Suppression of the UV-sensitive phenotype of Escherichia coli recF mutants by recA(Srf) and recA(Tif) mutations requires recJ+.

PubMed Central

Thoms, B; Wackernagel, W

1988-01-01

Mutations in recA, such as recA801(Srf) (suppressor of RecF) or recA441(Tif) (temperature-induced filamentation) partially suppress the deficiency in postreplication repair of UV damage conferred by recF mutations. We observed that spontaneous recA(Srf) mutants accumulated in cultures of recB recC sbcB sulA::Mu dX(Ap lac) lexA51 recF cells because they grew faster than the parental strain. We show that in a uvrA recB+ recC+ genetic background there are two prerequisites for the suppression by recA(Srf) of the UV-sensitive phenotype of recF mutants. (i) The recA(Srf) protein must be provided in increased amounts either by SOS derepression or by a recA operator-constitutive mutation in a lexA(Ind) (no induction of SOS functions) genetic background. (ii) The gene recJ, which has been shown previously to be involved in the recF pathway of recombination and repair, must be functional. The level of expression of recJ in a lexA(Ind) strain suffices for full suppression. Suppression by recA441 at 30 degrees C also depends on recJ+. The hampered induction by UV of the SOS gene uvrA seen in a recF mutant was improved by a recA(Srf) mutation. This improvement did not require recJ+. We suggest that recA(Srf) and recA(Tif) mutant proteins can operate in postreplication repair independent of recF by using the recJ+ function. PMID:2841294

Cancer-associated variant expression and interaction of CIZ1 with cyclin A1 in differentiating male germ cells.

PubMed

Greaves, Erin A; Copeland, Nikki A; Coverley, Dawn; Ainscough, Justin F X

2012-05-15

CIZ1 is a nuclear-matrix-associated DNA replication factor unique to higher eukaryotes, for which alternatively spliced isoforms have been associated with a range of disorders. In vitro, the CIZ1 N-terminus interacts with cyclin E and cyclin A at distinct sites, enabling functional cooperation with cyclin-A-Cdk2 to promote replication initiation. C-terminal sequences anchor CIZ1 to fixed sites on the nuclear matrix, imposing spatial constraint on cyclin-dependent kinase activity. Here we demonstrate that CIZ1 is predominantly expressed as a predicted full-length product throughout mouse development, consistent with a ubiquitous role in cell and tissue renewal. CIZ1 is expressed in proliferating stem cells of the testis, but is notably downregulated following commitment to differentiation. Significantly, CIZ1 is re-expressed at high levels in non-proliferative spermatocytes before meiotic division. Sequence analysis identifies at least seven alternatively spliced variants, including a dominant cancer-associated form and a set of novel isoforms. Furthermore, we show that in these post-replicative cells, CIZ1 interacts with germ-cell-specific cyclin A1, which has been implicated in the repair of DNA double-strand breaks. Consistent with this role, antibody depletion of CIZ1 reduces the capacity for testis extract to repair digested plasmid DNA in vitro. Together, the data imply post-replicative roles for CIZ1 in germ cell differentiation that might include meiotic recombination - a process intrinsic to genome stability and diversification.

DNA Repair at Telomeres: Keeping the Ends Intact

PubMed Central

Webb, Christopher J.; Wu, Yun; Zakian, Virginia A.

2013-01-01

The molecular era of telomere biology began with the discovery that telomeres usually consist of G-rich simple repeats and end with 3′ single-stranded tails. Enormous progress has been made in identifying the mechanisms that maintain and replenish telomeric DNA and the proteins that protect them from degradation, fusions, and checkpoint activation. Although telomeres in different organisms (or even in the same organism under different conditions) are maintained by different mechanisms, the disparate processes have the common goals of repairing defects caused by semiconservative replication through G-rich DNA, countering the shortening caused by incomplete replication, and postreplication regeneration of G tails. In addition, standard DNA repair mechanisms must be suppressed or modified at telomeres to prevent their being recognized and processed as DNA double-strand breaks. Here, we discuss the players and processes that maintain and regenerate telomere structure. PMID:23732473

Influence of oxidized purine processing on strand directionality of mismatch repair.

PubMed

Repmann, Simone; Olivera-Harris, Maite; Jiricny, Josef

2015-04-17

Replicative DNA polymerases are high fidelity enzymes that misincorporate nucleotides into nascent DNA with a frequency lower than [1/10(5)], and this precision is improved to about [1/10(7)] by their proofreading activity. Because this fidelity is insufficient to replicate most genomes without error, nature evolved postreplicative mismatch repair (MMR), which improves the fidelity of DNA replication by up to 3 orders of magnitude through correcting biosynthetic errors that escaped proofreading. MMR must be able to recognize non-Watson-Crick base pairs and excise the misincorporated nucleotides from the nascent DNA strand, which carries by definition the erroneous genetic information. In eukaryotes, MMR is believed to be directed to the nascent strand by preexisting discontinuities such as gaps between Okazaki fragments in the lagging strand or breaks in the leading strand generated by the mismatch-activated endonuclease of the MutL homologs PMS1 in yeast and PMS2 in vertebrates. We recently demonstrated that the eukaryotic MMR machinery can make use also of strand breaks arising during excision of uracils or ribonucleotides from DNA. We now show that intermediates of MutY homolog-dependent excision of adenines mispaired with 8-oxoguanine (G(O)) also act as MMR initiation sites in extracts of human cells or Xenopus laevis eggs. Unexpectedly, G(O)/C pairs were not processed in these extracts and failed to affect MMR directionality, but extracts supplemented with exogenous 8-oxoguanine DNA glycosylase (OGG1) did so. Because OGG1-mediated excision of G(O) might misdirect MMR to the template strand, our findings suggest that OGG1 activity might be inhibited during MMR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Inducible DNA-repair systems in yeast: competition for lesions.

PubMed

Mitchel, R E; Morrison, D P

1987-03-01

DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate that in this lower eukaryote, mutagen exposure does not necessarily result in a fixed risk of mutation, but that the risk can be markedly influenced by a variety of external stimuli including heat shock or exposure to other mutagens.

Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes

PubMed Central

Chakraborty, Anirban; Tapryal, Nisha; Venkova, Tatiana; Horikoshi, Nobuo; Pandita, Raj K.; Sarker, Altaf H.; Sarkar, Partha S.; Pandita, Tej K.; Hazra, Tapas K.

2016-01-01

DNA double-strand breaks (DSBs) leading to loss of nucleotides in the transcribed region can be lethal. Classical non-homologous end-joining (C-NHEJ) is the dominant pathway for DSB repair (DSBR) in adult mammalian cells. Here we report that during such DSBR, mammalian C-NHEJ proteins form a multiprotein complex with RNA polymerase II and preferentially associate with the transcribed genes after DSB induction. Depletion of C-NHEJ factors significantly abrogates DSBR in transcribed but not in non-transcribed genes. We hypothesized that nascent RNA can serve as a template for restoring the missing sequences, thus allowing error-free DSBR. We indeed found pre-mRNA in the C-NHEJ complex. Finally, when a DSB-containing plasmid with several nucleotides deleted within the E. coli lacZ gene was allowed time to repair in lacZ-expressing mammalian cells, a functional lacZ plasmid could be recovered from control but not C-NHEJ factor-depleted cells, providing important mechanistic insights into C-NHEJ-mediated error-free DSBR of the transcribed genome. PMID:27703167

Measuring strand discontinuity-directed mismatch repair in yeast Saccharomyces cerevisiae by cell-free nuclear extracts.

PubMed

Yuan, Fenghua; Lai, Fangfang; Gu, Liya; Zhou, Wen; El Hokayem, Jimmy; Zhang, Yanbin

2009-05-01

Mismatch repair corrects biosynthetic errors generated during DNA replication, whose deficiency causes a mutator phenotype and directly underlies hereditary non-polyposis colorectal cancer and sporadic cancers. Because of remarkably high conservation of the mismatch repair machinery between the budding yeast (Saccharomyces cerevisiae) and humans, the study of mismatch repair in yeast has provided tremendous insights into the mechanisms of this repair pathway in humans. In addition, yeast cells possess an unbeatable advantage over human cells in terms of the easy genetic manipulation, the availability of whole genome deletion strains, and the relatively low cost for setting up the system. Although many components of eukaryotic mismatch repair have been identified, it remains unclear if additional factors, such as DNA helicase(s) and redundant nuclease(s) besides EXO1, participate in eukaryotic mismatch repair. To facilitate the discovery of novel mismatch repair factors, we developed a straightforward in vitro cell-free repair system. Here, we describe the practical protocols for preparation of yeast cell-free nuclear extracts and DNA mismatch substrates, and the in vitro mismatch repair assay. The validity of the cell-free system was confirmed by the mismatch repair deficient yeast strain (Deltamsh2) and the complementation assay with purified yeast MSH2-MSH6.

Association between mismatch repair gene MSH3 codons 1036 and 222 polymorphisms and sporadic prostate cancer in the Iranian population.

PubMed

Jafary, Fariba; Salehi, Mansoor; Sedghi, Maryam; Nouri, Nayereh; Jafary, Farzaneh; Sadeghi, Farzaneh; Motamedi, Shima; Talebi, Maede

2012-01-01

The mismatch repair system (MMR) is a post-replicative DNA repair mechanism whose defects can lead to cancer. The MSH3 protein is an essential component of the system. We postulated that MSH3 gene polymorphisms might therefore be associated with prostate cancer (PC). We studied MSH3 codon 222 and MSH3 codon 1036 polymorphisms in a group of Iranian sporadic PC patients. A total of 60 controls and 18 patients were assessed using the polymerase chain reaction and single strand conformational polymorphism. For comparing the genotype frequencies of patients and controls the chi-square test was applied. The obtained result indicated that there was significantly association between G/A genotype of MSH3 codon 222 and G/G genotype of MSH3 codon 1036 with an increased PC risk (P=0.012 and P=0.02 respectively). Our results demonstrated that MSH3 codon 222 and MSH3 codon 1036 polymorphisms may be risk factors for sporadic prostate cancer in the Iranian population.

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

PubMed

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

TopBP1-mediated DNA processing during mitosis.

PubMed

Gallina, Irene; Christiansen, Signe Korbo; Pedersen, Rune Troelsgaard; Lisby, Michael; Oestergaard, Vibe H

2016-01-01

Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells. (1) Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

PubMed

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

Absence of MutSbeta leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks

PubMed Central

Slean, Meghan M.; Panigrahi, Gagan B.; Castel, Arturo López; Pearson, August B.; Tomkinson, Alan E.; Pearson, Christopher E.

2016-01-01

Typically disease-causing CAG/CTG repeats expand, but rare affected families can display high levels of contraction of the expanded repeat amongst offspring. Understanding instability is important since arresting expansions or enhancing contractions could be clinically beneficial. The MutSβ mismatch repair complex is required for CAG/CTG expansions in mice and patients. Oddly, by unknown mechanisms MutSβ-deficient mice incur contractions instead of expansions. Replication using CTG or CAG as the lagging strand template is known to cause contractions or expansions respectively; however, the interplay between replication and repair leading to this instability remains unclear. Towards understanding how repeat contractions may arise, we performed in vitro SV40-mediated replication of repeat-containing plasmids in the presence or absence of mismatch repair. Specifically, we separated repair from replication: Replication mediated by MutSβ- and MutSα-deficient human cells or cell extracts produced slipped-DNA heteroduplexes in the contraction- but not expansion-biased replication direction. Replication in the presence of MutSβ disfavoured the retention of replication products harbouring slipped-DNA heteroduplexes. Post-replication repair of slipped-DNAs by MutSβ-proficient extracts eliminated slipped-DNAs. Thus, a MutSβ-deficiency likely enhances repeat contractions because MutSβ protects against contractions by repairing template strand slip-outs. Replication deficient in LigaseI or PCNA-interaction mutant LigaseI revealed slipped-DNA formation at lagging strands. Our results reveal that distinct mechanisms lead to expansions or contractions and support inhibition of MutSβ as a therapeutic strategy to enhance the contraction of expanded repeats. PMID:27155933

Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae.

PubMed

Morey, Natalie J; Doetsch, Paul W; Jinks-Robertson, Sue

2003-06-01

Cellular metabolic processes constantly generate reactive species that damage DNA. To counteract this relentless assault, cells have developed multiple pathways to resist damage. The base excision repair (BER) and nucleotide excision repair (NER) pathways remove damage whereas the recombination (REC) and postreplication repair (PRR) pathways bypass the damage, allowing deferred removal. Genetic studies in yeast indicate that these pathways can process a common spontaneous lesion(s), with mutational inactivation of any pathway increasing the burden on the remaining pathways. In this study, we examine the consequences of simultaneously compromising three or more of these pathways. Although the presence of a functional BER pathway alone is able to support haploid growth, retention of the NER, REC, or PRR pathway alone is not, indicating that BER is the key damage resistance pathway in yeast and may be responsible for the removal of the majority of either spontaneous DNA damage or specifically those lesions that are potentially lethal. In the diploid state, functional BER, NER, or REC alone can support growth, while PRR alone is insufficient for growth. In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions.

DNA double strand break repair in human bladder cancer is error prone and involves microhomology-associated end-joining

PubMed Central

Bentley, Johanne; Diggle, Christine P.; Harnden, Patricia; Knowles, Margaret A.; Kiltie, Anne E.

2004-01-01

In human cells DNA double strand breaks (DSBs) can be repaired by the non-homologous end-joining (NHEJ) pathway. In a background of NHEJ deficiency, DSBs with mismatched ends can be joined by an error-prone mechanism involving joining between regions of nucleotide microhomology. The majority of joins formed from a DSB with partially incompatible 3′ overhangs by cell-free extracts from human glioblastoma (MO59K) and urothelial (NHU) cell lines were accurate and produced by the overlap/fill-in of mismatched termini by NHEJ. However, repair of DSBs by extracts using tissue from four high-grade bladder carcinomas resulted in no accurate join formation. Junctions were formed by the non-random deletion of terminal nucleotides and showed a preference for annealing at a microhomology of 8 nt buried within the DNA substrate; this process was not dependent on functional Ku70, DNA-PK or XRCC4. Junctions were repaired in the same manner in MO59K extracts in which accurate NHEJ was inactivated by inhibition of Ku70 or DNA-PKcs. These data indicate that bladder tumour extracts are unable to perform accurate NHEJ such that error-prone joining predominates. Therefore, in high-grade tumours mismatched DSBs are repaired by a highly mutagenic, microhomology-mediated, alternative end-joining pathway, a process that may contribute to genomic instability observed in bladder cancer. PMID:15466592

Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes.

PubMed

Supek, Fran; Lehner, Ben

2017-07-27

Many processes can cause the same nucleotide change in a genome, making the identification of the mechanisms causing mutations a difficult challenge. Here, we show that clustered mutations provide a more precise fingerprint of mutagenic processes. Of nine clustered mutation signatures identified from >1,000 tumor genomes, three relate to variable APOBEC activity and three are associated with tobacco smoking. An additional signature matches the spectrum of translesion DNA polymerase eta (POLH). In lymphoid cells, these mutations target promoters, consistent with AID-initiated somatic hypermutation. In solid tumors, however, they are associated with UV exposure and alcohol consumption and target the H3K36me3 chromatin of active genes in a mismatch repair (MMR)-dependent manner. These regions normally have a low mutation rate because error-free MMR also targets H3K36me3 chromatin. Carcinogens and error-prone repair therefore redistribute mutations to the more important regions of the genome, contributing a substantial mutation load in many tumors, including driver mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.

PubMed

Lu, Wei-Ting; Hawley, Ben R; Skalka, George L; Baldock, Robert A; Smith, Ewan M; Bader, Aldo S; Malewicz, Michal; Watts, Felicity Z; Wilczynska, Ania; Bushell, Martin

2018-02-07

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage. Depletion of Drosha significantly reduces DNA repair by both homologous recombination (HR) and non-homologous end joining (NHEJ). Drosha is required within minutes of break induction, suggesting a central and early role for RNA processing in DNA repair. Sequencing of DNA:RNA hybrids reveals RNA invasion around DNA break sites in a Drosha-dependent manner. Removal of the RNA component of these structures results in impaired repair. These results show how RNA can be a direct and critical mediator of DNA damage repair in human cells.

Effect of the SOS response on the mean fitness of unicellular populations: a quasispecies approach.

PubMed

Kama, Amit; Tannenbaum, Emmanuel

2010-11-30

The goal of this paper is to develop a mathematical model that analyzes the selective advantage of the SOS response in unicellular organisms. To this end, this paper develops a quasispecies model that incorporates the SOS response. We consider a unicellular, asexually replicating population of organisms, whose genomes consist of a single, double-stranded DNA molecule, i.e. one chromosome. We assume that repair of post-replication mismatched base-pairs occurs with probability , and that the SOS response is triggered when the total number of mismatched base-pairs is at least . We further assume that the per-mismatch SOS elimination rate is characterized by a first-order rate constant . For a single fitness peak landscape where the master genome can sustain up to mismatches and remain viable, this model is analytically solvable in the limit of infinite sequence length. The results, which are confirmed by stochastic simulations, indicate that the SOS response does indeed confer a fitness advantage to a population, provided that it is only activated when DNA damage is so extensive that a cell will die if it does not attempt to repair its DNA.

Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms.

PubMed

Tannenbaum, Emmanuel; Sherley, James L; Shakhnovich, Eugene I

2005-04-01

This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) "immortal DNA strand" co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

Evolutionary dynamics of adult stem cells: Comparison of random and immortal-strand segregation mechanisms

NASA Astrophysics Data System (ADS)

Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.

2005-04-01

This paper develops a point-mutation model describing the evolutionary dynamics of a population of adult stem cells. Such a model may prove useful for quantitative studies of tissue aging and the emergence of cancer. We consider two modes of chromosome segregation: (1) random segregation, where the daughter chromosomes of a given parent chromosome segregate randomly into the stem cell and its differentiating sister cell and (2) “immortal DNA strand” co-segregation, for which the stem cell retains the daughter chromosomes with the oldest parent strands. Immortal strand co-segregation is a mechanism, originally proposed by [Cairns Nature (London) 255, 197 (1975)], by which stem cells preserve the integrity of their genomes. For random segregation, we develop an ordered strand pair formulation of the dynamics, analogous to the ordered strand pair formalism developed for quasispecies dynamics involving semiconservative replication with imperfect lesion repair (in this context, lesion repair is taken to mean repair of postreplication base-pair mismatches). Interestingly, a similar formulation is possible with immortal strand co-segregation, despite the fact that this segregation mechanism is age dependent. From our model we are able to mathematically show that, when lesion repair is imperfect, then immortal strand co-segregation leads to better preservation of the stem cell lineage than random chromosome segregation. Furthermore, our model allows us to estimate the optimal lesion repair efficiency for preserving an adult stem cell population for a given period of time. For human stem cells, we obtain that mispaired bases still present after replication and cell division should be left untouched, to avoid potentially fixing a mutation in both DNA strands.

Mechanisms of viral mutation.

PubMed

Sanjuán, Rafael; Domingo-Calap, Pilar

2016-12-01

The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus- and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.

Mutagenesis during plant responses to UVB radiation.

PubMed

Holá, M; Vágnerová, R; Angelis, K J

2015-08-01

We tested an idea that induced mutagenesis due to unrepaired DNA lesions, here the UV photoproducts, underlies the impact of UVB irradiation on plant phenotype. For this purpose we used protonemal culture of the moss Physcomitrella patens with 50% of apical cells, which mimics actively growing tissue, the most vulnerable stage for the induction of mutations. We measured the UVB mutation rate of various moss lines with defects in DNA repair (pplig4, ppku70, pprad50, ppmre11), and in selected clones resistant to 2-Fluoroadenine, which were mutated in the adenosine phosphotrasferase gene (APT), we analysed induced mutations by sequencing. In parallel we followed DNA break repair and removal of cyclobutane pyrimidine dimers with a half-life τ = 4 h 14 min determined by comet assay combined with UV dimer specific T4 endonuclease V. We show that UVB induces massive, sequence specific, error-prone bypass repair that is responsible for a high mutation rate owing to relatively slow, though error-free, removal of photoproducts by nucleotide excision repair (NER). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

PubMed

Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

2006-06-01

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Repair of 8-oxo-7,8-dihydroguanine in prokaryotic and eukaryotic cells: Properties and biological roles of the Fpg and OGG1 DNA N-glycosylases.

PubMed

Boiteux, Serge; Coste, Franck; Castaing, Bertrand

2017-06-01

Oxidatively damaged DNA results from the attack of sugar and base moieties by reactive oxygen species (ROS), which are formed as byproducts of normal cell metabolism and during exposure to endogenous or exogenous chemical or physical agents. Guanine, having the lowest redox potential, is the DNA base the most susceptible to oxidation, yielding products such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2-6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). In DNA, 8-oxoG was shown to be mutagenic yielding GC to TA transversions upon incorporation of dAMP opposite this lesion by replicative DNA polymerases. In prokaryotic and eukaryotic cells, 8-oxoG is primarily repaired by the base excision repair pathway (BER) initiated by a DNA N-glycosylase, Fpg and OGG1, respectively. In Escherichia coli, Fpg cooperates with MutY and MutT to prevent 8-oxoG-induced mutations, the "GO-repair system". In Saccharomyces cerevisiae, OGG1 cooperates with nucleotide excision repair (NER), mismatch repair (MMR), post-replication repair (PRR) and DNA polymerase η to prevent mutagenesis. Human and mouse cells mobilize all these pathways using OGG1, MUTYH (MutY-homolog also known as MYH), MTH1 (MutT-homolog also known as NUDT1), NER, MMR, NEILs and DNA polymerases η and λ, to prevent 8-oxoG-induced mutations. In fact, mice deficient in both OGG1 and MUTYH develop cancer in different organs at adult age, which points to the critical impact of 8-oxoG repair on genetic stability in mammals. In this review, we will focus on Fpg and OGG1 proteins, their biochemical and structural properties as well as their biological roles. Other DNA N-glycosylases able to release 8-oxoG from damaged DNA in various organisms will be discussed. Finally, we will report on the role of OGG1 in human disease and the possible use of 8-oxoG DNA N-glycosylases as therapeutic targets. Copyright © 2017 Elsevier Inc. All rights reserved.

[Dot1 and Set2 Histone Methylases Control the Spontaneous and UV-Induced Mutagenesis Levels in the Saccharomyces cerevisiae Yeasts].

PubMed

Kozhina, T N; Evstiukhina, T A; Peshekhonov, V T; Chernenkov, A Yu; Korolev, V G

2016-03-01

In the Saccharomyces cerevisiae yeasts, the DOT1 gene product provides methylation of lysine 79 (K79) of hi- stone H3 and the SET2 gene product provides the methylation of lysine 36 (K36) of the same histone. We determined that the dot1 and set2 mutants suppress the UV-induced mutagenesis to an equally high degree. The dot1 mutation demonstrated statistically higher sensitivity to the low doses of MMC than the wild type strain. The analysis of the interaction between the dot1 and rad52 mutations revealed a considerable level of spontaneous cell death in the double dot1 rad52 mutant. We observed strong suppression of the gamma-in- duced mutagenesis in the set2 mutant. We determined that the dot1 and set2 mutations decrease the sponta- neous mutagenesis rate in both single and d ouble mutants. The epistatic interaction between the dot1 and set2 mutations and almost similar sensitivity of the corresponding mutants to the different types of DNA damage allow one to conclude that both genes are involved in the control of the same DNA repair pathways, the ho- mologous-recombination-based and the postreplicative DNA repair.

Late complication of open inguinal hernia repair: small bowel obstruction caused by intraperitoneal mesh migration.

PubMed

Ferrone, Roberto; Scarone, Pier Carlo; Natalini, Gianni

2003-09-01

We describe a case of small bowel obstruction due to prosthetic mesh migration. A 67-year-old male, who had undergone prosthetic repair of inguinal hernia 3 years before, was admitted for a mechanical small bowel obstruction. Laparotomy revealed the penultimate ileal loop choked by an adhesion drawing it towards a polypropylene mesh, firmly attached to the parietal peritoneum of the inguinal region. The intestinal loop was released; the mesh was embedded deep with continuous whip suture after folding the parietal peritoneum. The patient was dismissed on the 11th postoperative day surgically healed. The "tension-free" technique is undoubtedly the gold standard for hernia repair. However, it is not free of complications, mostly due to technical errors, of which the surgeon must be aware, both when he is responsible for correcting defects in the wall, as well as when he has to face an occlusion in a patient who has undergone plastic surgery for inguinal hernia.

DNA Damage Levels Determine Cyclobutyl Pyrimidine Dimer Repair Mechanisms in Alfalfa Seedlings.

PubMed Central

Quaite, F. E.; Takayanagi, S.; Ruffini, J.; Sutherland, J. C.; Sutherland, B. M.

1994-01-01

Ultraviolet radiation in sunlight damages DNA in plants, but little is understood about the types, lesion capacity, and coordination of repair pathways. We challenged intact alfalfa seedlings with UV doses that induced different initial levels of cyclobutyl pyrimidine dimers and measured repair by excision and photoreactivation. By using alkaline gel electrophoresis of nonradioactive DNAs treated with a cyclobutyl pyrimidine dimer-specific UV endonuclease, we quantitated ethidium-stained DNA by electronic imaging and calculated lesion frequencies from the number average molecular lengths. At low initial dimer frequencies (less than ~30 dimers per million bases), the seedlings used only photoreactivation to repair dimers; excision repair was not significant. At higher damage levels, both excision and photorepair contributed significantly. This strategy would allow plants with low damage levels to use error-free repair requiring only an external light energy source, whereas seedlings subjected to higher damage frequencies could call on additional repair processes requiring cellular energy. Characterization of repair in plants thus requires an investigation of a range of conditions, including the level of initial damage. PMID:12244228

DNA strand breaks signal the induction of DNA double-strand break repair in Saccharomyces cerevisiae.

PubMed

Singh, Rakesh Kumar; Krishna, Malini

2005-12-01

Genotoxic stress induces a checkpoint signaling cascade to generate a stress response. Saccharomyces cerevisiae shows an altered radiation response under different type of stress. Although the induction of repair has been implicated in enhanced survival after exposure to the challenging stress, the nature of the signal remains poorly understood. This study demonstrates that low doses of gamma radiation and bleomycin induce RAD52-dependent recombination repair pathway in the wild-type strain D-261. Prior exposure of cells to DNA-damaging agents (gamma radiation or bleomycin) equips them better for the subsequent damage caused by challenging doses. However, exposure to UV light, which does not cause strand breaks, was ineffective. This was confirmed by PFGE studies. This indicates that the strand breaks probably serve as the signal for induction of the recombination repair pathway while pyrimidine dimers do not. The nature of the induced repair was investigated by mutation scoring in special strain D-7, which showed that the induced repair is essentially error free.

Effect of caffeine on the ultraviolet light induction of SV40 virus from transformed hamster cells

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

Zamansky, G.B.; Kleinman, L.F.; Little, J.B.

1976-01-01

The effect of caffeine on the uv light induction of SV40 virus from two transformed hamster cell lines heterogeneous for the induction of infectious virus was studied. The amount of virus induced was significantly increased in both cell lines when exposure to uv light was followed by treatment with caffeine. Caffeine in the absence of uv irradiation did not stimulate virus induction, nor did it stimulate SV40 replication in a lytic infection. There was an apparent difference in the concentrations of caffeine which maximally stimulated SV40 virus induction in the two cell lines. This effect could not be explained bymore » differences in cell survival after exposure to uv light and caffeine. Since caffeine is known to cause the accumulation of gaps formed in DNA during postreplication repair of uv-irradiated rodent cells, our results support the hypothesis that the formation of gaps or breaks in DNA is an important early step in virus induction.« less

Broken replication forks trigger heritable DNA breaks in the terminus of a circular chromosome

PubMed Central

Possoz, Christophe; Durand, Adeline; Desfontaines, Jean-Michel; Barre, François-Xavier; Leach, David R. F.

2018-01-01

It was recently reported that the recBC mutants of Escherichia coli, deficient for DNA double-strand break (DSB) repair, have a decreased copy number of their terminus region. We previously showed that this deficit resulted from DNA loss after post-replicative breakage of one of the two sister-chromosome termini at cell division. A viable cell and a dead cell devoid of terminus region were thus produced and, intriguingly, the reaction was transmitted to the following generations. Using genome marker frequency profiling and observation by microscopy of specific DNA loci within the terminus, we reveal here the origin of this phenomenon. We observed that terminus DNA loss was reduced in a recA mutant by the double-strand DNA degradation activity of RecBCD. The terminus-less cell produced at the first cell division was less prone to divide than the one produced at the next generation. DNA loss was not heritable if the chromosome was linearized in the terminus and occurred at chromosome termini that were unable to segregate after replication. We propose that in a recB mutant replication fork breakage results in the persistence of a linear DNA tail attached to a circular chromosome. Segregation of the linear and circular parts of this “σ-replicating chromosome” causes terminus DNA breakage during cell division. One daughter cell inherits a truncated linear chromosome and is not viable. The other inherits a circular chromosome attached to a linear tail ending in the chromosome terminus. Replication extends this tail, while degradation of its extremity results in terminus DNA loss. Repeated generation and segregation of new σ-replicating chromosomes explains the heritability of post-replicative breakage. Our results allow us to determine that in E. coli at each generation, 18% of cells are subject to replication fork breakage at dispersed, potentially random, chromosomal locations. PMID:29522563

Characterization of an Escherichia coli mutant (radB101) sensitive to. gamma. and uv radiation, and methyl methanesulfonate

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

Sargentini, N.J.; Smith, K.C.

1983-03-01

After N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis of Escherichia coli K-12 (xthA14), an X-ray-sensitive mutant was isolated. This sensitivity is due to a mutation, radB101, which is located at 56.5 min on the E.coli K-12 linkage map. The radB101 mutation sensitized wild-type cells to ..gamma.. and uv radiation, and to methyl methanesulfonate. When known DNA repair-deficient mutants were ranked for their ..gamma..-radiation sensitivity relative to their uv-radiation sensitivity, their order was (starting with the most selectively ..gamma..-radiation-sensitive strain): recB21, radB101, wild type, polA1, recF143, lexA101, recA56, uvrD3, and uvrA6. The radB mutant was normal for ..gamma..- and uv-radiation mutagenesis, it showed only a slightmore » enhancement of ..gamma..- and uv-radiation-induced DNA degradation, and it was approx. 60% deficient in recombination ability. The radB gene is suggested to play a role in the recA gene-dependent (Type III) repair of DNA single-strand breaks after ..gamma.. irradiation and in postreplication repair after uv irradiation for the following reasons: the radB strain was normal for the host-cell reactivation of ..gamma..- and uv-irradiated bacteriophage lambda; the radB mutation did not sensitize a recA strain, but did sensitize a polA strain to ..gamma.. and uv radiation; the radB mutation sensitized a uvrB strain to uv radiation.« less

Cellular Dynamics of Rad51 and Rad54 in Response to Postreplicative Stress and DNA Damage in HeLa Cells.

PubMed

Choi, Eui-Hwan; Yoon, Seobin; Hahn, Yoonsoo; Kim, Keun P

2017-02-01

Homologous recombination (HR) is necessary for maintenance of genomic integrity and prevention of various mutations in tumor suppressor genes and proto-oncogenes. Rad51 and Rad54 are key HR factors that cope with replication stress and DNA breaks in eukaryotes. Rad51 binds to single-stranded DNA (ssDNA) to form the presynaptic filament that promotes a homology search and DNA strand exchange, and Rad54 stimulates the strand-pairing function of Rad51. Here, we studied the molecular dynamics of Rad51 and Rad54 during the cell cycle of HeLa cells. These cells constitutively express Rad51 and Rad54 throughout the entire cell cycle, and the formation of foci immediately increased in response to various types of DNA damage and replication stress, except for caffeine, which suppressed the Rad51-dependent HR pathway. Depletion of Rad51 caused severe defects in response to postreplicative stress. Accordingly, HeLa cells were arrested at the G2-M transition although a small amount of Rad51 was steadily maintained in HeLa cells. Our results suggest that cell cycle progression and proliferation of HeLa cells can be tightly controlled by the abundance of HR proteins, which are essential for the rapid response to postreplicative stress and DNA damage stress.

Error-free versus mutagenic processing of genomic uracil--relevance to cancer.

PubMed

Krokan, Hans E; Sætrom, Pål; Aas, Per Arne; Pettersen, Henrik Sahlin; Kavli, Bodil; Slupphaug, Geir

2014-07-01

Genomic uracil is normally processed essentially error-free by base excision repair (BER), with mismatch repair (MMR) as an apparent backup for U:G mismatches. Nuclear uracil-DNA glycosylase UNG2 is the major enzyme initiating BER of uracil of U:A pairs as well as U:G mismatches. Deficiency in UNG2 results in several-fold increases in genomic uracil in mammalian cells. Thus, the alternative uracil-removing glycosylases, SMUG1, TDG and MBD4 cannot efficiently complement UNG2-deficiency. A major function of SMUG1 is probably to remove 5-hydroxymethyluracil from DNA with general back-up for UNG2 as a minor function. TDG and MBD4 remove deamination products U or T mismatched to G in CpG/mCpG contexts, but may have equally or more important functions in development, epigenetics and gene regulation. Genomic uracil was previously thought to arise only from spontaneous cytosine deamination and incorporation of dUMP, generating U:G mismatches and U:A pairs, respectively. However, the identification of activation-induced cytidine deaminase (AID) and other APOBEC family members as DNA-cytosine deaminases has spurred renewed interest in the processing of genomic uracil. Importantly, AID triggers the adaptive immune response involving error-prone processing of U:G mismatches, but also contributes to B-cell lymphomagenesis. Furthermore, mutational signatures in a substantial fraction of other human cancers are consistent with APOBEC-induced mutagenesis, with U:G mismatches as prime suspects. Mutations can be caused by replicative polymerases copying uracil in U:G mismatches, or by translesion polymerases that insert incorrect bases opposite abasic sites after uracil-removal. In addition, kataegis, localized hypermutations in one strand in the vicinity of genomic rearrangements, requires APOBEC protein, UNG2 and translesion polymerase REV1. What mechanisms govern error-free versus error prone processing of uracil in DNA remains unclear. In conclusion, genomic uracil is an essential intermediate in adaptive immunity and innate antiviral responses, but may also be a fundamental cause of a wide range of malignancies. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The indirect effect of radiation reduces the repair fidelity of NHEJ as verified in repair deficient CHO cell lines exposed to different radiation qualities and potassium bromate.

PubMed

Bajinskis, Ainars; Olsson, Gunilla; Harms-Ringdahl, Mats

2012-03-01

The complexity of DNA lesions induced by ionizing radiation is mainly dependent on radiation quality, where the indirect action of radiation may contribute to different extent depending on the type of radiation under study. The effect of indirect action of radiation can be investigated by using agents that induce oxidative DNA damage or by applying free radical scavengers. The aim of this study was to investigate the role of the indirect effect of radiation for the repair fidelity of non-homologous end-joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER) when DNA damage of different complexity was induced by gamma radiation, alpha particles or from base damages (8-oxo-dG) induced by potassium bromate (KBrO(3)). CHO cells lines deficient in XRCC3 (HRR) irs1SF, XRCC7 (NHEJ) V3-3 and XRCC1 (BER) EM9 were irradiated in the absence or presence of the free radical scavenger dimethyl sulfoxide (DMSO). The endpoints investigated included rate of cell proliferation by the DRAG assay, clonogenic cell survival and the level of primary DNA damage by the comet assay. The results revealed that the indirect effect of low-LET radiation significantly reduced the repair fidelity of both NHEJ and HRR pathways. For high-LET radiation the indirect effect of radiation also significantly reduced the repair fidelity for the repair deficient cell lines. The results suggest further that the repair fidelity of the error prone NHEJ repair pathway is more impaired by the indirect effect of high-LET radiation relative to the other repair pathways studied. The response to bromate observed for the two DSB repair deficient cell lines strongly support earlier studies that bromate induces complex DNA damages. The significantly reduced repair fidelity of irs1SF and V3-3 suggests that NHEJ as well as HRR are needed for the repair, and that complex DSBs are formed after bromate exposure. Copyright © 2011 Elsevier B.V. All rights reserved.

Self-checking self-repairing computer nodes using the mirror processor

NASA Technical Reports Server (NTRS)

Tamir, Yuval

1992-01-01

Circuitry added to fault-tolerant systems for concurrent error deduction usually reduces performance. Using a technique called micro rollback, it is possible to eliminate most of the performance penalty of concurrent error detection. Error detection is performed in parallel with intermodule communication, and erroneous state changes are later undone. The author reports on the design and implementation of a VLSI RISC microprocessor, called the Mirror Processor (MP), which is capable of micro rollback. In order to achieve concurrent error detection, two MP chips operate in lockstep, comparing external signals and a signature of internal signals every clock cycle. If a mismatch is detected, both processors roll back to the beginning of the cycle when the error occurred. In some cases the erroneous state is corrected by copying a value from the fault-free processor to the faulty processor. The architecture, microarchitecture, and VLSI implementation of the MP, emphasizing its error-detection, error-recovery, and self-diagnosis capabilities, are described.

tif-Stimulated deoxyribonucleic acid repair in Escherichia coli K-12.

PubMed Central

Castellazzi, M; Jacques, M; George, J

1980-01-01

Bacterial survival is significantly increased after ultraviolet irradiation in tif sfi cells, provided that the thermosensitive tif mutation has been expressed at 41 degrees C before irradiation. This tif-mediated "reactivation of ultraviolet irradiated bacteria" needs de novo protein synthesis, as is the case for the tif-mediated reactivation of ultraviolet-irradiated phage lambda. However, in striking contrast to the phage reactivation process, this tif-mediated reactivation is no longer associated with mutagenesis. It also requires the presence of the uvrA+ excision function. These results strongly suggest the existence in Escherichia coli K-12 of a repair pathway acting on bacterial deoxyribonucleic acid which is inducible, error free, and uvr dependent. PMID:6451614

Avoidance of APOBEC3B-induced mutation by error-free lesion bypass

PubMed Central

Hoopes, James I.; Hughes, Amber L.; Hobson, Lauren A.; Cortez, Luis M.; Brown, Alexander J.

2017-01-01

Abstract APOBEC cytidine deaminases mutate cancer genomes by converting cytidines into uridines within ssDNA during replication. Although uracil DNA glycosylases limit APOBEC-induced mutation, it is unknown if subsequent base excision repair (BER) steps function on replication-associated ssDNA. Hence, we measured APOBEC3B-induced CAN1 mutation frequencies in yeast deficient in BER endonucleases or DNA damage tolerance proteins. Strains lacking Apn1, Apn2, Ntg1, Ntg2 or Rev3 displayed wild-type frequencies of APOBEC3B-induced canavanine resistance (CanR). However, strains without error-free lesion bypass proteins Ubc13, Mms2 and Mph1 displayed respective 4.9-, 2.8- and 7.8-fold higher frequency of APOBEC3B-induced CanR. These results indicate that mutations resulting from APOBEC activity are avoided by deoxyuridine conversion to abasic sites ahead of nascent lagging strand DNA synthesis and subsequent bypass by error-free template switching. We found this mechanism also functions during telomere re-synthesis, but with a diminished requirement for Ubc13. Interestingly, reduction of G to C substitutions in Ubc13-deficient strains uncovered a previously unknown role of Ubc13 in controlling the activity of the translesion synthesis polymerase, Rev1. Our results highlight a novel mechanism for error-free bypass of deoxyuridines generated within ssDNA and suggest that the APOBEC mutation signature observed in cancer genomes may under-represent the genomic damage these enzymes induce. PMID:28334887

Importance of DNA repair in tumor suppression

NASA Astrophysics Data System (ADS)

Brumer, Yisroel; Shakhnovich, Eugene I.

2004-12-01

The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. On a specific single fitness peak landscape, the repair-free semiconservative system is shown to mimic a conservative system exactly. We postulate that inactivation of post-methylation repair mechanisms is fundamental to the progression of a tumor cell and hence these mechanisms act as a method for the prevention and destruction of cancerous genomes.

Induction and repair of DNA double strand breaks: the increasing spectrum of non-homologous end joining pathways.

PubMed

Mladenov, Emil; Iliakis, George

2011-06-03

A defining characteristic of damage induced in the DNA by ionizing radiation (IR) is its clustered character that leads to the formation of complex lesions challenging the cellular repair mechanisms. The most widely investigated such complex lesion is the DNA double strand break (DSB). DSBs undermine chromatin stability and challenge the repair machinery because an intact template strand is lacking to assist restoration of integrity and sequence in the DNA molecule. Therefore, cells have evolved a sophisticated machinery to detect DSBs and coordinate a response on the basis of inputs from various sources. A central function of cellular responses to DSBs is the coordination of DSB repair. Two conceptually different mechanisms can in principle remove DSBs from the genome of cells of higher eukaryotes. Homologous recombination repair (HRR) uses as template a homologous DNA molecule and is therefore error-free; it functions preferentially in the S and G2 phases. Non-homologous end joining (NHEJ), on the other hand, simply restores DNA integrity by joining the two ends, is error prone as sequence is only fortuitously preserved and active throughout the cell cycle. The basis of DSB repair pathway choice remains unknown, but cells of higher eukaryotes appear programmed to utilize preferentially NHEJ. Recent work suggests that when the canonical DNA-PK dependent pathway of NHEJ (D-NHEJ), becomes compromised an alternative NHEJ pathway and not HRR substitutes in a quasi-backup function (B-NHEJ). Here, we outline aspects of DSB induction by IR and review the mechanisms of their processing in cells of higher eukaryotes. We place particular emphasis on backup pathways of NHEJ and summarize their increasing significance in various cellular processes, as well as their potential contribution to carcinogenesis. 2011 Elsevier B.V. All rights reserved.

The 5'-poly(A) leader of poxvirus mRNA confers a translational advantage that can be achieved in cells with impaired cap-dependent translation

PubMed Central

Dhungel, Pragyesh; Cao, Shuai

2017-01-01

The poly(A) leader at the 5’-untranslated region (5’-UTR) is an unusually striking feature of all poxvirus mRNAs transcribed after viral DNA replication (post-replicative mRNAs). These poly(A) leaders are non-templated and of heterogeneous lengths; and their function during poxvirus infection remains a long-standing question. Here, we discovered that a 5’-poly(A) leader conferred a selective translational advantage to mRNA in poxvirus-infected cells. A constitutive and uninterrupted 5’-poly(A) leader with 12 residues was optimal. Because the most frequent lengths of the 5’-poly(A) leaders are 8–12 residues, the result suggests that the poly(A) leader has been evolutionarily optimized to boost poxvirus protein production. A 5’-poly(A) leader also could increase protein production in the bacteriophage T7 promoter-based expression system of vaccinia virus, the prototypic member of poxviruses. Interestingly, although vaccinia virus post-replicative mRNAs do have 5’- methylated guanosine caps and can use cap-dependent translation, in vaccinia virus-infected cells, mRNA with a 5’-poly(A) leader could also be efficiently translated in cells with impaired cap-dependent translation. However, the translation was not mediated through an internal ribosome entry site (IRES). These results point to a fundamental mechanism poxvirus uses to efficiently translate its post-replicative mRNAs. PMID:28854224

DNA Replication Origins and Fork Progression at Mammalian Telomeres

PubMed Central

Higa, Mitsunori; Fujita, Masatoshi; Yoshida, Kazumasa

2017-01-01

Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions. PMID:28350373

Implication of RuvABC and RecG in homologous recombination in Streptomyces ambofaciens.

PubMed

Hoff, Grégory; Bertrand, Claire; Piotrowski, Emilie; Thibessard, Annabelle; Leblond, Pierre

2017-01-01

Most bacterial organisms rely on homologous recombination to repair DNA double-strand breaks and for the post-replicative repair of DNA single-strand gaps. Homologous recombination can be divided into three steps: (i) a pre-synaptic step in which the DNA 3'-OH ends are processed, (ii) a recA-dependent synaptic step allowing the invasion of an intact copy and the formation of Holliday junctions, and (iii) a post-synaptic step consisting of migration and resolution of these junctions. Currently, little is known about factors involved in homologous recombination, especially for the post-synaptic step. In Escherichia coli, branch migration and resolution are performed by the RuvABC complex, but could also rely on the RecG helicase in a redundant manner. In this study, we show that recG and ruvABC are well-conserved among Streptomyces. ΔruvABC, ΔrecG and ΔruvABC ΔrecG mutant strains were constructed. ΔruvABC ΔrecG is only slightly affected by exposure to DNA damage (UV). We also show that conjugational recombination decreases in the absence of RuvABC and RecG, but that intra-chromosomal recombination is not affected. These data suggest that RuvABC and RecG are indeed involved in homologous recombination in Streptomyces ambofaciens and that alternative factors are able to take over Holliday junction in Streptomyces. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Rifampin-stimulated uv resistance of phage lambda on Escherichia coli K12

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

Bronner, C.E.; Fluke, D.J.; Pollard, E.C.

1983-01-01

The plaque survival of uv-irradiated phage lambda on excision-proficient E.coli strain AB1157 is greater if the host cells are exposed to rifampin for 10 minutes prior to infection. This repair is accompanied by little or no clear-plaque mutagenesis. Host cells uv-irradiated and incubated for 30 minutes in growth medium prior to treatment with rifampin show some Weigle-reactivation in addition to the repair stimulated by rifampin. Some clear-plaque Weigle-mutagenesis is also observed in the presence of rifampin: however, the amount is less than that seen in the absence of rifampin treatment. In contrast, the uv sensitivity of lambda on strain AB1886,more » an excision-repair deficient mutant, is unchanged by pre-treating the cells with rifampin, and no Weigle-reactivation is observed. These results suggest that repair of lambda on unirradiated cells in the presence of rifampin is an excision-dependent, error-free phenomenon. Since initiation of replication of lambda DNA requires RNA polymerase, and since rifampin blocks transcription by that polymerase, the effect of rifampin on the survival of lambda may be to delay phage replication, thereby allowing more time for excision repair to operate. 6 figures.« less

Immunofluorescence-based methods to monitor DNA end resection

PubMed Central

Mukherjee, Bipasha; Tomimatsu, Nozomi; Burma, Sandeep

2017-01-01

Summary Double-strand breaks (DSBs) are the most deleterious amongst all types of DNA damage that can occur in the cell. These breaks arise from both endogenous (for example, DNA replication stress) as well as exogenous insults (for example, ionizing radiation). DSBs are principally repaired by one of two major pathways: non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ is an error-prone process that can occur in all phases of the cell cycle, while HR is limited to the S and G2 phases of the cell cycle when a sister chromatid is available as a template for error-free repair. The first step in HR is “DNA end resection”, a process during which the broken DNA end is converted into a long stretch of 3′-ended single-stranded DNA (ssDNA). In recent years, DNA end resection has been identified as a pivotal step that controls “repair pathway choice” i.e., the appropriate choice between NHEJ and HR for DSB repair. Therefore, methods to quantitatively or semi-quantitatively assess DNA end resection have gained importance in laboratories working on DNA repair. In this chapter, we describe two simple immunofluorescence-based techniques to monitor DNA end resection in mammalian cells. The first technique involves immuno-detection of Replication Protein A (RPA), a ssDNA-binding protein that binds to resected DNA. The second technique involves labeling of genomic DNA with 5-bromo-2′-deoxyuridine (BrdU) that can be detected by anti-BrdU antibody only after the DNA becomes single stranded due to resection. These methods are not complicated, do not involve sophisticated instrumentation or reporter constructs, and can be applied to most mammalian cell lines, and therefore, should be of broad utility as simple ways of monitoring DNA end resection in vivo. PMID:25804748

Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination.

PubMed

Yousif, Ashraf S; Stanlie, Andre; Begum, Nasim A; Honjo, Tasuku

2014-10-01

Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR. © The Japanese Society for Immunology. 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Heft Lemisphere: Exchanges Predominate in Segmental Speech Errors

ERIC Educational Resources Information Center

Nooteboom, Sieb G.; Quene, Hugo

2013-01-01

In most collections of segmental speech errors, exchanges are less frequent than anticipations and perseverations. However, it has been suggested that in inner speech exchanges might be more frequent than either anticipations or perseverations, because many half-way repaired errors (Yew...uhh...New York) are classified as repaired anticipations,…

Darwinian demons, evolutionary complexity, and information maximization.

PubMed

Krakauer, David C

2011-09-01

Natural selection is shown to be an extended instance of a Maxwell's demon device. A demonic selection principle is introduced that states that organisms cannot exceed the complexity of their selective environment. Thermodynamic constraints on error repair impose a fundamental limit to the rate that information can be transferred from the environment (via the selective demon) to the genome. Evolved mechanisms of learning and inference can overcome this limitation, but remain subject to the same fundamental constraint, such that plastic behaviors cannot exceed the complexity of reward signals. A natural measure of evolutionary complexity is provided by mutual information, and niche construction activity--the organismal contribution to the construction of selection pressures--might in principle lead to its increase, bounded by thermodynamic free energy required for error correction.

MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

PubMed

Tran, An Hue Vy; Han, Se Hee; Kim, Joon; Grasso, Francesca; Kim, In San; Han, Ye Sun

2017-07-01

Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DNA polymerase ɛ and δ exonuclease domain mutations in endometrial cancer

PubMed Central

Church, David N.; Briggs, Sarah E.W.; Palles, Claire; Domingo, Enric; Kearsey, Stephen J.; Grimes, Jonathon M.; Gorman, Maggie; Martin, Lynn; Howarth, Kimberley M.; Hodgson, Shirley V.; Kaur, Kulvinder; Taylor, Jenny; Tomlinson, Ian P.M.

2013-01-01

Accurate duplication of DNA prior to cell division is essential to suppress mutagenesis and tumour development. The high fidelity of eukaryotic DNA replication is due to a combination of accurate incorporation of nucleotides into the nascent DNA strand by DNA polymerases, the recognition and removal of mispaired nucleotides (proofreading) by the exonuclease activity of DNA polymerases δ and ɛ, and post-replication surveillance and repair of newly synthesized DNA by the mismatch repair (MMR) apparatus. While the contribution of defective MMR to neoplasia is well recognized, evidence that faulty DNA polymerase activity is important in cancer development has been limited. We have recently shown that germline POLE and POLD1 exonuclease domain mutations (EDMs) predispose to colorectal cancer (CRC) and, in the latter case, to endometrial cancer (EC). Somatic POLE mutations also occur in 5–10% of sporadic CRCs and underlie a hypermutator, microsatellite-stable molecular phenotype. We hypothesized that sporadic ECs might also acquire somatic POLE and/or POLD1 mutations. Here, we have found that missense POLE EDMs with good evidence of pathogenic effects are present in 7% of a set of 173 endometrial cancers, although POLD1 EDMs are uncommon. The POLE mutations localized to highly conserved residues and were strongly predicted to affect proofreading. Consistent with this, POLE-mutant tumours were hypermutated, with a high frequency of base substitutions, and an especially large relative excess of G:C>T:A transversions. All POLE EDM tumours were microsatellite stable, suggesting that defects in either DNA proofreading or MMR provide alternative mechanisms to achieve genomic instability and tumourigenesis. PMID:23528559

Aging impairs double-strand break repair by homologous recombination in Drosophila germ cells.

PubMed

Delabaere, Laetitia; Ertl, Henry A; Massey, Dashiell J; Hofley, Carolyn M; Sohail, Faraz; Bienenstock, Elisa J; Sebastian, Hans; Chiolo, Irene; LaRocque, Jeannine R

2017-04-01

Aging is characterized by genome instability, which contributes to cancer formation and cell lethality leading to organismal decline. The high levels of DNA double-strand breaks (DSBs) observed in old cells and premature aging syndromes are likely a primary source of genome instability, but the underlying cause of their formation is still unclear. DSBs might result from higher levels of damage or repair defects emerging with advancing age, but repair pathways in old organisms are still poorly understood. Here, we show that premeiotic germline cells of young and old flies have distinct differences in their ability to repair DSBs by the error-free pathway homologous recombination (HR). Repair of DSBs induced by either ionizing radiation (IR) or the endonuclease I-SceI is markedly defective in older flies. This correlates with a remarkable reduction in HR repair measured with the DR-white DSB repair reporter assay. Strikingly, most of this repair defect is already present at 8 days of age. Finally, HR defects correlate with increased expression of early HR components and increased recruitment of Rad51 to damage in older organisms. Thus, we propose that the defect in the HR pathway for germ cells in older flies occurs following Rad51 recruitment. These data reveal that DSB repair defects arise early in the aging process and suggest that HR deficiencies are a leading cause of genome instability in germ cells of older animals. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Direct detection of methylation in genomic DNA

PubMed Central

Bart, A.; van Passel, M. W. J.; van Amsterdam, K.; van der Ende, A.

2005-01-01

The identification of methylated sites on bacterial genomic DNA would be a useful tool to study the major roles of DNA methylation in prokaryotes: distinction of self and nonself DNA, direction of post-replicative mismatch repair, control of DNA replication and cell cycle, and regulation of gene expression. Three types of methylated nucleobases are known: N6-methyladenine, 5-methylcytosine and N4-methylcytosine. The aim of this study was to develop a method to detect all three types of DNA methylation in complete genomic DNA. It was previously shown that N6-methyladenine and 5-methylcytosine in plasmid and viral DNA can be detected by intersequence trace comparison of methylated and unmethylated DNA. We extended this method to include N4-methylcytosine detection in both in vitro and in vivo methylated DNA. Furthermore, application of intersequence trace comparison was extended to bacterial genomic DNA. Finally, we present evidence that intrasequence comparison suffices to detect methylated sites in genomic DNA. In conclusion, we present a method to detect all three natural types of DNA methylation in bacterial genomic DNA. This provides the possibility to define the complete methylome of any prokaryote. PMID:16091626

Mutational signatures of non-homologous and polymerase theta-mediated end-joining in embryonic stem cells.

PubMed

Schimmel, Joost; Kool, Hanneke; van Schendel, Robin; Tijsterman, Marcel

2017-12-15

Cells employ potentially mutagenic DNA repair mechanisms to avoid the detrimental effects of chromosome breaks on cell survival. While classical non-homologous end-joining (cNHEJ) is largely error-free, alternative end-joining pathways have been described that are intrinsically mutagenic. Which end-joining mechanisms operate in germ and embryonic cells and thus contribute to heritable mutations found in congenital diseases is, however, still largely elusive. Here, we determined the genetic requirements for the repair of CRISPR/Cas9-induced chromosomal breaks of different configurations, and establish the mutational consequences. We find that cNHEJ and polymerase theta-mediated end-joining (TMEJ) act both parallel and redundant in mouse embryonic stem cells and account for virtually all end-joining activity. Surprisingly, mutagenic repair by polymerase theta (Pol θ, encoded by the Polq gene) is most prevalent for blunt double-strand breaks (DSBs), while cNHEJ dictates mutagenic repair of DSBs with protruding ends, in which the cNHEJ polymerases lambda and mu play minor roles. We conclude that cNHEJ-dependent repair of DSBs with protruding ends can explain de novo formation of tandem duplications in mammalian genomes. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.

PubMed

Pećina-Šlaus, Nives; Kafka, Anja; Bukovac, Anja; Vladušić, Tomislav; Tomas, Davor; Hrašćan, Reno

2017-07-01

Postreplicative mismatch repair safeguards the stability of our genome. The defects in its functioning will give rise to microsatellite instability. In this study, 50 meningiomas were investigated for microsatellite instability. Two major mismatch repair genes, MLH1 and MSH2, were analyzed using microsatellite markers D1S1611 and BAT26 amplified by polymerase chain reaction and visualized by gel electrophoresis on high-resolution gels. Furthermore, genes DVL3 (D3S1262), AXIN1 (D16S3399), and CDH1 (D16S752) were also investigated for microsatellite instability. Our study revealed constant presence of microsatellite instability in meningioma patients when compared to their autologous blood DNA. Altogether 38% of meningiomas showed microsatellite instability at one microsatellite locus, 16% on two, and 13.3% on three loci. The percent of detected microsatellite instability for MSH2 gene was 14%, and for MLH1, it was 26%, for DVL3 22.9%, for AXIN1 17.8%, and for CDH1 8.3%. Since markers also allowed for the detection of loss of heterozygosity, gross deletions of MLH1 gene were found in 24% of meningiomas. Genetic changes between MLH1 and MSH2 were significantly positively correlated (p = 0.032). We also noted a positive correlation between genetic changes of MSH2 and DVL3 genes (p = 0.034). No significant associations were observed when MLH1 or MSH2 was tested against specific histopathological meningioma subtype or World Health Organization grade. However, genetic changes in DVL3 were strongly associated with anaplastic histology of meningioma (χ 2  = 9.14; p = 0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.

Mutational signatures reveal the role of RAD52 in p53-independent p21-driven genomic instability.

PubMed

Galanos, Panagiotis; Pappas, George; Polyzos, Alexander; Kotsinas, Athanassios; Svolaki, Ioanna; Giakoumakis, Nickolaos N; Glytsou, Christina; Pateras, Ioannis S; Swain, Umakanta; Souliotis, Vassilis L; Georgakilas, Alexandros G; Geacintov, Nicholas; Scorrano, Luca; Lukas, Claudia; Lukas, Jiri; Livneh, Zvi; Lygerou, Zoi; Chowdhury, Dipanjan; Sørensen, Claus Storgaard; Bartek, Jiri; Gorgoulis, Vassilis G

2018-03-16

Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21 WAF1/Cip1 , showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery. We now demonstrate that p21 WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities. Consequently, fewer single nucleotide substitutions (SNSs) occur, while formation of highly deleterious DNA double-strand breaks (DSBs) is enhanced, crafting a characteristic mutational signature landscape. Guided by the mutational signatures formed, we find that the DSBs are repaired by Rad52-dependent break-induced replication (BIR) and single-strand annealing (SSA) repair pathways. Conversely, the error-free synthesis-dependent strand annealing (SDSA) repair route is deficient. Surprisingly, Rad52 is activated transcriptionally in an E2F1-dependent manner, rather than post-translationally as is common for DNA repair factor activation. Our results signify the importance of mutational signatures as guides to disclose the repair history leading to genomic instability. We unveil how chronic p21 WAF1/Cip1 expression rewires the repair process and identifies Rad52 as a source of genomic instability and a candidate therapeutic target.

DNA double-strand-break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice.

PubMed

Schipler, Agnes; Iliakis, George

2013-09-01

Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice.

Absence of Mutagenic Activity of Hycanthone in Serratia marcescens,

DTIC Science & Technology

1986-05-29

repair system but is enhanced by the plasmid pKMl01, which mediates the inducible error-prone repair system. Hycanthone, like proflavin , .1...enhanced by the plasmid pKM10, which mediates the inducible error-prone repair system. Hycanthone, like proflavin , intercalates between the stacked bases...Roth (1974) lave suggested that proflavin , which has a planar triple ring structure similar to hycanthone, interacts with DNA, which upon replication

Welding technology transfer task/laser based weld joint tracking system for compressor girth welds

NASA Technical Reports Server (NTRS)

Looney, Alan

1991-01-01

Sensors to control and monitor welding operations are currently being developed at Marshall Space Flight Center. The laser based weld bead profiler/torch rotation sensor was modified to provide a weld joint tracking system for compressor girth welds. The tracking system features a precision laser based vision sensor, automated two-axis machine motion, and an industrial PC controller. The system benefits are elimination of weld repairs caused by joint tracking errors which reduces manufacturing costs and increases production output, simplification of tooling, and free costly manufacturing floor space.

Caffeine enhances real-world language processing: evidence from a proofreading task.

PubMed

Brunyé, Tad T; Mahoney, Caroline R; Rapp, David N; Ditman, Tali; Taylor, Holly A

2012-03-01

Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a commonplace language task that required readers to identify and correct 4 error types in extended discourse: simple local errors (misspelling 1- to 2-syllable words), complex local errors (misspelling 3- to 5-syllable words), simple global errors (incorrect homophones), and complex global errors (incorrect subject-verb agreement and verb tense). In 2 placebo-controlled, double-blind studies using repeated-measures designs, we found higher detection and repair rates for complex global errors, asymptoting at 200 mg in low consumers (Experiment 1) and peaking at 400 mg in high consumers (Experiment 2). In both cases, covariate analyses demonstrated that arousal state mediated the relationship between caffeine consumption and the detection and repair of complex global errors. Detection and repair rates for the other 3 error types were not affected by caffeine consumption. Taken together, we demonstrate that caffeine has differential effects on error detection and repair as a function of dose and error type, and this relationship is closely tied to caffeine's effects on subjective arousal state. These results support the notion that central nervous system stimulants may enhance global processing of language-based materials and suggest that such effects may originate in caffeine-related right hemisphere brain processes. Implications for understanding the relationships between caffeine consumption and real-world cognitive functioning are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Role of Double-Strand Break End-Tethering during Gene Conversion in Saccharomyces cerevisiae

PubMed Central

Haber, James E.

