WorldWideScience

Sample records for repair mechanism choice

  1. DNA DSB repair pathway choice: an orchestrated handover mechanism.

    Science.gov (United States)

    Kakarougkas, A; Jeggo, P A

    2014-03-01

    DNA double strand breaks (DSBs) are potential lethal lesions but can also lead to chromosome rearrangements, a step promoting carcinogenesis. DNA non-homologous end-joining (NHEJ) is the major DSB rejoining process and occurs in all cell cycle stages. Homologous recombination (HR) can additionally function to repair irradiation-induced two-ended DSBs in G2 phase. In mammalian cells, HR predominantly uses a sister chromatid as a template for DSB repair; thus HR functions only in late S/G2 phase. Here, we review current insight into the interplay between HR and NHEJ in G2 phase. We argue that NHEJ represents the first choice pathway, repairing approximately 80% of X-ray-induced DSBs with rapid kinetics. However, a subset of DSBs undergoes end resection and repair by HR. 53BP1 restricts resection, thereby promoting NHEJ. During the switch from NHEJ to HR, 53BP1 is repositioned to the periphery of enlarged irradiation-induced foci (IRIF) via a BRCA1-dependent process. K63-linked ubiquitin chains, which also form at IRIF, are also repositioned as well as receptor-associated protein 80 (RAP80), a ubiquitin binding protein. RAP80 repositioning requires POH1, a proteasome component. Thus, the interfacing barriers to HR, 53BP1 and RAP80 are relieved by POH1 and BRCA1, respectively. Removal of RAP80 from the IRIF core is required for loss of the ubiquitin chains and 53BP1, and for efficient replication protein A foci formation. We propose that NHEJ is used preferentially to HR because it is a compact process that does not necessitate extensive chromatin changes in the DSB vicinity.

  2. Is the Dresden technique a mechanical design of choice suitable for the repair of middle third Achilles tendon ruptures? A biomechanical study.

    Science.gov (United States)

    de la Fuente, C; Carreño-Zillmann, G; Marambio, H; Henríquez, H

    2016-01-01

    To compare the mechanical failure of the Dresden technique for Achilles tendon repair with the double modified Kessler technique controlled repair technique. The maximum resistance of the two repair techniques are also compared. A total of 30 Achilles tendon ruptures in bovine specimens were repaired with an Ethibond(®) suture to 4.5cm from the calcaneal insertion. Each rupture was randomly distributed into one of two surgical groups. After repair, each specimen was subjected to a maximum traction test. The mechanical failure (tendon, suture, or knot) rates (proportions) were compared using the exact Fisher test (α=.05), and the maximum resistances using the Student t test (α=.05). There was a difference in the proportions of mechanical failures, with the most frequent being a tendon tear in the Dresden technique, and a rupture of the suture in the Kessler technique. The repair using the Dresden technique performed in the open mode, compared to the Kessler technique, has a more suitable mechanical design for the repair of middle third Achilles tendon ruptures on developing a higher tensile resistance in 58.7%. However, its most common mechanical failure was a tendon tear, which due to inappropriate loads could lead to lengthening of the Achilles tendon. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. New tools to study DNA double-strand break repair pathway choice.

    Directory of Open Access Journals (Sweden)

    Daniel Gomez-Cabello

    Full Text Available A broken DNA molecule is difficult to repair, highly mutagenic, and extremely cytotoxic. Such breaks can be repaired by homology-independent or homology-directed mechanisms. Little is known about the network that controls the repair pathway choice except that a licensing step for homology-mediated repair exists, called DNA-end resection. The choice between these two repair pathways is a key event for genomic stability maintenance, and an imbalance of the ratio is directly linked with human diseases, including cancer. Here we present novel reporters to study the balance between both repair options in human cells. In these systems, a double-strand break can be alternatively repaired by homology-independent or -dependent mechanisms, leading to the accumulation of distinct fluorescent proteins. These reporters thus allow the balance between both repair pathways to be analyzed in different experimental setups. We validated the reporters by analyzing the effect of protein downregulation of the DNA end resection and non-homologous end-joining pathways. Finally, we analyzed the role of the DNA damage response on double-strand break (DSB repair mechanism selection. Our reporters could be used in the future to understand the roles of specific factors, whole pathways, or drugs in DSB repair pathway choice, or for genome-wide screening. Moreover, our findings can be applied to increase gene-targeting efficiency, making it a beneficial tool for a broad audience in the biological sciences.

  4. Repair Pathway Choices and Consequences at the Double-Strand Break.

    Science.gov (United States)

    Ceccaldi, Raphael; Rondinelli, Beatrice; D'Andrea, Alan D

    2016-01-01

    DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.

  5. [Laparoscopic incisional hernia repair as first therapeutic choice].

    Science.gov (United States)

    Verbo, A; Petito, L; Pedretti, G; Manno, A; Rizzo, G; Masi, A; Coco, C

    2005-08-01

    Incisional hernias are one of the most frequent complications of open abdominal surgery. Historically, the best results have been obtained with the open rives-stoppa approach. This is done by fixing a large piece of prosthetic mesh behind the rectus muscle. Laparoscopic approach allows similar mesh placement with minimal dissection and lower recurrence rate compared to the open mesh repair. Between October 2001 to September 2003, 75 consecutive patients were scheduled to undergo laparoscopic incisional hernia repair with ePTFE mesh (Gore-Tex Dualmesh Plus). Postoperative complications were recorded and analysed. Most were obese affected by multiple wall defects Conversion to open surgery was required in 1 case Postoperative complications occurred 13.3%. Recurrence occurred in one only case. The key to the success of this procedure is avoidance of complications. The laparoscopic approach is safe, effective and relatively complication-free option in the management of patients presenting with a first time or recurrent incisional hernia and recommended as the treatment of choice.

  6. Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.

    Science.gov (United States)

    Lee, Kyung-Jong; Saha, Janapriya; Sun, Jingxin; Fattah, Kazi R; Wang, Shu-Chi; Jakob, Burkhard; Chi, Linfeng; Wang, Shih-Ya; Taucher-Scholz, Gisela; Davis, Anthony J; Chen, David J

    2016-02-29

    Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.

  7. RAG2’s Acidic Hinge Restricts Repair-Pathway Choice and Promotes Genomic Stability

    Directory of Open Access Journals (Sweden)

    Marc A. Coussens

    2013-09-01

    Full Text Available V(DJ recombination-associated DNA double-strand breaks (DSBs are normally repaired by the high-fidelity classical nonhomologous end-joining (cNHEJ machinery. Previous studies implicated the recombination-activating gene (RAG/DNA postcleavage complex (PCC in regulating pathway choice by preventing access to inappropriate repair mechanisms such as homologous recombination (HR and alternative NHEJ (aNHEJ. Here, we report that RAG2’s “acidic hinge,” previously of unknown function, is critical for several key steps. Mutations that reduce the hinge’s negative charge destabilize the PCC, disrupt pathway choice, permit repair of RAG-mediated DSBs by the translocation-prone aNHEJ machinery, and reduce genomic stability in developing lymphocytes. Structural predictions and experimental results support our hypothesis that reduced flexibility of the hinge underlies these outcomes. Furthermore, sequence variants present in the human population reduce the hinge’s negative charge, permit aNHEJ, and diminish genomic integrity.

  8. Careers Canada. Volume 3, Mechanical Repair Occupations.

    Science.gov (United States)

    Department of Manpower and Immigration, Ottawa (Ontario).

    This pamphlet, published by the Canadian Department of Manpower and Immigration, is the third of a Careers-Canada series and describes careers in mechanical repair occupations. The pamphlet is divided into eight major sections: (1) history and importance; (2) fields of work; (3) nature of work (this section is subdivided into automotive repair…

  9. Regulation of DNA double-strand break repair pathway choice

    Institute of Scientific and Technical Information of China (English)

    Meena Shrivastav; Leyma P De Haro; Jac A Nickoloff

    2008-01-01

    DNA double-strand breaks (DSBs) are critical lesions that can result in cell death or a wide variety of genetic alterations including large- or small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR), and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources includ-ing reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1 (XRS2) complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM.

  10. DNA double-strand break repair: a tale of pathway choices

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Xingzhi Xu

    2016-01-01

    Deoxyribonucleic acid double-strand breaks (DSBs) are cytotoxic lesions that must be repaired either through homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways.DSB repair is critical for genome integrity,cellular homeostasis and also constitutes the biological foundation for radiotherapy and the majority of chemotherapy.The choice between HR and NHEJ is a complex yet not completely understood process that will entail more future efforts.Herein we review our current understandings about how the choice is made over an antagonizing balance between p53-binding protein 1 and breast cancer 1 in the context of cell cycle stages,downstream effects,and distinct chromosomal histone marks.These exciting areas of research will surely bring more mechanistic insights about DSB repair and be utilized in the clinical settings.

  11. REPAIR MECHANISM IN FOREIGN LANGUAGE CLASSROOM INTERACTION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper presents practical research on repair mechanismand its four repair trajectories in FL classroom interaction. Thisshows that it is effective and efficient in assisting FL learners todevelop their communicative competence and understand theprocess of language acquisition. Repair strategies that are ofgreat value to FL teachers in FL classroom teaching are also ex-pounded.

  12. MOF phosphorylation by ATM regulates 53BP1-mediated double-strand break repair pathway choice.

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R; Hegde, Muralidhar L; Chakraborty, Sharmistha; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh, Mayank; Ramnarain, Deepti B; Hittelman, Walter N; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K; Ludwig, Thomas; Pandita, Raj K; Tyler, Jessica K; Pandita, Tej K

    2014-07-10

    Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ) or homologous recombination (HR). Here, we report that double-strand breaks (DSBs) induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF colocalizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S and G2 phase but not G1 phase cells. Expression of MOF-T392A also blocks the reduction in DSB-associated 53BP1 seen in wild-type S/G2 phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair, and decreased cell survival following irradiation. These data support a model whereby ATM-mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2 phase.

  13. MOF Phosphorylation by ATM Regulates 53BP1-Mediated Double-Strand Break Repair Pathway Choice

    Directory of Open Access Journals (Sweden)

    Arun Gupta

    2014-07-01

    Full Text Available Cell-cycle phase is a critical determinant of the choice between DNA damage repair by nonhomologous end-joining (NHEJ or homologous recombination (HR. Here, we report that double-strand breaks (DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase phosphorylation (p-T392-MOF and that phosphorylated MOF colocalizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A impedes DNA repair in S and G2 phase but not G1 phase cells. Expression of MOF-T392A also blocks the reduction in DSB-associated 53BP1 seen in wild-type S/G2 phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair, and decreased cell survival following irradiation. These data support a model whereby ATM-mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2 phase.

  14. MOF phosphorylation by ATM regulates 53BP1-mediated DSB repair pathway choice

    Science.gov (United States)

    Gupta, Arun; Hunt, Clayton R.; Hegdec, Muralidhar L.; Chakraborty, Sharmistha; Udayakumar, Durga; Horikoshi, Nobuo; Singh1, Mayank; Ramnarain, Deepti B.; Hittelman, Walter N.; Namjoshi, Sarita; Asaithamby, Aroumougame; Hazra, Tapas K.; Ludwig, Thomas; Pandita, Raj K.; Tyler, Jessica K.; Pandita, Tej K.

    2014-01-01

    Cell cycle phase is a critical determinant of the choice between DNA damage repair by non-homologous end joining (NHEJ) or homologous recombination (HR). Here we report that DSBs induce ATM-dependent MOF (a histone H4 acetyl-transferase) phosphorylation (p-T392-MOF) and that phosphorylated MOF co-localizes with γ-H2AX, ATM, and 53BP1 foci. Mutation of the phosphorylation site (MOF-T392A) impedes DNA repair in S- and G2-phase but not G1-phase cells. Expression of MOF-T392A also reverses the reduction in DSB associated 53BP1 seen in wild type S/G2-phase cells, resulting in enhanced 53BP1 and reduced BRCA1 association. Decreased BRCA1 levels at DSB sites correlates with defective repairosome formation, reduced HR repair and decreased cell survival following irradiation. These data support a model whereby ATM mediated MOF-T392 phosphorylation modulates 53BP1 function to facilitate the subsequent recruitment of HR repair proteins, uncovering a regulatory role for MOF in DSB repair pathway choice during S/G2-phase. PMID:24953651

  15. DNA repair mechanisms in C. elegans

    NARCIS (Netherlands)

    Brouwer, K.|info:eu-repo/dai/nl/336462557

    2009-01-01

    DNA is the carrier of genetic information. DNA is constantly damaged by, for example, UV light and X-rays. Cells can utilize a large number of proteins that can repair the damages, thereby avoiding changes in the DNA sequence. Damages that are not repaired result in an increase in the number of muta

  16. Wound repair and regeneration: Mechanisms, signaling, and translation

    Science.gov (United States)

    Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

    2015-01-01

    The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

  17. RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of 'alternative NHEJ'.

    Science.gov (United States)

    Gigi, Vered; Lewis, Susanna; Shestova, Olga; Mijušković, Martina; Deriano, Ludovic; Meng, Wenzhao; Luning Prak, Eline T; Roth, David B

    2014-06-01

    DNA double-stranded breaks (DSBs) can be repaired by several mechanisms, including classical NHEJ (c-NHEJ) and a poorly defined, error-prone process termed alternative NHEJ (a-NHEJ). How cells choose between these alternatives to join physiologic DSBs remains unknown. Here, we show that deletion of RAG2's C-terminus allows a-NHEJ to repair RAG-mediated DSBs in developing lymphocytes from both c-NHEJ-proficient and c-NHEJ-deficient mice, demonstrating that the V(D)J recombinase influences repair pathway choice in vivo. Analysis of V(D)J junctions revealed that, contrary to expectation, junctional characteristics alone do not reliably distinguish between a-NHEJ and c-NHEJ. These data suggest that a-NHEJ is not necessarily mutagenic, and may be more prevalent than previously appreciated. Whole genome sequencing of a lymphoma arising in a p53(-/-) mouse bearing a C-terminal RAG2 truncation reveals evidence of a-NHEJ and also of aberrant recognition of DNA sequences resembling RAG recognition sites.

  18. DEVELOPMENT OF PERMANENT MECHANICAL REPAIR SLEEVE FOR PLASTIC PIPE

    Energy Technology Data Exchange (ETDEWEB)

    Hitesh Patadia

    2004-09-30

    The report presents a comprehensive summary of the project status related to the development of a permanent mechanical repair fitting intended to be installed on damaged PE mains under blowing gas conditions. Specifically, the product definition has been developed taking into account relevant codes and standards and industry input. A conceptual design for the mechanical repair sleeve has been developed which meets the product definition.

  19. Molecular mechanisms of DNA repair inhibition by caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Selby, C.P.; Sancar, A. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))

    1990-05-01

    Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.

