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Sample records for break-induced replication bir

  1. 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....

  2. 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.

  3. 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.

  4. 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.

  5. A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements.

    Science.gov (United States)

    Kohmoto, Tomohiro; Okamoto, Nana; Naruto, Takuya; Murata, Chie; Ouchi, Yuya; Fujita, Naoko; Inagaki, Hidehito; Satomura, Shigeko; Okamoto, Nobuhiko; Saito, Masako; Masuda, Kiyoshi; Kurahashi, Hiroki; Imoto, Issei

    2017-01-01

    Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single

  6. 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.

  7. 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 ...

  8. 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.

  9. Mangrove forest against dyke-break-induced tsunami on rapidly subsiding coasts

    Science.gov (United States)

    Takagi, Hiroshi; Mikami, Takahito; Fujii, Daisuke; Esteban, Miguel; Kurobe, Shota

    2016-07-01

    Thin coastal dykes typically found in developing countries may suddenly collapse due to rapid land subsidence, material ageing, sea-level rise, high wave attack, earthquakes, landslides, or a collision with vessels. Such a failure could trigger dam-break tsunami-type flooding, or "dyke-break-induced tsunami", a possibility which has so far been overlooked in the field of coastal disaster science and management. To analyse the potential consequences of one such flooding event caused by a dyke failure, a hydrodynamic model was constructed based on the authors' field surveys of a vulnerable coastal location in Jakarta, Indonesia. In a 2 m land subsidence scenario - which is expected to take place in the study area after only about 10-20 years - the model results show that the floodwaters rapidly rise to a height of nearly 3 m, resembling the flooding pattern of earthquake-induced tsunamis. The depth-velocity product criterion suggests that many of the narrow pedestrian paths behind the dyke could experience strong flows, which are far greater than the safe limits that would allow pedestrian evacuation. A couple of alternative scenarios were also considered to investigate how such flood impacts could be mitigated by creating a mangrove belt in front of the dyke as an additional safety measure. The dyke-break-induced tsunamis, which in many areas are far more likely than regular earthquake tsunamis, cannot be overlooked and thus should be considered in disaster management and urban planning along the coasts of many developing countries.

  10. 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...

  11. DNA and chromosome breaks induced by 123I-estrogen in CHO cells

    International Nuclear Information System (INIS)

    Schwartz, J.L.

    1997-01-01

    The effects of the Auger electron-emitting isotope I-123, covalently bound to estrogen, on DNA single- and double-strand breakage and on chromosome breakage was determined in estrogen positive Chinese hamster ovary (CHO-ER) cells. Exposure to the 123 I-estrogen induced both single- and double-strand breaks with a ratio of single- to double-strand breaks of 2.2. The corresponding ratio with 60 Co gamma rays was 15.6. The dose-response was biphasic suggesting that either receptor sites are saturated at high does, or that there is a nonrandom distribution of breaks induced by the 123 I-estrogen. The 123 I-estrogen treatment induced chromosome aberrations with an efficiency of about 1 aberration for each 1,000 disintegrations per cell. This corresponds to the mean lethal dose of 123 I-estrogen for these cells suggesting that the lethal event induced by the Auger electron emitter bound to estrogen is a chromosome aberration. Most of the chromosome-type aberrations were dicentrics and rings, suggesting that 123 I-estrogen-induced chromosome breaks are rejoined. The F-ratio, the ratio of dicentrics to centric rings, was 5.8 ± 1.7, which is similar to that seen with high LET radiations. Their results suggest that I-123 bound to estrogen is an efficient clastogenic agent, that the cytotoxic damage produced by I-123 bound to estrogen is very like high LET-induced damage, and the I-123 in the estrogen-receptor-DNA complex is probably in close proximity to the sugar-phosphate backbone of the DNA

  12. Nbs1 ChIP-Seq Identifies Off-Target DNA Double-Strand Breaks Induced by AID in Activated Splenic B Cells.

    Directory of Open Access Journals (Sweden)

    Lyne Khair

    2015-08-01

    Full Text Available Activation-induced cytidine deaminase (AID is required for initiation of Ig class switch recombination (CSR and somatic hypermutation (SHM of antibody genes during immune responses. AID has also been shown to induce chromosomal translocations, mutations, and DNA double-strand breaks (DSBs involving non-Ig genes in activated B cells. To determine what makes a DNA site a target for AID-induced DSBs, we identify off-target DSBs induced by AID by performing chromatin immunoprecipitation (ChIP for Nbs1, a protein that binds DSBs, followed by deep sequencing (ChIP-Seq. We detect and characterize hundreds of off-target AID-dependent DSBs. Two types of tandem repeats are highly enriched within the Nbs1-binding sites: long CA repeats, which can form Z-DNA, and tandem pentamers containing the AID target hotspot WGCW. These tandem repeats are not nearly as enriched at AID-independent DSBs, which we also identified. Msh2, a component of the mismatch repair pathway and important for genome stability, increases off-target DSBs, similar to its effect on Ig switch region DSBs, which are required intermediates during CSR. Most of the off-target DSBs are two-ended, consistent with generation during G1 phase, similar to DSBs in Ig switch regions. However, a minority are one-ended, presumably due to conversion of single-strand breaks to DSBs during replication. One-ended DSBs are repaired by processes involving homologous recombination, including break-induced replication repair, which can lead to genome instability. Off-target DSBs, especially those present during S phase, can lead to chromosomal translocations, deletions and gene amplifications, resulting in the high frequency of B cell lymphomas derived from cells that express or have expressed AID.

  13. 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...

  14. 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...

  15. 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...

  16. 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

  17. 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

  18. 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.

  19. Formation of plasmid DNA strand breaks induced by low-energy ion beam: indication of nuclear stopping effects

    International Nuclear Information System (INIS)

    Chen Yu; Jiang Bingyao; Chen Youshan; Ding Xingzhao; Liu Xianghuai; Chen Ceshi; Guo Xinyou; Yin Guanglin

    1998-01-01

    Plasmid pGEM 3zf(+) was irradiated by nitrogen ion beam with energies between 20 and 100 keV and the fluence kept as 1 x 10 12 ions/cm 2 . The irradiated plasmid was assayed by neutral electrophoresis and quantified by densitometry. The yields of DNA with single-strand and double-strand breaks first increased then decreased with increasing ion energy. There was a maximal yield value in the range of 20-100 keV. The relationship between DNA double-strand breaks (DSB) cross-section and linear energy transfer (LET) also showed a peak-shaped distribution. To understand the physical process during DNA strand breaks, a Monte Carlo calculation code known as TRIM (Transport of Ions in Matter) was used to simulate energy losses due to nuclear stopping and to electronic stopping. It can be assumed that nuclear stopping plays a more important role in DNA strand breaks than electronic stopping in this energy range. The physical mechanisms of DNA strand breaks induced by a low-energy ion beam are also discussed. (orig.)

  20. Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Larraza, Daniel M. [IMBICE, C.C. 403, 1900 La Plata (Argentina)]. E-mail: danielop@imbice.org.ar; Padron, Juan [IMBICE, C.C. 403, 1900 La Plata (Argentina); Ronci, Natalia E. [IMBICE, C.C. 403, 1900 La Plata (Argentina); Vidal Rioja, Lidia A. [IMBICE, C.C. 403, 1900 La Plata (Argentina)

    2006-08-30

    Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 {sup o}C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells.

  1. Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin

    International Nuclear Information System (INIS)

    Lopez-Larraza, Daniel M.; Padron, Juan; Ronci, Natalia E.; Vidal Rioja, Lidia A.

    2006-01-01

    Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 o C. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

  2. 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...

  3. 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...

  4. 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 ...

  5. 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...

  6. 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.

  7. 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...

  8. DNA double-strand breaks induced by high-energy neon and iron ions in human fibroblasts. I. Pulsed-field gel electrophoresis method

    International Nuclear Information System (INIS)

    Rydberg, B.; Loebrich, M.; Cooper, P.K.

    1994-01-01

    The relative effectiveness of high-energy neon and iron ions for the production of DNA double-strand breaks was measured in one transformed and one nontransformed human fibroblast cell line using pulsed-field gel electrophoresis. The DNA released from the gel plug (fraction of activity released: FAR) as well as the size distribution of the DNA entering the gel were used to compare the effects of the heavy-ion exposure with X-ray exposure. Both methods gave similar results, indicating similar distributions of breaks over megabase-pair distances for the heavy ions and the X rays. The relative biological effectiveness (RBE) compared to 225 kVp X rays of initially induced DNA double-strand breaks was found to be 0.85 for 425 MeV/u neon ions (LET 32 keV/μm) and 0.42-0.55 for 250-600 MeV/u iron ions (LET 190-350 keV/μm). Postirradiation incubation showed less efficient repair of breaks induced by the neon ions and the 600 MeV/u iron ions compared to X rays. Survival experiments demonstrated RBE values larger than one for cell killing by the heavy ions in parallel experiments (neon: RBE = 1.2, iron: RBE = 2.3-3.0, based on D 10 values). It is concluded that either the initial yield of DNA double-strand breaks induced by the high-energy particles is lower than the yield for X rays, or the breaks induced by heavy ions are present in clusters that cannot be resolved with the technique used. These results are confirmed in the accompanying paper. 48 refs., 5 figs., 2 tabs

  9. 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....

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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....

  19. 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...

  20. 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.

  1. 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…

  2. Different G2/M accumulation in M059J and M059K cells after exposure to DNA double-strand break-inducing agents

    International Nuclear Information System (INIS)

    Holgersson, Asa; Heiden, Thomas; Castro, Juan; Edgren, Margareta R.; Lewensohn, Rolf; Meijer, Annelie E.

    2005-01-01

    Purpose: To investigate and compare the cell cycle progression in relation to cell death in the human glioma cell lines, M059J and M059K, after exposure to DNA double-strand break-inducing agents. Methods and materials: The M059J and M059K cells, deficient and proficient in the catalytic subunit of the DNA-dependent protein kinase, respectively, were exposed to 1 and 4 Gy of photons or accelerated nitrogen ions. In addition, M059J and M059K cells were treated with 10 and 40 μg/mL of bleomycin for 30 min, respectively. Cell cycle progression, monitored by DNA flow cytometry, was measured up to 72 h after treatment. Results: M059J, but not M059K, cells displayed G 2 /M accumulation after low linear energy transfer irradiation. High linear energy transfer radiation exposure however, resulted in a substantial increase of M059K cells in the G 2 /M phase detected at 48 h. At 72 h, the number of cells in the G 2 /M phase was equivalent to its control. M059J cells accumulated mainly in S phase after high linear energy transfer irradiation. In contrast to M059K, M059J cells were still blocked at 72 h. Bleomycin induced G 2 /M accumulation for both M059J and M059K cells detected 24 h after treatment. At 48 h, the percentage of bleomycin-treated M059J cells in G 2 /M phase remained high, and the number of M059K cells had decreased to control levels. Neither cell line showed cell cycle arrest (≤10 h) after exposure to these agents. Conclusion: Distinct cell cycle block and release is dependent on the complexity of the induced DNA damage and the presence of the DNA-dependent protein kinase catalytic subunit

  3. 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...

  4. 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...

  5. 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

  6. 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

  7. 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.

  8. 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)

  9. 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 ...

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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...

  15. 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...

  16. 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

  17. 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...

  18. 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...

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. 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…

  5. 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

  6. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

    Science.gov (United States)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. 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...

  8. 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.

  9. 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

  10. 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.

  11. 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 ...

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents

    International Nuclear Information System (INIS)

    Jaspers, N.G.; de Wit, J.; Regulski, M.R.; Bootsma, D.

    1982-01-01

    The effect of different carcinogenic agents on the rate of semiconservative DNA replication in normal and ataxia telangiectasis (AT) cells was investigated. The rate of DNA synthesis in all AT cell strains tested was depressed to a significantly lesser extent than in normal cells after exposure to X-rays under oxia or hypoxia or to bleomycin, agents to which AT cells are hypersensitive. In contrast, inhibition of DNA replication in normal human and AT cells was similar after treatment with some DNA-methylating agents or mitomycin C. Colony-forming ability of AT cells treated with these agents was not different from normal cells. Treatment with 4-nitroquinoline 1-oxide elicited a variable response in both AT and normal cell strains. In some strains, including those shown to be hypersensitive to the drug by other workers, the inhibition of DNA synthesis was more pronounced than in other cell strains, but no significant difference between AT and normal cells could be detected. The rejoining of DNA strand breaks induced by X-rays, measured by DNA elution techniques, occurred within l2 hr after treatment and could not be correlated with the difference in DNA synthesis inhibition in AT and normal cells. After low doses of X-rays, AT cells rejoined single-strand breaks slightly more slowly than did normal cells. The rate of DNA replication in X-irradiation AT and normal cells was not affected by nicotinamide, an inhibitor of poly(adenosine diphosphate ribose) synthesis. These data indicate that the diminished inhibition of DNA replication in carcinogen-treated AT cells (a) is a general characteristic of all AT cell strains, (b) correlates with AT cellular hypersensitivity, (c) is not directly caused by the bulk of the DNA strand breaks produced by carcinogenic agents, and (d) is not based on differences in the induction of poly(adenosine diphosphate ribose) synthesis between X-irradiated AT and normal cells

  1. 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

  2. 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

  3. 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…

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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.

  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. 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

  13. 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

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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 ...

  19. 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

  20. 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.

  1. 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

  2. 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...

  3. 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...

  4. 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

  5. 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

  6. 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.

  7. 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…

  8. 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

  9. 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…

  10. 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.

  11. 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...

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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,

  18. 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

  19. 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.

  20. 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...

  1. 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.

  2. 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...

  3. 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...

  4. 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...

  5. 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

  6. 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.

  7. 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....

  8. 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

  9. 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...

  10. 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...

  11. 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....

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.)

  18. 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.

  19. 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.

  20. 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

  1. 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...

  2. 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.

  3. 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...

  4. 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

  5. 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 ...

  6. 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.

  7. 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

  8. 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...

  9. 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...

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. 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.

  2. 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

  3. 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…

  4. 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…

  5. 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…

  6. 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

  7. 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…

  8. 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…

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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...

  19. 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. ...

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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...

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  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. 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

  8. 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.

  9. 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

  10. 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.)

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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

  19. 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...

  20. 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

  1. 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. 

  2. 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)

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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....

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. /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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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)

  4. 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.

  5. 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

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. 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)

  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. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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.

  20. 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).

  1. 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...

  2. 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

  3. 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

  4. 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.

  5. 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...

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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:…

  15. 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...

  16. 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...

  17. 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.

  18. 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

  19. 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 ...

  20. 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

  1. 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.

  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. 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.

  6. 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...

  7. 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.

  8. 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...

  9. 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....