2016-01-01

Correct repair of DNA double-strand breaks (DSBs) is critical for maintaining genome stability. Whereas gene conversion (GC)-mediated repair is mostly error-free, repair by break-induced replication (BIR) is associated with non-reciprocal translocations and loss of heterozygosity. We have previously shown that a Recombination Execution Checkpoint (REC) mediates this competition by preventing the BIR pathway from acting on DSBs that can be repaired by GC. Here, we asked if the REC can also determine whether the ends that are engaged in a GC-compatible configuration belong to the same break, since repair involving ends from different breaks will produce potentially deleterious translocations. We report that the kinetics of repair are markedly delayed when the two DSB ends that participate in GC belong to different DSBs (termed Trans) compared to the case when both DSB ends come from the same break (Cis). However, repair in Trans still occurs by GC rather than BIR, and the overall efficiency of repair is comparable. Hence, the REC is not sensitive to the “origin” of the DSB ends. When the homologous ends for GC are in Trans, the delay in repair appears to reflect their tethering to sequences on the other side of the DSB that themselves recombine with other genomic locations with which they share sequence homology. These data support previous observations that the two ends of a DSB are usually tethered to each other and that this tethering facilitates both ends encountering the same donor sequence. We also found that the presence of homeologous/repetitive sequences in the vicinity of a DSB can distract the DSB end from finding its bona fide homologous donor, and that inhibition of GC by such homeologous sequences is markedly increased upon deleting Sgs1 but not Msh6. PMID:27074148

DNA double-strand–break complexity levels and their possible contributions to the probability for error-prone processing and repair pathway choice

PubMed Central

Schipler, Agnes; Iliakis, George

2013-01-01

Although the DNA double-strand break (DSB) is defined as a rupture in the double-stranded DNA molecule that can occur without chemical modification in any of the constituent building blocks, it is recognized that this form is restricted to enzyme-induced DSBs. DSBs generated by physical or chemical agents can include at the break site a spectrum of base alterations (lesions). The nature and number of such chemical alterations define the complexity of the DSB and are considered putative determinants for repair pathway choice and the probability that errors will occur during this processing. As the pathways engaged in DSB processing show distinct and frequently inherent propensities for errors, pathway choice also defines the error-levels cells opt to accept. Here, we present a classification of DSBs on the basis of increasing complexity and discuss how complexity may affect processing, as well as how it may cause lethal or carcinogenic processing errors. By critically analyzing the characteristics of DSB repair pathways, we suggest that all repair pathways can in principle remove lesions clustering at the DSB but are likely to fail when they encounter clusters of DSBs that cause a local form of chromothripsis. In the same framework, we also analyze the rational of DSB repair pathway choice. PMID:23804754

IPTV multicast with peer-assisted lossy error control

NASA Astrophysics Data System (ADS)

Li, Zhi; Zhu, Xiaoqing; Begen, Ali C.; Girod, Bernd

2010-07-01

Emerging IPTV technology uses source-specific IP multicast to deliver television programs to end-users. To provide reliable IPTV services over the error-prone DSL access networks, a combination of multicast forward error correction (FEC) and unicast retransmissions is employed to mitigate the impulse noises in DSL links. In existing systems, the retransmission function is provided by the Retransmission Servers sitting at the edge of the core network. In this work, we propose an alternative distributed solution where the burden of packet loss repair is partially shifted to the peer IP set-top boxes. Through Peer-Assisted Repair (PAR) protocol, we demonstrate how the packet repairs can be delivered in a timely, reliable and decentralized manner using the combination of server-peer coordination and redundancy of repairs. We also show that this distributed protocol can be seamlessly integrated with an application-layer source-aware error protection mechanism called forward and retransmitted Systematic Lossy Error Protection (SLEP/SLEPr). Simulations show that this joint PARSLEP/ SLEPr framework not only effectively mitigates the bottleneck experienced by the Retransmission Servers, thus greatly enhancing the scalability of the system, but also efficiently improves the resistance to the impulse noise.

Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1

PubMed Central

Cantor, Sharon B; Guillemette, Shawna

2011-01-01

It is clear that FANCJ, also known as BACH1 or BRIP1, is an essential tumor suppressor gene based on the identification of clinically relevant mutations not only in breast cancer, but also the childhood cancer syndrome, Fanconi anemia. This conclusion is further supported by the direct and functional interaction between FANCJ and the hereditary breast cancer-associated gene product BRCA1. In the absence of the FANCJ DNA helicase or its interaction with BRCA1, cells have defects in several aspects of the DNA damage response. In particular, the BRCA1–FANCJ interaction is essential for promoting error-free repair, checkpoint control and for limiting DNA damage tolerance. As the number of FANCJ clinical mutations and affected patients accumulate, it will be critical to understand whether the associated tumors resemble BRCA-associated tumors. If so, FANCJ patients could also benefit from new therapies that selectively sensitize DNA repair-defective tumors and spare healthy cells. In this article, we summarize the breast cancer-associated FANCJ mutations and discuss functional outcomes for DNA repair and tumor suppression. PMID:21345144

Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage

PubMed Central

Rao, Timsi; Gao, Rui; Takada, Saeko; Al Abo, Muthana; Chen, Xiang; Walters, Kylie J.; Pommier, Yves; Aihara, Hideki

2016-01-01

Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5′-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA–Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. PMID:27543075

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

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

Dong, Hui; Shi, Qiong; Song, Xiufang

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observedmore » phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

Working memory capacity and self-repair behavior in first and second language oral production.

PubMed

Mojavezi, Ahmad; Ahmadian, Mohammad Javad

2014-06-01

This study explores the relationship between working memory capacity and self-repair behavior in first (L1) and second language (L2) oral production. 40 Iranian intermediate EFL learners participated in this study. Their working memory capacity was measured via a version of listening span test. The participants performed two oral narrative tasks, one in their L2 (English) and one in their L1 (Farsi). Then, they were asked to listen to their own narrations and comment on the repairs they made in their speech. Self-repairs were analyzed and categorized taking into account the participants' stimulated recall comments. Results of the analyses pointed to positive correlations between the participants' working memory capacity and self-repairs in the L2 but not in the L1. Also, results revealed that whereas in the case of L1, the participants effectuated different-information and appropriacy repairs more than error-repairs, in the case of L2 more error-repairs were made.

Mitotic effects of monochromatic ultraviolet radiation at 225, 265, and 280 nm on eleven stages of the cell cycle of the grasshopper neuroblast in culture. I. Overall retardation from the stage irradiated to nuclear membrane breakdown

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

Carlson, J.G.

1976-10-01

Neuroblasts of Chortophaga viridifasciata (DeGeer) in culture were exposed to different doses of 225, 265, or 280 nm ultraviolet radiations at 11 different stages and substages of the mitotic cycle and individually selected cells were timed to breakdown of the nuclear membrane. Comparisons of the effectiveness of different wavelengths on the different stages were based on the dose that reduced the cell progression rate to 67 percent of normal (D/sub 67/) and the slope of the regression line, i.e., the control to treated time (C/T) ratio change/erg/mm/sup 2/ at the D/sub 67/ level. Cells of the prereplication period (metaphase +more » anaphase + early telophase) and the S phase (middle and late telophase + interphase + very early prophase) are equally sensitive to uv and contrast sharply with the much lower sensitivity of those in the postreplication period (early and middle prophase). This can best be interpreted if chromosomal DNA is the chromophore for uv-induced mitotic retardation. Cells in the prereplication period at exposure show no wavelength effect. In the S phase all stages except middle telophase and all stages combined are significantly more sensitive to 265 and 280 nm than to 225 nm. Of the postreplication stages, early prophase is retarded significantly more by 280 than by 225 or 265 nm. The C/T ratio/erg/mm/sup 2/ is greater after exposure to 265 nm at all prereplication and replication stages, but exhibits no consistent wavelength pattern during the postreplication period. Evidence based on the orientation of the neuroblast with respect to the uv-source suggests that the chromophore for mitotic retardation does not reside within the centrosome and related structures, but may be present, at least partly, in the nucleolus.« less

Psycho-Motor and Error Enabled Simulations: Modeling Vulnerable Skills in the Pre-Mastery Phase Medical Practice Initiative Procedural Skill Decay and Maintenance (MPI-PSD)

DTIC Science & Technology

2014-04-01

laparoscopic ventral hernia repair. Additional simulation stations were added to the standards and purchases (including a motion tracking system) were...framework for laparoscopic ventral hernia; Incorporation of error-based simulators into an exit assessment of chief surgical residents; Development of...simulating a laparoscopic ventral hernia (LVH) repair. Based on collected data, the lab worked to finalize the incorporation of error-based simulators

The Spectrum of Replication Errors in the Absence of Error Correction Assayed Across the Whole Genome of Escherichia coli.

PubMed

Niccum, Brittany A; Lee, Heewook; MohammedIsmail, Wazim; Tang, Haixu; Foster, Patricia L

2018-06-15

When the DNA polymerase that replicates the Escherichia coli chromosome, DNA Pol III, makes an error, there are two primary defenses against mutation: proofreading by the epsilon subunit of the holoenzyme and mismatch repair. In proofreading deficient strains, mismatch repair is partially saturated and the cell's response to DNA damage, the SOS response, may be partially induced. To investigate the nature of replication errors, we used mutation accumulation experiments and whole genome sequencing to determine mutation rates and mutational spectra across the entire chromosome of strains deficient in proofreading, mismatch repair, and the SOS response. We report that a proofreading-deficient strain has a mutation rate 4,000-fold greater than wild-type strains. While the SOS response may be induced in these cells, it does not contribute to the mutational load. Inactivating mismatch repair in a proofreading-deficient strain increases the mutation rate another 1.5-fold. DNA polymerase has a bias for converting G:C to A:T base pairs, but proofreading reduces the impact of these mutations, helping to maintain the genomic G:C content. These findings give an unprecedented view of how polymerase and error-correction pathways work together to maintain E. coli' s low mutation rate of 1 per thousand generations. Copyright © 2018, Genetics.

EUVL Mask Blank Repair

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

Barty, A; Mirkarimi, P; Stearns, D G

2002-05-22

EUV mask blanks are fabricated by depositing a reflective Mo/Si multilayer film onto super-polished substrates. Small defects in this thin film coating can significantly alter the reflected field and introduce defects in the printed image. Ideally one would want to produce defect-free mask blanks; however, this may be very difficult to achieve in practice. One practical way to increase the yield of mask blanks is to effectively repair multilayer defects, and to this effect they present two complementary defect repair strategies for use on multilayer-coated EUVL mask blanks. A defect is any area on the mask which causes unwanted variationsmore » in EUV dose in the aerial image obtained in a printing tool, and defect repair is correspondingly defined as any strategy that renders a defect unprintable during exposure. The term defect mitigation can be adopted to describe any strategy which renders a critical defect non-critical when printed, and in this regard a non-critical defect is one that does not adversely affect device function. Defects in the patterned absorber layer consist of regions where metal, typically chrome, is unintentionally added or removed from the pattern leading to errors in the reflected field. There currently exists a mature technology based on ion beam milling and ion beam assisted deposition for repairing defects in the absorber layer of transmission lithography masks, and it is reasonable to expect that this technology will be extended to the repair of absorber defects in EUVL masks. However, techniques designed for the repair of absorber layers can not be directly applied to the repair of defects in the mask blank, and in particular the multilayer film. In this paper they present for the first time a new technique for the repair of amplitude defects as well as recent results on the repair of phase defects.« less

[Transplantation of free latissimus dorsimyocutaneous flaps for repairing head and neck defect after tumor resection].

PubMed

Chen, Jin; Wang, Zhaohui; Tang, Tao; Li, Chunhua; Cai, Yongcong

2015-12-01

To explore the value of free latissimus dorsimyocutaneous flap in repairing severe defect of head and neck after resection of tumor. Free latissimus dorsimyocutaneous flap was used to repair defect after resection of tumor in 12 patients (13 sides) with head and neck tumors. Of them 2 cases underwent radical radiotherapy before operation. and 3 cases received adjuvant radiotherapy postoperatively. Aside from one flap with necrosis, other 12 flaps survived after operation including 5 cases with radiotherapy. Free latissimus dorsimyocutaneous flap can afford large tissue, has reliable blood supply, is easy to survive, and resist to radiotherapy, which is fit for repairing severe defect of head and neck.

Laser microbeams for DNA damage induction, optical tweezers for the search on blood pressure relaxing drugs: contributions to ageing research

NASA Astrophysics Data System (ADS)

Grigaravicius, P.; Monajembashi, S.; Hoffmann, M.; Altenberg, B.; Greulich, K. O.

2009-08-01

One essential cause of human ageing is the accumulation of DNA damages during lifetime. Experimental studies require quantitative induction of damages and techniques to visualize the subsequent DNA repair. A new technique, the "immuno fluorescent comet assay", is used to directly visualize DNA damages in the microscope. Using DNA repair proteins fluorescently labeled with green fluorescent protein, it could be shown that the repair of the most dangerous DNA double strand breaks starts with the inaccurate "non homologous end joining" pathway and only after 1 - 1 ½ minutes may switch to the more accurate "homologous recombination repair". One might suggest investigating whether centenarians use "homologous recombination repair" differently from those ageing at earlier years and speculate whether it is possible, for example by nutrition, to shift DNA repair to a better use of the error free pathway and thus promote healthy ageing. As a complementary technique optical tweezers, and particularly its variant "erythrocyte mediated force application", is used to simulate the effects of blood pressure on HUVEC cells representing the inner lining of human blood vessels. Stimulating one cell induces in the whole neighbourhood waves of calcium and nitric oxide, known to relax blood vessels. NIFEDIPINE and AMLODIPINE, both used as drugs in the therapy of high blood pressure, primarily a disease of the elderly, prolong the availability of nitric oxide. This partially explains their mode of action. In contrast, VERAPAMILE, also a blood pressure reducing drug, does not show this effect, indicating that obviously an alternative mechanism must be responsible for vessel relaxation.

A defect in homologous recombination leads to increased translesion synthesis in E. coli

PubMed Central

Naiman, Karel; Pagès, Vincent; Fuchs, Robert P.

2016-01-01

DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli. In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the ‘SOS signal’. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. PMID:27257075

Investigating Deinococcus radiodurans RecA protein filament formation on dsDNA by a real-time single-molecule approach

PubMed Central

Hsu, Hsin-Fang; Ngo, Khanh V.; Chitteni-Pattu, Sindhu; Cox, Michael M.; Li, Hung-Wen

2011-01-01

With the aid of an efficient, precise, and almost error-free DNA repair system, Deinococcus radiodurans can survive hundreds of double strand breaks inflicted by high doses of irradiation or desiccation. The RecA of Deinococcus radiodurans (DrRecA) plays a central role both in the early phase of repair by an extended synthesis-dependent strand annealing process and in the later more general homologous recombination phase. Both roles likely require DrRecA filament formation on duplex DNA. We have developed single-molecule tethered particle motion (TPM) experiments to study the assembly dynamics of RecA proteins on individual duplex DNA molecules by observing changes in DNA tether length resulting from RecA binding. We demonstrate that DrRecA nucleation on dsDNA is much faster than Escherichia coli (Ec) RecA protein, but the extension is slower. This combination of attributes would tend to increase the number and decrease the length of DrRecA filaments relative to those of EcRecA, a feature that may reflect the requirement to repair hundreds of genomic double strand breaks concurrently in irradiated Deinococcus cells. PMID:21853996

The Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex promotes trinucleotide repeat expansions independently of homologous recombination.

PubMed

Ye, Yanfang; Kirkham-McCarthy, Lucy; Lahue, Robert S

2016-07-01

Trinucleotide repeats (TNRs) are tandem arrays of three nucleotides that can expand in length to cause at least 17 inherited human diseases. Somatic expansions in patients can occur in differentiated tissues where DNA replication is limited and cannot be a primary source of somatic mutation. Instead, mouse models of TNR diseases have shown that both inherited and somatic expansions can be suppressed by the loss of certain DNA repair factors. It is generally believed that these repair factors cause misprocessing of TNRs, leading to expansions. Here we extend this idea to show that the Mre11-Rad50-Xrs2 (MRX) complex of Saccharomyces cerevisiae is a causative factor in expansions of short TNRs. Mutations that eliminate MRX subunits led to significant suppression of expansions whereas mutations that inactivate Rad51 had only a minor effect. Coupled with previous evidence, this suggests that MRX drives expansions of short TNRs through a process distinct from homologous recombination. The nuclease function of Mre11 was dispensable for expansions, suggesting that expansions do not occur by Mre11-dependent nucleolytic processing of the TNR. Epistasis between MRX and post-replication repair (PRR) was tested. PRR protects against expansions, so a rad5 mutant gave a high expansion rate. In contrast, the mre11 rad5 double mutant gave a suppressed expansion rate, indistinguishable from the mre11 single mutant. This suggests that MRX creates a TNR substrate for PRR. Protein acetylation was also tested as a mechanism regulating MRX activity in expansions. Six acetylation sites were identified in Rad50. Mutation of all six lysine residues to arginine gave partial bypass of a sin3 HDAC mutant, suggesting that Rad50 acetylation is functionally important for Sin3-mediated expansions. Overall we conclude that yeast MRX helps drive expansions of short TNRs by a mechanism distinct from its role in homologous recombination and independent of the nuclease function of Mre11. Copyright © 2016 Elsevier B.V. All rights reserved.

Alternative end-joining repair pathways are the ultimate backup for abrogated classical non-homologous end-joining and homologous recombination repair: Implications for the formation of chromosome translocations.

PubMed

Iliakis, George; Murmann, Tamara; Soni, Aashish

2015-11-01

DNA double strand breaks (DSB) are the most deleterious lesions for the integrity of the genome, as their misrepair can lead to the formation of chromosome translocations. Cells have evolved two main repair pathways to suppress the formation of these genotoxic lesions: homology-dependent, error-free homologous recombination repair (HRR), and potentially error-prone, classical, DNA-PK-dependent non-homologous end-joining (c-NHEJ). The most salient feature of c-NHEJ, speed, will largely suppress chromosome translocation formation, while sequence alterations at the junction remain possible. It is now widely accepted that when c-NHEJ is inactivated, globally or locally, an alternative form of end-joining (alt-EJ) removes DSBs. Alt-EJ operates with speed and fidelity markedly lower than c-NHEJ, causing thus with higher probability chromosome translocations, and generating more extensive sequence alterations at the junction. Our working hypothesis is that alt-EJ operates as a backup to c-NHEJ. Recent results show that alt-EJ can also backup abrogated HRR in G2 phase cells, again at the cost of elevated formation of chromosome translocations. These observations raise alt-EJ to a global rescuing mechanism operating on ends that have lost their chromatin context in ways that compromise processing by HRR or c-NHEJ. While responsible for eliminating from the genome highly cytotoxic DNA ends, alt-EJ provides this function at the price of increased translocation formation. Here, we analyze recent literature on the mechanisms of chromosome translocation formation and propose a functional hierarchy among DSB processing pathways that makes alt-EJ the global backup pathway. We discuss possible ramifications of this model in cellular DSB management and pathway choice, and analyze its implications in radiation carcinogenesis and the design of novel therapeutic approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation Aspects of Building Structures Reconstructed After a Failure or Catastrophe

NASA Astrophysics Data System (ADS)

Krentowski, Janusz R.; Knyziak, Piotr

2017-10-01

The article presents the characteristics of several steel structures, among others modernized industrial dye house, school sports hall, truck repair workshop, that have been rebuilt after a disaster or a catastrophe. The structures were analyzed in detail, and the evaluation and reconstruction processes were described. The emergencies that occurred during exploitation of the buildings were the result of multiple mistakes: incorrectly defined intervals between inspections, errors during periodic inspections, incorrect repair work recommendations. The concepts of reinforcement work implemented by the authors, enabling the long-term future failure-free operation of the objects, were presented. Recommendations for monitoring of the facilities, applied after reinforcement or reconstruction, have been formulated. The methodology for the implementation of specialized investigations, such as geodetic, optical, geological, chemical strength tests, both destructive and non-destructive, has been defined. The need to determine the limit values of deformations, deflections, damage or other faults of structural elements and the entire rebuilt facilities, as well as defining conditions for objects’ withdrawal from operation in subsequent exceptional situations was indicated.

The nature of articulation errors in Egyptian Arabic-speaking children with velopharyngeal insufficiency due to cleft palate.

PubMed

Abou-Elsaad, Tamer; Baz, Hemmat; Afsah, Omayma; Mansy, Alzahraa

2015-09-01

Even with early surgical repair, the majority of cleft palate children demonstrate articulation errors and have typical cleft palate speech. Was to determine the nature of articulation errors of Arabic consonants in Egyptian Arabic-speaking children with velopharyngeal insufficiency (VPI). Thirty Egyptian Arabic-speaking children with VPI due to cleft palate (whether primary repaired or secondary repaired) were studied. Auditory perceptual assessment (APA) of children speech was conducted. Nasopharyngoscopy was done to assess the velopharyngeal port (VPP) movements while the child was repeating speech tasks. Mansoura Arabic Articulation test (MAAT) was performed to analyze the consonants articulation of these children. The most frequent type of articulatory errors observed was substitution, more specifically, backing. Pharyngealization of anterior fricatives was the most frequent substitution, especially for the /s/ sound. The most frequent substituting sounds for other sounds were /ʔ/ followed by /k/ and /n/ sounds. Significant correlations were found between the degrees of the open nasality and VPP closure and the articulation errors. On the other hand, the sounds (/ʔ/,/ħ/,/ʕ/,/n/,/w/,/j/) were normally articulated in all studied group. The determination of articulation errors in VPI children could guide the therapists for designing appropriate speech therapy programs for these cases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The identification and repair of anomalous measurements in the measurement of big diameter based on rolling-wheel method

NASA Astrophysics Data System (ADS)

Chen, Haiou; Yu, Xiaofen

2011-05-01

Rolling-wheel method is an effective way of measuring big diameter. After amending the temperature error and pressure error, the uncertainty of measurement can not be φ =5um/m stably because of the influence of skid. The traditional method of identifying skid loses sight of the influences of the unstable motor speed, the appearance form error and the eccentric of installation of the big axis and rolling wheel and so on, so the method has its limitation. In this paper, a new method of multiple identification and repair is introduced, namely n diameters are measured and Chauvenet standard is used for identifying the anomalous measurements one by one, and then the average value of the remaining data is used for repairing identified anomalous measurements, and the next round identification and repair is carried out until the accuracy requirement of the measurement is satisfied. The result of experiments indicates that the method can identify anomalous measurements whose offsets caused by the skid are greater than 0.2φ , and the uncertainty of measurement has improved substantially.

Characterizing quantum channels with non-separable states of classical light

NASA Astrophysics Data System (ADS)

Ndagano, Bienvenu; Perez-Garcia, Benjamin; Roux, Filippus S.; McLaren, Melanie; Rosales-Guzman, Carmelo; Zhang, Yingwen; Mouane, Othmane; Hernandez-Aranda, Raul I.; Konrad, Thomas; Forbes, Andrew

2017-04-01

High-dimensional entanglement with spatial modes of light promises increased security and information capacity over quantum channels. Unfortunately, entanglement decays due to perturbations, corrupting quantum links that cannot be repaired without performing quantum tomography on the channel. Paradoxically, the channel tomography itself is not possible without a working link. Here we overcome this problem with a robust approach to characterize quantum channels by means of classical light. Using free-space communication in a turbulent atmosphere as an example, we show that the state evolution of classically entangled degrees of freedom is equivalent to that of quantum entangled photons, thus providing new physical insights into the notion of classical entanglement. The analysis of quantum channels by means of classical light in real time unravels stochastic dynamics in terms of pure state trajectories, and thus enables precise quantum error correction in short- and long-haul optical communication, in both free space and fibre.

Alternating phase-shifting masks: phase determination and impact of quartz defects--theoretical and experimental results

NASA Astrophysics Data System (ADS)

Griesinger, Uwe A.; Dettmann, Wolfgang; Hennig, Mario; Heumann, Jan P.; Koehle, Roderick; Ludwig, Ralf; Verbeek, Martin; Zarrabian, Mardjan

2002-07-01

In optical lithography balancing the aerial image of an alternating phase shifting mask (alt. PSM) is a major challenge. For the exposure wavelengths (currently 248nm and 193nm) an optimum etching method is necessary to overcome imbalance effects. Defects play an important role in the imbalances of the aerial image. In this contribution defects will be discussed by using the methodology of global phase imbalance control also for local imbalances which are a result of quartz defects. The effective phase error can be determined with an AIMS-system by measuring the CD width between the images of deep- and shallow trenches at different focus settings. The AIMS results are analyzed in comparison to the simulated and lithographic print results of the alternating structures. For the analysis of local aerial image imbalances it is necessary to investigate the capability of detecting these phase defects with state of the art inspection systems. Alternating PSMs containing programmed defects were inspected with different algorithms to investigate the capture rate of special phase defects in dependence on the defect size. Besides inspection also repair of phase defects is an important task. In this contribution we show the effect of repair on the optical behavior of phase defects. Due to the limited accuracy of the repair tools the repaired area still shows a certain local phase error. This error can be caused either by residual quartz material or a substrate damage. The influence of such repair induced phase errors on the aerial image were investigated.

Inducible error-prone repair in B. subtilis. Final report, September 1, 1979-June 30, 1981

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

Yasbin, R. E.

1981-06-01

The research performed under this contract has been concentrated on the relationship between inducible DNA repair systems, mutagenesis and the competent state in the gram positive bacterium Bacillus subtilis. The following results have been obtained from this research: (1) competent Bacillus subtilis cells have been developed into a sensitive tester system for carcinogens; (2) competent B. subtilis cells have an efficient excision-repair system, however, this system will not function on bacteriophage DNA taken into the cell via the process of transfection; (3) DNA polymerase III is essential in the mechanism of the process of W-reactivation; (4) B. subtilis strains curedmore » of their defective prophages have been isolated and are now being developed for gene cloning systems; (5) protoplasts of B. subtilis have been shown capable of acquiring DNA repair enzymes (i.e., enzyme therapy); and (6) a plasmid was characterized which enhanced inducible error-prone repair in a gram positive organism.« less

Comparison between single-row and double-row rotator cuff repair: a biomechanical study.

PubMed

Milano, Giuseppe; Grasso, Andrea; Zarelli, Donatella; Deriu, Laura; Cillo, Mario; Fabbriciani, Carlo

2008-01-01

The aim of this study was to compare the mechanical behavior under cyclic loading test of single-row and double-row rotator cuff repair with suture anchors in an ex-vivo animal model. For the present study, 50 fresh porcine shoulders were used. On each shoulder, a crescent-shaped full-thickness tear of the infraspinatus was performed. Width of the tendon tear was 2 cm. The lesion was repaired using metal suture anchors. Shoulders were divided in four groups, according the type of repair: single-row tension-free repair (Group 1); single-row tension repair (Group 2); double-row tension-free repair (Group 3); double-row tension repair (Group 4); and a control group. Specimens were subjected to a cyclic loading test. Number of cycles at 5 mm of elongation and at failure, and total elongation were calculated. Single-row tension repair showed significantly poorest results for all the variables considered, when compared with the other groups. Regarding the mean number of cycles at 5 mm of elongation and at failure, there was a nonsignificant difference between Groups 3 and 4, and both of them were significantly greater than Group 1. For mean total elongation, the difference between Groups 1, 3, and 4 was not significant, but all of them were significantly lower than the control group. A single-row repair is particularly weak when performed under tension. Double-row repair is significantly more resistant to cyclic displacement than single-row repair in both tension-free and tension repair. Double-row repair technique can be primarily considered for large, unstable rotator cuff tears to improve mechanical strength of primary fixation of tendons to bone.

Comparison of shrinkage related properties of various patch repair materials

NASA Astrophysics Data System (ADS)

Kristiawan, S. A.; Fitrianto, R. S.

2017-02-01

A patch repair material has been developed in the form of unsaturated polyester resin (UPR)-mortar. The performance and durability of this material are governed by its compatibility with the concrete being repaired. One of the compatibility issue that should be tackled is the dimensional compatibility as a result of differential shrinkage between the repair material and the concrete substrate. This research aims to evaluate such shrinkage related properties of UPR-mortar and to compare with those of other patch repair materials. The investigation includes the following aspects: free shrinkage, resistance to delamination and cracking. The results indicate that UPR-mortar poses a lower free shrinkage, lower risk of both delamination and cracking tendency in comparison to other repair materials.

Inhibition of nonhomologous end joining to increase the specificity of CRISPR/Cas9 genome editing.

PubMed

Vartak, Supriya V; Raghavan, Sathees C

2015-11-01

DNA repair, one of the fundamental processes occurring in a cell, safeguards the genome and maintains its integrity. Among various DNA lesions, double-strand breaks are considered to be the most deleterious, as they can lead to potential loss of genetic information, if not repaired. Nonhomologous end joining (NHEJ) and homologous recombination are two major double-strand break repair pathways. SCR7, a DNA ligase IV inhibitor, was recently identified and characterized as a potential anticancer compound. Interestingly, SCR7 was shown to have several applications, owing to its unique property as an NHEJ inhibitor. Here, we focus on three main areas of research in which SCR7 is actively being used, and discuss one of the applications, i.e. genome editing via CRISPR/Cas, in detail. In the past year, different studies have shown that SCR7 significantly increases the efficiency of precise genome editing by inhibiting NHEJ, and favouring the error-free homologous recombination pathway, both in vitro and in vivo. Overall, we discuss the current applications of SCR7 to shed light on the unique property of the small molecule of having distinct applications in normal and cancer cells, when used at different cellular concentrations. © 2015 FEBS.

Reproduce and die! Why aging? Part II.

PubMed

Schuiling, Gerard A

2005-06-01

Whilst in part I of this diptych on aging the question why aging exists at all is discussed; this part deals with the question which mechanisms underly aging and, ultimately, dying. It appears that aging is not just an active process as such--although all kinds of internal (e.g., oxigen-free radicals) and external (e.g., UV radiation; disease) actively damage the organism--but more a passive one: it is mainly the result of a diminishing capacity to resist damaging internal and external influences, notably the capacity to repair the ensuing damage of DNA, until, indeed, the genome is entirely beyond repair and all kinds of vital functions detoriate with as a result that, in the end, the body collapses due to some final internal (e.g., a neoplasm or a CVA) or external (e.g., some infection, accident or attack) push. The time-course with which the capacity to repair DNA diminishes, however, is genetically fixed, and is associated with (even determined by) the reproductive strategy of the species in question: once the phase of reproduction is over, the reins are loosened and all kinds of genetic and physiological errors accumulate, giving rise to a large variety of pathology which ultimately carries the pertinent individual to the grave.

Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals.

PubMed

Spampinato, Claudia P

2017-05-01

The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.

Technique and outcomes of laparoscopic bulge repair after abdominal free flap reconstruction.

PubMed

Lee, Johnson C; Whipple, Lauren A; Binetti, Brian; Singh, T Paul; Agag, Richard

2016-01-21

Bulges and hernias after abdominal free flap surgery are uncommon with rates ranging from as low as 0-36%. In the free flap breast reconstruction population, there are no clear guidelines or optimal strategies to treating postoperative bulges. We describe our minimally invasive technique and outcomes in managing bulge complications in abdominal free flap breast reconstruction patients. A retrospective review was performed on all abdominal free flap breast reconstruction patients at Albany Medical Center from 2011 to 2014. All patients with bulges on clinical exam underwent abdominal CT imaging prior to consultation with a minimally invasive surgeon. Confirmed symptomatic bulges were repaired laparoscopically and patients were monitored regularly in the outpatient setting. Sixty-two patients received a total of 80 abdominal free flap breast reconstructions. Flap types included 41 deep inferior epigastric perforator (DIEP), 36 muscle-sparing transverse rectus abdominus myocutaneous (msTRAM), 2 superficial inferior epigastric artery, and 1 transverse rectus abdominus myocutaneous flap. There were a total of 9 (14.5%) bulge complications, with the majority of patients having undergone msTRAM or DIEP reconstruction. There were no complications, revisions, or recurrences from laparoscopic bulge repair after an average follow-up of 181 days. Although uncommon, bulge formation after abdominal free flap reconstruction can create significant morbidity to patients. Laproscopic hernia repair using composite mesh underlay offers an alternative to traditional open hernia repair and can be successfully used to minimize scarring, infection, and pain to free flap patients who have already undergone significant reconstructive procedures. © 2016 Wiley Periodicals, Inc. Microsurgery, 2016. © 2016 Wiley Periodicals, Inc.

Making Sense of Missense in the Lynch Syndrome: The Clinical Perspective

PubMed Central

Lynch, Henry T.; Jascur, Thomas; Lanspa, Stephen; Boland, C. Richard

2010-01-01

The DNA mismatch repair system provides critical genetic housekeeping, and its failure is associated with tumorigenesis. Through distinct domains on the DNA mismatch repair proteins, the system recognizes and repairs errors occurring during DNA synthesis, but signals apoptosis when the DNA damage cannot be repaired. Certain missense mutations in the mismatch repair genes can selectively alter just one of these functions. This impacts the clinical features of tumors associated with defective DNA mismatch repair activity. New work reported by Xie et al. in this issue of the journal (beginning on page XXX) adds to the understanding of DNA mismatch repair. PMID:20978117

Investigating the Inner Speech of People Who Stutter: Evidence for (and against) the Covert Repair Hypothesis

ERIC Educational Resources Information Center

Brocklehurst, Paul H.; Corley, Martin

2011-01-01

In their Covert Repair Hypothesis, Postma and Kolk (1993) suggest that people who stutter make greater numbers of phonological encoding errors, which are detected during the monitoring of inner speech and repaired, with stuttering-like disfluencies as a consequence. Here, we report an experiment that documents the frequency with which such errors…

From classical mutagenesis to nuclease-based breeding - directing natural DNA repair for a natural end-product.

PubMed

Pacher, Michael; Puchta, Holger

2017-05-01

Production of mutants of crop plants by the use of chemical or physical genotoxins has a long tradition. These factors induce the natural DNA repair machinery to repair damage in an error-prone way. In the case of radiation, multiple double-strand breaks (DSBs) are induced randomly in the genome, leading in very rare cases to a desirable phenotype. In recent years the use of synthetic, site-directed nucleases (SDNs) - also referred to as sequence-specific nucleases - like the CRISPR/Cas system has enabled scientists to use exactly the same naturally occurring DNA repair mechanisms for the controlled induction of genomic changes at pre-defined sites in plant genomes. As these changes are not necessarily associated with the permanent integration of foreign DNA, the obtained organisms per se cannot be regarded as genetically modified as there is no way to distinguish them from natural variants. This applies to changes induced by DSBs as well as single-strand breaks, and involves repair by non-homologous end-joining and homologous recombination. The recent development of SDN-based 'DNA-free' approaches makes mutagenesis strategies in classical breeding indistinguishable from SDN-derived targeted genome modifications, even in regard to current regulatory rules. With the advent of new SDN technologies, much faster and more precise genome editing becomes available at reasonable cost, and potentially without requiring time-consuming deregulation of newly created phenotypes. This review will focus on classical mutagenesis breeding and the application of newly developed SDNs in order to emphasize similarities in the context of the regulatory situation for genetically modified crop plants. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants

NASA Technical Reports Server (NTRS)

Asaad, N. A.; Zeng, Z. C.; Guan, J.; Thacker, J.; Iliakis, G.

2000-01-01

The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.

Without his shirt off he saved the child from almost drowning: interpreting an uncertain input

PubMed Central

Frazier, Lyn; Clifton, Charles

2014-01-01

Unedited speech and writing often contains errors, e.g., the blending of alternative ways of expressing a message. As a result comprehenders are faced with decisions about what the speaker may have intended, which may not be the same as the grammatically-licensed compositional interpretation of what was said. Two experiments investigated the comprehension of inputs that may have resulted from blending two syntactic forms. The results of the experiments suggest that readers and listeners tend to repair such utterances, restoring them to the presumed intended structure, and they assign the interpretation of the corrected utterance. Utterances that are repaired are expected to also be acceptable when they are easy to diagnose/repair and they are “familiar”, i.e., they correspond to natural speech errors. The results of the experiments established a continuum ranging from outright linguistic illusions with no indication that listeners and readers detected the error (the inclusion of almost in A passerby rescued a child from almost being run over by a bus.), to a majority of unblended interpretations for doubled quantifier sentences (Many students often turn in their assignments late) to only a third undoubled implicit negation (I just like the way the president looks without his shirt off.) The repair or speech error reversal account offered here is contrasted with the noisy channel approach (Gibson et al., 2013) and the good enough processing approach (Ferreiera et al., 2002). PMID:25984551

A collaborative inventory model for vendor-buyer system with inspection errors, unequal sized shipment, and repairable item

NASA Astrophysics Data System (ADS)

Hamdani, Irfan Hilmi; Jauhari, Wakhid Ahmad; Rosyidi, Cucuk Nur

2017-11-01

This paper develops an integrated inventory model consisting of single-vendor and single-buyer system. The demand in buyer side is deterministic and the production process is imperfect and produces a certain number of defective items. The delivery within a single production batch from vendor to buyer is increasing by a fixed factor. After the delivery arrives at the buyer, an inspection process is conducted. The inspection process in not perfect. Errors may occur when the inspector is misclassifies a non-defective item as defective ne, or incorrectly classifies a defective item as non-defective. All the product which defective will be repair by repair-shop. After the defective arrives at repair shop, will perfect inspection. The defective item will repair and back to buyer. This model provides an optimal solution for the expected integrated total annual cost of the vendor and the buyer. The result from numerical examples shows that the integrated model will result in lower joint total cost in comparison with the equal-sized policy.

Simultaneous repair of bilateral inguinal hernias: a prospective, randomized study of open, tension-free versus laparoscopic approach.

PubMed

Sarli, L; Iusco, D R; Sansebastiano, G; Costi, R

2001-08-01

No randomized trial exists that specifically addresses the issue of laparoscopic bilateral inguinal hernia repair. The purpose of the present prospective, randomized, controlled, clinical study was to assess short- and long-term results when comparing simultaneous bilateral hernia repair by an open, tension-free anterior approach with laparoscopic "bikini mesh" posterior repair. Forty-three low-risk male patients with bilateral primary inguinal hernia were randomly assigned to undergo either laparoscopic preperitoneal "bikini mesh" hernia repair (TAPP) or open Lichtenstein hernioplasty. There was no difference in operating time between the two groups. The mean cost of laparoscopic hernioplasty was higher (P < 0.001). The intensity of postoperative pain was greater in the open hernia repair group at 24 hours, 48 hours, and 7 days after surgery (P < 0.001), with a greater consumption of pain medication among these patients (P < 0.05). The median time to return to work was 30 days for the open hernia repair group and 16 days for the laparoscopic "bikini mesh" repair group (P < 0.05). Only 1 asymptomatic recurrence (4.3%) was discovered in the open group. The laparoscopic approach to bilateral hernia with "bikini mesh" appears to be preferable to the open Lichtenstein tension-free hernioplasty in terms of the postoperative quality of life and interruption of occupational activity.

APOBEC3B cytidine deaminase targets the non-transcribed strand of tRNA genes in yeast.

PubMed

Saini, Natalie; Roberts, Steven A; Sterling, Joan F; Malc, Ewa P; Mieczkowski, Piotr A; Gordenin, Dmitry A

2017-05-01

Variations in mutation rates across the genome have been demonstrated both in model organisms and in cancers. This phenomenon is largely driven by the damage specificity of diverse mutagens and the differences in DNA repair efficiency in given genomic contexts. Here, we demonstrate that the single-strand DNA-specific cytidine deaminase APOBEC3B (A3B) damages tRNA genes at a 1000-fold higher efficiency than other non-tRNA genomic regions in budding yeast. We found that A3B-induced lesions in tRNA genes were predominantly located on the non-transcribed strand, while no transcriptional strand bias was observed in protein coding genes. Furthermore, tRNA gene mutations were exacerbated in cells where RNaseH expression was completely abolished (Δrnh1Δrnh35). These data suggest a transcription-dependent mechanism for A3B-induced tRNA gene hypermutation. Interestingly, in strains proficient in DNA repair, only 1% of the abasic sites formed upon excision of A3B-deaminated cytosines were not repaired leading to mutations in tRNA genes, while 18% of these lesions failed to be repaired in the remainder of the genome. A3B-induced mutagenesis in tRNA genes was found to be efficiently suppressed by the redundant activities of both base excision repair (BER) and the error-free DNA damage bypass pathway. On the other hand, deficiencies in BER did not have a profound effect on A3B-induced mutations in CAN1, the reporter for protein coding genes. We hypothesize that differences in the mechanisms underlying ssDNA formation at tRNA genes and other genomic loci are the key determinants of the choice of the repair pathways and consequently the efficiency of DNA damage repair in these regions. Overall, our results indicate that tRNA genes are highly susceptible to ssDNA-specific DNA damaging agents. However, increased DNA repair efficacy in tRNA genes can prevent their hypermutation and maintain both genome and proteome homeostasis. Published by Elsevier B.V.

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

PubMed Central

Weeden, Clare E.; Chen, Yunshun; Ma, Stephen B.; Hu, Yifang; Ramm, Georg; Sutherland, Kate D.; Smyth, Gordon K.

2017-01-01

Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC. PMID:28125611

Use of Single-Cysteine Variants for Trapping Transient States in DNA Mismatch Repair.

PubMed

Friedhoff, Peter; Manelyte, Laura; Giron-Monzon, Luis; Winkler, Ines; Groothuizen, Flora S; Sixma, Titia K

2017-01-01

DNA mismatch repair (MMR) is necessary to prevent incorporation of polymerase errors into the newly synthesized DNA strand, as they would be mutagenic. In humans, errors in MMR cause a predisposition to cancer, called Lynch syndrome. The MMR process is performed by a set of ATPases that transmit, validate, and couple information to identify which DNA strand requires repair. To understand the individual steps in the repair process, it is useful to be able to study these large molecular machines structurally and functionally. However, the steps and states are highly transient; therefore, the methods to capture and enrich them are essential. Here, we describe how single-cysteine variants can be used for specific cross-linking and labeling approaches that allow trapping of relevant transient states. Analysis of these defined states in functional and structural studies is instrumental to elucidate the molecular mechanism of this important DNA MMR process. © 2017 Elsevier Inc. All rights reserved.

Poly(ADP-ribose) polymerases covalently modify strand break termini in DNA fragments in vitro

PubMed Central

Talhaoui, Ibtissam; Lebedeva, Natalia A.; Zarkovic, Gabriella; Saint-Pierre, Christine; Kutuzov, Mikhail M.; Sukhanova, Maria V.; Matkarimov, Bakhyt T.; Gasparutto, Didier; Saparbaev, Murat K.; Lavrik, Olga I.; Ishchenko, Alexander A.

2016-01-01

Poly(ADP-ribose) polymerases (PARPs/ARTDs) use nicotinamide adenine dinucleotide (NAD+) to catalyse the synthesis of a long branched poly(ADP-ribose) polymer (PAR) attached to the acceptor amino acid residues of nuclear proteins. PARPs act on single- and double-stranded DNA breaks by recruiting DNA repair factors. Here, in in vitro biochemical experiments, we found that the mammalian PARP1 and PARP2 proteins can directly ADP-ribosylate the termini of DNA oligonucleotides. PARP1 preferentially catalysed covalent attachment of ADP-ribose units to the ends of recessed DNA duplexes containing 3′-cordycepin, 5′- and 3′-phosphate and also to 5′-phosphate of a single-stranded oligonucleotide. PARP2 preferentially ADP-ribosylated the nicked/gapped DNA duplexes containing 5′-phosphate at the double-stranded termini. PAR glycohydrolase (PARG) restored native DNA structure by hydrolysing PAR-DNA adducts generated by PARP1 and PARP2. Biochemical and mass spectrometry analyses of the adducts suggested that PARPs utilise DNA termini as an alternative to 2′-hydroxyl of ADP-ribose and protein acceptor residues to catalyse PAR chain initiation either via the 2′,1″-O-glycosidic ribose-ribose bond or via phosphodiester bond formation between C1′ of ADP-ribose and the phosphate of a terminal deoxyribonucleotide. This new type of post-replicative modification of DNA provides novel insights into the molecular mechanisms underlying biological phenomena of ADP-ribosylation mediated by PARPs. PMID:27471034

Tumors overexpressing RNF168 show altered DNA repair and responses to genotoxic treatments, genomic instability and resistance to proteotoxic stress.

PubMed

Chroma, K; Mistrik, M; Moudry, P; Gursky, J; Liptay, M; Strauss, R; Skrott, Z; Vrtel, R; Bartkova, J; Kramara, J; Bartek, J

2017-04-27

Chromatin DNA damage response (DDR) is orchestrated by the E3 ubiquitin ligase ring finger protein 168 (RNF168), resulting in ubiquitin-dependent recruitment of DDR factors and tumor suppressors breast cancer 1 (BRCA1) and p53 binding protein 1 (53BP1). This ubiquitin signaling regulates pathway choice for repair of DNA double-strand breaks (DSB), toxic lesions whose frequency increases during tumorigenesis. Recruitment of 53BP1 curbs DNA end resection, thereby limiting homologous recombination (HR) and directing DSB repair toward error-prone non-homologous end joining (NHEJ). Under cancer-associated ubiquitin starvation conditions reflecting endogenous or treatment-evoked proteotoxic stress, the ubiquitin-dependent accrual of 53BP1 and BRCA1 at the DNA damage sites is attenuated or lost. Challenging this current paradigm, here we identified diverse human cancer cell lines that display 53BP1 recruitment to DSB sites even under proteasome inhibitor-induced proteotoxic stress, that is, under substantial depletion of free ubiquitin. We show that central to this unexpected phenotype is overabundance of RNF168 that enables more efficient exploitation of the residual-free ubiquitin. Cells with elevated RNF168 are more resistant to combined treatment by ionizing radiation and proteasome inhibition, suggesting that such aberrant RNF168-mediated signaling might reflect adaptation to chronic proteotoxic and genotoxic stresses experienced by tumor cells. Moreover, the overabundant RNF168 and the ensuing unorthodox recruitment patterns of 53BP1, RIF1 and REV7 (monitored on laser micro-irradiation-induced DNA damage) shift the DSB repair balance from HR toward NHEJ, a scenario accompanied by enhanced chromosomal instability/micronuclei formation and sensitivity under replication stress-inducing treatments with camptothecin or poly(ADP-ribose) polymerase (PARP) inhibitor. Overall, our data suggest that the deregulated RNF168/53BP1 pathway could promote tumorigenesis by selecting for a more robust, better stress-adapted cancer cell phenotype, through altered DNA repair, fueling genomic instability and tumor heterogeneity. Apart from providing insights into cancer (patho)biology, the elevated RNF168, documented here also by immunohistochemistry on human clinical tumor specimens, may impact responses to standard-of-care and some emerging targeted cancer therapies.

A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

PubMed

Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

2012-03-01

Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

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

Batista, Antonio J. N.; Santos, Bruno; Fernandes, Ana

The data acquisition and control instrumentation cubicles room of the ITER tokamak will be irradiated with neutrons during the fusion reactor operation. A Virtex-6 FPGA from Xilinx (XC6VLX365T-1FFG1156C) is used on the ATCA-IO-PROCESSOR board, included in the ITER Catalog of I and C products - Fast Controllers. The Virtex-6 is a re-programmable logic device where the configuration is stored in Static RAM (SRAM), functional data stored in dedicated Block RAM (BRAM) and functional state logic in Flip-Flops. Single Event Upsets (SEU) due to the ionizing radiation of neutrons causes soft errors, unintended changes (bit-flips) to the values stored in statemore » elements of the FPGA. The SEU monitoring and soft errors repairing, when possible, were explored in this work. An FPGA built-in Soft Error Mitigation (SEM) controller detects and corrects soft errors in the FPGA configuration memory. Novel SEU sensors with Error Correction Code (ECC) detect and repair the BRAM memories. Proper management of SEU can increase reliability and availability of control instrumentation hardware for nuclear applications. The results of the tests performed using the SEM controller and the BRAM SEU sensors are presented for a Virtex-6 FPGA (XC6VLX240T-1FFG1156C) when irradiated with neutrons from the Portuguese Research Reactor (RPI), a 1 MW nuclear fission reactor operated by IST in the neighborhood of Lisbon. Results show that the proposed SEU mitigation technique is able to repair the majority of the detected SEU errors in the configuration and BRAM memories. (authors)« less

Advanced repair solution of clear defects on HTPSM by using nanomachining tool

NASA Astrophysics Data System (ADS)

Lee, Hyemi; Kim, Munsik; Jung, Hoyong; Kim, Sangpyo; Yim, Donggyu

2015-10-01

As the mask specifications become tighter for low k1 lithography, more aggressive repair accuracy is required below sub 20nm tech. node. To meet tight defect specifications, many maskshops select effective repair tools according to defect types. Normally, pattern defects are repaired by the e-beam repair tool and soft defects such as particles are repaired by the nanomachining tool. It is difficult for an e-beam repair tool to remove particle defects because it uses chemical reaction between gas and electron, and a nanomachining tool, which uses physical reaction between a nano-tip and defects, cannot be applied for repairing clear defects. Generally, film deposition process is widely used for repairing clear defects. However, the deposited film has weak cleaning durability, so it is easily removed by accumulated cleaning process. Although the deposited film is strongly attached on MoSiN(or Qz) film, the adhesive strength between deposited Cr film and MoSiN(or Qz) film becomes weaker and weaker by the accumulated energy when masks are exposed in a scanner tool due to the different coefficient of thermal expansion of each materials. Therefore, whenever a re-pellicle process is needed to a mask, all deposited repair points have to be confirmed whether those deposition film are damaged or not. And if a deposition point is damaged, repair process is needed again. This process causes longer and more complex process. In this paper, the basic theory and the principle are introduced to recover clear defects by using nanomachining tool, and the evaluated results are reviewed at dense line (L/S) patterns and contact hole (C/H) patterns. Also, the results using a nanomachining were compared with those using an e-beam repair tool, including the cleaning durability evaluated by the accumulated cleaning process. Besides, we discuss the phase shift issue and the solution about the image placement error caused by phase error.

Laser tissue soldering for hypospadias repair: results of a controlled prospective clinical trial.

PubMed

Kirsch, A J; Cooper, C S; Gatti, J; Scherz, H C; Canning, D A; Zderic, S A; Snyder, H M

2001-02-01

Laser tissue soldering has been shown to provide safe and effective tissue closure by creating an immediate leak-free anastomosis with minimal scar formation. We compared the results of laser tissue soldering and conventional suturing for hypospadias repair. A consecutive group of 138 boys 4 months to 8 years old (mean age 15 months) was divided into a standard suturing (84) and a sutureless laser (54) hypospadias repair group. Urethral repair was defined as simple (Thiersch-Duplay or Snodgrass) and complex (onlay island flap or tube) in 101 and 37 cases, respectively. Laser tissue soldering was performed with 50% human albumin solder doped with 2.5 mg./ml. indocyanine green dye using an 808 nm. diode laser at 0.5 W. In the laser group sutures were used for tissue alignment only. At surgery neourethral and penile length, operative time for neourethral construction and the number of sutures or throws were measured. Postoperatively patients were examined for complications of wound healing, stricture or fistula. Mean patient age, urethral defect severity, type of repair, neourethral length and stenting time plus or minus standard error of mean were not significantly different in the 2 groups. Mean operative time was a fifth as long for laser tissue soldering in simple and complex hypospadias repair compared to controls (1.5 +/- 0.1 and 5.1 +/- 0.3 versus 8.5 +/- 0.8 and 26.7 +/- 1.7 minutes, respectively, p <0.001). The mean number of sutures used for tissue alignment in the laser group for simple and complex repair was significantly less than in controls (3.0 +/- 0.2 and 8.2 +/- 0.6 versus 8.5 +/- 0.8 and 23.2 +/- 1.5, respectively, p <0.001). All patients were followed a mean of 12 months (minimum 6, maximum 22). The complication rate was 4.7% in the laser group and 10.7% in controls with fistula in 2 of 54 cases, and fistula and meatal stenosis in 7 and 2 of 84, respectively. These preliminary results indicate that laser tissue soldering for hypospadias repair may be performed in almost sutureless fashion and more rapidly than conventional suturing. The ease of the laser technique and the lower complication rate in the laser group indicate that laser tissue soldering is an acceptable means of tissue closure in hypospadias repair.

Development of Gutless Adenoviral Vectors Encoding Anti Angiogenic Proteins for Therapy of Prostate Cancer

DTIC Science & Technology

2005-01-01

PRINCIPAL INVESTIGATOR: Calvin J. Kuo, M.D., Ph.D. CONTRACTING ORGANIZATION : Stanford University Stanford, California 94305-5401 REPORT DATE: January...cloned in between the I-Scel site and the T’. This extra DNA fragment is used as a stuffer DNA in order to increase the size of the viral genome up to...regularly increasing sizes above the 2 fragments specific for the virus left and right ends can only be explained by the phenomenon known as ’postreplicative

Involvement of Escherichia coli DNA Polymerase IV in Tolerance of Cytotoxic Alkylating DNA Lesions in Vivo

PubMed Central

Bjedov, Ivana; Dasgupta, Chitralekha Nag; Slade, Dea; Le Blastier, Sophie; Selva, Marjorie; Matic, Ivan

2007-01-01

Escherichia coli PolIV, a DNA polymerase capable of catalyzing synthesis past replication-blocking DNA lesions, belongs to the most ubiquitous branch of Y-family DNA polymerases. The goal of this study is to identify spontaneous DNA damage that is bypassed specifically and accurately by PolIV in vivo. We increased the amount of spontaneous DNA lesions using mutants deficient for different DNA repair pathways and measured mutation frequency in PolIV-proficient and -deficient backgrounds. We found that PolIV performs an error-free bypass of DNA damage that accumulates in the alkA tag genetic background. This result indicates that PolIV is involved in the error-free bypass of cytotoxic alkylating DNA lesions. When the amount of cytotoxic alkylating DNA lesions is increased by the treatment with chemical alkylating agents, PolIV is required for survival in an alkA tag-proficient genetic background as well. Our study, together with the reported involvement of the mammalian PolIV homolog, Polκ, in similar activity, indicates that Y-family DNA polymerases from the DinB branch can be added to the list of evolutionarily conserved molecular mechanisms that counteract cytotoxic effects of DNA alkylation. This activity is of major biological relevance because alkylating agents are continuously produced endogenously in all living cells and are also present in the environment. PMID:17483416

Collaborative Repair in EFL Classroom Talk.

ERIC Educational Resources Information Center

Iles, Zara

1996-01-01

Drawing data from audiotaped lessons with 10 native-speaker English-as-a-Foreign-Language (EFL) teachers and 12 EFL learners of varied linguistic backgrounds, a study explored some of the ways in which classroom talk by learners is collaboratively built to repair errors, misunderstandings, and non-communication. Focus is on both explicit and…

Skin Regeneration in Adult Axolotls: A Blueprint for Scar-Free Healing in Vertebrates

PubMed Central

Seifert, Ashley W.; Monaghan, James R.; Voss, S. Randal; Maden, Malcolm

2012-01-01

While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair. PMID:22485136

A Systematic Approach to Error Free Telemetry

DTIC Science & Technology

2017-06-28

A SYSTEMATIC APPROACH TO ERROR FREE TELEMETRY 412TW-TIM-17-03 DISTRIBUTION A: Approved for public release. Distribution is...Systematic Approach to Error-Free Telemetry) was submitted by the Commander, 412th Test Wing, Edwards AFB, California 93524. Prepared by...Technical Information Memorandum 3. DATES COVERED (From - Through) February 2016 4. TITLE AND SUBTITLE A Systematic Approach to Error-Free

PrimPol prevents APOBEC/AID family mediated DNA mutagenesis

PubMed Central

Pilzecker, Bas; Buoninfante, Olimpia Alessandra; Pritchard, Colin; Blomberg, Olga S.; Huijbers, Ivo J.; van den Berk, Paul C.M.; Jacobs, Heinz

2016-01-01

Abstract PrimPol is a DNA damage tolerant polymerase displaying both translesion synthesis (TLS) and (re)-priming properties. This led us to study the consequences of a PrimPol deficiency in tolerating mutagenic lesions induced by members of the APOBEC/AID family of cytosine deaminases. Interestingly, during somatic hypermutation, PrimPol counteracts the generation of C>G transversions on the leading strand. Independently, mutation analyses in human invasive breast cancer confirmed a pro-mutagenic activity of APOBEC3B and revealed a genome-wide anti-mutagenic activity of PRIMPOL as well as most Y-family TLS polymerases. PRIMPOL especially prevents APOBEC3B targeted cytosine mutations within TpC dinucleotides. As C transversions induced by APOBEC/AID family members depend on the formation of AP-sites, we propose that PrimPol reprimes preferentially downstream of AP-sites on the leading strand, to prohibit error-prone TLS and simultaneously stimulate error-free homology directed repair. These in vivo studies are the first demonstrating a critical anti-mutagenic activity of PrimPol in genome maintenance. PMID:26926109

[Monitoring of Crack Propagation in Repaired Structures Based on Characteristics of FBG Sensors Reflecting Spectra].

PubMed

Yuan, Shen-fang; Jin, Xin; Qiu, Lei; Huang, Hong-mei

2015-03-01

In order to improve the security of aircraft repaired structures, a method of crack propagation monitoring in repaired structures is put forward basing on characteristics of Fiber Bragg Grating (FBG) reflecting spectra in this article. With the cyclic loading effecting on repaired structure, cracks propagate, while non-uniform strain field appears nearby the tip of crack which leads to the FBG sensors' reflecting spectra deformations. The crack propagating can be monitored by extracting the characteristics of FBG sensors' reflecting spectral deformations. A finite element model (FEM) of the specimen is established. Meanwhile, the distributions of strains which are under the action of cracks of different angles and lengths are obtained. The characteristics, such as main peak wavelength shift, area of reflecting spectra, second and third peak value and so on, are extracted from the FBGs' reflecting spectral which are calculated by transfer matrix algorithm. An artificial neural network is built to act as the model between the characteristics of the reflecting spectral and the propagation of crack. As a result, the crack propagation of repaired structures is monitored accurately and the error of crack length is less than 0.5 mm, the error of crack angle is less than 5 degree. The accurately monitoring problem of crack propagation of repaired structures is solved by taking use of this method. It has important significance in aircrafts safety improvement and maintenance cost reducing.

Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae

PubMed Central

Symington, Lorraine S.; Rothstein, Rodney; Lisby, Michael

2014-01-01

Homology-dependent exchange of genetic information between DNA molecules has a profound impact on the maintenance of genome integrity by facilitating error-free DNA repair, replication, and chromosome segregation during cell division as well as programmed cell developmental events. This chapter will focus on homologous mitotic recombination in budding yeast Saccharomyces cerevisiae. However, there is an important link between mitotic and meiotic recombination (covered in the forthcoming chapter by Hunter et al. 2015) and many of the functions are evolutionarily conserved. Here we will discuss several models that have been proposed to explain the mechanism of mitotic recombination, the genes and proteins involved in various pathways, the genetic and physical assays used to discover and study these genes, and the roles of many of these proteins inside the cell. PMID:25381364

A history of the DNA repair and mutagenesis field: The discovery of base excision repair.

PubMed

Friedberg, Errol C

2016-01-01

This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme-catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases. Copyright © 2015. Published by Elsevier B.V.

Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions.

