republic period would not be wrong. In this research, one of abroad travelbook after second constitutional is scrutinized, using imagology as a method. Mehmed Enisi Yalkı, jounalist and writer from the time ofconstitutional, proposes German/Germany model in order to build up a newnation, a western type Turk, in his travelbook Alman Ruhu which is still nottranscripted from Arabic Alphabet to Latin. This model is analysed in terms ofimagery. Being resound as a background, the exclamations such as work like aGerman, immovable like a German, fortify your spirit like a German, run afterjustice like a German are the signs of proposing Germany as a model. At theend of research it is determined that ottoman intellectuals who experienced thecrisis of building a new nation wrote travelbook to educate and direct society, topresent an alternative life or culture for it rather than literary concern duringthe time from Reorganization to Republic. II. Meşrutiyet dönemi, Tanzimat ile Cumhuriyet arasındaki geçişi sağlaması yönüyle son derece önemli bir evre olduğu gibi, yeni bir ulusun kimliğinin oluşumunda rol oynayan etkenleri barındırması yönüyle de öncü bir dönemdir. Bir ulusun kimliğinin oluşmasında edebiyat eserlerinin çok önemli bir görev üstlendiği açık bir gerçektir. Bu bağlamda II. Meşrutiyet dönemi gibi kritik bir zaman zarfında ortaya konan kimi edebi eserlerin

  4. Histone modifications: Cycling with chromosomal replication

    DEFF Research Database (Denmark)

    Thon, Genevieve

    2008-01-01

    Histone modifications tend to be lost during chromosome duplication. Several recent studies suggest that the RNA interference pathway becomes active during the weakened transcriptional repression occurring at centromeres in S phase, resulting in the re-establishment of histone modifications...

  5. Effector-Triggered Self-Replication in Coupled Subsystems.

    Science.gov (United States)

    Komáromy, Dávid; Tezcan, Meniz; Schaeffer, Gaël; Marić, Ivana; Otto, Sijbren

    2017-11-13

    In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Causation and the origin of life. Metabolism or replication first?

    Science.gov (United States)

    Pross, Addy

    2004-06-01

    The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.

  7. Regulated eukaryotic DNA replication origin firing with purified proteins.

    Science.gov (United States)

    Yeeles, Joseph T P; Deegan, Tom D; Janska, Agnieszka; Early, Anne; Diffley, John F X

    2015-03-26

    Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric minichromosome maintenance (MCM) complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45-MCM-GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin-dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4-dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication.

  8. Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells

    Directory of Open Access Journals (Sweden)

    Marleny Cabral

    2016-11-01

    Full Text Available There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs in ribosomal DNA (rDNA and non-rDNA locations (e.g., silent replication origins and tRNA genes. The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p. Conditions of caloric restriction (CR, which extend life span, also cause reduced replication pausing at the 5S rDNA and at tRNA genes. In aged and CR cells, the RPSs are less occupied by their specific non-histone protein complexes (e.g., the preinitiation complex TFIIIC, likely because members of these complexes have primarily cytosolic localization. These conditions may lead to reduced replication pausing and may lower replication stress at these sites during aging.

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

    Science.gov (United States)

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

    2017-01-09

    DNA replication is tightly regulated to occur once and only once per cell cycle. How chromatin, the physiological substrate of DNA replication machinery, regulates DNA replication remains largely unknown. Here we show that histone H3 lysine 9 demethylase Kdm4d regulates DNA replication in eukaryotic cells. Depletion of Kdm4d results in defects in DNA replication, which can be rescued by the expression of H3K9M, a histone H3 mutant transgene that reverses the effect of Kdm4d on H3K9 methylation. Kdm4d interacts with replication proteins, and its recruitment to DNA replication origins depends on the two pre-replicative complex components (origin recognition complex [ORC] and minichromosome maintenance [MCM] complex). Depletion of Kdm4d impairs the recruitment of Cdc45, proliferating cell nuclear antigen (PCNA), and polymerase δ, but not ORC and MCM proteins. These results demonstrate a novel mechanism by which Kdm4d regulates DNA replication by reducing the H3K9me3 level to facilitate formation of pre-initiative complex. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Identification of the determinants of efficient Pestivirus replication

    OpenAIRE

    Risager, Peter Christian; Belsham, Graham; Rasmussen, Thomas Bruun

    2013-01-01

    The key for the survival of a virus is to copy its own genome into progeny genomes that allows continued reproduction. The mechanism behind this "copy function" or "replication" is a wellorganized process that involves the formation of a replication complex in the cell and interactions between the viral proteins. The replication process in single-stranded RNA viruses of positive polarity requires a particular enzyme, an RNA dependent RNA polymerase, that has no direct counterpart elsewhere in...

  11. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...only allow entirely new investigations into the replication of these viruses, but also how this method can be applied to any virus with a known...localization, TurboFISH, hemorrhagic fever virus replication 1. Introduction RNA FISH was developed as a method to visualize cellular RNA by binding a

  12. Molecular analysis of the replication program in unicellular model organisms

    OpenAIRE

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

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program o...