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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...

  18. 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

  19. 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

  20. 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 ...

  1. 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...

  2. 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.

  3. 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.

  4. 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 ...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.)

  17. 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.

  18. 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'.

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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...

  4. 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

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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.

  10. 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.

  11. Mevlana’nın Menkıbeleri Üzerine Folklorik Bir İnceleme A Folkloric Analysis on the Legends of Mevlana

    Directory of Open Access Journals (Sweden)

    Gülay KARAMAN

    2012-09-01

    article these topics are determined in Menâkıbu’l-Ârifîn to analysis: Places, occupations, belongings, manner of dressing, food and drinks, custom and traditions, medical treatments. Arapça bir kelime olan menkabe sözlükte övünülecek güzel iş, davranış anlamına gelmektedir. Çoğulu menâkıb olan kelime bu anlamıyla ilk defa, IX. yüzyıldan itibaren yazılıp derlenmeye başlayan hadis külliyatlarında Hz. Peygamber ve ashabının faziletlerini anlatmak için kullanılmıştır. Bundan başka tarihî şahsiyetlerin hal tercümeleri, önemli kişilerin övülecek işleri ve hatta bazı mukaddes şehirlerin tasvirinden ibaret yazılara da menâkıb denilmiştir. Başlangıçta, Hz. Peygamber ve sahabelerinin üstün ahlâkını ve yaşantılarını anlatmak üzere oluşturulan menâkıbnâmeler daha sonraları tasavvuf ve tarikat erbabının hayatlarını da konu edinmişlerdir. Türk menâkıbnâme edebiyatının bilinen ilk örneği Karahanlı dönemine ait Tezkire-i Satuk Buğra Han isimli eserdir. Tezkire-i Satuk Buğra Han’la başlayan Türk menâkıbnâme edebiyatı, göçlerle Anadolu’ya gelip yerleşen Müslüman Türkler arasında hızlı bir biçimde yayılmaya devam etmiştir. Yazar kendi toplumunun bir üyesi olduğu için doğal olarak eser de kendi çağının sosyal, kültürel ekonomik, politik yaşamına ayna olacaktır. Velilerin olağanüstü hayat hikâyelerini anlatan menâkıbnâmeler bu sebepten dolayı; özellikle tarih, kültür, halkbilimi ve edebiyat için çok önemli bilgi kaynaklarıdır. Menkıbeler üzerinde yapılacak dikkatli çalışmalar sonucunda çok zengin bir bilgi kaynağına ulaşmak mümkün olacaktır. Türkiye’de menâkıbnâmelerin bilimsel çalışmalarda kullanılmasına dikkat çeken ilk isim Türk Edebiyatında İlk Mutasavvıflar adlı eseriyle Fuad Köprülü’dür. Bu çalışmada Mevlana ve diğer Mevlevi büyüklerinin menkıbelerini anlatan bir menâkıbnâme olan Men

  12. Synaptic theory of Replicator-like melioration

    Directory of Open Access Journals (Sweden)

    Yonatan Loewenstein

    2010-06-01

    Full Text Available According to the theory of Melioration, organisms in repeated choice settings shift their choice preference in favor of the alternative that provides the highest return. The goal of this paper is to explain how this learning behavior can emerge from microscopic changes in the efficacies of synapses, in the context of two-alternative repeated-choice experiment. I consider a large family of synaptic plasticity rules in which changes in synaptic efficacies are driven by the covariance between reward and neural activity. I construct a general framework that predicts the learning dynamics of any decision-making neural network that implements this synaptic plasticity rule and show that melioration naturally emerges in such networks. Moreover, the resultant learning dynamics follows the Replicator equation which is commonly used to phenomenologically describe changes in behavior in operant conditioning experiments. Several examples demonstrate how the learning rate of the network is affected by its properties and by the specifics of the plasticity rule. These results help bridge the gap between cellular physiology and learning behavior.

  13. Factor Copula Models for Replicated Spatial Data

    KAUST Repository

    Krupskii, Pavel

    2016-12-19

    We propose a new copula model that can be used with replicated spatial data. Unlike the multivariate normal copula, the proposed copula is based on the assumption that a common factor exists and affects the joint dependence of all measurements of the process. Moreover, the proposed copula can model tail dependence and tail asymmetry. The model is parameterized in terms of a covariance function that may be chosen from the many models proposed in the literature, such as the Matérn model. For some choice of common factors, the joint copula density is given in closed form and therefore likelihood estimation is very fast. In the general case, one-dimensional numerical integration is needed to calculate the likelihood, but estimation is still reasonably fast even with large data sets. We use simulation studies to show the wide range of dependence structures that can be generated by the proposed model with different choices of common factors. We apply the proposed model to spatial temperature data and compare its performance with some popular geostatistics models.

  14. Cellular Aspects of Prion Replication In Vitro

    Science.gov (United States)

    Grassmann, Andrea; Wolf, Hanna; Hofmann, Julia; Graham, James; Vorberg, Ina

    2013-01-01

    Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered β-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and propagation of prions derived from cell culture experiments. We discuss recent findings on the trafficking of cellular and pathologic PrP, the potential sites of abnormal prion protein synthesis and potential co-factors involved in prion entry and propagation. PMID:23340381

  15. Factor Copula Models for Replicated Spatial Data

    KAUST Repository

    Krupskii, Pavel; Huser, Raphaë l; Genton, Marc G.

    2016-01-01

    We propose a new copula model that can be used with replicated spatial data. Unlike the multivariate normal copula, the proposed copula is based on the assumption that a common factor exists and affects the joint dependence of all measurements of the process. Moreover, the proposed copula can model tail dependence and tail asymmetry. The model is parameterized in terms of a covariance function that may be chosen from the many models proposed in the literature, such as the Matérn model. For some choice of common factors, the joint copula density is given in closed form and therefore likelihood estimation is very fast. In the general case, one-dimensional numerical integration is needed to calculate the likelihood, but estimation is still reasonably fast even with large data sets. We use simulation studies to show the wide range of dependence structures that can be generated by the proposed model with different choices of common factors. We apply the proposed model to spatial temperature data and compare its performance with some popular geostatistics models.

  16. Nicotinamide extends replicative lifespan of human cells.

    Science.gov (United States)

    Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

    2006-10-01

    We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

  17. Minority games, evolving capitals and replicator dynamics

    International Nuclear Information System (INIS)

    Galla, Tobias; Zhang, Yi-Cheng

    2009-01-01

    We discuss a simple version of the minority game (MG) in which agents hold only one strategy each, but in which their capitals evolve dynamically according to their success and in which the total trading volume varies in time accordingly. This feature is known to be crucial for MGs to reproduce stylized facts of real market data. The stationary states and phase diagram of the model can be computed, and we show that the ergodicity breaking phase transition common for MGs, and marked by a divergence of the integrated response, is present also in this simplified model. An analogous majority game turns out to be relatively void of interesting features, and the total capital is found to diverge in time. Introducing a restraining force leads to a model akin to the replicator dynamics of evolutionary game theory, and we demonstrate that here a different type of phase transition is observed. Finally we briefly discuss the relation of this model with one strategy per player to more sophisticated minority games with dynamical capitals and several trading strategies per agent

  18. Modelling the Replication Management in Information Systems

    Directory of Open Access Journals (Sweden)

    Cezar TOADER

    2017-01-01

    Full Text Available In the modern economy, the benefits of Web services are significant because they facilitates the activities automation in the framework of Internet distributed businesses as well as the cooperation between organizations through interconnection process running in the computer systems. This paper presents the development stages of a model for a reliable information system. This paper describes the communication between the processes within the distributed system, based on the message exchange, and also presents the problem of distributed agreement among processes. A list of objectives for the fault-tolerant systems is defined and a framework model for distributed systems is proposed. This framework makes distinction between management operations and execution operations. The proposed model promotes the use of a central process especially designed for the coordination and control of other application processes. The execution phases and the protocols for the management and the execution components are presented. This model of a reliable system could be a foundation for an entire class of distributed systems models based on the management of replication process.

  19. Metindilbilimi Metindilbilimsel Bağdaşıklık ve Haldun Taner’in Onikiye Bir Var Adlı Öyküsünde Metindilbilimsel Bağdaşıklık Görünümleri

    OpenAIRE

    ÖZKAN, Bülent

    2013-01-01

    This article is a comprehensive summary of the seminar study whose name is “Text Linguistics And Text Linguistics Cohesion At The Story ‘Onikiye Bir Var’ by Haldun TANER” In this article we aimed to research what ‘text linguistics’ and ‘text linguistic chosion’ are and how the text linguistic chosion is reflected in the story ‘Onikiye Bir Var’ by Haldun TANER Key words: Text Linguistics Text Linguistics Cohesion Haldun TANER

  20. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

    Science.gov (United States)

    Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

    2009-12-01

    Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

  1. Standart Türkçeye Bir Katkı: us+(uk- A Contribution To The Literary Turkish: us+(uk-

    Directory of Open Access Journals (Sweden)

    İ. Gülsel SEV

    2013-07-01

    Full Text Available A language has two dimensions namely colloquial and literary. Dialects within the colloquial language have important places. Literary language, which is static and resistant to changes, improves and gets richer with the help of dialects. The best examples of this process wereobserved during the language revolution when words, notions andterms were transferred to the literary language from with collectionsfrom dialects.The focus of the present study is the usuk- verb which means‘become wise, to get silent, to calm down’ in the dialects of Turkish.usuk- was derived with the deverbal suffix +(Ik- from the noun us‘wisdom’. Us is related both u- which means to understand and -ū whichmeans ‘to be able to, to have the power’.The suffix +(Ik- is not widely used in Turkish, there are a fewexamples such as acık-, birik-, gecik-, gözük-. However, there are manyexamples of this suffix in the historical and modern dialects.us-(uk- or with the forms in dialects as usukmak ve usuhmah hasseveral meanings such as ‘to get wise, to calm down after an offence oranger, to get silent because of astonishment, not to be able to talk, toget calm’. It is stated in the article that usuk whose implied meaningwere nor encountered in the historical dialects must be transferred tothe literary language with the meanings of ‘to get wise, to get silent andto calm down’. Besides, it is expected to take a step to increase thenumber of example verbs derived with +(Ik-, considering the examplesin the historical dialects. Dilin yazı dili ve konuşma dili olmak üzere iki yönü vardır. Konuşma dili içerisinde yer alan ağızlar apayrı bir yere sahiptir. Kolay kolay değişmeyen, durgun bir yapıya sahip olan yazı dili; canlı, gelişime ve değişime açık ağızlardan beslenerek gelişir ve zenginleşir. Bunun en güzel örneklerini dil devrimi sırasında halk ağızlarından yapılan derlemelerin, sözcük, terim ve kavram olarak yazı diline kazand

  2. Rolling replication of UV-irradiated duplex DNA in the phi X174 replicative-form----single-strand replication system in vitro

    International Nuclear Information System (INIS)

    Shavitt, O.; Livneh, Z.

    1989-01-01

    Cloning of the phi X174 viral origin of replication into phage M13mp8 produced an M13-phi X174 chimera, the DNA of which directed efficient replicative-form----single-strand rolling replication in vitro. This replication assay was performed with purified phi X174-encoded gene A protein, Escherichia coli rep helicase, single-stranded DNA-binding protein, and DNA polymerase III holoenzyme. The nicking of replicative-form I (RFI) DNA by gene A protein was essentially unaffected by the presence of UV lesions in the DNA. However, unwinding of UV-irradiated DNA by the rep helicase was inhibited twofold as compared with unwinding of the unirradiated substrate. UV irradiation of the substrate DNA caused a strong inhibition in its ability to direct DNA synthesis. However, even DNA preparations that contained as many as 10 photodimers per molecule still supported the synthesis of progeny full-length single-stranded DNA. The appearance of full-length radiolabeled products implied at least two full rounds of replication, since the first round released the unlabeled plus viral strand of the duplex DNA. Pretreatment of the UV-irradiated DNA substrate with purified pyrimidine dimer endonuclease from Micrococcus luteus, which converted photodimer-containing supercoiled RFI DNA into relaxed, nicked RFII DNA and thus prevented its replication, reduced DNA synthesis by 70%. Analysis of radiolabeled replication products by agarose gel electrophoresis followed by autoradiography revealed that this decrease was due to a reduction in the synthesis of progeny full-length single-stranded DNA. This implies that 70 to 80% of the full-length DNA products produced in this system were synthesized on molecules that carried photodimers

  3. Parallelizing Federated SPARQL Queries in Presence of Replicated Data

    DEFF Research Database (Denmark)

    Minier, Thomas; Montoya, Gabriela; Skaf-Molli, Hala

    2017-01-01

    Federated query engines have been enhanced to exploit new data localities created by replicated data, e.g., Fedra. However, existing replication aware federated query engines mainly focus on pruning sources during the source selection and query decomposition in order to reduce intermediate result...

  4. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  5. Three attempts to replicate the moral licensing effect

    NARCIS (Netherlands)

    Blanken, I.; van de Ven, N.; Zeelenberg, M.; Meijers, Marijn H. C.

    2014-01-01

    The present work includes three attempts to replicate the moral licensing effect by Sachdeva, Iliev, and Medin (2009). The original authors found that writing about positive traits led to lower donations to charity and decreased cooperative behavior. The first two replication attempts (student

  6. CRISPR-mediated control of the bacterial initiation of replication

    NARCIS (Netherlands)

    Wiktor, J.M.; Lesterlin, Christian; Sherratt, David J.; Dekker, C.

    2016-01-01

    Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is

  7. The Alleged Crisis and the Illusion of Exact Replication

    NARCIS (Netherlands)

    Stroebe, Wolfgang; Strack, Fritz

    There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a replication crisis in psychology. Psychologists are encouraged to conduct more exact

  8. An Inadvertent Concurrent Replication: Same Roadmap, Different Journey

    Science.gov (United States)

    Lemons, Christopher J.; King, Seth A.; Davidson, Kimberly A.; Berryessa, Teresa L.; Gajjar, Shimul A.; Sacks, Lia H.

    2016-01-01

    Replication is a critical aspect of scientific inquiry that presents a variety of challenges to researchers, even under the best of conditions. We conducted a review of replication rates in special education journals similar to the review conducted by Makel et al. in this issue. Unknowingly conducting independent reviews allowed for an unexpected…

  9. Replication of Psycholinguistic Experiments and the Resolution of Inconsistencies

    Science.gov (United States)

    Rákosi, Csilla

    2017-01-01

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

  10. Focus Article: Replication in Second Language Writing Research

    Science.gov (United States)

    Porte, Graeme; Richards, Keith

    2012-01-01

    This paper discusses the meaning and range of replication in L2 research from both quantitative and qualitative perspectives. In the first half of the paper, it will be argued that key quantitative studies need to be replicated to have their robustness and generalizability tested and that this is a requirement of scientific inquiry. Such research…

  11. Chromatin maturation depends on continued DNA-replication

    International Nuclear Information System (INIS)

    Schlaeger, E.J.; Puelm, W.; Knippers, R.