PubMed

Lo, Te-Wen; Pickle, Catherine S; Lin, Steven; Ralston, Edward J; Gurling, Mark; Schartner, Caitlin M; Bian, Qian; Doudna, Jennifer A; Meyer, Barbara J

2013-10-01

Exploitation of custom-designed nucleases to induce DNA double-strand breaks (DSBs) at genomic locations of choice has transformed our ability to edit genomes, regardless of their complexity. DSBs can trigger either error-prone repair pathways that induce random mutations at the break sites or precise homology-directed repair pathways that generate specific insertions or deletions guided by exogenously supplied DNA. Prior editing strategies using site-specific nucleases to modify the Caenorhabditis elegans genome achieved only the heritable disruption of endogenous loci through random mutagenesis by error-prone repair. Here we report highly effective strategies using TALE nucleases and RNA-guided CRISPR/Cas9 nucleases to induce error-prone repair and homology-directed repair to create heritable, precise insertion, deletion, or substitution of specific DNA sequences at targeted endogenous loci. Our robust strategies are effective across nematode species diverged by 300 million years, including necromenic nematodes (Pristionchus pacificus), male/female species (Caenorhabditis species 9), and hermaphroditic species (C. elegans). Thus, genome-editing tools now exist to transform nonmodel nematode species into genetically tractable model organisms. We demonstrate the utility of our broadly applicable genome-editing strategies by creating reagents generally useful to the nematode community and reagents specifically designed to explore the mechanism and evolution of X chromosome dosage compensation. By developing an efficient pipeline involving germline injection of nuclease mRNAs and single-stranded DNA templates, we engineered precise, heritable nucleotide changes both close to and far from DSBs to gain or lose genetic function, to tag proteins made from endogenous genes, and to excise entire loci through targeted FLP-FRT recombination.

Somatic stem cells and the kinetics of mutagenesis and carcinogenesis

PubMed Central

Cairns, John

2002-01-01

There is now strong experimental evidence that epithelial stem cells arrange their sister chromatids at mitosis such that the same template DNA strands stay together through successive divisions; DNA labeled with tritiated thymidine in infancy is still present in the stem cells of adult mice even though these cells are incorporating (and later losing) bromodeoxyuridine [Potten, C. S., Owen, G., Booth, D. & Booth, C. (2002) J. Cell Sci.115, 2381–2388]. But a cell that preserves “immortal strands” will avoid the accumulation of replication errors only if it inhibits those pathways for DNA repair that involve potentially error-prone resynthesis of damaged strands, and this appears to be a property of intestinal stem cells because they are extremely sensitive to the lethal effects of agents that damage DNA. It seems that the combination, in the stem cell, of immortal strands and the choice of death rather than error-prone repair makes epithelial stem cell systems resistant to short exposures to DNA-damaging agents, because the stem cell accumulates few if any errors, and any errors made by the daughters are destined to be discarded. This paper discusses these issues and shows that they lead to a model that explains the strange kinetics of mutagenesis and carcinogenesis in adult mammalian tissues. Coincidentally, the model also can explain why cancers arise even though the spontaneous mutation rate of differentiated mammalian cells is not high enough to generate the multiple mutations needed to form a cancer and why loss of nucleotide-excision repair does not significantly increase the frequency of the common internal cancers. PMID:12149477

REV7 counteracts DNA double-strand break resection and impacts PARP inhibition

PubMed Central

Xu, Guotai; Yuan, Jingsong; Mistrik, Martin; Bouwman, Peter; Bartkova, Jirina; Gogola, Ewa; Warmerdam, Daniël; Barazas, Marco; Jaspers, Janneke E.; Watanabe, Kenji; Pieterse, Mark; Kersbergen, Ariena; Sol, Wendy; Celie, Patrick H. N.; Schouten, Philip C.; van den Broek, Bram; Salman, Ahmed; Nieuwland, Marja; de Rink, Iris; de Ronde, Jorma; Jalink, Kees; Boulton, Simon J.; Chen, Junjie; van Gent, Dik C.; Bartek, Jiri; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2015-01-01

Summary Error-free repair of DNA double-strand breaks (DSB) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway1. In the absence of BRCA1-mediated HR, administration of PARP inhibitors induces synthetic lethality of tumor cells of patients with breast or ovarian cancers2,3. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration4. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases5. In particular, little is known about BRCA1-independent restoration of HR. Here, we show that loss of REV7 (also known as MAD2L2) re-establishes CtIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and appears to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance6. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining (NHEJ) during immunoglobulin class switch recombination. Our results reveal an unexpected critical function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells. PMID:25799992

Error recovery to enable error-free message transfer between nodes of a computer network

DOEpatents

Blumrich, Matthias A.; Coteus, Paul W.; Chen, Dong; Gara, Alan; Giampapa, Mark E.; Heidelberger, Philip; Hoenicke, Dirk; Takken, Todd; Steinmacher-Burow, Burkhard; Vranas, Pavlos M.

2016-01-26

An error-recovery method to enable error-free message transfer between nodes of a computer network. A first node of the network sends a packet to a second node of the network over a link between the nodes, and the first node keeps a copy of the packet on a sending end of the link until the first node receives acknowledgment from the second node that the packet was received without error. The second node tests the packet to determine if the packet is error free. If the packet is not error free, the second node sets a flag to mark the packet as corrupt. The second node returns acknowledgement to the first node specifying whether the packet was received with or without error. When the packet is received with error, the link is returned to a known state and the packet is sent again to the second node.

Analysis of Free-Space Coupling to Photonic Lanterns in the Presence of Tilt Errors

DTIC Science & Technology

2017-05-01

Analysis of Free- Space Coupling to Photonic Lanterns in the Presence of Tilt Errors Timothy M. Yarnall, David J. Geisler, Curt M. Schieler...Massachusetts Avenue Cambridge, MA 02139, USA Abstract—Free space coupling to photonic lanterns is more tolerant to tilt errors and F -number mismatch than...these errors. I. INTRODUCTION Photonic lanterns provide a means for transitioning from the free space regime to the single-mode fiber (SMF) regime by

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage

PubMed Central

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C.M.; Jansen, Jacob G.; Hogenbirk, Marc A.; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (PcnaK164R) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. PMID:25505145

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Goods re-entered after repair or alteration in... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.1034 - Goods re-entered after repair or alteration in Korea.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Korea Free Trade Agreement Goods Returned After Repair Or Alteration § 10.1034 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.1034 - Goods re-entered after repair or alteration in Korea.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Korea Free Trade Agreement Goods Returned After Repair Or Alteration § 10.1034 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.827 - Goods re-entered after repair or alteration in Bahrain.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Goods re-entered after repair or alteration in... States-Bahrain Free Trade Agreement Goods Returned After Repair Or Alteration § 10.827 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.827 - Goods re-entered after repair or alteration in Bahrain.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Bahrain Free Trade Agreement Goods Returned After Repair Or Alteration § 10.827 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.490 - Goods re-entered after repair or alteration in Chile.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Goods re-entered after repair or alteration in... States-Chile Free Trade Agreement Goods Returned After Repair Or Alteration § 10.490 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Goods re-entered after repair or alteration in... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.490 - Goods re-entered after repair or alteration in Chile.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Goods re-entered after repair or alteration in... States-Chile Free Trade Agreement Goods Returned After Repair Or Alteration § 10.490 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Goods re-entered after repair or alteration in... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.827 - Goods re-entered after repair or alteration in Bahrain.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Bahrain Free Trade Agreement Goods Returned After Repair Or Alteration § 10.827 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.570 - Goods re-entered after repair or alteration in Singapore.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Singapore Free Trade Agreement Goods Returned After Repair Or Alteration § 10.570 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.827 - Goods re-entered after repair or alteration in Bahrain.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Goods re-entered after repair or alteration in... States-Bahrain Free Trade Agreement Goods Returned After Repair Or Alteration § 10.827 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.827 - Goods re-entered after repair or alteration in Bahrain.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Bahrain Free Trade Agreement Goods Returned After Repair Or Alteration § 10.827 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.1034 - Goods re-entered after repair or alteration in Korea.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Korea Free Trade Agreement Goods Returned After Repair Or Alteration § 10.1034 Goods re-entered... alterations” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment...

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Goods re-entered after repair or alteration in... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.490 - Goods re-entered after repair or alteration in Chile.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Chile Free Trade Agreement Goods Returned After Repair Or Alteration § 10.490 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.787 - Goods re-entered after repair or alteration in Morocco.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Morocco Free Trade Agreement Goods Returned After Repair Or Alteration § 10.787 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.490 - Goods re-entered after repair or alteration in Chile.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Chile Free Trade Agreement Goods Returned After Repair Or Alteration § 10.490 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.490 - Goods re-entered after repair or alteration in Chile.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Chile Free Trade Agreement Goods Returned After Repair Or Alteration § 10.490 Goods re-entered...” means restoration, addition, renovation, re-dyeing, cleaning, re-sterilizing, or other treatment which...

19 CFR 10.8 - Articles exported for repairs or alterations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles exported for repairs or alterations. 10.8...; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported and Returned § 10.8 Articles exported for repairs or alterations. (a) Except as otherwise...

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

PubMed Central

Noordam, Lisanne; Sprengers, Dave; Boor, Patrick P. C.; Mancham, Shanta; Menon, Anand G.; Lange, Johan F.; Burger, Pim J. W. A.; Brandt, Alexandra; Galjart, Boris; Kwekkeboom, Jaap; Bruno, Marco J.

2018-01-01

ABSTRACT Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

Reoperations after tricuspid valve repair: re-repair versus replacement

PubMed Central

Hwang, Ho Young; Kim, Kyung-Hwan; Kim, Ki-Bong

2016-01-01

Background Data demonstrating results of reoperation after initial tricuspid valve repair are scarce. We evaluated outcomes of tricuspid reoperations after tricuspid valve repair and compared the results of tricuspid re-repair with those of tricuspid valve replacement (TVR). Methods From 1994 to 2012, 53 patients (56±15 years, male:female =14:39) underwent tricuspid reoperations due to recurrent tricuspid regurgitation (TR) after initial repair. Twenty-two patients underwent tricuspid re-repair (TAP group) and 31 patients underwent TVR (TVR group). Results Early mortality occurred in 6 patients (11%). Early mortality and incidence of postoperative complications were similar between the 2 groups. There were 14 cases of late mortality including 9 cardiac deaths. Five- and 10-year free from cardiac death rates were 82% and 67%, respectively, without any intergroup difference. Recurrent TR (> moderate) developed in 6 TAP group patients and structural valve deterioration occurred in 1 TVR group patient (P=0.002). Isolated tricuspid valve surgery (P=0.044) and presence of atrial fibrillation during the follow-up (P=0.051) were associated with recurrent TR after re-repair. However, the overall tricuspid valve-related event rates were similar between the 2 groups with 5- and 10-year rates of 61% and 41%, respectively. Conclusions Tricuspid valve reoperation after initial repair resulted in high rates of operative mortality and complications. Long-term event-free rate was similar regardless of the type of surgery. However, great care might be needed when performing re-repair in patients with atrial fibrillation and those who had isolated tricuspid valve disease due to high recurrence of TR after re-repair. PMID:26904221

76 FR 8365 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

... ID number EPA-HQ- OECA-2010-0357, to (1) EPA online using www.regulations.gov (our preferred method... leaking equipment, repair methods used to stop the leaks, and dates of repair. The time period for this... correction of a mathematical error. There are no annual capital and O&M costs to the regulated entities...

19 CFR 10.890 - Goods re-entered after repair or alteration in Oman.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Goods re-entered after repair or alteration in... States-Oman Free Trade Agreement Goods Returned After Repair Or Alteration § 10.890 Goods re-entered...” means restoration, renovation, cleaning, re-sterilizing, or other treatment which does not destroy the...

19 CFR 10.890 - Goods re-entered after repair or alteration in Oman.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Goods re-entered after repair or alteration in... States-Oman Free Trade Agreement Goods Returned After Repair Or Alteration § 10.890 Goods re-entered...” means restoration, renovation, cleaning, re-sterilizing, or other treatment which does not destroy the...

19 CFR 10.890 - Goods re-entered after repair or alteration in Oman.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Goods re-entered after repair or alteration in... States-Oman Free Trade Agreement Goods Returned After Repair Or Alteration § 10.890 Goods re-entered...” means restoration, renovation, cleaning, re-sterilizing, or other treatment which does not destroy the...

19 CFR 10.890 - Goods re-entered after repair or alteration in Oman.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Goods re-entered after repair or alteration in... States-Oman Free Trade Agreement Goods Returned After Repair Or Alteration § 10.890 Goods re-entered...” means restoration, renovation, cleaning, re-sterilizing, or other treatment which does not destroy the...

Triple-Loaded Suture Anchors Versus a Knotless Rip Stop Construct in a Single-Row Rotator Cuff Repair Model.

PubMed

Noyes, Matthew P; Lederman, Evan; Adams, Christopher R; Denard, Patrick J

2018-05-01

To compare the biomechanical properties of single-row repair with triple-loaded (TL) anchor repair versus a knotless rip stop (KRS) repair in a rotator cuff repair model. Rotator cuff tears were created in 8 cadaveric matched-pair specimens and repaired with a TL anchor or KRS construct. In the TL construct, anchors were placed in the greater tuberosity and then all suture limbs were passed through the rotator cuff as simple sutures and tied. In the KRS construct, a 2-mm suture tape was passed through the tendon in an inverted mattress fashion, and a free suture was passed medial to the suture tape to create a rip-stop. Then, the suture tape and free suture were secured with knotless anchors. Displacement was observed with video tracking after cyclic loading, and specimens were loaded to failure. The mean load to failure was 438 ± 59 N in TL anchor repairs compared with 457 ± 110 N in KRS repairs (P = .582). The mean displacement with cyclic loading was 3.8 ± 1.6 mm in TL anchor repairs versus 4.3 ± 1.8 mm in the KRS group (P = .297). Mode of failure was consistent in both groups, with 6 of 8 failures in the TL anchor group and 7 of 8 failures in KRS group occurring from anchor pullout. There is no statistical difference in load to failure and cyclic loading between TL anchor and KRS single-row repair techniques. KRS repair technique may be an alternative method of repairing full-thickness supraspinatus tendon tears with a single-row construct. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Arthroscopic labral repair of the hip, using a through-labral double-stranded single-pass suture technique.

PubMed

Ye, Ken; Singh, Parminder J

2014-10-01

The normal labrum is crucial to the biomechanical function of the hip joint, not only increasing the surface area and depth of the acetabulum but also maintaining a suction seal to assist in normal synovial fluid flow from the peripheral to the central compartment. Simple loop suture repairs of the labrum may evert the labrum, thus losing the optimal seal, as well as causing abrasion of the articular cartilage. Vertical mattress suture and labral base fixation techniques aim to leave the free edge of the labrum intact and undisturbed, therefore improving the contact of the labrum to the femoral head and neck to improve the seal of the acetabulum. We aim to describe a double-stranded single-pass vertical mattress suture technique that may allow greater versatility to the surgeon in repairing thinner labrums while still achieving a free and continuous free edge.

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

PubMed

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

A CLIPS based personal computer hardware diagnostic system

NASA Technical Reports Server (NTRS)

Whitson, George M.

1991-01-01

Often the person designated to repair personal computers has little or no knowledge of how to repair a computer. Described here is a simple expert system to aid these inexperienced repair people. The first component of the system leads the repair person through a number of simple system checks such as making sure that all cables are tight and that the dip switches are set correctly. The second component of the system assists the repair person in evaluating error codes generated by the computer. The final component of the system applies a large knowledge base to attempt to identify the component of the personal computer that is malfunctioning. We have implemented and tested our design with a full system to diagnose problems for an IBM compatible system based on the 8088 chip. In our tests, the inexperienced repair people found the system very useful in diagnosing hardware problems.

Model-free and model-based reward prediction errors in EEG.

PubMed

Sambrook, Thomas D; Hardwick, Ben; Wills, Andy J; Goslin, Jeremy

2018-05-24

Learning theorists posit two reinforcement learning systems: model-free and model-based. Model-based learning incorporates knowledge about structure and contingencies in the world to assign candidate actions with an expected value. Model-free learning is ignorant of the world's structure; instead, actions hold a value based on prior reinforcement, with this value updated by expectancy violation in the form of a reward prediction error. Because they use such different learning mechanisms, it has been previously assumed that model-based and model-free learning are computationally dissociated in the brain. However, recent fMRI evidence suggests that the brain may compute reward prediction errors to both model-free and model-based estimates of value, signalling the possibility that these systems interact. Because of its poor temporal resolution, fMRI risks confounding reward prediction errors with other feedback-related neural activity. In the present study, EEG was used to show the presence of both model-based and model-free reward prediction errors and their place in a temporal sequence of events including state prediction errors and action value updates. This demonstration of model-based prediction errors questions a long-held assumption that model-free and model-based learning are dissociated in the brain. Copyright © 2018 Elsevier Inc. All rights reserved.

Laparoscopic extraperitoneal inguinal hernia repair versus open mesh repair: a prospective randomized controlled trial.

PubMed

Andersson, Bodil; Hallén, Magnus; Leveau, Per; Bergenfelz, Anders; Westerdahl, Johan

2003-05-01

This study was designed to compare an open tension-free technique (Lichtenstein repair) with a laparoscopic totally extraperitoneal hernia repair (TEP). One hundred sixty-eight men aged 30 to 65 years with primary or recurrent inguinal hernia were randomized to TEP or open mesh technique in the manner of Lichtenstein. Follow-up was after 1 and 6 weeks, and 1 year. Eighty-one patients were randomized to TEP, and 87 to open repair. For 1 patient in each group, the operation was converted to a different type of repair. No difference was seen in overall complications between the 2 groups. However, 1 patient in the TEP group underwent operation for small bowel obstruction after surgery. A higher frequency of postoperative hematomas was seen in the open group (P <.05). Patients in the TEP group consumed less analgesic after surgery (P <.001), returned to work earlier (P <.01), and had a shorter time to full recovery (P <.01). Two recurrences occurred in the TEP group 1 year after surgery. The TEP technique was associated with less postoperative pain, a shorter time to full recovery, and an earlier return to work compared with the open tension-free repair. No difference was seen in overall complications. However, 2 recurrences did occur after 1 year in the TEP group.

Prevalence and types of articulation errors in Saudi Arabic-speaking children with repaired cleft lip and palate.

PubMed

Albustanji, Yusuf M; Albustanji, Mahmoud M; Hegazi, Mohamed M; Amayreh, Mousa M

2014-10-01

The purpose of this study was to assess prevalence and types of consonant production errors and phonological processes in Saudi Arabic-speaking children with repaired cleft lip and palate, and to determine the relationship between frequency of errors on one hand and the type of the cleft. Possible relationship between age, gender and frequency of errors was also investigated. Eighty Saudi children with repaired cleft lip and palate aged 6-15 years (mean 6.7 years), underwent speech, language, and hearing evaluation. The diagnosis of articulation deficits was based on the results of an Arabic articulation test. Phonological processes were reported based on the productivity scale of a minimum 20% of occurrence. Diagnosis of nasality was based on a 5-point scale that reflects severity from 0 through 4. All participants underwent intraoral examination, informal language assessment, and hearing evaluation to assess their speech and language abilities. The Chi-Square test for independence was used to analyze the results of consonant production as a function of type of CLP and age. Out of 80 participants with CLP, 21 participants had normal articulation and resonance, 59 of participants (74%) showed speech abnormalities. Twenty-one of these 59 participants showed only articulation errors; 17 showed only hypernasality; and 21 showed both articulation and resonance deficits. CAs were observed in 20 participant. The productive phonological processes were consonant backing, final consonant deletion, gliding, and stopping. At age 6 and older, 37% of participants had persisting hearing loss. Despite early age at time of surgery (mean 6.7 months) for the studied CLP participants in this study, a substantial number of them demonstrated articulation errors and hypernasality. The results showed desirable findings for diverse languages. It is especially interesting to consider the prevalence of glottal stops and pharyngeal fricatives in a population for whom these sound are phonemic. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

46 CFR 160.151-43 - Conditions at servicing facilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... liferaft, can be easily cleaned, and is kept clean and free from oil, grease, and abrasive material; (6) Is... areas or rooms for storage of liferafts awaiting servicing, repair, or delivery; for repair and painting...

46 CFR 160.151-43 - Conditions at servicing facilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... liferaft, can be easily cleaned, and is kept clean and free from oil, grease, and abrasive material; (6) Is... areas or rooms for storage of liferafts awaiting servicing, repair, or delivery; for repair and painting...

46 CFR 160.151-43 - Conditions at servicing facilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... liferaft, can be easily cleaned, and is kept clean and free from oil, grease, and abrasive material; (6) Is... areas or rooms for storage of liferafts awaiting servicing, repair, or delivery; for repair and painting...

46 CFR 160.151-43 - Conditions at servicing facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... liferaft, can be easily cleaned, and is kept clean and free from oil, grease, and abrasive material; (6) Is... areas or rooms for storage of liferafts awaiting servicing, repair, or delivery; for repair and painting...

Assessing the impact of short-term surgical education on practice: a retrospective study of the introduction of mesh for inguinal hernia repair in sub-Saharan Africa.

PubMed

Wang, Y T; Meheš, M M; Naseem, H-R; Ibrahim, M; Butt, M A; Ahmed, N; Wahab Bin Adam, M A; Issah, A-W; Mohammed, I; Goldstein, S D; Cartwright, K; Abdullah, F

2014-08-01

Inguinal hernia repair is the most common general surgery operation performed globally. However, the adoption of tension-free hernia repair with mesh has been limited in low-income settings, largely due to a lack of technical training and resources. The present study evaluates the impact of a 2-day training course instructing use of polypropylene mesh for inguinal hernia repair on the practice patterns of sub-Saharan African physicians. A surgical training course on tension-free mesh repair of hernias was provided to 16 physicians working in rural Ghanaian and Liberian hospitals. Three physicians were requested to prospectively record all their inguinal hernia surgeries, performed with or without mesh, during the 14-month period following the training. Demographic variables, diagnoses, and complications were collected by an independent data collector for mesh and non-mesh procedures. Surgery with mesh increased significantly following intervention, from near negligible levels prior to the training to 8.1 % of all inguinal hernia repairs afterwards. Mesh repair accounted for 90.8 % of recurrent hernia repairs and 2.9 % of primary hernia repairs after training. Overall complication rates between mesh and non-mesh procedures were not significantly different (p = 0.20). Three physicians who participated in an intensive education course were routinely using mesh for inguinal hernia repair 14 months after the training. This represents a significant change in practice pattern. Complication rates between patients who underwent inguinal hernia repairs with and without mesh were comparable. The present study provides evidence that short-term surgical training initiatives can have a substantial impact on local healthcare practice in resource-limited settings.

DNA repair in mammalian mitochondria: Much more than we thought?

PubMed

Liu, Pingfang; Demple, Bruce

2010-06-01

For many years, the repair of most damage in mitochondrial DNA (mtDNA) was thought limited to short-patch base excision repair (SP-BER), which replaces a single nucleotide by the sequential action of DNA glycosylases, an apurinic/apyrimidinic (AP) endonuclease, the mitochondrial DNA polymerase gamma, an abasic lyase activity, and mitochondrial DNA ligase. However, the likely array of lesions inflicted on mtDNA by oxygen radicals and the possibility of replication errors and disruptions indicated that such a restricted repair repertoire would be inadequate. Recent studies have considerably expanded our knowledge of mtDNA repair to include long-patch base excision repair (LP-BER), mismatch repair, and homologous recombination and nonhomologous end-joining. In addition, elimination of mutagenic 8-oxodeoxyguanosine triphosphate (8-oxodGTP) helps prevent cell death due to the accumulation of this oxidation product in mtDNA. Although it was suspected for many years that irreparably damaged mtDNA might be targeted for degradation, only recently was clear evidence provided for this hypothesis. Therefore, multiple DNA repair pathways and controlled degradation of mtDNA function together to maintain the integrity of mitochondrial genome.

Exploring Senior Residents' Intraoperative Error Management Strategies: A Potential Measure of Performance Improvement.

PubMed

Law, Katherine E; Ray, Rebecca D; D'Angelo, Anne-Lise D; Cohen, Elaine R; DiMarco, Shannon M; Linsmeier, Elyse; Wiegmann, Douglas A; Pugh, Carla M

The study aim was to determine whether residents' error management strategies changed across 2 simulated laparoscopic ventral hernia (LVH) repair procedures after receiving feedback on their initial performance. We hypothesize that error detection and recovery strategies would improve during the second procedure without hands-on practice. Retrospective review of participant procedural performances of simulated laparoscopic ventral herniorrhaphy. A total of 3 investigators reviewed procedure videos to identify surgical errors. Errors were deconstructed. Error management events were noted, including error identification and recovery. Residents performed the simulated LVH procedures during a course on advanced laparoscopy. Participants had 30 minutes to complete a LVH procedure. After verbal and simulator feedback, residents returned 24 hours later to perform a different, more difficult simulated LVH repair. Senior (N = 7; postgraduate year 4-5) residents in attendance at the course participated in this study. In the first LVH procedure, residents committed 121 errors (M = 17.14, standard deviation = 4.38). Although the number of errors increased to 146 (M = 20.86, standard deviation = 6.15) during the second procedure, residents progressed further in the second procedure. There was no significant difference in the number of errors committed for both procedures, but errors shifted to the late stage of the second procedure. Residents changed the error types that they attempted to recover (χ 2 5 =24.96, p<0.001). For the second procedure, recovery attempts increased for action and procedure errors, but decreased for strategy errors. Residents also recovered the most errors in the late stage of the second procedure (p < 0.001). Residents' error management strategies changed between procedures following verbal feedback on their initial performance and feedback from the simulator. Errors and recovery attempts shifted to later steps during the second procedure. This may reflect residents' error management success in the earlier stages, which allowed further progression in the second simulation. Incorporating error recognition and management opportunities into surgical training could help track residents' learning curve and provide detailed, structured feedback on technical and decision-making skills. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

45 CFR 286.205 - How will we determine if a Tribe fails to meet the minimum work participation rate(s)?

Code of Federal Regulations, 2012 CFR

2012-10-01

..., financial records, and automated data systems; (ii) The data are free from computational errors and are... records, financial records, and automated data systems; (ii) The data are free from computational errors... records, and automated data systems; (ii) The data are free from computational errors and are internally...

‘Why should I care?’ Challenging free will attenuates neural reaction to errors

PubMed Central

Pourtois, Gilles; Brass, Marcel

2015-01-01

Whether human beings have free will has been a philosophical question for centuries. The debate about free will has recently entered the public arena through mass media and newspaper articles commenting on scientific findings that leave little to no room for free will. Previous research has shown that encouraging such a deterministic perspective influences behavior, namely by promoting cursory and antisocial behavior. Here we propose that such behavioral changes may, at least partly, stem from a more basic neurocognitive process related to response monitoring, namely a reduced error detection mechanism. Our results show that the error-related negativity, a neural marker of error detection, was reduced in individuals led to disbelieve in free will. This finding shows that reducing the belief in free will has a specific impact on error detection mechanisms. More generally, it suggests that abstract beliefs about intentional control can influence basic and automatic processes related to action control. PMID:24795441

A Human Amnion-Derived Extracellular Matrix-Coated Cell-Free Scaffold for Cartilage Repair: In Vitro and In Vivo Studies.

PubMed

Nogami, Makiko; Kimura, Tomoatsu; Seki, Shoji; Matsui, Yoshito; Yoshida, Toshiko; Koike-Soko, Chika; Okabe, Motonori; Motomura, Hiraku; Gejo, Ryuichi; Nikaido, Toshio

2016-04-01

Extracellular matrix (ECM) derived from human amniotic mesenchymal cells (HAMs) has various biological activities. In this study, we developed a novel HAM-derived ECM-coated polylactic-co-glycolic acid (ECM-PLGA) scaffold, examined its property on mesenchymal cells, and investigated its potential as a cell-free scaffold for cartilage repair. ECM-PLGA scaffolds were developed by inoculating HAM on a PLGA. After decellularization by irradiation, accumulated ECM was examined. Exogenous cell growth and differentiation of rat mesenchymal stem cells (MSCs) on the ECM-PLGA were analyzed in vitro by cell attachment/proliferation assay and reverse transcription-polymerase chain reaction. The cell-free ECM-PLGA scaffolds were implanted into osteochondral defects in the trochlear groove of rat knees. After 4, 12, or 24 weeks, the animals were sacrificed and the harvested tissues were examined histologically. The ECM-PLGA contained ECM that mimicked natural amniotic stroma that contains type I collagen, fibronectin, hyaluronic acid, and chondroitin sulfates. The ECM-PLGA showed excellent properties of cell attachment and proliferation. MSCs inoculated on the ECM-PLGA scaffold showed accelerated type II collagen mRNA expression after 3 weeks in culture. The ECM-PLGA implanted into an osteochondral defect in rat knees induced gradual tissue regeneration and resulted in hyaline cartilage repair, which was better than that in the empty control group. These in vitro and in vivo experiments show that the cell-free scaffold composed of HAM-derived ECM and PLGA provides a favorable growth environment for MSCs and facilitates the cartilage repair process. The ECM-PLGA may become a "ready-made" biomaterial for cartilage repair therapy.

Understanding the dynamics of correct and error responses in free recall: evidence from externalized free recall.

PubMed

Unsworth, Nash; Brewer, Gene A; Spillers, Gregory J

2010-06-01

The dynamics of correct and error responses in a variant of delayed free recall were examined in the present study. In the externalized free recall paradigm, participants were presented with lists of words and were instructed to subsequently recall not only the words that they could remember from the most recently presented list, but also any other words that came to mind during the recall period. Externalized free recall is useful for elucidating both sampling and postretrieval editing processes, thereby yielding more accurate estimates of the total number of error responses, which are typically sampled and subsequently edited during free recall. The results indicated that the participants generally sampled correct items early in the recall period and then transitioned to sampling more erroneous responses. Furthermore, the participants generally terminated their search after sampling too many errors. An examination of editing processes suggested that the participants were quite good at identifying errors, but this varied systematically on the basis of a number of factors. The results from the present study are framed in terms of generate-edit models of free recall.

[Analysis of intrusion errors in free recall].

PubMed

Diesfeldt, H F A

2017-06-01

Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so. Bivariate regression analyses revealed that participants who committed intrusion errors were more deficient on measures of eight-word recognition memory, delayed visual recognition and tests of executive control (the Behavioral Dyscontrol Scale and the ADST-Graphical Sequences as measures of response inhibition). Using hierarchical multiple regression, only free recall and delayed visual recognition retained an independent effect in the association with intrusion errors, such that deficient scores on tests of episodic memory were sufficient to explain the occurrence of intrusion errors. Measures of inhibitory control did not add significantly to the explanation of intrusion errors in free recall, which makes insufficient strength of memory traces rather than a primary deficit in inhibition the preferred account for intrusion errors in free recall.

Free-Standing Biodegradable Poly(lactic acid) Nanosheet for Sealing Operations in Surgery.

PubMed

Okamura, Yosuke; Kabata, Koki; Kinoshita, Manabu; Saitoh, Daizoh; Takeoka, Shinji

2009-11-20

A free-standing biodegradable nanosheet composed of poly(L-lactic acid) (PLLA) was shown to have excellent sealing efficacy for a gastric incision as a novel wound dressing material that did not require adhesive agents, and the PLLA nanosheet-induced wound repair showed neither scars nor tissue adhesion. This material may, therefore, be an ideal alternative to conventional tissue repairing procedures using suture/ligation in surgery. Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Adaptive Kalman filter based on variance component estimation for the prediction of ionospheric delay in aiding the cycle slip repair of GNSS triple-frequency signals

NASA Astrophysics Data System (ADS)

Chang, Guobin; Xu, Tianhe; Yao, Yifei; Wang, Qianxin

2018-01-01

In order to incorporate the time smoothness of ionospheric delay to aid the cycle slip detection, an adaptive Kalman filter is developed based on variance component estimation. The correlations between measurements at neighboring epochs are fully considered in developing a filtering algorithm for colored measurement noise. Within this filtering framework, epoch-differenced ionospheric delays are predicted. Using this prediction, the potential cycle slips are repaired for triple-frequency signals of global navigation satellite systems. Cycle slips are repaired in a stepwise manner; i.e., for two extra wide lane combinations firstly and then for the third frequency. In the estimation for the third frequency, a stochastic model is followed in which the correlations between the ionospheric delay prediction errors and the errors in the epoch-differenced phase measurements are considered. The implementing details of the proposed method are tabulated. A real BeiDou Navigation Satellite System data set is used to check the performance of the proposed method. Most cycle slips, no matter trivial or nontrivial, can be estimated in float values with satisfactorily high accuracy and their integer values can hence be correctly obtained by simple rounding. To be more specific, all manually introduced nontrivial cycle slips are correctly repaired.

Salvage hypospadias repairs

PubMed Central

Sripathi, V.; Satheesh, M.; Shubha, K.

2008-01-01

Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children – buccal mucosal grafts (BMGs) in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5–15 years (mean 4.5). Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50%) with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely – a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4–6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised. PMID:20011495

Salvage hypospadias repairs.

PubMed

Sripathi, V; Satheesh, M; Shubha, K

2008-10-01

Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs) in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. The age of children ranged from 1.5-15 years (mean 4.5). Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50%) with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

Free-Inertial and Damped-Inertial Navigation Mechanization and Error Equations

DTIC Science & Technology

1975-04-18

AD-A014 356 FREE-INERTIAL AND DAMPED-INERTIAL NAVIGATION MECHANIZATION AND ERROR EQUATIONS Warren G. Heller Analytic Sciences Corporation Prepared...IHI IL JI -J THE ANALYTIC SCIENCES CORPORATION TR-312-1-1 FREE-INERTIAL AND DAMPED-INERTIAL NAViGATION MECHANIZATION AND ERROR EQUATIONS Ap~ril 18...PERIOO COVC/REO Fr-,- 1wer l and Dmped-Inertial Navigation Technical Mechanization and Error Equations 8/20-73 - 8/20/74 S. PjLtFORJ4djNjOjO, REPORT

Genomic stability and telomere regulation in skeletal muscle tissue.

PubMed

Trajano, Larissa Alexsandra da Silva Neto; Trajano, Eduardo Tavares Lima; Silva, Marco Aurélio Dos Santos; Stumbo, Ana Carolina; Mencalha, Andre Luiz; Fonseca, Adenilson de Souza da

2018-02-01

Muscle injuries are common, especially in sports and cumulative trauma disorder, and their repair is influenced by free radical formation, which causes damages in lipids, proteins and DNA. Oxidative DNA damages are repaired by base excision repair and nucleotide excision repair, ensuring telomeric and genomic stability. There are few studies on this topic in skeletal muscle cells. This review focuses on base excision repair and nucleotide excision repair, telomere regulation and how telomeric stabilization influences healthy muscle, injured muscle, exercise, and its relationship with aging. In skeletal muscle, genomic stabilization and telomere regulation seem to play an important role in tissue health, influencing muscle injury repair. Thus, therapies targeting mechanisms of DNA repair and telomeric regulation could be new approaches for improving repair and prevention of skeletal muscle injuries in young and old people. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

California's "Free" Universities

ERIC Educational Resources Information Center

Cudhea, David

1974-01-01

Heliotrope, Orpheus, and Communiversity, San Francisco's three free universities, offer curricula with combinations of alchemy, magic, Volkswagen repairs, options in education, dance, conversational Mandarin, basic plumbing, and brain wave experiences. (Author/PG)

Parecoxib sodium in the treatment of postoperative pain after Lichtenstein tension-free mesh inguinal hernia repair.

PubMed

Kyriakidis, A V; Perysinakis, I; Alexandris, I; Athanasiou, K; Papadopoulos, Ch; Mpesikos, I

2011-02-01

This prospective, randomized, double-blind study compared the analgesic efficacy and safety of parecoxib sodium versus lornoxicam and diclofenac, after Lichtenstein tension-free mesh inguinal hernia repair. Patients were randomly assigned to receive parecoxib 80 mg daily i.v. (Group A), lornoxicam 16 mg daily i.v. (Group B) or diclofenac 150 mg daily i.m. (Group C). Rescue analgesia in all groups consisted of pethidine 25 mg i.m. Pain was measured with an analogue scale (pain intensity score). Patients treated with parecoxib 80 mg reported significantly lower summed pain intensity scores compared with lornoxicam and diclofenac-treated patients. Duration of analgesia was also significantly longer with parecoxib than with lornoxicam and diclofenac. Adverse events were significantly less common in the parecoxib and lornoxicam group, compared with diclofenac group. Multiple-day administration of parecoxib 40 mg twice daily is more effective than equivalent doses of lornoxicam and diclofenac, and generally better tolerated than diclofenac after Lichtenstein tension-free mesh inguinal hernia repair.

Effect of tif expression, irradiation of recipient and presence of plasmid pKM101 on recovery of a marker from a donor exposed to ultraviolet light prior to conjugation.

PubMed

von Wright, A; Bridges, B A

1980-08-01

To detect the effect of the postulated inducible error-prone repair system ('SOS repair') on the bacterial chromosome, an Hfr Escherichia coli strain JC5088 recA was u.v.-irradiated immediately before mating it with recipients in which SOS repair was supposed to be functioning through tif expression, u.v. irradiation or the presence of plasmid pKM101. The recombinant yields of these crosses were compared with those obtained in corresponding crosses with recipients in which SOS repair either was not induced or was totally eliminated by the lexA mutation. No difference in marker recovery efficiency could be detected between these two sets of recipients and thus no induced repair process acting on donor DNA could be demonstrated. The possible reasons for this finding are discussed.

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage.

PubMed

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C M; Jansen, Jacob G; Hogenbirk, Marc A; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (Pcna(K164R)) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn 4CaO 5-cluster in photosystem II

DOE PAGES

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; ...

2017-07-18

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4CaO 5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4CaO 5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water moleculesmore » largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4CaO 5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.« less

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II.

PubMed

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina

2017-07-18

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4 CaO 5 -cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4 CaO 5 -cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4 CaO 5 -cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn 4 CaO 5 -cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.

Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli.

PubMed

Moore, Jessica M; Correa, Raul; Rosenberg, Susan M; Hastings, P J

2017-07-01

Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS oxidation of DNA potentially regulated by ROS regulators.

Persistent damaged bases in DNA allow mutagenic break repair in Escherichia coli

PubMed Central

Moore, Jessica M.; Correa, Raul; Rosenberg, Susan M.

2017-01-01

Bacteria, yeast and human cancer cells possess mechanisms of mutagenesis upregulated by stress responses. Stress-inducible mutagenesis potentially accelerates adaptation, and may provide important models for mutagenesis that drives cancers, host pathogen interactions, antibiotic resistance and possibly much of evolution generally. In Escherichia coli repair of double-strand breaks (DSBs) becomes mutagenic, using low-fidelity DNA polymerases under the control of the SOS DNA-damage response and RpoS general stress response, which upregulate and allow the action of error-prone DNA polymerases IV (DinB), II and V to make mutations during repair. Pol IV is implied to compete with and replace high-fidelity DNA polymerases at the DSB-repair replisome, causing mutagenesis. We report that up-regulated Pol IV is not sufficient for mutagenic break repair (MBR); damaged bases in the DNA are also required, and that in starvation-stressed cells, these are caused by reactive-oxygen species (ROS). First, MBR is reduced by either ROS-scavenging agents or constitutive activation of oxidative-damage responses, both of which reduce cellular ROS levels. The ROS promote MBR other than by causing DSBs, saturating mismatch repair, oxidizing proteins, or inducing the SOS response or the general stress response. We find that ROS drive MBR through oxidized guanines (8-oxo-dG) in DNA, in that overproduction of a glycosylase that removes 8-oxo-dG from DNA prevents MBR. Further, other damaged DNA bases can substitute for 8-oxo-dG because ROS-scavenged cells resume MBR if either DNA pyrimidine dimers or alkylated bases are induced. We hypothesize that damaged bases in DNA pause the replisome and allow the critical switch from high fidelity to error-prone DNA polymerases in the DSB-repair replisome, thus allowing MBR. The data imply that in addition to the indirect stress-response controlled switch to MBR, a direct cis-acting switch to MBR occurs independently of DNA breakage, caused by ROS oxidation of DNA potentially regulated by ROS regulators. PMID:28727736

CARDS - comprehensive aerological reference data set. Station history, Version 2.1

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

NONE

1994-03-01

The possibility of anthropogenic climate change has reached the attention of Government officials and researchers. However, one cannot study climate change without climate data. The CARDS project will produce high-quality upper-air data for the research community and for policy-makers. The authors intend to produce a dataset which is: easy to use, as complete as possible, as free of random errors as possible. They will also attempt to identify biases and remove them whenever possible. In this report, they relate progress toward their goal. They created a robust new format for archiving upper-air data, and designed a relational database structure tomore » hold them. The authors have converted 13 datasets to the new format and have archived over 10,000,000 individual soundings from 10 separate data sources. They produce and archive a metadata summary of each sounding they load. They have researched station histories, and have built a preliminary upper-air station history database. They have converted station-sorted data from their primary database into synoptic-sorted data in a parallel database. They have tested and will soon implement an advanced quality-control procedure, capable of detecting and often repairing errors in geopotential height, temperature, humidity, and wind. This unique quality-control method uses simultaneous vertical, horizontal, and temporal checks of several meteorological variables. It can detect errors other methods cannot. This report contains the station histories for the CARDS data set.« less

Achieving unequal error protection with convolutional codes

NASA Technical Reports Server (NTRS)

Mills, D. G.; Costello, D. J., Jr.; Palazzo, R., Jr.

1994-01-01

This paper examines the unequal error protection capabilities of convolutional codes. Both time-invariant and periodically time-varying convolutional encoders are examined. The effective free distance vector is defined and is shown to be useful in determining the unequal error protection (UEP) capabilities of convolutional codes. A modified transfer function is used to determine an upper bound on the bit error probabilities for individual input bit positions in a convolutional encoder. The bound is heavily dependent on the individual effective free distance of the input bit position. A bound relating two individual effective free distances is presented. The bound is a useful tool in determining the maximum possible disparity in individual effective free distances of encoders of specified rate and memory distribution. The unequal error protection capabilities of convolutional encoders of several rates and memory distributions are determined and discussed.

[Vascular crisis after multiple tissue transplantation for thumb and other finger reconstruction by toe-to-hand transfer].

PubMed

Zhang, Jian; Huang, Jian; Pan, Jiadong; Zhou, Danya; Yin, Shanqing; Li, Junjie; Wang, Xin

2017-03-01

To explore the causes of vascular crisis after thumb and other finger reconstruction by toe-to-hand transfer and effective treatment methods so as to improve the survival rate of transplanted tissues. Between February 2012 and October 2015, 59 cases of thumb and other finger defects were repaired with different hallux nail flaps with the same vascular pedicle flap to reconstruct thumb and other fingers and repair skin defect. The donor site was repaired by a perforator flap. A total of 197 free tissues were involved. There were 46 males and 13 females with the average age of 30.6 years (range, 18-42 years). Vascular crisis occurred in 21 free tissues (10.7%) of 17 patients, including 9 arterial crisis (4.6%) of 8 cases, and 12 venous crisis (6.1%) of 10 cases. Conservative treatment was performed first; in 8 free tissues of 7 cases after failure of conservative treatment, anastomotic thrombosis was found in 5 free tissues of 4 cases, twisted vascular pedicle in 1 free tissue of 1 case, surrounding hematoma in 1 free tissue of 1 case, and anastomotic thrombosis associated with hematoma in 1 free tissue of 1 case, which underwent clearing hematoma, resecting embolization, regulating vascular tension, re-anastomosis or vascular transplantation. In 8 cases of arterial crisis, 5 free tissues of 5 cases survived after conservative treatment; partial necrosis occurred in 1 free tissue (1 case) of 4 free tissues (3 cases) undergoing surgical exploration. In 10 cases of venous crisis, 1 free tissue necrosis and 1 free tissue partial necrosis occurred in 8 free tissues (6 cases) undergoing conservative treatment; partial necrosis occurred in 1 free tissue of 4 free tissues (4 cases) undergoing surgical exploration. Free flap and skin graft were performed on 2 free tissues of 4 cases having flap necrosis respectively. Vascular crisis is complex and harmful to survival of transplanted tissue in reconstruction of the thumb and other fingers. Immediate intervention is helpful to obtain a higher survival rate.

Low intensity infrared laser affects expression of oxidative DNA repair genes in mitochondria and nucleus

NASA Astrophysics Data System (ADS)

Fonseca, A. S.; Magalhães, L. A. G.; Mencalha, A. L.; Geller, M.; Paoli, F.

2014-11-01

Practical properties and physical characteristics of low intensity lasers have made possible their application to treat soft tissue diseases. Excitation of intracellular chromophores by red and infrared radiation at low energy fluences with increase of mitochondrial metabolism is the basis of the biostimulation effect but free radicals can be produced. DNA lesions induced by free radicals are repaired by the base excision repair pathway. In this work, we evaluate the expression of POLγ and APEX2 genes related to repair of mitochondrial and nuclear DNA, respectively. Skin and muscle tissue of Wistar rats were exposed to low intensity infrared laser at different fluences. One hour and 24 hours after laser exposure, tissue samples were withdrawn for total RNA extraction, cDNA synthesis, and evaluation of POLγ and APEX2 mRNA expression by real time quantitative polymerase chain reaction. Skin and muscle tissue of Wistar rats exposed to laser radiation show different expression of POLγ and APEX2 mRNA depending of the fluence and time after exposure. Our study suggests that a low intensity infrared laser affects expression of genes involved in repair of oxidative lesions in mitochondrial and nuclear DNA.

Chromosomal bands affected by acute oil exposure and DNA repair errors.

PubMed

Monyarch, Gemma; de Castro Reis, Fernanda; Zock, Jan-Paul; Giraldo, Jesús; Pozo-Rodríguez, Francisco; Espinosa, Ana; Rodríguez-Trigo, Gema; Verea, Hector; Castaño-Vinyals, Gemma; Gómez, Federico P; Antó, Josep M; Coll, Maria Dolors; Barberà, Joan Albert; Fuster, Carme

2013-01-01

In a previous study, we showed that individuals who had participated in oil clean-up tasks after the wreckage of the Prestige presented an increase of structural chromosomal alterations two years after the acute exposure had occurred. Other studies have also reported the presence of DNA damage during acute oil exposure, but little is known about the long term persistence of chromosomal alterations, which can be considered as a marker of cancer risk. We analyzed whether the breakpoints involved in chromosomal damage can help to assess the risk of cancer as well as to investigate their possible association with DNA repair efficiency. Cytogenetic analyses were carried out on the same individuals of our previous study and DNA repair errors were assessed in cultures with aphidicolin. Three chromosomal bands, 2q21, 3q27 and 5q31, were most affected by acute oil exposure. The dysfunction in DNA repair mechanisms, expressed as chromosomal damage, was significantly higher in exposed-oil participants than in those not exposed (p= 0.016). The present study shows that breaks in 2q21, 3q27 and 5q31 chromosomal bands, which are commonly involved in hematological cancer, could be considered useful genotoxic oil biomarkers. Moreover, breakages in these bands could induce chromosomal instability, which can explain the increased risk of cancer (leukemia and lymphomas) reported in chronically benzene-exposed individuals. In addition, it has been determined that the individuals who participated in clean-up of the oil spill presented an alteration of their DNA repair mechanisms two years after exposure.

Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene.

PubMed

Chakravarti, D; Mailander, P C; Li, K M; Higginbotham, S; Zhang, H L; Gross, M L; Meza, J L; Cavalieri, E L; Rogan, E G

2001-11-29

Treatment of SENCAR mouse skin with dibenzo[a,l]pyrene results in abundant formation of abasic sites that undergo error-prone excision repair, forming oncogenic H-ras mutations in the early preneoplastic period. To examine whether the abundance of abasic sites causes repair infidelity, we treated SENCAR mouse skin with estradiol-3,4-quinone (E(2)-3,4-Q) and determined adduct levels 1 h after treatment, as well as mutation spectra in the H-ras gene between 6 h and 3 days after treatment. E(2)-3,4-Q formed predominantly (> or =99%) the rapidly-depurinating 4-hydroxy estradiol (4-OHE(2))-1-N3Ade adduct and the slower-depurinating 4-OHE(2)-1-N7Gua adduct. Between 6 h and 3 days, E(2)-3,4-Q induced abundant A to G mutations in H-ras DNA, frequently in the context of a 3'-G residue. Using a T.G-DNA glycosylase (TDG)-PCR assay, we determined that the early A to G mutations (6 and 12 h) were in the form of G.T heteroduplexes, suggesting misrepair at A-specific depurination sites. Since G-specific mutations were infrequent in the spectra, it appears that the slow rate of depurination of the N7Gua adducts during active repair may not generate a threshold level of G-specific abasic sites to affect repair fidelity. These results also suggest that E(2)-3,4-Q, a suspected endogenous carcinogen, is a genotoxic compound and could cause mutations.

Changes in the frequencies of abdominal wall hernias and the preferences for their repair: a multicenter national study from Turkey.

PubMed

Seker, Gaye; Kulacoglu, Hakan; Öztuna, Derya; Topgül, Koray; Akyol, Cihangir; Çakmak, Atıl; Karateke, Faruk; Özdoğan, Mehmet; Ersoy, Eren; Gürer, Ahmet; Zerbaliyev, Elbrus; Seker, Duray; Yorgancı, Kaya; Pergel, Ahmet; Aydın, Ibrahim; Ensari, Cemal; Bilecik, Tuna; Kahraman, İzzettin; Reis, Erhan; Kalaycı, Murat; Canda, Aras Emre; Demirağ, Alp; Kesicioğlu, Tuğrul; Malazgirt, Zafer; Gündoğdu, Haldun; Terzi, Cem

2014-01-01

Abdominal wall hernias are a common problem in the general population. A Western estimate reveals that the lifetime risk of developing a hernia is about 2%. As a result, hernia repairs likely comprise the most frequent general surgery operations. More than 20 million hernias are estimated to be repaired every year around the world. Numerous repair techniques have been described to date however tension-free mesh repairs are widely used today because of their low hernia recurrence rates. Nevertheless, there are some ongoing debates regarding the ideal approach (open or laparoscopic), the ideal anesthesia (general, local, or regional), and the ideal mesh (standard polypropylene or newer meshes).

Free tarsomarginal graft for large congenital coloboma repair in patients with Tessier number 10 clefts.

PubMed

Fu, Yao; Shao, Chunyi; Lu, Wenjuan; Li, Jin; Fan, Xianqun

2016-08-01

The aim of this study was to evaluate the long-term outcome when a free tarsomarginal graft is used to repair a large congenital coloboma in patients with a Tessier number 10 cleft. This was a retrospective, interventional case series. The medical records were reviewed for five children (six eyes) diagnosed as having Tessier number 10 cleft with large upper eyelid defects and symblepharon. These children were referred to the Department of Ophthalmology of Shanghai Ninth People's Hospital, between May 2007 and December 2012. Reconstructive techniques included repair of the upper eyelid defect with a free tarsomarginal graft taken from the lower eyelid, and reconstruction of the conjunctival fornix by using a conjunctival autograft after symblepharon lysis. All the children were followed up for more than 2 years. Postoperative upper eyelid contour, viability and function for corneal protection, and recurrence of symblepharon were assessed. A one-stage reconstruction procedure was used in all children. All reconstructed eyelids achieved a surgical goal of providing corneal protection and improved cosmesis, with marked improvement of exposure keratopathy and no associated lagophthalmos. Adequate reconstruction of the upper fornix was obtained, and there was no obvious recurrence of symblepharon. A free tarsomarginal graft is beneficial and seems to be an adequate method for reconstruction of large eyelid defects in children with a Tessier number 10 cleft. Symblepharon lysis with a conjunctival autograft for reconstruction of the ocular surface can be performed at the same time as eyelid repair as a one-stage procedure. Copyright © 2016. Published by Elsevier Ltd.

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

PubMed Central

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

2017-01-01

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

Repair of damaged DNA in-vivo. Comprehensive progress report, August 1980-August 1983

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

Hanawalt, P.C.

1983-07-01

We have extended our characterization of long patch excision repair (LPER) and have demonstrated that LPER is not mutagenic (or error-prone); that the recA function is required for LPER, at least for its regulation; that the substrate for LPER is produced as a linear (not an exponential) function of uv (254 nm) dose; and that LPER can occur in uvr/sup -/ cells treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG). We have developed 3 methods for measuring the frequency of interstrand crosslinks in DNA and are now applying these methods to the study of the formation and repair of DNA crosslinks in E.Coli. Wemore » have developed a monoclonal antibody specific for thymine glycol in DNA, and are using it to study the repair of thymine glycol in E. coli.« less

Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.

PubMed

Schrank, Benjamin R; Aparicio, Tomas; Li, Yinyin; Chang, Wakam; Chait, Brian T; Gundersen, Gregg G; Gottesman, Max E; Gautier, Jean

2018-06-20

DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters. Actin-driven movements specifically affect double-strand breaks repaired by homology-directed repair in G2 cell cycle phase; inhibition of actin nucleation impairs DNA end-processing and homology-directed repair. By contrast, ARP2/3 is not enriched at double-strand breaks repaired by non-homologous end joining and does not regulate non-homologous end joining. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.

Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers.

PubMed

Shlien, Adam; Campbell, Brittany B; de Borja, Richard; Alexandrov, Ludmil B; Merico, Daniele; Wedge, David; Van Loo, Peter; Tarpey, Patrick S; Coupland, Paul; Behjati, Sam; Pollett, Aaron; Lipman, Tatiana; Heidari, Abolfazl; Deshmukh, Shriya; Avitzur, Na'ama; Meier, Bettina; Gerstung, Moritz; Hong, Ye; Merino, Diana M; Ramakrishna, Manasa; Remke, Marc; Arnold, Roland; Panigrahi, Gagan B; Thakkar, Neha P; Hodel, Karl P; Henninger, Erin E; Göksenin, A Yasemin; Bakry, Doua; Charames, George S; Druker, Harriet; Lerner-Ellis, Jordan; Mistry, Matthew; Dvir, Rina; Grant, Ronald; Elhasid, Ronit; Farah, Roula; Taylor, Glenn P; Nathan, Paul C; Alexander, Sarah; Ben-Shachar, Shay; Ling, Simon C; Gallinger, Steven; Constantini, Shlomi; Dirks, Peter; Huang, Annie; Scherer, Stephen W; Grundy, Richard G; Durno, Carol; Aronson, Melyssa; Gartner, Anton; Meyn, M Stephen; Taylor, Michael D; Pursell, Zachary F; Pearson, Christopher E; Malkin, David; Futreal, P Andrew; Stratton, Michael R; Bouffet, Eric; Hawkins, Cynthia; Campbell, Peter J; Tabori, Uri

2015-03-01

DNA replication-associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from children with inherited biallelic mismatch repair deficiency (bMMRD). High-grade bMMRD brain tumors exhibited massive numbers of substitution mutations (>250/Mb), which was greater than all childhood and most cancers (>7,000 analyzed). All ultra-hypermutated bMMRD cancers acquired early somatic driver mutations in DNA polymerase ɛ or δ. The ensuing mutation signatures and numbers are unique and diagnostic of childhood germ-line bMMRD (P < 10(-13)). Sequential tumor biopsy analysis revealed that bMMRD/polymerase-mutant cancers rapidly amass an excess of simultaneous mutations (∼600 mutations/cell division), reaching but not exceeding ∼20,000 exonic mutations in <6 months. This implies a threshold compatible with cancer-cell survival. We suggest a new mechanism of cancer progression in which mutations develop in a rapid burst after ablation of replication repair.

Software Health Management: A Short Review of Challenges and Existing Techniques

NASA Technical Reports Server (NTRS)

Pipatsrisawat, Knot; Darwiche, Adnan; Mengshoel, Ole J.; Schumann, Johann

2009-01-01

Modern spacecraft (as well as most other complex mechanisms like aircraft, automobiles, and chemical plants) rely more and more on software, to a point where software failures have caused severe accidents and loss of missions. Software failures during a manned mission can cause loss of life, so there are severe requirements to make the software as safe and reliable as possible. Typically, verification and validation (V&V) has the task of making sure that all software errors are found before the software is deployed and that it always conforms to the requirements. Experience, however, shows that this gold standard of error-free software cannot be reached in practice. Even if the software alone is free of glitches, its interoperation with the hardware (e.g., with sensors or actuators) can cause problems. Unexpected operational conditions or changes in the environment may ultimately cause a software system to fail. Is there a way to surmount this problem? In most modern aircraft and many automobiles, hardware such as central electrical, mechanical, and hydraulic components are monitored by IVHM (Integrated Vehicle Health Management) systems. These systems can recognize, isolate, and identify faults and failures, both those that already occurred as well as imminent ones. With the help of diagnostics and prognostics, appropriate mitigation strategies can be selected (replacement or repair, switch to redundant systems, etc.). In this short paper, we discuss some challenges and promising techniques for software health management (SWHM). In particular, we identify unique challenges for preventing software failure in systems which involve both software and hardware components. We then present our classifications of techniques related to SWHM. These classifications are performed based on dimensions of interest to both developers and users of the techniques, and hopefully provide a map for dealing with software faults and failures.

Understanding DNA Repair in Hyperthermophilic Archaea: Persistent Gaps and Other Reasons to Focus on the Fork

PubMed Central

Grogan, Dennis W.

2015-01-01

Although hyperthermophilic archaea arguably have a great need for efficient DNA repair, they lack members of several DNA repair protein families broadly conserved among bacteria and eukaryotes. Conversely, the putative DNA repair genes that do occur in these archaea often do not generate the expected phenotype when deleted. The prospect that hyperthermophilic archaea have some unique strategies for coping with DNA damage and replication errors has intellectual and technological appeal, but resolving this question will require alternative coping mechanisms to be proposed and tested experimentally. This review evaluates a combination of four enigmatic properties that distinguishes the hyperthermophilic archaea from all other organisms: DNA polymerase stalling at dU, apparent lack of conventional NER, lack of MutSL homologs, and apparent essentiality of homologous recombination proteins. Hypothetical damage-coping strategies that could explain this set of properties may provide new starting points for efforts to define how archaea differ from conventional models of DNA repair and replication fidelity. PMID:26146487

Next Generation Mesenchymal Stem Cell (MSC)–Based Cartilage Repair Using Scaffold-Free Tissue Engineered Constructs Generated with Synovial Mesenchymal Stem Cells

PubMed Central

Shimomura, Kazunori; Ando, Wataru; Moriguchi, Yu; Sugita, Norihiko; Yasui, Yukihiko; Koizumi, Kota; Fujie, Hiromichi; Hart, David A.; Yoshikawa, Hideki

2015-01-01

Because of its limited healing capacity, treatments for articular cartilage injuries are still challenging. Since the first report by Brittberg, autologous chondrocyte implantation has been extensively studied. Recently, as an alternative for chondrocyte-based therapy, mesenchymal stem cell–based therapy has received considerable research attention because of the relative ease in handling for tissue harvest, and subsequent cell expansion and differentiation. This review summarizes latest development of stem cell therapies in cartilage repair with special attention to scaffold-free approaches. PMID:27340513

Can We Fix This? Parent-Child Repair Processes and Preschoolers' Regulatory Skills.

PubMed

Kemp, Christine J; Lunkenheimer, Erika; Albrecht, Erin C; Chen, Deborah

2016-10-01

The repair of difficult parent-child interactions is a marker of healthy functioning in infancy, but less is known about repair processes during early childhood. We used dynamic systems methods to investigate dyadic repair in mothers and their 3-year-old children ( N = 96) and its prediction of children's emotion regulation and behavior problems at a four-month follow-up. Mothers and children completed free play and challenging puzzle tasks. Repair was operationalized as the conditional probability of moving into a dyadic adaptive behavior region after individual or dyadic maladaptive behavior (e.g., child noncompliance, parental criticism). Overall, dyads repaired approximately half their maladaptive behaviors. A greater likelihood of repair during the puzzle task predicted better child emotion regulation and fewer behavior problems in preschool. Results suggest dyadic repair is an important process in early childhood and provide further evidence for the connection between parent-child coregulation and children's developing regulatory capacities. Implications for family-based interventions are discussed.

Description of Communication Breakdown Repair Strategies Produced by Nonverbal Students with Developmental Disabilities

ERIC Educational Resources Information Center

Dincer, Baris; Erbas, Dilek

2010-01-01

This study describes the communication repair behaviors used by nonverbal students with developmental disabilities in the interactions they were involved in with their teachers during free play activities. All children were students at centers serving student with developmental disabilities at Anadolu University in Turkey. Data were collected by…

Algorithm for repairing the damaged images of grain structures obtained from the cellular automata and measurement of grain size

NASA Astrophysics Data System (ADS)

Ramírez-López, A.; Romero-Romo, M. A.; Muñoz-Negron, D.; López-Ramírez, S.; Escarela-Pérez, R.; Duran-Valencia, C.