  20. Long-term anisotropic mechanical response of surgical meshes used to repair abdominal wall defects.

    Science.gov (United States)

    Hernández-Gascón, B; Peña, E; Pascual, G; Rodríguez, M; Bellón, J M; Calvo, B

    2012-01-01

    Routine hernia repair surgery involves the implant of synthetic mesh. However, this type of procedure may give rise to pain and bowel incarceration and strangulation, causing considerable patient disability. The purpose of this study was to compare the long-term behaviour of three commercial meshes used to repair the partially herniated abdomen in New Zealand White rabbits: the heavyweight (HW) mesh, Surgipro(®) and lightweight (LW) mesh, Optilene(®), both made of polypropylene (PP), and a mediumweight (MW) mesh, Infinit(®), made of polytetrafluoroethylene (PTFE). The implanted meshes were mechanical and histological assessed at 14, 90 and 180 days post-implant. This behaviour was compared to the anisotropic mechanical behaviour of the unrepaired abdominal wall in control non-operated rabbits. Both uniaxial mechanical tests conducted in craneo-caudal and perpendicular directions and histological findings revealed substantial collagen growth over the repaired hernial defects causing stiffness in the repair zone, and thus a change in the original properties of the meshes. The mechanical behaviour of the healthy tissue in the craneo-caudal direction was not reproduced by any of the implanted meshes after 14 days or 90 days of implant, whereas in the perpendicular direction, SUR and OPT achieved similar behaviour. From a mechanical standpoint, the anisotropic PP-lightweight meshes may be considered a good choice in the long run, which correlates with the structure of the regenerated tissue. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Platinum drugs and DNA repair mechanisms in lung cancer.

    Science.gov (United States)

    Bonanno, Laura; Favaretto, Adolfo; Rosell, Rafael

    2014-01-01

    The standard first-line treatment for around 80% of newly-diagnosed advanced non-small cell lung cancer (NSCLC) is chemotherapy. Currently, patients are allocated to chemotherapy on the basis of clinical conditions, comorbidities and histology. If feasible, platinum-based chemotherapy is considered as the most efficacious option. Due to the heterogeneity in terms of platinum-sensitivity among patients with NSCLC, great efforts have been made in order to identify molecular predictive markers of platinum resistance. Based on the mechanism of action of platinum, several components of DNA repair pathways have been investigated as potential predictive markers. The main DNA repair pathways involved in the repair of platinum-induced DNA damage are nucleotide excision repair and homologous recombination. The most studied potential predictive markers of platinum-sensitivity are Excision Repair Cross Complementing-1 (ERCC1) and Brest Cancer Type-I Susceptibility protein (BRCA1); however, increasing biological knowledge about DNA repair pathways suggests the potential clinical usefulness of integrated analysis of multiple DNA repair components.

  2. Mechanisms and functions of DNA mismatch repair

    Institute of Scientific and Technical Information of China (English)

    Guo MinLi

    2008-01-01

    DNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated dur-ing DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homo-logs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including he-reditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.

  3. Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

    Science.gov (United States)

    Franke, O; Durst, K; Maier, V; Göken, M; Birkholz, T; Schneider, H; Hennig, F; Gelse, K

    2007-11-01

    Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies.

  4. Self-repair networks a mechanism design

    CERN Document Server

    Ishida, Yoshiteru

    2015-01-01

    This book describes the struggle to introduce a mechanism that enables next-generation information systems to maintain themselves. Our generation observed the birth and growth of information systems, and the Internet in particular. Surprisingly information systems are quite different from conventional (energy, material-intensive) artificial systems, and rather resemble biological systems (information-intensive systems). Many artificial systems are designed based on (Newtonian) physics assuming that every element obeys simple and static rules; however, the experience of the Internet suggests a different way of designing where growth cannot be controlled but self-organized with autonomous and selfish agents. This book suggests using game theory, a mechanism design in particular, for designing next-generation information systems which will be self-organized by collective acts with autonomous components. The challenge of mapping a probability to time appears repeatedly in many forms throughout this book. The book...

  5. An end-joining repair mechanism in Escherichia coli

    Science.gov (United States)

    Chayot, Romain; Montagne, Benjamin; Mazel, Didier; Ricchetti, Miria

    2010-01-01

    Bridging broken DNA ends via nonhomologous end-joining (NHEJ) contributes to the evolution and stability of eukaryote genomes. Although some bacteria possess a simplified NHEJ mechanism, the human commensal Escherichia coli is thought to rely exclusively on homology-directed mechanisms to repair DNA double-strand breaks (DSBs). We show here that laboratory and pathogenic E. coli strains possess a distinct end-joining activity that repairs DSBs and generates genome rearrangements. This mechanism, named alternative end-joining (A-EJ), does not rely on the key NHEJ proteins Ku and Ligase-D which are absent in E. coli. Differently from classical NHEJ, A-EJ is characterized by extensive end-resection largely due to RecBCD, by overwhelming usage of microhomology and extremely rare DNA synthesis. We also show that A-EJ is dependent on the essential Ligase-A and independent on Ligase-B. Importantly, mutagenic repair requires a functional Ligase-A. Although generally mutagenic, accurate A-EJ also occurs and is frequent in some pathogenic bacteria. Furthermore, we show the acquisition of an antibiotic-resistance gene via A-EJ, refuting the notion that bacteria gain exogenous sequences only by recombination-dependent mechanisms. This finding demonstrates that E. coli can integrate unrelated, nonhomologous exogenous sequences by end-joining and it provides an alternative strategy for horizontal gene transfer in the bacterial genome. Thus, A-EJ contributes to bacterial genome evolution and adaptation to environmental challenges. Interestingly, the key features of A-EJ also appear in A-NHEJ, an alternative end-joining mechanism implicated in chromosomal translocations associated with human malignancies, and we propose that this mutagenic repair might have originated in bacteria. PMID:20133858

  6. Initiation of DNA double strand break repair: signaling and single-stranded resection dictate the choice between homologous recombination, non-homologous end-joining and alternative end-joining.

    Science.gov (United States)

    Grabarz, Anastazja; Barascu, Aurélia; Guirouilh-Barbat, Josée; Lopez, Bernard S

    2012-01-01

    A DNA double strand break (DSB) is a highly toxic lesion, which can generate genetic instability and profound genome rearrangements. However, DSBs are required to generate diversity during physiological processes such as meiosis or the establishment of the immune repertoire. Thus, the precise regulation of a complex network of processes is necessary for the maintenance of genomic stability, allowing genetic diversity but protecting against genetic instability and its consequences on oncogenesis. Two main strategies are employed for DSB repair: homologous recombination (HR) and non-homologous end-joining (NHEJ). HR is initiated by single-stranded DNA (ssDNA) resection and requires sequence homology with an intact partner, while NHEJ requires neither resection at initiation nor a homologous partner. Thus, resection is an pivotal step at DSB repair initiation, driving the choice of the DSB repair pathway employed. However, an alternative end-joining (A-EJ) pathway, which is highly mutagenic, has recently been described; A-EJ is initiated by ssDNA resection but does not require a homologous partner. The choice of the appropriate DSB repair system, for instance according the cell cycle stage, is essential for genome stability maintenance. In this context, controlling the initial events of DSB repair is thus an essential step that may be irreversible, and the wrong decision should lead to dramatic consequences. Here, we first present the main DSB repair mechanisms and then discuss the importance of the choice of the appropriate DSB repair pathway according to the cell cycle phase. In a third section, we present the early steps of DSB repair i.e., DSB signaling, chromatin remodeling, and the regulation of ssDNA resection. In the last part, we discuss the competition between the different DSB repair mechanisms. Finally, we conclude with the importance of the fine tuning of this network for genome stability maintenance and for tumor protection in fine.

  7. Defective DNA repair mechanisms in prostate cancer: impact of olaparib

    Directory of Open Access Journals (Sweden)

    De Felice F

    2017-03-01

    Full Text Available Francesca De Felice,1 Vincenzo Tombolini,1 Francesco Marampon,2 Angela Musella,3 Claudia Marchetti3 1Department of Radiotherapy, Policlinico Umberto I, “Sapienza” University of Rome, Rome, 2Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, L’Aquila, 3Department of Gynecological and Obstetrical Sciences and Urological Sciences, “Sapienza” University of Rome, Rome, Italy Abstract: The field of prostate oncology has continued to change dramatically. It has truly become a field that is intensely linked to molecular genetic alterations, especially DNA-repair defects. Germline breast cancer 1 gene (BRCA1 and breast cancer 2 gene (BRCA2 mutations are implicated in the highest risk of prostate cancer (PC predisposition and aggressiveness. Poly adenosine diphosphate ribose polymerase (PARP proteins play a key role in DNA repair mechanisms and represent a valid target for new therapies. Olaparib is an oral PARP inhibitor that blocks DNA repair pathway and coupled with BRCA mutated-disease results in tumor cell death. In phase II clinical trials, including patients with advanced castration-resistant PC, olaparib seems to be efficacious and well tolerated. Waiting for randomized phase III trials, olaparib should be considered as a promising treatment option for PC. Keywords: prostate cancer, metastatic disease, castration resistant, BRCA, DNA-repair, PARP, olaparib

  8. Mechanisms of Choice Behavior Shift Using Cue-approach Training

    Directory of Open Access Journals (Sweden)

    Akram eBakkour

    2016-03-01

    Full Text Available Cue-approach training has been shown to effectively shift choices for snack food items by associating a cued button-press motor response to particular food items. Furthermore, attention is biased toward previously cued items, even when the cued item is not chosen for real consumption during a choice phase. However, the exact mechanism by which preferences shift during cue-approach training is not entirely clear. In three experiments, we shed light on the possible underlying mechanisms at play during this novel paradigm: 1 Uncued, wholly predictable motor responses paired with particular food items were not sufficient to elicit a preference shift; 2 Cueing motor responses early – concurrently with food item onset – and thus eliminating the need for heightened top-down attention to the food stimulus in preparation for a motor response also eliminated the shift in food preferences. This finding reinforces our hypothesis that heightened attention at behaviorally relevant points in time is key to changing choice behavior in the cue-approach task; 3 Crucially, indicating choice using eye movements rather than manual button presses preserves the effect, thus demonstrating that the shift in preferences is not governed by a learned motor response but more likely via modulation of subjective value in higher associative regions, consistent with previous neuroimaging results. Cue-approach training drives attention at behaviorally relevant points in time to modulate the subjective value of individual items, providing a mechanism for behavior change that does not rely on external reinforcement and that holds great promise for developing real world behavioral interventions.

  9. Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology

    Institute of Scientific and Technical Information of China (English)

    Sarah C Shuck; Emily A Short; John J Turchi

    2008-01-01

    Repair of bulky DNA adducts by the nucleotide excision repair (NER) pathway is one of the more versatile DNA repair pathways for the removal of DNA lesions. There are two subsets of the NER pathway, global genomic-NER (GG-NER) and transcription-coupled NER (TC-NER), which differ only in the step involving recognition of the DNA lesion. Following recognition of the damage, the sub-pathways then converge for the incision/excision steps and subsequent gap filling and ligation steps. This review will focus on the GGR sub-pathway of NER while the TCR sub-pathway will be covered in another article in this issue. The ability of the NER pathway to repair a wide array of adducts stems, in part, from the mechanisms involved in the initial recognition step of the damaged DNA and results in NER impacting an equally wide array of human physiological responses and events. In this review, the impact of NER on carcinogenesis, neurological function, sensitivity to environmental factors and sensitivity to cancer therapeutics will be discussed. The knowledge generated in our understanding of the NER pathway over the past 40 years has resulted from advances in the fields of animal model systems, mammalian genetics and in vitro biochemistry, as well as from reconstitution studies and structural analyses of the proteins and enzymes that participate in this pathway. Each of these avenues of research has contributed significantly to our understanding of how the NER pathway works and how alterations in NER activity, both positive and negative, influence human biology.

  10. DNA repair mechanisms in eukaryotes: Special focus in Entamoeba histolytica and related protozoan parasites.

    Science.gov (United States)

    López-Camarillo, César; Lopez-Casamichana, Mavil; Weber, Christian; Guillen, Nancy; Orozco, Esther; Marchat, Laurence A

    2009-12-01

    Eukaryotic cell viability highly relies on genome stability and DNA integrity maintenance. The cellular response to DNA damage mainly consists of six biological conserved pathways known as homologous recombination repair (HRR), non-homologous end-joining (NHEJ), base excision repair (BER), mismatch repair (MMR), nucleotide excision repair (NER), and methyltransferase repair that operate in a concerted way to minimize genetic information loss due to a DNA lesion. Particularly, protozoan parasites survival depends on DNA repair mechanisms that constantly supervise chromosomes to correct damaged nucleotides generated by cytotoxic agents, host immune pressure or cellular processes. Here we reviewed the current knowledge about DNA repair mechanisms in the most relevant human protozoan pathogens. Additionally, we described the recent advances to understand DNA repair mechanisms in Entamoeba histolytica with special emphasis in the use of genomic approaches based on bioinformatic analysis of parasite genome sequence and microarrays technology.

  11. Repair of Composites: Design Choices Leading to Lower Life-Cycle Cost

    Science.gov (United States)

    Kassapoglou, Christos; Rangelov, Konstantin; Rangelov, Svilen

    2016-11-01

    The fabrication cost of composite aircraft structures is revisited and the effect of part size on cost is examined with emphasis on design decisions which affect the ease of (bonded) repair and the total cost of the part and subsequent repairs. The case of moderately loaded stiffened fuselage or wing panels under compression is analysed in detail and the fabrication cost of the panel made as a single piece or as an assembly of smaller identical components or modules is determined. The cost of special purpose repairs for two different damage sizes is compared to removing and replacing damaged modules. Hand layup and automated processing are compared. It is found that for certain repair sizes removing and replacing modules leads to lower overall cost as compared to applying a special purpose repair.

  12. Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

    DEFF Research Database (Denmark)

    Bendtsen, Kristian Moss; Juul, Jeppe Søgaard; Trusina, Ala

    2012-01-01

    DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn...... to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity. Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity...... of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders...

  13. Mechanism of DNA loading by the DNA repair helicase XPD.

    Science.gov (United States)

    Constantinescu-Aruxandei, Diana; Petrovic-Stojanovska, Biljana; Penedo, J Carlos; White, Malcolm F; Naismith, James H

    2016-04-07

    The xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor IIH complex in eukaryotes and plays an essential role in DNA repair in the nucleotide excision repair pathway. XPD is a 5' to 3' helicase with an essential iron-sulfur cluster. Structural and biochemical studies of the monomeric archaeal XPD homologues have aided a mechanistic understanding of this important class of helicase, but several important questions remain open. In particular, the mechanism for DNA loading, which is assumed to require large protein conformational change, is not fully understood. Here, DNA binding by the archaeal XPD helicase from Thermoplasma acidophilum has been investigated using a combination of crystallography, cross-linking, modified substrates and biochemical assays. The data are consistent with an initial tight binding of ssDNA to helicase domain 2, followed by transient opening of the interface between the Arch and 4FeS domains, allowing access to a second binding site on helicase domain 1 that directs DNA through the pore. A crystal structure of XPD from Sulfolobus acidocaldiarius that lacks helicase domain 2 has an otherwise unperturbed structure, emphasizing the stability of the interface between the Arch and 4FeS domains in XPD.