    1983-01-01

    The structure of [ 3 H]thymidine pulse-labeled chromatin in lymphocytes differs from that of non-replicating chromatin by several operational criteria which are related to the higher nuclease sensitivity of replicating chromatin. These structural features of replicating chromatin rapidly disappear when the [ 3 H]thymidine pulse is followed by a chase in the presence of an excess of non-radioactive thymidine. However, when the rate of DNA replication is reduced, as in cycloheximide-treated lymphocytes, chromatin maturation is retarded. No chromatin maturation is observed when nuclei from pulse-labeled lymphocytes are incubated in vitro in the absence of DNA precursors. In contrast, when these nuclei are incubated under conditions known to be optimal for DNA replication, the structure of replicating chromatin is efficiently converted to that of 'mature', non-replicating chromatin. The authors conclude that the properties of nascent DNA and/or the distance from the replication fork are important factors in chromatin maturation. (Auth.)

  12. Perfectionism in Gifted Adolescents: A Replication and Extension

    Science.gov (United States)

    Margot, Kelly C.; Rinn, Anne N.

    2016-01-01

    To provide further generalizability for the results garnered by two previous studies, the authors conducted a methodological replication. In addition to adding to the body of replication research done with gifted students, the purpose of this study was to examine perfectionism differences among gifted adolescents in regards to gender, birth order,…

  13. Replication of Special Education Research: Necessary but Far Too Rare

    Science.gov (United States)

    Makel, Matthew C.; Plucker, Jonathan A.; Freeman, Jennifer; Lombardi, Allison; Simonsen, Brandi; Coyne, Michael

    2016-01-01

    Increased calls for rigor in special education have often revolved around the use of experimental research design. However, the replicability of research results is also a central tenet to the scientific research process. To assess the prevalence, success rate, and authorship history of replications in special education, we investigated the…

  14. Oblique roughness replication in strained SiGe/Si multilayers

    NARCIS (Netherlands)

    Holy, V.; Darhuber, A.A.; Stangl, J.; Bauer, G.; Nützel, J.-F.; Abstreiter, G.

    1998-01-01

    The replication of the interface roughness in SiGe/Si multilayers grown on miscut Si(001) substrates has been studied by means of x-ray reflectivity reciprocal space mapping. The interface profiles were found to be highly correlated and the direction of the maximal replication was inclined with

  15. Bayesian evaluation of effect size after replicating an original study

    NARCIS (Netherlands)

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

    2017-01-01

    The vast majority of published results in the literature is statistically significant, which raises concerns about their reliability. The Reproducibility Project Psychology (RPP) and Experimental Economics Replication Project (EE-RP) both replicated a large number of published studies in psychology

  16. Enzymes involved in organellar DNA replication in photosynthetic eukaryotes.

    Science.gov (United States)

    Moriyama, Takashi; Sato, Naoki

    2014-01-01

    Plastids and mitochondria possess their own genomes. Although the replication mechanisms of these organellar genomes remain unclear in photosynthetic eukaryotes, several organelle-localized enzymes related to genome replication, including DNA polymerase, DNA primase, DNA helicase, DNA topoisomerase, single-stranded DNA maintenance protein, DNA ligase, primer removal enzyme, and several DNA recombination-related enzymes, have been identified. In the reference Eudicot plant Arabidopsis thaliana, the replication-related enzymes of plastids and mitochondria are similar because many of them are dual targeted to both organelles, whereas in the red alga Cyanidioschyzon merolae, plastids and mitochondria contain different replication machinery components. The enzymes involved in organellar genome replication in green plants and red algae were derived from different origins, including proteobacterial, cyanobacterial, and eukaryotic lineages. In the present review, we summarize the available data for enzymes related to organellar genome replication in green plants and red algae. In addition, based on the type and distribution of replication enzymes in photosynthetic eukaryotes, we discuss the transitional history of replication enzymes in the organelles of plants.

  17. Universal Temporal Profile of Replication Origin Activation in Eukaryotes

    Science.gov (United States)

    Goldar, Arach

    2011-03-01

    The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

  18. Reconsidering Replication: New Perspectives on Large-Scale School Improvement

    Science.gov (United States)

    Peurach, Donald J.; Glazer, Joshua L.

    2012-01-01

    The purpose of this analysis is to reconsider organizational replication as a strategy for large-scale school improvement: a strategy that features a "hub" organization collaborating with "outlet" schools to enact school-wide designs for improvement. To do so, we synthesize a leading line of research on commercial replication to construct a…

  19. Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe.

    Science.gov (United States)

    Margalef, Pol; Kotsantis, Panagiotis; Borel, Valerie; Bellelli, Roberto; Panier, Stephanie; Boulton, Simon J

    2018-01-25

    Telomere maintenance critically depends on the distinct activities of telomerase, which adds telomeric repeats to solve the end replication problem, and RTEL1, which dismantles DNA secondary structures at telomeres to facilitate replisome progression. Here, we establish that reversed replication forks are a pathological substrate for telomerase and the source of telomere catastrophe in Rtel1 -/- cells. Inhibiting telomerase recruitment to telomeres, but not its activity, or blocking replication fork reversal through PARP1 inhibition or depleting UBC13 or ZRANB3 prevents the rapid accumulation of dysfunctional telomeres in RTEL1-deficient cells. In this context, we establish that telomerase binding to reversed replication forks inhibits telomere replication, which can be mimicked by preventing replication fork restart through depletion of RECQ1 or PARG. Our results lead us to propose that telomerase inappropriately binds to and inhibits restart of reversed replication forks within telomeres, which compromises replication and leads to critically short telomeres. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Elma Üretiminde Pazarlama Etkinliğinin Belirlenmesi Üzerine Bir Araştırma: Isparta Senirkent İlçesi Örneği

    OpenAIRE

    ERDOĞAN, Esra; ADANACIOĞLU, Hakan; ORMECI KART, Murside

    2016-01-01

    Türkiye’nin birçok bölgesinde ekonomik anlamda yetiştiriciliği yapılan elmanın eski bir kültür bitkisi olması nedeniyle elma üretiminde pazarlama etkinliğinin belirlenmesi önem taşımaktadır. Bu çalışmada hem dolaylı hem de doğrudan pazarlama kanallarında elma üreticilerinin pazarlama  etkinlikleri karşılaştırılmalı olarak incelenmiştir. Bunun yanında çalışmada, üreticilerin pazarlama etkinliğini geliştirmek için kullanılan pazarlama stratejilerine yönelik bazı öneriler getirilmiştir. Bu çalış...

  1. Türkiye’de Franchising Sisteminin Gelişimi ve Franchise Alan Girişimcilerin İş Memnuniyeti Belirleyicilerinin Analizi Üzerine Bir Araştırma

    OpenAIRE

    Nart, Sima

    2005-01-01

    Bu çalışmada, Türkiye’de Franchising sisteminin gelişimi ve bugünkü konumu incelendikten sonra Ulusal Franchising Derneği (UFRAD) üyesi Franchise-veren firmalardan Franchise-alan girişimcilerin iş memnuniyetlerini belirleyen etkenler üzerine bir anket çalışması yapılmıştır. Bulgular, franchise-alan işletmelerin memnuniyetlerinde sistem motivasyonu, işbirliği, güç dengesi, beklentiler ve franchise veren firmanın imajının belirleyici rol oynadığını göstermektedir. Araştırma sonuçları franchisev...

  2. Growth Hacking, Dünyayı İşgal Eden Büyüklere Karşı Bir Kurtuluş Savaşı Olabilir mi?

    OpenAIRE

    FETTAHLIOĞLU, H. Seçil; AKDEMİR, Mehmet Alper

    2016-01-01

    Bilgi ekonomisinin etkisinin hissedildiği günümüz ortamında, internetin pazarlama üzerindeki rolü hızla artmaktadır. Dijital pazarlama, içerik pazarlaması, online pazarlama gibi bir çok başlık altında toplanabilecek olan; bilgi teknolojileri vasıtasıyla pazarlama faaliyetlerini ifade eden kavramlar “Growth Hacking (Büyüme Korsanlığı)” ile birlikte anılmaktadır. Büyüme korsanlığı, genellikle online girişimlerin, hızlı bir şekilde dijital pazarlama ve yazılım araçları vasıtasıyla büyütülmesi iç...

  3. Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.

    Science.gov (United States)

    Stoeck, Ina Karen; Lee, Ji-Young; Tabata, Keisuke; Romero-Brey, Inés; Paul, David; Schult, Philipp; Lohmann, Volker; Kaderali, Lars; Bartenschlager, Ralf

    2018-01-01

    Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes massive rearrangements of intracellular membranes, resulting in a membranous web (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic details on the source and recruitment of cholesterol to the viral replication organelle are only partially known. Here we focused on selected lipid transfer proteins implicated in direct lipid transfer at various endoplasmic reticulum (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown identified several hitherto unknown HCV dependency factors, such as steroidogenic acute regulatory protein-related lipid transfer domain protein 3 (STARD3), oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann-Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and required for efficient HCV RNA replication but not for replication of the closely related dengue virus. Focusing on NPC1, we found that knockdown or pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles concomitant with decreased cholesterol abundance at sites containing the viral replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs, arguing for NPC1-mediated endosomal cholesterol transport to the viral replication organelle. Consistent with cholesterol being an important structural component of DMVs, reducing NPC1-dependent endosomal cholesterol transport impaired MW integrity. This suggests that HCV usurps lipid transfer proteins, such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit cholesterol to the viral replication organelle, where it contributes to MW functionality. IMPORTANCE A key feature of the replication of positive-strand RNA viruses is the rearrangement of the host cell

  4. Diversity of the DNA Replication System in the Archaea Domain

    Directory of Open Access Journals (Sweden)

    Felipe Sarmiento

    2014-01-01

    Full Text Available The precise and timely duplication of the genome is essential for cellular life. It is achieved by DNA replication, a complex process that is conserved among the three domains of life. Even though the cellular structure of archaea closely resembles that of bacteria, the information processing machinery of archaea is evolutionarily more closely related to the eukaryotic system, especially for the proteins involved in the DNA replication process. While the general DNA replication mechanism is conserved among the different domains of life, modifications in functionality and in some of the specialized replication proteins are observed. Indeed, Archaea possess specific features unique to this domain. Moreover, even though the general pattern of the replicative system is the same in all archaea, a great deal of variation exists between specific groups.

  5. Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

    Directory of Open Access Journals (Sweden)

    Antonio Postigo

    2017-05-01

    Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.

  6. ATR prohibits replication catastrophe by preventing global exhaustion of RPA.

    Science.gov (United States)

    Toledo, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt; Lukas, Claudia; Larsen, Dorthe Helena; Povlsen, Lou Klitgaard; Bekker-Jensen, Simon; Mailand, Niels; Bartek, Jiri; Lukas, Jiri

    2013-11-21

    ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Initiation of DNA replication requires actin dynamics and formin activity.

    Science.gov (United States)

    Parisis, Nikolaos; Krasinska, Liliana; Harker, Bethany; Urbach, Serge; Rossignol, Michel; Camasses, Alain; Dewar, James; Morin, Nathalie; Fisher, Daniel

    2017-11-02

    Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms. © 2017 The Authors.

  8. Autophagy Facilitates Salmonella Replication in HeLa Cells

    Science.gov (United States)

    Yu, Hong B.; Croxen, Matthew A.; Marchiando, Amanda M.; Ferreira, Rosana B. R.; Cadwell, Ken; Foster, Leonard J.; Finlay, B. Brett

    2014-01-01

    ABSTRACT Autophagy is a process whereby a double-membrane structure (autophagosome) engulfs unnecessary cytosolic proteins, organelles, and invading pathogens and delivers them to the lysosome for degradation. We examined the fate of cytosolic Salmonella targeted by autophagy and found that autophagy-targeted Salmonella present in the cytosol of HeLa cells correlates with intracellular bacterial replication. Real-time analyses revealed that a subset of cytosolic Salmonella extensively associates with autophagy components p62 and/or LC3 and replicates quickly, whereas intravacuolar Salmonella shows no or very limited association with p62 or LC3 and replicates much more slowly. Replication of cytosolic Salmonella in HeLa cells is significantly decreased when autophagy components are depleted. Eventually, hyperreplication of cytosolic Salmonella potentiates cell detachment, facilitating the dissemination of Salmonella to neighboring cells. We propose that Salmonella benefits from autophagy for its cytosolic replication in HeLa cells. PMID:24618251

  9. USP7 is a SUMO deubiquitinase essential for DNA replication

    DEFF Research Database (Denmark)

    Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia

    2016-01-01

    Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment...... is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads...... to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7...

  10. Chromatin Constrains the Initiation and Elongation of DNA Replication.

    Science.gov (United States)

    Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

    2017-01-05

    Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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

    2017-06-01

    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. © 2017 Riera et al.; Published by Cold Spring Harbor Laboratory Press.

  12. Haber Etiği ve Bir Siyasi Haber İncelemesi / News Ethics and An Analysis of a Political News

    Directory of Open Access Journals (Sweden)

    Buğra KARDAN

    2015-07-01

    Full Text Available Medyada haber etiği ve habercilik ahlakı tartışmaları, medya tarihi kadar eski bir olgudur. İletişim teknolojisinin sağladığı imkânlarla faaliyet çeşitliliği, etki gücü ve etki alanı hızla artan basın-yayın sektörü, siyasi ve/veya mali hedefler gözeten birer araç olarak artık daha sık kullanılmakta ve ortaya çıkan etik (ve adli sorunlar, medyada haber etiği tartışmalarının güncel kalması sonucunu doğurmaktadır. Bu çalışmada medyada haber etiği konusu, siyasi bir haber (bir siyasi parti genel başkanına dönük şiddet eylemi haberi çerçevesinde ele alınmış; olayın farklı siyasi duruşlardaki bazı medya organları (gazeteler tarafından haberleştirilme biçimi, belirli kıstaslar altında toplanan veriler eşliğinde, haber etiği perspektifiyle ve karşılaştırmalı olarak incelenmiştir. Yapılan inceleme sonuçlarına göre, özellikle bazı gazetelerde söz konusu haberin sunuş biçimi üzerinde medya organlarının siyasi pozisyonlarının etkili olabildiği gözlemlenmiştir. / Debates on ethics in media and journalism has a long-standing history, just as the history of media. Due to the opportunities provided by communication technologies, power, influence and functions of the press and media increase and so that play an instrumental role in maximization of the political and/or financial ambitions of political or economic actors. Hence, debates on news ethics continue forever to be a major issue. This study focuses on ethical issues in the news and more specifically political news; elaborates on a news about the violence that a political party leader faced in Turkey, and analyzes how media (newspapers from different political views reflected the case. As a result of the study, it has been observed that newspapers presented the event largely according to their political positions and worldviews.