2012-10-01

Computational models are developed to create grain structures using mathematical algorithms based on the chaos theory such as cellular automaton, geometrical models, fractals, and stochastic methods. Because of the chaotic nature of grain structures, some of the most popular routines are based on the Monte Carlo method, statistical distributions, and random walk methods, which can be easily programmed and included in nested loops. Nevertheless, grain structures are not well defined as the results of computational errors and numerical inconsistencies on mathematical methods. Due to the finite definition of numbers or the numerical restrictions during the simulation of solidification, damaged images appear on the screen. These images must be repaired to obtain a good measurement of grain geometrical properties. Some mathematical algorithms were developed to repair, measure, and characterize grain structures obtained from cellular automata in the present work. An appropriate measurement of grain size and the corrected identification of interfaces and length are very important topics in materials science because they are the representation and validation of mathematical models with real samples. As a result, the developed algorithms are tested and proved to be appropriate and efficient to eliminate the errors and characterize the grain structures.

RADH, a gene of Saccharomyces cerevisiae encoding a putative DNA helicase involved in DNA repair. Characteristics of radH mutants and sequence of the gene.

PubMed

Aboussekhra, A; Chanet, R; Zgaga, Z; Cassier-Chauvat, C; Heude, M; Fabre, F

1989-09-25

A new type of radiation-sensitive mutant of S. cerevisiae is described. The recessive radH mutation sensitizes to the lethal effect of UV radiations haploids in the G1 but not in the G2 mitotic phase. Homozygous diploids are as sensitive as G1 haploids. The UV-induced mutagenesis is depressed, while the induction of gene conversion is increased. The mutation is believed to channel the repair of lesions engaged in the mutagenic pathway into a recombination process, successful if the events involve sister-chromatids but lethal if they involve homologous chromosomes. The sequence of the RADH gene reveals that it may code for a DNA helicase, with a Mr of 134 kDa. All the consensus domains of known DNA helicases are present. Besides these consensus regions, strong homologies with the Rep and UvrD helicases of E. coli were found. The RadH putative helicase appears to belong to the set of proteins involved in the error-prone repair mechanism, at least for UV-induced lesions, and could act in coordination with the Rev3 error-prone DNA polymerase.

XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes.

PubMed Central

van der Spek, P J; Eker, A; Rademakers, S; Visser, C; Sugasawa, K; Masutani, C; Hanaoka, F; Bootsma, D; Hoeijmakers, J H

1996-01-01

The xeroderma pigmentosum syndrome complementation group C (XP-C) is due to a defect in the global genome repair subpathway of nucleotide excision repair (NER). The XPC protein is complexed with HHR23B, one of the two human homologs of the yeast NER protein, RAD23 (Masutani at al. (1994) EMBO J. 8, 1831-1843). Using heparin chromatography, gel filtration and native gel electrophoresis we demonstrate that the majority of HHR23B is in a free, non-complexed form, and that a minor fraction is tightly associated with XPC. In contrast, we cannot detect any bound HHR23A. Thus the HHR23 proteins may have an additional function independent of XPC. The fractionation behaviour suggests that the non-bound forms of the HHR23 proteins are not necessary for the core of the NER reaction. Although both HHR23 proteins share a high level of overall homology, they migrate very differently on native gels, pointing to a difference in conformation. Gel filtration suggests the XPC-HHR23B heterodimer resides in a high MW complex. However, immunodepletion studies starting from repair-competent Manley extracts fall to reveal a stable association of a significant fraction of the HHR23 proteins or the XPC-HHR23B complex with the basal transcription/repair factor TFIIH, or with the ERCC1 repair complex. Consistent with a function in repair or DNA/chromatin metabolism, immunofluorescence studies show all XPC, HHR23B and (the free) HHR23A to reside in the nucleus. PMID:8692695

Single-Stage Cartilage Repair Using Platelet-Rich Fibrin Scaffolds With Autologous Cartilaginous Grafts.

PubMed

Wong, Chin-Chean; Chen, Chih-Hwa; Chan, Wing P; Chiu, Li-Hsuan; Ho, Wei-Pin; Hsieh, Fon-Jou; Chen, You-Tzung; Yang, Tsung-Lin

2017-11-01

To avoid complicated procedures requiring in vitro chondrocyte expansion for cartilage repair, the development of a culture-free, 1-stage approach combining platelet-rich fibrin (PRF) and autologous cartilage grafts may be the solution. To develop a feasible 1-step procedure to combine PRF and autologous cartilage grafts for articular chondral defects. Controlled laboratory study Methods: The chemotactic effects of PRF on chondrocytes harvested from the primary culture of rabbit cartilage were evaluated in vitro and ex vivo. The rabbit chondrocytes were cultured with different concentrations of PRF media and evaluated for their cell proliferation, chondrogenic gene expression, cell viability, and extracellular matrix synthesis abilities. For the in vivo study, the chondral defects were created on established animal models of rabbits. The gross anatomy, histology, and objective scores were evaluated to validate the treatment results. PRF improved the chemotaxis, proliferation, and viability of the cultured chondrocytes. The gene expression of the chondrogenic markers, including type II collagen and aggrecan, revealed that PRF induced the chondrogenic differentiation of cultured chondrocytes. PRF increased the formation and deposition of the cartilaginous matrix produced by cultured chondrocytes. The efficacy of PRF on cell viability was comparable with that of fetal bovine serum. In animal disease models, morphologic, histological, and objectively quantitative evaluation demonstrated that PRF combined with cartilage granules was feasible in facilitating chondral repair. PRF enhances the migration, proliferation, viability, and differentiation of chondrocytes, thus showing an appealing capacity for cartilage repair. The data altogether provide evidence to confirm the feasibility of 1-stage, culture-free method of combining PRF and autologous cartilage graft for repairing articular chondral defects. The single-stage, culture-free method of combining PRF and autologous cartilage is useful for repairing articular chondral defects. These advantages benefit clinical translation by simplifying and potentiating the efficacy of autologous cartilage transplantation.

Model-based influences on humans’ choices and striatal prediction errors

PubMed Central

Daw, Nathaniel D.; Gershman, Samuel J.; Seymour, Ben; Dayan, Peter; Dolan, Raymond J.

2011-01-01

Summary The mesostriatal dopamine system is prominently implicated in model-free reinforcement learning, with fMRI BOLD signals in ventral striatum notably covarying with model-free prediction errors. However, latent learning and devaluation studies show that behavior also shows hallmarks of model-based planning, and the interaction between model-based and model-free values, prediction errors and preferences is underexplored. We designed a multistep decision task in which model-based and model-free influences on human choice behavior could be distinguished. By showing that choices reflected both influences we could then test the purity of the ventral striatal BOLD signal as a model-free report. Contrary to expectations, the signal reflected both model-free and model-based predictions in proportions matching those that best explained choice behavior. These results challenge the notion of a separate model-free learner and suggest a more integrated computational architecture for high-level human decision-making. PMID:21435563

Does topical rifampicin reduce the risk of surgical field infection in hernia repair?

PubMed Central

Kahramanca, Şahin; Kaya, Oskay; Azılı, Cem; Celep, Bahadır; Gökce, Emre; Küçükpınar, Tevfik

2013-01-01

Objective: Inguinal hernia operations are common procedures in general surgery. There have been many approaches in the historical development of hernia repair; tension free repair with mesh being the most commonly used technique today. Although it is a clean wound, antibiotic use is still controversial due to concerns about infection related to synthetic mesh. We aimed to determine the probable role of topical rifampicin in patients with tension-free hernia repair and mesh support. Material and Methods: The charts of patients who underwent tension-free inguinal hernia repair were retrospectively analyzed. Information and operative notes on patients, in whom synthetic materials were used, were identified. The patients were divided into two groups, placebo group (G1) and patients with application of topical rifampicin on the mesh (G2). Infection rates between the groups in the early postoperative period were compared. Results: The mean age of the 278 patients who were included in the study was 49.6±15.39 and the female/male ratio was 10/268. There were recurrent hernias in four patients and superficial wound infections in 22 patients in the early period. One patient had testicle torsion and underwent an orchiectomy. There were no significant differences between the groups in terms of age and gender. The types of hernia and body mass index were homogenous between the two groups. In the early postoperative period the infection rates were 16/144 (11.1%) and 6/134 (4.48%) in the groups, respectively, with the difference being statistically significant (p=0.041). Conclusion: We suggest that applying rifampicin locally can decrease surgical site infection in hernia operations where meshes are used. PMID:25931846

Cost effectiveness of ergonomic redesign of electronic motherboard.

PubMed

Sen, Rabindra Nath; Yeow, Paul H P

2003-09-01

A case study to illustrate the cost effectiveness of ergonomic redesign of electronic motherboard was presented. The factory was running at a loss due to the high costs of rejects and poor quality and productivity. Subjective assessments and direct observations were made on the factory. Investigation revealed that due to motherboard design errors, the machine had difficulty in placing integrated circuits onto the pads, the operators had much difficulty in manual soldering certain components and much unproductive manual cleaning (MC) was required. Consequently, there were high rejects and occupational health and safety (OHS) problems, such as, boredom and work discomfort. Also, much labour and machine costs were spent on repairs. The motherboard was redesigned to correct the design errors, to allow more components to be machine soldered and to reduce MC. This eliminated rejects, reduced repairs, saved US dollars 581495/year and improved operators' OHS. The customer also saved US dollars 142105/year on loss of business.

Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases

PubMed Central

DeBalsi, Karen L.; Hoff, Kirsten E.; Copeland, William C.

2016-01-01

As regulators of bioenergetics in the cell and the primary source of endogenous reactive oxygen species (ROS), dysfunctional mitochondria have been implicated for decades in the process of aging and age-related diseases. Mitochondrial DNA (mtDNA) is replicated and repaired by nuclear-encoded mtDNA polymerase γ (Pol γ) and several other associated proteins, which compose the mtDNA replication machinery. Here, we review evidence that errors caused by this replication machinery and failure to repair these mtDNA errors results in mtDNA mutations. Clonal expansion of mtDNA mutations results in mitochondrial dysfunction, such as decreased electron transport chain (ETC) enzyme activity and impaired cellular respiration. We address the literature that mitochondrial dysfunction, in conjunction with altered mitochondrial dynamics, is a major driving force behind aging and age-related diseases. Additionally, interventions to improve mitochondrial function and attenuate the symptoms of aging are examined. PMID:27143693

Anterior transversalis fascia approach versus preperitoneal space approach for inguinal hernia repair in residents in northern China: study protocol for a prospective, multicentre, randomised, controlled trial

PubMed Central

Fan, Qing; Zhang, De-wei; Yang, Da-ye; Li, Hong-wu; Wei, Shi-bo; Yang, Liang; Yang, Fu-quan; Zhang, Shao-jun; Wu, Yao-qiang; An, Wei-de; Dai, Zhong-shu; Jiang, Hui-yong; Wang, Fu-rong; Qiao, Shi-feng; Li, Hang-yu

2017-01-01

Introduction Many surgical techniques have been used to repair abdominal wall defects in the inguinal region based on the anatomic characteristics of this region and can be categorised as ‘tension’ repair or ‘tension-free’ repair. Tension-free repair is the preferred technique for inguinal hernia repair. Tension-free repair of inguinal hernia can be performed through either the anterior transversalis fascia approach or the preperitoneal space approach. There are few large sample, randomised controlled trials investigating the curative effects of the anterior transversalis fascia approach versus the preperitoneal space approach for inguinal hernia repair in patients in northern China. Methods and analysis This will be a prospective, large sample, multicentre, randomised, controlled trial. Registration date is 1 December 2016. Actual study start date is 6 February 2017. Estimated study completion date is June 2020. A cohort of over 720 patients with inguinal hernias will be recruited from nine institutions in Liaoning Province, China. Patient randomisation will be stratified by centre to undergo inguinal hernia repair via the anterior transversalis fascia approach or the preperitoneal approach. Primary and secondary outcome assessments will be performed at baseline (prior to surgery), predischarge and at postoperative 1 week, 1 month, 3 months, 1 year and 2 years. The primary outcome is the incidence of postoperative chronic inguinal pain. The secondary outcome is postoperative complications (including rates of wound infection, haematoma, seroma and hernia recurrence). Ethics and dissemination This trial will be conducted in accordance with the Declaration of Helsinki and supervised by the institutional review board of the Fourth Affiliated Hospital of China Medical University (approval number 2015–027). All patients will receive information about the trial in verbal and written forms and will give informed consent before enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number NCT02984917; preresults. PMID:28860228

Laparoscopic extraperitoneal inguinal hernia repair versus open mesh repair: long-term follow-up of a randomized controlled trial.

PubMed

Hallén, Magnus; Bergenfelz, Anders; Westerdahl, Johan

2008-03-01

We have conducted a randomized controlled trial of totally extraperitoneal hernia repair (TEP) versus tension-free open repair (Lichtenstein repair); we have presented the results previously up to 1 year after the operation. The aim of this study was to compare patient outcome in both groups at a median follow-up of 7.3 years after operation. Of 168 patients included in a prospective, randomized controlled trial designed to compare TEP with an open tension-free technique, 154 patients (92%) answered a questionnaire and 147 patients (88%) were followed up at an outpatient clinic after a minimum of 6 years after operation. Overall, 89% of patients in the TEP group and 95% of patients in the open group reported complete long-term recovery (P = .23). Permanent impaired inguinal sensibility was more common in the open group (P = .004), whereas the proportion of patients with reported testicular pain was higher in the TEP group (P = .003). Three recurrences were found in the TEP group, and 4 recurrences were found in the open group (P = .99). Four patients in the TEP group underwent operations for complications related to the hernia repair (small bowel obstruction, umbilical hernia, testicular pain, and neuralgia). Overall, both groups showed good long-term results with low rates of recurrences. However, the TEP group was associated with a higher proportion of patients with long-term testicular pain, whereas impaired inguinal sensibility was more common in the open group.

Error-correcting codes on scale-free networks

NASA Astrophysics Data System (ADS)

Kim, Jung-Hoon; Ko, Young-Jo

2004-06-01

We investigate the potential of scale-free networks as error-correcting codes. We find that irregular low-density parity-check codes with the highest performance known to date have degree distributions well fitted by a power-law function p (k) ˜ k-γ with γ close to 2, which suggests that codes built on scale-free networks with appropriate power exponents can be good error-correcting codes, with a performance possibly approaching the Shannon limit. We demonstrate for an erasure channel that codes with a power-law degree distribution of the form p (k) = C (k+α)-γ , with k⩾2 and suitable selection of the parameters α and γ , indeed have very good error-correction capabilities.

Systems Maintenance Automated Repair Tasks (SMART)

NASA Technical Reports Server (NTRS)

Schuh, Joseph; Mitchell, Brent; Locklear, Louis; Belson, Martin A.; Al-Shihabi, Mary Jo Y.; King, Nadean; Norena, Elkin; Hardin, Derek

2010-01-01

SMART is a uniform automated discrepancy analysis and repair-authoring platform that improves technical accuracy and timely delivery of repair procedures for a given discrepancy (see figure a). SMART will minimize data errors, create uniform repair processes, and enhance the existing knowledge base of engineering repair processes. This innovation is the first tool developed that links the hardware specification requirements with the actual repair methods, sequences, and required equipment. SMART is flexibly designed to be useable by multiple engineering groups requiring decision analysis, and by any work authorization and disposition platform (see figure b). The organizational logic creates the link between specification requirements of the hardware, and specific procedures required to repair discrepancies. The first segment in the SMART process uses a decision analysis tree to define all the permutations between component/ subcomponent/discrepancy/repair on the hardware. The second segment uses a repair matrix to define what the steps and sequences are for any repair defined in the decision tree. This segment also allows for the selection of specific steps from multivariable steps. SMART will also be able to interface with outside databases and to store information from them to be inserted into the repair-procedure document. Some of the steps will be identified as optional, and would only be used based on the location and the current configuration of the hardware. The output from this analysis would be sent to a work authoring system in the form of a predefined sequence of steps containing required actions, tools, parts, materials, certifications, and specific requirements controlling quality, functional requirements, and limitations.

Changes in the Frequencies of Abdominal Wall Hernias and the Preferences for Their Repair: A Multicenter National Study From Turkey

PubMed Central

Şeker, Gaye; Kulacoglu, Hakan; Öztuna, Derya; Topgül, Koray; Akyol, Cihangir; Çakmak, Atıl; Karateke, Faruk; Özdoğan, Mehmet; Ersoy, Eren; Gürer, Ahmet; Zerbaliyev, Elbrus; Seker, Duray; Yorgancı, Kaya; Pergel, Ahmet; Aydın, İbrahim; Ensari, Cemal; Bilecik, Tuna; Kahraman, İzzettin; Reis, Erhan; Kalaycı, Murat; Canda, Aras Emre; Demirağ, Alp; Kesicioğlu, Tuğrul; Malazgirt, Zafer; Gündoğdu, Haldun; Terzi, Cem

2014-01-01

Abdominal wall hernias are a common problem in the general population. A Western estimate reveals that the lifetime risk of developing a hernia is about 2%.1–3 As a result, hernia repairs likely comprise the most frequent general surgery operations. More than 20 million hernias are estimated to be repaired every year around the world.4 Numerous repair techniques have been described to date however tension-free mesh repairs are widely used today because of their low hernia recurrence rates. Nevertheless, there are some ongoing debates regarding the ideal approach (open or laparoscopic),5,6 the ideal anesthesia (general, local, or regional),7,8 and the ideal mesh (standard polypropylene or newer meshes).9,10 PMID:25216417

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II

PubMed Central

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina

2017-01-01

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn4CaO5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn4CaO5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn4CaO5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate. DOI: http://dx.doi.org/10.7554/eLife.26933.001 PMID:28718766

Free tissue transfer of the rectus abdominis myoperitoneal flap for oral reconstruction in a dog.

PubMed

Lanz, O I

2001-12-01

A five-month-old intact/male Boxer dog was presented 5-days following bite wound trauma to the maxillary region resulting in an oronasal fistula extending from the maxillary canine teeth to the soft palate. Multiple surgical procedures using local, buccal mucosal flaps failed to repair the oronasal fistula. Free tissue transfer of the rectus abdominis myoperitoneal flap using microvascular surgical techniques was successful in providing soft tissue reconstruction of the hard palate area. Complications of these surgical techniques included muscle contraction and subsequent muzzle distortion. Small, refractory oronasal fistulae at the perimeter of the myoperitoneal flap were repaired by primary wound closure.

Panorama of Reconstruction of Skull Base Defects: From Traditional Open to Endonasal Endoscopic Approaches, from Free Grafts to Microvascular Flaps

PubMed Central

Reyes, Camilo; Mason, Eric; Solares, C. Arturo

2014-01-01

Introduction A substantial body of literature has been devoted to the distinct characteristics and surgical options to repair the skull base. However, the skull base is an anatomically challenging location that requires a three-dimensional reconstruction approach. Furthermore, advances in endoscopic skull base surgery encompass a wide range of surgical pathology, from benign tumors to sinonasal cancer. This has resulted in the creation of wide defects that yield a new challenge in skull base reconstruction. Progress in technology and imaging has made this approach an internationally accepted method to repair these defects. Objectives Discuss historical developments and flaps available for skull base reconstruction. Data Synthesis Free grafts in skull base reconstruction are a viable option in small defects and low-flow leaks. Vascularized flaps pose a distinct advantage in large defects and high-flow leaks. When open techniques are used, free flap reconstruction techniques are often necessary to repair large entry wound defects. Conclusions Reconstruction of skull base defects requires a thorough knowledge of surgical anatomy, disease, and patient risk factors associated with high-flow cerebrospinal fluid leaks. Various reconstruction techniques are available, from free tissue grafting to vascularized flaps. Possible complications that can befall after these procedures need to be considered. Although endonasal techniques are being used with increasing frequency, open techniques are still necessary in selected cases. PMID:25992142

Error-free replicative bypass of (6–4) photoproducts by DNA polymerase ζ in mouse and human cells

PubMed Central

Yoon, Jung-Hoon; Prakash, Louise; Prakash, Satya

2010-01-01

The ultraviolet (UV)-induced (6–4) pyrimidine–pyrimidone photoproduct [(6–4) PP] confers a large structural distortion in DNA. Here we examine in human cells the roles of translesion synthesis (TLS) DNA polymerases (Pols) in promoting replication through a (6–4) TT photoproduct carried on a duplex plasmid where bidirectional replication initiates from an origin of replication. We show that TLS contributes to a large fraction of lesion bypass and that it is mostly error-free. We find that, whereas Pol η and Pol ι provide alternate pathways for mutagenic TLS, surprisingly, Pol ζ functions independently of these Pols and in a predominantly error-free manner. We verify and extend these observations in mouse cells and conclude that, in human cells, TLS during replication can be markedly error-free even opposite a highly distorting DNA lesion. PMID:20080950

Is bone transplantation the gold standard for repair of alveolar bone defects?

PubMed

Raposo-Amaral, Cassio Eduardo; Bueno, Daniela Franco; Almeida, Ana Beatriz; Jorgetti, Vanda; Costa, Cristiane Cabral; Gouveia, Cecília Helena; Vulcano, Luiz Carlos; Fanganiello, Roberto D; Passos-Bueno, Maria Rita; Alonso, Nivaldo

2014-01-01

New strategies to fulfill craniofacial bone defects have gained attention in recent years due to the morbidity of autologous bone graft harvesting. We aimed to evaluate the in vivo efficacy of bone tissue engineering strategy using mesenchymal stem cells associated with two matrices (bovine bone mineral and α-tricalcium phosphate), compared to an autologous bone transfer. A total of 28 adult, male, non-immunosuppressed Wistar rats underwent a critical-sized osseous defect of 5 mm diameter in the alveolar region. Animals were divided into five groups. Group 1 (n = 7) defects were repaired with autogenous bone grafts; Group 2 (n = 5) defects were repaired with bovine bone mineral free of cells; Group 3 (n = 5) defects were repaired with bovine bone mineral loaded with mesenchymal stem cells; Group 4 (n = 5) defects were repaired with α-tricalcium phosphate free of cells; and Group 5 (n = 6) defects were repaired with α-tricalcium phosphate loaded with mesenchymal stem cells. Groups 2-5 were compared to Group 1, the reference group. Healing response was evaluated by histomorphometry and computerized tomography. Histomorphometrically, Group 1 showed 60.27% ± 16.13% of bone in the defect. Groups 2 and 3 showed 23.02% ± 8.6% (p = 0.01) and 38.35% ± 19.59% (p = 0.06) of bone in the defect, respectively. Groups 4 and 5 showed 51.48% ± 11.7% (p = 0.30) and 61.80% ± 2.14% (p = 0.88) of bone in the defect, respectively. Animals whose bone defects were repaired with α-tricalcium phosphate and mesenchymal stem cells presented the highest bone volume filling the defects; both were not statistically different from autogenous bone.

A Study to Determine the Feasibility of Establishing an Ambulatory Surgery Program at Keller Army Community Hospital, West Point, New York

DTIC Science & Technology

1987-05-01

18.79 Other plastic repair of external ear Otoplasty; Postauricular skin graft ; Repair of lop ear 19.4 Myringoplasty Epitympanic, type I; Myringoplasty...of lip 27.53 Closure of fistula of mouth * 27.54 Repair of cleft lip * 27.55 Bill-thickness skin graft to lip and mouth * 27.56 Other skin graft to...structure 86.60 Free skin graft , not otherwise specified *d :935 Empire Blue Cross and Blue Shield- New York Dvisior 56 INTEGUMENTARY SYSTIA continued

Rescheduling with iterative repair

NASA Technical Reports Server (NTRS)

Zweben, Monte; Davis, Eugene; Daun, Brian; Deale, Michael

1992-01-01

This paper presents a new approach to rescheduling called constraint-based iterative repair. This approach gives our system the ability to satisfy domain constraints, address optimization concerns, minimize perturbation to the original schedule, and produce modified schedules quickly. The system begins with an initial, flawed schedule and then iteratively repairs constraint violations until a conflict-free schedule is produced. In an empirical demonstration, we vary the importance of minimizing perturbation and report how fast the system is able to resolve conflicts in a given time bound. These experiments were performed within the domain of Space Shuttle ground processing.

Somatic immunoglobulin hypermutation

PubMed Central

Diaz, Marilyn; Casali, Paolo

2015-01-01

Immunoglobulin hypermutation provides the structural correlate for the affinity maturation of the antibody response. Characteristic modalities of this mechanism include a preponderance of point-mutations with prevalence of transitions over transversions, and the mutational hotspot RGYW sequence. Recent evidence suggests a mechanism whereby DNA-breaks induce error-prone DNA synthesis in immunoglobulin V(D)J regions by error-prone DNA polymerases. The nature of the targeting mechanism and the trans-factors effecting such breaks and their repair remain to be determined. PMID:11869898

Free kick instead of cross-validation in maximum-likelihood refinement of macromolecular crystal structures

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

Pražnikar, Jure; University of Primorska,; Turk, Dušan, E-mail: dusan.turk@ijs.si

2014-12-01

The maximum-likelihood free-kick target, which calculates model error estimates from the work set and a randomly displaced model, proved superior in the accuracy and consistency of refinement of crystal structures compared with the maximum-likelihood cross-validation target, which calculates error estimates from the test set and the unperturbed model. The refinement of a molecular model is a computational procedure by which the atomic model is fitted to the diffraction data. The commonly used target in the refinement of macromolecular structures is the maximum-likelihood (ML) function, which relies on the assessment of model errors. The current ML functions rely on cross-validation. Theymore » utilize phase-error estimates that are calculated from a small fraction of diffraction data, called the test set, that are not used to fit the model. An approach has been developed that uses the work set to calculate the phase-error estimates in the ML refinement from simulating the model errors via the random displacement of atomic coordinates. It is called ML free-kick refinement as it uses the ML formulation of the target function and is based on the idea of freeing the model from the model bias imposed by the chemical energy restraints used in refinement. This approach for the calculation of error estimates is superior to the cross-validation approach: it reduces the phase error and increases the accuracy of molecular models, is more robust, provides clearer maps and may use a smaller portion of data for the test set for the calculation of R{sub free} or may leave it out completely.« less

[SOS response of DNA repair and genetic cell instability under hypoxic conditions].

PubMed

Vasil'eva, S V; Strel'tsova, D A

2011-01-01

The SOS DNA repair pathway is induced in E. coli as a multifunctional cell response to a wide variety of signals: UV, X or gamma-irradiation, mitomycin C or nalidixic acid treatment, thymine starvation, etc. Triggering of the system can be used as a general and early sign of DNA damage. Additionally, the SOS-response is known to be an "error-prone" DNA repair pathway and one of the sources of genetic instability. Hypoxic conditions are established to be the major factor of genetic instability as well. In this paper we for the first time studied the SOS DNA repair response under hypoxic conditions induced by the well known aerobic SOS-inducers. The SOS DNA repair response was examined as a reaction of E. coli PQ37 [sfiA::lacZ] cells to UVC, NO-donating agents and 4NQO. Here we provide evidence that those agents were able to induce the SOS DNA repair response in E. coli at anaerobic growth conditions. The process does not depend on the transcriptional activity of the universal protein of E. col anaerobic growth Fnr [4Fe-4S]2+ or can not be referred to as an indicator of genetic instability in hypoxic conditions.

Palm Mutants in DNA Polymerases α and η Alter DNA Replication Fidelity and Translesion Activity

PubMed Central

Niimi, Atsuko; Limsirichaikul, Siripan; Yoshida, Shonen; Iwai, Shigenori; Masutani, Chikahide; Hanaoka, Fumio; Kool, Eric T.; Nishiyama, Yukihiro; Suzuki, Motoshi

2004-01-01

We isolated active mutants in Saccharomyces cerevisiae DNA polymerase α that were associated with a defect in error discrimination. Among them, L868F DNA polymerase α has a spontaneous error frequency of 3 in 100 nucleotides and 570-fold lower replication fidelity than wild-type (WT) polymerase α. In vivo, mutant DNA polymerases confer a mutator phenotype and are synergistic with msh2 or msh6, suggesting that DNA polymerase α-dependent replication errors are recognized and repaired by mismatch repair. In vitro, L868F DNA polymerase α catalyzes efficient bypass of a cis-syn cyclobutane pyrimidine dimer, extending the 3′ T 26,000-fold more efficiently than the WT. Phe34 is equivalent to residue Leu868 in translesion DNA polymerase η, and the F34L mutant of S. cerevisiae DNA polymerase η has reduced translesion DNA synthesis activity in vitro. These data suggest that high-fidelity DNA synthesis by DNA polymerase α is required for genomic stability in yeast. The data also suggest that the phenylalanine and leucine residues in translesion and replicative DNA polymerases, respectively, might have played a role in the functional evolution of these enzyme classes. PMID:15024063

An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for Wireless Sensor Networks

PubMed Central

Abba, Sani; Lee, Jeong-A

2015-01-01

We propose an autonomous self-aware and adaptive fault-tolerant routing technique (ASAART) for wireless sensor networks. We address the limitations of self-healing routing (SHR) and self-selective routing (SSR) techniques for routing sensor data. We also examine the integration of autonomic self-aware and adaptive fault detection and resiliency techniques for route formation and route repair to provide resilience to errors and failures. We achieved this by using a combined continuous and slotted prioritized transmission back-off delay to obtain local and global network state information, as well as multiple random functions for attaining faster routing convergence and reliable route repair despite transient and permanent node failure rates and efficient adaptation to instantaneous network topology changes. The results of simulations based on a comparison of the ASAART with the SHR and SSR protocols for five different simulated scenarios in the presence of transient and permanent node failure rates exhibit a greater resiliency to errors and failure and better routing performance in terms of the number of successfully delivered network packets, end-to-end delay, delivered MAC layer packets, packet error rate, as well as efficient energy conservation in a highly congested, faulty, and scalable sensor network. PMID:26295236

An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for Wireless Sensor Networks.

PubMed

Abba, Sani; Lee, Jeong-A

2015-08-18

We propose an autonomous self-aware and adaptive fault-tolerant routing technique (ASAART) for wireless sensor networks. We address the limitations of self-healing routing (SHR) and self-selective routing (SSR) techniques for routing sensor data. We also examine the integration of autonomic self-aware and adaptive fault detection and resiliency techniques for route formation and route repair to provide resilience to errors and failures. We achieved this by using a combined continuous and slotted prioritized transmission back-off delay to obtain local and global network state information, as well as multiple random functions for attaining faster routing convergence and reliable route repair despite transient and permanent node failure rates and efficient adaptation to instantaneous network topology changes. The results of simulations based on a comparison of the ASAART with the SHR and SSR protocols for five different simulated scenarios in the presence of transient and permanent node failure rates exhibit a greater resiliency to errors and failure and better routing performance in terms of the number of successfully delivered network packets, end-to-end delay, delivered MAC layer packets, packet error rate, as well as efficient energy conservation in a highly congested, faulty, and scalable sensor network.

The importance of intra-hospital pharmacovigilance in the detection of medication errors

PubMed

Villegas, Francisco; Figueroa-Montero, David; Barbero-Becerra, Varenka; Juárez-Hernández, Eva; Uribe, Misael; Chávez-Tapia, Norberto; González-Chon, Octavio

2018-01-01

Hospitalized patients are susceptible to medication errors, which represent between the fourth and the sixth cause of death. The department of intra-hospital pharmacovigilance intervenes in the entire process of medication with the purpose to prevent, repair and assess damages. To analyze medication errors reported by Mexican Fundación Clínica Médica Sur pharmacovigilance system and their impact on patients. Prospective study carried out from 2012 to 2015, where medication prescriptions given to patients were recorded. Owing to heterogeneity, data were described as absolute numbers in a logarithmic scale. 292 932 prescriptions of 56 368 patients were analyzed, and 8.9% of medication errors were identified. The treating physician was responsible of 83.32% of medication errors, residents of 6.71% and interns of 0.09%. No error caused permanent damage or death. This is the pharmacovigilance study with the largest sample size reported. Copyright: © 2018 SecretarÍa de Salud.

Tape Versus Suture in Arthroscopic Rotator Cuff Repair: Biomechanical Analysis and Assessment of Failure Rates at 6 Months

PubMed Central

Liu, Rui Wen; Lam, Patrick Hong; Shepherd, Henry M.; Murrell, George A. C.

2017-01-01

Background: Rotator cuff retears after surgical repair are associated with poorer subjective and objectives clinical outcomes than intact repairs. Purpose: The aims of this study were to (1) examine the biomechanical differences between rotator cuff repair using No. 2 suture and tape in an ovine model and (2) compare early clinical outcomes between patients who had rotator cuff repair with tape and patients who had repair with No. 2 suture. Study Design: Controlled laboratory study and cohort study; Level of evidence, 3. Methods: Biomechanical testing of footprint contact pressure and load to failure were conducted with 16 ovine shoulders using a tension band repair technique with 2 different types of sutures (No. 2 suture [FiberWire; Arthrex] and tape [FiberTape; Arthrex]) with the same knotless anchor system. A retrospective study of 150 consecutive patients (tape, n = 50; suture, n = 100) who underwent arthroscopic rotator cuff repair by a single surgeon with tear size larger than 1.5 × 1 cm was conducted. Ultrasound was used to evaluate the repair integrity at 6 months postsurgery. Results: Rotator cuff repair using tape had greater footprint contact pressure (mean ± standard error of the mean, 0.33 ± 0.03 vs 0.11 ± 0.3 MPa; P < .0001) compared with repair using No. 2 sutures at 0° abduction with a 30-N load applied across the repaired tendon. The ultimate failure load of the tape repair was greater than that for suture repair (217 ± 28 vs 144 ± 14 N; P < .05). The retear rate was similar between the tape (16%; 8/50) and suture groups (17%; 17/100). Conclusion: Rotator cuff repair with the wider tape compared with No. 2 suture did not affect the retear rate at 6 months postsurgery, despite having superior biomechanical properties. PMID:28451619

A difference in the pattern of repair in a large genomic region in UV-irradiated normal human and Cockayne syndrome cells.

PubMed

Shanower, G A; Kantor, G J

1997-11-01

Xeroderma pigmentosum group C cells repair DNA damaged by ultraviolet radiation in an unusual pattern throughout the genome. They remove cyclobutane pyrimidine dimers only from the DNA of transcriptionally active chromatin regions and only from the strand that contains the transcribed strand. The repair proceeds in a manner that creates damage-free islands which are in some cases much larger than the active gene associated with them. For example, the small transcriptionally active beta-actin gene (3.5 kb) is repaired as part of a 50 kb single-stranded region. The repair responsible for creating these islands requires active transcription, suggesting that the two activities are coupled. A preferential repair pathway in normal human cells promotes repair of actively transcribed DNA strands and is coupled to transcription. It is not known if similar large islands, referred to as repair domains, are preferentially created as a result of the coupling. Data are presented showing that in normal cells, preferential repair in the beta-actin region is associated with the creation of a large, completely repaired region in the partially repaired genome. Repair at other genomic locations which contain inactive genes (insulin, 754) does not create similar large regions as quickly. In contrast, repair in Cockayne syndrome cells, which are defective in the preferential repair pathway but not in genome-overall repair, proceeds in the beta-actin region by a mechanism which does not create preferentially a large repaired region. Thus a correlation between the activity required to preferentially repair active genes and that required to create repaired domains is detected. We propose an involvement of the transcription-repair coupling factor in a coordinated repair pathway for removing DNA damage from entire transcription units.

Model-based influences on humans' choices and striatal prediction errors.

PubMed

Daw, Nathaniel D; Gershman, Samuel J; Seymour, Ben; Dayan, Peter; Dolan, Raymond J

2011-03-24

The mesostriatal dopamine system is prominently implicated in model-free reinforcement learning, with fMRI BOLD signals in ventral striatum notably covarying with model-free prediction errors. However, latent learning and devaluation studies show that behavior also shows hallmarks of model-based planning, and the interaction between model-based and model-free values, prediction errors, and preferences is underexplored. We designed a multistep decision task in which model-based and model-free influences on human choice behavior could be distinguished. By showing that choices reflected both influences we could then test the purity of the ventral striatal BOLD signal as a model-free report. Contrary to expectations, the signal reflected both model-free and model-based predictions in proportions matching those that best explained choice behavior. These results challenge the notion of a separate model-free learner and suggest a more integrated computational architecture for high-level human decision-making. Copyright © 2011 Elsevier Inc. All rights reserved.

Rhodium metalloinsertor binding generates a lesion with selective cytotoxicity for mismatch repair-deficient cells.

PubMed

Bailis, Julie M; Weidmann, Alyson G; Mariano, Natalie F; Barton, Jacqueline K

2017-07-03

The DNA mismatch repair (MMR) pathway recognizes and repairs errors in base pairing and acts to maintain genome stability. Cancers that have lost MMR function are common and comprise an important clinical subtype that is resistant to many standard of care chemotherapeutics such as cisplatin. We have identified a family of rhodium metalloinsertors that bind DNA mismatches with high specificity and are preferentially cytotoxic to MMR-deficient cells. Here, we characterize the cellular mechanism of action of the most potent and selective complex in this family, [Rh(chrysi)(phen)(PPO)] 2+ (Rh-PPO). We find that Rh-PPO binding induces a lesion that triggers the DNA damage response (DDR). DDR activation results in cell-cycle blockade and inhibition of DNA replication and transcription. Significantly, the lesion induced by Rh-PPO is not repaired in MMR-deficient cells, resulting in selective cytotoxicity. The Rh-PPO mechanism is reminiscent of DNA repair enzymes that displace mismatched bases, and is differentiated from other DNA-targeted chemotherapeutics such as cisplatin by its potency, cellular mechanism, and selectivity for MMR-deficient cells.

Alterations in Synthesis and Repair of DNA during the Development of Loach Misgurnus fossilis

PubMed Central

Gening, Leonid V.; Lakhin, Andrei V.; Makarova, Irina V.; Nenasheva, Valentina V.; Andreeva, Ludmila E.; Tarantul, Vyacheslav Z.

2016-01-01

Using a modified radiolabeled primer extension method (we named this modification misGvA—“misincorporation of G versus A”) we have investigated the DNA synthesis and repair at early and late stages of development of loach Misgurnus fossilis. The misincorporation activity of DNA polymerase iota (Pol ι) in wild-type loach could not be detected by this method at any stage of loach development. In transgenic loach overexpressing human Pol ι we have shown that the bypassing of DNA synthesis arrest after incorporation of mismatched nucleotide by Pol ι (the T-stop) was not associated with this enzyme. Non-transgenic loach larvae are virtually lacking the capacity for error correction of DNA duplex containing a mismatched nucleotide. Such repair activity develops only in the adult fish. It appears that the initial stages of development are characterized by more intensive DNA synthesis, while in terminal stages the repair activities become more prominent. The misGvA approach clearly indicates substantial changes in the DNA synthesis intensity, although the role of particular replicative and repair DNA polymerases in this process requires further study. PMID:29615575

Narrative-compression coding for a channel with errors. Professional paper for period ending June 1987

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

Bond, J.W.

1988-01-01

Data-compression codes offer the possibility of improving the thruput of existing communication systems in the near term. This study was undertaken to determine if data-compression codes could be utilized to provide message compression in a channel with up to a 0.10-bit error rate. The data-compression capabilities of codes were investigated by estimating the average number of bits-per-character required to transmit narrative files. The performance of the codes in a channel with errors (a noisy channel) was investigated in terms of the average numbers of characters-decoded-in-error and of characters-printed-in-error-per-bit-error. Results were obtained by encoding four narrative files, which were resident onmore » an IBM-PC and use a 58-character set. The study focused on Huffman codes and suffix/prefix comma-free codes. Other data-compression codes, in particular, block codes and some simple variants of block codes, are briefly discussed to place the study results in context. Comma-free codes were found to have the most-promising data compression because error propagation due to bit errors are limited to a few characters for these codes. A technique was found to identify a suffix/prefix comma-free code giving nearly the same data compressions as a Huffman code with much less error propagation than the Huffman codes. Greater data compression can be achieved through the use of this comma-free code word assignments based on conditioned probabilities of character occurrence.« less

The Witness-Voting System

NASA Astrophysics Data System (ADS)

Gerck, Ed

We present a new, comprehensive framework to qualitatively improve election outcome trustworthiness, where voting is modeled as an information transfer process. Although voting is deterministic (all ballots are counted), information is treated stochastically using Information Theory. Error considerations, including faults, attacks, and threats by adversaries, are explicitly included. The influence of errors may be corrected to achieve an election outcome error as close to zero as desired (error-free), with a provably optimal design that is applicable to any type of voting, with or without ballots. Sixteen voting system requirements, including functional, performance, environmental and non-functional considerations, are derived and rated, meeting or exceeding current public-election requirements. The voter and the vote are unlinkable (secret ballot) although each is identifiable. The Witness-Voting System (Gerck, 2001) is extended as a conforming implementation of the provably optimal design that is error-free, transparent, simple, scalable, robust, receipt-free, universally-verifiable, 100% voter-verified, and end-to-end audited.

Error control techniques for satellite and space communications

NASA Technical Reports Server (NTRS)

Costello, Daniel J., Jr.

1990-01-01

An expurgated upper bound on the event error probability of trellis coded modulation is presented. This bound is used to derive a lower bound on the minimum achievable free Euclidean distance d sub (free) of trellis codes. It is shown that the dominant parameters for both bounds, the expurgated error exponent and the asymptotic d sub (free) growth rate, respectively, can be obtained from the cutoff-rate R sub O of the transmission channel by a simple geometric construction, making R sub O the central parameter for finding good trellis codes. Several constellations are optimized with respect to the bounds.

Error control techniques for satellite and space communications

NASA Technical Reports Server (NTRS)

Costello, Daniel J., Jr.

1994-01-01

The unequal error protection capabilities of convolutional and trellis codes are studied. In certain environments, a discrepancy in the amount of error protection placed on different information bits is desirable. Examples of environments which have data of varying importance are a number of speech coding algorithms, packet switched networks, multi-user systems, embedded coding systems, and high definition television. Encoders which provide more than one level of error protection to information bits are called unequal error protection (UEP) codes. In this work, the effective free distance vector, d, is defined as an alternative to the free distance as a primary performance parameter for UEP convolutional and trellis encoders. For a given (n, k), convolutional encoder, G, the effective free distance vector is defined as the k-dimensional vector d = (d(sub 0), d(sub 1), ..., d(sub k-1)), where d(sub j), the j(exp th) effective free distance, is the lowest Hamming weight among all code sequences that are generated by input sequences with at least one '1' in the j(exp th) position. It is shown that, although the free distance for a code is unique to the code and independent of the encoder realization, the effective distance vector is dependent on the encoder realization.

DNA repair efficiency in germ cells and early mouse embryos and consequences for radiation-induced transgenerational genomic damage

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

Marchetti, Francesco; Wyrobek, Andrew J.

Exposure to ionizing radiation and other environmental agents can affect the genomic integrity of germ cells and induce adverse health effects in the progeny. Efficient DNA repair during gametogenesis and the early embryonic cycles after fertilization is critical for preventing transmission of DNA damage to the progeny and relies on maternal factors stored in the egg before fertilization. The ability of the maternal repair machinery to repair DNA damage in both parental genomes in the fertilizing egg is especially crucial for the fertilizing male genome that has not experienced a DNA repair-competent cellular environment for several weeks prior to fertilization.more » During the DNA repair-deficient period of spermatogenesis, DNA lesions may accumulate in sperm and be carried into the egg where, if not properly repaired, could result in the formation of heritable chromosomal aberrations or mutations and associated birth defects. Studies with female mice deficient in specific DNA repair genes have shown that: (i) cell cycle checkpoints are activated in the fertilized egg by DNA damage carried by the sperm; and (ii) the maternal genotype plays a major role in determining the efficiency of repairing genomic lesions in the fertilizing sperm and directly affect the risk for abnormal reproductive outcomes. There is also growing evidence that implicates DNA damage carried by the fertilizing gamete as a mediator of postfertilization processes that contribute to genomic instability in subsequent generations. Transgenerational genomic instability most likely involves epigenetic mechanisms or error-prone DNA repair processes in the early embryo. Maternal and embryonic DNA repair processes during the early phases of mammalian embryonic development can have far reaching consequences for the genomic integrity and health of subsequent generations.« less

Ontology Alignment Repair through Modularization and Confidence-Based Heuristics

PubMed Central

Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M.

2015-01-01

Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system. PMID:26710335

Ontology Alignment Repair through Modularization and Confidence-Based Heuristics.

PubMed

Santos, Emanuel; Faria, Daniel; Pesquita, Catia; Couto, Francisco M

2015-01-01

Ontology Matching aims at identifying a set of semantic correspondences, called an alignment, between related ontologies. In recent years, there has been a growing interest in efficient and effective matching methods for large ontologies. However, alignments produced for large ontologies are often logically incoherent. It was only recently that the use of repair techniques to improve the coherence of ontology alignments began to be explored. This paper presents a novel modularization technique for ontology alignment repair which extracts fragments of the input ontologies that only contain the necessary classes and relations to resolve all detectable incoherences. The paper presents also an alignment repair algorithm that uses a global repair strategy to minimize both the degree of incoherence and the number of mappings removed from the alignment, while overcoming the scalability problem by employing the proposed modularization technique. Our evaluation shows that our modularization technique produces significantly small fragments of the ontologies and that our repair algorithm produces more complete alignments than other current alignment repair systems, while obtaining an equivalent degree of incoherence. Additionally, we also present a variant of our repair algorithm that makes use of the confidence values of the mappings to improve alignment repair. Our repair algorithm was implemented as part of AgreementMakerLight, a free and open-source ontology matching system.

Growth Factor Stimulation Improves the Structure and Properties of Scaffold-Free Engineered Auricular Cartilage Constructs

PubMed Central

Rosa, Renata G.; Joazeiro, Paulo P.; Bianco, Juares; Kunz, Manuela; Weber, Joanna F.; Waldman, Stephen D.

2014-01-01

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation. PMID:25126941

Hernia repair in the Lombardy region in 2000: preliminary results.

PubMed

Ferrante, F; Rusconi, A; Galimberti, A; Grassi, M

2004-08-01

Hernia repair is the most common surgical procedure in general surgery in Italy and in the Lombardy region. In the last decade, the use of mesh, the concept of a tension-free technique, and the postoperative rate of recurrences after Bassini or Shouldice operations have completely changed the surgical approach to hernia repair. For this reason, we sent a questionnaire to 148 surgical departments in the Lombardy region to investigate about total hernia operations performed in 2000 in Lombardy, the surgical approach, the surgical techniques used, the type of anesthesia and the hospital stay. One hundred five out of 148 surgical departments returned the questionnaire, and we collected information on a total of 16,935 surgical operations for hernia: 16,494 were performed using tension-free techniques. The inguinal anterior approach is the one of choice for primary and recurrent inguinal hernia, whereas the open preperitoneal and laparoscopic approaches are limited to bilateral and recurrent hernias. The majority of cases were treated under locoregional anesthesia and with a hospital stay of two nights.

Fade-resistant forward error correction method for free-space optical communications systems

DOEpatents

Johnson, Gary W.; Dowla, Farid U.; Ruggiero, Anthony J.

2007-10-02

Free-space optical (FSO) laser communication systems offer exceptionally wide-bandwidth, secure connections between platforms that cannot other wise be connected via physical means such as optical fiber or cable. However, FSO links are subject to strong channel fading due to atmospheric turbulence and beam pointing errors, limiting practical performance and reliability. We have developed a fade-tolerant architecture based on forward error correcting codes (FECs) combined with delayed, redundant, sub-channels. This redundancy is made feasible though dense wavelength division multiplexing (WDM) and/or high-order M-ary modulation. Experiments and simulations show that error-free communications is feasible even when faced with fades that are tens of milliseconds long. We describe plans for practical implementation of a complete system operating at 2.5 Gbps.

37. Photograph of plan for repairs to computer room, 1958, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. Photograph of plan for repairs to computer room, 1958, prepared by the Public Works Office, Underwater Sound Laboratory. Drawing on file at Caretaker Site Office, Naval Undersea Warfare Center, New London. Copyright-free. - Naval Undersea Warfare Center, Bowditch Hall, 600 feet east of Smith Street & 350 feet south of Columbia Cove, West bank of Thames River, New London, New London County, CT

Control of a free-flying robot manipulator system

NASA Technical Reports Server (NTRS)

Alexander, H.

1986-01-01

The development of and test control strategies for self-contained, autonomous free flying space robots are discussed. Such a robot would perform operations in space similar to those currently handled by astronauts during extravehicular activity (EVA). Use of robots should reduce the expense and danger attending EVA both by providing assistance to astronauts and in many cases by eliminating altogether the need for human EVA, thus greatly enhancing the scope and flexibility of space assembly and repair activities. The focus of the work is to develop and carry out a program of research with a series of physical Satellite Robot Simulator Vehicles (SRSV's), two-dimensionally freely mobile laboratory models of autonomous free-flying space robots such as might perform extravehicular functions associated with operation of a space station or repair of orbiting satellites. It is planned, in a later phase, to extend the research to three dimensions by carrying out experiments in the Space Shuttle cargo bay.

Multiconfiguration Pair-Density Functional Theory Is Free From Delocalization Error.

PubMed

Bao, Junwei Lucas; Wang, Ying; He, Xiao; Gagliardi, Laura; Truhlar, Donald G

2017-11-16

Delocalization error has been singled out by Yang and co-workers as the dominant error in Kohn-Sham density functional theory (KS-DFT) with conventional approximate functionals. In this Letter, by computing the vertical first ionization energy for well separated He clusters, we show that multiconfiguration pair-density functional theory (MC-PDFT) is free from delocalization error. To put MC-PDFT in perspective, we also compare it with some Kohn-Sham density functionals, including both traditional and modern functionals. Whereas large delocalization errors are almost universal in KS-DFT (the only exception being the very recent corrected functionals of Yang and co-workers), delocalization error is removed by MC-PDFT, which bodes well for its future as a step forward from KS-DFT.

Endovascular Retrieval of Entrapped Elephant Trunk Graft During Complex Hybrid Aortic Arch Repair

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

Damodharan, Karthikeyan, E-mail: drdkarthik@hotmail.com; Chao, Victor T. T., E-mail: victor.chao.t.t@singhealth.com.sg; Tay, Kiang Hiong, E-mail: tay.kiang.hiong@singhealth.com.sg

Entrapment of the elephant trunk graft within the false lumen is a rare complication of surgical repair of an aortic dissection. This is normally retrieved by emergent open surgery. We describe a technique of endovascular retrieval of the dislodged graft, during hybrid aortic arch repair. The elephant trunk was cannulated through and through from a femoral access and the free end of the wire was snared and retrieved from a brachial access. The wire was externalised from both accesses and was used to reposition the graft into the true lumen using a body flossing technique.

Recent evolutions in flexor tendon repairs and rehabilitation.

PubMed

Tang, Jin Bo

2018-06-01

This article reviews some recent advancements in repair and rehabilitation of the flexor tendons. These include placing sparse or no peripheral suture when the core suture is strong and sufficiently tensioned, allowing the repair site to be slightly bulky, aggressively releasing the pulleys (including the entire A2 pulley or both the A3 and A4 pulleys when necessary), placing a shorter splint with less restricted wrist positioning, and allowing out-of-splint active motion. The reported outcomes have been favourable with few or no repair ruptures and no function-disturbing tendon bowstringing. These changes favour easier surgeries. The recent reports have cause to re-evaluate long-held guidelines of a non-bulky repair site and the necessity of a standard peripheral suture. Emerging understanding posits that minor clinically noticeable tendon bowstringing does not affect hand function, and that free wrist positioning and out-of-splint motion are safe when strong surgical repairs are used and the pulleys are properly released.

Liver repair and hemorrhage control by using laser soldering of liquid albumin in a porcine model.

PubMed

Wadia, Y; Xie, H; Kajitani, M

2000-01-01

We evaluated laser soldering by using liquid albumin for welding liver injuries. Major liver trauma has a high mortality because of immediate exsanguination and a delayed morbidity from septicemia, peritonitis, biliary fistulae, and delayed secondary hemorrhage. Eight laceration (6 x 2 cm) and eight nonanatomic resection injuries (raw surface, 6 x 2 cm) were repaired. An 805-nm laser was used to weld 50% liquid albumin-indocyanine green solder to the liver surface, reinforcing it with a free autologous omental scaffold. The animals were heparinized and hepatic inflow occlusion was used for vascular control. All 16 soldering repairs were evaluated at 3 hours. All 16 laser mediated liver repairs had minimal blood loss as compared with the suture controls. No dehiscence, hemorrhage, or bile leakage was seen in any of the laser repairs after 3 hours. Laser fusion repair of the liver is a reliable technique to gain hemostasis on the raw surface as well as weld lacerations. Copyright 2000 Wiley-Liss, Inc.

PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways

PubMed Central

Wang, Minli; Wu, Weizhong; Wu, Wenqi; Rosidi, Bustanur; Zhang, Lihua; Wang, Huichen; Iliakis, George

2006-01-01

Poly(ADP-ribose)polymerase 1 (PARP-1) recognizes DNA strand interruptions in vivo and triggers its own modification as well as that of other proteins by the sequential addition of ADP-ribose to form polymers. This modification causes a release of PARP-1 from DNA ends and initiates a variety of responses including DNA repair. While PARP-1 has been firmly implicated in base excision and single strand break repair, its role in the repair of DNA double strand breaks (DSBs) remains unclear. Here, we show that PARP-1, probably together with DNA ligase III, operates in an alternative pathway of non-homologous end joining (NHEJ) that functions as backup to the classical pathway of NHEJ that utilizes DNA-PKcs, Ku, DNA ligase IV, XRCC4, XLF/Cernunnos and Artemis. PARP-1 binds to DNA ends in direct competition with Ku. However, in irradiated cells the higher affinity of Ku for DSBs and an excessive number of other forms of competing DNA lesions limit its contribution to DSB repair. When essential components of the classical pathway of NHEJ are absent, PARP-1 is recruited for DSB repair, particularly in the absence of Ku and non-DSB lesions. This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer. PMID:17088286

The Effect of Furlow Palatoplasty Timing on Speech Outcomes in Submucous Cleft Palate.

PubMed

Swanson, Jordan W; Mitchell, Brianne T; Cohen, Marilyn; Solot, Cynthia; Jackson, Oksana; Low, David; Bartlett, Scott P; Taylor, Jesse A

2017-08-01

Because some patients with submucous cleft palate (SMCP) are asymptomatic, surgical treatment is conventionally delayed until hypernasal resonance is identified during speech production. We aim to identify whether speech outcomes after repair of a SMCP is influenced by age of repair. We retrospectively studied nonsyndromic children with SMCP. Speech results, before and after any surgical treatment or physical management of the palate were compared using the Pittsburgh Weighted Speech Scoring system. Furlow palatoplasty was performed on 40 nonsyndromic patients with SMCP, and 26 patients were not surgically treated. Total composite speech scores improved significantly among children repaired between 3 and 4 years of age (P = 0.02), but not older than 4 years (P = 0.63). Twelve (86%) of 14 patients repaired who are older than 4 years had borderline or incompetent speech (composite Pittsburgh Weighted Speech Scoring ≥3) compared with 2 (29%) of 7 repaired between 3 and 4 years of age (P = 0.0068), despite worse prerepair scores in the latter group. Resonance improved in children repaired who are older than 4 years, but articulation errors persisted to a greater degree than those treated before 4 years of age (P = 0.01.) CONCLUSIONS: Submucous cleft palate repair before 4 years of age appears associated with lower ultimate rates of borderline or incompetent speech. Speech of patients repaired at or after 4 years of age seems to be characterized by persistent misarticulation. These findings highlight the importance of timely diagnosis and management.

Altered Hematopoiesis in Mice Lacking DNA Polymerase μ Is Due to Inefficient Double-Strand Break Repair

PubMed Central

Lucas, Daniel; Escudero, Beatriz; Ligos, José Manuel; Segovia, Jose Carlos; Estrada, Juan Camilo; Terrados, Gloria; Blanco, Luis; Samper, Enrique; Bernad, Antonio

2009-01-01

Polymerase mu (Polμ) is an error-prone, DNA-directed DNA polymerase that participates in non-homologous end-joining (NHEJ) repair. In vivo, Polμ deficiency results in impaired Vκ-Jκ recombination and altered somatic hypermutation and centroblast development. In Polμ−/− mice, hematopoietic development was defective in several peripheral and bone marrow (BM) cell populations, with about a 40% decrease in BM cell number that affected several hematopoietic lineages. Hematopoietic progenitors were reduced both in number and in expansion potential. The observed phenotype correlates with a reduced efficiency in DNA double-strand break (DSB) repair in hematopoietic tissue. Whole-body γ-irradiation revealed that Polμ also plays a role in DSB repair in non-hematopoietic tissues. Our results show that Polμ function is required for physiological hematopoietic development with an important role in maintaining early progenitor cell homeostasis and genetic stability in hematopoietic and non-hematopoietic tissues. PMID:19229323

Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius.

PubMed

Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

2015-11-01

Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. © 2015 Anatomical Society.

Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius

PubMed Central

Peacock, Hanna M; Gilbert, Emily A B; Vickaryous, Matthew K

2015-01-01

Cutaneous wounds heal with two possible outcomes: scarification or near-perfect integumentary restoration. Whereas scar formation has been intensively investigated, less is known about the tissue-level events characterising wounds that spontaneously heal scar-free, particularly in non-foetal amniotes. Here, a spatiotemporal investigation of scar-free cutaneous wound healing following full-thickness excisional biopsies to the tail and body of leopard geckos (Eublepharis macularius) is provided. All injuries healed without scarring. Cutaneous repair involves the development of a cell-rich aggregate within the wound bed, similar to scarring wounds. Unlike scar formation, scar-free healing involves a more rapid closure of the wound epithelium, and a delay in blood vessel development and collagen deposition within the wound bed. It was found that, while granulation tissue of scarring wounds is hypervascular, scar-free wound healing conspicuously does not involve a period of exuberant blood vessel formation. In addition, during scar-free wound healing the newly formed blood vessels are typically perivascular cell-supported. Immunohistochemistry revealed widespread expression of both the pro-angiogenic factor vascular endothelial growth factor A and the anti-angiogenic factor thrombospondin-1 within the healing wound. It was found that scar-free wound healing is an intrinsic property of leopard gecko integument, and involves a modulation of the cutaneous scar repair program. This proportional revascularisation is an important factor in scar-free wound healing. PMID:26360824

ON ESTIMATING FORCE-FREENESS BASED ON OBSERVED MAGNETOGRAMS

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

Zhang, X. M.; Zhang, M.; Su, J. T., E-mail: xmzhang@nao.cas.cn

It is a common practice in the solar physics community to test whether or not measured photospheric or chromospheric vector magnetograms are force-free, using the Maxwell stress as a measure. Some previous studies have suggested that magnetic fields of active regions in the solar chromosphere are close to being force-free whereas there is no consistency among previous studies on whether magnetic fields of active regions in the solar photosphere are force-free or not. Here we use three kinds of representative magnetic fields (analytical force-free solutions, modeled solar-like force-free fields, and observed non-force-free fields) to discuss how measurement issues such asmore » limited field of view (FOV), instrument sensitivity, and measurement error could affect the estimation of force-freeness based on observed magnetograms. Unlike previous studies that focus on discussing the effect of limited FOV or instrument sensitivity, our calculation shows that just measurement error alone can significantly influence the results of estimates of force-freeness, due to the fact that measurement errors in horizontal magnetic fields are usually ten times larger than those in vertical fields. This property of measurement errors, interacting with the particular form of a formula for estimating force-freeness, would result in wrong judgments of the force-freeness: a truly force-free field may be mistakenly estimated as being non-force-free and a truly non-force-free field may be estimated as being force-free. Our analysis calls for caution when interpreting estimates of force-freeness based on measured magnetograms, and also suggests that the true photospheric magnetic field may be further away from being force-free than it currently appears to be.« less

[Applications of DNA methylation markers in forensic medicine].

PubMed

Zhao, Gui-sen; Yang, Qing-en

2005-02-01

DNA methylation is a post-replication modification that is predominantly found in cytosines of the dinucleotide sequence CpG. Epigenetic information is stored in the distribution of the modified base 5-methylcytosine. DNA methylation profiles represent a more chemically and biologically stable source of molecular diagnostic information than RNA or most proteins. Recent advances attest to the great promise of DNA methylation markers as powerful future tools in the clinic. In the past decade, DNA methylation analysis has been revolutionized by two technological advances--bisulphite modification of DNA and methylation-specific polymerase chain reaction (MSP). The methylation pattern of human genome is space-time specific, sex-specific, parent-of-origin specific and disease specific, providing us an alternative way to solve forensic problems.