  14. Mechanism of DNA loading by the DNA repair helicase XPD

    Science.gov (United States)

    Constantinescu-Aruxandei, Diana; Petrovic-Stojanovska, Biljana; Penedo, J. Carlos; White, Malcolm F.; Naismith, James H.

    2016-01-01

    The xeroderma pigmentosum group D (XPD) helicase is a component of the transcription factor IIH complex in eukaryotes and plays an essential role in DNA repair in the nucleotide excision repair pathway. XPD is a 5′ to 3′ helicase with an essential iron–sulfur cluster. Structural and biochemical studies of the monomeric archaeal XPD homologues have aided a mechanistic understanding of this important class of helicase, but several important questions remain open. In particular, the mechanism for DNA loading, which is assumed to require large protein conformational change, is not fully understood. Here, DNA binding by the archaeal XPD helicase from Thermoplasma acidophilum has been investigated using a combination of crystallography, cross-linking, modified substrates and biochemical assays. The data are consistent with an initial tight binding of ssDNA to helicase domain 2, followed by transient opening of the interface between the Arch and 4FeS domains, allowing access to a second binding site on helicase domain 1 that directs DNA through the pore. A crystal structure of XPD from Sulfolobus acidocaldiarius that lacks helicase domain 2 has an otherwise unperturbed structure, emphasizing the stability of the interface between the Arch and 4FeS domains in XPD. PMID:26896802

  15. DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities

    NARCIS (Netherlands)

    A. Shibata (Atsushi); D. Moiani (Davide); A.S. Arvai (Andrew); J. Perry (Jefferson); S.M. Harding (Shane); M.-M. Genois (Marie-Michelle); R. Maity (Ranjan); S.E. van Rossum-Fikkert (Sari); A. Kertokalio (Aryandi); F. Romoli (Filippo); A. Ismail (Amani); E. Ismalaj (Ermal); E. Petricci (Elena); M.J. Neale (Matthew); R.G. Bristow (Robert); J.-Y. Masson (Jean-Yves); C. Wyman (Claire); P.A. Jeggo (Penny); J.A. Tainer (John)

    2014-01-01

    textabstractMRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employ

  16. DNA Double-Strand Break Repair Pathway Choice Is Directed by Distinct MRE11 Nuclease Activities

    NARCIS (Netherlands)

    A. Shibata (Atsushi); D. Moiani (Davide); A.S. Arvai (Andrew); J. Perry (Jefferson); S.M. Harding (Shane); M.-M. Genois (Marie-Michelle); R. Maity (Ranjan); S.E. van Rossum-Fikkert (Sari); A. Kertokalio (Aryandi); F. Romoli (Filippo); A. Ismail (Amani); E. Ismalaj (Ermal); E. Petricci (Elena); M.J. Neale (Matthew); R.G. Bristow (Robert); J.-Y. Masson (Jean-Yves); C. Wyman (Claire); P.A. Jeggo (Penny); J.A. Tainer (John)

    2014-01-01

    textabstractMRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we

  17. Surgical repair of chronic tears of the hip abductor mechanism.

    Science.gov (United States)

    Davies, Hywel; Zhaeentan, Sohelia; Tavakkolizadeh, Adel; Janes, Gregory

    2009-01-01

    Lateral sided hip pain frequently presents to the orthopaedic clinic. The most common cause of this pain is trochanteric bursitis. This usually improves with conservative treatment. In a few cases it doesn't settle and warrants further investigation and treatment. We present a series of 28 patients who underwent MRI scanning for such pain, 16 were found to have a tear of their abductors. All 16 underwent surgical repair using multiple soft tissue anchors inserted into the greater trochanter of the hip to reattach the abductors. There were 15 females and 1 male. All patients completed a self-administered questionnaire pre-operatively and 1 year post-operatively. Data collected included: A visual analogue score for hip pain, Charnley modification of the Merle D'Aubigne and Postel hip score, Oxford hip score, Kuhfuss score of Trendelenburg and SF36 scores.Of the 16 patients who underwent surgery 5 had a failure of surgical treatment. There were 4 re ruptures, 3 of which were revised and 1 deep infection which required debridement. In the remaining 11 patients there were statistically significant improvements in hip symptoms. The mean change in visual analogue score was 5 out of 10 (p=0.0024) The mean change of Oxford hip score was 20.5 (p=0.00085). The mean improvement in SF-36 PCS was 8.5 (P=0.0020) and MCS 13.7 (P=0.134). 6 patients who had a Trendelenburg gait pre-surgery had normal gait 1 year following surgery.We conclude that hip abductor mechanism tear is a frequent cause of recalcitrant trochanteric pain that should be further investigated with MRI scanning. Surgical repair is a successful operation for reduction of pain and improvement of function. However there is a relatively high failure rate.

  18. Interplay between mechanisms of damage and repair in multiple sclerosis.

    Science.gov (United States)

    Stadelmann, Christine; Brück, Wolfgang

    2008-03-01

    The neuropathology of multiple sclerosis is characterised by focal damage to white matter. However, tissue damage is also present in the cortical grey matter, with a particularly high prevalence of cortical demyelination being observed in secondary progressive and primary progressive forms of the disease. The presence of meningeal B-cell follicle-like structures, which frequently appear during the secondary progressive phase of disease, may be involved in the formation of these subpial cortical lesions. Diffuse white matter inflammation accompanied by axonal damage can also be observed in normal appearing white matter and, again, this is more prominent in chronic progressive forms of multiple sclerosis than in acute stages of disease. Axonal damage is a particularly important component of the pathology of multiple sclerosis and appears to be a critical determinant of clinical outcome. Axons appear to become vulnerable to injury as a result of loss of their myelin sheaths. Remyelination represents an important mechanism of tissue repair in multiple sclerosis and already occurs at an early stage of lesion development and in both white and grey matter lesions. The extent of remyelination appears to be greater in cortical lesions and in lesions further from the ventricles. There is important heterogeneity between patients in terms of the extent of remyelination, which may reflect underlying differences in pathogenetic mechanisms between patients.

  19. Impact of occupational mechanical exposures on risk of lateral and medial inguinal hernia requiring surgical repair

    DEFF Research Database (Denmark)

    Vad, Marie Vestergaard; Frost, Poul; Bay-Nielsen, Morten;

    2012-01-01

    We undertook a register-based cohort study to evaluate exposure-response relations between cumulative occupational mechanical exposures, and risk of lateral and medial inguinal hernia repair.......We undertook a register-based cohort study to evaluate exposure-response relations between cumulative occupational mechanical exposures, and risk of lateral and medial inguinal hernia repair....

  20. Mechanism and Durability of Repair Systems in Polymer-Modified Cement Mortars

    Directory of Open Access Journals (Sweden)

    Ru Wang

    2015-01-01

    Full Text Available This paper investigated the mechanism and durability of repair systems made of ordinary cement-based repair mortar and three kinds of polymer-modified repair mortars with old concrete, SBR dispersion, SAE dispersion, and SAE powder. By comparing the bonding properties of mortars before and after erosion, it was found that polymers could effectively improve the durability of the repair system and SAE powder had the best improvement. Micromorphology study of the repair mortar and the interface of repair mortar with old concrete through SEM showed that the polymer film formed from SAE powder whatever in the mortar or at the interface was dense and tough, the film formed from SAE dispersion was loose and weak, while the film formed from SBR dispersion was in between them, which explained the difference in the tensile bond strength and the durability of the repair systems.

  1. Control of gene editing by manipulation of DNA repair mechanisms.

    Science.gov (United States)

    Danner, Eric; Bashir, Sanum; Yumlu, Saniye; Wurst, Wolfgang; Wefers, Benedikt; Kühn, Ralf

    2017-04-03

    DNA double-strand breaks (DSBs) are produced intentionally by RNA-guided nucleases to achieve genome editing through DSB repair. These breaks are repaired by one of two main repair pathways, classic non-homologous end joining (c-NHEJ) and homology-directed repair (HDR), the latter being restricted to the S/G2 phases of the cell cycle and notably less frequent. Precise genome editing applications rely on HDR, with the abundant c-NHEJ formed mutations presenting a barrier to achieving high rates of precise sequence modifications. Here, we give an overview of HDR- and c-NHEJ-mediated DSB repair in gene editing and summarize the current efforts to promote HDR over c-NHEJ.

  2. A Common Mechanism Underlying Food Choice and Social Decisions.

    Science.gov (United States)

    Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

    2015-10-01

    People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

  3. A Common Mechanism Underlying Food Choice and Social Decisions.

    Directory of Open Access Journals (Sweden)

    Ian Krajbich

    2015-10-01

    Full Text Available People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others' benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making.

  4. A Common Mechanism Underlying Food Choice and Social Decisions

    Science.gov (United States)

    Krajbich, Ian; Hare, Todd; Bartling, Björn; Morishima, Yosuke; Fehr, Ernst

    2015-01-01

    People make numerous decisions every day including perceptual decisions such as walking through a crowd, decisions over primary rewards such as what to eat, and social decisions that require balancing own and others’ benefits. The unifying principles behind choices in various domains are, however, still not well understood. Mathematical models that describe choice behavior in specific contexts have provided important insights into the computations that may underlie decision making in the brain. However, a critical and largely unanswered question is whether these models generalize from one choice context to another. Here we show that a model adapted from the perceptual decision-making domain and estimated on choices over food rewards accurately predicts choices and reaction times in four independent sets of subjects making social decisions. The robustness of the model across domains provides behavioral evidence for a common decision-making process in perceptual, primary reward, and social decision making. PMID:26460812

  5. Effects of scuba diving on vascular repair mechanisms.

    Science.gov (United States)

    Culic, Vedrana Cikes; Van Craenenbroeck, Emeline; Muzinic, Nikolina Rezic; Ljubkovic, Marko; Marinovic, Jasna; Conraads, Viviane; Dujic, Zeljko

    2014-01-01

    A single air dive causes transient endothelial dysfunction. Endothelial progenitor cells (EPCs) and circulating angiogenic cells (CAC) contribute synergistically to endothelial repair. In this study (1) the acute effects of diving on EPC numbers and CAC migration and (2) the influence of the gas mixture (air/nitrox-36) was investigated. Ten divers performed two dives to 18 meters on Day (D) 1 and D3, using air. After 15 days, dives were repeated with nitrox-36. Blood sampling took place before and immediately after diving. Circulating EPCs were quantified by flow cytometry, CAC migration of culture was assessed on D7. When diving on air, a trend for reduced EPC numbers is observed post-dive, which is persistent on D1 and D3. CAC migration tends to improve acutely following diving. These effects are more pronounced with nitrox-36 dives. Diving acutely affects EPC numbers and CAC function, and to a larger extent when diving with nitrox-36. The diving-induced oxidative stress may influence recruitment or survival of EPC. The functional improvement of CAC could be a compensatory mechanism to maintain endothelial homeostasis.

  6. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Directory of Open Access Journals (Sweden)

    Erhong Meng

    2015-07-01

    Full Text Available Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair. Aberrant activation of the Hedgehog (Hh signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  7. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Erhong; Hanna, Ann; Samant, Rajeev S.; Shevde, Lalita A., E-mail: lsamant@uab.edu [Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, WTI320D, 1824 6th Avenue South, Birmingham, AL 35233 (United States)

    2015-07-21

    Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer.

  8. Is Utilitarianism Risky? How the Same Antecedents and Mechanism Produce Both Utilitarian and Risky Choices.

    Science.gov (United States)

    Lucas, Brian J; Galinsky, Adam D

    2015-07-01

    Philosophers and psychologists have long been interested in identifying factors that influence moral judgment. In the current analysis, we compare the literatures on moral psychology and decision making under uncertainty to propose that utilitarian choices are driven by the same forces that lead to risky choices. Spanning from neurocognitive to hormonal to interpersonal levels of analysis, we identify six antecedents that increase both utilitarian and risky choices (ventromedial prefrontal cortex brain lesions, psychopathology, testosterone, incidental positive affect, power, and social connection) and one antecedent that reduces these choices (serotonin activity). We identify the regulation of negative affect as a common mechanism through which the effects of each antecedent on utilitarian and risky choices are explained. By demonstrating that the same forces and the same underlying mechanism that produce risky choices also promote utilitarian choices, we offer a deeper understanding of how basic psychological systems underlie moral judgment. © The Author(s) 2015.

  9. A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining

    DEFF Research Database (Denmark)

    Grabarz, Anastazja; Guirouilh-Barbat, Josée; Barascu, Aurelia

    2013-01-01

    The choice of the appropriate double-strand break (DSB) repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp) generated by alternative end-joining (A-EJ). BLM r...

  10. Thermo-Mechanical Compatibility of Viscoelastic Mortars for Stone Repair

    Directory of Open Access Journals (Sweden)

    Thibault Demoulin

    2016-01-01

    Full Text Available The magnitude of the thermal stresses that originate in an acrylic-based repair material used for the reprofiling of natural sandstone is analyzed. This kind of artificial stone was developed in the late 1970s for its peculiar property of reversibility in an organic solvent. However, it displays a high thermal expansion coefficient, which can be a matter of concern for the durability either of the repair or of the underlying original stone. To evaluate this risk we propose an analytical solution that considers the viscoelasticity of the repair layer. The temperature profile used in the numerical evaluation has been measured in a church where artificial stone has been used in a recent restoration campaign. The viscoelasticity of the artificial stone has been characterized by stress relaxation experiments. The numerical analysis shows that the relaxation time of the repair mortar, originating from a low T g , allows relief of most of the thermal stresses. It explains the good durability of this particular repair material, as observed by the practitioners, and provides a solid scientific basis for considering that the problem of thermal expansion mismatch is not an issue for this type of stone under any possible conditions of natural exposure.

  11. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms

    Science.gov (United States)

    Bezine, Elisabeth; Malaisé, Yann; Loeuillet, Aurore; Chevalier, Marianne; Boutet-Robinet, Elisa; Salles, Bernard; Mirey, Gladys; Vignard, Julien

    2016-01-01

    The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity. PMID:27775089

  12. The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage.

    Science.gov (United States)

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

    The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer.

  13. Refrigeration Controls: Electrical & Mechanical; Appliance Repair 3: 9027.02.

    Science.gov (United States)

    Dade County Public Schools, Miami, FL.