  13. KONSEP MᾹQᾹṢID AL-SYᾹRĪAH MENURUT ṬᾹHᾹ JᾹBIR AL-‘ALWᾹNĪ

    Directory of Open Access Journals (Sweden)

    Chasnak Najidah

    2017-03-01

    Full Text Available One discourse which is receiving considerable attention from scholars of Islam is about the objectives of Islamic law (maqasid al-shari'ah. Taha Jabir al-'Alwānī as one reviewer of Maqasid al-shari'ah contemporary formulate the concept of maqasid al-shari'ah different from previous scholars. This article describes the concept of maqasid al-shari'ah by Taha Jabir al-'Alwānī. According to him, there are three levels of hierarchical of Maqasid al-Sharia. The highest value of maqasid al-shari'ah says is what he describes as al-Maqasid al-'ulyā al-Hakimah (intentions of the highest shari'ah and a legal basis, which consists of three main elements, namely al-Tawhid ( Onesess of God, al-Tazkiyah (purification and al-'umrān (prosperity. The position of the second al-shari'ah Maqasid are universal values such as justice, freedom, and equality. While the third position is the formulation of the previous scholars regarding maqasid al-shari'ah consisting of ḍarūriyyat, ḥājiyyāt, and taḥsīniyyāt. In terms of methodological, Taha Jabir al-'Alwānī basing the new system for Maqasid al-syarī'ahnya on the methods of al-jam'u Baina al-qirā'atain, a reading of the two entities: the revelation of God and the universe. With this basis, he argues that the maqasid al-shari'ah formulations are qaṭ'ī, so it can be a reference to the scholars in solving the problems of contemporary law.   [Salah satu diskursus yang mendapat perhatian cukup besar dari para akademisi Islam adalah seputar tujuan-tujuan hukum islam  (maqāṣid al-syarī'ah. Ṭāhā Jābir al-‘Alwānī sebagai salah satu ulama pengkaji maqāṣid asy-syarī’ahkontemporer merumuskan konsep maqāṣid asy-syarī’ahyang berbeda dari ulama sebelumnya. Artikel ini mendeskripsikan konsep maqāṣid asy-syarī’ahmenurut Ṭāhā Jābir al-‘Alwānī. Menurutnya, ada tiga tingkatan hierarkis maqāṣid al-syarī'ah. Nilai tertinggi maqāṣid asy-syarī’ahmenurutnya adalah apa

  14. An Alternative Form of Replication Protein A Prevents Viral Replication in Vitro*

    OpenAIRE

    Mason, Aaron C.; Haring, Stuart J.; Pryor, John M.; Staloch, Cathy A.; Gan, Tze Fei; Wold, Marc S.

    2009-01-01

    Replication protein A (RPA), the eukaryotic single-stranded DNA-binding complex, is essential for multiple processes in cellular DNA metabolism. The “canonical” RPA is composed of three subunits (RPA1, RPA2, and RPA3); however, there is a human homolog to the RPA2 subunit, called RPA4, that can substitute for RPA2 in complex formation. We demonstrate that the resulting “alternative” RPA (aRPA) complex has solution and DNA binding properties indistinguishable from the c...

  15. 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)

  16. Flock House virus subgenomic RNA3 is replicated and its replication correlates with transactivation of RNA2

    International Nuclear Information System (INIS)

    Eckerle, Lance D.; Albarino, Cesar G.; Ball, L. Andrew.

    2003-01-01

    The nodavirus Flock House virus has a bipartite genome composed of RNAs 1 and 2, which encode the catalytic component of the RNA-dependent RNA polymerase (RdRp) and the capsid protein precursor, respectively. In addition to catalyzing replication of the viral genome, the RdRp also transcribes from RNA1 a subgenomic RNA3, which is both required for and suppressed by RNA2 replication. Here, we show that in the absence of RNA1 replication, FHV RdRp replicated positive-sense RNA3 transcripts fully and copied negative-sense RNA3 transcripts into positive strands. The two nonstructural proteins encoded by RNA3 were dispensable for replication, but sequences in the 3'-terminal 58 nucleotides were required. RNA3 variants that failed to replicate also failed to transactivate RNA2. These results imply that RNA3 is naturally produced both by transcription from RNA1 and by subsequent RNA1-independent replication and that RNA3 replication may be necessary for transactivation of RNA2

  17. Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation

    Energy Technology Data Exchange (ETDEWEB)

    Eyre, Nicholas S., E-mail: nicholas.eyre@adelaide.edu.au [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Hampton-Smith, Rachel J.; Aloia, Amanda L. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia); Eddes, James S. [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Simpson, Kaylene J. [Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, East Melbourne (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville (Australia); Hoffmann, Peter [Adelaide Proteomics Centre, School of Biological Sciences, University of Adelaide, Adelaide (Australia); Institute for Photonics and Advanced Sensing (IPAS), University of Adelaide, Adelaide (Australia); Beard, Michael R. [School of Biological Sciences and Research Centre for Infectious Diseases, University of Adelaide, Adelaide (Australia); Centre for Cancer Biology, SA Pathology, Adelaide (Australia)

    2016-04-15

    Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using ‘APEX2’-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIα) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIα. - Highlights: • NS5A residues Ser-222, Ser-235 and Thr-348 are phosphorylated during HCV infection. • Phosphorylation of Ser-235 is essential to HCV RNA replication. • Mutation of Ser-235 alters replication compartment localization and morphology. • Phosphatidylinositol-4 kinase III alpha is important for Ser-235 phosphorylation.

  18. Research Methods Used in Library and Information Science Theses: An Evaluation Kütüphanecilik ve Bilgi Bilim Tezlerinde Kullanılan Bilimsel Araştırma Yöntemleri : Bir Değerlendirme

    Directory of Open Access Journals (Sweden)

    S. Serap Kurbanoğlu

    1996-12-01

    Full Text Available A literature analysis and an evaluation are made on the findings of researches which examine the research methods employed in library science and information science dissertations. The data suggest some changes regarding to research methods used in library science dissertations. Separate examinations of library science dissertations and information science dissertations suggest that there are differences as much assimilarities between these sister disciplines. Kütüphanecilik ve bilgi bilim tezlerinde kullanılan araştırma yöntemleri konusunda yapılan araştırmaların bulguları üzerine bir literatür çalışması ve bir değerlendirme yapılmıştır. Bulgular kütüphanecilik tezlerinde kullanılan araştırma yöntemleri konusunda zaman içinde bir çeşitlenme olduğunu göstermektedir. Kütüphanecilik ve bilgi bilim tezleri üzerinde ayrı ayrı yürütülen incelemeler ise bu iki kardeş disiplin arasında benzerlikler kadar farklılıklar da olduğunu ortaya koymaktadır.

  19. ABD liderliğindeki Irak işgali sonrası körfez işbirliği konseyi (KİK) : Güvenlik topluluğu'na doğru

    OpenAIRE

    Çetinoğlu, Nur

    2010-01-01

    ABD liderliğindeki Irak işgalinin sonuçları sadece Irak'la sınırlı kalmamış, sınırlarının ötesine taşmıştır. O tarihe kadar gevşek bir ittifak olarak kabul edilen Körfez İşbirliği Konseyi (KİK), söz konusu işgalin sonuçlarından en çok etkilenen birimlerden olmuştur. Bu makale, KİK 'in henüz bir güvenlik topluluğu olmamasına rağmen, bu yolda aşama kaydettiğini iddia etmektedir. Irak savaşı sonrası dönemde hem KİK dışında yaşanan gelişmelerin hem de KİK bünyesinde kaydedilen ilerlemelerin anali...

  20. Marka İmajının Sosyal Ağ Analizi ile İncelenmesi: Turkcell ve Vodafone Markalarına Yönelik Bir Araştırma

    OpenAIRE

    BAŞFIRINCI, Çiğdem

    2016-01-01

    Marka imajı, günümüzün pazarlama literatüründeki önemli konu başlıklarından bir tanesidir. Ne var ki, yöntembilimsel bir bakış açısıyla, marka imajını sosyal ağ analizi ile inceleyen çalışmaların sayısının son derece sınırlı olduğu görülmektedir. Bu kapsamda bu araştırmanın amacı markaya ilişkin çağrışımların keşfedilmesinde alternatif ve kullanışlı bir yöntem olarak sosyal ağ analizini tanıtmak ve bu yöntemin marka imajlarının derinlemesine ve rekabetçi biçimde keşfine nasıl olanak sağladığı...

  1. iktisat ve işletmede istatistiksel anlamda indeksin önemi ve hesaplama teknikleri üzerine bir açıklama

    Directory of Open Access Journals (Sweden)

    Adnan MAZMANOĞLU

    2012-04-01

    Full Text Available Bu makalemizde doğrudan matematiksel hesaplamalarla ilgili olmakla beraber, indeks veya indeks sayılarının, bir değişkenin veya değişkenler grubunun zaman veya mekân (bölge içerisindeki değişimlerini gösteren istatistiksel bir ölçü olduğunu derinlemesine incelemeye çalışacağız (Yoğurtçugil, 1977. İşletme, İktisat ile ilgili konularda kullanılması yaygın olmakla beraber diğer alanlarda da kullanılan indeks, ekonomik yaşamın vazgeçilmez kavramları olan fiyat veya miktar karşılaştırmaları yapmak, üretim veya fiyatların zaman içindeki gelişmelerini izlemek indekslerle mümkündür. Fiyatlardaki, üretimdeki ve yaşama düzeylerindeki değişimi ölçmekten başka, farklı yıllar ya da farklı bölgeler için öğrencilerin zekâ oranlarını karşılaştırmak da indekslerle (indeks sayılarıyla yapılabilmektedir. Örneğin nasıl ki paranın satın alma gücündeki değişebilirlik nedeniyle anlamlı karşılaştırmalar yapabilmek için bazı malların fiyatları yükseltilirken bazılarınki düşürülüyorsa, bu inceleme için indeksleri bilmenin gerekli olduğunu göstereceğiz ( Akdeniz, 1984.

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

    Science.gov (United States)

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

    2007-12-19

    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 deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (approximately 3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint

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

    Science.gov (United States)

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

    2007-01-01

    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 deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in

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

    Directory of Open Access Journals (Sweden)

    Scott Donna

    2007-12-01

    Full Text Available 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 deoxyribonucleoside triphosphates (dNTPs and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR or cds1 (which encodes the fission yeast homologue of Chk2. Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3% behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild

  5. The transcription elongation factor Bur1-Bur2 interacts with replication protein A and maintains genome stability during replication stress

    DEFF Research Database (Denmark)

    Clausing, Emanuel; Mayer, Andreas; Chanarat, Sittinan

    2010-01-01

    Multiple DNA-associated processes such as DNA repair, replication, and recombination are crucial for the maintenance of genome integrity. Here, we show a novel interaction between the transcription elongation factor Bur1-Bur2 and replication protein A (RPA), the eukaryotic single-stranded DNA......-binding protein with functions in DNA repair, recombination, and replication. Bur1 interacted via its C-terminal domain with RPA, and bur1-¿C mutants showed a deregulated DNA damage response accompanied by increased sensitivity to DNA damage and replication stress as well as increased levels of persisting Rad52...... foci. Interestingly, the DNA damage sensitivity of an rfa1 mutant was suppressed by bur1 mutation, further underscoring a functional link between these two protein complexes. The transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress....

  6. Viral replication. Structural basis for RNA replication by the hepatitis C virus polymerase.

    Science.gov (United States)

    Appleby, Todd C; Perry, Jason K; Murakami, Eisuke; Barauskas, Ona; Feng, Joy; Cho, Aesop; Fox, David; Wetmore, Diana R; McGrath, Mary E; Ray, Adrian S; Sofia, Michael J; Swaminathan, S; Edwards, Thomas E

    2015-02-13

    Nucleotide analog inhibitors have shown clinical success in the treatment of hepatitis C virus (HCV) infection, despite an incomplete mechanistic understanding of NS5B, the viral RNA-dependent RNA polymerase. Here we study the details of HCV RNA replication by determining crystal structures of stalled polymerase ternary complexes with enzymes, RNA templates, RNA primers, incoming nucleotides, and catalytic metal ions during both primed initiation and elongation of RNA synthesis. Our analysis revealed that highly conserved active-site residues in NS5B position the primer for in-line attack on the incoming nucleotide. A β loop and a C-terminal membrane-anchoring linker occlude the active-site cavity in the apo state, retract in the primed initiation assembly to enforce replication of the HCV genome from the 3' terminus, and vacate the active-site cavity during elongation. We investigated the incorporation of nucleotide analog inhibitors, including the clinically active metabolite formed by sofosbuvir, to elucidate key molecular interactions in the active site. Copyright © 2015, American Association for the Advancement of Science.

  7. The DNA Replication Stress Hypothesis of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yuri B. Yurov

    2011-01-01

    Full Text Available A well-recognized theory of Alzheimer’s disease (AD pathogenesis suggests ectopic cell cycle events to mediate neurodegeneration. Vulnerable neurons of the AD brain exhibit biomarkers of cell cycle progression and DNA replication suggesting a reentry into the cell cycle. Chromosome reduplication without proper cell cycle completion and mitotic division probably causes neuronal cell dysfunction and death. However, this theory seems to require some inputs in accordance with the generally recognized amyloid cascade theory as well as to explain causes and consequences of genomic instability (aneuploidy in the AD brain. We propose that unscheduled and incomplete DNA replication (replication stress destabilizes (epigenomic landscape in the brain and leads to DNA replication “catastrophe” causing cell death during the S phase (replicative cell death. DNA replication stress can be a key element of the pathogenetic cascade explaining the interplay between ectopic cell cycle events and genetic instabilities in the AD brain. Abnormal cell cycle reentry and somatic genome variations can be used for updating the cell cycle theory introducing replication stress as a missing link between cell genetics and neurobiology of AD.

  8. Initiation preference at a yeast origin of replication.

    Science.gov (United States)

    Brewer, B J; Fangman, W L

    1994-04-12

    Replication origins in the yeast Saccharomyces cerevisiae are identified as autonomous replication sequence (ARS) elements. To examine the effect of origin density on replication initiation, we have analyzed the replication of a plasmid that contains two copies of the same origin, ARS1. The activation of origins and the direction that replication forks move through flanking sequences can be physically determined by analyzing replication intermediates on two-dimensional agarose gels. We find that only one of the two identical ARSs on the plasmid initiates replication on any given plasmid molecule; that is, this close spacing of ARSs results in an apparent interference between the potential origins. Moreover, in the particular plasmid that we constructed, one of the two identical copies of ARS1 is used four times more frequently than the other one. These results show that the plasmid context is critical for determining the preferred origin. This origin preference is also exhibited when the tandem copies of ARS1 are introduced into a yeast chromosome. The sequences responsible for establishing the origin preference have been identified by deletion analysis and are found to reside in a portion of the yeast URA3 gene.