Coordinating DNA polymerase traffic during high and low fidelity synthesis.

PubMed

Sutton, Mark D

2010-05-01

With the discovery that organisms possess multiple DNA polymerases (Pols) displaying different fidelities, processivities, and activities came the realization that mechanisms must exist to manage the actions of these diverse enzymes to prevent gratuitous mutations. Although many of the Pols encoded by most organisms are largely accurate, and participate in DNA replication and DNA repair, a sizeable fraction display a reduced fidelity, and act to catalyze potentially error-prone translesion DNA synthesis (TLS) past lesions that persist in the DNA. Striking the proper balance between use of these different enzymes during DNA replication, DNA repair, and TLS is essential for ensuring accurate duplication of the cell's genome. This review highlights mechanisms that organisms utilize to manage the actions of their different Pols. A particular emphasis is placed on discussion of current models for how different Pols switch places with each other at the replication fork during high fidelity replication and potentially error-pone TLS. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Radiation damage and repair in cells and cell components. Progress report, 1980-1981

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

Not Available

1981-01-01

One aim has been to see whether, in E.coli, the various phenomena which were ascribed to the induction of the recA gene produce (p-recA) are really manifestations of one process. It was concluded that this is true for septum inhibition, Weigle-reactivation, induced inhibition of post radiation DNA degradation, and with the additional concept of a premutational lesion, for uv mutagenesis. lambda prophage induction may perhaps be brought into line with p-recA induction with the consideration of the additional secondary aspects of (a) activation of p-recA to make it enzymatically active and (b) the need to have the concentration of activatedmore » p-recA high enough to keep up with the rate of production of lambda-repressors. Revertants seem to be in more than one class and two of these can not easily be explained by the idea that p-recA contains an error-prone repair enzyme that makes errors at mutagenic lesions.« less

[Repairing of soft tissue defect in leg by free vascularized thoracoumbilical flap with reversed flow].

PubMed

Xu, Y Q; Li, Z Y; Li, J

2000-11-01

To investigate the clinical effect of free vascularized thoracoumbilical flap with reversal flow in repairing the soft tissue defect in leg with tibia exposure. Forty-four casting mould specimens of leg arteries were studied firstly. Then 25 cases with soft tissue defect and tibia exposure in the proximal-middle segment of leg were adopted in this study. Among them, 18 cases had long distance thrombosis of the anterior tibial vessels or posterior tibial vessels due to traumatic lesion. The maximal size of defect was 28 cm x 11 cm and the minimal size of defect was 11 cm x 9 cm. In operation, the thoracoumbilical flap which was based on the inferior epigastric vessels was anastomosed to the distal end of the anterior tibial vessels or posterior tibial vessels. Anterior tibial artery, posterior tibial artery and fibular artery had rich communication branches in foot and ankle. All the flaps survived, the color and cosmetic result of them were good. The free vascularized thoracoumbilical flap with reversed flow is practical in repairing the soft tissue defect of leg with tibia exposure. Either the anterior tibial vessels or the posterior tibial vessels is normal, and the distal end of injured blood vessels is available, this technique can be adopted.

Reduction of errors during practice facilitates fundamental movement skill learning in children with intellectual disabilities.

PubMed

Capio, C M; Poolton, J M; Sit, C H P; Eguia, K F; Masters, R S W

2013-04-01

Children with intellectual disabilities (ID) have been found to have inferior motor proficiencies in fundamental movement skills (FMS). This study examined the effects of training the FMS of overhand throwing by manipulating the amount of practice errors. Participants included 39 children with ID aged 4-11 years who were allocated into either an error-reduced (ER) training programme or a more typical programme in which errors were frequent (error-strewn, ES). Throwing movement form, throwing accuracy, and throwing frequency during free play were evaluated. The ER programme improved movement form, and increased throwing activity during free play to a greater extent than the ES programme. Furthermore, ER learners were found to be capable of engaging in a secondary cognitive task while manifesting robust throwing accuracy performance. The findings support the use of movement skills training programmes that constrain practice errors in children with ID, suggesting that such approach results in improved performance and heightened movement engagement in free play. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

Portable and Error-Free DNA-Based Data Storage.

PubMed

Yazdi, S M Hossein Tabatabaei; Gabrys, Ryan; Milenkovic, Olgica

2017-07-10

DNA-based data storage is an emerging nonvolatile memory technology of potentially unprecedented density, durability, and replication efficiency. The basic system implementation steps include synthesizing DNA strings that contain user information and subsequently retrieving them via high-throughput sequencing technologies. Existing architectures enable reading and writing but do not offer random-access and error-free data recovery from low-cost, portable devices, which is crucial for making the storage technology competitive with classical recorders. Here we show for the first time that a portable, random-access platform may be implemented in practice using nanopore sequencers. The novelty of our approach is to design an integrated processing pipeline that encodes data to avoid costly synthesis and sequencing errors, enables random access through addressing, and leverages efficient portable sequencing via new iterative alignment and deletion error-correcting codes. Our work represents the only known random access DNA-based data storage system that uses error-prone nanopore sequencers, while still producing error-free readouts with the highest reported information rate/density. As such, it represents a crucial step towards practical employment of DNA molecules as storage media.

Arthroscopic suture anchor repair of the lateral ligament ankle complex: a cadaveric study.

PubMed

Giza, Eric; Shin, Edward C; Wong, Stephanie E; Acevedo, Jorge I; Mangone, Peter G; Olson, Kirstina; Anderson, Matthew J

2013-11-01

Operative treatment of mechanical ankle instability is indicated for patients with multiple sprains and continued episodes of instability. Open repair of the lateral ankle ligaments involves exposure of the attenuated ligaments and advancement back to their anatomic insertions on the fibula using bone tunnels or suture implants. Open and arthroscopic fixation are equal in strength to failure for anatomic Broström repair. Controlled laboratory study. Seven matched pairs of human cadaveric ankle specimens were randomized into 2 groups of anatomic Broström repair: open or arthroscopic. The calcaneofibular ligament and anterior talofibular ligament were excised from their origin on the fibula. In the open repair group, 2 suture anchors were used to reattach the ligaments to their anatomic origins. In the arthroscopic repair group, identical suture anchors were used for repair via an arthroscopic technique. The ligaments were cyclically loaded 20 times and then tested to failure. Torque to failure, degrees to failure, initial stiffness, and working stiffness were measured. A matched-pair analysis was performed. Power analysis of 0.8 demonstrated that 7 pairs needed to show a difference of 30%, with a 15% standard error at a significance level of α = .05. There was no difference in the degrees to failure, torque to failure, or stiffness for the repaired ligament complex. Nine of 14 specimens failed at the suture anchor. There is no statistical difference in strength or stiffness of a traditional open repair as compared with an arthroscopic anatomic repair of the lateral ligaments of the ankle. An arthroscopic technique can be considered for lateral ligament stabilization in patients with mild to moderate mechanical instability.

Proximity to AGCT sequences dictates MMR-independent versus MMR-dependent mechanisms for AID-induced mutation via UNG2

PubMed Central

Thientosapol, Eddy Sanchai; Sharbeen, George; Lau, K.K. Edwin; Bosnjak, Daniel; Durack, Timothy; Stevanovski, Igor; Weninger, Wolfgang

2017-01-01

Abstract AID deaminates C to U in either strand of Ig genes, exclusively producing C:G/G:C to T:A/A:T transition mutations if U is left unrepaired. Error-prone processing by UNG2 or mismatch repair diversifies mutation, predominantly at C:G or A:T base pairs, respectively. Here, we show that transversions at C:G base pairs occur by two distinct processing pathways that are dictated by sequence context. Within and near AGCT mutation hotspots, transversion mutation at C:G was driven by UNG2 without requirement for mismatch repair. Deaminations in AGCT were refractive both to processing by UNG2 and to high-fidelity base excision repair (BER) downstream of UNG2, regardless of mismatch repair activity. We propose that AGCT sequences resist faithful BER because they bind BER-inhibitory protein(s) and/or because hemi-deaminated AGCT motifs innately form a BER-resistant DNA structure. Distal to AGCT sequences, transversions at G were largely co-dependent on UNG2 and mismatch repair. We propose that AGCT-distal transversions are produced when apyrimidinic sites are exposed in mismatch excision patches, because completion of mismatch repair would require bypass of these sites. PMID:28039326

Nuclear import of human MLH1, PMS2, and MutLalpha: redundancy is the key.

PubMed

Leong, Vivian; Lorenowicz, Jessica; Kozij, Natalie; Guarné, Alba

2009-08-01

DNA mismatch repair maintains genomic stability by correcting errors that have escaped polymerase proofreading. Defects on mismatch repair genes lead to an increased mutation rate, microsatellite instability and predisposition to human non-polyposis colorectal cancer (HNPCC). Human MutLalpha is a heterodimer formed by the interaction of MLH1 and PMS2 that coordinates a series of key events in mismatch repair. It has been proposed that nuclear import of MutLalpha may be the first regulatory step on the activation of the mismatch repair pathway. Using confocal microscopy and mismatch repair deficient cells, we have identified the sequence determinants that drive nuclear import of human MLH1, PMS2, and MutLalpha. Transient transfection of the individual proteins reveals that MLH1 has a bipartite and PMS2 has a single monopartite nuclear localization signal. Although dimerization is not required for nuclear localization, the MutLalpha heterodimer is imported more efficiently than the MLH1 or PMS2 monomers. Interestingly, the bipartite localization signal of MLH1 can direct import of MutLalpha even when PMS2 encompasses a mutated localization signal. Hence we conclude that the presence of redundant nuclear localization signals guarantees nuclear transport of MutLalpha and, consequently, efficient mismatch repair.

[SOS-repair--60 years].

PubMed

Zavil'gel'skiĭ, G B

2013-01-01

This review integrates 60 years of research on SOS-repair and SOS-mutagenesis in procaryotes and eucaryotes, from Jean Weigle experiment in 1953 year (mutagenesis of lambda bacteriophage in UV-irradiated bacteria) to the latest achievements in studying SOS-mutagenesis on all living organisms--Eukarya, Archaea and Bacteria. A key role in establishing of a biochemical basis for SOS-mutagenesis belonges to the finding in 1998-1999 years that specific error-prone DNA polymerases (PolV and others) catalysed translesion synthesis on damaged DNA. This review focuses on recent studies addressing the new models for SOS-induced mutagenesis in Escherichia coli and Home sapiens cells.

"Bad Luck Mutations": DNA Mutations Are not the Whole Answer to Understanding Cancer Risk.

PubMed

Trosko, James E; Carruba, Giuseppe

2017-01-01

It has been proposed that many human cancers are generated by intrinsic mechanisms that produce "Bad Luck" mutations by the proliferation of organ-specific adult stem cells. There have been serious challenges to this interpretation, including multiple extrinsic factors thought to be correlated with mutations found in cancers associated with these exposures. While support for both interpretations provides some validity, both interpretations ignore several concepts of the multistage, multimechanism process of carcinogenesis, namely, (1) mutations can be generated by both "errors of DNA repair" and "errors of DNA replication," during the "initiation" process of carcinogenesis; (2) "initiated" stem cells must be clonally amplified by nonmutagenic, intrinsic or extrinsic epigenetic mechanisms; (3) organ-specific stem cell numbers can be modified during in utero development, thereby altering the risk to cancer later in life; and (4) epigenetic tumor promoters are characterized by species, individual genetic-, gender-, developmental state-specificities, and threshold levels to be active; sustained and long-term exposures; and exposures in the absence of antioxidant "antipromoters." Because of the inevitability of some of the stem cells generating "initiating" mutations by either "errors of DNA repair" or "errors of DNA replication," a tumor is formed depending on the promotion phase of carcinogenesis. While it is possible to reduce our frequencies of mutagenic "initiated" cells, one can never reduce it to zero. Because of the extended period of the promotion phase of carcinogenesis, strategies to reduce the appearance of cancers must involve the interruption of the promotion of these initiated cells.

Metabolite damage and repair in metabolic engineering design.

PubMed

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Metabolite damage and repair in metabolic engineering design

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

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields,more » and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.« less

Radiative flux and forcing parameterization error in aerosol-free clear skies.

PubMed

Pincus, Robert; Mlawer, Eli J; Oreopoulos, Lazaros; Ackerman, Andrew S; Baek, Sunghye; Brath, Manfred; Buehler, Stefan A; Cady-Pereira, Karen E; Cole, Jason N S; Dufresne, Jean-Louis; Kelley, Maxwell; Li, Jiangnan; Manners, James; Paynter, David J; Roehrig, Romain; Sekiguchi, Miho; Schwarzkopf, Daniel M

2015-07-16

Radiation parameterizations in GCMs are more accurate than their predecessorsErrors in estimates of 4 ×CO 2 forcing are large, especially for solar radiationErrors depend on atmospheric state, so global mean error is unknown.

Mutagenic cost of ribonucleotides in bacterial DNA

PubMed Central

Schroeder, Jeremy W.; Randall, Justin R.; Hirst, William G.; O’Donnell, Michael E.; Simmons, Lyle A.

2017-01-01

Replicative DNA polymerases misincorporate ribonucleoside triphosphates (rNTPs) into DNA approximately once every 2,000 base pairs synthesized. Ribonucleotide excision repair (RER) removes ribonucleoside monophosphates (rNMPs) from genomic DNA, replacing the error with the appropriate deoxyribonucleoside triphosphate (dNTP). Ribonucleotides represent a major threat to genome integrity with the potential to cause strand breaks. Furthermore, it has been shown in the bacterium Bacillus subtilis that loss of RER increases spontaneous mutagenesis. Despite the high rNTP error rate and the effect on genome integrity, the mechanism underlying mutagenesis in RER-deficient bacterial cells remains unknown. We performed mutation accumulation lines and genome-wide mutational profiling of B. subtilis lacking RNase HII, the enzyme that incises at single rNMP residues initiating RER. We show that loss of RER in B. subtilis causes strand- and sequence-context–dependent GC → AT transitions. Using purified proteins, we show that the replicative polymerase DnaE is mutagenic within the sequence context identified in RER-deficient cells. We also found that DnaE does not perform strand displacement synthesis. Given the use of nucleotide excision repair (NER) as a backup pathway for RER in RNase HII-deficient cells and the known mutagenic profile of DnaE, we propose that misincorporated ribonucleotides are removed by NER followed by error-prone resynthesis with DnaE. PMID:29078353

Automatic-repeat-request error control schemes

NASA Technical Reports Server (NTRS)

Lin, S.; Costello, D. J., Jr.; Miller, M. J.

1983-01-01

Error detection incorporated with automatic-repeat-request (ARQ) is widely used for error control in data communication systems. This method of error control is simple and provides high system reliability. If a properly chosen code is used for error detection, virtually error-free data transmission can be attained. Various types of ARQ and hybrid ARQ schemes, and error detection using linear block codes are surveyed.

A New KE-Free Online ICALL System Featuring Error Contingent Feedback

ERIC Educational Resources Information Center

Tokuda, Naoyuki; Chen, Liang

2004-01-01

As a first step towards implementing a human language teacher, we have developed a new template-based on-line ICALL (intelligent computer assisted language learning) system capable of automatically diagnosing learners' free-format translated inputs and returning error contingent feedback. The system architecture we have adopted allows language…

Laser Engineered Net Shape (LENS) Technology for the Repair of Ni-Base Superalloy Turbine Components

NASA Astrophysics Data System (ADS)

Liu, Dejian; Lippold, John C.; Li, Jia; Rohklin, Stan R.; Vollbrecht, Justin; Grylls, Richard

2014-09-01

The capability of the laser engineered net shape (LENS) process was evaluated for the repair of casting defects and improperly machined holes in gas turbine engine components. Various repair geometries, including indentations, grooves, and through-holes, were used to simulate the actual repair of casting defects and holes in two materials: Alloy 718 and Waspaloy. The influence of LENS parameters, including laser energy density, laser scanning speed, and deposition pattern, on the repair of these defects and holes was studied. Laser surface remelting of the substrate prior to repair was used to remove machining defects and prevent heat-affected zone (HAZ) liquation cracking. Ultrasonic nondestructive evaluation techniques were used as a possible approach for detecting lack-of-fusion in repairs. Overall, Alloy 718 exhibited excellent repair weldability, with essentially no defects except for some minor porosity in repairs representative of deep through-holes and simulated large area casting defects. In contrast, cracking was initially observed during simulated repair of Waspaloy. Both solidification cracking and HAZ liquation cracking were observed in the repairs, especially under conditions of high heat input (high laser power and/or low scanning speed). For Waspaloy, the degree of cracking was significantly reduced and, in most cases, completely eliminated by the combination of low laser energy density and relatively high laser scanning speeds. It was found that through-hole repairs of Waspaloy made using a fine powder size exhibited excellent repair weldability and were crack-free relative to repairs using coarser powder. Simulated deep (7.4 mm) blind-hole repairs, representative of an actual Waspaloy combustor case, were successfully produced by the combination use of fine powder and relatively high laser scanning speeds.

[A case of vesicovaginal fistula repair with rectus abdominus myofascial interposition flap after radical hysterectomy and radiation therapy].

PubMed

Endo, Yuki; Iigaya, Shigeki; Nishimura, Taiji; Ishii, Naohiro; Kitaoka, Yoshihisa; Kawashima, Toshifumi; Ohara, Chiharu; Hamasaki, Tsutomu; Kondo, Yukihiro

2014-10-01

Vesicovaginal fistulas (VVFs) caused after radiation are difficult to repair and require interposition of non-irradiated, well-vascularized tissue between urinary bladder and vagina. A 48-year-old female suffered cervical cancer and underwent radical hysterectomy followed by radiation therapy which caused VVF. The initial surgical repair performed 3 months after development of VVF, was unsuccessful because of the absence of peritoneum or omentum to interpose between urinary bladder and vagina probably due to history of cesarean section and radical hysterectomy. The second surgical repair was performed 15 months after the first surgery utilizing a rectus abdominus myofascial (RAM) interposition flap. Fifteen months after the second operation, she remains free from incontinence. This case suggests that RAM is useful even for postradiation VVF.

[Umbilical hernia repair in conjunction with abdominoplasty].

PubMed

Bai, Ming; Dai, Meng-Hua; Huang, Jiu-Zuo; Qi, Zheng; Lin, Chen; Ding, Wen-Yun; Zhao, Ru

2012-09-01

To investigate the feasibility and clinical benefits of umbilical hernia repair in conjunction with abdominoplasty. The incision was designed in accord with abdominoplasty. The skin and subcutaneous tissue was dissected toward the costal arch, and then the anterior sheath of rectus abdominus was exposed. After exposure and dissection of the sac of umbilical hernia, tension-free hernioplasty was performed with polypropylene mesh. After dissecting the redundant skin and subcutaneous tissue, the abdominal wall was tightened. Between May 2008 and May 2011, ten patients were treated in the way mentioned above. The repair of umbilical hernia and the correction of abdominal wall laxity were satisfactory. There was no recurrence of umbilical hernia, hematoma, seroma or fat liquefaction. Through careful selection of patients, repair of umbilical hernia and body contouring could be achieved simultaneously.

Mitochondrial DNA Damage and its Consequences for Mitochondrial Gene Expression

PubMed Central

Cline, Susan D.

2012-01-01

How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression. PMID:22728831

Repair of high performance multilayer coatings

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

Gaines, D.P.; Ceglio, N.M.; Vernon, S.P.

1991-07-01

Fabrication and environmental damage issues may require that the multilayer x-ray reflection coatings used in soft x-ray projection lithography be replaced or repaired. Two repair strategies were investigated. The first was to overcoat defective multilayers with a new multilayer. The feasibility of this approach was demonstrated by depositing high reflectivity (61% at 130 {Angstrom}) molybdenum silicon (Mo/Si) multilayers onto fused silica figured optics that had already been coated with a Mo/Si multilayer. Because some types of damage mechanisms and fabrication errors are not repairable by this method, a second method of repair was investigated. The multilayer was stripped from themore » optical substrate by etching a release layer which was deposited onto the substrate beneath the multilayer. The release layer consisted of a 1000 {Angstrom} aluminum film deposited by ion beam sputtering or by electron beam evaporation, with a 300 {Angstrom} SiO{sub 2} protective overcoat. The substrates were superpolished zerodur optical flats. The normal incidence x-ray reflectivity of multilayers deposited on these aluminized substrates was degraded, presumably due to the roughness of the aluminum films. Multilayers, and the underlying release layers, have been removed without damaging the substrates.« less

COMPARISON OF ARTIFICIAL NEOCHORDAE AND NATIVE CHORDAL TRANSFER IN THE REPAIR OF A FLAIL POSTERIOR MITRAL LEAFLET: AN EXPERIMENTAL STUDY

PubMed Central

Padala, Muralidhar; Cardinau, Benedicte; Gyoneva, Lazarina I.; Thourani, Vinod H.

2013-01-01

BACKGROUND Surgical reconstruction of a flail posterior leaflet is a routine mitral valve repair, the techniques for which have evolved from leaflet resection to leaflet preservation. Artificial ePTFE neochordae are frequently used to stabilize the flail leaflet, and seldom translocation of the native secondary chordae of the valve to the leaflet free edge is used. In this study, we sought to investigate the efficacy of the two techniques to correct posterior leaflet prolapse and reduce mitral regurgitation, and quantify the acute post-repair leaflet kinematics. METHODS Adult porcine mitral valves (N =7) were studied in a pulsatile left heart experimental model in which isolated P2 flail was mimicked by marginal chordal transection. Baseline conditions were established in each valve under normal conditions (control), and followed by induction of isolated P2 flail by transecting the two marginal chordae on the posterior leaflet free edge (disease). The flail posterior leaflet was reconstructed using artificial neochordae (repair 1) and then native chordal translocation (repair 2). Reduction in leaflet flail, changes in mitral regurgitation fraction, leaflet coaptation length, and posterior leaflet mobility were measured using B-mode echocardiography or color doppler. RESULTS At baseline, all the valves were competent with no mitral regurgitation. After transection of the marginal chordae on the posterior leaflet, isolated P2 flail was evident with 13.7±13% regurgitation. Reconstruction with artificial neochordae eliminated leaflet flail and reduced mitral regurgitation to 3.2± 2.8%, and with chordal translocation leaflet flail was corrected and mitral regurgitation was measured at 2.3±2.6%. Using either repair techniques, leaflet coaptation and mobility of the repaired leaflets were adequate and comparable to the baseline measurements. CONCLUSIONS Comparable reduction leaflet flail and regurgitation, and restoration of physiological leaflet coaptation with the two techniques indicates that under acute conditions, use of artificial neochordae or native chordal translocations have similar benefits. PMID:23291143

Tension-free repair during extensive radical surgery for cecal cancer with abdominal wall invasion and inguinal lymph node metastasis

PubMed Central

Xu, Kaiwu; Chen, Zhihui; Song, Xinming

2014-01-01

We report a case of cecal cancer with invasion of the abdominal wall and right inguinal lymph node metastasis. This patient had undergone an appendectomy 2 years previously. He underwent extensive radical right hemicolectomy with anastomosis and tension-free repair of the damaged right lower abdominal wall. The surgery progressed successfully, and the vital signs of the patient were stable (approximately 200 mL blood loss). Postoperative diagnosis revealed moderately to poorly differentiated adenocarcinoma of the cecum with invasion of the abdominal wall and metastasis of the inguinal lymph nodes (pT4bN2bM1, IV4a). The patient has remained well post-surgery. PMID:24855366

Multiple point mutations in a shuttle vector propagated in human cells: evidence for an error-prone DNA polymerase activity.

PubMed

Seidman, M M; Bredberg, A; Seetharam, S; Kraemer, K H

1987-07-01

Mutagenesis was studied at the DNA-sequence level in human fibroblast and lymphoid cells by use of a shuttle vector plasmid, pZ189, containing a suppressor tRNA marker gene. In a series of experiments, 62 plasmids were recovered that had two to six base substitutions in the 160-base-pair marker gene. Approximately 20-30% of the mutant plasmids that were recovered after passing ultraviolet-treated pZ189 through a repair-proficient human fibroblast line contained these multiple mutations. In contrast, passage of ultraviolet-treated pZ189 through an excision-repair-deficient (xeroderma pigmentosum) line yielded only 2% multiple base substitution mutants. Introducing a single-strand nick in otherwise unmodified pZ189 adjacent to the marker, followed by passage through the xeroderma pigmentosum cells, resulted in about 66% multiple base substitution mutants. The multiple mutations were found in a 160-base-pair region containing the marker gene but were rarely found in an adjacent 170-base-pair region. Passing ultraviolet-treated or nicked pZ189 through a repair-proficient human B-cell line also yielded multiple base substitution mutations in 20-33% of the mutant plasmids. An explanation for these multiple mutations is that they were generated by an error-prone polymerase while filling gaps. These mutations share many of the properties displayed by mutations in the immunoglobulin hypervariable regions.

Determinants of spontaneous mutation in the bacterium Escherichia coli as revealed by whole-genome sequencing

PubMed Central

Foster, Patricia L.; Lee, Heewook; Popodi, Ellen; Townes, Jesse P.; Tang, Haixu

2015-01-01

A complete understanding of evolutionary processes requires that factors determining spontaneous mutation rates and spectra be identified and characterized. Using mutation accumulation followed by whole-genome sequencing, we found that the mutation rates of three widely diverged commensal Escherichia coli strains differ only by about 50%, suggesting that a rate of 1–2 × 10−3 mutations per generation per genome is common for this bacterium. Four major forces are postulated to contribute to spontaneous mutations: intrinsic DNA polymerase errors, endogenously induced DNA damage, DNA damage caused by exogenous agents, and the activities of error-prone polymerases. To determine the relative importance of these factors, we studied 11 strains, each defective for a major DNA repair pathway. The striking result was that only loss of the ability to prevent or repair oxidative DNA damage significantly impacted mutation rates or spectra. These results suggest that, with the exception of oxidative damage, endogenously induced DNA damage does not perturb the overall accuracy of DNA replication in normally growing cells and that repair pathways may exist primarily to defend against exogenously induced DNA damage. The thousands of mutations caused by oxidative damage recovered across the entire genome revealed strong local-sequence biases of these mutations. Specifically, we found that the identity of the 3′ base can affect the mutability of a purine by oxidative damage by as much as eightfold. PMID:26460006

Combined open proximal and stent-graft distal repair for distal arch aneurysms: an alternative to total debranching.

PubMed

Zierer, Andreas; Sanchez, Luis A; Moon, Marc R

2009-07-01

We present herein a novel, combined, simultaneous open proximal and stent-graft distal repair for complex distal aortic arch aneurysms involving the descending aorta. In the first surgical step, the transverse arch is opened during selective antegrade cerebral perfusion, and a Dacron graft (DuPont, Wilmington, DE) is positioned down the descending aorta in an elephant trunk-like fashion with its proximal free margin sutured circumferentially to the aorta just distal to the left subclavian or left common carotid artery. With the graft serving as the new proximal landing zone, subsequent endovascular repair is performed antegrade during rewarming through the ascending aorta.

Rescheduling with iterative repair

NASA Technical Reports Server (NTRS)

Zweben, Monte; Davis, Eugene; Daun, Brian; Deale, Michael

1992-01-01

This paper presents a new approach to rescheduling called constraint-based iterative repair. This approach gives our system the ability to satisfy domain constraints, address optimization concerns, minimize perturbation to the original schedule, produce modified schedules, quickly, and exhibits 'anytime' behavior. The system begins with an initial, flawed schedule and then iteratively repairs constraint violations until a conflict-free schedule is produced. In an empirical demonstration, we vary the importance of minimizing perturbation and report how fast the system is able to resolve conflicts in a given time bound. We also show the anytime characteristics of the system. These experiments were performed within the domain of Space Shuttle ground processing.

Language Loss and the Crisis of Cognition: Between Socio- and Psycholinguistics.

ERIC Educational Resources Information Center

Kenny, K. Dallas

A non-structural model is proposed for quantifying and analyzing the dynamics of language attrition, particularly among immigrants in a second language environment, based on examination of disfluencies (hesitations, errors, and repairs). The first chapter discusses limitations of the conventional synchronic textual approach to analyzing language…

CRISPR/Cas9-Induced Double-Strand Break Repair in Arabidopsis Nonhomologous End-Joining Mutants.

PubMed

Shen, Hexi; Strunks, Gary D; Klemann, Bart J P M; Hooykaas, Paul J J; de Pater, Sylvia

2017-01-05

Double-strand breaks (DSBs) are one of the most harmful DNA lesions. Cells utilize two main pathways for DSB repair: homologous recombination (HR) and nonhomologous end-joining (NHEJ). NHEJ can be subdivided into the KU-dependent classical NHEJ (c-NHEJ) and the more error-prone KU-independent backup-NHEJ (b-NHEJ) pathways, involving the poly (ADP-ribose) polymerases (PARPs). However, in the absence of these factors, cells still seem able to adequately maintain genome integrity, suggesting the presence of other b-NHEJ repair factors or pathways independent from KU and PARPs. The outcome of DSB repair by NHEJ pathways can be investigated by using artificial sequence-specific nucleases such as CRISPR/Cas9 to induce DSBs at a target of interest. Here, we used CRISPR/Cas9 for DSB induction at the Arabidopsis cruciferin 3 (CRU3) and protoporphyrinogen oxidase (PPO) genes. DSB repair outcomes via NHEJ were analyzed using footprint analysis in wild-type plants and plants deficient in key factors of c-NHEJ (ku80), b-NHEJ (parp1 parp2), or both (ku80 parp1 parp2). We found that larger deletions of >20 bp predominated after DSB repair in ku80 and ku80 parp1 parp2 mutants, corroborating with a role of KU in preventing DSB end resection. Deletion lengths did not significantly differ between ku80 and ku80 parp1 parp2 mutants, suggesting that a KU- and PARP-independent b-NHEJ mechanism becomes active in these mutants. Furthermore, microhomologies and templated insertions were observed at the repair junctions in the wild type and all mutants. Since these characteristics are hallmarks of polymerase θ-mediated DSB repair, we suggest a possible role for this recently discovered polymerase in DSB repair in plants. Copyright © 2017 Shen et al.

BCR/ABL downregulates DNA-PK(CS)-dependent and upregulates backup non-homologous end joining in leukemic cells.

PubMed

Poplawski, Tomasz; Blasiak, Janusz

2010-06-01

Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PK(CS); D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PK(CS) (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PK(CS), did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells.

ERCC1-XPF Endonuclease Facilitates DNA Double-Strand Break Repair▿ †

PubMed Central

Ahmad, Anwaar; Robinson, Andria Rasile; Duensing, Anette; van Drunen, Ellen; Beverloo, H. Berna; Weisberg, David B.; Hasty, Paul; Hoeijmakers, Jan H. J.; Niedernhofer, Laura J.

2008-01-01

ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease. In Saccharomyces cerevisiae, orthologs of ERCC1-XPF (Rad10-Rad1) participate in the repair of double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB repair pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To determine if ERCC1-XPF participates in DSB repair in mammals, mutant cells and mice were screened for sensitivity to gamma irradiation. ERCC1-XPF-deficient fibroblasts were hypersensitive to gamma irradiation, and γH2AX foci, a marker of DSBs, persisted in irradiated mutant cells, consistent with a defect in DSB repair. Mutant mice were also hypersensitive to irradiation, establishing an essential role for ERCC1-XPF in protecting against DSBs in vivo. Mice defective in both ERCC1-XPF and Ku86 were not viable. However, Ercc1−/− Ku86−/− fibroblasts were hypersensitive to gamma irradiation compared to single mutants and accumulated significantly greater chromosomal aberrations. Finally, in vitro repair of DSBs with 3′ overhangs led to large deletions in the absence of ERCC1-XPF. These data support the conclusion that, as in yeast, ERCC1-XPF facilitates DSB repair via an end-joining mechanism that is Ku86 independent. PMID:18541667

Primary repair of the anterior cruciate ligament: A paradigm shift.

PubMed

van der List, Jelle P; DiFelice, Gregory S

2017-06-01

Over the last century, many surgical treatments have been developed in the orthopedic field, including treatments of anterior cruciate ligament (ACL) injuries. These treatments ideally evolve in a process of trial and error with prospective comparison of new treatments to the current treatment standard. However, these evolutions are sometimes not linear and periodically undergo paradigm shifts. In this article, we review the evolution of ACL treatment and explain how it underwent a paradigm shift. Open primary ACL repair was the most common treatment in the 1970s and 1980s, but because multiple studies noted deterioration of outcomes at mid-term follow-up, in addition to several randomized clinical trials (RCTs) that noted better outcomes following ACL reconstruction, the open primary repair technique was abandoned. At the end of the primary repair era, however, several studies showed that outcomes of open primary repair were good to excellent and did not deteriorate when this technique was selectively performed in patients with proximal ACL tears, whereas primary repair led to disappointing and unpredictable results in patients with mid-substance tears. Unfortunately, enrollment of patients in the aforementioned RCTs was already finished, ultimately leading to abandoning of open primary repair, despite the advantages of ligament preservation. In this review, we discuss (I) why the evolution of ACL treatment underwent a paradigm shift, (II) which factors may have played a role in this and (III) what the future role of arthroscopic primary ACL repair is in the evolution of ACL treatments. Copyright © 2016. Published by Elsevier Ltd.

Proteolytic activities in yeast after UV irradiation. II. Variation in proteinase levels in mutants blocked in DNA-repair pathways.

PubMed

Schwencke, J; Moustacchi, E

1982-01-01

When the levels of three common yeast proteinases in exponentially growing cells of mutants blocked in different repair pathways are compared to that of isogenic wild-type cells, it can be seen that the level of proteinase B is enhanced in the mutants whereas the levels of leucin aminopeptidase (Leu.AP) and lysine aminopeptidase (Lys.AP) are similar in all strains. As in its corresponding wild type, the level of proteinase B activity is further enhanced after UV-irradiation in a mutant blocked in excision-repair (rad1-3). In contrast, following the same treatment the level of proteinase B remains almost constant in a mutant blocked in a general error-prone repair system (rad6-1) and in a mutant defective in a more specific mutagenic repair pathway (pso2-1). Cycloheximide, an inhibitor of protein synthesis, blocks the post-UV enhancement in proteinase B activity observed in rad1-3 indicating that, as in the wild-type cells, an inducible process is involved. The levels of Lys.AP and Leu.AP are, respectively, either unaffected or only moderately increased following UV-treatment of the repair defective mutants, as in wild-type strains. It is obvious that the induction of protease B activity following UV-treatment in Saccharomyces cannot be equated to the induction of the recA protein in Escherichia coli. However the correlation found between the block in mutagenic repair and the lack of UV-induction of protease B activity leads to questions on the possible role of certain protease activities in mutagenic repair in eucaryotic cells.

The Effects of Observation Errors on the Attack Vulnerability of Complex Networks

DTIC Science & Technology

2012-11-01

more detail, to construct a true network we select a topology (erdos- renyi (Erdos & Renyi , 1959), scale-free (Barabási & Albert, 1999), small world...Efficiency of Scale-Free Networks: Error and Attack Tolerance. Physica A, Volume 320, pp. 622-642. 6. Erdos, P. & Renyi , A., 1959. On Random Graphs, I

Error-Free Text Typing Performance of an Inductive Intra-Oral Tongue Computer Interface for Severely Disabled Individuals.

PubMed

Andreasen Struijk, Lotte N S; Bentsen, Bo; Gaihede, Michael; Lontis, Eugen R

2017-11-01

For severely paralyzed individuals, alternative computer interfaces are becoming increasingly essential for everyday life as social and vocational activities are facilitated by information technology and as the environment becomes more automatic and remotely controllable. Tongue computer interfaces have proven to be desirable by the users partly due to their high degree of aesthetic acceptability, but so far the mature systems have shown a relatively low error-free text typing efficiency. This paper evaluated the intra-oral inductive tongue computer interface (ITCI) in its intended use: Error-free text typing in a generally available text editing system, Word. Individuals with tetraplegia and able bodied individuals used the ITCI for typing using a MATLAB interface and for Word typing for 4 to 5 experimental days, and the results showed an average error-free text typing rate in Word of 11.6 correct characters/min across all participants and of 15.5 correct characters/min for participants familiar with tongue piercings. Improvements in typing rates between the sessions suggest that typing ratescan be improved further through long-term use of the ITCI.

Comparison of hybrid endovascular and open surgical repair for proximal aortic arch diseases.

PubMed

Kang, Woong Chol; Ko, Young-Guk; Shin, Eak Kyun; Park, Chul-Hyun; Choi, Donghoon; Youn, Young Nam; Lee, Do Yun

2016-01-15

To compare the outcomes of hybrid endovascular and open surgical repair for proximal aortic arch diseases. A total of 55 consecutive patients with aortic arch aneurysm or aortic dissection involving any of zone 0 to 1 (39 male, age 63.4 ± 14.3 years) underwent a hybrid endovascular repair (n=35) or open surgical repair (n=20) from 2006 to 2014 were analyzed retrospectively. Perioperative and late outcomes were compared. Baseline characteristics were similar between the two groups, except age and EuroSCORE II, which were higher in the hybrid group. Perioperative mortality or stroke was not significantly different between the two groups, however, tended to be lower in the hybrid repair group than in the open repair group (11.4% vs. 30.0%, p=0.144). Incidences of other morbidities did not differ. During follow-up, over-all survival was similar between the hybrid and the open repair was similar (87.3% vs. 79.7% at 1 year and 83.8% vs. 72.4% at 3 years; p=0.319). However, reintervention-free survival was significantly lower for hybrid repair compared with open repair (83.8% vs. 100% at 1 year and 65.7% vs. 100% at 3 years; p=0.022). Hybrid repair of proximal aortic disease showed comparable perioperative and late outcomes compared with open surgical repair despite a higher reintervention rate during follow-up. Therefore, hybrid repair may be considered as an acceptable treatment alternative to surgery especially in patients at high surgical risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Exception handling for sensor fusion

NASA Astrophysics Data System (ADS)

Chavez, G. T.; Murphy, Robin R.

1993-08-01

This paper presents a control scheme for handling sensing failures (sensor malfunctions, significant degradations in performance due to changes in the environment, and errant expectations) in sensor fusion for autonomous mobile robots. The advantages of the exception handling mechanism are that it emphasizes a fast response to sensing failures, is able to use only a partial causal model of sensing failure, and leads to a graceful degradation of sensing if the sensing failure cannot be compensated for. The exception handling mechanism consists of two modules: error classification and error recovery. The error classification module in the exception handler attempts to classify the type and source(s) of the error using a modified generate-and-test procedure. If the source of the error is isolated, the error recovery module examines its cache of recovery schemes, which either repair or replace the current sensing configuration. If the failure is due to an error in expectation or cannot be identified, the planner is alerted. Experiments using actual sensor data collected by the CSM Mobile Robotics/Machine Perception Laboratory's Denning mobile robot demonstrate the operation of the exception handling mechanism.

Urethroplasty for urethral strictures: quality assessment of an in-home algorithm.

PubMed

Lumen, Nicolaas; Hoebeke, Piet; Oosterlinck, Willem

2010-02-01

To evaluate the outcome of different techniques of urethroplasty and to assess the quality of an in-home algorithm. Two hundred fifty-two male patients underwent urethroplasty. Mean patient's age was 48 years (range 1-85 years). Data were analyzed for the failure rate of the different techniques of urethroplasty. An additional analysis was done based on an in-home algorithm. Median follow up was 37 months (range: 6-92 months). Global failure rate was 14.9%, with an individual failure rate of 11.7%, 16.0%, 20.7% and 20.8% for anastomotic repair, free graft urethroplasty, pedicled flap urethroplasty and combined urethroplasty, respectively. In free graft urethroplasty, results were significantly worse when extrapreputial skin was used. Anastomotic repair was the principle technique for short strictures (83.3%), at the bulbar and posterior urethra (respectively 50.8 and 100%). Free graft urethroplasty was mainly used for 3-10 cm strictures (58.6%). Anastomotic repair and free graft urethroplasty were more used in case of no previous interventions or after urethrotomy/dilation. Pedicled flap urethroplasty was the main technique at the penile urethra (40.7%). Combined urethroplasty was necessary in 41 and 47.1% in the treatment of, respectively, >10 cm or panurethral/multifocal anterior urethral strictures and was the most important technique in these circumstances. Two-stage urethroplasty or perineostomy were only used in 2% as first-line treatment but were already used in 14.9% after failed urethroplasty. Urethroplasty has good results at intermediate follow up. Different types of techniques must be used for different types of strictures.

Mutational analysis of the human nucleotide excision repair gene ERCC1.

PubMed Central

Sijbers, A M; van der Spek, P J; Odijk, H; van den Berg, J; van Duin, M; Westerveld, A; Jaspers, N G; Bootsma, D; Hoeijmakers, J H

1996-01-01

The human DNA repair protein ERCC1 resides in a complex together with the ERCC4, ERCC11 and XP-F correcting activities, thought to perform the 5' strand incision during nucleotide excision repair (NER). Its yeast counterpart, RAD1-RAD10, has an additional engagement in a mitotic recombination pathway, probably required for repair of DNA cross-links. Mutational analysis revealed that the poorly conserved N-terminal 91 amino acids of ERCC1 are dispensable for both repair functions, in contrast to a deletion of only four residues from the C-terminus. A database search revealed a strongly conserved motif in this C-terminus sharing sequence homology with many DNA break processing proteins, indicating that this part is primarily required for the presumed structure-specific endonuclease activity of ERCC1. Most missense mutations in the central region give rise to an unstable protein (complex). Accordingly, we found that free ERCC1 is very rapidly degraded, suggesting that protein-protein interactions provide stability. Survival experiments show that the removal of cross-links requires less ERCC1 than UV repair. This suggests that the ERCC1-dependent step in cross-link repair occurs outside the context of NER and provides an explanation for the phenotype of the human repair syndrome xeroderma pigmentosum group F. PMID:8811092

Low power lasers on genomic stability.

PubMed

Trajano, Larissa Alexsandra da Silva Neto; Sergio, Luiz Philippe da Silva; Stumbo, Ana Carolina; Mencalha, Andre Luiz; Fonseca, Adenilson de Souza da

2018-03-01

Exposure of cells to genotoxic agents causes modifications in DNA, resulting to alterations in the genome. To reduce genomic instability, cells have DNA damage responses in which DNA repair proteins remove these lesions. Excessive free radicals cause DNA damages, repaired by base excision repair and nucleotide excision repair pathways. When non-oxidative lesions occur, genomic stability is maintained through checkpoints in which the cell cycle stops and DNA repair occurs. Telomere shortening is related to the development of various diseases, such as cancer. Low power lasers are used for treatment of a number of diseases, but they are also suggested to cause DNA damages at sub-lethal levels and alter transcript levels from DNA repair genes. This review focuses on genomic and telomere stabilization modulation as possible targets to improve therapeutic protocols based on low power lasers. Several studies have been carried out to evaluate the laser-induced effects on genome and telomere stabilization suggesting that exposure to these lasers modulates DNA repair mechanisms, telomere maintenance and genomic stabilization. Although the mechanisms are not well understood yet, low power lasers could be effective against DNA harmful agents by induction of DNA repair mechanisms and modulation of telomere maintenance and genomic stability. Copyright © 2018 Elsevier B.V. All rights reserved.

Sutureless liver repair and hemorrhage control using laser-mediated fusion of human albumin as a solder.

PubMed

Wadia, Y; Xie, H; Kajitani, M

2001-07-01

Major liver trauma has a high mortality because of immediate exsanguination and a delayed morbidity from septicemia, peritonitis, biliary fistulae, and delayed secondary hemorrhage. We evaluated laser soldering using liquid albumin for welding liver injuries. Fourteen lacerations (6 x 2 cm) and 13 nonanatomic resection injuries (raw surface, 8 x 2 cm) were repaired. An 805-nm laser was used to weld 53% liquid albumin-indocyanine green solder to the liver surface, reinforcing it by welding a free autologous omental scaffold. The animals were heparinized and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, 16 soldering repairs were evaluated acutely at 3 hours. Eleven animals were evaluated chronically, two at 2 weeks and nine at 4 weeks. All 27 laser mediated-liver repairs had minimal blood loss compared with the suture controls. No dehiscence, hemorrhage, or bile leakage was seen in any of the laser repairs after 3 hours. All 11 chronic repairs healed without complication. This modality effectively seals the liver surface, joins lacerations with minimal thermal injury, and works independently of the patient's coagulation status.

Understanding and reduction of defects on finished EUV masks

NASA Astrophysics Data System (ADS)

Liang, Ted; Sanchez, Peter; Zhang, Guojing; Shu, Emily; Nagpal, Rajesh; Stivers, Alan

2005-05-01

To reduce the risk of EUV lithography adaptation for the 32nm technology node in 2009, Intel has operated a EUV mask Pilot Line since early 2004. The Pilot Line integrates all the necessary process modules including common tool sets shared with current photomask production as well as EUV specific tools. This integrated endeavor ensures a comprehensive understanding of any issues, and development of solutions for the eventual fabrication of defect-free EUV masks. Two enabling modules for "defect-free" masks are pattern inspection and repair, which have been integrated into the Pilot Line. This is the first time we are able to look at real defects originated from multilayer blanks and patterning process on finished masks over entire mask area. In this paper, we describe our efforts in the qualification of DUV pattern inspection and electron beam mask repair tools for Pilot Line operation, including inspection tool sensitivity, defect classification and characterization, and defect repair. We will discuss the origins of each of the five classes of defects as seen by DUV pattern inspection tool on finished masks, and present solutions of eliminating and mitigating them.

Outcomes of using a modified anteromedial thigh perforator flap for repairing the anterolateral thigh free flap donor site: A retrospective clinical review.

PubMed

Zhou, Xiao; Wang, Jin; Qiang, Li; Rui, Yongjun; Xue, Mingyu

2018-04-01

The anterolateral thigh (ALT) flap plays an essential part in plastic and reconstructive surgery. However, repair of the anterolateral donor site has not been the focus of the clinicians.To assess the clinical value and feasibility of using a modified anteromedial thigh (AMT) perforator flap for repairing the ALT free flap donor site.In this retrospective study, 16 ALT flaps were transferred to resurface large soft-tissue defects (ranged from 7 × 5 to 13 × 8 cm) in the foot or hand from June 2012 to March 2013. The donor sites were repaired with an advancement flap pedicled with an AMT perforator. Sensation within the advancement flap, return-to-work (RTW) time, the aesthetic appearance of the donor sites, and functional recovery were measured.All 15 flaps survived completely without necrosis. One flap developed partial necrosis in the tip but healed with dressing changes after 1 week. The medain follow-up period was 3.5 months (range, 3-6 months). The average median time was 9.5 weeks (range 8-13 weeks). There was no numbness of the advancement flap. Additionally, there was no specific complication at both the recipient and donor sites. Thigh quadriceps muscle strength and activities of the knee were normal. All patients were satisfied with the aesthetic outcome postoperatively at the 3-month to 6-month follow-up.The modified advancement flap pedicled with an AMT perforator is an ideal option for repairing the anterolateral donor site.

Combined Endoscopic Transorbital and Endonasal Repair of High Flow Orbital Apex/Middle Fossa Cerebrospinal Fluid Leak with a Nasoseptal Flap.

PubMed

Lucke-Wold, Brandon; Mendez, Gustavo; Cua, David; Akins, Paul; Gillham, Haley; Ciporen, Jeremy

2018-01-01

High flow orbital apex or middle fossa cerebrospinal fluid (CSF) leaks can be life threatening and complex to repair. These leaks associated with large dural defects are most commonly repaired with an open temporalis muscle patch or free flaps, but these flaps do not always stop the leak. A 65-year-old patient presented two years after orbital exenteration and radiation for squamous cell carcinoma. He developed multi-organism meningitis and pneumocephalus secondary to a large high-flow orbital apex/middle fossa CSF leak. To repair the leak, a combined endoscopic transorbital/endonasal approach with pedicled nasospetal flap and dermis fat graft was used. We describe the unique endoscopic technique that was used to treat the life threatening high flow orbital apex/middle fossa CSF leak. The technique allowed the use of the transposed pedicled flap, which is an alternative to the free flap in controlling CSF leak. Cisternogram post-operatively and clinical exam confirmed resolution of CSF leak. Although a critically ill patient at admission with a modified Rankin scale (MRS) of 5, he was discharged home on continued IV antibiotic therapy with a MRS of 3. Endoscopic evaluation at three months after treatment showed the effectiveness of the flap and he continued to improve clinically. This is the first case to describe a combined endoscopic transorbital and endonasal repair of high flow orbital apex/middle fossa CSF leak with a pedicled nasoseptal flap. These techniques can be utilized during initial reconstruction after orbital exenteration or as a salvage flap.

Laparoscopic inguinal hernia repair.

PubMed

Hussein, M K; Khoury, G S; Taha, A M

1998-01-01

Open hernia repair is associated with significant postoperative pain and disability resulting in delayed return to full activity. Laparoscopic hernia repair has been advocated as the procedure that combines the benefit of tension-free repair with the preservation of the basic anatomy of the inguinal area. We present our experience with 803 laparoscopic hernia repairs in 517 patients over a period of 66 months (August 92 to February 98). The effects of the learning curve and the refinement of the technique had their impact on earlier results and complications. However, with more experience we found that the laparoscopic preperitoneal approach is safe and efficacious. There was no mortality. Most patients (85%) were discharged home within 24 h of the procedure and returned to full activity within 10 days. Patient satisfaction was excellent. The complication rate decreased and operative time was reduced with experience. This procedure is clearly indicated in patients who have recurrent or bilateral hernias. It is associated with shorter convalescence and a quick return to work.

Modeling non-homologous end joining.

PubMed

Li, Yongfeng; Cucinotta, Francis A

2011-08-21

Non-homologous end joining (NHEJ) is an important DNA repair pathway for DNA double-strand breaks. Several proteins, including Ku, DNA-PKcs, Artemis, XRCC4/Ligase IV and XLF, are involved in the NHEJ for the DNA damage detection, DNA free end processing and ligation. The classical model of NHEJ is a sequential model in which DNA-PKcs is first recruited by the Ku bound DNA prior to any other repair proteins. Recent experimental study (McElhinny et al., 2000; Costantini et al., 2007; Mari et al., 2006; Yano and Chen, 2008) suggested that the recruitment ordering is not crucial. In this work, by proposing a mathematical model in terms of biochemical reaction network and performing stability and related analysis, we demonstrate theoretically that if DSB repair pathway independent of DNA-PKcs exists, then the classical sequential model and new two-phase model are essentially indistinguishable in the sense that DSB can be repaired thoroughly in both models when the repair proteins are sufficient. Published by Elsevier Ltd.

Use of buccal mucosa patch graft for recurrent large urethrocutaneous fistula after hypospadias repair.

PubMed

Kiss, András; Pirót, László; Karsza, Levente; Merksz, Miklós

2004-01-01

To assess the effectiveness of buccal mucosa patch graft in the treatment of recurrent large urethrocutaneous fistula after hypospadias repair. A free graft of buccal mucosa was used for closure in 7 boys (mean age 4.8 years) with large (>4 mm) urethocutaneous fistula. Four fistulas were in the midshaft, 2 of them penoscrotal and 1 coronal type. All patients had undergone at least two previous unsuccessful fistula repairs, and 3 of them had undergone three attempts for closure. Fistula repairs were similar in all cases. The repair was successful in 6 out of 7 cases, and in these cases the urinary stream was good after the removal of the catheter. The unsuccessful case was the coronal one. Based on our experience it seems that in cases with recurrent large fistula after hypospadias reconstruction, the use of buccal mucosa patch graft for closure is a good treatment choice. Copyright 2004 S. Karger AG, Basel

Economic and technical aspects of repair, servicing, and retrieval of low earth orbit free flying spacecraft

NASA Technical Reports Server (NTRS)

Cepollina, F. J.

1982-01-01

The economic and technical aspects of the Solar Maximum Observatory Repair Mission at NASA are presented, in an effort to demonstrate the Space Shuttle capability to rendezvous with and repair on-orbit the Solar Maximum Observatory (SMM). A failure in the Attitude Control Subsystem (ACS) after 10 months of operation caused a loss in precision pointing capability. The Multimission Modular Spacecraft (MMS) used for the mission, was designed with on-orbit repairability, and to correct various instrument anomalies, repiar kits such as an electronics box, a thermal aperture closure, and a high energy particle reflection baffle will be used. In addition, a flight support system will be used to berth, electrically safe, and support all the repair activities. A two year effort is foreseen, and the economic return on SMM will be $176 M, in addition to two to three years of solar observation. The mission will eventually conduct studies on flare as a function of solar cycle.

Checkpoint-based forward recovery using lookahead execution and rollback validation in parallel and distributed systems. Ph.D. Thesis, 1992

NASA Technical Reports Server (NTRS)

Long, Junsheng

1994-01-01

This thesis studies a forward recovery strategy using checkpointing and optimistic execution in parallel and distributed systems. The approach uses replicated tasks executing on different processors for forwared recovery and checkpoint comparison for error detection. To reduce overall redundancy, this approach employs a lower static redundancy in the common error-free situation to detect error than the standard N Module Redundancy scheme (NMR) does to mask off errors. For the rare occurrence of an error, this approach uses some extra redundancy for recovery. To reduce the run-time recovery overhead, look-ahead processes are used to advance computation speculatively and a rollback process is used to produce a diagnosis for correct look-ahead processes without rollback of the whole system. Both analytical and experimental evaluation have shown that this strategy can provide a nearly error-free execution time even under faults with a lower average redundancy than NMR.

Error Free Software

NASA Technical Reports Server (NTRS)

1985-01-01

A mathematical theory for development of "higher order" software to catch computer mistakes resulted from a Johnson Space Center contract for Apollo spacecraft navigation. Two women who were involved in the project formed Higher Order Software, Inc. to develop and market the system of error analysis and correction. They designed software which is logically error-free, which, in one instance, was found to increase productivity by 600%. USE.IT defines its objectives using AXES -- a user can write in English and the system converts to computer languages. It is employed by several large corporations.

Comparison of Lichtenstein inguinal hernia repair with the tension-free Desarda technique: a clinical audit and review of the literature.

PubMed

Zulu, Halalisani Goodman; Mewa Kinoo, Suman; Singh, Bhugwan

2016-07-01

Ours was a retrospective chart review of all elective open inguinal hernia repairs performed in a single unit at King Edward VIII Hospital, South Africa over an 18-month period. Comparison was made regarding duration of operation, length of hospital stay and complications such as pain, haematoma formation and recurrence between the Lichtenstein and Desarda techniques. The latter was noted to have a shorter operative time and avoided cost and possible complications of mesh usage, which are significant in resource-deprived settings. A larger comparative study with longer follow-up is needed to evaluate the wider suitability of the Desarda repair. © The Author(s) 2016.

Process Approach to Determining Quality Inspection Deployment

DTIC Science & Technology

2015-06-08

27 B.1 The Deming Rule...inspection is effective. The Deming rule is explained in more detail in Appendix B. Basically the probability of error is compared to the cost of...cost or risk to repair defects escaped from inspection justify reducing inspectors. (See Appendix B for Deming rule discussion.) Three quantities must

Antigenic Variation in the Lyme Spirochete: Insights into Recombinational Switching with a Suggested Role for Error-Prone Repair.

PubMed

Verhey, Theodore B; Castellanos, Mildred; Chaconas, George

2018-05-29

The Lyme disease spirochete, Borrelia burgdorferi, uses antigenic variation as a strategy to evade the host's acquired immune response. New variants of surface-localized VlsE are generated efficiently by unidirectional recombination from 15 unexpressed vls cassettes into the vlsE locus. Using algorithms to analyze switching from vlsE sequencing data, we characterize a population of over 45,000 inferred recombination events generated during mouse infection. We present evidence for clustering of these recombination events within the population and along the vlsE gene, a role for the direct repeats flanking the variable region in vlsE, and the importance of sequence homology in determining the location of recombination, despite RecA's dispensability. Finally, we report that non-templated sequence variation is strongly associated with recombinational switching and occurs predominantly at the 5' end of conversion tracts. This likely results from an error-prone repair mechanism operational during recombinational switching that elevates the mutation rate > 5,000-fold in switched regions. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Treatment of Ulnar Collateral Ligament Tears of the Elbow: Is Repair a Viable Option?

PubMed

Erickson, Brandon J; Bach, Bernard R; Verma, Nikhil N; Bush-Joseph, Charles A; Romeo, Anthony A

2017-01-01

Ulnar collateral ligament (UCL) tears have become common, and UCL reconstruction (UCLR) is currently the preferred surgical treatment method for treating UCL tears. The purpose of this study was to review the literature surrounding UCL repair and determine the viability of new repair techniques for treatment of UCL tears. We hypothesized that UCL repair techniques will provide comparable results to UCLR for treatment of UCL tears. Systematic review and meta-analysis; Level of evidence, 4. A systematic review was registered with PROSPERO and performed with PRISMA guidelines using 3 publicly available free databases. Biomechanical and clinical outcome investigations reporting on UCL repair with levels of evidence 1 through 4 were eligible for inclusion. Descriptive statistics were calculated for each study and parameter/variable analyzed. Of the 46 studies eligible, 4 studies (3 clinical and 1 biomechanical) were included. There were 92 patients (n = 92 elbows; 61 males [62.3%]; mean age, 21.9 ± 4.7 years) included in the clinical studies, with a mean follow-up of 49 ± 14.4 months. Eighty-six percent of repairs performed were on the dominant elbow, and 38% were in college athletes. Most UCL repairs (66.3%) were performed via suture anchors. After UCL repair, 87.0% of patients were able to return to sport. Overall, 94.9% of patients scored excellent/good on the Andrews-Carson score. Patients who were able to return to sport after UCL repair did so within 6 months after surgery. Biomechanically, when UCL repair was compared with the modified Jobe technique, the repair group showed significantly less gap formation than the reconstruction group. In patients for whom repair is properly indicated, UCL repair provides similar return-to-sport rates and clinical outcomes with shorter return-to-sport timing after repair compared with UCL reconstruction. Future outcome studies evaluating UCL repair with internal bracing are necessary before recommending this technique.

Characterization of Free Phenytoin Concentrations in End-Stage Renal Disease Using the Winter-Tozer Equation.

PubMed

Soriano, Vincent V; Tesoro, Eljim P; Kane, Sean P

2017-08-01

The Winter-Tozer (WT) equation has been shown to reliably predict free phenytoin levels in healthy patients. In patients with end-stage renal disease (ESRD), phenytoin-albumin binding is altered and, thus, affects interpretation of total serum levels. Although an ESRD WT equation was historically proposed for this population, there is a lack of data evaluating its accuracy. The objective of this study was to determine the accuracy of the ESRD WT equation in predicting free serum phenytoin concentration in patients with ESRD on hemodialysis (HD). A retrospective analysis of adult patients with ESRD on HD and concurrent free and total phenytoin concentrations was conducted. Each patient's true free phenytoin concentration was compared with a calculated value using the ESRD WT equation and a revised version of the ESRD WT equation. A total of 21 patients were included for analysis. The ESRD WT equation produced a percentage error of 75% and a root mean square error of 1.76 µg/mL. Additionally, 67% of the samples had an error >50% when using the ESRD WT equation. A revised equation was found to have high predictive accuracy, with only 5% of the samples demonstrating >50% error. The ESRD WT equation was not accurate in predicting free phenytoin concentration in patients with ESRD on HD. A revised ESRD WT equation was found to be significantly more accurate. Given the small study sample, further studies are required to fully evaluate the clinical utility of the revised ESRD WT equation.

DNA Double Strand Break Response and Limited Repair Capacity in Mouse Elongated Spermatids.

PubMed

Ahmed, Emad A; Scherthan, Harry; de Rooij, Dirk G

2015-12-16

Spermatids are extremely sensitive to genotoxic exposures since during spermiogenesis only error-prone non homologous end joining (NHEJ) repair pathways are available. Hence, genomic damage may accumulate in sperm and be transmitted to the zygote. Indirect, delayed DNA fragmentation and lesions associated with apoptotic-like processes have been observed during spermatid elongation, 27 days after irradiation. The proliferating spermatogonia and early meiotic prophase cells have been suggested to retain a memory of a radiation insult leading later to this delayed fragmentation. Here, we used meiotic spread preparations to localize phosphorylate histone H2 variant (γ-H2AX) foci marking DNA double strand breaks (DSBs) in elongated spermatids. This technique enabled us to determine the background level of DSB foci in elongated spermatids of RAD54/RAD54B double knockout (dko) mice, severe combined immunodeficiency SCID mice, and poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP1) inhibitor (DPQ)-treated mice to compare them with the appropriate wild type controls. The repair kinetics data and the protein expression patterns observed indicate that the conventional NHEJ repair pathway is not available for elongated spermatids to repair the programmed and the IR-induced DSBs, reflecting the limited repair capacity of these cells. However, although elongated spermatids express the proteins of the alternative NHEJ, PARP1-inhibition had no effect on the repair kinetics after IR, suggesting that DNA damage may be passed onto sperm. Finally, our genetic mutant analysis suggests that an incomplete or defective meiotic recombinational repair of Spo11-induced DSBs may lead to a carry-over of the DSB damage or induce a delayed nuclear fragmentation during the sensitive programmed chromatin remodeling occurring in elongated spermatids.