    This booklet outlines a course designed to equip major appliance service students with the fundamental knowledge and understanding of procedures, basic electrical circuitry, and nomenclatures of components necessary in successfully tracing a circuit and repairing or replacing a malfunctioning component. Course content includes goals, specific…

  14. Biological effects of exposure to intermediate neutron and repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi; Sasaki, Masao [Kyoto Univ. (Japan); Onishi, Takeo; Onizuka, Masahiko

    2000-01-01

    An investigation was made on cytotoxic effects of neutron capture using chicken B-cell line mutants, DT40, KURO{sup -/-}, RAD54 {sup -/-} and KU70{sup -/-} / RAD54{sup -/-}. Suspensions of these cells were exposed to two times X-radiation at various doses and the cell surviving was evaluated. The sensitivity to radiation was highest in the double defective mutant, KU70{sup -/-} / RAD54{sup -/-} and followed by that of RAD54 {sup -/-}, a homologous recombination mutant, whereas KURO {sup -/-} cell, a non-homologous end-joining mutant showed a peculiar surviving curve composed of two phases and the cell was highly sensitive to a low-dose radiation. This indicates that there are two different DNA repair systems for double-strand breaks and the system for non-homologous end-joining repair can be involved in all phases of cell cycle, but the system for the homologous one is involved only in S-phase. Therefore, it was thought that variation of sensitivity to radiation exposure depending to the phase of cell cycle might explain the alternation of repair system depending to the phase progressing of cell cycle. It was thus likely that the recovery from radiation injury, which is still a black box might be explained with the double strand breaks of DNA. (M.N.)

  15. Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Farjana Fattah

    2010-02-01

    Full Text Available The repair of DNA double-strand breaks (DSBs is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR and non-homologous end joining (NHEJ. In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or "classic" NHEJ (C-NHEJ pathway and an "alternative" NHEJ (A-NHEJ pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs, XLF, and LIGIV, and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs, XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.

  16. Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Farjana Fattah

    2010-02-01

    Full Text Available The repair of DNA double-strand breaks (DSBs is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR and non-homologous end joining (NHEJ. In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or "classic" NHEJ (C-NHEJ pathway and an "alternative" NHEJ (A-NHEJ pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs, XLF, and LIGIV, and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs, XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.

  17. Mechanisms of renal cell repair and regeneration after acute renal failure.

    Science.gov (United States)

    Nony, Paul A; Schnellmann, Rick G

    2003-03-01

    In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is reversed in over half of those who acquire it. Studies using in vivo and in vitro models have demonstrated the importance of proliferation, migration, and repair of physiological functions of injured renal proximal tubular cells (RPTC) in the reversal of ARF. Growth factors have been shown to produce migration and proliferation of injured RPTC, although the specific mechanisms through which growth factors promote renal regeneration in vivo are unclear. Recently, interactions between integrins and extracellular matrix proteins such as collagen IV were shown to promote the repair of physiological functions in injured RPTC. Specifically, collagen IV synthesis and deposition following cellular injury restored integrin polarity and promoted repair of mitochondrial function and active Na(+) transport. Furthermore, exogenous collagen IV, but not collagen I, fibronectin, or laminin, promoted the repair of physiological functions without stimulating proliferation. These findings suggest the importance of establishing and/or maintaining collagen IV-integrin interactions in the stimulation of repair of physiological functions following sublethal cellular injury. Furthermore, the pathway that stimulates repair is distinct from that of proliferation and migration and may be a viable target for pharmacological intervention.

  18. Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model.

    Science.gov (United States)

    Delacôte, Fabien; Lopez, Bernard S

    2008-01-01

    A DNA double-strand break (DSB) is a highly harmful lesion that can lead to genome rearrangements. Two main pathways compete for DSB repair: homologous recombination (HR) and nonhomologous end-joining (NHEJ). Depending on the cell cycle phase, the choice of one DSB repair pathway over the other will secure genome stability maintenance or in contrast will increase the risk of genetic instability. HR with the sister chromatid is an efficient way to maintain genome stability, for damage occurring at a post-replication stage. However, in G(1) checkpoint-defective cells, DSBs produced in the G(1) phase and not repaired by NHEJ, can progress through S phase and be processed by HR in late S/G(2) phase. We propose the "trans-S DSB repair" model to account for these data. In this situation HR cannot use the sister chromatid (which is also broken at the same locus) and is thus forced to use ectopic homologous sequences dispersed through the genome, increasing the risk of genetic instability. This shows that the two DSB repair pathways can compete through the cell cycle and underlines the importance of the association between the cell cycle checkpoint and the appropriate DNA repair pathway for genome stability maintenance.

  19. Mechanisms and Evidence of Genital Coevolution: The Roles of Natural Selection, Mate Choice, and Sexual Conflict

    National Research Council Canada - National Science Library

    Brennan, Patricia L R; Prum, Richard O

    2015-01-01

    .... Here we review the diverse mechanisms of genital coevolution that include natural selection, female mate choice, male-male competition, and how their interactions generate sexual conflict that can...

  20. DREMECELS: A Curated Database for Base Excision and Mismatch Repair Mechanisms Associated Human Malignancies.

    Directory of Open Access Journals (Sweden)

    Ankita Shukla

    Full Text Available DNA repair mechanisms act as a warrior combating various damaging processes that ensue critical malignancies. DREMECELS was designed considering the malignancies with frequent alterations in DNA repair pathways, that is, colorectal and endometrial cancers, associated with Lynch syndrome (also known as HNPCC. Since lynch syndrome carries high risk (~40-60% for both cancers, therefore we decided to cover all three diseases in this portal. Although a large population is presently affected by these malignancies, many resources are available for various cancer types but no database archives information on the genes specifically for only these cancers and disorders. The database contains 156 genes and two repair mechanisms, base excision repair (BER and mismatch repair (MMR. Other parameters include some of the regulatory processes that have roles in these disease progressions due to incompetent repair mechanisms, specifically BER and MMR. However, our unique database mainly provides qualitative and quantitative information on these cancer types along with methylation, drug sensitivity, miRNAs, copy number variation (CNV and somatic mutations data. This database would serve the scientific community by providing integrated information on these disease types, thus sustaining diagnostic and therapeutic processes. This repository would serve as an excellent accompaniment for researchers and biomedical professionals and facilitate in understanding such critical diseases. DREMECELS is publicly available at http://www.bioinfoindia.org/dremecels.

  1. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Directory of Open Access Journals (Sweden)

    Jinpeng Qi

    Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  2. Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

    Directory of Open Access Journals (Sweden)

    Rajesh P. Rastogi

    2010-01-01

    Full Text Available DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR (mainly UV-B: 280–315 nm is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs, 6-4 photoproducts (6-4PPs, and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER, nucleotide excision repair (NER, and mismatch repair (MMR. Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining, SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms.

  3. Experimental Observation of the Skeletal Adaptive Repair Mechanism and Bionic Topology Optimization Method

    Directory of Open Access Journals (Sweden)

    Kaysar Rahman

    2014-01-01

    Full Text Available Bone adaptive repair theory considers that the external load is the direct source of bone remodeling; bone achieves its maintenance by remodeling some microscopic damages due to external load during the process. This paper firstly observes CT data from the whole self-repairing process in bone defects in rabbit femur. Experimental result shows that during self-repairing process there exists an interaction relationship between spongy bone and enamel bone volume changes of bone defect, that is when volume of spongy bone increases, enamel bone decreases, and when volume of spongy bone decreases, enamel bone increases. Secondly according to this feature a bone remodeling model based on cross-type reaction-diffusion system influenced by mechanical stress is proposed. Finally, this model coupled with finite element method by using the element adding and removing process is used to simulate the self-repairing process and engineering optimization problems by considering the idea of bionic topology optimization.

  4. Thermo-mechanical cracking of a new and laser repair welded die casting die

    Directory of Open Access Journals (Sweden)

    D. Klobčar

    2012-07-01

    Full Text Available The paper presents the analysis of thermo-mechanical fatigue cracking of die casting die during industrial use. An innovative, production friendly approach to monitor the surface crack dimensions was introduced, which is based on measuring defect-fin on the casting part. A new four moulds die casting die was monitored 40 000 cycles in order to complete the production series. The production was stopped three times for laser repair welding of cracks since the defect-fins were not acceptable. The defect-fin heights were measured every 1 000 cycles on the castings before and after repair welding of die surface cracks. The in-service die life can be prolonged with laser repair welding for several times, even thought that in-service die life for a particular repair varies.

  5. Sharpening the ends for repair: mechanisms and regulation of DNA resection

    Institute of Scientific and Technical Information of China (English)

    Sharad C.Paudyal; Zhongsheng You

    2016-01-01

    DNA end resection is a key process in the cellular response to DNA double-strand break damage that is essential for genome maintenance and cell survival.Resection involves selective processing of 5' ends of broken DNA to generate ssDNA overhangs,which in turn control both DNA repair and checkpoint signaling.DNA resection is the first step in homologous recombination-mediated repair and a prerequisite for the activation of the ataxia telangiectasia mutated and Rad3-related (ATR)-dependent checkpoint that coordinates repair with cell cycle progression and other cellular processes.Resection occurs in a cell cycle-dependent manner and is regulated by multiple factors to ensure an optimal amount of ssDNA required for proper repair and genome stability.Here,we review the latest findings on the molecular mechanisms and regulation of the DNA end resection process and their implications for cancer formation and treatment.

  6. Neural mechanisms of dissonance: an fMRI investigation of choice justification.

    Science.gov (United States)

    Kitayama, Shinobu; Chua, Hannah Faye; Tompson, Steven; Han, Shihui

    2013-04-01

    Cognitive dissonance theory proposes that difficult choice produces negatively arousing cognitive conflict (called dissonance), which motivates the chooser to justify her decision by increasing her preference for the chosen option while decreasing her preference for the rejected option. At present, however, neural mechanisms of dissonance are poorly understood. To address this gap of knowledge, we scanned 24 young Americans as they made 60 choices between pairs of popular music CDs. As predicted, choices between CDs that were close (vs. distant) in attractiveness (referred to as difficult vs. easy choices) resulted in activations of the dorsal anterior cingulate cortex (dACC), a brain region associated with cognitive conflict, and the left anterior insula (left aINS), a region often linked with aversive emotional arousal. Importantly, a separate analysis showed that choice-justifying attitude change was predicted by the in-choice signal intensity of the posterior cingulate cortex (PCC), a region that is linked to self-processing. The three regions identified (dACC, left aINS, and PCC) were correlated, within-subjects, across choices. The results were interpreted to support the hypothesis that cognitive dissonance plays a key role in producing attitudes that justify the choice. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. DNA damage by reactive species: Mechanisms, mutation and repair.

    Science.gov (United States)

    Jena, N R

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA-protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA-protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented.

  8. DNA damage by reactive species: Mechanisms, mutation and repair

    Indian Academy of Sciences (India)

    N R Jena

    2012-07-01

    DNA is continuously attacked by reactive species that can affect its structure and function severely. Structural modifications to DNA mainly arise from modifications in its bases that primarily occur due to their exposure to different reactive species. Apart from this, DNA strand break, inter- and intra-strand crosslinks and DNA–protein crosslinks can also affect the structure of DNA significantly. These structural modifications are involved in mutation, cancer and many other diseases. As it has the least oxidation potential among all the DNA bases, guanine is frequently attacked by reactive species, producing a plethora of lethal lesions. Fortunately, living cells are evolved with intelligent enzymes that continuously protect DNA from such damages. This review provides an overview of different guanine lesions formed due to reactions of guanine with different reactive species. Involvement of these lesions in inter- and intra-strand crosslinks, DNA–protein crosslinks and mutagenesis are discussed. How certain enzymes recognize and repair different guanine lesions in DNA are also presented.

  9. Plasticity of intermediate mechanics students’ coordinate system choice

    Directory of Open Access Journals (Sweden)

    Eleanor C. Sayre

    2008-11-01

    Full Text Available We investigate the interplay between mathematics and physics resources in intermediate mechanics students. In the mechanics course, the selection and application of coordinate systems is a consistent thread. At the University of Maine, students often start the course with a strong preference to use Cartesian coordinates, in accordance with their prior physics and mathematics classes. In small-group interviews and in homework help sessions, we ask students to define a coordinate system and set up the equations of motion for a simple pendulum for which polar coordinates are more appropriate. We analyze video data from several encounters using a combination of Process/Object theory and Resource Theory. We find that students sometimes persist in using an inappropriate Cartesian system. Furthermore, students often derive (rather than recall the details of the polar coordinate system, indicating that their knowledge is far from solid. To describe our work more precisely, we define a scale of plasticity and several heuristics for defining resources and their plasticity.

  10. The impact of a firm's internal control mechanisms on the choice of innovation mode

    Institute of Scientific and Technical Information of China (English)

    LIU Xinmin; LI Yuan; SU Zhongfeng; FENG Jinlu

    2007-01-01

    A finn's internal control mechanisms may have a significant influence on the choice of innovation mode. Therefore, based on the research on the internal control mechanisms of companies, we developed a model to explore the relationship between a finn's internal control mechanisms and the choice of innovation mode. Using a sample of 585 Chinese finns, this study tests the proposed model. Results show that strategic control has a positive relationship with radical innovation, but a negative relationship with incremental innovation, while financial control has a negative relationship with radical innovation, but a positive relationship with incremental innovation.

  11. Cetuximab Induces Eme1-Mediated DNA Repair: a Novel Mechanism for Cetuximab Resistance

    Directory of Open Access Journals (Sweden)

    Agnieszka Weinandy

    2014-03-01

    Full Text Available Overexpression of the epidermal growth factor receptor (EGFR is observed in a large number of neoplasms. The monoclonal antibody cetuximab/Erbitux is frequently applied to treat EGFR-expressing tumors. However, the application of cetuximab alone or in combination with radio- and/or chemotherapy often yields only little benefit for patients. In the present study, we describe a mechanism that explains resistance of both tumor cell lines and cultured primary human glioma cells to cetuximab. Treatment of these cells with cetuximab promoted DNA synthesis in the absence of increased proliferation, suggesting that DNA repair pathways were activated. Indeed, we observed that cetuximab promoted the activation of the DNA damage response pathway and prevented the degradation of essential meiotic endonuclease 1 homolog 1 (Eme1, a heterodimeric endonuclease involved in DNA repair. The increased levels of Eme1 were necessary for enhanced DNA repair, and the knockdown of Eme1 was sufficient to prevent efficient DNA repair in response to ultraviolet-C light or megavoltage irradiation. These treatments reduced the survival of tumor cells, an effect that was reversed by cetuximab application. Again, this protection was dependent on Eme1. Taken together, these results suggest that cetuximab initiates pathways that result in the stabilization of Eme1, thereby resulting in enhanced DNA repair. Accordingly, cetuximab enhances DNA repair, reducing the effectiveness of DNA-damaging therapies. This aspect should be considered when using cetuximab as an antitumor agent and suggests that Eme1 is a negative predictive marker.