  13. Estetik Bir Öğe Olarak Sinemada Ses Tasarımı Ve Örnek Bir Film Çözümlemesi Sound Design As An Aesthetical Element In Cinema And An Example Of A Film Analysis

    Directory of Open Access Journals (Sweden)

    Mustafa SÖZEN

    2013-09-01

    Full Text Available It is a well-known fact that the image itself, even in a film having the simplest story, does not provide enough message. Due to a spesific aesthetic predication of audio phonemena, the films, right from the beginning, started to be shown in accompany with sound. The soundelement in cinematography which produces the semantic expression asa parlance by means of images and sounds has its own ways of use.The sound universe of cinematography is composed of dialogs, effectsand music each having different ontologies. In today’s cinematography,all these three elements were given in. For all that, in some filmsproduced for certain aesthetic considerations and in limited numbersthe usage of effects and music are avoided. Looking at the elementsmaking up the universe of sound in a film from the perspective ofessential functions it is seen that the dialogs are used to provideinformation, effects to create a real spatial and temporal feeling, andmusic to conceive the ambiance required by narrative. By doing so,matching the sounds in harmony with images is achieved and so theenhancement of the narrative’s reality illusion is expected. Somedirectors on the other hand, by pushing the sound out of its basicfunctions, rendering images and sounds contrary oppose this approachgo in search of producing different and new meanings. This studyinvestigates the how the sound universe design of the film “Deli DeliOlma” directed by Murat Saracoğlu, as an aesthetic element ismanipulated. In analysis, sound universe has been assesed either bystructural or dramatic functional dimensions. En basit öyküye sahip bir filmde bile sadece görüntülerin yeteri kadar ileti sağlamadığı bilinen bir gerçekliktir. Ses olgusunun kendine özgü estetik bir yükleme sahip oluşundan ötürü, sinemanın ilk anlarından itibaren filmler ses eşliğinde gösterilmeye başlanmıştır. Bir dil olarak anlamsal ifadeyi görüntü ve sesler aracılığıyla üreten sinemada ses

  14. Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Sester Urban

    2008-06-01

    Full Text Available Abstract Background Cytomegalovirus (CMV seronegative recipients (R- of kidney transplants (KT from seropositive donors (D+ are at higher risk for CMV replication and ganciclovir(GCV-resistance than CMV R(+. We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+-patients with D(+ or D(- donors. Methods We prospectively evaluated 73 consecutive KT-patients [48 R(+, 25 D(+R(-] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-γ (IFN-γ responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools using intracellular cytokine staining and flow cytometry. Results Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+R(- than in R(+patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033. Receiver operated curve analysis associated CMV-pp65 CD4+ responses of > 0.03% in R(+-patients with absence of concurrent (p = 0.003 and future CMV replication in the following 8 weeks (p = 0.036. GCV-resistant CMV replication occurred in 3 R(+-patients (6.3% with pp65- CD4+ frequencies Conclusion The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and future CMV replication during the

  15. Specificity and function of Archaeal DNA replication initiator proteins

    DEFF Research Database (Denmark)

    Samson, Rachel Y.; Xu, Yanqun; Gadelha, Catarina

    2013-01-01

    Chromosomes with multiple DNA replication origins are a hallmark of Eukaryotes and some Archaea. All eukaryal nuclear replication origins are defined by the origin recognition complex (ORC) that recruits the replicative helicase MCM(2-7) via Cdc6 and Cdt1. We find that the three origins...... to investigate the role of ATP binding and hydrolysis in initiator function in vivo and in vitro. We find that the ATP-bound form of Orc1-1 is proficient for replication and implicates hydrolysis of ATP in downregulation of origin activity. Finally, we reveal that ATP and DNA binding by Orc1-1 remodels...

  16. Electrochemically replicated smooth aluminum foils for anodic alumina nanochannel arrays

    International Nuclear Information System (INIS)

    Biring, Sajal; Tsai, K-T; Sur, Ujjal Kumar; Wang, Y-L

    2008-01-01

    A fast electrochemical replication technique has been developed to fabricate large-scale ultra-smooth aluminum foils by exploiting readily available large-scale smooth silicon wafers as the masters. Since the adhesion of aluminum on silicon depends on the time of surface pretreatment in water, it is possible to either detach the replicated aluminum from the silicon master without damaging the replicated aluminum and master or integrate the aluminum film to the silicon substrate. Replicated ultra-smooth aluminum foils are used for the growth of both self-organized and lithographically guided long-range ordered arrays of anodic alumina nanochannels without any polishing pretreatment

  17. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress

    DEFF Research Database (Denmark)

    Bhowmick, Rahul; Minocherhomji, Sheroy; Hickson, Ian D

    2016-01-01

    Homologous recombination (HR) is necessary to counteract DNA replication stress. Common fragile site (CFS) loci are particularly sensitive to replication stress and undergo pathological rearrangements in tumors. At these loci, replication stress frequently activates DNA repair synthesis in mitosis...... replication stress at CFS loci during S-phase. In contrast, MiDAS is RAD52 dependent, and RAD52 is required for the timely recruitment of MUS81 and POLD3 to CFSs in early mitosis. Our results provide further mechanistic insight into MiDAS and define a specific function for human RAD52. Furthermore, selective...