  9. CRISPR-mediated control of the bacterial initiation of replication.

    Science.gov (United States)

    Wiktor, Jakub; Lesterlin, Christian; Sherratt, David J; Dekker, Cees

    2016-05-05

    Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is accurately regulated by the DnaA protein, which promotes the unwinding of DNA at oriC We demonstrate that the binding of CRISPR/dCas9 to any position within origin or replication blocks the initiation of replication. Serial-dilution plating, single-cell fluorescence microscopy, and flow-cytometry experiments show that ongoing rounds of chromosome replication are finished upon CRISPR/dCas9 binding, but no new rounds are initiated. Upon arrest, cells stay metabolically active and accumulate cell mass. We find that elevating the temperature from 37 to 42°C releases the CRISR/dCas9 replication inhibition, and we use this feature to recover cells from the arrest. Our simple and robust method of controlling the bacterial cell cycle is a useful asset for synthetic biology and DNA-replication studies in particular. The inactivation of CRISPR/dCas9 binding at elevated temperatures may furthermore be of wide interest for CRISPR/Cas9 applications in genomic engineering. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. The Alleged Crisis and the Illusion of Exact Replication.

    Science.gov (United States)

    Stroebe, Wolfgang; Strack, Fritz

    2014-01-01

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

  11. DNA replication origins-where do we begin?

    Science.gov (United States)

    Prioleau, Marie-Noëlle; MacAlpine, David M

    2016-08-01

    For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages. © 2016 Prioleau and MacAlpine; Published by Cold Spring Harbor Laboratory Press.

  12. 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.

  13. Pyrimidine dimers block simian virus 40 replication forks

    International Nuclear Information System (INIS)

    Berger, C.A.; Edenberg, H.J.

    1986-01-01

    UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion? We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement

  14. DNA replication origins—where do we begin?

    Science.gov (United States)

    Prioleau, Marie-Noëlle; MacAlpine, David M.

    2016-01-01

    For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages. PMID:27542827

  15. 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...

  16. Autonomous model protocell division driven by molecular replication.

    Science.gov (United States)

    Taylor, J W; Eghtesadi, S A; Points, L J; Liu, T; Cronin, L

    2017-08-10

    The coupling of compartmentalisation with molecular replication is thought to be crucial for the emergence of the first evolvable chemical systems. Minimal artificial replicators have been designed based on molecular recognition, inspired by the template copying of DNA, but none yet have been coupled to compartmentalisation. Here, we present an oil-in-water droplet system comprising an amphiphilic imine dissolved in chloroform that catalyses its own formation by bringing together a hydrophilic and a hydrophobic precursor, which leads to repeated droplet division. We demonstrate that the presence of the amphiphilic replicator, by lowering the interfacial tension between droplets of the reaction mixture and the aqueous phase, causes them to divide. Periodic sampling by a droplet-robot demonstrates that the extent of fission is increased as the reaction progresses, producing more compartments with increased self-replication. This bridges a divide, showing how replication at the molecular level can be used to drive macroscale droplet fission.Coupling compartmentalisation and molecular replication is essential for the development of evolving chemical systems. Here the authors show an oil-in-water droplet containing a self-replicating amphiphilic imine that can undergo repeated droplet division.

  17. Cell lethality after selective irradiation of the DNA replication fork

    International Nuclear Information System (INIS)

    Hofer, K.G.; Warters, R.L.

    1985-01-01

    It has been suggested that nascent DNA located at the DNA replication fork may exhibit enhanced sensitivity to radiation damage. To evaluate this hypothesis, Chinese hamster ovary cells (CHO) were labeled with 125 I-iododeoxyuridine ( 125 IUdR) either in the presence or absence of aphidicolin. Aphidicolin (5 μg/ml) reduced cellular 125 IUdR incorporation to 3-5% of the control value. The residual 125 I incorporation appeared to be restricted to low molecular weight (sub-replicon sized) fragments of DNA which were more sensitive to micrococcal nuclease attack and less sensitive to high salt DNase I digestion than randomly labeled DNA. These findings suggest that DNA replicated in the presence of aphidicolin remains localized at the replication fork adjacent to the nuclear matrix. Based on these observations an attempt was made to compare the lethal consequences of 125 I decays at the replication fork to that of 125 I decays randomly distributed over the entire genome. Regardless of the distribution of decay events, all treatment groups exhibited identical dose-response curves (D 0 : 101 125 I decays/cell). Since differential irradiation of the replication complex did not result in enhanced cell lethality, it can be concluded that neither the nascent DNA nor the protein components (replicative enzymes, nuclear protein matrix) associated with the DNA replication site constitute key radiosensitive targets within the cellular genome. (orig.)

  18. Gene organization inside replication domains in mammalian genomes

    Science.gov (United States)

    Zaghloul, Lamia; Baker, Antoine; Audit, Benjamin; Arneodo, Alain

    2012-11-01

    We investigate the large-scale organization of human genes with respect to "master" replication origins that were previously identified as bordering nucleotide compositional skew domains. We separate genes in two categories depending on their CpG enrichment at the promoter which can be considered as a marker of germline DNA methylation. Using expression data in mouse, we confirm that CpG-rich genes are highly expressed in germline whereas CpG-poor genes are in a silent state. We further show that, whether tissue-specific or broadly expressed (housekeeping genes), the CpG-rich genes are over-represented close to the replication skew domain borders suggesting some coordination of replication and transcription. We also reveal that the transcription of the longest CpG-rich genes is co-oriented with replication fork progression so that the promoter of these transcriptionally active genes be located into the accessible open chromatin environment surrounding the master replication origins that border the replication skew domains. The observation of a similar gene organization in the mouse genome confirms the interplay of replication, transcription and chromatin structure as the cornerstone of mammalian genome architecture.

  19. Structural properties of replication origins in yeast DNA sequences

    International Nuclear Information System (INIS)

    Cao Xiaoqin; Zeng Jia; Yan Hong

    2008-01-01

    Sequence-dependent DNA flexibility is an important structural property originating from the DNA 3D structure. In this paper, we investigate the DNA flexibility of the budding yeast (S. Cerevisiae) replication origins on a genome-wide scale using flexibility parameters from two different models, the trinucleotide and the tetranucleotide models. Based on analyzing average flexibility profiles of 270 replication origins, we find that yeast replication origins are significantly rigid compared with their surrounding genomic regions. To further understand the highly distinctive property of replication origins, we compare the flexibility patterns between yeast replication origins and promoters, and find that they both contain significantly rigid DNAs. Our results suggest that DNA flexibility is an important factor that helps proteins recognize and bind the target sites in order to initiate DNA replication. Inspired by the role of the rigid region in promoters, we speculate that the rigid replication origins may facilitate binding of proteins, including the origin recognition complex (ORC), Cdc6, Cdt1 and the MCM2-7 complex

  20. DNA replication stress restricts ribosomal DNA copy number

    Science.gov (United States)

    Salim, Devika; Bradford, William D.; Freeland, Amy; Cady, Gillian; Wang, Jianmin

    2017-01-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number. PMID:28915237

  1. DNA replication stress restricts ribosomal DNA copy number.

    Science.gov (United States)

    Salim, Devika; Bradford, William D; Freeland, Amy; Cady, Gillian; Wang, Jianmin; Pruitt, Steven C; Gerton, Jennifer L

    2017-09-01

    Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  2. DNA replication stress restricts ribosomal DNA copy number.

    Directory of Open Access Journals (Sweden)

    Devika Salim

    2017-09-01

    Full Text Available Ribosomal RNAs (rRNAs in budding yeast are encoded by ~100-200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how "normal" copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a "normal" rDNA copy number.

  3. Initiation at closely spaced replication origins in a yeast chromosome.

    Science.gov (United States)

    Brewer, B J; Fangman, W L

    1993-12-10

    Replication of eukaryotic chromosomes involves initiation at origins spaced an average of 50 to 100 kilobase pairs. In yeast, potential origins can be recognized as autonomous replication sequences (ARSs) that allow maintenance of plasmids. However, there are more ARS elements than active chromosomal origins. The possibility was examined that close spacing of ARSs can lead to inactive origins. Two ARSs located 6.5 kilobase pairs apart can indeed interfere with each other. Replication is initiated from one or the other ARS with equal probability, but rarely (< 5%) from both ARSs on the same DNA molecule.

  4. The Replication Mechanism in a Romanian ERP System Environment

    Directory of Open Access Journals (Sweden)

    Iuliana SCORTA

    2008-01-01

    Full Text Available Modern Relational Database Management Systems have Replication technology. Large enterprises are often spread around the country, and although WANs can be very fast and reliable these days, it is often better for each location to have a local copy of data rather than have a single database at a central location. This usually means that replication is a requirement in order for each location to have the most up-to-date data. This paper reveals a replication mechanism implemented in a Romanian ERP system environment.

  5. Evolution of complexity in RNA-like replicator systems

    Directory of Open Access Journals (Sweden)

    Hogeweg Paulien

    2008-03-01

    Full Text Available Abstract Background The evolution of complexity is among the most important questions in biology. The evolution of complexity is often observed as the increase of genetic information or that of the organizational complexity of a system. It is well recognized that the formation of biological organization – be it of molecules or ecosystems – is ultimately instructed by the genetic information, whereas it is also true that the genetic information is functional only in the context of the organization. Therefore, to obtain a more complete picture of the evolution of complexity, we must study the evolution of both information and organization. Results Here we investigate the evolution of complexity in a simulated RNA-like replicator system. The simplicity of the system allows us to explicitly model the genotype-phenotype-interaction mapping of individual replicators, whereby we avoid preconceiving the functionality of genotypes (information or the ecological organization of replicators in the model. In particular, the model assumes that interactions among replicators – to replicate or to be replicated – depend on their secondary structures and base-pair matching. The results showed that a population of replicators, originally consisting of one genotype, evolves to form a complex ecosystem of up to four species. During this diversification, the species evolve through acquiring unique genotypes with distinct ecological functionality. The analysis of this diversification reveals that parasitic replicators, which have been thought to destabilize the replicator's diversity, actually promote the evolution of diversity through generating a novel "niche" for catalytic replicators. This also makes the current replicator system extremely stable upon the evolution of parasites. The results also show that the stability of the system crucially depends on the spatial pattern formation of replicators. Finally, the evolutionary dynamics is shown to

  6. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

    Directory of Open Access Journals (Sweden)

    Olivier Reynard

    2015-12-01

    Full Text Available The current outbreak of Ebola virus (EBOV in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

  7. Culture in the cockpit: do Hofstede's dimensions replicate?

    Science.gov (United States)

    Merritt, A.; Helmreich, R. L. (Principal Investigator)

    2000-01-01

    Survey data collected from 9,400 male commercial airline pilots in 19 countries were used in a replication study of Hofstede's indexes of national culture. The analysis that removed the constraint of item equivalence proved superior, both conceptually and empirically, to the analysis using Hofstede's items and formulae as prescribed, and rendered significant replication correlations for all indexes (Individualism-Collectivism .96, Power Distance .87, Masculinity-Femininity .75, and Uncertainty Avoidance .68). The successful replication confirms that national culture exerts an influence on cockpit behavior over and above the professional culture of pilots, and that "one size fits all" training is inappropriate.

  8. Muhasebe Meslek Mensuplarında Tükenmişlik Sendromu Üzerine Bir Araştırma

    OpenAIRE

    DOĞAN, Prof. Dr. Zeki; NAZLIOĞLU, Elif Hilal

    2010-01-01

    Bu çalışmanın amacı, muhasebe meslek mensuplarının tükenmişlik sendromu yaşayıp-yaşamadıklarını incelemek ve eğer yaşıyorlarsa bunun boyutunu araştırmaktır. Bunun için Kayseri ilinde faaliyet gösteren muhasebe meslek mensuplarının tükenmişlik düzeylerinin ölçümüne ve tükenmişliğin alt boyutlarında nedensellik ilişkilerinin yönünün tespitine ilişkin bir anket çalışması yapılmıştır. Elde edilen verilerden hareketle ilk olarak Maslach Tükenmişlik Ölçeği hesaplanmış ve daha sonra nedensellik test...

  9. Sosyal Ağlar ve E-Paylaşım: Kalitatif Bir Analiz / Social Media and Word of Mouse: A Qualitative Research

    OpenAIRE

    OZTURK, Eda

    2018-01-01

    Ağızdan ağıza reklam en eski reklam türlerinden biridir. Son yıllardaki hızlı gelişiminin altında yatan güç ise internetin yükselişi olmuştur. İnternet ağızdan ağıza reklam için yeni kanallar yaratmıştır. Sosyal Paylaşım siteleri bu yeni kanallar içerisinde en önde gelenlerden birini oluşturmaktadır. Tüm bu gelişmelere rağmen internette ağızdan ağıza reklam halen yeni bir olgudur ve alanda konuya dair sınırlı sayıda çalışma bulunmaktadır. Bu nedenle bu çalışmada önce uygulamanın gelişimine ye...

  10. Wushenziye Formula Improves Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus via PTP1B-IRS1-Akt-GLUT4 Signaling Pathway.

    Science.gov (United States)

    Tian, Chunyu; Chang, Hong; La, Xiaojin; Li, Ji-An

    2017-01-01

    Background. Wushenziye formula (WSZYF) is an effective traditional Chinese medicine in the treatment of type 2 diabetes mellitus (T2DM). Aim. This study aimed to identify the effects and underlying mechanisms of WSZYF on improving skeletal muscle insulin resistance in T2DM. Methods. An animal model of T2DM was induced by Goto-Kakizaki diabetes prone rats fed with high fat and sugar for 4 weeks. Insulin resistance model was induced in skeletal muscle cell. Results. In vivo , WSZYF improved general conditions and decreased significantly fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, insulin concentration, and insulin resistance index of T2DM rats. In vitro , WSZYF enhanced glucose consumption in insulin resistance model of skeletal muscle cell. Furthermore, WSZYF affected the expressions of molecules in regulating T2DM, including increasing the expressions of p-IRS1, p-Akt, and GLUT4, reducing PTP1B expression. Conclusion . These findings displayed the potential of WSZYF as a new drug candidate in the treatment of T2DM and the antidiabetic mechanism of WSZYF is probably mediated through modulating the PTP1B-IRS1-Akt-GLUT4 signaling pathway.