  12. Ex Ante Efficiency in School Choice Mechanisms: An Experimental Investigation. NBER Working Paper No. 14618

    Science.gov (United States)

    Featherstone, Clayton; Niederle, Muriel

    2008-01-01

    Criteria for evaluating school choice mechanisms are first, whether truth-telling is sometimes punished and second, how efficient the match is. With common knowledge preferences, Deferred Acceptance (DA) dominates the Boston mechanism by the first criterion and is ambiguously ranked by the second. Our laboratory experiments confirm this. A new ex…

  13. Mechanical ventilation injury and repair in extremely and very preterm lungs.

    Directory of Open Access Journals (Sweden)

    Nadine Brew

    Full Text Available BACKGROUND: Extremely preterm infants often receive mechanical ventilation (MV, which can contribute to bronchopulmonary dysplasia (BPD. However, the effects of MV alone on the extremely preterm lung and the lung's capacity for repair are poorly understood. AIM: To characterise lung injury induced by MV alone, and mechanisms of injury and repair, in extremely preterm lungs and to compare them with very preterm lungs. METHODS: Extremely preterm lambs (0.75 of term were transiently exposed by hysterotomy and underwent 2 h of injurious MV. Lungs were collected 24 h and at 15 d after MV. Immunohistochemistry and morphometry were used to characterise injury and repair processes. qRT-PCR was performed on extremely and very preterm (0.85 of term lungs 24 h after MV to assess molecular injury and repair responses. RESULTS: 24 h after MV at 0.75 of term, lung parenchyma and bronchioles were severely injured; tissue space and myofibroblast density were increased, collagen and elastin fibres were deformed and secondary crest density was reduced. Bronchioles contained debris and their epithelium was injured and thickened. 24 h after MV at 0.75 and 0.85 of term, mRNA expression of potential mediators of lung repair were significantly increased. By 15 days after MV, most lung injury had resolved without treatment. CONCLUSIONS: Extremely immature lungs, particularly bronchioles, are severely injured by 2 h of MV. In the absence of continued ventilation these injured lungs are capable of repair. At 24 h after MV, genes associated with injurious MV are unaltered, while potential repair genes are activated in both extremely and very preterm lungs.

  14. DNA Repair and Photoprotection: Mechanisms of Overcoming Environmental Ultraviolet Radiation Exposure in Halophilic Archaea

    Directory of Open Access Journals (Sweden)

    Daniel L. Jones

    2017-09-01

    Full Text Available Halophilic archaea push the limits of life at several extremes. In particular, they are noted for their biochemical strategies in dealing with osmotic stress, low water activity and cycles of desiccation in their hypersaline environments. Another feature common to their habitats is intense ultraviolet (UV radiation, which is a challenge that microorganisms must overcome. The consequences of high UV exposure include DNA lesions arising directly from bond rearrangement of adjacent bipyrimidines, or indirectly from oxidative damage, which may ultimately result in mutation and cell death. As such, these microorganisms have evolved a number of strategies to navigate the threat of DNA damage, which we differentiate into two categories: DNA repair and photoprotection. Photoprotection encompasses damage avoidance strategies that serve as a “first line of defense,” and in halophilic archaea include pigmentation by carotenoids, mechanisms of oxidative damage avoidance, polyploidy, and genomic signatures that make DNA less susceptible to photodamage. Photolesions that do arise are addressed by a number of DNA repair mechanisms that halophilic archaea efficiently utilize, which include photoreactivation, nucleotide excision repair, base excision repair, and homologous recombination. This review seeks to place DNA damage, repair, and photoprotection in the context of halophilic archaea and the solar radiation of their hypersaline environments. We also provide new insight into the breadth of strategies and how they may work together to produce remarkable UV-resistance for these microorganisms.

  15. CtIP-BRCA1 modulates the choice of DNA double-strand break repair pathway throughout the cell cycle

    OpenAIRE

    Yun, Maximina H.; Hiom, Kevin

    2009-01-01

    The repair of DNA double-strand breaks (DSB) is tightly regulated during the cell cycle. In G1 phase, the absence of a sister chromatid means that repair of DSB occurs through non-homologous end-joining (NHEJ) or microhomology-mediated end-joining (MMEJ)1. These pathways often involve loss of DNA sequences at the break site and are therefore error-prone. In late S and G2 phases, even though DNA end-joining pathways remain functional2, there is an increase in repair of DSB by homologous recomb...

  16. Cellular mechanisms of neurovascular damage and repair after stroke.

    Science.gov (United States)

    Arai, Ken; Lok, Josephine; Guo, Shuzhen; Hayakawa, Kazuhide; Xing, Changhong; Lo, Eng H

    2011-09-01

    The biological processes underlying stroke are complex, and patients have a narrow repertoire of therapeutic opportunities. After the National Institutes of Health (NIH) convened the Stroke Progress Review Group in 2001, stroke research shifted from having a purely neurocentric focus to adopting a more integrated view wherein dynamic interactions between all cell types contribute to function and dysfunction in the brain. This so-called "neurovascular unit" provides a conceptual framework that emphasizes cell-cell interactions between neuronal, glial, and vascular elements. Under normal conditions, signaling within the neurovascular unit helps maintain homeostasis. After stroke, cell-cell signaling is disturbed, leading to pathophysiology. More recently, emerging data now suggest that these cell-cell signaling mechanisms may also mediate parallel processes of neurovascular remodeling during stroke recovery. Because plasticity is a signature feature of the young and developing brain, these concepts may have special relevance to how the pediatric brain responds after stroke.

  17. When Public Acts Like Private: The Failure of Estonia's School Choice Mechanism

    Science.gov (United States)

    Poder, Kaire; Lauri, Triin

    2014-01-01

    This article aims to show the segregating effect of the market-like matching of students and schools at the basic school level. The natural experiment case is Tallinn, the capital of Estonia. The current school choice mechanism applied in this case is based on entrance tests. There are increasingly over-subscribed intra-catchment area public…

  18. A Role for BLM in Double-Strand Break Repair Pathway Choice: Prevention of CtIP/Mre11-Mediated Alternative Nonhomologous End-Joining

    Directory of Open Access Journals (Sweden)

    Anastazja Grabarz

    2013-10-01

    Full Text Available The choice of the appropriate double-strand break (DSB repair pathway is essential for the maintenance of genomic stability. Here, we show that the Bloom syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions (>200 bp generated by alternative end-joining (A-EJ. BLM represses A-EJ in an epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation-induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB end resection. These data highlight a dual role for BLM that influences the DSB repair pathway choice: (1 protection against CtIP/MRE11 long-range deletions associated with A-EJ and (2 promotion of DNA resection. These antagonist roles can be regulated, according to cell-cycle stage, by interacting partners such as 53BP1 and TopIII, to avoid unscheduled resection that might jeopardize genome integrity.

  19. UV-induced dark repair mechanisms in bacteria associated with drinking water.

    Science.gov (United States)

    Jungfer, Christina; Schwartz, Thomas; Obst, Ursula

    2007-01-01

    Caulobacter crescentus and Aquabacterium commune, both isolated from drinking water, as well as environmental isolates of Pseudomonas aeruginosa and Enterococcus faecium were treated with different UV fluences to study their capacity to restore induced DNA damages. Here, the induction of a key mechanism of bacterial dark repair, the so-called recA system, was analysed. With newly designed probes, the specific recA mRNA was detected by Northern blot. Additionally, the RecA protein was measured by the Western blot technique using a specific antibody. In drinking water bacteria as well as in opportunistic microorganisms, a specific induction of dark repair mechanisms was found even at UV fluences higher than 400J/m(2), the German standard for UV disinfection. This induction depended on the incubation time after UV treatment. Nevertheless, the UV-induced recA expressions were found to differ in the bacteria under investigation.

  20. The effects of multiple repairs on Inconel 718 weld mechanical properties

    Science.gov (United States)

    Russell, C. K.; Nunes, A. C., Jr.; Moore, D.

    1991-01-01

    Inconel 718 weldments were repaired 3, 6, 9, and 13 times using the gas tungsten arc welding process. The welded panels were machined into mechanical test specimens, postweld heat treated, and nondestructively tested. Tensile properties and high cycle fatigue life were evaluated and the results compared to unrepaired weld properties. Mechanical property data were analyzed using the statistical methods of difference in means for tensile properties and difference in log means and Weibull analysis for high cycle fatigue properties. Statistical analysis performed on the data did not show a significant decrease in tensile or high cycle fatigue properties due to the repeated repairs. Some degradation was observed in all properties, however, it was minimal.

  1. The cellular and molecular mechanisms of tissue repair and regeneration as revealed by studies in Xenopus

    Science.gov (United States)

    Li, Jingjing; Zhang, Siwei

    2016-01-01

    Abstract Survival of any living organism critically depends on its ability to repair and regenerate damaged tissues and/or organs during its lifetime following injury, disease, or aging. Various animal models from invertebrates to vertebrates have been used to investigate the molecular and cellular mechanisms of wound healing and tissue regeneration. It is hoped that such studies will form the framework for identifying novel clinical treatments that will improve the healing and regenerative capacity of humans. Amongst these models, Xenopus stands out as a particularly versatile and powerful system. This review summarizes recent findings using this model, which have provided fundamental knowledge of the mechanisms responsible for efficient and perfect tissue repair and regeneration.

  2. Playful Mobility Choices: Motivating informed mobility decision making by applying game mechanics

    Directory of Open Access Journals (Sweden)

    A. Millonig

    2014-10-01

    Full Text Available Motivating people to change their mobility behaviour patterns towards more sustainable forms of mobility is one of the major challenges regarding climate change and quality of life. Recently, an increasing amount of attempts to use gamification for triggering such behavioural changes can be observed. However, little is known about the actual impact of using game elements. This contribution describes a concept for systematically analysing the group-specific effects of different game mechanics on mobility decision processes (e.g. mode and route choice. Based on theoretical findings concerning player types and mobility styles we developed a framework for identifying effective game mechanics motivating users to explore mobility alternatives and take more informed and more sustainable mode or route choice decisions. The results will form the basis for implementing game mechanics in mobility information services motivating users to explore unfamiliar but more sustainable mobility options.

  3. Understanding the Molecular Mechanism(s) of Formaldehyde-induced DNA-protein Crosslink Repair

    Science.gov (United States)

    Although formaldehyde has been shown to induce many kinds of DNA damage both in in vitro and in vivo assay systems, initial DNA-protein crosslink (DPC) formation might play a major role in FA-induced mutagenesis and carcinogenesis. Several DNA repair pathways, such as base excisi...

  4. Physicochemical Mechanism of Light-Driven DNA Repair by (6-4) Photolyases

    Science.gov (United States)

    Faraji, Shirin; Dreuw, Andreas

    2014-04-01

    DNA photolyases are light-activated enzymes that repair DNA damage induced by ultraviolet (UV) radiation. UV radiation causes two of the most abundant mutagenic and cytotoxic DNA lesions: cyclobutane pyrimidine dimers and 6-4 photolesions. Photolyases selectively bind to DNA and initiate the splitting of mutagenic pyrimidine dimers via photoinduced electron transfer from a flavin adenine dinucleotide anion (FADH-) to the lesion triggering its repair. This review discusses the consecutive steps of the repair process, from both experimental and theoretical points of view. It covers the following issues: the process of how photolyases accommodate the lesion into their binding pockets, excitation energy transfer between two involved catalytic cofactors, photoinduced electron transfer to the lesion, the splitting of the pyrimidine dimer radical anion, and the fate of the unstable radical species created after the splitting of the thymine dimer. In particular, mechanisms of the splitting and restoration of the original bases are described in detail, and the most probable repair pathways are outlined.

  5. Mechanical and toughness properties of robotic-FSW repair welds in 6061-T6 aluminium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Brinckmann, S.; Strombeck, A. v.; Schilling, C.; Santos, J.F. dos; Kocak, M. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Materialforschung; Lohwasser, D. [DaimlerChrysler Aerospace Airbus GmbH, Bremen (Germany)

    2000-07-01

    Panel or structures welded in fixed installations might require local repair of eventual process induced defects. Ideally such repair operations should take place outside the production line to avoid interruption of the manufacturing flow. Robotic FSW systems offer the required flexibility to perform such repairs. The main objective of this work was to conduct a preliminary investigation on the microstructural, mechanical and toughness properties of robotic friction stir repair welds. To achieve this objective defective welds have been purposely produced and subsequently repaired. Specimens for microstructural analysis, mechanical and fracture toughness testing have been obtained from repaired and defect-free welds as well as from the base plate for comparison purposes. The mechanical properties have been established using standard tests, i.e. hardness, bending and tensile. Toughness properties of the joints have been determined using small (compact tension - CT) and large (M(T)) scale specimens. Fatigue pre-cracks were positioned in the nugget and HAZ. Crack resistance curves (R-Curves) were determined using the potential drop technique. The obtained results indicated that the additional thermal cycle and deformation process imposed by the repair weld did not adversely affect the mechanical and toughness properties of the nugget area. Both defect-free and repair welds showed higher toughness than the base material. Pre-cracks positioned in the nugget region were deviated into the lower strength TMAZ after initiation and ductile crack growth within the nugget area due to strength undermatch. Later propagation remained within the TMAZ. (orig.) [German] Das Schweissen von Elementen oder Strukturen kann eine lokale Reparatur erfordern, wenn durch den Fuegeprozess ausgeloeste Fehler auftreten. Vorteilhafterweise sollten die Reparaturen ausserhalb der Fertigungslinie erfolgen, um den Produktionsablauf nicht zu stoeren. Robotergestuetzte FSW-Systeme bieten die benoetigte

  6. Hybrid female mate choice as a species isolating mechanism: environment matters.

    Science.gov (United States)

    Schmidt, E M; Pfennig, K S

    2016-04-01

    A fundamental goal of biology is to understand how new species arise and are maintained. Female mate choice is potentially critical to the speciation process: mate choice can prevent hybridization and thereby generate reproductive isolation between potentially interbreeding groups. Yet, in systems where hybridization occurs, mate choice by hybrid females might also play a key role in reproductive isolation by affecting hybrid fitness and contributing to patterns of gene flow between species. We evaluated whether hybrid mate choice behaviour could serve as such an isolating mechanism using spadefoot toad hybrids of Spea multiplicata and Spea bombifrons. We assessed the mate preferences of female hybrid spadefoot toads for sterile hybrid males vs. pure-species males in two alternative habitat types in which spadefoots breed: deep or shallow water. We found that, in deep water, hybrid females preferred the calls of sterile hybrid males to those of S. multiplicata males. Thus, maladaptive hybrid mate preferences could serve as an isolating mechanism. However, in shallow water, the preference for hybrid male calls was not expressed. Moreover, hybrid females did not prefer hybrid calls to those of S. bombifrons in either environment. Because hybrid female mate choice was context-dependent, its efficacy as a reproductive isolating mechanism will depend on both the environment in which females choose their mates as well as the relative frequencies of males in a given population. Thus, reproductive isolation between species, as well as habitat specific patterns of gene flow between species, might depend critically on the nature of hybrid mate preferences and the way in which they vary across environments.