Precision genome editing in the CRISPR era.

PubMed

Salsman, Jayme; Dellaire, Graham

2017-04-01

With the introduction of precision genome editing using CRISPR-Cas9 technology, we have entered a new era of genetic engineering and gene therapy. With RNA-guided endonucleases, such as Cas9, it is possible to engineer DNA double strand breaks (DSB) at specific genomic loci. DSB repair by the error-prone non-homologous end-joining (NHEJ) pathway can disrupt a target gene by generating insertions and deletions. Alternatively, Cas9-mediated DSBs can be repaired by homology-directed repair (HDR) using an homologous DNA repair template, thus allowing precise gene editing by incorporating genetic changes into the repair template. HDR can introduce gene sequences for protein epitope tags, delete genes, make point mutations, or alter enhancer and promoter activities. In anticipation of adapting this technology for gene therapy in human somatic cells, much focus has been placed on increasing the fidelity of CRISPR-Cas9 and increasing HDR efficiency to improve precision genome editing. In this review, we will discuss applications of CRISPR technology for gene inactivation and genome editing with a focus on approaches to enhancing CRISPR-Cas9-mediated HDR for the generation of cell and animal models, and conclude with a discussion of recent advances and challenges towards the application of this technology for gene therapy in humans.

Mutational Analysis of Mismatch Repair Genes, hMLH1 and hMSH2, in Sporadic Endometrial Carcinomas with Microsatellite Instability

PubMed Central

Kobayashi, Kanji; Matsushima, Mieko; Koi, Sumiko; Saito, Hiroko; Sagae, Satoru; Kudo, Ryuichi

1996-01-01

Microsatellite instability, monitored by replication error (RER), bas been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch‐repair system. We previously reported that nearly one‐quarter of sporadic endometrial carcinomas examined revealed an RER‐positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch‐repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch‐repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch‐repair system. PMID:8609062

An improved estimator for the hydration of fat-free mass from in vivo measurements subject to additive technical errors.

PubMed

Kinnamon, Daniel D; Lipsitz, Stuart R; Ludwig, David A; Lipshultz, Steven E; Miller, Tracie L

2010-04-01

The hydration of fat-free mass, or hydration fraction (HF), is often defined as a constant body composition parameter in a two-compartment model and then estimated from in vivo measurements. We showed that the widely used estimator for the HF parameter in this model, the mean of the ratios of measured total body water (TBW) to fat-free mass (FFM) in individual subjects, can be inaccurate in the presence of additive technical errors. We then proposed a new instrumental variables estimator that accurately estimates the HF parameter in the presence of such errors. In Monte Carlo simulations, the mean of the ratios of TBW to FFM was an inaccurate estimator of the HF parameter, and inferences based on it had actual type I error rates more than 13 times the nominal 0.05 level under certain conditions. The instrumental variables estimator was accurate and maintained an actual type I error rate close to the nominal level in all simulations. When estimating and performing inference on the HF parameter, the proposed instrumental variables estimator should yield accurate estimates and correct inferences in the presence of additive technical errors, but the mean of the ratios of TBW to FFM in individual subjects may not.

Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography

PubMed Central

Marwah, Nikhil

2016-01-01

ABSTRACT Objective: The aim of our study is to use cone beam computed tomography (CBCT) to assess the dimensional changes in the nasopharyngeal soft-tissue characteristics in children of Indian origin with repaired cleft lip and palate (CLP) and to compare the results with patients with ideal occlusion. Materials and methods: A sample of 20 children (10 girls, 10 boys) with repaired CLP was selected. Cone beam computed tomography scans were taken to measure the nasopharyngeal airway changes in terms of linear measurements and sagittal cross-sectional areas. Error analysis was performed to prevent systematic or random errors. Independent means t-tests and Pearson correlation analysis were used to evaluate sex differences and the correlations among the variables. Results: Nasopharyngeal soft-tissue characteristics were different in the control and the study groups. Subjects with repaired CLP had lesser lower aerial width, lower adenoidal width and lower airway width. The upper airway width was also significantly lesser. The retropalatal and the total airway area were significantly greater in the control group. Conclusion: The narrow pharyngeal airway in patients with CLP might result in functional impairment of breathing in patients. Further investigations are necessary to clarify the relationship between pharyngeal structure and airway function in patients with CLP. How to cite this article: Agarwal A, Marwah N. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography. Int J Clin Pediatr Dent 2016;9(1):5-9. PMID:27274147

PSO4: a novel gene involved in error-prone repair in Saccharomyces cerevisiae.

PubMed

Henriques, J A; Vicente, E J; Leandro da Silva, K V; Schenberg, A C

1989-09-01

The haploid xs9 mutant, originally selected for on the basis of a slight sensitivity to the lethal effect of X-rays, was found to be extremely sensitive to inactivation by 8-methoxypsoralen (8MOP) photoaddition, especially when cells are treated in the G2 phase of the cell cycle. As the xs9 mutation showed no allelism with any of the 3 known pso mutations, it was now given the name of pso4-1. Regarding inactivation, the pso4-1 mutant is also sensitive to mono- (HN1) or bi-functional (HN2) nitrogen mustards, it is slightly sensitive to 254 nm UV radiation (UV), and shows nearly normal sensitivity to 3-carbethoxypsoralen (3-CPs) photoaddition or methyl methanesulfonate (MMS). Regarding mutagenesis, the pso4-1 mutation completely blocks reverse and forward mutations induced by either 8MOP or 3CPs photoaddition, or by gamma-rays. In the cases of UV, HN1, HN2 or MMS treatments, while reversion induction is still completely abolished, forward mutagenesis is only partially inhibited for UV, HN1, or MMS, and it is unaffected for HN2. Besides severely inhibiting induced mutagenesis, the pso4-1 mutation was found to be semi-dominant, to block sporulation, to abolish the diploid resistance effect, and to block induced mitotic recombination, which indicates that the PSO4 gene is involved in a recombinational pathway of error-prone repair, comparable to the E. coli SOS repair pathway.

Adjusting for radiotelemetry error to improve estimates of habitat use.

Treesearch

Scott L. Findholt; Bruce K. Johnson; Lyman L. McDonald; John W. Kern; Alan Ager; Rosemary J. Stussy; Larry D. Bryant

2002-01-01

Animal locations estimated from radiotelemetry have traditionally been treated as error-free when analyzed in relation to habitat variables. Location error lowers the power of statistical tests of habitat selection. We describe a method that incorporates the error surrounding point estimates into measures of environmental variables determined from a geographic...

Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23.

PubMed Central

Masutani, C; Sugasawa, K; Yanagisawa, J; Sonoyama, T; Ui, M; Enomoto, T; Takio, K; Tanaka, K; van der Spek, P J; Bootsma, D

1994-01-01

Complementation group C of xeroderma pigmentosum (XP) represents one of the most common forms of this cancer-prone DNA repair syndrome. The primary defect is located in the subpathway of the nucleotide excision repair system, dealing with the removal of lesions from the non-transcribing sequences ('genome-overall' repair). Here we report the purification to homogeneity and subsequent cDNA cloning of a repair complex by in vitro complementation of the XP-C defect in a cell-free repair system containing UV-damaged SV40 minichromosomes. The complex has a high affinity for ssDNA and consists of two tightly associated proteins of 125 and 58 kDa. The 125 kDa subunit is an N-terminally extended version of previously reported XPCC gene product which is thought to represent the human homologue of the Saccharomyces cerevisiae repair gene RAD4. The 58 kDa species turned out to be a human homologue of yeast RAD23. Unexpectedly, a second human counterpart of RAD23 was identified. All RAD23 derivatives share a ubiquitin-like N-terminus. The nature of the XP-C defect implies that the complex exerts a unique function in the genome-overall repair pathway which is important for prevention of skin cancer. Images PMID:8168482

Lead exposure in radiator repair workers: a survey of Washington State radiator repair shops and review of occupational lead exposure registry data.

PubMed

Whittaker, Stephen G

2003-07-01

Radiator repair workers in Washington State have the greatest number of very elevated (> or =60 microg/dL) blood lead levels of any other worker population. The goals of this study were to determine the number of radiator repair workers potentially exposed to lead; estimate the extent of blood lead data underreporting to the Occupational Lead Exposure Registry; describe current safety and health practices in radiator repair shops; and determine appropriate intervention strategies to reduce exposure and increase employer and worker awareness. Lead exposure in Washington State's radiator repair workers was assessed by reviewing Registry data and conducting a statewide survey of radiator repair businesses. This study revealed that a total of 226 workers in Washington State (including owner-operators and all employees) conduct repair activities that could potentially result in excessive exposures to lead. Approximately 26% of radiator repair workers with elevated blood lead levels (> or =25 microg/dL) were determined to report to Washington State's Registry. This study also revealed a lack of awareness of lead's health effects, appropriate industrial hygiene controls, and the requirements of the Lead Standard. Survey respondents requested information on a variety of workplace health and safety issues and waste management; 80% requested a confidential, free-of-charge consultation. Combining data derived from an occupational health surveillance system and a statewide mail survey proved effective at characterizing lead exposures and directing public health intervention in Washington State.

Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways to Breaking Free.

PubMed

Lyman, Stephen; Nakamura, Norimasa; Cole, Brian J; Erggelet, Christoph; Gomoll, Andreas H; Farr, Jack

2016-08-03

Articular cartilage defects strongly predispose patients to developing early joint degeneration and osteoarthritis, but for more than 15 years, no new cartilage-repair technologies that we know of have been approved by the U.S. Food and Drug Administration. Many studies examining novel approaches to cartilage repair, including cell, tissue, or matrix-based techniques, have shown great promise, but completing randomized controlled trials (RCTs) to establish safety and efficacy has been challenging, providing a major barrier to bringing these innovations into clinical use. In this article, we review reasons that surgical innovations are not well-suited for testing through RCTs. We also discuss how analytical methods for reducing bias, such as propensity scoring, make prospective observational studies a potentially viable alternative for testing the safety and efficacy of cartilage-repair and other novel therapies, offering the real possibility of therapeutic innovation. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Method for characterizing mask defects using image reconstruction from X-ray diffraction patterns

DOEpatents

Hau-Riege, Stefan Peter [Fremont, CA

2007-05-01

The invention applies techniques for image reconstruction from X-ray diffraction patterns on the three-dimensional imaging of defects in EUVL multilayer films. The reconstructed image gives information about the out-of-plane position and the diffraction strength of the defect. The positional information can be used to select the correct defect repair technique. This invention enables the fabrication of defect-free (since repaired) X-ray Mo--Si multilayer mirrors. Repairing Mo--Si multilayer-film defects on mask blanks is a key for the commercial success of EUVL. It is known that particles are added to the Mo--Si multilayer film during the fabrication process. There is a large effort to reduce this contamination, but results are not sufficient, and defects continue to be a major mask yield limiter. All suggested repair strategies need to know the out-of-plane position of the defects in the multilayer.

Construction and characterization of mismatch-containing circular DNA molecules competent for assessment of nick-directed human mismatch repair in vitro.

PubMed

Larson, Erik D; Nickens, David; Drummond, James T

2002-02-01

The ability of cell-free extracts to correct DNA mismatches has been demonstrated in both prokaryotes and eukaryotes. Such an assay requires a template containing both a mismatch and a strand discrimination signal, and the multi-step construction process can be technically difficult. We have developed a three-step procedure for preparing DNA heteroduplexes containing a site-specific nick. The mismatch composition, sequence context, distance to the strand signal, and the means for assessing repair in each strand are adjustable features built into a synthetic oligonucleotide. Controlled ligation events involving three of the four DNA strands incorporate the oligonucleotide into a circular template and generate the repair-directing nick. Mismatch correction in either strand of a prototype G.T mismatch was achieved by placing a nick 10-40 bp away from the targeted base. This proximity of nick and mismatch represents a setting where repair has not been well characterized, but the presence of a nick was shown to be essential, as was the MSH2/MSH6 heterodimer, although low levels of repair occurred in extract defective in each protein. All repair events were inhibited by a peptide that interacts with proliferating cell nuclear antigen and inhibits both mismatch repair and long-patch replication.

Liver repair and hemorrhage control using laser soldering of liquid albumin in a porcine model

NASA Astrophysics Data System (ADS)

Wadia, Yasmin; Xie, Hua; Kajitani, Michio; Gregory, Kenton W.; Prahl, Scott A.

2000-05-01

The purpose of this study was to evaluate laser soldering using liquid albumin for welding liver lacerations and sealing raw surfaces created by segmental resection of a lobe. Major liver trauma has a high mortality due to immediate exsanguination and a delayed morbidity and mortality from septicemia, peritonitis, biliary fistulae and delayed secondary hemorrhage. Eight laceration injuries (6 cm long X 2 cm deep) and eight non-anatomical resection injuries (raw surface 6 cm X 2 cm) were repaired. An 805 nm laser was used to weld 53% liquid albumin-ICG solder to the liver surface, reinforcing it with a free autologous omental scaffold. The animals were heparinized to simulate coagulation failure and hepatic inflow occlusion was used for vascular control. For both laceration and resection injuries, eight soldering repairs each were evaluated at three hours. A single suture repair of each type was evaluated at three hours. All 16 laser mediated liver repairs were accompanied by minimal blood loss as compared to the suture controls. No dehiscence, hemorrhage or bile leakage was seen in any of the laser repairs after three hours. In conclusion laser fusion repair of the liver is a quick and reliable technique to gain hemostasis on the cut surface as well as weld lacerations.

Flow-Through Free Fibula Osteocutaneous Flap in Reconstruction of Tibial Bone, Soft Tissue, and Main Artery Segmental Defects.

PubMed

Li, Zonghuan; Yu, Aixi; Qi, Baiwen; Pan, Zhenyu; Ding, Junhui

2017-08-01

The aim of this report was to present the use of flow-through free fibula osteocutaneous flap for the repair of complex tibial bone, soft tissue, and main artery segmental defects. Five patients with bone, soft tissue, and segmental anterior tibial artery defects were included. The lengths of injured tibial bones ranged from 4 to 7 cm. The sizes of impaired soft tissues were between 9 × 4 and 15 × 6 cm. The lengths of defect of anterior tibial artery segments ranged from 6 to 10 cm. Two patients had distal limb perfusion problems. Flow-through free fibula osteocutaneous flap was performed for all 5 patients. Patients were followed for 12 to 18 months. All wounds healed after 1-stage operation, and all flow-through flaps survived. The distal perfusion after vascular repair was normal in all patients. Superficial necrosis of flap edge was noted in 1 case. After the local debridement and partial thickness skin graft, the flap healed uneventfully, and the surgical operation did not increase injury to the donor site. Satisfactory bone union was achieved in all patients in 2 to 4 months postoperation. Enlargement of fibula graft was observed during follow-up from 12 to 18 months. The functions of adjacent joints were recovered, and all patients were able to walk normally. Flow-through free fibula osteocutaneous flap was shown to be an effective and efficient technique for repairing composite tibial bone, soft tissue, and main artery segmental defects. This 1-stage operation should be useful in clinical practice for the treatment of complex bone, soft tissue, and vessel defects.

Postoperative stiff shoulder after open rotator cuff repair: a 3- to 20-year follow-up study.

PubMed

Vastamäki, H; Vastamäki, M

2014-12-01

Stiffness after a rotator cuff tear is common. So is stiffness after an arthroscopic rotator cuff repair. In the literature, however, postoperative restriction of passive range of motion after open rotator cuff repair in shoulders with free passive range of motion at surgery has seldom been recognized. We hypothesize that this postoperative stiffness is more frequent than recognized and slows the primary postoperative healing after a rotator cuff reconstruction. We wondered how common is postoperative restriction of both active and passive range of motion after open rotator cuff repair in shoulders with free passive preoperative range of motion, how it recovers, and whether this condition influences short- and long-term results of surgery. We also explored factors predicting postoperative shoulder stiffness. We retrospectively identified 103 postoperative stiff shoulders among 416 consecutive open rotator cuff repairs, evaluating incidence and duration of stiffness, short-term clinical results and long-term range of motion, pain relief, shoulder strength, and functional results 3-20 (mean 8.7) years after surgery in 56 patients. The incidence of postoperative shoulder stiffness was 20%. It delayed primary postoperative healing by 3-6 months and resolved during a mean 6.3 months postoperatively. External rotation resolved first, corresponding to that of the controls at 3 months; flexion and abduction took less than 1 year after surgery. The mean summarized range of motion (flexion + abduction + external rotation) increased as high as 93% of the controls' range of motion by 6 months and 100% by 1 year. Flexion, abduction, and internal rotation improved to the level of the contralateral shoulders as did pain, strength, and function. Age at surgery and condition of the biceps tendon were related to postoperative stiffness. Postoperative stiff shoulder after open rotator cuff repair is a common complication resolving in 6-12 months with good long-term results. © The Finnish Surgical Society 2013.

19 CFR 181.44 - Calculation of drawback.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Restrictions on Drawback and Duty-Deferral... is repaired in the United States using imported parts from Korea on which $160.00 in duties have been...

Laparoscopic totally extraperitoneal inguinal hernia repair: lessons learned from 3,100 hernia repairs over 15 years.

PubMed

Dulucq, Jean-Louis; Wintringer, Pascal; Mahajna, Ahmad

2009-03-01

Two revolutions in inguinal hernia repair surgery have occurred during the last two decades. The first was the introduction of tension-free hernia repair by Liechtenstein in 1989 and the second was the application of laparoscopic surgery to the treatment of inguinal hernia in the early 1990s. The purposes of this study were to assess the safety and effectiveness of laparoscopic totally extraperitoneal (TEP) repair and to discuss the technical changes that we faced on the basis of our accumulative experience. Patients who underwent an elective inguinal hernia repair at the Department of Abdominal Surgery at the Institute of Laparoscopic Surgery (ILS), Bordeaux, between June 1990 and May 2005 were enrolled retrospectively in this study. Patient demographic data, operative and postoperative course, and outpatient follow-up were studied. A total of 3,100 hernia repairs were included in the study. The majority of the hernias were repaired by TEP technique; the repair was done by transabdominal preperitoneal (TAPP) repair in only 3%. Eleven percent of the hernias were recurrences after conventional repair. Mean operative time was 17 min in unilateral hernia and 24 min in bilateral hernia. There were 36 hernias (1.2%) that required conversion: 12 hernias were converted to open anterior Liechtenstein and 24 to laparoscopic TAPP technique. The incidence of intraoperative complications was low. Most of the patients were discharged at the second day of the surgery. The overall postoperative morbidity rate was 2.2%. The incidence of recurrence rate was 0.35%. The recurrence rate for the first 200 repairs was 2.5%, but it decreased to 0.47% for the subsequent 1,254 hernia repairs According to our experience, in the hands of experienced laparoscopic surgeons, laparoscopic hernia repair seems to be the favored approach for most types of inguinal hernias. TEP is preferred over TAPP as the peritoneum is not violated and there are fewer intra-abdominal complications.

Fixation free femoral hernia repair with a 3D dynamic responsive implant. A case series report.

PubMed

Amato, G; Romano, G; Agrusa, A; Gordini, L; Gulotta, E; Erdas, E; Calò, P G

2018-04-23

To date, no gold standard for the surgical treatment of femoral hernia exists. Pure tissue repair as well as mesh/plug implantation, open or laparoscopic, are the most performed methods. Nevertheless, all these techniques need sutures or mesh fixation. This implies the risk of damaging sensitive structures of the femoral area, along with complications related to tissue tear and postoperative discomfort consequent to poor quality mesh incorporation. The present retrospective multicenter case series highlights the results of femoral hernia repair procedures performed with a 3D dynamic responsive implant in a cohort of 32 patients during a mean follow up of 27 months. Aiming to simplify the surgical procedure and reduce complications, a 3D dynamic responsive implant was delivered for femoral hernia repair, in a patient cohort. After returning the hernia sack to the abdominal cavity, the implant was simply delivered into the hernia defect where it remained, thanks to its inherent centrifugal expansion, obliterating the hernia opening without need of fixation. Postoperative pain assessment was determined using the VAS score system. The use of the 3D prosthetic device allowed for easier and faster surgical repair in a fixation free fashion. None of the typical fixation related complications occurred in the examined patients. Postoperative pain assessment with VAS score showed a very low level of pain, allowing the return of patients to normal activities in extremely reduced times. In the late postoperative period, no discomfort or chronic pain was reported. Femoral hernia repair with the 3D dynamic revealed a quick and safe placement procedure. The reduced pain intensity, as well as the absence of adverse events consequent to sutures or mesh fixation, seems to be a significant benefit of the motile compliance of the device. Furthermore, this 3D prosthesis has already proven to induce an enhanced probiotic response showing ingrowth in the implant of the typical tissue components of the abdominal wall, instead of the low quality tissue ingrowth typical in conventional meshes and plugs. The highlighted features seem to represent a more physiologic and updated repair concept of femoral protrusions. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Hybrid endovascular repair for aortic arch pathology: intermediate outcomes and complications: a retrospective analysis.

PubMed

Kang, Woong Chol; Shin, Eak Kyun; Park, Chul-Hyun; Kang, Jin Mo; Ko, Young-Guk; Choi, Donghoon; Youn, Young Nam; Shim, Won-Heum

2013-08-01

To evaluate the outcomes of hybrid endovascular repair for aortic arch pathology. This study was a retrospective analysis involving patients who underwent hybrid endovascular repair for aortic arch pathologies. Twenty-one patients (16 men; mean age, 64.7 ± 16.2 years) with aortic arch pathologies were treated by hybrid endovascular repair. The indications for treatment included increased aneurysm size in 16 cases (71.4%), rupture or impending aneurysmal rupture in 5 cases (23.8%), and rapid growth of aortic dissection (≥ 10 mm/y) in 1 case (4.8%). Supra-aortic vessel transposition and stent-graft implantation were achieved in all cases. Two types of stent-graft was used, as follows: the Seal thoracic stent-graft in 14 patients (66.7%); and the Valiant stent grafts in 7 patients (33.3%). Perioperative complications affected 5 patients (23.8%), as follows: bleeding (n = 4, 19.0%); stroke (n = 3, 14.3%); renal failure (n = 2, 9.5%); vascular injury (n = 1, 4.8%), and respiratory failure (n = 1, 4.8%). Two patients died within 30 days (9.5%). Technical success was achieved in 15 patients (71.5%). Early endoleaks were noted in 4 patients (19.0%). One patient died during follow-up (mean, 21.3 ± 11.6 months) due to a de novo intramural hematoma. Persistent early endoleaks were noted in 4 patients (19.0%); 2 of the 4 patients were successfully managed with implantation of additional stent-grafts. No late onset endoleaks were noted. The death-free survival and reintervention-free survival rates during follow-up were 85.7% and 90.5%, respectively. Hybrid treatment with supra-aortic vessel transposition and endovascular repair may be an option in frail patients in who open procedures is too risky. © 2013 Wiley Periodicals, Inc.

Medical Error Avoidance in Intraoperative Neurophysiological Monitoring: The Communication Imperative.

PubMed

Skinner, Stan; Holdefer, Robert; McAuliffe, John J; Sala, Francesco

2017-11-01

Error avoidance in medicine follows similar rules that apply within the design and operation of other complex systems. The error-reduction concepts that best fit the conduct of testing during intraoperative neuromonitoring are forgiving design (reversibility of signal loss to avoid/prevent injury) and system redundancy (reduction of false reports by the multiplication of the error rate of tests independently assessing the same structure). However, error reduction in intraoperative neuromonitoring is complicated by the dichotomous roles (and biases) of the neurophysiologist (test recording and interpretation) and surgeon (intervention). This "interventional cascade" can be given as follows: test → interpretation → communication → intervention → outcome. Observational and controlled trials within operating rooms demonstrate that optimized communication, collaboration, and situational awareness result in fewer errors. Well-functioning operating room collaboration depends on familiarity and trust among colleagues. Checklists represent one method to initially enhance communication and avoid obvious errors. All intraoperative neuromonitoring supervisors should strive to use sufficient means to secure situational awareness and trusted communication/collaboration. Face-to-face audiovisual teleconnections may help repair deficiencies when a particular practice model disallows personal operating room availability. All supervising intraoperative neurophysiologists need to reject an insular or deferential or distant mindset.

Stop Stalling: Mus81 Required for Efficient Replication | Center for Cancer Research

Cancer.gov

DNA replication is precisely controlled to ensure that daughter cells receive intact, accurate genetic information. Each segment of DNA must be copied only once, and the rate of replication coordinated genome-wide. Mild replication stress slows DNA synthesis and activates a pathway involving the Mus81 endonuclease, which generates a series of DNA breaks that are rapidly repaired, allowing the cell to avoid activating the S-phase checkpoint and its potentially damaging outcomes of apoptosis or error-prone repair. Mirit Aladjem, Ph.D., of CCR’s Developmental Therapeutics Branch, and her colleagues wondered whether Mus81 also plays a role in regulating the replication rate during growth in the absence of stress.

Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining.

PubMed

Moscariello, Mario; Wieloch, Radi; Kurosawa, Aya; Li, Fanghua; Adachi, Noritaka; Mladenov, Emil; Iliakis, George

2015-07-01

Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA double-strand breaks that are processed either by homologous recombination repair (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ). Chemical or genetic inactivation of factors involved in C-NHEJ or HRR, but also their local failure in repair proficient cells, promotes an alternative, error-prone end-joining pathway that serves as backup (A-EJ). There is evidence for the involvement of Artemis endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR or C-NHEJ Artemis processes DNA termini at complex DSBs. Whether Artemis has a role in A-EJ remains unknown. Here, we analyze using pulsed-field gel electrophoresis (PFGE) and specialized reporter assays, DSB repair in wild-type pre-B NALM-6 lymphocytes, as well as in their Artemis(-/-), DNA ligase 4(-/-) (LIG4(-/-)), and LIG4(-/-)/Artemis(-/-) double mutant counterparts, under conditions allowing evaluation of A-EJ. Our results substantiate the suggested roles of Artemis in C-NHEJ and HRR, but also demonstrate a role for the protein in A-EJ that is confirmed in Artemis deficient normal human fibroblasts. We conclude that Artemis is a nuclease participating in DSB repair by all major repair pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

Genotoxicity of diphenyl diselenide in bacteria and yeast.

PubMed

Rosa, Renato Moreira; Sulzbacher, Krisley; Picada, Jaqueline Nascimento; Roesler, Rafael; Saffi, Jenifer; Brendel, Martin; Henriques, João Antonio Pêgas

2004-10-10

Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. This may increase the risk of human exposure to the chemical at the workplace. We have determined its mutagenic potential in the Salmonella/microsome assay and used the yeast Saccharomyces cerevisiae to assay for putative genotoxicity, recombinogenicity and to determine whether DNA damage produced by DPDS is repairable. Only in exponentially growing cultures was DPDS able to induce frameshift mutations in S. typhimurium and haploid yeast and to increase crossing over and gene conversion frequencies in diploid strains of S. cerevisiae. Thus, DPDS presents a behavior similar to that of an intercalating agent. Mutants defective in excision-resynthesis repair (rad3, rad1), in error-prone repair (rad6) and in recombinational repair (rad52) showed higher than WT-sensitivity to DPDS. It appears that this compound is capable of inducing single and/or double strand breaks in DNA. An epistatic interaction was shown between rad3-e5 and rad52-1 mutant alleles, indicating that excision-resynthesis and strand-break repair may possess common steps in the repair of DNA damage induced by DPDS. DPDS was able to enhance the mutagenesis induced by oxidative mutagens in bacteria. N-acetylcysteine, a glutathione biosynthesis precursor, prevented mutagenesis induced by DPDS in yeast. We have shown that DPDS is a weak mutagen which probably generates DNA strand breaks through both its intercalating action and pro-oxidant effect.

Using an Integrative Approach To Teach Hebrew Grammar in an Elementary Immersion Class.

ERIC Educational Resources Information Center

Eckstein, Peter

The 12-week program described here was designed to improve a Hebrew language immersion class' ability to correctly use the simple past and present tenses. The target group was a sixth-grade class that achieved a 65.68 percent error-free rate on a pre-test; the project's objective was to achieve 90 percent error free tests, using student…

Repair of a mandibular defect with a free vascularized coccygeal vertebra transfer in a dog.

PubMed

Yeh, L S; Hou, S M

1994-01-01

Bilateral mandibular defects in a male mongrel dog were repaired. On the left side, a free vascularized coccygeal bone graft that included the median caudal artery and caudal vein was used to correct the defect. On the right side, the defect was bridged with a bone plate and screws. For further immobilization, the muzzle was temporarily taped for 3 weeks and a pharyngostomy tube was used for nutritional support. The dog was able to eat dry commercial food satisfactorily within 2 months of surgery despite mild malocclusion. Radiographs taken 2 months and 18 months postoperatively showed bony union with graft hypertrophy in the left mandible, whereas the right mandibular defect showed protracted nonunion. The results indicate that vascularized coccygeal vertebra transfer provides an alternative for the management of canine mandibular defects.

Follow-Up of the Novel Free Margin Running Suture Technique for Mitral Valve Repair.

PubMed

Agnino, Alfonso; Lanzone, Alberto Maria; Albertini, Andrea; Anselmi, Amedeo

2018-06-13

The free margin running suture (FMRS) is a novel technique for nonresection correction of degenerative mitral regurgitation. It was employed in 37 minimally invasive mitral repair cases. We performed a retrospective collection of in-hospital data and a clinical/echocardiographic follow-up. All patients were discharged with none or mild mitral regurgitation, except one who had mild-to-moderate (2+) regurgitation. At follow-up (average: 2.1 years), all patients were alive; there were no instances of recurrent regurgitation, one case of 2+ regurgitation, and no valve-related complications. Average mitral valve area, mean gradient, and coaptation length were 2.9 cm 2  ±0.1, 3.5 mm Hg ±0.9, and 1.1 cm ±0.2. Georg Thieme Verlag KG Stuttgart · New York.

Simple, accurate formula for the average bit error probability of multiple-input multiple-output free-space optical links over negative exponential turbulence channels.

PubMed

Peppas, Kostas P; Lazarakis, Fotis; Alexandridis, Antonis; Dangakis, Kostas

2012-08-01

In this Letter we investigate the error performance of multiple-input multiple-output free-space optical communication systems employing intensity modulation/direct detection and operating over strong atmospheric turbulence channels. Atmospheric-induced strong turbulence fading is modeled using the negative exponential distribution. For the considered system, an approximate yet accurate analytical expression for the average bit error probability is derived and an efficient method for its numerical evaluation is proposed. Numerically evaluated and computer simulation results are further provided to demonstrate the validity of the proposed mathematical analysis.

Approaching Error-Free Customer Satisfaction through Process Change and Feedback Systems

ERIC Educational Resources Information Center

Berglund, Kristin M.; Ludwig, Timothy D.

2009-01-01

Employee-based errors result in quality defects that can often impact customer satisfaction. This study examined the effects of a process change and feedback system intervention on error rates of 3 teams of retail furniture distribution warehouse workers. Archival records of error codes were analyzed and aggregated as the measure of quality. The…

A constrained-gradient method to control divergence errors in numerical MHD

NASA Astrophysics Data System (ADS)

Hopkins, Philip F.

2016-10-01

In numerical magnetohydrodynamics (MHD), a major challenge is maintaining nabla \\cdot {B}=0. Constrained transport (CT) schemes achieve this but have been restricted to specific methods. For more general (meshless, moving-mesh, ALE) methods, `divergence-cleaning' schemes reduce the nabla \\cdot {B} errors; however they can still be significant and can lead to systematic errors which converge away slowly. We propose a new constrained gradient (CG) scheme which augments these with a projection step, and can be applied to any numerical scheme with a reconstruction. This iteratively approximates the least-squares minimizing, globally divergence-free reconstruction of the fluid. Unlike `locally divergence free' methods, this actually minimizes the numerically unstable nabla \\cdot {B} terms, without affecting the convergence order of the method. We implement this in the mesh-free code GIZMO and compare various test problems. Compared to cleaning schemes, our CG method reduces the maximum nabla \\cdot {B} errors by ˜1-3 orders of magnitude (˜2-5 dex below typical errors if no nabla \\cdot {B} cleaning is used). By preventing large nabla \\cdot {B} at discontinuities, this eliminates systematic errors at jumps. Our CG results are comparable to CT methods; for practical purposes, the nabla \\cdot {B} errors are eliminated. The cost is modest, ˜30 per cent of the hydro algorithm, and the CG correction can be implemented in a range of numerical MHD methods. While for many problems, we find Dedner-type cleaning schemes are sufficient for good results, we identify a range of problems where using only Powell or `8-wave' cleaning can produce order-of-magnitude errors.

Minimising Same Error Repetition and Maximising Progress in SLA: An Integrated Method

ERIC Educational Resources Information Center

Gadd, Anna

2016-01-01

Alderson teaches us that, "progress should be the aim of all learning". With the purpose of ensuring progress and enhancing first year students' learning of Italian as a second language, research into feedback and repair was undertaken at The University of Western Australia. The research--funded by the UWA Centre for the Advancement of…

Perception of Place of Articulation by Children with Cleft Palate and Posterior Placement.

ERIC Educational Resources Information Center

Whitehill, Tara L.; Francis, Alexander L.; Ching, Christine K-Y.

2003-01-01

A study examined if 10 children (ages 4-12) with repaired cleft palate who demonstrate posterior placement of alveolar targets differed from 10 children with cleft palate without such error patterns, and from 10 controls in the perception of alveolar targets. Children with posterior placement appeared unable to distinguish alveolar targets.…

The Weekly Fab Five: Things You Should Do Every Week To Keep Your Computer Running in Tip-Top Shape.

ERIC Educational Resources Information Center

Crispen, Patrick

2001-01-01

Describes five steps that school librarians should follow every week to keep their computers running at top efficiency. Explains how to update virus definitions; run Windows update; run ScanDisk to repair errors on the hard drive; run a disk defragmenter; and backup all data. (LRW)

A Recovery-Oriented Approach to Dependable Services: Repairing Past Errors with System-Wide Undo

DTIC Science & Technology

2003-12-01

54 4.5.3 Handling propagating paradoxes: the squash interface . . . . . . . . . . . . . . . . . . . 54 4.6 Discussion...84 6.3.3 Compensating for paradoxes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 6.3.4 Squashing propagating...the service and comparing the behavior of the replicas to detect and squash misbehaving replicas. While on paper Byzantine fault tolerance may seem to

The Occurrence and the Success Rate of Self-Initiated Self-Repair

ERIC Educational Resources Information Center

Sato, Rintaro; Takatsuka, Shigenobu

2016-01-01

Errors naturally appear in spontaneous speeches and conversations. Particularly in a second or foreign language, it is only natural that mistakes happen as a part of the learning process. After an inappropriate expression is detected, it can be corrected. This act of correcting can be initiated either by the speaker (non-native speaker) or the…

Genetics Home Reference: Lynch syndrome

MedlinePlus

... or EPCAM gene increase the risk of developing Lynch syndrome . The MLH1 , MSH2 , MSH6 , and PMS2 genes are involved in the repair of errors that ... B, Eisinger F, Hutter P, Olschwang S. Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) - update 2012. Eur J Hum Genet. 2013 ...

Development of dopant-free conductive bioelastomers

PubMed Central

Xu, Cancan; Huang, Yihui; Yepez, Gerardo; Wei, Zi; Liu, Fuqiang; Bugarin, Alejandro; Tang, Liping; Hong, Yi

2016-01-01

Conductive biodegradable materials are of great interest for various biomedical applications, such as tissue repair and bioelectronics. They generally consist of multiple components, including biodegradable polymer/non-degradable conductive polymer/dopant, biodegradable conductive polymer/dopant or biodegradable polymer/non-degradable inorganic additives. The dopants or additives induce material instability that can be complex and possibly toxic. Material softness and elasticity are also highly expected for soft tissue repair and soft electronics. To address these concerns, we designed a unicomponent dopant-free conductive polyurethane elastomer (DCPU) by chemically linking biodegradable segments, conductive segments, and dopant molecules into one polymer chain. The DCPU films which had robust mechanical properties with high elasticity and conductivity can be degraded enzymatically and by hydrolysis. It exhibited great electrical stability in physiological environment with charge. Mouse 3T3 fibroblasts survived and proliferated on these films exhibiting good cytocompatibility. Polymer degradation products were non-toxic. DCPU could also be processed into a porous scaffold and in an in vivo subcutaneous implantation model, exhibited good tissue compatibility with extensive cell infiltration over 2 weeks. Such biodegradable DCPU with good flexibility and elasticity, processability, and electrical stability may find broad applications for tissue repair and soft/stretchable/wearable bioelectronics. PMID:27686216

Can renal dysfunction after infra-renal aortic aneurysm repair be modified by multi-antioxidant supplementation?

PubMed

Wijnen, M H W A; Vader, H L; Van Den Wall Bake, A W L; Roumen, R M H

2002-08-01

Renal failure after lower torso ischemia is a serious problem, partly caused by hypotension and indirect reperfusion injury. This injury is partly due to the formation of oxygen free radicals by activated neutrophils. This injury results in albuminuria and renal function impairment. There are indications that free radical damage in indirect reperfusion injury can be diminished by administering extra antioxidants before and during reperfusion. In this prospective randomised study we have looked at the influence of a multi-antioxidant supplementation on renal function in patients undergoing an elective open infrarenal abdominal aneurysm repair. The patients received either standard treatment (n=22) or standard treatment with additional antioxidants perioperatively (Allopurinol, vitamin E and C, N-acetylcysteine and mannitol). For renal function we have looked at the albumin/creatinine ratio in urine and 24 hr creatinine clearance. Despite significantly increased serum total antioxidant capacity, the group receiving extra antioxidants showed no decrease in the albumin/creatinine ratio in urine. There was however a significantly higher creatinine clearance in this group at day 2. The results indicate that the diminished renal function after infrarenal aneurysm repair may be influenced by antioxidant therapy.

How to deal with multiple binding poses in alchemical relative protein-ligand binding free energy calculations.

PubMed

Kaus, Joseph W; Harder, Edward; Lin, Teng; Abel, Robert; McCammon, J Andrew; Wang, Lingle

2015-06-09

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the ligands. This improved the root-mean-square error (RMSE) for the predicted binding free energy from 1.9 kcal/mol with the original partial charges to 1.3 kcal/mol with the corrected partial charges.

How To Deal with Multiple Binding Poses in Alchemical Relative Protein–Ligand Binding Free Energy Calculations

PubMed Central

2016-01-01

Recent advances in improved force fields and sampling methods have made it possible for the accurate calculation of protein–ligand binding free energies. Alchemical free energy perturbation (FEP) using an explicit solvent model is one of the most rigorous methods to calculate relative binding free energies. However, for cases where there are high energy barriers separating the relevant conformations that are important for ligand binding, the calculated free energy may depend on the initial conformation used in the simulation due to the lack of complete sampling of all the important regions in phase space. This is particularly true for ligands with multiple possible binding modes separated by high energy barriers, making it difficult to sample all relevant binding modes even with modern enhanced sampling methods. In this paper, we apply a previously developed method that provides a corrected binding free energy for ligands with multiple binding modes by combining the free energy results from multiple alchemical FEP calculations starting from all enumerated poses, and the results are compared with Glide docking and MM-GBSA calculations. From these calculations, the dominant ligand binding mode can also be predicted. We apply this method to a series of ligands that bind to c-Jun N-terminal kinase-1 (JNK1) and obtain improved free energy results. The dominant ligand binding modes predicted by this method agree with the available crystallography, while both Glide docking and MM-GBSA calculations incorrectly predict the binding modes for some ligands. The method also helps separate the force field error from the ligand sampling error, such that deviations in the predicted binding free energy from the experimental values likely indicate possible inaccuracies in the force field. An error in the force field for a subset of the ligands studied was identified using this method, and improved free energy results were obtained by correcting the partial charges assigned to the ligands. This improved the root-mean-square error (RMSE) for the predicted binding free energy from 1.9 kcal/mol with the original partial charges to 1.3 kcal/mol with the corrected partial charges. PMID:26085821

Endovascular Repair of a Ruptured Mycotic Aneurysm of the Common Iliac Artery

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

Mofidi, R., E-mail: rmofidi@doctors.net.uk; Bhat, R.; Nagy, J.

2007-09-15

This report describes the case of a ruptured mycotic aneurysm of the left common iliac artery, successfully treated with endovascular stent-grafting. A 64-year-old woman underwent diagnostic coronary angiography complicated by an infected hematoma of the left groin. Seven days later, she developed methicillin-resistant Staphylococcus aureus septicemia and CT scan evidence of perivascular inflammation around the left common iliac artery. This was followed by rupture of a mycotic aneurysm of the left common iliac artery. The lesion was successfully treated with a stent-graft and prolonged antibiotic therapy, and the patient remains free of infection 10 months later. Accumulating evidence suggests thatmore » endovascular repair can be used safely for the repair of ruptured infected aneurysms.« less

Durability of Aortic Valve Cusp Repair With and Without Annular Support.

PubMed

Zeeshan, Ahmad; Idrees, Jay J; Johnston, Douglas R; Rajeswaran, Jeevanantham; Roselli, Eric E; Soltesz, Edward G; Gillinov, A Marc; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Pettersson, Gösta B; Blackstone, Eugene H; Sabik, Joseph F; Svensson, Lars G

2018-03-01

To determine the value of aortic valve repair rather than replacement for valve dysfunction, we assessed late outcomes of various repair techniques in the contemporary era. From January 2001 to January 2011, aortic valve repair was planned in 1,124 patients. Techniques involved commissural figure-of-8 suspension sutures (n = 63 [6.2%]), cusp repair with commissuroplasty (n = 481 [48%]), debridement (n = 174 [17%]), free-margin plication (n = 271 [27%]) or resection (n = 75) or both, or annulus repair with resuspension (n = 230 [23%]), root reimplantation (n = 252 [25%]), or remodeling (n = 35 [3.5%]). Planned repair was aborted for replacement in 115 patients (10%); risk factors included greater severity of aortic regurgitation (AR; p = 0.0002) and valve calcification (p < 0.0001). In-hospital outcomes for the remaining 1,009 patients included death (12 [1.2%]), stroke (13 [1.3%]), and reoperation for valve dysfunction (14 [1.4%]). Freedom from aortic valve reoperation at 1, 5, and 10 years was 97%, 93%, and 90%, respectively. Figure-of-8 suspension sutures, valve resuspension, and root repair and replacement were least likely to require reoperation; cusp repair with commissural sutures, plication, and commissuroplasty was most likely (p < 0.05). Survival at 1, 5, and 10 years was 96%, 92%, and 83%. Immediate postoperative AR grade was none-mild (94%), moderate (5%), and severe (1%). At 10 years after repair, AR grade was none (20%), mild (33%), moderate (26%), and severe (21%). Patients undergoing root procedures were less likely to have higher-grade postoperative AR (p < 0.0001). Valve repair is effective and durable for treating aortic valve dysfunction. Greater severity of AR preoperatively is associated with higher likelihood of repair failure. Commissural figure-of-8 suspension sutures and repair with annular support have the best long-term durability. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Radiative flux and forcing parameterization error in aerosol-free clear skies

DOE PAGES

Pincus, Robert; Mlawer, Eli J.; Oreopoulos, Lazaros; ...

2015-07-03

This article reports on the accuracy in aerosol- and cloud-free conditions of the radiation parameterizations used in climate models. Accuracy is assessed relative to observationally validated reference models for fluxes under present-day conditions and forcing (flux changes) from quadrupled concentrations of carbon dioxide. Agreement among reference models is typically within 1 W/m 2, while parameterized calculations are roughly half as accurate in the longwave and even less accurate, and more variable, in the shortwave. Absorption of shortwave radiation is underestimated by most parameterizations in the present day and has relatively large errors in forcing. Error in present-day conditions is essentiallymore » unrelated to error in forcing calculations. Recent revisions to parameterizations have reduced error in most cases. As a result, a dependence on atmospheric conditions, including integrated water vapor, means that global estimates of parameterization error relevant for the radiative forcing of climate change will require much more ambitious calculations.« less

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

PubMed Central

Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

2016-01-01

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modelling and Repair

PubMed Central

Tiburcy, Malte; Hudson, James E.; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Liao, Mei-Ling Chang; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D.; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W.; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A.; Unger, Andreas; Linke, Wolfgang A.; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C.; Zimmermann, Wolfram-Hubertus

2017-01-01

Background Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modelling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) towards an adult phenotype under defined conditions. Methods We systematically investigated cell composition, matrix and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We employed morphological, functional, and transcriptome analyses to benchmark maturation of EHM. Results EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M-bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency-response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β1- and β2-adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and NT-proBNP release; all are classical hallmarks of heart failure. Additionally, we demonstrate scalability of EHM according to anticipated clinical demands for cardiac repair. Conclusions We provide proof-of-concept for a universally applicable technology for the engineering of macro-scale human myocardium for disease modelling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. PMID:28167635

Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

PubMed

Tiburcy, Malte; Hudson, James E; Balfanz, Paul; Schlick, Susanne; Meyer, Tim; Chang Liao, Mei-Ling; Levent, Elif; Raad, Farah; Zeidler, Sebastian; Wingender, Edgar; Riegler, Johannes; Wang, Mouer; Gold, Joseph D; Kehat, Izhak; Wettwer, Erich; Ravens, Ursula; Dierickx, Pieterjan; van Laake, Linda W; Goumans, Marie Jose; Khadjeh, Sara; Toischer, Karl; Hasenfuss, Gerd; Couture, Larry A; Unger, Andreas; Linke, Wolfgang A; Araki, Toshiyuki; Neel, Benjamin; Keller, Gordon; Gepstein, Lior; Wu, Joseph C; Zimmermann, Wolfram-Hubertus

2017-05-09

Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions. We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions. We used morphological, functional, and transcriptome analyses to benchmark maturation of EHM. EHM demonstrated important structural and functional properties of postnatal myocardium, including: (1) rod-shaped cardiomyocytes with M bands assembled as a functional syncytium; (2) systolic twitch forces at a similar level as observed in bona fide postnatal myocardium; (3) a positive force-frequency response; (4) inotropic responses to β-adrenergic stimulation mediated via canonical β 1 - and β 2 -adrenoceptor signaling pathways; and (5) evidence for advanced molecular maturation by transcriptome profiling. EHM responded to chronic catecholamine toxicity with contractile dysfunction, cardiomyocyte hypertrophy, cardiomyocyte death, and N-terminal pro B-type natriuretic peptide release; all are classical hallmarks of heart failure. In addition, we demonstrate the scalability of EHM according to anticipated clinical demands for cardiac repair. We provide proof-of-concept for a universally applicable technology for the engineering of macroscale human myocardium for disease modeling and heart repair from embryonic and induced pluripotent stem cell-derived cardiomyocytes under defined, serum-free conditions. © 2017 American Heart Association, Inc.

24 CFR 3280.706 - Oil piping systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... installation extension, alteration, or repair, of any oil piping systems shall be new and free from defects or... used to join sections of threaded pipe. Right and left nipples or couplings shall not be used. (h...

Optimization of Trade-offs in Error-free Image Transmission

NASA Astrophysics Data System (ADS)

Cox, Jerome R.; Moore, Stephen M.; Blaine, G. James; Zimmerman, John B.; Wallace, Gregory K.

1989-05-01

The availability of ubiquitous wide-area channels of both modest cost and higher transmission rate than voice-grade lines promises to allow the expansion of electronic radiology services to a larger community. The band-widths of the new services becoming available from the Integrated Services Digital Network (ISDN) are typically limited to 128 Kb/s, almost two orders of magnitude lower than popular LANs can support. Using Discrete Cosine Transform (DCT) techniques, a compressed approximation to an image may be rapidly transmitted. However, intensity or resampling transformations of the reconstructed image may reveal otherwise invisible artifacts of the approximate encoding. A progressive transmission scheme reported in ISO Working Paper N800 offers an attractive solution to this problem by rapidly reconstructing an apparently undistorted image from the DCT coefficients and then subse-quently transmitting the error image corresponding to the difference between the original and the reconstructed images. This approach achieves an error-free transmission without sacrificing the perception of rapid image delivery. Furthermore, subsequent intensity and resampling manipulations can be carried out with confidence. DCT coefficient precision affects the amount of error information that must be transmitted and, hence the delivery speed of error-free images. This study calculates the overall information coding rate for six radiographic images as a function of DCT coefficient precision. The results demonstrate that a minimum occurs for each of the six images at an average coefficient precision of between 0.5 and 1.0 bits per pixel (b/p). Apparently undistorted versions of these six images can be transmitted with a coding rate of between 0.25 and 0.75 b/p while error-free versions can be transmitted with an overall coding rate between 4.5 and 6.5 b/p.

Estrogen Drives Cellular Transformation and Mutagenesis in Cells Expressing the Breast Cancer-Associated R438W DNA Polymerase Lambda Protein.

PubMed

Nemec, Antonia A; Bush, Korie B; Towle-Weicksel, Jamie B; Taylor, B Frazier; Schulz, Vincent; Weidhaas, Joanne B; Tuck, David P; Sweasy, Joann B

2016-11-01

Repair of DNA damage is critical for maintaining the genomic integrity of cells. DNA polymerase lambda (POLL/Pol λ) is suggested to function in base excision repair (BER) and nonhomologous end-joining (NHEJ), and is likely to play a role in damage tolerance at the replication fork. Here, using next-generation sequencing, it was discovered that the POLL rs3730477 single-nucleotide polymorphism (SNP) encoding R438W Pol λ was significantly enriched in the germlines of breast cancer patients. Expression of R438W Pol λ in human breast epithelial cells induces cellular transformation and chromosomal aberrations. The role of estrogen was assessed as it is commonly used in hormone replacement therapies and is a known breast cancer risk factor. Interestingly, the combination of estrogen treatment and the expression of the R438W Pol λ SNP drastically accelerated the rate of transformation. Estrogen exposure produces 8-oxoguanine lesions that persist in cells expressing R438W Pol λ compared with wild-type (WT) Pol λ-expressing cells. Unlike WT Pol λ, which performs error-free bypass of 8-oxoguanine lesions, expression of R438W Pol λ leads to an increase in mutagenesis and replicative stress in cells treated with estrogen. Together, these data suggest that individuals who carry the rs3730477 POLL germline variant have an increased risk of estrogen-associated breast cancer. The Pol λ R438W mutation can serve as a biomarker to predict cancer risk and implicates that treatment with estrogen in individuals with this mutation may further increase their risk of breast cancer. Mol Cancer Res; 14(11); 1068-77. ©2016 AACR. ©2016 American Association for Cancer Research.

[Clinical and economic evaluation of laparoscopic surgery for inguinal hernia. Return of a difficult clinical choice].

PubMed

Bataille, N

2002-06-01

In the year 2000, the ANAES (National Agency for Accreditation and Evaluation of Health Care) published a technological and economic evaluation of the laparascopic approach to the repair of inguinal hernias based principally on the analysis of randomized studies. This analysis was all the more difficult because of the heterogeneity of the studies for which end results had a very weak level of proof. Laparascopic surgical techniques for inguinal hernia repair require the systematic use of mesh prosthesis and also general anesthesia. Published results are insufficient to compare specific laparascopic techniques with each other. The efficacy of laparoscopic repair compared to open repair with regard to hernia recurrence (the principal criteria of efficacy) has not been demonstrated--mainly because longterm results are not yet available. The overall evaluation of complications is too heterogeneous to show a difference between laparascopic and open surgery. There are, however, certain complications specific to laparascopic repair which, though rare, are potentially very serious. Excellent results reported with laparascopic repair may be due more to the systematic placement of mesh than-to to the approach itself--as has been shown in studies of open repairs "with tension" and "tension free." Superiority of the laparoscopic approach for specific types of hernia (primary unilateral, bilateral, recurrent) has not been demonstrated. Open surgery costs less than laparascopic hernia repair. The evaluation to date for laparascopic inguinal hernia repair is insufficient. Controlled studies with rigorous longterm follow-up and analysis of economic impact must be performed in comparable populations of patients.

DNA repair in Chromobacterium violaceum.

PubMed

Duarte, Fábio Teixeira; Carvalho, Fabíola Marques de; Bezerra e Silva, Uaska; Scortecci, Kátia Castanho; Blaha, Carlos Alfredo Galindo; Agnez-Lima, Lucymara Fassarella; Batistuzzo de Medeiros, Silvia Regina

2004-03-31

Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage.

Expression of DNA repair proteins MSH2, MLH1 and MGMT in human benign and malignant thyroid lesions: An immunohistochemical study

PubMed Central

Giaginis, Constantinos; Michailidi, Christina; Stolakis, Vasileios; Alexandrou, Paraskevi; Tsourouflis, Gerasimos; Klijanienko, Jerzy; Delladetsima, Ioanna; Theocharis, Stamatios

2011-01-01

Summary Background DNA repair is a major defense mechanism, which contributes to the maintenance of genetic sequence, and minimizes cell death, mutation rates, replication errors, DNA damage persistence and genomic instability. Alterations in the expression levels of proteins participating in DNA repair mechanisms have been associated with several aspects of cancer biology. The present study aimed to evaluate the clinical significance of DNA repair proteins MSH2, MLH1 and MGMT in benign and malignant thyroid lesions. Material/Methods MSH2, MLH1 and MGMT protein expression was assessed immunohistochemically on paraffin-embedded thyroid tissues from 90 patients with benign and malignant lesions. Results The expression levels of MLH1 was significantly upregulated in cases with malignant compared to those with benign thyroid lesions (p=0.038). The expression levels of MGMT was significantly downregulated in malignant compared to benign thyroid lesions (p=0.001). Similar associations for both MLH1 and MGMT between cases with papillary carcinoma and hyperplastic nodules were also noted (p=0.014 and p=0.026, respectively). In the subgroup of malignant thyroid lesions, MSH2 downregulation was significantly associated with larger tumor size (p=0.031), while MLH1 upregulation was significantly associated with the presence of lymphatic and vascular invasion (p=0.006 and p=0.002, respectively). Conclusions Alterations in the mismatch repair proteins MSH2 and MLH1 and the direct repair protein MGMT may result from tumor development and/or progression. Further studies are recommended to draw definite conclusions on the clinical significance of DNA repair proteins in thyroid neoplasia. PMID:21358597

HTLV-I Tax Increases Genetic Instability by Inducing DNA Double Strand Breaks during DNA Replication and Switching Repair to NHEJ

PubMed Central

Baydoun, Hicham H.; Bai, Xue Tao; Shelton, Shary; Nicot, Christophe

2012-01-01

Background Appropriate responses to damaged DNA are indispensible for preserving genome stability and preventing cancer. Tumor viruses often target DNA repair machinery to achieve transformation. The Human T-cell leukemia virus type I (HTLV-I) is the only known transforming human retrovirus and the etiological agent of Adult T-cell Leukemia (ATLL). Although HTLV-I-transformed leukemic cells have numerous genetic lesions, the precise role of the viral tax gene in this process is not fully understood. Results Our results show a novel function of HTLV-I oncoprotein Tax as an inducer of genomic DNA double strand breaks (DDSB) during DNA replication. We also found that Tax acts as a potent inhibitor of homologous recombination (HR) DNA repair through the activation of the NF-kB pathway. These results were confirmed using HTLV-I molecular clones expressing Tax at physiological levels in a natural context. We further found that HTLV-I- and Tax-transformed cells are not more susceptible to DNA damaging agents and repair DNA lesions at a rate similar to that of normal cells. Finally, we demonstrated that during S phase, Tax-associated DDSB are preferentially repaired using the error-prone non-homologous end joining (NHEJ) pathway. Conclusions This study provides new insights in Tax effects on DNA repair and genome instability. Although it may not be self sufficient, the creation of DNA breaks and subsequent abnormal use of the non-conservative NHEJ DNA repair during the S phase in HTLV-I-infected Tax-expressing cells may cooperate with other factors to increase genetic and genome instability and favor transformation. PMID:22916124

Correcting intensity loss errors in the absence of texture-free reference samples during pole figure measurement

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

Saleh, Ahmed A., E-mail: asaleh@uow.edu.au

Even with the use of X-ray polycapillary lenses, sample tilting during pole figure measurement results in a decrease in the recorded X-ray intensity. The magnitude of this error is affected by the sample size and/or the finite detector size. These errors can be typically corrected by measuring the intensity loss as a function of the tilt angle using a texture-free reference sample (ideally made of the same alloy as the investigated material). Since texture-free reference samples are not readily available for all alloys, the present study employs an empirical procedure to estimate the correction curve for a particular experimental configuration.more » It involves the use of real texture-free reference samples that pre-exist in any X-ray diffraction laboratory to first establish the empirical correlations between X-ray intensity, sample tilt and their Bragg angles and thereafter generate correction curves for any Bragg angle. It will be shown that the empirically corrected textures are in very good agreement with the experimentally corrected ones. - Highlights: •Sample tilting during X-ray pole figure measurement leads to intensity loss errors. •Texture-free reference samples are typically used to correct the pole figures. •An empirical correction procedure is proposed in the absence of reference samples. •The procedure relies on reference samples that pre-exist in any texture laboratory. •Experimentally and empirically corrected textures are in very good agreement.« less

Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats.

PubMed

Warmerdam, Daniël O; van den Berg, Jeroen; Medema, René H

2016-03-22

rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Msh2-Msh3 Interferes with Okazaki Fragment Processing to Promote Trinucleotide Repeat Expansions

PubMed Central

Kantartzis, Athena; Williams, Gregory M.; Balakrishnan, Lata; Roberts, Rick L.; Surtees, Jennifer A.; Bambara, Robert A.

2012-01-01

Summary Trinucleotide repeat (TNR) expansions are the underlying cause of more than forty neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington’s disease. Although genetic evidence has attributed the cause of these diseases to errors in DNA replication and/or repair, clear molecular mechanisms have not been described. We have focused on the role of the mismatch repair complex Msh2-Msh3 in promoting TNR expansions. We demonstrate that Msh2-Msh3 promotes CTG and CAG repeat expansions in vivo in Saccharomyces cerevisiae. We further provide biochemical evidence that Msh2-Msh3 directly interferes with normal Okazaki fragment processing by flap endonuclease1 (Rad27) and DNA Ligase I (Cdc9) in the presence of TNR sequences, thereby producing small, incremental expansion events. We believe that this is the first mechanistic evidence showing the interplay of replication and repair proteins in the expansion of sequences during lagging strand DNA replication. PMID:22938864

Msh2-Msh3 interferes with Okazaki fragment processing to promote trinucleotide repeat expansions.

PubMed

Kantartzis, Athena; Williams, Gregory M; Balakrishnan, Lata; Roberts, Rick L; Surtees, Jennifer A; Bambara, Robert A

2012-08-30

Trinucleotide repeat (TNR) expansions are the underlying cause of more than 40 neurodegenerative and neuromuscular diseases, including myotonic dystrophy and Huntington's disease. Although genetic evidence points to errors in DNA replication and/or repair as the cause of these diseases, clear molecular mechanisms have not been described. Here, we focused on the role of the mismatch repair complex Msh2-Msh3 in promoting TNR expansions. We demonstrate that Msh2-Msh3 promotes CTG and CAG repeat expansions in vivo in Saccharomyces cerevisiae. Furthermore, we provide biochemical evidence that Msh2-Msh3 directly interferes with normal Okazaki fragment processing by flap endonuclease1 (Rad27) and DNA ligase I (Cdc9) in the presence of TNR sequences, thereby producing small, incremental expansion events. We believe that this is the first mechanistic evidence showing the interplay of replication and repair proteins in the expansion of sequences during lagging-strand DNA replication. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.