  11. Wushenziye Formula Improves Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus via PTP1B-IRS1-Akt-GLUT4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chunyu Tian

    2017-01-01

    Full Text Available Background. Wushenziye formula (WSZYF is an effective traditional Chinese medicine in the treatment of type 2 diabetes mellitus (T2DM. Aim. This study aimed to identify the effects and underlying mechanisms of WSZYF on improving skeletal muscle insulin resistance in T2DM. Methods. An animal model of T2DM was induced by Goto-Kakizaki diabetes prone rats fed with high fat and sugar for 4 weeks. Insulin resistance model was induced in skeletal muscle cell. Results. In vivo, WSZYF improved general conditions and decreased significantly fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, insulin concentration, and insulin resistance index of T2DM rats. In vitro, WSZYF enhanced glucose consumption in insulin resistance model of skeletal muscle cell. Furthermore, WSZYF affected the expressions of molecules in regulating T2DM, including increasing the expressions of p-IRS1, p-Akt, and GLUT4, reducing PTP1B expression. Conclusion. These findings displayed the potential of WSZYF as a new drug candidate in the treatment of T2DM and the antidiabetic mechanism of WSZYF is probably mediated through modulating the PTP1B-IRS1-Akt-GLUT4 signaling pathway.

  12. Çocuk Kitaplarına Yeni Bir Yaklaşım: İnternet'te Resimli Çocuk Kitapları (e-books

    Directory of Open Access Journals (Sweden)

    Mübeccel Gönen

    2002-06-01

    Full Text Available Elektronik kitaplar (e-books yurtdışında oldukça yaygın bir biçimde kullanılmakta ve kullanıcı sayısı da giderek artmaktadır. İnternette yer alan bu kitaplar, her yaştaki insanın ilgi alanına hizmet edecek kadar çok ve çeşitlidir. Bu tür kitaplara internette yer alan kütüphanelerden, yayınevlerinden ve yazarlardan ulaşılmaktadır. Çocuk edebiyatı ile ilgili sitelerden de her konuda resimli çocuk kitaplarına ulaşılabilir. İnternette Türkçe resimli çocuk kitapları ve çocuk edebiyatı ile ilgili sitelere rastlanmamaktadır. Ancak elektronik çocuk kitaplarına yabancı sitelerden ulaşılabilir ve bazı sitelerden ücretsiz olarak da temin edilebilir. Bu yeni uygulama ile ülkemizde bulunan yayınevleri ve yazarların, iletişim ve bilgi teknolojisinden yararlanarak daha fazla aileye, okul ve çocuğa hizmet götürebileceği düşünülmektedir.

  13. Post-modernizm Gelişmek İçin Bir Adım mıdır?

    OpenAIRE

    Cirhinlioğlu, Zafer

    2003-01-01

    Günümüzde dünyanın ikiye bölündüğü yaygın kabul görmektedir; gelişmiş ve gelişmemiş, ülkeler. Gelişmemiş ülkeler sadece bir seçenekle karşı karşıyadırlar artık; gelişmek ya da modernleşmek. Bu dönemde, Batı uygarlığı bazı temel değerlere/kavramlara işaret etmektedir; kapitalizm, bireyselcilik, laiklik, insan hakları, tüketim ve bunlardan önemlisi, rasyonalite. Fakat, Batıdaki aydınlar, Batının, rasyonalite ve özellikle pozitif metodolojinin ilkelerine dayanarak kazandığı, göreli imtiyazları v...

  14. Sabit Odaklı Silindirik Parabolik Bir Yoğunlaştırıcıda Kızgın Su Elde Edilmesi

    OpenAIRE

    Halıcı, Fethi

    2018-01-01

    Bu çalışn1ada, odağı sabit yansıtıcısı ha reketli olarak imal edilen silindirik parabolik yoğunlaştırıcıda (SPY) kızgın su ve sıcak su için yapılan deney sonuçları ve pe rfoımans değerleri verilmiştir. (SPY) 'nın yansıtıcı yüzeyi 2ınx3 m boyutlarında olup toplam açıklık alanı 6 ın2 dir. Odaktaki yut ucu yüzey yan yana yerleştirilen 2 kanatlı borudan imal edilmiştir. Odak uzaklığı 6 m olan (SPY) kuzey güney doğrultusu nda yerleştirilerek özel yapılan bir ınekanizma ile güneşi doğu batı do...

  15. Türkiye’de Eğitim Ekonomik Büyümeyi Etkiliyor mu? Nedensellik Analizleriyle Bir İnceleme

    Directory of Open Access Journals (Sweden)

    Süleyman Yurtkuran

    2015-12-01

    Full Text Available         ÖzBu çalışmada ekonomik büyüme ve eğitim arasındaki ilişkiler Standart Granger nedensellik, Hsiao’nun Granger nedensellik ve Dolado-Lütkepohl VAR nedensellik yöntemleriyle 1950-2012 dönemi Türkiye ekonomisi için ampirik yönden incelenmiştir. Ekonometrik analizler, ekonomik büyümeden yükseköğretim mezunu sayısına; meslek lisesi ve genel lise mezun sayısından ekonomik büyümeye doğru pozitif bir nedenselliğin olduğunu göstermektedir.Anahtar Kelimeler: Türkiye, Büyüme, Eğitim, Nedensellik, VARJEL Sınıflandırma Kodları: C22, I21, O11, I25  

  16. Iznīqī and Jābir, Sirr and Miftāḥ: Two Authors, Four Titles, One Alchemical Treatise

    Directory of Open Access Journals (Sweden)

    Paola Carusi

    2017-03-01

    Full Text Available An alchemical Arabic treatise alternatively entitled Miftāḥ al-ḥikma, Miftāḥ jannāt al-khuld, Sirr al-asrār and Sirr al-sārr wa-sirr al-asrār is attributed in its manuscripts to two different authors: al-Iznīqī and Jābir b. Ḥayyān. In this article I briefly discuss some characteristic aspects of the treatise and its significance for the history of alchemy. These aspects include its ancient and important sources, such as the Muṣḥaf al-jamā‛a (Turba philosophorum and the Kitāb al-Ḥabīb, and its connection with the tradition of the artists and the activity of the workshop and laboratory, which first comes to the fore in Greek alchemy and later in Islamic alchemy. Furthermore, the work includes references to alchemical physical theories in which the influence of Islamic theology may perhaps be traced. This article, which summarises the results of investigations carried out over the last few years, could be considered as a kind of introduction to the edition and translation of the text currently in progress.

  17. Evlilik İçi Zorla Cinsel İlişki Üzerine Bir Anket Çalışması

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Yavuz

    1998-08-01

    Full Text Available Bu çalışmada, 170’i hukuk mezunu, 480’i toplumun çeşitli kesimlerinden olmak üzere toplam 650 kişinin evlilikiçi zorla cinsel ilişki konusundaki görüşlerini belirleyen anket formlarının sonuçları değerlendirilmiştir. Çalışmaya katılanların % 65’inin, hukukçuların % 45’inin ve toplumdan katılanların % 71’inin kocanın karısıyla zorla cinsel ilişkide bulunmasının bir ırza geçme suçu oluşturacağına inandıkları görülmektedir.Çalışmaya katılanların yarıdan fazlasının bu görüşte olması evlilikiçi zorla cinsel ilişkinin ırza geçme suçu olarak düzenlenmesi yolundaki tartışmalara basamak oluşturmaktadır. Anahtar kelimeler: Evlilik, Irza geçme.

  18. İşbirliği İle Bireyselleştirilmiş Eğitim Programı Geliştirme Süreci: Durum Çalışması

    Directory of Open Access Journals (Sweden)

    Sezgin Vuran

    2017-07-01

    Full Text Available Bu çalışmanın amacı Zihin Engelliler Öğretmenliği Programı öğretmen adaylarının Bireyselleştirilmiş Eğitim Programlarının Hazırlanması ve Öğretimin Bireyselleştirilmesi dersinde, işbirliği ile Bireyselleştirilmiş Eğitim Programları (BEP geliştirmeleri ve bir ekiple birlikte çalışma becerilerini kazanmaları sürecinin ve sonuçlarının betimlenmesidir. Çalışma nitel araştırma yöntemi olan durum çalışması olarak yürütülmüştür. Çalışmaya toplam 100 öğretmen adayı ve üç öğretim elemanı katılmıştır. Çalışmada veriler; katılımcı gözlem, saha notları, öğretmen adayı ödevleri, öğretmen adayı günlükleri ve öğretim elemanı görüşleri kullanılarak toplanmıştır. Toplanan veriler içerik analizi yapılarak analiz edilmiştir. Çalışmada uygulama sürecinde işbirliği ile öğretim ve öğrenme yaklaşımları benimsenmiştir. İşbirliği ile öğrenme yolu ile ekip üyelerinin BEP hazırlama becerilerin gelişmesinin yanı sıra BEP’in önemli gerekliliklerinden biri olan ekiple çalışma becerileri de gelişmiştir. Ayrıca dersin işbirliği ile öğretim yolu ile yürütülmesi öğretmen adaylarına işbirliği ile çalışmaya iyi bir model oluşturmuştur. Bu çalışma sonucunda öğretmen adayları hem bireysel hem grup olarak BEP hazırlama aşamalarını izleyerek özel gereksinimi olan bir öğrencinin gereksinimlerine uygun bir BEP hazırlamışlar ve öğretim uyarlamaları yapmışlardır. Ek olarak, işbirliği ile BEP hazırlama sürecinde öğretmen adaylarının birbirleriyle etkili bir iletişim kurdukları ve oldukça hevesli şekilde derse katıldıkları gözlenmiştir. Bu çalışmanın bulguları öğretmen adaylarının ileride yaşayabilecekleri zorluklarla baş etmeleri ve sürece hazırlanmaları için öğretmenlere yardımcı olacaktır. The purpose of this study is to reveal the process and the results of the development of an

  19. A Fuzzy Modeling Approach for Replicated Response Measures Based on Fuzzification of Replications with Descriptive Statistics and Golden Ratio

    Directory of Open Access Journals (Sweden)

    Özlem TÜRKŞEN

    2018-03-01

    Full Text Available Some of the experimental designs can be composed of replicated response measures in which the replications cannot be identified exactly and may have uncertainty different than randomness. Then, the classical regression analysis may not be proper to model the designed data because of the violation of probabilistic modeling assumptions. In this case, fuzzy regression analysis can be used as a modeling tool. In this study, the replicated response values are newly formed to fuzzy numbers by using descriptive statistics of replications and golden ratio. The main aim of the study is obtaining the most suitable fuzzy model for replicated response measures through fuzzification of the replicated values by taking into account the data structure of the replications in statistical framework. Here, the response and unknown model coefficients are considered as triangular type-1 fuzzy numbers (TT1FNs whereas the inputs are crisp. Predicted fuzzy models are obtained according to the proposed fuzzification rules by using Fuzzy Least Squares (FLS approach. The performances of the predicted fuzzy models are compared by using Root Mean Squared Error (RMSE criteria. A data set from the literature, called wheel cover component data set, is used to illustrate the performance of the proposed approach and the obtained results are discussed. The calculation results show that the combined formulation of the descriptive statistics and the golden ratio is the most preferable fuzzification rule according to the well-known decision making method, called TOPSIS, for the data set.

  20. İskenderun Mezar Taşı Sözleri Üzerine Bir İnceleme A Research on İskenderun Gravestone Words

    Directory of Open Access Journals (Sweden)

    Hüseyin Kürşat TÜRKAN

    2012-12-01

    şına dikilen mezar taşlarının her biri ayrı anlam ifade etmektedir. Hemen hemen her kültürde görülen mezar taşları, ait olduğu kültürün öz değerlerine göre şekil alırlar. Bu şekillenme ölen kişinin inanışına, geleneklerine, sosyal ve ekonomik durumuna göre değişiklik gösterir. Ele alınan bu makalede Hatay’ın İskenderun ilçesinde yer alan mezar taşı sözleri üzerinde inceleme yapılarak bu sözlerin kültürel değerleri ortaya konulmaya çalışılmıştır. Sosyokültürel yaşamda toplum içindeki bireyler için kaçınılmaz bir sondur ölüm. Doğumla başlayan sürecin en son noktasıdır. Çoğu zaman üzerinde derinlemesine konuşulmaktan kaçınılan ölüm, kimi toplumlar için bir sonun başlangıcıyken kimi zaman da bir başlangıcın sonudur. İnsan hayatını böylesine derinlemesine etkileyen ölüm mefhumunda birçok ulusta olduğu gibi İslamiyeti benimseyen Türk milletinde de çeşitli ritüeller vardır. Bunların en başında şüphesiz ki ölene duyulan saygıdan dolayı ve ölünün yerinin kaybolmaması için mezarın başına dikilen taşlar gelir. Bu taşların üzerinde yer alan figür, resim ve yazıların Türk kültürünün ifadesi bakımından önemli bir yere sahip olduğu şüphesizdir.Mezar taşları tarihli olmaları ile etnografik ve sanat eserleri için birer belge hüviyeti taşırlar. Ayrıca yazılı mezar taşları Türk’ün bu topraklarda yaşadığına, varlığını ebedileştirdiğine en canlı birer şahit ve aynı zaman da estetik ve etnografik kıymetli haiz vesikalardır. Bu itibarla şehir, kaza ve köy tarihleri hazırlanırken mezar taşları önemlidir. Kısaca, mezar taşları yapıldıkları çevrenin ve devrin inançlarının, adetlerin, sanat geleneklerinin tabiî, iktisadi ve sosyal şartlarının ortak ürünüdür. Bu bakımdan sanat tarihimiz için olduğu kadar, kültür tarihimiz yönünden de büyük önem taşımaktadır (http://www.mezartaslari.com.

  1. Replication stress activates DNA repair synthesis in mitosis

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Ying, Songmin; Bjerregaard, Victoria A

    2015-01-01

    Oncogene-induced DNA replication stress has been implicated as a driver of tumorigenesis. Many chromosomal rearrangements characteristic of human cancers originate from specific regions of the genome called common fragile sites (CFSs). CFSs are difficult-to-replicate loci that manifest as gaps...... into mitotic prophase triggers the recruitment of MUS81 to CFSs. The nuclease activity of MUS81 then promotes POLD3-dependent DNA synthesis at CFSs, which serves to minimize chromosome mis-segregation and non-disjunction. We propose that the attempted condensation of incompletely duplicated loci in early...... mitosis serves as the trigger for completion of DNA replication at CFS loci in human cells. Given that this POLD3-dependent mitotic DNA synthesis is enhanced in aneuploid cancer cells that exhibit intrinsically high levels of chromosomal instability (CIN(+)) and replicative stress, we suggest...