  7. Quantum mechanics/molecular mechanics study on the oxygen binding and substrate hydroxylation step in AlkB repair enzymes.

    Science.gov (United States)

    Quesne, Matthew G; Latifi, Reza; Gonzalez-Ovalle, Luis E; Kumar, Devesh; de Visser, Sam P

    2014-01-07

    AlkB repair enzymes are important nonheme iron enzymes that catalyse the demethylation of alkylated DNA bases in humans, which is a vital reaction in the body that heals externally damaged DNA bases. Its mechanism is currently controversial and in order to resolve the catalytic mechanism of these enzymes, a quantum mechanics/molecular mechanics (QM/MM) study was performed on the demethylation of the N(1) -methyladenine fragment by AlkB repair enzymes. Firstly, the initial modelling identified the oxygen binding site of the enzyme. Secondly, the oxygen activation mechanism was investigated and a novel pathway was found, whereby the catalytically active iron(IV)-oxo intermediate in the catalytic cycle undergoes an initial isomerisation assisted by an Arg residue in the substrate binding pocket, which then brings the oxo group in close contact with the methyl group of the alkylated DNA base. This enables a subsequent rate-determining hydrogen-atom abstraction on competitive σ- and π-pathways on a quintet spin-state surface. These findings give evidence of different locations of the oxygen and substrate binding channels in the enzyme and the origin of the separation of the oxygen-bound intermediates in the catalytic cycle from substrate. Our studies are compared with small model complexes and the effect of protein and environment on the kinetics and mechanism is explained.

  8. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    Science.gov (United States)

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  9. Alternative mechanisms of telomere lengthening: Permissive mutations, DNA repair proteins and tumorigenic progression

    Energy Technology Data Exchange (ETDEWEB)

    Gocha, April Renee Sandy; Harris, Julia [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210 (United States); Groden, Joanna, E-mail: joanna.groden@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210 (United States)

    2013-03-15

    Highlights: ► Neoplastic cells maintain telomeres by telomerase or ALT. ► Genetic mutations in p53, ATRX, DAXX or H3F3A may activate ALT. ► Many DNA repair proteins are involved in ALT. ► Tumor progression is favored by telomerase expression. - Abstract: Telomeres protect chromosome termini to maintain genomic stability and regulate cellular lifespan. Maintenance of telomere length is required for neoplastic cells after the acquisition of mutations that deregulate cell cycle control and increase cellular proliferation, and can occur through expression of the enzyme telomerase or in a telomerase-independent manner termed alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are unknown, although cellular origin may favor one or the other mechanisms. ALT pathways are incompletely understood to date; however, recent publications have increasingly broadened our understanding of how ALT is activated, how it proceeds, and how it influences tumor growth. Specific mutational events influence ALT activation, as mutations in genes that suppress recombination and/or alterations in the regulation of telomerase expression are associated with ALT. Once engaged, ALT uses DNA repair proteins to maintain telomeres in the absence of telomerase; experiments that manipulate the expression of specific proteins in cells using ALT are illuminating some of its mechanisms. Furthermore, ALT may influence tumor growth, as experimental and clinical data suggest that telomerase expression may favor tumor progression. This review summarizes recent findings in mammalian cells and models, as well as clinical data, that identify the genetic mutations permissive to ALT, the DNA repair proteins involved in ALT mechanisms and the importance of telomere maintenance mechanisms for tumor progression. A comprehensive understanding of the mechanisms that permit tumor cell immortalization will be important for identifying

  10. Mechanical Complication with Broviac Repair Kit in a 4-Year-Old Boy with MEN 2a

    Directory of Open Access Journals (Sweden)

    Sergio B. Sesia

    2009-01-01

    Full Text Available Background. Mechanical complications in the use of indwelling central venous catheters (CVCs such as the Broviac catheter (BC include kinking, occlusion, dislocation or leaking. We report on a mechanical complication after using a repair kit for the BC. Method. A 4-year old boy, suffering from multiple endocrine neoplasia type 2a (MEN 2a, intestinal aganglionosis (Hirschsprung's disease, and short bowel syndrome, required a BC for home parenteral nutrition. Result. Due to recurrent leakage of the BC, 5 subsequent repairs were necessary within seven months. During one repair a metallic tube belonging to the repair kit was found to have migrated proximally to the skin entrance level within the BC and requiring surgical removal. Conclusion. To our knowledge, this is the first report focusing on such a serious complication using a BC and its repair kit. The proximal migration of this metallic tube constitutes a distinct theoretical risk of endothoracic foreign body embolization.

  11. 'Prudent habitat choice': a novel mechanism of size-assortative mating.

    Science.gov (United States)

    Taborsky, B; Guyer, L; Demus, P

    2014-06-01

    Assortative mating, an ubiquitous form of nonrandom mating, strongly impacts Darwinian fitness and can drive biological diversification. Despite its ecological and evolutionary importance, the behavioural processes underlying assortative mating are often unknown, and in particular, mechanisms not involving mate choice have been largely ignored so far. Here, we propose that assortative mating can arise from 'prudent habitat choice', a general mechanism that acts under natural selection, and that it can occur despite a complete mixing of phenotypes. We show that in the cichlid Eretmodus cyanostictus size-assortative mating ensues, because individuals of weaker competitive ability ignore high-quality but strongly competed habitat patches. Previous studies showed that in E. cyanostictus, size-based mate preferences are absent. By field and laboratory experiments, here we showed that (i) habitat quality and body size are correlated in this species; (ii) territories with more stone cover are preferred by both sexes in the absence of competition; and (iii) smaller fish prudently occupy vacant territories of worse quality than do larger fish. Prudent habitat choice is likely to be a widespread mechanism of assortative mating, as both preferences for and dominance-based access to high-quality habitats are generic phenomena in animals.

  12. Proposal for a quantum delayed-choice experiment with a spin-mechanical setup

    Science.gov (United States)

    Li, Peng-Bo; Li, Fu-Li

    2016-10-01

    We describe an experimentally feasible protocol for performing a variant of the quantum delayed-choice experiment with massive objects. In this scheme, a single nitrogen-vacancy (NV) center in diamond driven by microwave fields is dispersively coupled to a massive mechanical resonator. A double-pulse Ramsey interferometer can be implemented with the spin-mechanical setup, where the second Ramsey microwave pulse drives the spin conditioned on the number states of the resonator. The probability for finding the NV center in definite spin states exhibits interference fringes when the mechanical resonator is prepared in a specific number state. On the other hand, the interference is destroyed if the mechanical resonator stays in some other number states. The wavelike and particlelike behavior of the NV spin can be superposed by preparing the mechanical resonator in a superposition of two distinct number states. Thus a quantum version of Wheeler's delayed-choice experiment could be implemented, allowing fundamental tests of quantum mechanics on a macroscopic scale.

  13. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    Directory of Open Access Journals (Sweden)

    Wendell Q Sun

    2013-09-01

    Full Text Available Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix, and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the

  14. The structural and mechanical properties of the Achilles tendon 2 years after surgical repair.

    Science.gov (United States)

    Geremia, Jeam Marcel; Bobbert, Maarten Frank; Casa Nova, Mayra; Ott, Rafael Duvelius; Lemos, Fernando de Aguiar; Lupion, Raquel de Oliveira; Frasson, Viviane Bortoluzzi; Vaz, Marco Aurélio

    2015-06-01

    Acute ruptures of the Achilles tendon affect the tendon's structural and mechanical properties. The long-term effects of surgical repair on these properties remain unclear. To evaluate effects of early mobilization versus traditional immobilization rehabilitation programs 2 years after surgical Achilles tendon repair, by comparing force-elongation and stress-strain relationships of the injured tendon to those of the uninjured tendon. A group of males with previous Achilles tendon rupture (n=18) and a group of healthy male controls (n=9) participated. Achilles tendon rupture group consisted of patients that had received early mobilization (n=9) and patients that had received traditional immobilization with a plaster cast (n=9). Comparisons of tendon structural and mechanical properties were made between Achilles tendon rupture and healthy control groups, and between the uninjured and injured sides of the two rehabilitation groups in Achilles tendon rupture group. Ultrasound was used to determine bilaterally tendon cross-sectional area, tendon resting length, and tendon elongation as a function of torque during maximal voluntary plantar flexion. From these data, Achilles tendon force-elongation and stress-strain relationships were determined. The Achilles tendon rupture group uninjured side was not different from healthy control group. Structural and mechanical parameters of the injured side were not different between the Achilles tendon rupture early mobilization and the immobilization groups. Compared to the uninjured side, the injured side showed a reduction in stress at maximal voluntary force, in Young's modulus and in stiffness. Two years post-surgical repair, the Achilles tendon mechanical properties had not returned to the uninjured contralateral tendon values. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Repair mechanisms inducible to the DNA in I.M.M.S. biological systems; Mecanismos de reparacion inducible del ADN en sistemas biologicos I.M.M.S

    Energy Technology Data Exchange (ETDEWEB)

    Guzman, J.; Arceo, C.; Cortinas, C.; Rosa, M.E. De la; Olvera, O.; Cruces, M.; Pimentel, E

    1990-03-15

    Given the characteristics of the MMS and the relative antecedents to the repair mechanisms in eucariontes are sought to determine the effect of the MMS on the genetic material and their repair in Drosophila melanogaster. (Author)

  16. Sp1 facilitates DNA double-strand break repair through a nontranscriptional mechanism.

    Science.gov (United States)

    Beishline, Kate; Kelly, Crystal M; Olofsson, Beatrix A; Koduri, Sravanthi; Emrich, Jacqueline; Greenberg, Roger A; Azizkhan-Clifford, Jane

    2012-09-01

    Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H(2)O(2). Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant γH2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects.

  17. The mechanism of nucleotide excision repair-mediated UV-induced mutagenesis in nonproliferating cells.

    Science.gov (United States)

    Kozmin, Stanislav G; Jinks-Robertson, Sue

    2013-03-01

    Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such two-strand mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colony-color system was used to examine the genetic control of UV-induced mutagenesis in nondividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production of these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32, and Rad5) and in the early steps of the DNA-damage checkpoint response (Rad17, Mec3, Ddc1, Mec1, and Rad9) were required for the production of two-strand mutations. There was no involvement, however, for the Pol η translesion synthesis DNA polymerase, the Mms2-Ubc13 postreplication repair complex, downstream DNA-damage checkpoint factors (Rad53, Chk1, and Dun1), or the Exo1 exonuclease. Our data support models in which UV-induced mutagenesis in nondividing cells occurs during the Pol ζ-dependent filling of lesion-containing, NER-generated gaps. The requirement for specific DNA-damage checkpoint proteins suggests roles in recruiting and/or activating factors required to fill such gaps.

  18. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  19. [Mechanisms of reparative action of a new repair and protect toothpaste].

    Science.gov (United States)

    Elovikova, T M; Ermishina, E Yu; Mikheikina, N I

    The aim of the study was to assess clinical efficacy of Sensodyne repair and protect toothpaste as well as mechanics of its reparative action. Forty-eight patients (29 females and 19 males) were included in the study. The participants brushed twice daily with Sensodyne toothpaste. In 24 patients in addition to clinical examination fluoride, calcium and pH were measured in oral fluid. The study showed OHIS reduction by 40.24% and eradication of tooth hypersensitivity even after single use of the toothpaste in 90% of patients because of sodium monofluorophosphate action.

  20. Effect of repetitive loading on the mechanical properties of synthetic hernia repair materials.

    Science.gov (United States)

    Eliason, Braden J; Frisella, Margaret M; Matthews, Brent D; Deeken, Corey R

    2011-09-01

    Hernia repair materials undergo repeated loading while in the body, and the impact on mechanical properties is unknown. It was hypothesized that exposure to repetitive loading would lead to decreased tensile strength and increased strain, and that these differences would become more pronounced with greater loading and unloading sequences. Polypropylene, expanded polytetrafluoroethylene, composite barrier, and partially absorbable meshes were evaluated. Twenty specimens (7.5 × 7.5 cm) were prepared from each material. Five specimens were subjected to ball burst testing to determine baseline biomechanical properties. Cycles of 10, 100, and 1,000 loading sequences were also performed (n = 5 each). BardMesh (CR Bard/Davol), Dualmesh (WL Gore), and Prolene (Ethicon) exhibited significantly reduced tensile strength; BardMesh, Proceed (Ethicon), Prolene, ProLite (Atrium Medical), ProLite Ultra (Atrium Medical), and Ultrapro (Ethicon) exhibited significantly increased strain after exposure to 1,000 cycles compared with their baseline properties. BardMesh and Prolene demonstrated both reduced tensile strength and increased strain values after 1,000 cycles, suggesting that repetitive loading has the greatest effects on these materials. In addition, BardMesh and Prolene exhibited progressively worsening effects as the number of cycles was increased. Deterioration of the tensile strength of the mesh or an increase in the ability of the mesh material to stretch (ie, increased strain values) could potentially lead to hernia recurrence or a poor functional result. However, the results of this study should not be interpreted to mean that hernia repair materials will fail in the body after only 10, 100, or 1,000 cycles. The conditions used in this study were more extreme than most physiologic scenarios and were intended as a pilot investigation into how the mechanical properties of hernia repair materials are affected by in vitro cyclic testing. Copyright © 2011 American College

  1. A qualitative engineering analysis of occlusion effects on mandibular fracture repair mechanics.

    Science.gov (United States)

    Katona, Thomas R

    2011-01-01

    Objectives. The purpose of this analytical study was to examine and critique the engineering foundations of commonly accepted biomechanical principles of mandible fracture repair. Materials and Methods. Basic principles of static equilibrium were applied to intact and plated mandibles, but instead of the traditional lever forces, the mandibles were subjected to more realistic occlusal forces. Results. These loading conditions produced stress distributions within the intact mandible that were very different and more complex than the customary lever-based gradient. The analyses also demonstrated the entirely different mechanical environments within intact and plated mandibles. Conclusions. Because the loading and geometry of the lever-idealized mandible is incomplete, the associated widely accepted bone stress distribution (tension on top and compression on the bottom) should not be assumed. Furthermore, the stress gradients within the bone of an intact mandible should not be extrapolated to the mechanical environment within the plated regions of a fractured mandible.