PubMed

Mateos-Gomez, Pedro A; Kent, Tatiana; Deng, Sarah K; McDevitt, Shane; Kashkina, Ekaterina; Hoang, Trung M; Pomerantz, Richard T; Sfeir, Agnel

2017-12-01

Mammalian polymerase theta (Polθ) is a multifunctional enzyme that promotes error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here we present structure-function analyses that reveal that, in addition to the polymerase domain, Polθ-helicase activity plays a central role during double-strand break (DSB) repair. Our results show that the helicase domain promotes chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR). In vitro assays demonstrate that Polθ-helicase activity facilitates the removal of RPA from resected DSBs to allow their annealing and subsequent joining by alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ, inhibition of RPA1 enhances end joining and suppresses recombination. Taken together, our results reveal that the balance between HR and alt-NHEJ is controlled by opposing activities of Polθ and RPA, providing further insight into the regulation of repair-pathway choice in mammalian cells.

Patterns of prefrontal dysfunction in alcoholics with and without Korsakoff’s syndrome, patients with Parkinson’s disease, and patients with rupture and repair of the anterior communicating artery

PubMed Central

Dirksen, Courtney L; Howard, Julie A; Cronin-Golomb, Alice; Oscar-Berman, Marlene

2006-01-01

This study compared patterns of frontal-lobe dysfunction in alcoholics with Korsakoff’s syndrome (KS: n = 9), non-Korsakoff alcoholics (AL: n = 28), patients with Parkinson’s disease (PD: n = 18), and patients with rupture and repair of the anterior communicating artery (ACoA: n = 4) relative to healthy non-neurological control (NC) participants (n = 70). The tests administered were sensitive to functions of dorsolateral prefrontal and orbito-frontal subsystems. Measures included perseverative errors on the Wisconsin Card Sorting Test (WCST-pe), errors on object alternation (OA), errors on Trails B, number of words generated on the Controlled Oral Word Association Test (COWAT), and number of categories completed on the WCST (WCST-cc). KS patients were as impaired as AL participants on orbitofrontal measures and, on dorsolateral prefrontal measures, were impaired relative to AL participants, whose performance did not differ from controls. Patients with PD also were impaired on tests of orbitofrontal and dorsolateral prefrontal functioning but to a lesser extent than the KS patients. Moreover, most of the PD deficits were driven by the impaired performance of patients whose initial symptoms were on the right side of the body. The ACoA patients were significantly impaired on tests of orbitofrontal but not dorsolateral prefrontal functioning relative to the control group. Together, the results confirm different patterns of frontal-system impairments in patient groups having compromised frontal lobe functioning consequent to varying etiologies. PMID:19412479

Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

PubMed

Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

2017-06-01

Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

Assessment of Logistics Effectiveness for Expeditionary Units

DTIC Science & Technology

2017-12-01

navigating the bureaucracy when spending government money requires the ESU teams to be savvy supply experts. Figure 8. EOD Force Laydown. Source...main uses is to help free a trapped diver from any number of hazards. The MK-16 equipment must withstand these conditions and not puncture...of the valves being shipped to the units as repair parts. The pieces require an oxygen- free environment for testing, along with other stringent

Evaluating the Effectiveness of DART® Buoy Networks Based on Forecast Accuracy

NASA Astrophysics Data System (ADS)

Percival, Donald B.; Denbo, Donald W.; Gica, Edison; Huang, Paul Y.; Mofjeld, Harold O.; Spillane, Michael C.; Titov, Vasily V.

2018-04-01

A performance measure for a DART® tsunami buoy network has been developed. DART® buoys are used to detect tsunamis, but the full potential of the data they collect is realized through accurate forecasts of inundations caused by the tsunamis. The performance measure assesses how well the network achieves its full potential through a statistical analysis of simulated forecasts of wave amplitudes outside an impact site and a consideration of how much the forecasts are degraded in accuracy when one or more buoys are inoperative. The analysis uses simulated tsunami amplitude time series collected at each buoy from selected source segments in the Short-term Inundation Forecast for Tsunamis database and involves a set for 1000 forecasts for each buoy/segment pair at sites just offshore of selected impact communities. Random error-producing scatter in the time series is induced by uncertainties in the source location, addition of real oceanic noise, and imperfect tidal removal. Comparison with an error-free standard leads to root-mean-square errors (RMSEs) for DART® buoys located near a subduction zone. The RMSEs indicate which buoy provides the best forecast (lowest RMSE) for sections of the zone, under a warning-time constraint for the forecasts of 3 h. The analysis also shows how the forecasts are degraded (larger minimum RMSE among the remaining buoys) when one or more buoys become inoperative. The RMSEs provide a way to assess array augmentation or redesign such as moving buoys to more optimal locations. Examples are shown for buoys off the Aleutian Islands and off the West Coast of South America for impact sites at Hilo HI and along the US West Coast (Crescent City CA and Port San Luis CA, USA). A simple measure (coded green, yellow or red) of the current status of the network's ability to deliver accurate forecasts is proposed to flag the urgency of buoy repair.

Evaluating the Effectiveness of DART® Buoy Networks Based on Forecast Accuracy

NASA Astrophysics Data System (ADS)

Percival, Donald B.; Denbo, Donald W.; Gica, Edison; Huang, Paul Y.; Mofjeld, Harold O.; Spillane, Michael C.; Titov, Vasily V.

2018-03-01

A performance measure for a DART® tsunami buoy network has been developed. DART® buoys are used to detect tsunamis, but the full potential of the data they collect is realized through accurate forecasts of inundations caused by the tsunamis. The performance measure assesses how well the network achieves its full potential through a statistical analysis of simulated forecasts of wave amplitudes outside an impact site and a consideration of how much the forecasts are degraded in accuracy when one or more buoys are inoperative. The analysis uses simulated tsunami amplitude time series collected at each buoy from selected source segments in the Short-term Inundation Forecast for Tsunamis database and involves a set for 1000 forecasts for each buoy/segment pair at sites just offshore of selected impact communities. Random error-producing scatter in the time series is induced by uncertainties in the source location, addition of real oceanic noise, and imperfect tidal removal. Comparison with an error-free standard leads to root-mean-square errors (RMSEs) for DART® buoys located near a subduction zone. The RMSEs indicate which buoy provides the best forecast (lowest RMSE) for sections of the zone, under a warning-time constraint for the forecasts of 3 h. The analysis also shows how the forecasts are degraded (larger minimum RMSE among the remaining buoys) when one or more buoys become inoperative. The RMSEs provide a way to assess array augmentation or redesign such as moving buoys to more optimal locations. Examples are shown for buoys off the Aleutian Islands and off the West Coast of South America for impact sites at Hilo HI and along the US West Coast (Crescent City CA and Port San Luis CA, USA). A simple measure (coded green, yellow or red) of the current status of the network's ability to deliver accurate forecasts is proposed to flag the urgency of buoy repair.

Welding wire selection critical to jet engine repair work

NASA Astrophysics Data System (ADS)

1992-11-01

A review is provided of issues related to the selection of welding wire for aircraft gas-turbine engines emphasizing the importance of cleanliness in the welding wire product. A three-step metallurgical control process is described for the production of welding wire that is clean and suitable for turbine repair. The process is based on: (1) vacuum induction melting; (2) contamination-free processing of the wire; and (3) environmentally controlled packaging. Weld work on aerospace casting is shown to be useful and suitable for many alloy and superalloy materials with various filler materials.

Destabilization of the MutSα's protein-protein interface due to binding to the DNA adduct induced by anticancer agent carboplatin via molecular dynamics simulations.

PubMed

Negureanu, Lacramioara; Salsbury, Freddie R

2013-11-01

DNA mismatch repair (MMR) proteins maintain genetic integrity in all organisms by recognizing and repairing DNA errors. Such alteration of hereditary information can lead to various diseases, including cancer. Besides their role in DNA repair, MMR proteins detect and initiate cellular responses to certain type of DNA damage. Its response to the damaged DNA has made the human MMR pathway a useful target for anticancer agents such as carboplatin. This study indicates that strong, specific interactions at the interface of MutSα in response to the mismatched DNA recognition are replaced by weak, non-specific interactions in response to the damaged DNA recognition. Data suggest a severe impairment of the dimerization of MutSα in response to the damaged DNA recognition. While the core of MutSα is preserved in response to the damaged DNA recognition, the loss of contact surface and the rearrangement of contacts at the protein interface suggest a different packing in response to the damaged DNA recognition. Coupled in response to the mismatched DNA recognition, interaction energies, hydrogen bonds, salt bridges, and solvent accessible surface areas at the interface of MutSα and within the subunits are uncoupled or asynchronously coupled in response to the damaged DNA recognition. These pieces of evidence suggest that the loss of a synchronous mode of response in the MutSα's surveillance for DNA errors would possibly be one of the mechanism(s) of signaling the MMR-dependent programed cell death much wanted in anticancer therapies. The analysis was drawn from dynamics simulations.

Speech outcome in young children born with unilateral cleft lip and palate treated with one- or two-stage palatal repair and the impact of early intervention.

PubMed

Raud Westberg, Liisi; Höglund Santamarta, Lena; Karlsson, Jenny; Nyberg, Jill; Neovius, Erik; Lohmander, Anette

2017-10-25

The aim of this study was to describe speech at 1, 1;6 and 3 years of age in children born with unilateral cleft lip and palate (UCLP) and relate the findings to operation method and amount of early intervention received. A prospective trial of children born with UCLP operated with a one-stage (OS) palatal repair at 12 months or a two-stage repair (TS) with soft palate closure at 3-4 months and hard palate closure at 12 months was undertaken (Scandcleft). At 1 and 1;6 years the place and manner of articulation and number of different consonants produced in babbling were reported in 33 children. At three years of age percentage consonants correct adjusted for age (PCC-A) and cleft speech errors were assessed in 26 of the 33 children. Early intervention was not provided as part of the trial but according to the clinical routine and was extracted from patient records. At age 3, the mean PCC-A was 68% and 46% of the children produced articulation errors with no significant difference between the two groups. At one year there was a significantly higher occurrence of oral stops and anterior place consonants in the TS group. There were significant correlations between the consonant production between one and three years of age, but not with amount of early intervention received. The TS method was beneficial for consonant production at age 1, but not shown at 1;6 or 3 years. Behaviourally based early intervention still needs to be evaluated.

Riding the Waves: How Our Cells Send Signals | Center for Cancer Research

Cancer.gov

The ability of cells to perceive and respond to their environment is critical in order to maintain basic cellular functions such as development, tissue repair, and response to stress. This process happens through a complex system of communication, called cell signaling, which governs basic cellular activities and coordinates cell actions. Errors in cell signaling have been

Reliability and coverage analysis of non-repairable fault-tolerant memory systems

NASA Technical Reports Server (NTRS)

Cox, G. W.; Carroll, B. D.

1976-01-01

A method was developed for the construction of probabilistic state-space models for nonrepairable systems. Models were developed for several systems which achieved reliability improvement by means of error-coding, modularized sparing, massive replication and other fault-tolerant techniques. From the models developed, sets of reliability and coverage equations for the systems were developed. Comparative analyses of the systems were performed using these equation sets. In addition, the effects of varying subunit reliabilities on system reliability and coverage were described. The results of these analyses indicated that a significant gain in system reliability may be achieved by use of combinations of modularized sparing, error coding, and software error control. For sufficiently reliable system subunits, this gain may far exceed the reliability gain achieved by use of massive replication techniques, yet result in a considerable saving in system cost.

Experimental results of 5-Gbps free-space coherent optical communications with adaptive optics

NASA Astrophysics Data System (ADS)

Chen, Mo; Liu, Chao; Rui, Daoman; Xian, Hao

2018-07-01

In a free-space optical communication system with fiber optical components, the received signal beam must be coupled into a single-mode fiber (SMF) before being amplified and detected. The impacts analysis of tracking errors and wavefront distortion on SMF coupling show that under the condition of relatively strong turbulence, only the tracking errors compensation is not enough, and turbulence wavefront aberration is required to be corrected. Based on our previous study and design of SMF coupling system with a 137-element continuous surface deformable mirror AO unit, we perform an experiment of a 5-Gbps Free-space Coherent Optical Communication (FSCOC) system, in which the eye pattern and Bit-error Rate (BER) are displayed. The comparative results are shown that the influence of the atmospheric is fatal in FSCOC systems. The BER of coherent communication is under 10-6 with AO compensation, which drops significantly compared with the BER without AO correction.

Performance evaluation of FSO system using wavelength and time diversity over malaga turbulence channel with pointing errors

NASA Astrophysics Data System (ADS)

Balaji, K. A.; Prabu, K.

2018-03-01

There is an immense demand for high bandwidth and high data rate systems, which is fulfilled by wireless optical communication or free space optics (FSO). Hence FSO gained a pivotal role in research which has a added advantage of both cost-effective and licence free huge bandwidth. Unfortunately the optical signal in free space suffers from irradiance and phase fluctuations due to atmospheric turbulence and pointing errors which deteriorates the signal and degrades the performance of communication system over longer distance which is undesirable. In this paper, we have considered polarization shift keying (POLSK) system applied with wavelength and time diversity technique over Malaga(M)distribution to mitigate turbulence induced fading. We derived closed form mathematical expressions for estimating the systems outage probability and average bit error rate (BER). Ultimately from the results we can infer that wavelength and time diversity schemes enhances these systems performance.

Laparoscopic hernia surgery: an overview.

PubMed

Krähenbühl, L; Schäfer, M; Feodorovici, M A; Büchler, M W

1998-01-01

Despite the fact that laparoscopic hernia repair was already described in 1979, its value has still not been well defined. The standard treatment for uncomplicated primary hernia repair in Europe is an open anterior approach (i.e. Shouldice), and 'tension-free' mesh plug repair in the USA. At present, posterior mesh insertion is used to repair so-called complicated hernias with a complete myopectineal defect, and recurrent and bilateral hernias. Laparoscopic hernia repair (transabdominally and extraperitoneally) mimics this posterior mesh insertion and is therefore mostly used for treating complicated hernias. Whether or not a transabdominal or extraperitoneal approach is used depends on the type and size of the hernia, the risk to the patient, previous abdominal operations and the surgeon's experience. However, the extraperitoneal approach is now recommended because of its lower complication rate compared to the transabdominal approach. Compared to open surgical procedures the laparoscopic approach shows significant advantages in terms of less postoperative pain, decreased time off work and decreased overall costs. The disadvantages are increased operating time as well as difficulty in performing the procedure itself. A recent large randomized series has for the first time been able to demonstrate the advantages of the laparoscopic approach in a long-term follow-up. However, further studies are needed to define the exact place of laparoscopic hernia repair in the treatment of groin hernias.

First percutaneous Micra leadless pacemaker implantation and tricuspid valve repair with MitraClip NT for lead-associated severe tricuspid regurgitation.

PubMed

Tang, Gilbert H L; Kaple, Ryan; Cohen, Martin; Dutta, Tanya; Undemir, Cenap; Ahmad, Hasan; Poniros, Angelica; Bennett, Joanne; Feng, Cheng; Lansman, Steven

2017-02-03

Pacemaker lead-associated severe tricuspid regurgitation (TR) can lead to right heart failure and poor prognosis. Surgery in these patients carries significant morbidities. We describe a successful treatment of symptomatic severe TR by leadless pacemaker implantation followed by tricuspid valve (TV) repair with the MitraClip NT. A 71-year-old frail female with poor functional status, chronic atrial fibrillation and permanent pacemaker implantation in 2012 presented with symptomatic moderate-severe mitral regurgitation (MR) and severe TR with the pacemaker lead as the culprit. She was deemed extreme risk for double valve surgery and, because of her pacemaker dependency, the decision was to stage her interventions first with transcatheter mitral repair, then laser lead extraction and leadless pacemaker implantation to free the TV from tethering, then TV repair. An obstructive LAD lesion was identified and treated during mitral repair with the MitraClip NT. The Micra leadless pacemaker implantation and subsequent TV repair with the MitraClip NT were successful and the patient's MR improved to mild and TR to moderate, respectively. We report here a first successful transcatheter strategy to treat lead-associated severe TR by leadless pacemaker and MitraClip. Removing the pacemaker lead relieved leaflet tethering and improved the reparability of the TV.

Extending the Solvation-Layer Interface Condition Continum Electrostatic Model to a Linearized Poisson-Boltzmann Solvent.

PubMed

Molavi Tabrizi, Amirhossein; Goossens, Spencer; Mehdizadeh Rahimi, Ali; Cooper, Christopher D; Knepley, Matthew G; Bardhan, Jaydeep P

2017-06-13

We extend the linearized Poisson-Boltzmann (LPB) continuum electrostatic model for molecular solvation to address charge-hydration asymmetry. Our new solvation-layer interface condition (SLIC)/LPB corrects for first-shell response by perturbing the traditional continuum-theory interface conditions at the protein-solvent and the Stern-layer interfaces. We also present a GPU-accelerated treecode implementation capable of simulating large proteins, and our results demonstrate that the new model exhibits significant accuracy improvements over traditional LPB models, while reducing the number of fitting parameters from dozens (atomic radii) to just five parameters, which have physical meanings related to first-shell water behavior at an uncharged interface. In particular, atom radii in the SLIC model are not optimized but uniformly scaled from their Lennard-Jones radii. Compared to explicit-solvent free-energy calculations of individual atoms in small molecules, SLIC/LPB is significantly more accurate than standard parametrizations (RMS error 0.55 kcal/mol for SLIC, compared to RMS error of 3.05 kcal/mol for standard LPB). On parametrizing the electrostatic model with a simple nonpolar component for total molecular solvation free energies, our model predicts octanol/water transfer free energies with an RMS error 1.07 kcal/mol. A more detailed assessment illustrates that standard continuum electrostatic models reproduce total charging free energies via a compensation of significant errors in atomic self-energies; this finding offers a window into improving the accuracy of Generalized-Born theories and other coarse-grained models. Most remarkably, the SLIC model also reproduces positive charging free energies for atoms in hydrophobic groups, whereas standard PB models are unable to generate positive charging free energies regardless of the parametrized radii. The GPU-accelerated solver is freely available online, as is a MATLAB implementation.

Use of CCSDS and OSI Protocols on the Advanced Communications Technology Satellite

NASA Technical Reports Server (NTRS)

Chirieleison, Don

1996-01-01

Although ACTS (Advanced Communications Technology Satellite) provides an almost error-free channel during much of the day and under most conditions, there are times when it is not suitable for reliably error-free data communications when operating in the uncoded mode. Because coded operation is not always available to every earth station, measures must be taken in the end system to maintain adequate throughput when transferring data under adverse conditions. The most effective approach that we tested to improve performance was the addition of an 'outer' Reed-Solomon code through use of CCSDS (Consultative Committee for Space Data Systems) GOS 2 (a forward error correcting code). This addition can benefit all users of an ACTS channel including those applications that do not require totally reliable transport, but it is somewhat expensive because additional hardware is needed. Although we could not characterize the link noise statistically (it appeared to resemble uncorrelated white noise, the type that block codes are least effective in correcting), we did find that CCSDS GOS 2 gave an essentially error-free link at BER's (bit error rate) as high as 6x10(exp -4). For users that demand reliable transport, an ARQ (Automatic Repeat Queuing) protocol such as TCP (Transmission Control Protocol) or TP4 (Transport Protocol, Class 4) will probably be used. In this category, it comes as no surprise that the best choice of the protocol suites tested over ACTS was TP4 using CCSDS GOS 2. TP4 behaves very well over an error-free link which GOS 2 provides up to a point. Without forward error correction, however, TP4 service begins to degrade in the 10(exp -7)-10(exp -6) range and by 4x10(exp -6), it barely gives any throughput at all. If Congestion Avoidance is used in TP4, the degradation is even more pronounced. Fortunately, as demonstrated here, this effect can be more than compensated for by choosing the Selective Acknowledgment option. In fact, this option can enable TP4 to deliver some throughput at error rates as high as 10(exp -5).

Primary unilateral cleft lip repair.

PubMed

Adenwalla, H S; Narayanan, P V

2009-10-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

Primary unilateral cleft lip repair

PubMed Central

Adenwalla, H. S.; Narayanan, P. V.

2009-01-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web. PMID:19884683

Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks.

PubMed

Tichy, Elisia D; Pillai, Resmi; Deng, Li; Liang, Li; Tischfield, Jay; Schwemberger, Sandy J; Babcock, George F; Stambrook, Peter J

2010-11-01

Embryonic stem (ES) cells give rise to all cell types of an organism. Since mutations at this embryonic stage would affect all cells and be detrimental to the overall health of an organism, robust mechanisms must exist to ensure that genomic integrity is maintained. To test this proposition, we compared the capacity of murine ES cells to repair DNA double-strand breaks with that of differentiated cells. Of the 2 major pathways that repair double-strand breaks, error-prone nonhomologous end joining (NHEJ) predominated in mouse embryonic fibroblasts, whereas the high fidelity homologous recombinational repair (HRR) predominated in ES cells. Microhomology-mediated end joining, an emerging repair pathway, persisted at low levels in all cell types examined. The levels of proteins involved in HRR and microhomology-mediated end joining were highly elevated in ES cells compared with mouse embryonic fibroblasts, whereas those for NHEJ were quite variable, with DNA Ligase IV expression low in ES cells. The half-life of DNA Ligase IV protein was also low in ES cells. Attempts to increase the abundance of DNA Ligase IV protein by overexpression or inhibition of its degradation, and thereby elevate NHEJ in ES cells, were unsuccessful. When ES cells were induced to differentiate, however, the level of DNA Ligase IV protein increased, as did the capacity to repair by NHEJ. The data suggest that preferential use of HRR rather than NHEJ may lend ES cells an additional layer of genomic protection and that the limited levels of DNA Ligase IV may account for the low level of NHEJ activity.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

PubMed

Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

2015-11-09

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

PubMed Central

Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V. N.; Poh, Chueh Loo; Wang, Dong-An

2015-01-01

In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair. PMID:26549401

Evaluation of Asphalt Bridge Deck Joint Systems.

DOT National Transportation Integrated Search

2009-12-01

Asphaltic Plug Joint is an expansion joint that is used for new and rehabilitated bridges. It provides a smooth and watertight surface free of debris; and offers simple, easy and staged construction. Asphaltic plug joint can be repaired segmentally a...

Effect of slope errors on the performance of mirrors for x-ray free electron laser applications

DOE PAGES

Pardini, Tom; Cocco, Daniele; Hau-Riege, Stefan P.

2015-12-02

In this work we point out that slope errors play only a minor role in the performance of a certain class of x-ray optics for X-ray Free Electron Laser (XFEL) applications. Using physical optics propagation simulations and the formalism of Church and Takacs [Opt. Eng. 34, 353 (1995)], we show that diffraction limited optics commonly found at XFEL facilities posses a critical spatial wavelength that makes them less sensitive to slope errors, and more sensitive to height error. Given the number of XFELs currently operating or under construction across the world, we hope that this simple observation will help tomore » correctly define specifications for x-ray optics to be deployed at XFELs, possibly reducing the budget and the timeframe needed to complete the optical manufacturing and metrology.« less

Effect of slope errors on the performance of mirrors for x-ray free electron laser applications.

PubMed

Pardini, Tom; Cocco, Daniele; Hau-Riege, Stefan P

2015-12-14

In this work we point out that slope errors play only a minor role in the performance of a certain class of x-ray optics for X-ray Free Electron Laser (XFEL) applications. Using physical optics propagation simulations and the formalism of Church and Takacs [Opt. Eng. 34, 353 (1995)], we show that diffraction limited optics commonly found at XFEL facilities posses a critical spatial wavelength that makes them less sensitive to slope errors, and more sensitive to height error. Given the number of XFELs currently operating or under construction across the world, we hope that this simple observation will help to correctly define specifications for x-ray optics to be deployed at XFELs, possibly reducing the budget and the timeframe needed to complete the optical manufacturing and metrology.

Midline dorsal plication to repair recurrent chordee at reoperation for hypospadias surgery complication.

PubMed

Yucel, Selcuk; Sanli, Ahmet; Kukul, Erdal; Karaguzel, Gungor; Melikoglu, Mustafa; Guntekin, Erol

2006-02-01

Midline dorsal plication is an efficient and safe surgical technique to correct chordee. We investigated the efficacy of midline dorsal plication for recurrent chordee in complicated hypospadias reoperations. We retrospectively evaluated the charts of 25 boys who underwent reoperation between 1999 and 2004 due to complications of primary hypospadias repair other than meatal stenosis. A total of 15 cases were initially managed elsewhere for primary repair or complications. The etiology of recurrent chordee was defined at surgical correction. When recurrent chordee was noted a midline dorsal plication was performed. Of 25 patients 10 had previously undergone chordee repair. Nine of these patients were observed to have recurrent chordee and 1 had de novo chordee. A total of 10 patients had recurrent or delayed onset chordee. Mean patient age at primary repair was 6.28 years (range 1 to 33). Mean age at last operation for chordee was 15.9 years (range 4 to 66). Mean interval to recurrent chordee was 6 years (range 1 to 16), excluding a 66-year-old blind patient who did not know when recurrent chordee developed. Five patients had chordee recur before puberty at a mean interval of 2.6 years. Mean reoperation rate was 2.4 for recurrent chordee cases and 2.6 for chordee-free cases. Mean followup after midline dorsal plication for recurrent chordee repair was 22 months (range 8 to 56), while mean followup in pubertal and postpubertal cases was 20 months. No recurrence of chordee or surgery related morbidity was observed after recurrent chordee repair by midline dorsal plication. Chordee may recur during puberty following successful chordee repair. The midline dorsal plication technique is simple, efficient and safe even in patients who have undergone multiple surgeries for hypospadias and chordee repair.

Regulation of Gene Editing Activity Directed by Single-Stranded Oligonucleotides and CRISPR/Cas9 Systems

PubMed Central

Bialk, Pawel; Rivera-Torres, Natalia; Strouse, Bryan; Kmiec, Eric B.

2015-01-01

Single-stranded DNA oligonucleotides (ssODNs) can direct the repair of a single base mutation in human genes. While the regulation of this gene editing reaction has been partially elucidated, the low frequency with which repair occurs has hampered development toward clinical application. In this work a CRISPR/Cas9 complex is employed to induce double strand DNA breakage at specific sites surrounding the nucleotide designated for exchange. The result is a significant elevation in ssODN-directed gene repair, validated by a phenotypic readout. By analysing reaction parameters, we have uncovered restrictions on gene editing activity involving CRISPR/Cas9 complexes. First, ssODNs that hybridize to the non-transcribed strand direct a higher level of gene repair than those that hybridize to the transcribed strand. Second, cleavage must be proximal to the targeted mutant base to enable higher levels of gene editing. Third, DNA cleavage enables a higher level of gene editing activity as compared to single-stranded DNA nicks, created by modified Cas9 (Nickases). Fourth, we calculated the hybridization potential and free energy levels of ssODNs that are complementary to the guide RNA sequences of CRISPRs used in this study. We find a correlation between free energy potential and the capacity of single-stranded oligonucleotides to inhibit specific DNA cleavage activity, thereby indirectly reducing gene editing activity. Our data provide novel information that might be taken into consideration in the design and usage of CRISPR/Cas9 systems with ssODNs for gene editing. PMID:26053390

Regulation of Gene Editing Activity Directed by Single-Stranded Oligonucleotides and CRISPR/Cas9 Systems.

PubMed

Bialk, Pawel; Rivera-Torres, Natalia; Strouse, Bryan; Kmiec, Eric B

2015-01-01

Single-stranded DNA oligonucleotides (ssODNs) can direct the repair of a single base mutation in human genes. While the regulation of this gene editing reaction has been partially elucidated, the low frequency with which repair occurs has hampered development toward clinical application. In this work a CRISPR/Cas9 complex is employed to induce double strand DNA breakage at specific sites surrounding the nucleotide designated for exchange. The result is a significant elevation in ssODN-directed gene repair, validated by a phenotypic readout. By analysing reaction parameters, we have uncovered restrictions on gene editing activity involving CRISPR/Cas9 complexes. First, ssODNs that hybridize to the non-transcribed strand direct a higher level of gene repair than those that hybridize to the transcribed strand. Second, cleavage must be proximal to the targeted mutant base to enable higher levels of gene editing. Third, DNA cleavage enables a higher level of gene editing activity as compared to single-stranded DNA nicks, created by modified Cas9 (Nickases). Fourth, we calculated the hybridization potential and free energy levels of ssODNs that are complementary to the guide RNA sequences of CRISPRs used in this study. We find a correlation between free energy potential and the capacity of single-stranded oligonucleotides to inhibit specific DNA cleavage activity, thereby indirectly reducing gene editing activity. Our data provide novel information that might be taken into consideration in the design and usage of CRISPR/Cas9 systems with ssODNs for gene editing.

[Conversion methods of freshwater snail tissue dry mass and ash free dry mass].

PubMed

Zhao, Wei-Hua; Wang, Hai-Jun; Wang, Hong-Zhu; Liu, Xue-Qin

2009-06-01

Mollusk biomass is usually expressed as wet mass with shell, but this expression fails to represent real biomass due to the high calcium carbonate content in shells. Tissue dry mass and ash free dry mass are relatively close to real biomass. However, the determination process of these two parameters is very complicated, and thus, it is necessary to establish simple and practical conversion methods for these two parameters. A total of six taxa of freshwater snails (Bellamya sp., Alocinma longicornis, Parafossarulus striatulus, Parafossarulus eximius, Semisulcospira cancellata, and Radix sp.) common in the Yangtze Basin were selected to explore the relations of their five shell dimension parameters, dry and wet mass with shells with their tissue dry mass and ash free dry mass. The regressions of the tissue dry mass and ash free dry mass with the five shell dimension parameters were all exponential (y = ax(b)). Among them, shell width and shell length were more precise (the average percentage error between observed and predicted value being 22.0% and 22.5%, respectively) than the other three parameters in the conversion of dry mass. Wet mass with shell could be directly converted to tissue dry mass and ash free dry mass, with an average percentage error of 21.7%. According to the essence of definition and the errors of conversion, ash free dry mass would be the optimum parameter to express snail biomass.

Laparoscopic repair of traumatic perforation of the urinary bladder.

PubMed

Cottam, D; Gorecki, P J; Curvelo, M; Shaftan, G W

2001-12-01

Laparoscopy as a diagnostic modality in trauma has been reported. However, therapeutic laparoscopy for trauma remains a controversial subject. We present a case of laparoscopic repair of a traumatic bladder rupture. A 25-year-old man was brought to the emergency room after a head-on collision. Physical examination was unremarkable with the exception of gross hematuria upon insertion of a urinary catheter. Computed tomography scan of the abdomen demonstrated a small amount of free intraperitoneal fluid. An anteroposterior cystogram was obtained which showed no intraperitoneal or extraperitoneal leak. Repeat examinations of the abdomen revealed a mild tenderness in the lower abdomen. Because of the presence of unexplained free intraperitoneal fluid and equivocal signs of peritoneal irritation, exploratory laparoscopy was performed. Three 5-mm ports and a 5-mm laparoscope were used. Laparoscopic examination of the abdomen revealed a 4-cm rupture at the dome of the bladder. The laceration was sutured in two layers using an intracorporeal technique. The patient was discharged on the second postoperative day with indwelling urinary catheter. Eight days after the operation, a repeated cystogram revealed no evidence of leak. We believe that laparoscopic exploration for trauma in hemodynamically stable patients is feasible. The repair of simple intraabdominal injuries such as bladder rupture can be safely performed.

Stress free configuration of the human eye.

PubMed

Elsheikh, Ahmed; Whitford, Charles; Hamarashid, Rosti; Kassem, Wael; Joda, Akram; Büchler, Philippe

2013-02-01

Numerical simulations of eye globes often rely on topographies that have been measured in vivo using devices such as the Pentacam or OCT. The topographies, which represent the form of the already stressed eye under the existing intraocular pressure, introduce approximations in the analysis. The accuracy of the simulations could be improved if either the stress state of the eye under the effect of intraocular pressure is determined, or the stress-free form of the eye estimated prior to conducting the analysis. This study reviews earlier attempts to address this problem and assesses the performance of an iterative technique proposed by Pandolfi and Holzapfel [1], which is both simple to implement and promises high accuracy in estimating the eye's stress-free form. A parametric study has been conducted and demonstrated reliance of the error level on the level of flexibility of the eye model, especially in the cornea region. However, in all cases considered 3-4 analysis iterations were sufficient to produce a stress-free form with average errors in node location <10(-6)mm and a maximal error <10(-4)mm. This error level, which is similar to what has been achieved with other methods and orders of magnitude lower than the accuracy of current clinical topography systems, justifies the use of the technique as a pre-processing step in ocular numerical simulations. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

PubMed Central

Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

Ex vivo model unravelling cell distribution effect in hydrogels for cartilage repair.

PubMed

Mouser, Vivian H M; Dautzenberg, Noël M M; Levato, Riccardo; van Rijen, Mattie H P; Dhert, Wouter J A; Malda, Jos; Gawlitta, Debby

2018-01-01

The implantation of chondrocyte-laden hydrogels is a promising cartilage repair strategy. Chondrocytes can be spatially positioned in hydrogels and thus in defects, while current clinical cell therapies introduce chondrocytes in the defect depth. The main aim of this study was to evaluate the effect of spatial chondrocyte distribution on the reparative process. To reduce animal experiments, an ex vivo osteochondral plug model was used and evaluated. The role of the delivered and endogenous cells in the repair process was investigated. Full thickness cartilage defects were created in equine osteochondral plugs. Defects were filled with (A) chondrocytes at the bottom of the defect, covered with a cell-free hydrogel, (B) chondrocytes homogeneously encapsulated in a hydrogel, and (C, D) combinations of A and B with different cell densities. Plugs were cultured for up to 57 days, after which the cartilage and repair tissues were characterized and compared to baseline samples. Additionally, at day 21, the origin of cells in the repair tissue was evaluated. Best outcomes were obtained with conditions C and D, which resulted in well-integrated cartilage-like tissue that completely filled the defect, regardless of the initial cell density. A critical role of the spatial chondrocyte distribution in the repair process was observed. Moreover, the osteochondral plugs stimulated cartilage formation in the hydrogels when cultured in the defects. The resulting repair tissue originated from the delivered cells. These findings confirm the potential of the osteochondral plug model for the optimization of the composition of cartilage implants and for studying repair mechanisms.

Impact of hypertension on early outcomes and long-term survival of patients undergoing aortic repair with Stanford A dissection.

PubMed

Merkle, Julia; Sabashnikov, Anton; Deppe, Antje-Christin; Zeriouh, Mohamed; Eghbalzadeh, Kaveh; Weber, Carolyn; Rahmanian, Parwis; Kuhn, Elmar; Madershahian, Navid; Kroener, Axel; Choi, Yeong-Hoon; Kuhn-Régnier, Ferdinand; Liakopoulos, Oliver; Wahlers, Thorsten

2018-04-01

Stanford A acute aortic dissection (AAD) is a life-threatening emergency, typically occurring in hypertensive patients, requiring immediate surgical repair. The aim of this study was to evaluate early outcomes and long-term survival of hypertensive patients in comparison to normotensive patients suffering from Stanford A AAD. In our center, 240 patients with Stanford A AAD underwent aortic surgical repair from January 2006 to April 2015. After statistical and logistic regression analysis, Kaplan-Meier survival estimation was performed, with up to 9-year follow-up. The proportion of hypertensive patients suffering from Stanford A AAD was 75.4% (n=181). There were only few statistically significant differences in terms of basic demographics, comorbidities, preoperative baseline and clinical characteristics of hypertensive patients in comparison to normotensive patients. Hypertensive patients were significantly older (p=0.008), more frequently received hemi-arch repair (p=0.028) and selective brain perfusion (p=0.001). Our study showed similar statistical results in terms of 30-day mortality (p=0.196), long-term overall cumulative survival of patients (Log-Rank p=0.506) and survival of patients free from cerebrovascular events (Log-Rank p=0.186). Furthermore, subgroup analysis for long-term survival in terms of men (Log-Rank p=0.853), women (Log-Rank p=0.227), patients under and above 65 years of age (Log-Rank p=0.188 and Log-Rank p=0.602, respectively) and patients undergoing one of the three types of aortic repair surgery showed similar results for normotensive and hypertensive patient groups. Subgroup analysis for long-term survival of patients free from cerebrovascular events for women, patients under 65 years of age and patients undergoing aortic arch repair showed significant differences between the two groups in favor of hypertensive patients. Hypertensive patients suffering from Stanford A AAD were older, more frequently received hemi-arch replacement and were not associated with increased risk of 30-day mortality and poorer long-term survival compared to normotensive patients.

Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.

PubMed

Hinrichsen, Inga; Ernst, Benjamin Philipp; Nuber, Franziska; Passmann, Sandra; Schäfer, Dieter; Steinke, Verena; Friedrichs, Nicolaus; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

2014-01-24

Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.

Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1

PubMed Central

2014-01-01

Introduction Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Methods Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. Results MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. Conclusions These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1. PMID:24456667

Suppression of Poxvirus Replication by Resveratrol.

PubMed

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

2017-01-01

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

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

PubMed Central

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

2015-01-01

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

Design of an off-axis visual display based on a free-form projection screen to realize stereo vision

NASA Astrophysics Data System (ADS)

Zhao, Yuanming; Cui, Qingfeng; Piao, Mingxu; Zhao, Lidong

2017-10-01

A free-form projection screen is designed for an off-axis visual display, which shows great potential in applications such as flight training for providing both accommodation and convergence cues for pilots. The method based on point cloud is proposed for the design of the free-form surface, and the design of the point cloud is controlled by a program written in the macro-language. In the visual display based on the free-form projection screen, when the error of the screen along Z-axis is 1 mm, the error of visual distance at each filed is less than 1%. And the resolution of the design for full field is better than 1‧, which meet the requirement of resolution for human eyes.

Recent biological trends in management of fracture non-union

PubMed Central

Emara, Khaled M; Diab, Ramy Ahmed; Emara, Ahmed Khaled

2015-01-01

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. Currently, there is a plethora of different strategies to augment the impaired or “insufficient” bone-regeneration process, including the “gold standard” autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved “local” strategies in terms of tissue engineering and gene therapy, or even “systemic” enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. PMID:26396938

Articulatory Placement for /t/, /d/, /k/ and /g/ Targets in School Age Children with Speech Disorders Associated with Cleft Palate

ERIC Educational Resources Information Center

Gibbon, Fiona; Ellis, Lucy; Crampin, Lisa

2004-01-01

This study used electropalatography (EPG) to identify place of articulation for lingual plosive targets /t/, /d/, /k/ and /g/ in the speech of 15 school age children with repaired cleft palate. Perceptual judgements indicated that all children had correct velar placement for /k/, /g/ targets, but /t/, /d/ targets were produced as errors involving…

Improving P2P live-content delivery using SVC

NASA Astrophysics Data System (ADS)

Schierl, T.; Sánchez, Y.; Hellge, C.; Wiegand, T.

2010-07-01

P2P content delivery techniques for video transmission have become of high interest in the last years. With the involvement of client into the delivery process, P2P approaches can significantly reduce the load and cost on servers, especially for popular services. However, previous studies have already pointed out the unreliability of P2P-based live streaming approaches due to peer churn, where peers may ungracefully leave the P2P infrastructure, typically an overlay networks. Peers ungracefully leaving the system cause connection losses in the overlay, which require repair operations. During such repair operations, which typically take a few roundtrip times, no data is received from the lost connection. While taking low delay for fast-channel tune-in into account as a key feature for broadcast-like streaming applications, the P2P live streaming approach can only rely on a certain media pre-buffer during such repair operations. In this paper, multi-tree based Application Layer Multicast as a P2P overlay technique for live streaming is considered. The use of Flow Forwarding (FF), a.k.a. Retransmission, or Forward Error Correction (FEC) in combination with Scalable video Coding (SVC) for concealment during overlay repair operations is shown. Furthermore the benefits of using SVC over the use of AVC single layer transmission are presented.

Enhanced storage capacity with errors in scale-free Hopfield neural networks: An analytical study.

PubMed

Kim, Do-Hyun; Park, Jinha; Kahng, Byungnam

2017-01-01

The Hopfield model is a pioneering neural network model with associative memory retrieval. The analytical solution of the model in mean field limit revealed that memories can be retrieved without any error up to a finite storage capacity of O(N), where N is the system size. Beyond the threshold, they are completely lost. Since the introduction of the Hopfield model, the theory of neural networks has been further developed toward realistic neural networks using analog neurons, spiking neurons, etc. Nevertheless, those advances are based on fully connected networks, which are inconsistent with recent experimental discovery that the number of connections of each neuron seems to be heterogeneous, following a heavy-tailed distribution. Motivated by this observation, we consider the Hopfield model on scale-free networks and obtain a different pattern of associative memory retrieval from that obtained on the fully connected network: the storage capacity becomes tremendously enhanced but with some error in the memory retrieval, which appears as the heterogeneity of the connections is increased. Moreover, the error rates are also obtained on several real neural networks and are indeed similar to that on scale-free model networks.

Computer-Assisted Detection of 90% of EFL Student Errors

ERIC Educational Resources Information Center

Harvey-Scholes, Calum

2018-01-01

Software can facilitate English as a Foreign Language (EFL) students' self-correction of their free-form writing by detecting errors; this article examines the proportion of errors which software can detect. A corpus of 13,644 words of written English was created, comprising 90 compositions written by Spanish-speaking students at levels A2-B2…

Automatic detection of MLC relative position errors for VMAT using the EPID-based picket fence test

NASA Astrophysics Data System (ADS)

Christophides, Damianos; Davies, Alex; Fleckney, Mark

2016-12-01

Multi-leaf collimators (MLCs) ensure the accurate delivery of treatments requiring complex beam fluences like intensity modulated radiotherapy and volumetric modulated arc therapy. The purpose of this work is to automate the detection of MLC relative position errors  ⩾0.5 mm using electronic portal imaging device-based picket fence tests and compare the results to the qualitative assessment currently in use. Picket fence tests with and without intentional MLC errors were measured weekly on three Varian linacs. The picket fence images analysed covered a time period ranging between 14-20 months depending on the linac. An algorithm was developed that calculated the MLC error for each leaf-pair present in the picket fence images. The baseline error distributions of each linac were characterised for an initial period of 6 months and compared with the intentional MLC errors using statistical metrics. The distributions of median and one-sample Kolmogorov-Smirnov test p-value exhibited no overlap between baseline and intentional errors and were used retrospectively to automatically detect MLC errors in routine clinical practice. Agreement was found between the MLC errors detected by the automatic method and the fault reports during clinical use, as well as interventions for MLC repair and calibration. In conclusion the method presented provides for full automation of MLC quality assurance, based on individual linac performance characteristics. The use of the automatic method has been shown to provide early warning for MLC errors that resulted in clinical downtime.

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

PubMed Central

Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

2017-01-01

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

Towards defect free EUVL reticles: carbon and particle removal by single dry cleaning process and pattern repair by HIM

NASA Astrophysics Data System (ADS)

Koster, N. B.; Molkenboer, F. T.; van Veldhoven, E.; Oostrom, S.

2011-04-01

We report on our findings on EUVL reticle contamination removal, inspection and repair. We show that carbon contamination can be removed without damage to the reticle by our plasma process. Also organic particles, simulated by PSL spheres, can be removed from both the surface of the absorber as well as from the bottom of the trenches. The particles shrink in size during the plasma treatment until they are vanished. The determination of the necessary cleaning time for PSL spheres was conducted on Ru coated samples and the final experiment was performed on our dummy reticle. Finally we show that the Helium Ion Microscope in combination with a Gas Injection System is capable of depositing additional lines and squares on the reticle with sufficient resolution for pattern repair.

The Fanconi anemia pathway promotes replication-dependent DNA interstrand crosslink repair

PubMed Central

Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D.; Elledge, Stephen J.; Walter, Johannes C.

2010-01-01

Fanconi anemia is a human cancer predisposition syndrome caused by mutations in thirteen Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand crosslinks (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. We make use of a cell-free system to show that the FANCI-FANCD2 complex is required for replication-dependent ICL repair. Removal of FANCD2 from extracts inhibits nucleolytic incisions near the ICL as well as translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised. PMID:19965384

Drosophila TDP1 Ortholog Important for Longevity and Nervous System Maintenance | Center for Cancer Research

Cancer.gov

As the molecule responsible for encoding a cell’s hereditary information, DNA must maintain its integrity. However, nucleic acids are vulnerable to damage by a number of endogenous and exogenous insults, such as reactive oxygen species or enzymes that react with DNA. Thus, other enzymes are tasked with repairing damaged DNA, including tyrosyl-DNA phosphodiesterase 1 (TDP1), which frees the 3’ ends of DNA that are blocked by proteins and oxidized bases to allow the ligation of strand breaks. Yeast, mice, and humans that express mutants of TDP1 have a reduced capacity to repair oxidative or topoisomerase-induced damage. A Drosophila TDP1 ortholog, glaikit (gkt), has been reported, but its function in DNA repair has not been evaluated because, surprisingly, gkt knockout flies were not viable.

The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.

PubMed

Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D; Elledge, Stephen J; Walter, Johannes C

2009-12-18

Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.

Average capacity optimization in free-space optical communication system over atmospheric turbulence channels with pointing errors.

PubMed

Liu, Chao; Yao, Yong; Sun, Yun Xu; Xiao, Jun Jun; Zhao, Xin Hui

2010-10-01

A model is proposed to study the average capacity optimization in free-space optical (FSO) channels, accounting for effects of atmospheric turbulence and pointing errors. For a given transmitter laser power, it is shown that both transmitter beam divergence angle and beam waist can be tuned to maximize the average capacity. Meanwhile, their optimum values strongly depend on the jitter and operation wavelength. These results can be helpful for designing FSO communication systems.

Tunable error-free optical frequency conversion of a 4ps optical short pulse over 25 nm by four-wave mixing in a polarisation-maintaining optical fibre

NASA Astrophysics Data System (ADS)

Morioka, T.; Kawanishi, S.; Saruwatari, M.

1994-05-01

Error-free, tunable optical frequency conversion of a transform-limited 4.0 ps optical pulse signalis demonstrated at 6.3 Gbit/s using four-wave mixing in a polarization-maintaining optical fibre. The process generates 4.0-4.6 ps pulses over a 25nm range with time-bandwidth products of 0.31-0.43 and conversion power penalties of less than 1.5 dB.

Radiological Image Compression

NASA Astrophysics Data System (ADS)

Lo, Shih-Chung Benedict

The movement toward digital images in radiology presents the problem of how to conveniently and economically store, retrieve, and transmit the volume of digital images. Basic research into image data compression is necessary in order to move from a film-based department to an efficient digital -based department. Digital data compression technology consists of two types of compression technique: error-free and irreversible. Error -free image compression is desired; however, present techniques can only achieve compression ratio of from 1.5:1 to 3:1, depending upon the image characteristics. Irreversible image compression can achieve a much higher compression ratio; however, the image reconstructed from the compressed data shows some difference from the original image. This dissertation studies both error-free and irreversible image compression techniques. In particular, some modified error-free techniques have been tested and the recommended strategies for various radiological images are discussed. A full-frame bit-allocation irreversible compression technique has been derived. A total of 76 images which include CT head and body, and radiographs digitized to 2048 x 2048, 1024 x 1024, and 512 x 512 have been used to test this algorithm. The normalized mean -square-error (NMSE) on the difference image, defined as the difference between the original and the reconstructed image from a given compression ratio, is used as a global measurement on the quality of the reconstructed image. The NMSE's of total of 380 reconstructed and 380 difference images are measured and the results tabulated. Three complex compression methods are also suggested to compress images with special characteristics. Finally, various parameters which would effect the quality of the reconstructed images are discussed. A proposed hardware compression module is given in the last chapter.

Popliteal artery repair in massively transfused military trauma casualties: a pursuit to save life and limb.

PubMed

Fox, Charles J; Perkins, Jeremy G; Kragh, John F; Singh, Niten N; Patel, Bhavin; Ficke, James R

2010-07-01

Popliteal artery war wounds can bleed severely and historically have high rates of amputation associated with ligation (72%) and repair (32%). More than before, casualties are now surviving the initial medical evacuation and presenting with severely injured limbs that prompt immediate limb salvage decisions in the midst of life-saving maneuvers. A modern analysis of current results may show important changes because previous limb salvage strategies were limited by the resuscitation and surgical techniques of their eras. Because exact comparisons between wars are difficult, the objective of this study was to calculate a worst-case (a pulseless, fractured limb with massive hemorrhage from popliteal artery injury) amputation-free survival rate for the most severely wounded soldiers undergoing immediate reconstruction to save both life and limb. We performed a retrospective study of trauma casualties admitted to the combat support hospital at Ibn Sina Hospital in Baghdad, Iraq, between 2003 and 2007. US military casualties requiring a massive transfusion (> or = 10 blood units transfused within 24 hours of injury) were identified. We extracted data on the subset of casualties with a penetrating supra or infrageniculate popliteal arterial vascular injury. Demographics, injury mechanism, Injury Severity Score, tourniquet use, physiologic parameters, damage control adjuncts, surgical repair techniques, operative time, and outcomes (all-cause 30-day mortality, amputation rates, limb salvage failure, and graft patency) were investigated. Forty-six massively transfused male casualties, median age 24 years (range, 19-54 years; mean Injury Severity Score, 19 +/- 8.0), underwent immediate orthopedic stabilization and vascular reconstruction. There was one early death. The median operative time for the vascular repairs was 217 minutes (range, 94-630 minutes) and included all damage control procedures. Combined arterial and venous injuries occurred in 17 (37%). Ligation was performed for no arterial and 9 venous injuries. Amputations (transtibial or transfemoral) were considered limb salvage failures (14 of 48, 29.2%) and were grouped as immediate (< or = 48 hours, 5), early (>48 hours and < or = 30 days, 6), or late (>30 days, 3). Limb losses were from graft thrombosis, infection, or chronic pain. Combined arterial and venous injuries occurred in 17 (37%). Ligation was performed for no arterial and nine venous injuries. For a median follow-up (excluding death) of 48 months (range, 23-75 months), the amputation-free survival rate was 67%. This study, a worst-case study, showed comparable results to historical controls regarding limb salvage rates (71% for Iraq vs. 56-69% for the Vietnam War). Thirty-day survival (98%), 4-year amputation-free survival (67%), and complication-free rates (35%) fill knowledge gaps. Guidelines for managing popliteal artery injuries show promising results because current resuscitation practices and surgical care yielded similar amputation rates to prior conflicts despite more severe injuries. Significant transfusion requirements and injury severity may not indicate a life-over-limb strategy for popliteal arterial repairs. Future studies of limb salvage failures may help improve casualty care by reducing the complications that directly impact amputation-free survival.

X-ray computed tomography datasets for forensic analysis of vertebrate fossils.

PubMed

Rowe, Timothy B; Luo, Zhe-Xi; Ketcham, Richard A; Maisano, Jessica A; Colbert, Matthew W

2016-06-07

We describe X-ray computed tomography (CT) datasets from three specimens recovered from Early Cretaceous lakebeds of China that illustrate the forensic interpretation of CT imagery for paleontology. Fossil vertebrates from thinly bedded sediments often shatter upon discovery and are commonly repaired as amalgamated mosaics grouted to a solid backing slab of rock or plaster. Such methods are prone to inadvertent error and willful forgery, and once required potentially destructive methods to identify mistakes in reconstruction. CT is an efficient, nondestructive alternative that can disclose many clues about how a specimen was handled and repaired. These annotated datasets illustrate the power of CT in documenting specimen integrity and are intended as a reference in applying CT more broadly to evaluating the authenticity of comparable fossils.

X-ray computed tomography datasets for forensic analysis of vertebrate fossils

PubMed Central

Rowe, Timothy B.; Luo, Zhe-Xi; Ketcham, Richard A.; Maisano, Jessica A.; Colbert, Matthew W.

2016-01-01

We describe X-ray computed tomography (CT) datasets from three specimens recovered from Early Cretaceous lakebeds of China that illustrate the forensic interpretation of CT imagery for paleontology. Fossil vertebrates from thinly bedded sediments often shatter upon discovery and are commonly repaired as amalgamated mosaics grouted to a solid backing slab of rock or plaster. Such methods are prone to inadvertent error and willful forgery, and once required potentially destructive methods to identify mistakes in reconstruction. CT is an efficient, nondestructive alternative that can disclose many clues about how a specimen was handled and repaired. These annotated datasets illustrate the power of CT in documenting specimen integrity and are intended as a reference in applying CT more broadly to evaluating the authenticity of comparable fossils. PMID:27272251

Destabilization of the MutSα’s protein-protein interface due to binding to the DNA adduct induced by anticancer agent Carboplatin via molecular dynamics simulations

PubMed Central

Negureanu, Lacramioara; Salsbury, Freddie R

2013-01-01

DNA mismatch repair (MMR) proteins maintain genetic integrity in all organisms by recognizing and repairing DNA errors. Such alteration of hereditary information can lead to various diseases, including cancer. Besides their role in DNA repair, MMR proteins detect and initiate cellular responses to certain type of DNA damage. Its response to the damaged DNA has made the human MMR pathway a useful target for anticancer agents such as carboplatin. This study indicates that strong, specific interactions at the interface of MutSα in response to the mismatched DNA recognition are replaced by weak, non-specific interactions in response to the damaged DNA recognition. Data suggest a severe impairment of the dimerization of MutSα in response to the damaged DNA recognition. While the core of MutSα is preserved in response to the damaged DNA recognition, the loss of contact surface and the rearrangement of contacts at the protein interface suggest a different packing in response to the damaged DNA recognition. Coupled in response to the mismatched DNA recognition, interaction energies, hydrogen bonds, salt bridges, and solvent accessible surface areas at the interface of MutSα and within the subunits are uncoupled or asynchronously coupled in response to the damaged DNA recognition. These pieces of evidence suggest that the loss of a synchronous mode of response in the MutSα’s surveillance for DNA errors would possible be one of the mechanism(s) of signaling the MMR-dependent programed cell death much wanted in anticancer therapies. The analysis was drawn from dynamics simulations. PMID:24061854

Mechanical Strength of the Side-to-Side Versus Pulvertaft Weave Tendon Repair

PubMed Central

Brown, Stephen H. M.; Hentzen, Eric R.; Kwan, Alan; Ward, Samuel R.; Fridén, Jan; Lieber, Richard L.

2010-01-01

Purpose The side-to-side (SS) tendon suture technique was designed to function as a repair that permits immediate post-operative activation and mobilization of a transferred muscle. This study was designed to test the strength and stiffness of the SS technique against a variation of the Pulvertaft (PT) repair technique. Methods Flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) tendons were harvested from four fresh cadavers and used as a model system. Seven SS and six PT repairs were performed using the FDS as the donor and the FDP as the recipient tendon. For SS repairs, the FDS was woven through one incision in the FDP, and was joined with four cross-stitch running sutures down both sides, and one double-loop suture at each tendon free end; for PT repairs, FDS was woven through three incisions in FDP, joined with a double-loop suture at both ends of the overlap, and four evenly spaced mattress sutures between the ends. Tendon repairs were placed in a tensile testing machine, pre-conditioned and tested to failure. Results There were no statistically significant differences in cross-sectional area (p=0.99) or initial length (p=0.93) between SS and PT repairs. Therefore, all comparisons between methods were made using measures of loads and deformations, rather than stresses and strains.. All failures occurred in the repair region, rather than at the clamps. However, failure mechanisms were different between the two techniques—PT repairs failed by the suture knots either slipping or pulling through the tendon material, followed by the FDS tendon pulling through the FDP tendon; SS repairs failed by shearing of fibers within the FDS. Load at first failure (p < 0.01), ultimate load (p < 0.001), and repair stiffness (p < 0.05) were all significantly different between SS and PT techniques; in all cases the mean value for SS was higher than for PT. Discussion The SS repair, using a cross-stitch suture technique, was significantly stronger and stiffer compared to the PT repair using a mattress suture technique. This suggests that using SS repairs could enable patients to load the repair soon after surgery. Ultimately, this should reduce the risk of developing adhesions and result in improved functional outcome and fewer complications in the acute post-operative period. Future work will address the specific mechanisms (for example, suture-throw technique, tendon-weave technique) that underlie the improved strength and stiffness of the SS repair. PMID:20223604

Mismatch repair gene MSH3 polymorphism is associated with the risk of sporadic prostate cancer.

PubMed

Hirata, Hiroshi; Hinoda, Yuji; Kawamoto, Ken; Kikuno, Nobuyuki; Suehiro, Yutaka; Okayama, Naoko; Tanaka, Yuichiro; Dahiya, Rajvir

2008-05-01

The mismatch repair system is a DNA repair mechanism that corrects mispaired bases during DNA replication errors. Cancer cells deficient in MMR proteins have a 10(2) to 10(3)-fold increase in the mutation rate. Single nucleotide polymorphisms of mismatch repair genes have been shown to cause a decrease in DNA repair activity. We hypothesized that mismatch repair gene polymorphism could be a risk factor for prostate cancer and p53 Pro/Pro genotype carriers could influence MSH3 and MSH6 polymorphisms. DNA samples from 110 patients with prostate cancer and 110 healthy controls were analyzed by single strand conformational polymorphism and polymerase chain reaction-restriction fragment length polymorphism to determine the genotypic frequency of 5 polymorphic loci on 2 MMR genes (MSH3 and MSH6) and p53 codon72. The chi-square test was applied to compare genotype frequency between patients and controls. A significant increase in the G/A+A/A genotype of MSH3 Pro222Pro was observed in patients compared to controls (OR 1.87, 95% CI 1.0-3.5). The frequency of A/G + G/G genotypes of MSH3 exon23 Thr1036Ala also tended to increase in patients (OR 1.57, 95% CI 0.92-2.72). In p53 codon72 Arg/Pro + Pro/Pro carriers the frequency of the AG + GG genotype of MSH3 exon23 was significantly increased in patients compared to controls (OR 2.1, 95% CI 1.05-4.34). To our knowledge this is the first report of the association of MSH3 gene polymorphisms in prostate cancer. These results suggest that the MSH3 polymorphism may be a risk factor for prostate cancer.

Modeling Non-homologous End Joining

NASA Technical Reports Server (NTRS)

Li, Yongfeng

2013-01-01

Non-homologous end joining (NHEJ) is the dominant DNA double strand break (DSB) repair pathway and involves several NHEJ proteins such as Ku, DNA-PKcs, XRCC4, Ligase IV and so on. Once DSBs are generated, Ku is first recruited to the DNA end, followed by other NHEJ proteins for DNA end processing and ligation. Because of the direct ligation of break ends without the need for a homologous template, NHEJ turns out to be an error-prone but efficient repair pathway. Some mechanisms have been proposed of how the efficiency of NHEJ repair is affected. The type of DNA damage is an important factor of NHEJ repair. For instance, the length of DNA fragment may determine the recruitment efficiency of NHEJ protein such as Ku [1], or the complexity of the DNA breaks [2] is accounted for the choice of NHEJ proteins and subpathway of NHEJ repair. On the other hand, the chromatin structure also plays a role of the accessibility of NHEJ protein to the DNA damage site. In this talk, some mathematical models of NHEJ, that consist of series of biochemical reactions complying with the laws of chemical reaction (e.g. mass action, etc.), will be introduced. By mathematical and numerical analysis and parameter estimation, the models are able to capture the qualitative biological features and show good agreement with experimental data. As conclusions, from the viewpoint of modeling, how the NHEJ proteins are recruited will be first discussed for connection between the classical sequential model [4] and recently proposed two-phase model [5]. Then how the NHEJ repair pathway is affected, by the length of DNA fragment [6], the complexity of DNA damage [7] and the chromatin structure [8], will be addressed

The role of protease-activated receptors PAR-1 and PAR-2 in the repair of 16HBE 14o(-) epithelial cell monolayers in vitro.