  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. Replicate periodic windows in the parameter space of driven oscillators

    Energy Technology Data Exchange (ETDEWEB)

    Medeiros, E.S., E-mail: esm@if.usp.br [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil); Souza, S.L.T. de [Universidade Federal de Sao Joao del-Rei, Campus Alto Paraopeba, Minas Gerais (Brazil); Medrano-T, R.O. [Departamento de Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Diadema, Sao Paulo (Brazil); Caldas, I.L. [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil)

    2011-11-15

    Highlights: > We apply a weak harmonic perturbation to control chaos in two driven oscillators. > We find replicate periodic windows in the driven oscillator parameter space. > We find that the periodic window replication is associated with the chaos control. - Abstract: In the bi-dimensional parameter space of driven oscillators, shrimp-shaped periodic windows are immersed in chaotic regions. For two of these oscillators, namely, Duffing and Josephson junction, we show that a weak harmonic perturbation replicates these periodic windows giving rise to parameter regions correspondent to periodic orbits. The new windows are composed of parameters whose periodic orbits have the same periodicity and pattern of stable and unstable periodic orbits already existent for the unperturbed oscillator. Moreover, these unstable periodic orbits are embedded in chaotic attractors in phase space regions where the new stable orbits are identified. Thus, the observed periodic window replication is an effective oscillator control process, once chaotic orbits are replaced by regular ones.

  4. Function of BRCA1 at a DNA Replication Origin

    National Research Council Canada - National Science Library

    Lieberman, Paul

    2004-01-01

    ... and allow efficient repair of damaged DNA. In this proposal, we present preliminary data that BRCA1 functions in a DNA checkpoint response for the origin of Epstein-Barr Virus DNA replication (Ori P...

  5. Replication stress, a source of epigenetic aberrations in cancer?

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    . Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine 9 mono......-methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor-promoting insults is recognized as a significant source...... of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis....

  6. Mechanism of Archaeal MCM Helicase Recruitment to DNA Replication Origins

    Science.gov (United States)

    Samson, Rachel Y.; Abeyrathne, Priyanka D.; Bell, Stephen D.

    2015-01-01

    Summary Cellular DNA replication origins direct the recruitment of replicative helicases via the action of initiator proteins belonging to the AAA+ superfamily of ATPases. Archaea have a simplified subset of the eukaryotic DNA replication machinery proteins and possess initiators that appear ancestral to both eukaryotic Orc1 and Cdc6. We have reconstituted origin-dependent recruitment of the homohexameric archaeal MCM in vitro with purified recombinant proteins. Using this system, we reveal that archaeal Orc1-1 fulfills both Orc1 and Cdc6 functions by binding to a replication origin and directly recruiting MCM helicase. We identify the interaction interface between these proteins and reveal how ATP binding by Orc1-1 modulates recruitment of MCM. Additionally, we provide evidence that an open-ring form of the archaeal MCM homohexamer is loaded at origins. PMID:26725007

  7. EPA Lean Government Initiative: How to Replicate Lean Successes

    Science.gov (United States)

    This Lean Replication Primer describes how EPA Offices and Regions can identify and adapt successful practices from previous Lean projects to “replicate” their successes and generate further improvements.

  8. Symmetry of interactions rules in incompletely connected random replicator ecosystems.

    Science.gov (United States)

    Kärenlampi, Petri P

    2014-06-01

    The evolution of an incompletely connected system of species with speciation and extinction is investigated in terms of random replicators. It is found that evolving random replicator systems with speciation do become large and complex, depending on speciation parameters. Antisymmetric interactions result in large systems, whereas systems with symmetric interactions remain small. A co-dominating feature is within-species interaction pressure: large within-species interaction increases species diversity. Average fitness evolves in all systems, however symmetry and connectivity evolve in small systems only. Newcomers get extinct almost immediately in symmetric systems. The distribution in species lifetimes is determined for antisymmetric systems. The replicator systems investigated do not show any sign of self-organized criticality. The generalized Lotka-Volterra system is shown to be a tedious way of implementing the replicator system.

  9. A Transactional Asynchronous Replication Scheme for Mobile Database Systems

    Institute of Scientific and Technical Information of China (English)

    丁治明; 孟小峰; 王珊

    2002-01-01

    In mobile database systems, mobility of users has a significant impact on data replication. As a result, the various replica control protocols that exist today in traditional distributed and multidatabase environments are no longer suitable. To solve this problem, a new mobile database replication scheme, the Transaction-Level Result-Set Propagation (TLRSP)model, is put forward in this paper. The conflict detection and resolution strategy based on TLRSP is discussed in detail, and the implementation algorithm is proposed. In order to compare the performance of the TLRSP model with that of other mobile replication schemes, we have developed a detailed simulation model. Experimental results show that the TLRSP model provides an efficient support for replicated mobile database systems by reducing reprocessing overhead and maintaining database consistency.

  10. Genetic Analysis of a Mammalian Chromosomal Origin of Replication

    National Research Council Canada - National Science Library

    Altman, Amy

    2001-01-01

    The main goal of the research proposal was to develop an assay system for studying the specific genetic elements, if any, involved in the initiation of DNA replication in mammalian cells as outlined in Task 1...

  11. Framework Model for Database Replication within the Availability Zones

    OpenAIRE

    Al-Mughrabi, Ala'a Atallah; Owaied, Hussein

    2013-01-01

    This paper presents a proposed model for database replication model in private cloud availability regions, which is an enhancement of the SQL Server AlwaysOn Layers of Protection Model presents by Microsoft in 2012. The enhancement concentrates in the database replication for private cloud availability regions through the use of primary and secondary servers. The processes of proposed model during the client send Write/Read Request to the server, in synchronous and semi synchronous replicatio...

  12. Yeast replicative aging: a paradigm for defining conserved longevity interventions

    OpenAIRE

    Wasko, Brian M.; Kaeberlein, Matt

    2013-01-01

    The finite replicative life span of budding yeast mother cells was demonstrated as early as 1959, but the idea that budding yeast could be used to model aging of multicellular eukaryotes did not enter the scientific mainstream until relatively recently. Despite continued skepticism by some, there are now abundant data that several interventions capable of extending yeast replicative life span have a similar effect in multicellular eukaryotes including nematode worms, fruit flies, and rodents....

  13. Structural aspects of DNA in its replication and repair

    International Nuclear Information System (INIS)

    Mitra, S.; Pal, B.C.; Foote, R.S.; Bates, R.C.; Bhattacharyya, A.; Snow, E.T.; Wobbe, C.R.; Morse, C.C.; Snyder, C.E.

    1984-01-01

    The research objective of this laboratory is to investigate the structure of DNA, the mechanism of DNA replication and its regulation, and the mechanism and role of repair of the altered DNA in the expression of heritable changes. This research has two broad aims, namely investigation of (a) the regulation of DNA replication in mammals, using parvovirus DNA as a model system and (b) the role of DNA repair in mutagenesis and carcinogenesis induced by simple alkylating mutagens

  14. Insights into the Initiation of Eukaryotic DNA Replication.

    Science.gov (United States)

    Bruck, Irina; Perez-Arnaiz, Patricia; Colbert, Max K; Kaplan, Daniel L

    2015-01-01

    The initiation of DNA replication is a highly regulated event in eukaryotic cells to ensure that the entire genome is copied once and only once during S phase. The primary target of cellular regulation of eukaryotic DNA replication initiation is the assembly and activation of the replication fork helicase, the 11-subunit assembly that unwinds DNA at a replication fork. The replication fork helicase, called CMG for Cdc45-Mcm2-7, and GINS, assembles in S phase from the constituent Cdc45, Mcm2-7, and GINS proteins. The assembly and activation of the CMG replication fork helicase during S phase is governed by 2 S-phase specific kinases, CDK and DDK. CDK stimulates the interaction between Sld2, Sld3, and Dpb11, 3 initiation factors that are each required for the initiation of DNA replication. DDK, on the other hand, phosphorylates the Mcm2, Mcm4, and Mcm6 subunits of the Mcm2-7 complex. Sld3 recruits Cdc45 to Mcm2-7 in a manner that depends on DDK, and recent work suggests that Sld3 binds directly to Mcm2-7 and also to single-stranded DNA. Furthermore, recent work demonstrates that Sld3 and its human homolog Treslin substantially stimulate DDK phosphorylation of Mcm2. These data suggest that the initiation factor Sld3/Treslin coordinates the assembly and activation of the eukaryotic replication fork helicase by recruiting Cdc45 to Mcm2-7, stimulating DDK phosphorylation of Mcm2, and binding directly to single-stranded DNA as the origin is melted.

  15. 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....

  16. Replicability and Generalizability of Posttraumatic Stress Disorder (PTSD) Networks

    DEFF Research Database (Denmark)

    Fried, Eiko I.; Eidhof, Marloes B.; Palic, Sabina

    2018-01-01

    . This renders network structures in clinical data, and the extent to which networks replicate across data sets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four data sets of traumatized patients...... discuss the importance of future replicability efforts to improve clinical psychological science and provide code, model output, and correlation matrices to make the results of this article fully reproducible....

  17. Cyclophilin B facilitates the replication of Orf virus.

    Science.gov (United States)

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

    2017-06-15

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

  18. Cyclophilin B facilitates the replication of Orf virus

    OpenAIRE

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

    2017-01-01

    Background Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the f...

  19. Multiprocessor Real-Time Locking Protocols for Replicated Resources

    Science.gov (United States)

    2016-07-01

    assignment problem, the ac- tual identities of the allocated replicas must be known. When locking protocols are used, tasks may experience delays due to both...Multiprocessor Real-Time Locking Protocols for Replicated Resources ∗ Catherine E. Jarrett1, Kecheng Yang1, Ming Yang1, Pontus Ekberg2, and James H...replicas to execute. In prior work on replicated resources, k-exclusion locks have been used, but this restricts tasks to lock only one replica at a time. To

  20. The Hsk1(Cdc7) Replication Kinase Regulates Origin Efficiency

    OpenAIRE

    Patel, Prasanta K.; Kommajosyula, Naveen; Rosebrock, Adam; Bensimon, Aaron; Leatherwood, Janet; Bechhoefer, John; Rhind, Nicholas

    2008-01-01

    Origins of DNA replication are generally inefficient, with most firing in fewer than half of cell cycles. However, neither the mechanism nor the importance of the regulation of origin efficiency is clear. In fission yeast, origin firing is stochastic, leading us to hypothesize that origin inefficiency and stochasticity are the result of a diffusible, rate-limiting activator. We show that the Hsk1-Dfp1 replication kinase (the fission yeast Cdc7-Dbf4 homologue) plays such a role. Increasing or ...

  1. X-ray repair replication in L1210 leukemia cells

    International Nuclear Information System (INIS)

    Lee, Y.C.; Byfield, J.E.; Bennett, L.R.; Chan, P.Y.M.

    1974-01-01

    Repair replication has been studied in detail in mouse L1210 leukemia cells. A method of identifying and quantitating repair replication using a pre- and postradiation block of normal replication with cytosine arabinoside is illustrated. The method derived does not require isolation of DNA per se and appears to be satisfactory for screening for inhibitors of repair replication. Repair replication can be demonstrated at doses in the 1000-rad range in bromouridine deoxyriboside-substituted cells and at slightly higher doses in nonsubstituted cells. Drugs that are known to bind to DNA inhibit this x-ray-induced repair replication. Drugs with these properties may be identified by the methods described and compared quantitatively in their ability to inhibit this type of x-ray damage. Since these phenomena can be demonstrated for low radiation doses and at drug concentrations attainable in vivo during human cancer chemotherapy this class of anticancer agent may be worthy of closer study. Application to the L1210 leukemia system should permit comparison of in vitro and in vivo drug effects in the context of the extensive in vivo pharmacological data already available for L1210 cells. (U.S.)

  2. 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.)

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

    Science.gov (United States)

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

    2013-12-01

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

  4. Diverse Effects of Cyclosporine on Hepatitis C Virus Strain Replication

    Science.gov (United States)

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

    2006-01-01

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

  5. Late replication domains are evolutionary conserved in the Drosophila genome.

    Science.gov (United States)

    Andreyenkova, Natalya G; Kolesnikova, Tatyana D; Makunin, Igor V; Pokholkova, Galina V; Boldyreva, Lidiya V; Zykova, Tatyana Yu; Zhimulev, Igor F; Belyaeva, Elena S

    2013-01-01

    Drosophila chromosomes are organized into distinct domains differing in their predominant chromatin composition, replication timing and evolutionary conservation. We show on a genome-wide level that genes whose order has remained unaltered across 9 Drosophila species display late replication timing and frequently map to the regions of repressive chromatin. This observation is consistent with the existence of extensive domains of repressive chromatin that replicate extremely late and have conserved gene order in the Drosophila genome. We suggest that such repressive chromatin domains correspond to a handful of regions that complete replication at the very end of S phase. We further demonstrate that the order of genes in these regions is rarely altered in evolution. Substantial proportion of such regions significantly coincide with large synteny blocks. This indicates that there are evolutionary mechanisms maintaining the integrity of these late-replicating chromatin domains. The synteny blocks corresponding to the extremely late-replicating regions in the D. melanogaster genome consistently display two-fold lower gene density across different Drosophila species.

  6. DNA is a co-factor for its own replication in Xenopus egg extracts

    NARCIS (Netherlands)

    Lebofsky, Ronald; van Oijen, Antoine M.; Walter, Johannes C.

    Soluble Xenopus egg extracts efficiently replicate added plasmids using a physiological mechanism, and thus represent a powerful system to understand vertebrate DNA replication. Surprisingly, DNA replication in this system is highly sensitive to plasmid concentration, being undetectable below

  7. Spinoza’da İnsan Doğası-Siyaset İlişkisi Üzerine Bir Deneme

    Directory of Open Access Journals (Sweden)

    Mustafa Yıldız

    2012-09-01

    Full Text Available ÖzetBu makalenin başlıca amacı, siyaset ile insan doğası arasındaki ilişkiye dikkat çekmektir. Bu konu ile ilgili görüşlerini incelediğimiz Spinoza, insan doğasına en uygun yönetim biçiminin demokrasi olduğunu ileri sürdüğü gibi bunun ontolojik ve epistemolojik temellerini de ortaya koyar. Ontolojik temelde insan, doğanın bir parçası olduğu ölçüde kendi doğasından kaynaklanan her şeyi yapmaya hakkı vardır. Epistemolojik temelde ise insan, doğanın bilgisine sahip olduğu ölçüde var olan doğasını ikinci bir doğaya ulaştıracak siyasal bir örgütlenmeye ihtiyaç duyar. Sonuç olarak Spinoza siyaseti olabildiğince nesnel bir zeminde ele almaya çalışarak evrensel bir siyaset kuramı geliştirir. Siyasal alanda aşılması gereken yol, anlama yetisinin yetkinleşmesiyle hem bireysel hem de toplumsal düzlemde insan doğasının ikinci bir doğaya ulaşmasıdır. AbstractThe main purpose of this article is to point to the relationship between politics and human nature. In this regard, as Spinoza pronounces the most appropriate regime to the human nature as democracy, he presents ontological and epistemological basics of this. Human beings, in the ontological basis, are allowed to do anything they desire in the nature as long as they stay a part of the nature. As to in the epistemological basis, human beings are in need of a political organization that will convey its nature to the second nature, to a degree where they possess an acknowledge of the nature. To sum up, Spinoza tries to exhibit a universal ethical and political theory by taking human nature on the objective ground. The way that must be overcome in the political structure is the attainment of the human nature to a second nature where both individual and societal level by maturation of the understanding.RésuméLe but principal de cet article est d’attirer l’attention sur la relation entre la politique et la nature de l’homme. A cet

  8. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody.