  2. Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

    Science.gov (United States)

    Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

    2016-06-01

    Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

  3. [Metallothionein-I/II in brain injury repair mechanism and its application in forensic medicine].

    Science.gov (United States)

    Li, Dong; Li, Ru-bo; Lin, Ju-li

    2013-10-01

    Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.

  4. Understanding the molecular mechanism of formaldehyde-induced DNA-protein crosslink repair

    Science.gov (United States)

    Formaldehyde induces DNA-protein crosslinks (DPCs) in several experimental in vitro and in vivo test systems, as well as in exposed human workers. DPCs are repaired by several DNA repair pathways in different species, but the molecular understanding of DPC repair in human tissues...

  5. A new theoretical formula for fractionated radiotherapy based on a saturable cellular repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Reyes, A. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain)); Farrus, B. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain)); Biete, A. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain))

    1993-01-01

    Recently we have published a new model of survival cellular response to radiation based on the existence of a saturable cellular repair mechanism. In the present paper we extend the predictions of this model of calculating the change in total dose necessary to achieve an equal response in a tissue when the dose per fraction in a radiotherapy fractionation schedule is varied. The model provides a new explanation of the difference between late and early radiation reactions. Results obtained from the model for different tissues and standard fractionation schedules are approximately equal to those obtained by the L.Q. (linear-quadratic) model. The model is compatible with in vitro survival curves that are straight at high doses. (orig.).

  6. The Prevalence of Musculoskeletal Disorder and the Association with Risk Factors among Auto Repair Mechanics in Klang Valley, Malaysia

    Directory of Open Access Journals (Sweden)

    Ahmad Faisal AHMAD NASARUDDIN

    2015-10-01

    Full Text Available Background: The primary objective of this study was to determine the association between risk factors and the prevalence of musculoskeletal disorder (MSD among auto repair mechanics in Klang Valley, Malaysia.Methods: Overall, 191 mechanics from eight auto repair centers in Klang Valley, Malaysia were stratified sampling as participants of this study. A modified version of the general Standardized Nordic Questionnaire was used for analyses of perceived MSD in nine different parts of the body. Rapid Upper Limb Assessment (RULA, vibration measurement on hand power tool, questionnaire on job content, force exertion was used in this study. Direct logistic regression was performed to assess the impact of risk factors on the MSD prevalence. The probability limits for evaluating statistical significance was P < 0.05.Results: 87.4% of auto repair mechanics suffered from MSD. Logistic regression analysis revealed that factors were associated with symptoms on MSD: RULA (7.933, 95% CI 4.637-13.573 and orceful exertion (3.173, 95% CI 1.194 – 8.432. The magnitude of vibration of power tool exceeds action level 2.5m/s2 with (Mean=3.99+S.E. 0.071 and showed significant association with MSD in this study (P<0.05.Conclusion: Auto repair mechanics at auto repair centers in Klang Valley are likely to be exposed to a variety of ergonomic hazards and risk factors. Therefore, ergonomics awareness between employer and employee with training and information sharing shall be increase to reduce the prevalence of MSDs. Keywords: Musculoskeletal disorder (MSD, Auto repair mechanics, Hand arm vibration

  7. Physical microscopic free-choice model in the framework of a Darwinian approach to quantum mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Baladron, Carlos [Departamento de Fisica Teorica, Atomica y Optica, Universidad de Valladolid, E-47011, Valladolid (Spain)

    2017-06-15

    A compatibilistic model of free choice for a fundamental particle is built within a general framework that explores the possibility that quantum mechanics be the emergent result of generalised Darwinian evolution acting on the abstract landscape of possible physical theories. The central element in this approach is a probabilistic classical Turing machine -basically an information processor plus a randomiser- methodologically associated with every fundamental particle. In this scheme every system acts not under a general law, but as a consequence of the command of a particular, evolved algorithm. This evolved programme enables the particle to algorithmically anticipate possible future world configurations in information space, and as a consequence, without altering the natural forward causal order in physical space, to incorporate elements to the decision making procedure that are neither purely random nor strictly in the past, but in a possible future. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Dynamic Route Shortening and Route Repairing Mechanism for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    T. R. Rangaswamy

    2012-01-01

    Full Text Available Problem statement: Ad hoc Networks are wireless networks without any fixed infrastructure. The network topology changes frequently and unpredictably due to the random movement of the nodes. The ad hoc on Demand Distant Vector Routing (AODV protocol works in a dynamic fashion, by establishing a route on demand and continues that route until it breaks. Due to the changing network topology of ad hoc networks, if other routes with less hop count become available, the network topology is not able to adapt until the route break occurs. Hence in the route shortening scheme is some redundant nodes in the active route is replaced with a node that is not on the active route. When there is any link failure between any two nodes, the alternative route with optimum route to be constructed and not sending RRER message to the source node to initiate the route discovery process again. Approach: This study proposes a new routing protocol called, Dynamic Route Shortening and Repairing mechanism (DRSR. The route shortening is incorporated with route repairing mechanism, to improve the performance of the AODV. The route shortening scheme works by replacing some redundant nodes in the active route, with a node that is not on the active route. If there is a link failure between the two nodes, the route repairing mechanism repairs the route, by using the nodes that are close enough to the route to overhear the message. Whenever the links go down, the DRSR replaces the failed links with the optimum route that is adjacent to the main route and not sending and RRER message to the source node to initiate the route discovery process again. The alternative route construction process could be initiated at any time, not just when a route has failed. The dynamically constructed alternative route’s information is passed on to the upstream nodes, which then determine by themselves when to direct their packets to the Normal 0 false false false EN-US X

  9. Mechanical waves conceptual survey: Its modification and conversion to a standard multiple-choice test

    Science.gov (United States)

    Barniol, Pablo; Zavala, Genaro

    2016-06-01

    In this article we present several modifications of the mechanical waves conceptual survey, the most important test to date that has been designed to evaluate university students' understanding of four main topics in mechanical waves: propagation, superposition, reflection, and standing waves. The most significant changes are (i) modification of several test questions that had some problems in their original design, (ii) standardization of the number of options for each question to five, (iii) conversion of the two-tier questions to multiple-choice questions, and (iv) modification of some questions to make them independent of others. To obtain a final version of the test, we administered both the original and modified versions several times to students at a large private university in Mexico. These students were completing a course that covers the topics tested by the survey. The final modified version of the test was administered to 234 students. In this study we present the modifications for each question, and discuss the reasons behind them. We also analyze the results obtained by the final modified version and offer a comparison between the original and modified versions. In the Supplemental Material we present the final modified version of the test. It can be used by teachers and researchers to assess students' understanding of, and learning about, mechanical waves.

  10. DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Lee, Andrew H.; Symington, Lorraine S.

    2014-01-01

    SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

  11. DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Lee, Andrew H; Symington, Lorraine S; Fidock, David A

    2014-09-01

    Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen.

  12. The Molecular Mechanisms and the Role of hnRNP K Protein Post- Translational Modification in DNA Damage Repair.

    Science.gov (United States)

    Lu, Jing; Gao, Feng-Hou

    2017-01-01

    DNA damage repair is a kind of cellular self-protection mechanism in which some relevant proteins are activated when DNA damage response occurs in order to maintain the intracellular function stability and structure integrity. Post-translational modifications (PTMs) of proteins can rapidly confer to them more complicated structure and sophisticated function by covalently combining different small molecules with target proteins, which in turn plays an important regulatory role in DNA damage repair. It was reported that heterogeneous nuclear ribonucleoprotein K (hnRNP K) could be involved in DNA damage repair process under the regulation of its many post-translational modifications, including methylation, ubiquitination, sumoylation and phosphorylation. Here, we reviewed molecular mechanisms of hnRNP K protein post-translational modifications and their role in DNA damage repair, which will promote our understanding of how hnRNP K participating in the repair process to maintain the normal operation of biological activities in the cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Development of repair mechanism of FSX-414 based 1st stage nozzle of gas turbine

    Science.gov (United States)

    Rahman, Md. Tawfiqur

    2017-06-01

    This paper describes the failure mechanism and repair technology of 1st stage nozzle or vane of industrial gas turbine which is made of cobalt based super alloy FSX-414. 1st stage nozzles or vanes are important stationery components of gas turbine based power plant. Those are the parts of hot gas path components of gas turbine and their manufacturing process is casting. At present, it is widely accepted that gas turbine based combined cycle power plant is the most efficient and cost effective solution to generate electricity. One of the factors of high efficiency of this type of gas turbine is the increase of its turbine inlet temperature. As an effect of this factor and in conjunction with some other factors, the 1st stage nozzle of gas turbine operates under extremely high temperature and thermal stresses. As a result, the design lifetime of these components becomes limited. Furthermore, attention on nozzles or vanes is required in order to achieve their design lifetime. However, due to unfriendly operational condition and environmental effect, anytime failure can occur on these heat resistant alloy based components which may lead to severe damage of gas turbine. To mitigate these adverse effects, schedule maintenance is performed on a predetermined time interval of hot gas path components of gas turbine based power plant. This paper addresses common failures in gas turbine's 1st stage nozzles or vanes. Usually these are repaired by using ADH process but for several reasons ADH process is not used here. Hence the challenging task is performed using gas tungsten arc welding which is presented in this article systematically.

  14. Course Outline for Lesson Plans for Pre-Employment Laboratory Training in CVAE-VEH Farm and Ranch Mechanical Repair.

    Science.gov (United States)

    Texas A and M Univ., College Station. Vocational Instructional Services.

    This packet contains 88 lesson plans for a laboratory course in farm and ranch mechanical repair. The lesson plans are organized into six units covering the following topics: occupational information, construction and maintenance (safety, farm carpentry, farm water supply and sanitation, farm electricity, concrete), hot metal work (oxyacetylene…

  15. Introduction of a New Suture Method in Repair of Peripheral Nerves Injured with a Sharp Mechanism

    Directory of Open Access Journals (Sweden)

    Alireza Saied

    2015-09-01

    Full Text Available Background: The standard method for repair of an injured peripheal nerve is epineural repair with separate sutures. Herein we describe a method in which the nerve is sutured with continous sutures. In fact this method has not been utilized for nerve repair previously and our purpose was to compare it to the standard method. If it proved to be successful it would replace the standard method in certain circumstances. Methods: The proposal of the clinical trial was given a reference number form the ethics comitee. 25 dogs in which the scaitic nerve was cut by a sharp blade under genaeral anesthesia were divided randomly into three groups: control (5 dogs, repair of sciatic nerve with simple sutures (10 and repair with continous sutures (10. In the control group the nerve was not repaired at all. After 6 weeks the dogs were killed and the nerve was studied by light and electronic microscopes. The amount of consumed suture material, time of repair, myelin thickness and axon diiameter were examined. Ultrastructural studies were performed to assess degeneration and regeneration findings. Results: Time of repair and the amount of consumed suture material were significantly lower in the continous group (P

  16. Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

    Science.gov (United States)

    Cremers, Niels A. J.; Suttorp, Maarten; Gerritsen, Marlous M.; Wong, Ronald J.; van Run-van Breda, Coby; van Dam, Gooitzen M.; Brouwer, Katrien M.; Kuijpers-Jagtman, Anne Marie; Carels, Carine E. L.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

    2015-01-01

    Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orchestrate the defense against inflammatory and oxidative insults that drive fibrosis. Here, we investigated the activation of the HO-1 system in a splinted and non-splinted full-thickness excisional wound model using HO-1-luc transgenic mice. Effects of splinting on wound closure, HO-1 promoter activity, and markers of inflammation and fibrosis were assessed. After seven days, splinted wounds were more than three times larger than non-splinted wounds, demonstrating a delay in wound closure. HO-1 promoter activity rapidly decreased following removal of the (epi)dermis, but was induced in both splinted and non-splinted wounds during skin repair. Splinting induced more HO-1 gene expression in 7-day wounds; however, HO-1 protein expression remained lower in the epidermis, likely due to lower numbers of keratinocytes in the re-epithelialization tissue. Higher numbers of F4/80-positive macrophages, αSMA-positive myofibroblasts, and increased levels of the inflammatory genes IL-1β, TNF-α, and COX-2 were present in 7-day splinted wounds. Surprisingly, mRNA expression of newly formed collagen (type III) was lower in 7-day wounds after splinting, whereas, VEGF and MMP-9 were increased. In summary, these data demonstrate that splinting delays cutaneous wound closure and HO-1 protein induction. The pro-inflammatory environment following splinting may facilitate higher myofibroblast numbers and increase the risk of fibrosis and scar formation. Therefore, inducing HO-1 activity against mechanical stress-induced inflammation and fibrosis may be an interesting strategy to prevent negative effects of surgery on growth and function in patients with orofacial clefts or in patients with

  17. Cell and protein compatible 3D bioprinting of mechanically strong constructs for bone repair.

    Science.gov (United States)

    Sawkins, M J; Mistry, P; Brown, B N; Shakesheff, K M; Bonassar, L J; Yang, J

    2015-07-02

    Rapid prototyping of bone tissue engineering constructs often utilizes elevated temperatures, organic solvents and/or UV light for materials processing. These harsh conditions may prevent the incorporation of cells and therapeutic proteins in the fabrication processes. Here we developed a method for using bioprinting to produce constructs from a thermoresponsive microparticulate material based on poly(lactic-co-glycolic acid) at ambient conditions. These constructs could be engineered with yield stresses of up to 1.22 MPa and Young's moduli of up to 57.3 MPa which are within the range of properties of human cancellous bone. Further study showed that protein-releasing microspheres could be incorporated into the bioprinted constructs. The release of the model protein lysozyme from bioprinted constructs was sustainted for a period of 15 days and a high degree of protein activity could be measured up to day 9. This work suggests that bioprinting is a viable route to the production of mechanically strong constructs for bone repair under mild conditions which allow the inclusion of viable cells and active proteins.

  18. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

    Directory of Open Access Journals (Sweden)

    Zhi-yuan Guo

    2015-01-01

    Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

  19. Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants.

    Science.gov (United States)

    Ojini, Irene; Gammie, Alison

    2015-07-21

    Resistance to cancer therapy is a major obstacle in the long-term treatment of cancer. A greater understanding of drug resistance mechanisms will ultimately lead to the development of effective therapeutic strategies to prevent resistance from occurring. Here, we exploit the mutator phenotype of mismatch repair defective yeast cells combined with whole genome sequencing to identify drug resistance mutations in key pathways involved in the development of chemoresistance. The utility of this approach was demonstrated via the identification of the known CAN1 and TOP1 resistance targets for two compounds, canavanine and camptothecin, respectively. We have also experimentally validated the plasma membrane transporter HNM1 as the primary drug resistance target of mechlorethamine. Furthermore, the sequencing of mitoxantrone-resistant strains identified inactivating mutations within IPT1, a gene encoding inositolphosphotransferase, an enzyme involved in sphingolipid biosynthesis. In the case of bactobolin, a promising anticancer drug, the endocytosis pathway was identified as the drug resistance target responsible for conferring resistance. Finally, we show that that rapamycin, an mTOR inhibitor previously shown to alter the fitness of the ipt1 mutant, can effectively prevent the formation of mitoxantrone resistance. The rapid and robust nature of these techniques, using Saccharomyces cerevisiae as a model organism, should accelerate the identification of drug resistance targets and guide the development of novel therapeutic combination strategies to prevent the development of chemoresistance in various cancers.