PubMed

Ewen, D; Clarke, S L; Smith, J R; Berger, C; Salmon, G; Trevethick, M; Shute, J K

2010-03-01

We recently reported that repair following mechanical wounding of epithelial cell layers in vitro is dependent on fibrin formation and the activity of locally expressed coagulation cascade proteins. Serine proteases of the coagulation cascade are an important group of protease-activated receptor (PAR) activators and PAR-1 to 4 are expressed by the normal bronchial epithelium. We tested the hypothesis that activation of PAR-1 and PAR-2 by coagulation cascade proteases stimulates epithelial repair via effects on fibrin formation. Using mechanically wounded 16HBE 14o(-) epithelial cell layers in culture, we investigated the effect of PAR-1 and PAR-2 agonist peptides, control partially scrambled peptides and PAR-neutralizing antibodies on the rate of repair and fibrin formation. Coagulation factors in culture supernatants were measured by immunoblot. RT-PCR was used to investigate PAR-1, PAR-2 and PGE2 receptor (EP-1 to EP-4) expression in this model and qRT-PCR to quantify responses to wounding. Additionally, we investigated the effect of exogenously added factor Xa (FXa) and neutrophil elastase and the influence of PGE2 and indomethacin on the repair response. PAR-1 and PAR-2 peptide agonists stimulated the rate of repair and enhanced the formation of a fibrin provisional matrix to support the repair process. Conversely, PAR-neutralizing antibodies inhibited repair. Under serum-free culture conditions, 16HBE 14o(-) cells expressed EP-2 and EP-3, but not EP-1 or EP-4, receptors. Wounding induced an increased expression of EP-3 but did not alter EP-2, PAR-1 or PAR-2 expression. In the absence of PAR agonists, there was no evidence for a role for PGE2 in fibrin formation or the repair process. Indomethacin attenuated fibrin formation in wounded cultures only in the presence of the PAR-2 peptide. FXa stimulated epithelial repair while neutrophil elastase reduced the levels of coagulation factors and inhibited repair. Locally expressed serine proteases of the coagulation cascade activate PAR-1 and PAR-2 to enhance fibrin formation and bronchial epithelial repair.

Results of open pararenal abdominal aortic aneurysm repair: single centre series and pooled analysis of literature.

PubMed

van Lammeren, Guus W; Ünlü, Çağdaş; Verschoor, Sjoerd; van Dongen, Eric P; Wille, Jan; van de Pavoordt, Eric Dwm; de Vries-Werson, Debbie Ab; De Vries, Jean-Paul Pm

2017-06-01

Objectives Endovascular treatment of pararenal abdominal aortic aneurysm has gained terrain over the past decade, despite the substantial need for reinterventions during follow-up. However, open repair is still a well-established treatment option. With the current study we report the results of a consecutive series of elective primary open pararenal abdominal aortic aneurysm repair in a tertiary vascular referral centre, combined with an overview of current literature and pooled data analysis of perioperative mortality of open and endovascular pararenal abdominal aortic aneurysm repair. Methods A retrospective analysis of a prospective database of all elective open pararenal abdominal aortic aneurysm repairs in the St. Antonius Hospital between 2005 and 2014 was performed. Primary endpoint was 30-day mortality. Secondary endpoints were 30-day morbidity, new onset dialysis, reintervention free survival, and overall survival during follow-up. Results Between 2005 and 2014, 214 consecutive patients underwent elective open pararenal abdominal aortic aneurysm repair. Mean age was 69.8 (±7.1) years, 82.7% (177/214) were men, and mean abdominal aortic aneurysm diameter was 62 (±11) mm. Thirty-day mortality was 3.4%. Thirty-day morbidity was 27.1%, which predominantly consisted of pneumonia (18.7% (40/214)), cardiac events (3.3% (7/214)), and new onset dialysis (2.8% (6/214)). Estimated five-year overall survival rate was 74.2%. 0.9% (2/214) of patients required abdominal aortic aneurysm-related reintervention, and an additional 2.3% (5/214) required surgical repair of an incisional hernia. Pooled analysis of literature revealed a 30-day mortality of 3.0% for open pararenal repair and 1.9% for fenestrated endovascular repair. Conclusion Open pararenal abdominal aortic aneurysm repair in the era of increasing endovascular options results in acceptable perioperative morbidity and mortality rates. Mid-term reintervention rate is low compared to fenestrated endovascular aneurysm repair. Expertise with open repair still remains essential for treatment of pararenal abdominal aortic aneurysms in the near future, especially for those patients that are declined for endovascular treatment.

Performance analysis of 1-km free-space optical communication system over real atmospheric turbulence channels

NASA Astrophysics Data System (ADS)

Liu, Dachang; Wang, Zixiong; Liu, Jianguo; Tan, Jun; Yu, Lijuan; Mei, Haiping; Zhou, Yusong; Zhu, Ninghua

2017-10-01

The performance of a free-space optical communication system is highly affected by the atmospheric turbulence in terms of scintillation. An optical communication system based on intensity-modulation direct-detection was built with 1-km transmission distance to evaluate the bit error rate (BER) performance over real atmospheric turbulence. 2.5-, 5-, and 10-Gbps data rate transmissions were carried out, where error-free transmission could be achieved during over 37% of the 2.5-Gbps transmissions and over 43% of the 5-Gbps transmissions. In the rest of the transmissions, BER deteriorated as the refractive-index structure constant increased, while the two measured items have almost the same trend.

A phantom study for the comparison of different brands of computed tomography scanners and software packages for endovascular aneurysm repair sizing and planning.

PubMed

Velu, Juliëtte F; Groot Jebbink, Erik; de Vries, Jean-Paul Pm; van der Palen, Job Am; Slump, Cornelis H; Geelkerken, Robert H

2018-04-01

Objectives Correct sizing of endoprostheses used for the treatment of abdominal aortic aneurysms is important to prevent endoleaks and migration. Sizing requires several steps and each step introduces a possible sizing error. The goal of this study was to investigate the magnitude of these errors compared to the golden standard: a vessel phantom. This study focuses on the errors in sizing with three different brands of computed tomography angiography scanners in combination with three reconstruction software packages. Methods Three phantoms with a different diameter, altitude and azimuth were scanned with three computed tomography scanners: Toshiba Aquilion 64-slice, Philips Brilliance iCT 256-slice and Siemens Somatom Sensation 64-slice. The phantom diameters were determined in the stretched view after central lumen line reconstruction by three observers using Simbionix PROcedure Rehearsal Studio, 3mensio and TeraRecon planning software. The observers, all novices in sizing endoprostheses using planning software, measured 108 slices each. Two senior vascular surgeons set the tolerated error margin of sizing on ±1.0 mm. Results In total, 11.3% of the measurements (73/648) were outside the set margins of ±1.0 mm from the phantom diameter, with significant differences between the scanner types (14.8%, 12.1%, 6.9% for the Siemens scanner, Philips scanner and Toshiba scanner, respectively, p-value = 0.032), but not between the software packages (8.3%, 11.1%, 14.4%, p-value = 0.141) or the observers (10.6%, 9.7%, 13.4%, p-value = 0.448). Conclusions It can be concluded that the errors in sizing were independent of the used software packages, but the phantoms scanned with Siemens scanner were significantly more measured incorrectly than the phantoms scanned with the Toshiba scanner. Consequently, awareness on the type of computed tomography scanner and computed tomography scanner setting is necessary, especially in complex abdominal aortic aneurysms sizing for fenestrated or branched endovascular aneurysm repair if appropriate the sizing is of upmost importance.

Utilizing measure-based feedback in control-mastery theory: A clinical error.

PubMed

Snyder, John; Aafjes-van Doorn, Katie

2016-09-01

Clinical errors and ruptures are an inevitable part of clinical practice. Often times, therapists are unaware that a clinical error or rupture has occurred, leaving no space for repair, and potentially leading to patient dropout and/or less effective treatment. One way to overcome our blind spots is by frequently and systematically collecting measure-based feedback from the patient. Patient feedback measures that focus on the process of psychotherapy such as the Patient's Experience of Attunement and Responsiveness scale (PEAR) can be used in conjunction with treatment outcome measures such as the Outcome Questionnaire 45.2 (OQ-45.2) to monitor the patient's therapeutic experience and progress. The regular use of these types of measures can aid clinicians in the identification of clinical errors and the associated patient deterioration that might otherwise go unnoticed and unaddressed. The current case study describes an instance of clinical error that occurred during the 2-year treatment of a highly traumatized young woman. The clinical error was identified using measure-based feedback and subsequently understood and addressed from the theoretical standpoint of the control-mastery theory of psychotherapy. An alternative hypothetical response is also presented and explained using control-mastery theory. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Making classical ground-state spin computing fault-tolerant.

PubMed

Crosson, I J; Bacon, D; Brown, K R

2010-09-01

We examine a model of classical deterministic computing in which the ground state of the classical system is a spatial history of the computation. This model is relevant to quantum dot cellular automata as well as to recent universal adiabatic quantum computing constructions. In its most primitive form, systems constructed in this model cannot compute in an error-free manner when working at nonzero temperature. However, by exploiting a mapping between the partition function for this model and probabilistic classical circuits we are able to show that it is possible to make this model effectively error-free. We achieve this by using techniques in fault-tolerant classical computing and the result is that the system can compute effectively error-free if the temperature is below a critical temperature. We further link this model to computational complexity and show that a certain problem concerning finite temperature classical spin systems is complete for the complexity class Merlin-Arthur. This provides an interesting connection between the physical behavior of certain many-body spin systems and computational complexity.

Rectifying calibration error of Goldmann applanation tonometer is easy!

PubMed

Choudhari, Nikhil S; Moorthy, Krishna P; Tungikar, Vinod B; Kumar, Mohan; George, Ronnie; Rao, Harsha L; Senthil, Sirisha; Vijaya, Lingam; Garudadri, Chandra Sekhar

2014-11-01

Purpose: Goldmann applanation tonometer (GAT) is the current Gold standard tonometer. However, its calibration error is common and can go unnoticed in clinics. Its company repair has limitations. The purpose of this report is to describe a self-taught technique of rectifying calibration error of GAT. Materials and Methods: Twenty-nine slit-lamp-mounted Haag-Streit Goldmann tonometers (Model AT 900 C/M; Haag-Streit, Switzerland) were included in this cross-sectional interventional pilot study. The technique of rectification of calibration error of the tonometer involved cleaning and lubrication of the instrument followed by alignment of weights when lubrication alone didn't suffice. We followed the South East Asia Glaucoma Interest Group's definition of calibration error tolerance (acceptable GAT calibration error within ±2, ±3 and ±4 mm Hg at the 0, 20 and 60-mm Hg testing levels, respectively). Results: Twelve out of 29 (41.3%) GATs were out of calibration. The range of positive and negative calibration error at the clinically most important 20-mm Hg testing level was 0.5 to 20 mm Hg and -0.5 to -18 mm Hg, respectively. Cleaning and lubrication alone sufficed to rectify calibration error of 11 (91.6%) faulty instruments. Only one (8.3%) faulty GAT required alignment of the counter-weight. Conclusions: Rectification of calibration error of GAT is possible in-house. Cleaning and lubrication of GAT can be carried out even by eye care professionals and may suffice to rectify calibration error in the majority of faulty instruments. Such an exercise may drastically reduce the downtime of the Gold standard tonometer.

Control of free-flying space robot manipulator systems

NASA Technical Reports Server (NTRS)

Cannon, Robert H., Jr.

1990-01-01

New control techniques for self contained, autonomous free flying space robots were developed and tested experimentally. Free flying robots are envisioned as a key element of any successful long term presence in space. These robots must be capable of performing the assembly, maintenance, and inspection, and repair tasks that currently require human extravehicular activity (EVA). A set of research projects were developed and carried out using lab models of satellite robots and a flexible manipulator. The second generation space robot models use air cushion vehicle (ACV) technology to simulate in 2-D the drag free, zero g conditions of space. The current work is divided into 5 major projects: Global Navigation and Control of a Free Floating Robot, Cooperative Manipulation from a Free Flying Robot, Multiple Robot Cooperation, Thrusterless Robotic Locomotion, and Dynamic Payload Manipulation. These projects are examined in detail.

Alternative end-joining pathway(s): bricolage at DNA breaks.

PubMed

Frit, Philippe; Barboule, Nadia; Yuan, Ying; Gomez, Dennis; Calsou, Patrick

2014-05-01

To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Integrity of immunoglobulin variable regions is supported by GANP during AID-induced somatic hypermutation in germinal center B cells

PubMed Central

Eid, Mohammed Mansour Abbas; Shimoda, Mayuko; Singh, Shailendra Kumar; Almofty, Sarah Ameen; Pham, Phuong; Goodman, Myron F.; Maeda, Kazuhiko; Sakaguchi, Nobuo

2017-01-01

Abstract Immunoglobulin affinity maturation depends on somatic hypermutation (SHM) in immunoglobulin variable (IgV) regions initiated by activation-induced cytidine deaminase (AID). AID induces transition mutations by C→U deamination on both strands, causing C:G→T:A. Error-prone repairs of U by base excision and mismatch repairs (MMRs) create transversion mutations at C/G and mutations at A/T sites. In Neuberger’s model, it remained to be clarified how transition/transversion repair is regulated. We investigate the role of AID-interacting GANP (germinal center-associated nuclear protein) in the IgV SHM profile. GANP enhances transition mutation of the non-transcribed strand G and reduces mutation at A, restricted to GYW of the AID hotspot motif. It reduces DNA polymerase η hotspot mutations associated with MMRs followed by uracil-DNA glycosylase. Mutation comparison between IgV complementary and framework regions (FWRs) by Bayesian statistical estimation demonstrates that GANP supports the preservation of IgV FWR genomic sequences. GANP works to maintain antibody structure by reducing drastic changes in the IgV FWR in affinity maturation. PMID:28541550

Space Transportation System (STS)-117 External Tank (ET)-124 Hail Damage Repair Assessment

NASA Technical Reports Server (NTRS)

Wilson, Timmy R.; Gentz, Steven J.; Barth, Timothy S.; Minute, Stephen A.; Flowers, Cody P.; Hamilton, David A.; Null, Cynthia H.; Schafer, Charles F.

2009-01-01

Severe thunderstorms with associated hail and high winds struck the STS-117 stack on February 26, 2007. Peak winds were recorded at 62 knots with hail sizes ranging from 0.3 inch to 0.8 inch in diameter. As a result of the storm, the North Carolina Foam Institute (NCFI) type 24-124 Thermal Protection System (TPS) foam on the liquid oxygen (LO2) ogive acreage incurred significant impact damage. The NCFI on the ET intertank and the liquid hydrogen (LH2) acreage sustained hail damage. The Polymer Development Laboratory (PDL)-1034 foam of the LO2 ice frost ramps (IFRs) and the Super-Lightweight Ablator (SLA) of the LO2 cable tray also suffered minor damage. NASA Engineering and Safety Center (NESC) was asked to assess the technical feasibility of repairing the ET TPS, the reasonableness of conducting those repairs with the vehicle in a vertical, integrated configuration at the Kennedy Space Center (KSC) Vehicle Assemble Building (VAB), and to address attendant human factors considerations including worker fatigue and the potential for error. The outcome of the assessment is recorded in this document.

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets.

PubMed

Pinto-Fernandez, Adan; Kessler, Benedikt M

2016-01-01

Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors.

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

PubMed Central

Pinto-Fernandez, Adan; Kessler, Benedikt M.

2016-01-01

Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors. PMID:27516771

Flow interference in a variable porosity trisonic wind tunnel.

NASA Technical Reports Server (NTRS)

Davis, J. W.; Graham, R. F.

1972-01-01

Pressure data from a 20-degree cone-cylinder in a variable porosity wind tunnel for the Mach range 0.2 to 5.0 are compared to an interference free standard in order to determine wall interference effects. Four 20-degree cone-cylinder models representing an approximate range of percent blockage from one to six were compared to curve-fits of the interference free standard at each Mach number and errors determined at each pressure tap location. The average of the absolute values of the percent error over the length of the model was determined and used as the criterion for evaluating model blockage interference effects. The results are presented in the form of the percent error as a function of model blockage and Mach number.

Effect of retinal defocus on basketball free throw shooting performance.

PubMed

Bulson, Ryan C; Ciuffreda, Kenneth J; Hayes, John; Ludlam, Diana P

2015-07-01

Vision plays a critical role in athletic performance; however, previous studies have demonstrated that a variety of simulated athletic sensorimotor tasks can be surprisingly resilient to retinal defocus (blurred vision). The purpose of the present study was to extend this work to determine the effect of retinal defocus on overall basketball free throw performance, as well as for the factors gender, refractive error and experience. Forty-four young adult participants of both genders were recruited. They had a range of refractive errors and basketball experience. Each performed 20 standard basketball free throws under five lens defocus conditions in a randomised manner: plano, +1.50 D, +3.00 D, +4.50 D and +10.00 D. Overall, free throw performance was significantly reduced under the +10.00 D lens defocus condition only. Previous experience, but neither refractive error nor gender, yielded a statistically significant difference in performance. Consistent with previous studies of complex sensorimotor tasks, basketball free throw performance was resilient to low and moderate levels of retinal defocus. Thus, for a relatively non-dynamic motor task at a fixed far distance, such as the basketball free throw, precise visual clarity was not critical. Other factors such as motor memory may be important. However, in the dynamic athletic competitive environment it is likely that visual clarity plays a more critical role in one's performance level, at least for specific task demands. © 2015 The Authors. Clinical and Experimental Optometry © 2015 Optometry Australia.

Improved slow-light performance of 10 Gb/s NRZ, PSBT and DPSK signals in fiber broadband SBS.

PubMed

Yi, Lilin; Jaouen, Yves; Hu, Weisheng; Su, Yikai; Bigo, Sébastien

2007-12-10

We have demonstrated error-free operations of slow-light via stimulated Brillouin scattering (SBS) in optical fiber for 10-Gb/s signals with different modulation formats, including non-return-to-zero (NRZ), phase-shaped binary transmission (PSBT) and differential phase-shiftkeying (DPSK). The SBS gain bandwidth is broadened by using current noise modulation of the pump laser diode. The gain shape is simply controlled by the noise density function. Super-Gaussian noise modulation of the Brillouin pump allows a flat-top and sharp-edge SBS gain spectrum, which can reduce slow-light induced distortion in case of 10-Gb/s NRZ signal. The corresponding maximal delay-time with error-free operation is 35 ps. Then we propose the PSBT format to minimize distortions resulting from SBS filtering effect and dispersion accompanied with slow light because of its high spectral efficiency and strong dispersion tolerance. The sensitivity of the 10-Gb/s PSBT signal is 5.2 dB better than the NRZ case with a same 35-ps delay. The maximal delay of 51 ps with error-free operation has been achieved. Futhermore, the DPSK format is directly demodulated through a Gaussian-shaped SBS gain, which is achieved using Gaussian-noise modulation of the Brillouin pump. The maximal error-free time delay after demodulation of a 10-Gb/s DPSK signal is as high as 81.5 ps, which is the best demonstrated result for 10-Gb/s slow-light.

Improving the quality of marine geophysical track line data: Along-track analysis

NASA Astrophysics Data System (ADS)

Chandler, Michael T.; Wessel, Paul

2008-02-01

We have examined 4918 track line geophysics cruises archived at the U.S. National Geophysical Data Center (NGDC) using comprehensive error checking methods. Each cruise was checked for observation outliers, excessive gradients, metadata consistency, and general agreement with satellite altimetry-derived gravity and predicted bathymetry grids. Thresholds for error checking were determined empirically through inspection of histograms for all geophysical values, gradients, and differences with gridded data sampled along ship tracks. Robust regression was used to detect systematic scale and offset errors found by comparing ship bathymetry and free-air anomalies to the corresponding values from global grids. We found many recurring error types in the NGDC archive, including poor navigation, inappropriately scaled or offset data, excessive gradients, and extended offsets in depth and gravity when compared to global grids. While ˜5-10% of bathymetry and free-air gravity records fail our conservative tests, residual magnetic errors may exceed twice this proportion. These errors hinder the effective use of the data and may lead to mistakes in interpretation. To enable the removal of gross errors without over-writing original cruise data, we developed an errata system that concisely reports all errors encountered in a cruise. With such errata files, scientists may share cruise corrections, thereby preventing redundant processing. We have implemented these quality control methods in the modified MGD77 supplement to the Generic Mapping Tools software suite.

Suppression of vapor cell temperature error for spin-exchange-relaxation-free magnetometer

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

Lu, Jixi, E-mail: lujixi@buaa.edu.cn; Qian, Zheng; Fang, Jiancheng

2015-08-15

This paper presents a method to reduce the vapor cell temperature error of the spin-exchange-relaxation-free (SERF) magnetometer. The fluctuation of cell temperature can induce variations of the optical rotation angle, resulting in a scale factor error of the SERF magnetometer. In order to suppress this error, we employ the variation of the probe beam absorption to offset the variation of the optical rotation angle. The theoretical discussion of our method indicates that the scale factor error introduced by the fluctuation of the cell temperature could be suppressed by setting the optical depth close to one. In our experiment, we adjustmore » the probe frequency to obtain various optical depths and then measure the variation of scale factor with respect to the corresponding cell temperature changes. Our experimental results show a good agreement with our theoretical analysis. Under our experimental condition, the error has been reduced significantly compared with those when the probe wavelength is adjusted to maximize the probe signal. The cost of this method is the reduction of the scale factor of the magnetometer. However, according to our analysis, it only has minor effect on the sensitivity under proper operating parameters.« less

General error analysis in the relationship between free thyroxine and thyrotropin and its clinical relevance.

PubMed

Goede, Simon L; Leow, Melvin Khee-Shing

2013-01-01

This treatise investigates error sources in measurements applicable to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic set point computation. The hypothalamus-pituitary transfer characteristic (HP curve) describes the relationship between plasma free thyroxine [FT4] and thyrotropin [TSH]. We define the origin, types, causes, and effects of errors that are commonly encountered in TFT measurements and examine how we can interpret these to construct a reliable HP function for set point establishment. The error sources in the clinical measurement procedures are identified and analyzed in relation to the constructed HP model. The main sources of measurement and interpretation uncertainties are (1) diurnal variations in [TSH], (2) TFT measurement variations influenced by timing of thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4] (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4] range, (5) memory effects (rate-independent hysteresis effect). When the main uncertainties in thyroid function tests (TFT) are identified and analyzed, we can find the most acceptable model space with which we can construct the best HP function and the related set point area.

Nonanatomic free cartilage batten grafting with second intention healing for defects on the distal nose.

PubMed

Ibrahimi, Omar A; Campbell, Tracy; Youker, Summer; Eisen, Daniel B

2012-01-01

Defects of the distal nose, particularly the nasal ala, pose a reconstructive challenge due to the lack of loose adjacent tissue and proximity to a free margin. We report our experience using nonanatomic free cartilage batten grafts in combination with second intention healing for nasal ala defects. A retrospective study of distal nose defects repaired using nonanatomic free cartilage batten grafting with second intention healing was performed. Detailed data on the quality of the scar, post-operative complications, free margin distortion, functional impairments, and patient satisfaction were recorded. Digital images were also shown to an experienced fellowship-trained Mohs surgeon to assess the overall aesthetic outcome using a 5-point score ranging from poor to excellent. Sixteen subjects were included in the study. Complications were common, but minor. Five (~31%) subjects had subtle contour depressions, three (~18%) subjects had excessive granulation tissue, two (~12%) subjects had post-operative ear pain at the donor site lasting up to 10 days, and one (~6%) subject had a hypertrophic scar at the recipient site. There were two occurrences (~12%) of mild alar notching but no occurrences of significant alar margin distortion or nasal valve dysfunction. In terms of aesthetic outcome, seven (~43%) were assessed by an independent fellowship-trained Mohs surgeon as having excellent aesthetic outcomes, six (~38%) were very good, and three (~19%) were good. All sixteen subjects reported satisfaction on follow-up evaluation. Nonanatomic free cartilage grafting with second intention healing allows for facile, single-step repair of nasal ala defects with high patient satisfaction and aesthetically pleasing results. This provides an attractive alternative to other flap techniques, skin grafting, and healing via secondary intention.

Exploring the Retrieval Dynamics of Delayed and Final Free Recall: Further Evidence for Temporal-Contextual Search

ERIC Educational Resources Information Center

Unsworth, Nash

2008-01-01

Retrieval dynamics in free recall were explored based on a two-stage search model that relies on temporal-contextual cues. Participants were tested on both delayed and final free recall and correct recalls, errors, and latency measures were examined. In delayed free recall, participants began recall with the first word presented and tended to…

The expanding polymerase universe.

PubMed

Goodman, M F; Tippin, B

2000-11-01

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

Oxidative DNA damage background estimated by a system model of base excision repair

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

Sokhansanj, B A; Wilson, III, D M

Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parametersmore » from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.« less

Lead poisoning in automobile radiator mechanics.

PubMed

Goldman, R H; Baker, E L; Hannan, M; Kamerow, D B

1987-07-23

Exposure to lead occurs during automobile radiator repair when soldered joints are heated, but this relatively common hazard has received little public recognition. We therefore studied lead exposure among automobile radiator mechanics in the Boston area. Twenty-seven shops were surveyed, and most were found to be small and poorly ventilated. Seventy-five workers were interviewed and tested for blood lead and free erythrocyte protoporphyrin levels. Fifty-six of the 75 actually repaired radiators, and they had a mean blood lead level of 37.1 micrograms per deciliter (range, 16 to 73). Thirty-nine percent of these mechanics had levels higher than 40 micrograms per deciliter; hematologic, neurologic, and renal effects are known to develop at or above this blood lead level. Multiple regression analysis showed that the number of radiator repair work stations (an index of exposure) was the variable most significantly associated with increased blood lead levels. We conclude that excessive exposure to lead occurs frequently among radiator repair workers and should be prevented by improved ventilation, engineering controls, and the use of respirators (if indicated) while working.

SU-E-T-377: Inaccurate Positioning Might Introduce Significant MapCheck Calibration Error in Flatten Filter Free Beams

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

Wang, S; Chao, C; Columbia University, NY, NY

2014-06-01

Purpose: This study investigates the calibration error of detector sensitivity for MapCheck due to inaccurate positioning of the device, which is not taken into account by the current commercial iterative calibration algorithm. We hypothesize the calibration is more vulnerable to the positioning error for the flatten filter free (FFF) beams than the conventional flatten filter flattened beams. Methods: MapCheck2 was calibrated with 10MV conventional and FFF beams, with careful alignment and with 1cm positioning error during calibration, respectively. Open fields of 37cmx37cm were delivered to gauge the impact of resultant calibration errors. The local calibration error was modeled as amore » detector independent multiplication factor, with which propagation error was estimated with positioning error from 1mm to 1cm. The calibrated sensitivities, without positioning error, were compared between the conventional and FFF beams to evaluate the dependence on the beam type. Results: The 1cm positioning error leads to 0.39% and 5.24% local calibration error in the conventional and FFF beams respectively. After propagating to the edges of MapCheck, the calibration errors become 6.5% and 57.7%, respectively. The propagation error increases almost linearly with respect to the positioning error. The difference of sensitivities between the conventional and FFF beams was small (0.11 ± 0.49%). Conclusion: The results demonstrate that the positioning error is not handled by the current commercial calibration algorithm of MapCheck. Particularly, the calibration errors for the FFF beams are ~9 times greater than those for the conventional beams with identical positioning error, and a small 1mm positioning error might lead to up to 8% calibration error. Since the sensitivities are only slightly dependent of the beam type and the conventional beam is less affected by the positioning error, it is advisable to cross-check the sensitivities between the conventional and FFF beams to detect potential calibration errors due to inaccurate positioning. This work was partially supported by a DOD Grant No.; DOD W81XWH1010862.« less

Structural dynamics and interactions of Xeroderma pigmentosum complementation group A (XPA98-210) with damaged DNA.

PubMed

Pradhan, Sushmita; Mattaparthi, Venkata Satish Kumar

2017-10-25

Nucleotide excision repair (NER) in higher organisms repair massive DNA abrasions caused by ultraviolet rays, and various mutagens, where Xeroderma pigmentosum group A (XPA) protein is known to be involved in damage recognition step. Any mutations in XPA cause classical Xeroderma pigmentosum disease. The extent to which XPA is required in the NER is still unclear. Here, we present the comparative study on the structural and conformational changes in globular DNA binding domain of XPA 98-210 in DNA bound and DNA free state. Atomistic molecular dynamics simulation was carried out for both XPA 98-210 systems using AMBER force fields. We observed that XPA 98-210 in presence of damaged DNA exhibited more structural changes compared to XPA 98-210 in its free form. When XPA is in contact with DNA, we found marked stability of the complex due to the formation of characteristic longer antiparallel β-sheets consisting mainly lysine residues.

To repair or not to repair: with FAVOR there is no question

NASA Astrophysics Data System (ADS)

Garetto, Anthony; Schulz, Kristian; Tabbone, Gilles; Himmelhaus, Michael; Scheruebl, Thomas

2016-10-01

In the mask shop the challenges associated with today's advanced technology nodes, both technical and economic, are becoming increasingly difficult. The constant drive to continue shrinking features means more masks per device, smaller manufacturing tolerances and more complexity along the manufacturing line with respect to the number of manufacturing steps required. Furthermore, the extremely competitive nature of the industry makes it critical for mask shops to optimize asset utilization and processes in order to maximize their competitive advantage and, in the end, profitability. Full maximization of profitability in such a complex and technologically sophisticated environment simply cannot be achieved without the use of smart automation. Smart automation allows productivity to be maximized through better asset utilization and process optimization. Reliability is improved through the minimization of manual interactions leading to fewer human error contributions and a more efficient manufacturing line. In addition to these improvements in productivity and reliability, extra value can be added through the collection and cross-verification of data from multiple sources which provides more information about our products and processes. When it comes to handling mask defects, for instance, the process consists largely of time consuming manual interactions that are error prone and often require quick decisions from operators and engineers who are under pressure. The handling of defects itself is a multiple step process consisting of several iterations of inspection, disposition, repair, review and cleaning steps. Smaller manufacturing tolerances and features with higher complexity contribute to a higher number of defects which must be handled as well as a higher level of complexity. In this paper the recent efforts undertaken by ZEISS to provide solutions which address these challenges, particularly those associated with defectivity, will be presented. From automation of aerial image analysis to the use of data driven decision making to predict and propose the optimized back end of line process flow, productivity and reliability improvements are targeted by smart automation. Additionally the generation of the ideal aerial image from the design and several repair enhancement features offer additional capabilities to improve the efficiency and yield associated with defect handling.

Wound healing in mammals and amphibians: toward limb regeneration in mammals.

PubMed

Kawasumi, Aiko; Sagawa, Natsume; Hayashi, Shinichi; Yokoyama, Hitoshi; Tamura, Koji

2013-01-01

Mammalian fetal skin regenerates perfectly, but adult skin repairs by the formation of scar tissue. The cause of this imperfect repair by adult skin is not understood. In contrast, wounded adult amphibian (urodeles and anurans) skin is like mammalian fetal skin in that it repairs by regeneration, not scarring. Scar-free wound repair in adult Xenopus is associated with expression of the paired homeobox transcription factor Prx1 by mesenchymal cells of the wound, a feature shared by mesenchymal cells of the regeneration blastema of the axolotl limb. Furthermore, mesenchymal cells of Xenopus skin wounds that harbor the mouse Prx1-limb-enhancer as a transgene exhibit activation of the enhancer despite the fact that they are Xenopus cells, suggesting that the mouse Prx1 enhancer possesses all elements required for its activation in skin wound healing, even though activation of the same enhancer in the mouse is not seen in the wounded skin of an adult mouse. Elucidation of the role of the Prx1 gene in amphibian skin wound healing will help to clarify the molecular mechanisms of scarless wound healing. Shifting the molecular mechanism of wound repair in mammals to that of amphibians, including reactivation of the Prx1-limb-enhancer, will be an important clue to stimulate scarless wound repair in mammalian adult skin. Finding or creating Prx1-positive stem cells in adult mammal skin by activating the Prx1-limb-enhancer may be a fast and reliable way to provide for scarless skin wound repair, and even directly lead to limb regeneration in mammals.

Increasing the Elective Endovascular to Open Repair Ratio of Popliteal Artery Aneurysm.

PubMed

Wrede, Axel; Wiberg, Frans; Acosta, Stefan

2018-02-01

Open repair (OR) for popliteal artery aneurysm (PAA) has recently been challenged by endovascular repair (ER) as the primary choice of treatment. The aim of the present study was to evaluate time trends in treatment modality and compare outcomes between OR and ER among electively operated patients after start of screening in 2010 for abdominal aortic aneurysm (AAA), a disease highly associated with PAA. Between January 1, 2009, and April 30, 2017, 102 procedures and 36 acute and 66 elective repairs for PAA were identified. Over time, a trend ( P = .089) for an increasing elective to acute repair ratio of PAA and an increase in elective ER to OR ratio ( P = .003) was found. Among electively repaired PAAs, the ER group was older ( P = .047) and had a higher ankle-brachial index (ABI; P = .044). The ER group had fewer wound infections ( P = .003), fewer major bleeding complications ( P = .046), and shorter in-hospital stay ( P < .001). After 1 year of follow-up, the ER group had a higher rate of major amputations ( P = .037). Amputation-free survival at the end of follow-up did not differ between groups ( P = .68). Among the 17 patients with PAA eligible for AAA screening, 4 (24%) were diagnosed with PAA through the screening program of AAA. The epidemiology of elective repair of PAA has changed toward increased ER, although ER showed a higher rate of major amputations at 1 year. Confounding was considerable and a randomized trial is needed for evaluation of the best therapeutic option.

Generalized time-dependent model of radiation-induced chromosomal aberrations in normal and repair-deficient human cells.

PubMed

Ponomarev, Artem L; George, Kerry; Cucinotta, Francis A

2014-03-01

We have developed a model that can simulate the yield of radiation-induced chromosomal aberrations (CAs) and unrejoined chromosome breaks in normal and repair-deficient cells. The model predicts the kinetics of chromosomal aberration formation after exposure in the G₀/G₁ phase of the cell cycle to either low- or high-LET radiation. A previously formulated model based on a stochastic Monte Carlo approach was updated to consider the time dependence of DNA double-strand break (DSB) repair (proper or improper), and different cell types were assigned different kinetics of DSB repair. The distribution of the DSB free ends was derived from a mechanistic model that takes into account the structure of chromatin and DSB clustering from high-LET radiation. The kinetics of chromosomal aberration formation were derived from experimental data on DSB repair kinetics in normal and repair-deficient cell lines. We assessed different types of chromosomal aberrations with the focus on simple and complex exchanges, and predicted the DSB rejoining kinetics and misrepair probabilities for different cell types. The results identify major cell-dependent factors, such as a greater yield of chromosome misrepair in ataxia telangiectasia (AT) cells and slower rejoining in Nijmegen (NBS) cells relative to the wild-type. The model's predictions suggest that two mechanisms could exist for the inefficiency of DSB repair in AT and NBS cells, one that depends on the overall speed of joining (either proper or improper) of DNA broken ends, and another that depends on geometric factors, such as the Euclidian distance between DNA broken ends, which influences the relative frequency of misrepair.

Redox potentials and pKa for benzoquinone from density functional theory based molecular dynamics.

PubMed

Cheng, Jun; Sulpizi, Marialore; Sprik, Michiel

2009-10-21

The density functional theory based molecular dynamics (DFTMD) method for the computation of redox free energies presented in previous publications and the more recent modification for computation of acidity constants are reviewed. The method uses a half reaction scheme based on reversible insertion/removal of electrons and protons. The proton insertion is assisted by restraining potentials acting as chaperones. The procedure for relating the calculated deprotonation free energies to Brønsted acidities (pK(a)) and the oxidation free energies to electrode potentials with respect to the normal hydrogen electrode is discussed in some detail. The method is validated in an application to the reduction of aqueous 1,4-benzoquinone. The conversion of hydroquinone to quinone can take place via a number of alternative pathways consisting of combinations of acid dissociations, oxidations, or dehydrogenations. The free energy changes of all elementary steps (ten in total) are computed. The accuracy of the calculations is assessed by comparing the energies of different pathways for the same reaction (Hess's law) and by comparison to experiment. This two-sided test enables us to separate the errors related with the restrictions on length and time scales accessible to DFTMD from the errors introduced by the DFT approximation. It is found that the DFT approximation is the main source of error for oxidation free energies.

Error analysis regarding the calculation of nonlinear force-free field

NASA Astrophysics Data System (ADS)

Liu, S.; Zhang, H. Q.; Su, J. T.

2012-02-01

Magnetic field extrapolation is an alternative method to study chromospheric and coronal magnetic fields. In this paper, two semi-analytical solutions of force-free fields (Low and Lou in Astrophys. J. 352:343, 1990) have been used to study the errors of nonlinear force-free (NLFF) fields based on force-free factor α. Three NLFF fields are extrapolated by approximate vertical integration (AVI) Song et al. (Astrophys. J. 649:1084, 2006), boundary integral equation (BIE) Yan and Sakurai (Sol. Phys. 195:89, 2000) and optimization (Opt.) Wiegelmann (Sol. Phys. 219:87, 2004) methods. Compared with the first semi-analytical field, it is found that the mean values of absolute relative standard deviations (RSD) of α along field lines are about 0.96-1.19, 0.63-1.07 and 0.43-0.72 for AVI, BIE and Opt. fields, respectively. While for the second semi-analytical field, they are about 0.80-1.02, 0.67-1.34 and 0.33-0.55 for AVI, BIE and Opt. fields, respectively. As for the analytical field, the calculation error of <| RSD|> is about 0.1˜0.2. It is also found that RSD does not apparently depend on the length of field line. These provide the basic estimation on the deviation of extrapolated field obtained by proposed methods from the real force-free field.

Cloud-free resolution element statistics program

NASA Technical Reports Server (NTRS)

Liley, B.; Martin, C. D.

1971-01-01

Computer program computes number of cloud-free elements in field-of-view and percentage of total field-of-view occupied by clouds. Human error is eliminated by using visual estimation to compute cloud statistics from aerial photographs.

Oxygen-Free Welding Contact Tips

NASA Technical Reports Server (NTRS)

Pike, James F.

1993-01-01

Contact tips for gas/metal arc welding (GMAW) fabricated from oxygen-free copper. Prototype tips tested in robotic welding, for which application intended. Reduces electrical erosion, increases electrical conductivity, and reduces mechanical wear. Productivity of robotic welding increases while time during welding interrupted for removal and replacement of contact tips minimal. Improves alignment of joints and filler metal, reducing rate of rejection and repair of unacceptable weldments. Utility extends beyond aerospace industry to mass production of various types of hardware, including heavy off-highway construction equipment.

Healing of rotator cuff tendons using botulinum toxin A and immobilization in a rat model.

PubMed

Gilotra, Mohit N; Shorofsky, Michael J; Stein, Jason A; Murthi, Anand M

2016-03-15

We evaluated effects of botulinum toxin A (Botox) and cast immobilization on tendon healing in a rat model. Injection of Botox into rat supraspinatus was hypothesized to reduce muscle active force and improved healing. Eighty-four supraspinatus tendons were surgically transected and repaired in 42 Sprague-Dawley rats (transosseous technique). After repair, supraspinatus muscle was injected with saline or Botox (3 or 6 U/kg). Half the shoulders were cast-immobilized for the entire postoperative period; half were allowed free cage activity. Histology was examined at 2, 4, 8, and 12 weeks. A healing zone cross-sectional area was measured, and biomechanical testing of repair strength and tendon viscoelastic properties was conducted at 4 and 12 weeks. Botox alone and cast immobilization alone exhibited increased ultimate load compared with controls (saline injection, no immobilization) at 4 weeks. No difference in ultimate load occurred between Botox-only and cast-only groups. At 12 weeks, the Botox (6 U/kg) plus cast immobilization group was significantly weakest (p < 0.05). A trend was shown toward decreased healing zone cross-sectional areas in casted groups. Supraspinatus Botox injection after rotator cuff repair might help protect the repair. However, cast immobilization plus Botox administration is harmful to rotator cuff healing in a rat tendon model.

Use of a dynamic self-regulating prosthesis (P.A.D.) in inguinal hernia repair: our first experience in 214 patients.

PubMed

Ferranti, Fabrizio; Marzano, Marco; Quintiliani, Alberto

2009-01-01

Numerous techniques exist for inguinal hernia treatment. Currently, open mesh tension-free repair is regarded as the repair method of choice. In particular Lichtenstein repair is the most common procedure performed, although several articles have reported long-lasting postoperative pain and a higher recurrence rate than originally reported. This study describes the P.A.D. (Protesi Autoregolantesi Dinamica) prosthesis implantation technique and reports postoperative complications and long-term results. From June 2002 to May 2005 a total of 214 patients underwent P.A.D. prosthesis inguinal repair. All patients were male, with a mean age of 51 years. All hernias were treated via an open inguinal approach using the original technique described by Valenti, with slight modifications. A total of 171'patients (80%) were available to follow-up 3 years after surgery. Early postoperative complications occurred in 14 patients (8.4%). Four patients (12.1%), who had undergone regional anaesthesia, developed urinary retention. Wound infection occurred in 3 patients (1.4%). There were two direct recurrences (0.93%) whereas chronic postoperative inguinal pain was reported in 4.2% of patients. Within the limitations of a short follow-up, our results show that the P.A.D. prosthesis procedure is a reliable technique with a low recurrence rate and low postoperative morbidity.

Pullout repair of a medial meniscus posterior root tear using a FasT-Fix® all-inside suture technique.

PubMed

Kodama, Y; Furumatsu, T; Fujii, M; Tanaka, T; Miyazawa, S; Ozaki, T

2016-11-01

A medial meniscus posterior root tear (MMPRT) may increase the tibiofemoral contact pressure by decreasing the tibiofemoral contact area. Meniscal dysfunction induced by posterior root injury may lead to the development of osteoarthritic knees. Repair of a MMPRT can restore medial meniscus (MM) function and prevent knee osteoarthritis progression. Several surgical procedures have been reported for treating a MMPRT. However, these procedures are associated with several technical difficulties. Here, we describe a technique to stabilize a torn MM posterior root using the FasT-Fix ® all-inside meniscal suture device and a new aiming device. The uncut free-end of the FasT-Fix ® suture can be used as a thread for transtibial pullout repair. Our procedure might help overcome the technical difficulties in arthroscopic treatment of a MMPRT. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Case Report: Use of reinforced buccal mucosa graft over gracilis muscle flap in management of post high intensity focused ultrasound (HIFU) rectourethral fistula.

PubMed

Jai, Shrikant; Ganpule, Arvind; Singh, Abhishek; Vijaykumar, Mohankumar; Bopaiah, Vinod; Sabnis, Ravindra; Desai, Mahesh

2016-01-01

High intensity focused ultrasound (HIFU) has come forward as alternative treatment for carcinoma of the prostate. Though minimally invasive,HIFUhas potential side effects. Urethrorectal fistula is one such rare side effect. Management of these fistulas has been described by Vanni et al. This case report describes points of technique that will help successful management of resilient rectourethral fistula. Urinary and faecal diversion in the form of suprapubic catheter and colostomy is vital. Adequate time between stoma formation, fistula closure and then finally stoma closure is needed. Lithotomy position and perineal approach gives best exposure to the fistula. The rectum should be dissected 2cm above the fistula; this aids in tension free closure of the rectal defect. Similarly buccal mucosal graft was used on the urethra to achieve tension free closure. A good vascular pedicle gracilis muscle flap is used to interpose between the two repairs. This not only provides a physical barrier but also provides a vascular bed for BMG uptake. Perfect haemostasis is essential, as any collection may become a site of infection thus compromising results.  We strongly recommend rectourethral fistula be directly repaired with gracilis muscle flap with reinforced buccal mucosa graft without attempting any less invasive repairs because the "first chance is the best chance".

Case Report: Use of reinforced buccal mucosa graft over gracilis muscle flap in management of post high intensity focused ultrasound (HIFU) rectourethral fistula

PubMed Central

Jai, Shrikant; Ganpule, Arvind; Singh, Abhishek; Vijaykumar, Mohankumar; Bopaiah, Vinod; Sabnis, Ravindra; Desai, Mahesh

2017-01-01

High intensity focused ultrasound (HIFU) has come forward as alternative treatment for carcinoma of the prostate. Though minimally invasive,HIFUhas potential side effects. Urethrorectal fistula is one such rare side effect. Management of these fistulas has been described by Vanni et al. This case report describes points of technique that will help successful management of resilient rectourethral fistula. Urinary and faecal diversion in the form of suprapubic catheter and colostomy is vital. Adequate time between stoma formation, fistula closure and then finally stoma closure is needed. Lithotomy position and perineal approach gives best exposure to the fistula. The rectum should be dissected 2cm above the fistula; this aids in tension free closure of the rectal defect. Similarly buccal mucosal graft was used on the urethra to achieve tension free closure. A good vascular pedicle gracilis muscle flap is used to interpose between the two repairs. This not only provides a physical barrier but also provides a vascular bed for BMG uptake. Perfect haemostasis is essential, as any collection may become a site of infection thus compromising results.  We strongly recommend rectourethral fistula be directly repaired with gracilis muscle flap with reinforced buccal mucosa graft without attempting any less invasive repairs because the “first chance is the best chance”. PMID:28299181

Joint optimization of a partially coherent Gaussian beam for free-space optical communication over turbulent channels with pointing errors.

PubMed

Lee, It Ee; Ghassemlooy, Zabih; Ng, Wai Pang; Khalighi, Mohammad-Ali

2013-02-01

Joint beam width and spatial coherence length optimization is proposed to maximize the average capacity in partially coherent free-space optical links, under the combined effects of atmospheric turbulence and pointing errors. An optimization metric is introduced to enable feasible translation of the joint optimal transmitter beam parameters into an analogous level of divergence of the received optical beam. Results show that near-ideal average capacity is best achieved through the introduction of a larger receiver aperture and the joint optimization technique.

Lossless Brownian Information Engine

NASA Astrophysics Data System (ADS)

Paneru, Govind; Lee, Dong Yun; Tlusty, Tsvi; Pak, Hyuk Kyu

2018-01-01

We report on a lossless information engine that converts nearly all available information from an error-free feedback protocol into mechanical work. Combining high-precision detection at a resolution of 1 nm with ultrafast feedback control, the engine is tuned to extract the maximum work from information on the position of a Brownian particle. We show that the work produced by the engine achieves a bound set by a generalized second law of thermodynamics, demonstrating for the first time the sharpness of this bound. We validate a generalized Jarzynski equality for error-free feedback-controlled information engines.

Lossless Brownian Information Engine.

PubMed

Paneru, Govind; Lee, Dong Yun; Tlusty, Tsvi; Pak, Hyuk Kyu

2018-01-12

We report on a lossless information engine that converts nearly all available information from an error-free feedback protocol into mechanical work. Combining high-precision detection at a resolution of 1 nm with ultrafast feedback control, the engine is tuned to extract the maximum work from information on the position of a Brownian particle. We show that the work produced by the engine achieves a bound set by a generalized second law of thermodynamics, demonstrating for the first time the sharpness of this bound. We validate a generalized Jarzynski equality for error-free feedback-controlled information engines.

Left Ventricular Free Wall Rupture in Acute Myocardial Infarction

PubMed Central

Amir, Offer; Smith, Ronald; Nishikawa, Akaira; Gregoric, Igor D.; Smart, Frank W.

2005-01-01

We describe a case of subacute left ventricular free wall rupture during acute myocardial infarction in a 68-year-old man. The diagnosis was confirmed by echocardiography. The patient was supported by an intra-aortic balloon pump until the ruptured wall could be successfully repaired by suturing and gluing a pericardial patch over the defect and bypassing the left anterior descending coronary artery with a vein graft. This case demonstrates that left ventricular free wall rupture is not always fatal and that early diagnosis and institution of intra-aortic balloon pump support in such patients can allow successful bridging to definitive emergency surgical therapy. PMID:16392235

Approaching a parameter-free metadynamics.

PubMed

Dickson, Bradley M

2011-09-01

We present a unique derivation of metadynamics. This work leads to a more robust understanding of the error in the computed free energy than what has been obtained previously. Moreover, a formula for the exact free energy is introduced. The formula can be used to post-process any existing well-tempered metadynamics data, allowing one, in principle, to obtain an exact free energy regardless of the metadynamics parameters.

Approaching a parameter-free metadynamics

NASA Astrophysics Data System (ADS)

Dickson, Bradley M.

2011-09-01

We present a unique derivation of metadynamics. This work leads to a more robust understanding of the error in the computed free energy than what has been obtained previously. Moreover, a formula for the exact free energy is introduced. The formula can be used to post-process any existing well-tempered metadynamics data, allowing one, in principle, to obtain an exact free energy regardless of the metadynamics parameters.

Does the use of hernia mesh in surgical inguinal hernia repairs cause male infertility? A systematic review and descriptive analysis.

PubMed

Dong, Zhiyong; Kujawa, Stacy Ann; Wang, Cunchuan; Zhao, Hong

2018-04-23

The aim of this study was to systematically review the available clinical trials examining male infertility after inguinal hernias were repaired using mesh procedures. The Cochrane Library, PubMed, Embase, Web of Science, and Chinese Biomedical Medicine Database were investigated. The Jada score was used to evaluate the quality of the studies, "Oxford Centre for Evidence-based Medicine-Levels of Evidence" was used to assess the level of the trials, and descriptive analysis was used to evaluate the studies. Twenty nine related trials with a total of 36,552 patients were investigated, including seven randomized controlled trials (RCTs) with 616 patients and 10 clinical trials (1230 patients) with mesh or non-mesh repairs. The Jada score showed that there were six high quality RCTs and one low quality RCT. Levels of evidence determined from the Oxford Centre for Evidence-based Medicine further demonstrated that those six high quality RCTs also had high levels of evidence. It was found that serum testosterone, LH, and FSH levels declined in the laparoscopic group compared to the open group; however, the testicular volume only slightly increased without statistical significance. Testicular and sexual functions remained unchanged after both laparoscopic transabdominal preperitoneal hernia repair (TAPP) and totally extra-peritoneal repair (TEP). We also compared the different meshes used post-surgeries. VyproII/Timesh lightweight mesh had a diminished effect on sperm motility compared to Marlex heavyweight mesh after a one-year follow-up, but there was no effect after 3 years. Additionally, various open hernia repair procedures (Lichtenstein, mesh plug method, posterior pre-peritoneal mesh repair, and anterior tension-free repair) did not cause infertility. This systematic review suggests that hernia repair with mesh either in an open or a laparoscopic procedure has no significant effect on male fertility.

DNA repair properties of Escherichia coli tif-1, recAo281 and lexA1 strains deficient in single-strand DNA binding protein.

PubMed

Whittier, R F; Chase, J W

1983-01-01

Mutations affecting single-strand DNA binding protein (SSB) impair induction of mutagenic (SOS) repair. To further investigate the role of SSB in SOS induction and DNA repair, isogenic strains were constructed combining the ssb+, ssb-1 or ssb-113 alleles with one or more mutations known to alter regulation of damage inducible functions. As is true in ssb+ strains tif-1 (recA441) was found to allow thermal induction of prophage lambda + and Weigle reactivation in ssb-1 and ssb-113 strains. Furthermore, tif-1 decreased the UV sensitivity of the ssb-113 strain slightly and permitted UV induction of prophage lambda + at 30 degrees C. Strains carrying the recAo281 allele were also constructed. This mutation causes high constitutive levels of RecA protein synthesis and relieves much of the UV sensitivity conferred by lexA- alleles without restoring SOS (error-prone) repair. In contrast, the recAo281 allele failed to alleviate the UV sensitivity associated with either ssb- mutation. In a lexA1 recAo281 background the ssb-1 mutation increased the extent of postirradiation DNA degradation and concommitantly increased UV sensitivity 20-fold to the level exhibited by a recA1 strain. The ssb-113 mutation also increased UV sensitivity markedly in this background but did so without greatly increasing postirradiation DNA degradation. These results suggest a direct role for SSB in recombinational repair apart from and in addition to its role in facilitating induction of the recA-lexA regulon.

Randomized controlled trial of accelerated rehabilitation versus standard protocol following surgical repair of ruptured Achilles tendon.

PubMed

Porter, Mark D; Shadbolt, Bruce

2015-05-01

There is no consensus regarding the optimal management of the acutely ruptured Achilles tendon (TA). Functional bracing alone achieves outcomes similar to those of surgical repair. Surgical repair combined with immediate mobilization may improve the clinical outcome further. The purpose of our study was to determine if an accelerated rehabilitation programme following surgical repair of the ruptured TA could improve clinical outcome, relative to the standard protocol. Patients with an acutely ruptured TA were randomly allocated to undergo an accelerated programme (AP) or standard programme (SP), following surgery. Outcome was assessed at 12 months post-surgery using the Achilles tendon Total Rupture Score (ATRS), the heel-raise height and the time taken to return to running. Fifty-one patients completed the study, 25 in the AP group and 26 in the SP group. At 12 months post-surgery, the ATRS results were similar in the two treatment groups (87.46 in AP with standard error (SE) of 0.735 versus 87.12 in SP with SE of 0.75) while the AP group had less lengthening of the TA (0.385 cm, SE 0.166 versus 1.00 cm, SE 0.169) and a more rapid return to running (17.231 weeks, SE 0.401 versus 21.08 weeks, SE 0.409), than the SP group. The accelerated rehabilitation programme resulted in less tendon lengthening, more rapid return to running, but similar ATRS relative to the standard rehabilitation. Immobilization following TA repair may prolong recovery. © 2014 Royal Australasian College of Surgeons.

Calculating the free energy of transfer of small solutes into a model lipid membrane: Comparison between metadynamics and umbrella sampling

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

Bochicchio, Davide; Panizon, Emanuele; Ferrando, Riccardo

2015-10-14

We compare the performance of two well-established computational algorithms for the calculation of free-energy landscapes of biomolecular systems, umbrella sampling and metadynamics. We look at benchmark systems composed of polyethylene and polypropylene oligomers interacting with lipid (phosphatidylcholine) membranes, aiming at the calculation of the oligomer water-membrane free energy of transfer. We model our test systems at two different levels of description, united-atom and coarse-grained. We provide optimized parameters for the two methods at both resolutions. We devote special attention to the analysis of statistical errors in the two different methods and propose a general procedure for the error estimation inmore » metadynamics simulations. Metadynamics and umbrella sampling yield the same estimates for the water-membrane free energy profile, but metadynamics can be more efficient, providing lower statistical uncertainties within the same simulation time.« less

Dynamic Interaction of TTDA with TFIIH Is Stabilized by Nucleotide Excision Repair in Living Cells

PubMed Central

Theil, Arjan F; Mari, Pierre-Olivier; Hoogstraten, Deborah; Ng, Jessica M. Y; Dinant, Christoffel; Hoeijmakers, Jan H. J

2006-01-01

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER. PMID:16669699

Sac ligation in inguinal hernia repair: A meta-analysis of randomized controlled trials.

PubMed

Kao, Chun-Yu; Li, Ching-Li; Lin, Chao-Chun; Su, Chih-Ming; Chen, Chia-Che; Tam, Ka-Wai

2015-07-01

Traditionally, hernia sac ligation during inguinal hernia repair is considered mandatory to prevent postoperative development of hernia. However, ligation may induce postoperative pain. The aim of this study was to evaluate the outcomes of hernia sac ligation after inguinal hernia repair. We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the outcomes of hernia sac ligation for open or laparoscopic inguinal hernia repair. Incidence of hernia recurrence was assessed following the surgery. The secondary outcomes included pain scores and postoperative complications. Five trials were selected and their results were summarized. These 5 trials were published between 1984 and 2014, and the sample sizes ranged from 50 to 467 patients. Four trials had recruited patients with inguinal hernia who underwent open repair, and one study enrolled patients who underwent laparoscopic procedures. We observed no difference in the incidence of hernia recurrence and postoperative complications between the sac ligation and nonligation groups. Postoperatively, the intensity of pain was significantly higher in the ligation group than in the nonligation group at Day 7 (Weight mean difference 1.46; 95% confident interval: 0.98-1.95). Hernia sac ligation was associated with higher postoperative pain, and did not show any benefit over sac nonligation regarding the incidence of recurrence and postoperative complications in patients undergoing open tension-free mesh repair or laparoscopic procedures. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Characterization of the APLF FHA–XRCC1 phosphopeptide interaction and its structural and functional implications

PubMed Central

Kim, Kyungmin; Pedersen, Lars C.; Kirby, Thomas W.; DeRose, Eugene F.

2017-01-01

Abstract Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using crystallographic, NMR, and fluorescence polarization studies. The FHA–FBM interactions exhibit significant pH dependence in the physiological range as a consequence of the atypically high pK values of the phosphoserine and phosphothreonine residues and the preference for a dianionic charge state of FHA-bound pThr. These high pK values are characteristic of the polyanionic peptides typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced by residues flanking the crystallographically-defined recognition motif, apparently as a consequence of non-specific electrostatic interactions, supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain-dependent interaction of XRCC1 with APLF joins repair scaffolds that support single-strand break repair and non-homologous end joining (NHEJ). It is suggested that for double-strand DNA breaks that have initially formed a complex with PARP1 and its binding partner XRCC1, this interaction acts as a backup attempt to intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku and associated NHEJ factors. PMID:29059378

In vivo genome editing as a potential treatment strategy for inherited retinal dystrophies.

PubMed

Yanik, Mert; Müller, Brigitte; Song, Fei; Gall, Jacqueline; Wagner, Franziska; Wende, Wolfgang; Lorenz, Birgit; Stieger, Knut

2017-01-01

In vivo genome editing represents an emerging field in the treatment of monogenic disorders, as it may constitute a solution to the current hurdles in classic gene addition therapy, which are the low levels and limited duration of transgene expression. Following the introduction of a double strand break (DSB) at the mutational site by highly specific endonucleases, such as TALENs (transcription activator like effector nucleases) or RNA based nucleases (clustered regulatory interspaced short palindromic repeats - CRISPR-Cas), the cell's own DNA repair machinery restores integrity to the DNA strand and corrects the mutant sequence, thus allowing the cell to produce protein levels as needed. The DNA repair happens either through the error prone non-homologous end-joining (NHEJ) pathway or with high fidelity through homology directed repair (HDR) in the presence of a DNA donor template. A third pathway called microhomology mediated endjoining (MMEJ) has been recently discovered. In this review, the authors focus on the different DNA repair mechanisms, the current state of the art tools for genome editing and the particularities of the retina and photoreceptors with regard to in vivo therapeutic approaches. Finally, current attempts in the field of retinal in vivo genome editing are discussed and future directions of research identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acoustic evidence for phonologically mismatched speech errors.

PubMed

Gormley, Andrea

2015-04-01

Speech errors are generally said to accommodate to their new phonological context. This accommodation has been validated by several transcription studies. The transcription methodology is not the best choice for detecting errors at this level, however, as this type of error can be difficult to perceive. This paper presents an acoustic analysis of speech errors that uncovers non-accommodated or mismatch errors. A mismatch error is a sub-phonemic error that results in an incorrect surface phonology. This type of error could arise during the processing of phonological rules or they could be made at the motor level of implementation. The results of this work have important implications for both experimental and theoretical research. For experimentalists, it validates the tools used for error induction and the acoustic determination of errors free of the perceptual bias. For theorists, this methodology can be used to test the nature of the processes proposed in language production.

When is Testing Sufficient

NASA Technical Reports Server (NTRS)

Rosenberg, Linda H.; Arthur, James D.; Stapko, Ruth K.; Davani, Darush

1999-01-01

The Software Assurance Technology Center (SATC) at NASA Goddard Space Flight Center has been investigating how projects can determine when sufficient testing has been completed. For most projects, schedules are underestimated, and the last phase of the software development, testing, must be decreased. Two questions are frequently asked: "To what extent is the software error-free? " and "How much time and effort is required to detect and remove the remaining errors? " Clearly, neither question can be answered with absolute certainty. Nonetheless, the ability to answer these questions with some acceptable level of confidence is highly desirable. First, knowing the extent to which a product is error-free, we can judge when it is time to terminate testing. Secondly, if errors are judged to be present, we can perform a cost/benefit trade-off analysis to estimate when the software will be ready for use and at what cost. This paper explains the efforts of the SATC to help projects determine what is sufficient testing and when is the most cost-effective time to stop testing.

[Female stress urinary incontinence. Surgical repair with pubovaginal sling techniques].

PubMed

Escribano Patiño, Gregorio; Hernández Fernández, Carlos; Subirá Ríos, David; Castaño González, Irene; Moralejo Gárate, Mercedes; Martinez Salamanca, Juan Ignacio

2002-11-01

To review the treatment of female stress urinary incontinence by new systems of tension-free urethral sling TVT type (Tension free vaginal tape) or IVS (intravaginal slingplasty), and the bone anchoring trasvaginal sling procedure Infast. We describe the surgical techniques of the various procedures and perform a bibliographic review on the topic. The pubovaginal sling has become the gold standard in the treatment of female stress urinary incontinence, mainly if there is sphincter intrinsic dysfunction. The concept of tension free medium urethra support has been the most important contribution, that questions the classification of incontinence in types I, II and III, because the pubocervical tension free sling can correct all three. Tension free urethral sling techniques have demonstrated to be effective, minimally invasive with a low complication rate, easily reproducible, and with good continence results in the mid-term.