    Directory of Open Access Journals (Sweden)

    Frank Sainsbury

    2010-11-01

    Full Text Available The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product.To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER. Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO cell-produced 2G12.Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for

  9. pUL34 binding near the human cytomegalovirus origin of lytic replication enhances DNA replication and viral growth.

    Science.gov (United States)

    Slayton, Mark; Hossain, Tanvir; Biegalke, Bonita J

    2018-05-01

    The human cytomegalovirus (HCMV) UL34 gene encodes sequence-specific DNA-binding proteins (pUL34) which are required for viral replication. Interactions of pUL34 with DNA binding sites represses transcription of two viral immune evasion genes, US3 and US9. 12 additional predicted pUL34-binding sites are present in the HCMV genome (strain AD169) with three binding sites concentrated near the HCMV origin of lytic replication (oriLyt). We used ChIP-seq analysis of pUL34-DNA interactions to confirm that pUL34 binds to the oriLyt region during infection. Mutagenesis of the UL34-binding sites in an oriLyt-containing plasmid significantly reduced viral-mediated oriLyt-dependent DNA replication. Mutagenesis of these sites in the HCMV genome reduced the replication efficiencies of the resulting viruses. Protein-protein interaction analyses demonstrated that pUL34 interacts with the viral proteins IE2, UL44, and UL84, that are essential for viral DNA replication, suggesting that pUL34-DNA interactions in the oriLyt region are involved in the DNA replication cascade. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Sosyal Medyada Kitle Çeviri Üzerine Bir Araştırma / A Study on Crowdsourcing Translation in Social Media

    Directory of Open Access Journals (Sweden)

    Ezgi Keskin GAGA

    2017-05-01

    Full Text Available Bu araştırma, Türkiye’de “Sosyal Medya Çevirileri” örneğinde yaygınlaşan ve giderek po¬püler bir eylem haline geldiği düşünülen “Kitle Çeviri (crowdsourcing translation” yöntemini inceleme amacını taşımaktadır. Çalışmanın temel sorunsalları; kitle çeviri yöntemiyle kitlesel üretimi yapılan çeviri eyleminin giderek popüler kültür ürünü haline gelmesi, popüler zeminde üretilen bu çevirilerin kalitesi, çeviriyi üreten çevirmenlerin kimliğidir. Araştırma kapsamında sosyal medya sitelerinden Facebook incelenerek Facebook’un Türkçeye çevrilmesine katkıda bulunan gönüllü çevirmenlere 16 soruluk anket uygulanmıştır. Araştırma sonucu yapılan değerlendirmeler uygulanan anket çerçevesinde ortaya çıkmıştır. Değerlendirmeler yalnızca an-ket uygulanan grupla sınırlıdır. Araştırmanın ilk bölümünde kitle çevirinin popüler kültürdeki konumu değerlendirilmiş, ikinci bölümde sosyal medya sitesi Facebook örneğinde “kitle çeviri” olgusu incelenmiştir. Araştırmanın sonunda, kitle çeviri yöntemiyle kitlesel üretimi yapılan çeviri eyleminin nasıl bir dönüşüm içine girdiği izlenmektedir. Çeviri eyleminin giderek popüler kültür ürünü haline geldiği görülmektedir. / This research aims to examine the Crowdsourcing Translation that is supposed to become a popular action recently in the example of “Social Media Translation” in Turkey. The main problematic of the study is translation (as an action becoming popular culture material through crowdsourcing translation; the quality of the translations produced in that popular ground and identity of translators translating. Within the research, by examining one of the social media website called Facebook, 16 question survey was conducted to volunteer transla¬tors contributing Facebook Turkish translation. The results of the evaluation have emerged in the framework of the implementation of the

  11. Türk ve Yabancı Futbol Takımlarının Borsa Performansları Üzerine Bir Uygulama

    Directory of Open Access Journals (Sweden)

    Feyyaz ZEREN

    2013-09-01

    Full Text Available Bu çalışmanın amacı hisse senetleri borsada işlem gören yerli ve yabancı toplam 8 futbol takımının kendi liglerinde aldıkları maç sonuçları ile borsa performansları arasında bir ilişki olup olmadığını araştırmaktadır. Türk futbol takımlarını Beşiktaş, Galatasaray, Fenerbahçe ve Trabzonspor; yabancı takımları ise Roma, Borussia Dortmund, Olympique Lyon ve Juventus oluşturmaktadır. Çalışmada bu takımların 2007-2011 sezonlarında oynadıkları maçların sonuçları temel alınmıştır. Bu amaca ulaşmak üzere SPSS 15 programında T Testi uygulaması yapılmıştır. Yapılan analiz sonucunda 8 takım içerisinden aldığı galibiyetler ile borsa performansı arasında anlamlı ilişki tespit edilen tek takım Galatasaray olarak çıkmıştır. Mağlubiyetler ile borsa performansı arasında anlamlı ilişki tespit edilen takımlar ise Fenerbahçe, Juventus, Roma ve Borussia Dortmund takımlarıdır.

  12. İşitme Engelli Bir Çocuğun Okuma Yazma Becerilerinin Dil Deneyim Yaklaşımı İle Desteklenmesi

    Directory of Open Access Journals (Sweden)

    H. Pelin Karasu

    2015-01-01

    Full Text Available Dil Deneyim Yaklaşımı; dinleme, konuşma, okuma ve yazma becerilerinin bir arada kullanılması ve okuma materyallerinin öğrencilerin deneyimleriyle oluşturulması temeline dayanmaktadır. Bu araştırmanın amacı, işitme engelli bir çocuğun okuma yazma becerilerinin gelişiminin Dil Deneyim Yaklaşımı ile desteklenme sürecinin incelenmesidir. Araştırma, bu amaç doğrultusunda, eylem araştırması şeklinde desenlenmiştir. Araştırmanın katılımcıları; araştırmacı öğretmen, geçerlik komitesi üyeleri, ilkokul 2. sınıfa devam eden işitme engelli bir öğrenci ve sınıf öğretmenidir. Araştırma verileri; araştırmacı günlüğü, belgeler, görüşmeler, uygulama planları, uygulama videoteyp kayıtları ve formel olmayan değerlendirmeler kullanılarak elde edilmiştir. Araştırma bulguları, sürecin iki evrede gerçekleştiğini göstermektedir. Bu evreler; sıralı kartlardaki olayların sözlü ve yazılı dille paylaşılması ile kelime bankası ve sözdizimi etkinliğidir. Araştırma sonuçları; dil deneyim uygulamalarının sözlü dilin gelişmesi için fırsatlar sağladığını, sözel ipuçlarının kullanılmasına, düşüncelerin sözlü ve yazılı dille ifade edilmesine olanak verdiğini, sözcük dağarcığı ve sözdizimine ilişkin ihtiyaçların belirlenmesini sağlayarak öğrencinin düzeyine uygun etkinliklerin hazırlanmasına fırsat sağladığını göstermektedir.Anahtar Sözcükler: Dil deneyim yaklaşımı, okuma yazma becerileri, işitme engelli çocuk Supporting a Hearing Impaired Child’s Literacy Development With Language Experience Approach Abstract Language Experience Approach (LEA emphasizes the synergy among listening, speaking, reading and writing skills and suggests considering learners’ experiences while preparing reading materials. The aim of the current study is to investigate LEA’s supportive role in a hearing impaired child’s literacy development. In

  13. Etkileşimli Kitap Okuma: Dil ve Erken Okuryazarlık Becerilerinin Geliştirilmesinde Etkili Bir Yöntem

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    Cevriye Ergül

    2016-08-01

    Full Text Available Erken okuryazarlık, çocukların okul öncesi dönemde okuma ve yazmaya ilişkin kazanmaları gereken önkoşul bilgi, beceri ve tutumları içermektedir. Yapılan birçok çalışmada erken okuryazarlık becerilerinin gelecekteki okuma yazma ve akademik becerileri güçlü bir şekilde yordadığı gösterilmiştir. Araştırmalardan elde edilen sonuçlar kısa ve uzun dönemde okul başarısı üzerinde etkili olduğu gözlenen erken okuryazarlık becerilerinin, okul öncesi dönemde desteklenmesi gerektiğini ortaya koymaktadır. Yetişkinlerin ev ve okul ortamlarında çocuklarla gerçekleştirdikleri birlikte kitap okuma etkinlikleri de, erken okuryazarlık becerilerinin desteklenmesinde en sık kullanılan müdahale yöntemlerinden birisidir. Alanyazında, yetişkinin çocuğa yönelik öğretici davranışlarını içeren kitap okuma etkinliklerinin, çocukların dil gelişimleri üzerinde etkili olduğu gösterilmiştir. Bu bağlamda geliştirilen ve yetişkin ile çocuk arasında etkin bir iletişimi temel alan Etkileşimli Kitap Okuma (EKO uygulamaları ise yetişkinin okuma sırasında aktif dinleyici konumunda olması, çocuğa öykü ile ilgili sorular yönelterek konuşma fırsatları sağlaması, bilinmeyen sözcükleri tanımlaması ve çocuktan gelen yanıtları tekrarlayarak genişletmeler yapması bakımından geleneksel uygulamalardan farklılaşmaktadır. Çok sayıda çalışmada EKO’nun çocukların dil, erken okuryazarlık becerileri ve okumaya yönelik tutumları üzerindeki olumlu etkilerinin olduğu ve gelişen bu becerilerin akademik başarıya önemli katkılarının olduğu gösterilmiştir. Bu noktadan hareketle bu yazıda, EKO yöntemi ele alınmış ve uygulama adımlarına ilişkin bilgi verilmiştir. Early literacy includes prerequisite knowledge, skills, and attitudes that children should acquire in relation to reading and writing prior to primary education. Several studies have shown effectiveness of early

  14. Akademisyen Ücretlerine İlişkin Karşılaştırmalı Bir Analiz A Comparative Analysis Concerned With Academic Salaries

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    Hilmi SÜNGÜ

    2013-09-01

    Full Text Available It is proved fact through scientific studies that the pay has adirect influence on productivity and job satisfaction at the same time.The pay gained as a result of the performance is considered asinterrelated both with the increase in the productivity and improvementin the quality of the service. It is vital for the organizational justice thatpeople who have similar statues and who are performing similar tasksshould receive balanced payments. However, the diversity of the publicservices, redundancy of people and formal institutions providing publicservices make it hard to guarantee a fair payment policy. It is observedas a result of comparative studies that academicians are one of theseoccupational groups who are profoundly affected by the injustice in thepayments. In order to remove the injustice in the formal officers’incomes and attain the defined goals for the 100th anniversary of thefoundation of the Republic within the scope of 2023 vision, talentedindividuals must be encouraged to become academicians. When acomparison made between public officials on the national basis, it isrealized that academic staff working at public universities are not ableto benefit from yearly increases as much as the other public officers andit leads for the fresh academicians to move away from academicprofession. As for the international point of view, it is stated that thepayments that the Turkish academicians get are below the average incomparison to their colleagues. In this study, current situation ofmonthly income of the academicians working at public universities inTurkey and it’s the yearly increases in the payment in time arementioned, national comparisons are made between differentprofessions together with international comparisons betweenacademicians from different countries. Ücretin verimlilik ve iş doyumuna etkisi yapılan akademik çalışmalarda ortaya konulmuş bir gerçektir. Çalışanın verimliliğinin artırılması ve

  15. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication.

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J; Coyne, Carolyn B

    2016-05-15

    Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of BPIFB6 expression

  16. BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication

    Science.gov (United States)

    Morosky, Stefanie; Lennemann, Nicholas J.

    2016-01-01

    ABSTRACT Bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 3 (BPIFB3) is an endoplasmic reticulum (ER)-localized host factor that negatively regulates coxsackievirus B (CVB) replication through its control of the autophagic pathway. Here, we show that another member of the BPIFB family, BPIFB6, functions as a positive regulator of CVB, and other enterovirus, replication by controlling secretory pathway trafficking and Golgi complex morphology. We show that similar to BPIFB3, BPIFB6 localizes exclusively to the ER, where it associates with other members of the BPIFB family. However, in contrast to our findings that RNA interference (RNAi)-mediated silencing of BPIFB3 greatly enhances CVB replication, we show that silencing of BPIFB6 expression dramatically suppresses enterovirus replication in a pan-viral manner. Mechanistically, we show that loss of BPIFB6 expression induces pronounced alterations in retrograde and anterograde trafficking, which correlate with dramatic fragmentation of the Golgi complex. Taken together, these data implicate BPIFB6 as a key regulator of secretory pathway trafficking and viral replication and suggest that members of the BPIFB family participate in diverse host cell functions to regulate virus infections. IMPORTANCE Enterovirus infections are associated with a number of severe pathologies, such as aseptic meningitis, dilated cardiomyopathy, type I diabetes, paralysis, and even death. These viruses, which include coxsackievirus B (CVB), poliovirus (PV), and enterovirus 71 (EV71), co-opt the host cell secretory pathway, which controls the transport of proteins from the endoplasmic reticulum to the Golgi complex, to facilitate their replication. Here we report on the identification of a novel regulator of the secretory pathway, bactericidal/permeability-increasing protein (BPI) fold-containing family B, member 6 (BPIFB6), whose expression is required for enterovirus replication. We show that loss of

  17. Maintaining replication origins in the face of genomic change.

    Science.gov (United States)

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

    2012-10-01

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

  18. 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.

  19. Nuclear mitochondrial DNA activates replication in Saccharomyces cerevisiae.

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    Laurent Chatre

    Full Text Available The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in.

  20. Replication of genetic associations as pseudoreplication due to shared genealogy.

    Science.gov (United States)

    Rosenberg, Noah A; Vanliere, Jenna M

    2009-09-01

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