  18. Structure of replicating intermediates of human herpesvirus type 6

    International Nuclear Information System (INIS)

    Severini, Alberto; Sevenhuysen, Claire; Garbutt, Michael; Tipples, Graham A.

    2003-01-01

    We have studied the structure of the replicative intermediates of human herpesvirus 6 (HHV-6) using pulsed-field gel electrophoresis, partial digestion, two-dimensional gel electrophoresis, and sedimentation centrifugation. The results show that DNA replication of HHV-6 produces head-to-tail concatemeric intermediates as well as approximately equal amounts of circular monomers or oligomers. Unlike the situation in herpes simplex virus, the intermediates of human herpesvirus 6 replication are not highly branched, suggesting a difference in the mechanism of replication or a lower frequency of homologous recombination in human herpesvirus 6 compared to herpes simplex virus

  19. Birliktelik Kısıtları Altında Montaj Hattı Dengeleme Problemi İçin Bir Çözüm Yaklaşımı Önerisi ve Bir İşletmede Uygulama

    Directory of Open Access Journals (Sweden)

    Serkan Altuntaş

    2010-01-01

    Full Text Available Montaj Hattı Dengelemesinde, -çeşitli nedenlerle- belli iş elemanlarının birbirinden ayrılmaması ve aynı istasyona atanması istenebilir. Bu tür problemler, 'Birliktelik Kısıtları Altında Montaj Hattı Dengeleme (BKAMHD Problemi' olarak tanınmaktadır. Bu birliktelik kısıtı sayesinde, havaleli ürün imali, birlikte işlem görme gereği gibi özel isteklerden veya takım-kolaylık benzeri kaynakların ortak kullanımı düşüncesinden kaynaklanan 'konum ve bölge kısıtları' da karşılanabilmektedir. Bu tür hatlarda ayrıca, malzeme aktarma, takım ve kolaylık maliyetleri, yürüyüş mesafeleri, ayar süreleri ile tedarik süreleri de azalmaktadır. Uygulamada BKAMHD yapısındaki problemlerle yaygın olarak karşılaşılmasına karşın, bunlar üzerinde yapılan çalışmaların klasik montaj hattı dengeleme problemi ile ilgili yayınlara göre daha az olduğu görülmektedir. Bu çalışmanın amacı, özel konum kısıtları dolayısıyla-, bilinen Montaj Hattı Dengeleme yöntemlerinin uygulanamadığı büyük ölçekli bir montaj hattı için uygun bir hat dengeleme yöntemi geliştirmek ve bu yöntem ile söz konusu hattı dengelemek olmuştur. Çalışmanın başında, bu problemin çözümünde kullanılabilecek basit fakat etkili bir yol olarak tanınan 'En Büyük Aday' algoritmasında bazı değişiklikler yapılarak yeni bir yöntem geliştirilmiştir. Bu yöntemin uyarlanabilmesi için de montaj işlemlerinin yapıldığı atölyede çok yoğun bir metot ve zaman etüdü çalışması yürütmek gerekmiştir. Bu çalışma sonucunda derlenen verilerin geliştirilen yönteme uyarlanması sonucunda türetilen seçenekler değerlendirilerek karar vericiye sunulmuştur.

  20. Periodic expression of nuclear and mitochondrial DNA replication genes during the trypanosomatid cell cycle.

    Science.gov (United States)

    Pasion, S G; Brown, G W; Brown, L M; Ray, D S

    1994-12-01

    In trypanosomatids, DNA replication in the nucleus and in the single mitochondrion (or kinetoplast) initiates nearly simultaneously, suggesting that the DNA synthesis (S) phases of the nucleus and the mitochondrion are coordinately regulated. To investigate the basis for the temporal link between nuclear and mitochondrial DNA synthesis phases the expression of the genes encoding DNA ligase I, the 51 and 28 kDa subunits of replication protein A, dihydrofolate reductase and the mitochondrial type II topoisomerase were analyzed during the cell cycle progression of synchronous cultures of Crithidia fasciculata. These DNA replication genes were all expressed periodically, with peak mRNA levels occurring just prior to or at the peak of DNA synthesis in the synchronized cultures. A plasmid clone (pdN-1) in which TOP2, the gene encoding the mitochondrial topoisomerase, was disrupted by the insertion of a NEO drug-resistance cassette was found to express both a truncated TOP2 mRNA and a truncated topoisomerase polypeptide. The truncated mRNA was also expressed periodically coordinate with the expression of the endogenous TOP2 mRNA indicating that cis elements necessary for periodic expression are contained within cloned sequences. The expression of both TOP2 and nuclear DNA replication genes at the G1/S boundary suggests that regulated expression of these genes may play a role in coordinating nuclear and mitochondrial S phases in trypanosomatids.