  20. Effect of Mechanical Surface Treatment on the Repair Bond Strength of the Silorane-based Composite Resin

    Directory of Open Access Journals (Sweden)

    Parnian Alizadeh Oskoee

    2014-06-01

    Full Text Available Background and aims. A proper bond must be created between the existing composite resin and the new one for successful repair. The aim of this study was to compare the effect of three mechanical surface treatments, using diamond bur, air abrasion, and Er,Cr:YSGG laser, on the repair bond strength of the silorane-based composite resin. Materials and methods. Sixty cylindrical composite resin specimens (Filtek Silorane were fabricated and randomly divided into four groups according to surface treatment: group 1 (control group without any mechanical surface treatment, groups 24 were treated with air abrasion, Er,Cr:YSGG laser, and diamond bur, respectively. In addition, a positive control group was assigned in order to measure the cohesive strength. Silorane bonding agent was used in groups 14 before adding the new composite resin. Then, the specimens were subjected to a shear bond strength test and data was analyzed using one-way ANOVA and post hoc Tukey tests at a significance level of P < 0.05. The topographical effects of surface treatments were characterized under a scanning electron microscope. Results. There were statistically significant differences in the repair bond strength values between groups 1 and 2 and groups 3 and 4 (P < 0.001. There were no significant differences between groups 1 and 2 (P = 0.98 and groups 3 and 4 (P = 0.97. Conclusion. Surface treatment using Er,Cr:YSGG laser and diamond bur were effective in silorane-based composite resin repair.

  1. Horizontal gene transfer regulation in bacteria as a "spandrel" of DNA repair mechanisms.

    Directory of Open Access Journals (Sweden)

    Saliou Fall

    might have led the bacteria to hijack DNA repair mechanisms in order to generate genetic diversity without losing too much genomic stability.

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

    Science.gov (United States)

    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.

  3. Alkylation damage in DNA and RNA--repair mechanisms and medical significance

    DEFF Research Database (Denmark)

    Drabløs, Finn; Feyzi, Emadoldin; Aas, Per Arne

    2004-01-01

    Alkylation lesions in DNA and RNA result from endogenous compounds, environmental agents and alkylating drugs. Simple methylating agents, e.g. methylnitrosourea, tobacco-specific nitrosamines and drugs like temozolomide or streptozotocin, form adducts at N- and O-atoms in DNA bases. These lesions...... are mainly repaired by direct base repair, base excision repair, and to some extent by nucleotide excision repair (NER). The identified carcinogenicity of O(6)-methylguanine (O(6)-meG) is largely caused by its miscoding properties. Mutations from this lesion are prevented by O(6)-alkylG-DNA alkyltransferase......, inactivation of the MMR system in an AGT-defective background causes resistance to the killing effects of O(6)-alkylating agents, but not to the mutagenic effect. Bifunctional alkylating agents, such as chlorambucil or carmustine (BCNU), are commonly used anti-cancer drugs. DNA lesions caused by these agents...

  4. Dynamics and Mechanism of Efficient DNA Repair Reviewed by Active-Site Mutants

    Science.gov (United States)

    Tan, Chuang; Liu, Zheyun; Li, Jiang; Guo, Xunmin; Wang, Lijuan; Zhong, Dongping

    2010-06-01

    Photolyases repair the UV-induced pyrimidine dimers in damage DNA via a photoreaction which includes a series of light-driven electron transfers between the two-electron-reduced flavin cofactor FADH^- and the dimer. We report here our systematic studies of the repair dynamics in E. coli photolyase with mutation of several active-site residues. With femtosecond resolution, we observed the significant change in the forward electron transfer from the excited FADH^- to the dimer and the back electron transfer from the repaired thymines by mutation of E274A, R226A, R342A, N378S and N378C. We also found that the mutation of E274A accelerates the bond-breaking of the thymine dimer. The dynamics changes are consistent with the quantum yield study of these mutants. These results suggest that the active-site residues play a significant role, structurally and chemically, in the DNA repair photocycle.

  5. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals. (HLW)

  6. Case study. Health hazards of automotive repair mechanics: thermal and lighting comfort, particulate matter and noise.

    Science.gov (United States)

    Loupa, G

    2013-01-01

    An indoor environmental quality survey was conducted in a small private automotive repair shop during May 2009 (hot season) and February 2010 (cold season). It was established that the detached building, which is naturally ventilated and lit, had all the advantages of the temperate local climate. It provided a satisfactory microclimatic working environment, concerning the thermal and the lighting comfort, without excessive energy consumption for air-conditioning or lighting. Indoor number concentrations of particulate matter (PM) were monitored during both seasons. Their size distributions were strongly affected by the indoor activities and the air exchange rate of the building. During working hours, the average indoor/outdoor (I/O) number concentration ratio was 31 for PM0.3-1 in the hot season and 69 for the cold season. However I/O PM1-10 number concentration ratios were similar, 33 and 32 respectively, between the two seasons. The estimated indoor mass concentration of PM10 for the two seasons was on average 0.68 mg m(-3) and 1.19 mg m(-3), i.e., 22 and 36 times higher than outdoors, during the hot and the cold seasons, respectively. This is indicative that indoor air pollution may adversely affect mechanics' health. Noise levels were highly variable and the average LEX, 8 h of 69.3 dB(A) was below the European Union exposure limit value 87db (A). Noise originated from the use of manual hammers, the revving up of engines, and the closing of car doors or hoods. Octave band analysis indicated that the prevailing noise frequencies were in the area of the maximum ear sensitivity.

  7. Novel mechanism of regulation of the DNA repair enzyme OGG1 in tuberin-deficient cells

    Science.gov (United States)

    Habib, Samy L.; Bhandari, Besant K.; Sadek, Nahed; Abboud-Werner, Sherry L.; Abboud, Hanna E.

    2010-01-01

    Tuberin (protein encodes by tuberous sclerosis complex 2, Tsc2) deficiency is associated with the decrease in the DNA repair enzyme 8-oxoG-DNA glycosylase (OGG1) in tumour kidney of tuberous sclerosis complex (TSC) patients. The purpose of this study was to elucidate the mechanisms by which tuberin regulates OGG1. The partial deficiency in tuberin expression that occurs in the renal proximal tubular cells and kidney cortex of the Eker rat is associated with decreased activator protein 4 (AP4) and OGG1 expression. A complete deficiency in tuberin is associated with loss of AP4 and OGG1 expression in kidney tumour from Eker rats and the accumulation of significant levels of 8-oxo-deoxyguanosine. Knockdown of tuberin expression in human renal epithelial cells (HEK293) with small interfering RNA (siRNA) also resulted in a marked decrease in the expression of AP4 and OGG1. In contrast, overexpression of tuberin in HEK293 cells increased the expression of AP4 and OGG1 proteins. Downregulation of AP4 expression using siRNA resulted in a significant decrease in the protein expression of OGG1. Immunoprecipitation studies show that AP4 is associated with tuberin in cells. Gel shift analysis and chromatin immunoprecipitation identified the transcription factor AP4 as a positive regulator of the OGG1 promoter. AP4 DNA-binding activity is significantly reduced in Tsc2−/− as compared with Tsc2+/+ cells. Transcriptional activity of the OGG1 promoter is also decreased in tuberin-null cells compared with wild-type cells. These data indicate a novel role for tuberin in the regulation of OGG1 through the transcription factor AP4. This regulation may be important in the pathogenesis of kidney tumours in patients with TSC disease. PMID:20837600

  8. Motorcycle Repair.

    Science.gov (United States)

    Hein, Jim; Bundy, Mike

    This motorcycle repair curriculum guide contains the following ten areas of study: brake systems, clutches, constant mesh transmissions, final drives, suspension, mechanical starting mechanisms, electrical systems, fuel systems, lubrication systems, and overhead camshafts. Each area consists of one or more units of instruction. Each instructional…

  9. Approach to the classical radiation biology. Ionizing radiation effects and repair mechanism of DNA double strand breaks

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi [Kyoto Univ., Kumatori, Osaka (Japan). Research Reactor Inst

    2000-09-01

    Split-dose recovery has been observed under a variety of experimental conditions in many cell systems and believed to be the recovery of sublethal damage (SLD). It is considered to be one of the most widespread and important cellular responses in clinical radiotherapy. To study the molecular mechanism of this recovery, we analyzed the knockout mutants KU70{sup -/-}, RAD54{sup -/-}, and KU70{sup -/-}/ RAD54{sup -/-} of the chicken B-cell line, DT40. Rad54 participates in the homologous recombinational (HR) repair of DNA double-strand breaks (DSB), while Ku proteins are involved in non-homologous end-joining (NHEJ). Split-dose recovery was observed in the parent DT40 and KU70{sup -/-} cells. Moreover the split-dose survival enhancement had all of the characteristics of SLD recovery that had been demonstrated earlier: e.g., the reappearance of the shoulder of the survival curve with dose fractionation; repair at 25degC; and inhibition by the antibiotic actinomycin D. These results strongly suggest that SLD recovery is due to DSB repair via or mediated by HR, and that these breaks constitute SLD. The tonicity-sensitive potentially lethal damage (PLD) recovery was also found only in DT40 and KU70 {sup -/-} cells. Delayed-plating PLD recovery may be controlled by NHEJ repair that works through the cell cycle. These results lead to the conclusion that the repair of DSBs could explain the classical operational recovery phenomena. We have also investigated RBE/LET using those mutants. (author)

  10. Percutaneous mitral valve repair.

    Science.gov (United States)

    Gillinov, A Marc; Liddicoat, John R

    2006-01-01

    Surgical mitral valve repair is the procedure of choice to treat mitral regurgitation of all etiologies. Whereas annuloplasty is the cornerstone of mitral valve repair, a variety of other surgical techniques are utilized to correct dysfunction of the leaflets and subvalvular apparatus; in most cases, surgical repair entails application of multiple repair techniques in each patient. Preclinical studies and early human experience have demonstrated that some of these surgical repair techniques can be performed using percutaneous approaches. Specifically, there has been great progress in the development of novel technology to facilitate percutaneous annuloplasty and percutaneous edge-to-edge repair. The objectives of this report were to (1) discuss the surgical foundations for these percutaneous approaches; (2) review device design and experimental and clinical results of percutaneous valve repair; and (3) address future directions, including the key challenges of patient selection and clinical trial design.

  11. Delayed onset of tricuspid valve flow in repaired tetralogy of Fallot: an additional mechanism of diastolic dysfunction and interventricular dyssynchrony

    Directory of Open Access Journals (Sweden)

    Benson Lee N

    2011-08-01

    Full Text Available Abstract Background Diastolic dysfunction of the right ventricle (RV is common after repair of tetralogy of Fallot. While restrictive physiology in late diastole has been well known, dysfunction in early diastole has not been described. The present study sought to assess the prevalence and mechanism of early diastolic dysfunction of the RV defined as delayed onset of the tricuspid valve (TV flow after TOF repair. Methods The study population consisted of 31 children with repaired TOF (mean age ± SD, 12.3 ± 4.1 years who underwent postoperative cardiovascular magnetic resonance (CMR. The CMR protocol included simultaneous phase-contrast velocity mapping of the atrioventricular valves, which enabled direct comparison of the timing and patterns of tricuspid (TV and mitral (MV valve flow. The TV flow was defined to have delayed onset when its onset was > 20 ms later than the onset of the MV flow. The TV and MV flow from 14 normal children was used for comparison. The CMR results were correlated with the findings on echocardiography and electrocardiography. Result Delayed onset of the TV flow was observed in 16/31 patients and in none of the controls. The mean delay time was 64.81 ± 27.07 ms (8.7 ± 3.2% of R-R interval. The delay time correlated with the differences in duration of the TV and MV flow (55.94 ± 32.88 ms (r = 0.90, p Conclusions Early diastolic dysfunction with delayed onset of TV flow is common after TOF repair, and is associated with reduced RV ejection fraction. It is a further manifestation of interventricular dyssynchrony and represent an additional mechanism of ventricular diastolic dysfunction.

  12. Outer organic layer and internal repair mechanism protects pteropod Limacina helicina from ocean acidification

    Science.gov (United States)

    Peck, Victoria L.; Tarling, Geraint A.; Manno, Clara; Harper, Elizabeth M.; Tynan, Eithne

    2016-05-01

    Scarred shells of polar pteropod Limacina helicina collected from the Greenland Sea in June 2012 reveal a history of damage, most likely failed predation, in earlier life stages. Evidence of shell fracture and subsequent re-growth is commonly observed in specimens recovered from the sub-Arctic and further afield. However, at one site within sea-ice on the Greenland shelf, shells that had been subject to mechanical damage were also found to exhibit considerable dissolution. It was evident that shell dissolution was localised to areas where the organic, periostracal sheet that covers the outer shell had been damaged at some earlier stage during the animal's life. Where the periostracum remained intact, the shell appeared pristine with no sign of dissolution. Specimens which appeared to be pristine following collection were incubated for four days. Scarring of shells that received periostracal damage during collection only became evident in specimens that were incubated in waters undersaturated with respect to aragonite, ΩAr≤1. While the waters from which the damaged specimens were collected at the Greenland Sea sea-ice margin were not ΩAr≤1, the water column did exhibit the lowest ΩAr values observed in the Greenland and Barents Seas, and was likely to have approached ΩAr≤1 during the winter months. We demonstrate that L. helicina shells are only susceptible to dissolution where both the periostracum has been breached and the aragonite beneath the breach is exposed to waters of ΩAr≤1. Exposure of multiple layers of aragonite in areas of deep dissolution indicate that, as with many molluscs, L. helicina is able to patch up dissolution damage to the shell by secreting additional aragonite internally and maintain their shell. We conclude that, unless breached, the periostracum provides an effective shield for pteropod shells against dissolution in waters ΩAr≤1, and when dissolution does occur the animal has an effective means of self-repair. We suggest

  13. Pension helpdesk calls : A repair mechanism in the client communication of financial institutions

    NARCIS (Netherlands)

    Nell, Louise; Lentz, Leo; Pander Maat, Henk; Koole, Tom

    2015-01-01

    This paper analyzes the role of helpdesk calls in the client communication package of pension funds.Our audio-corpus of 77 helpdesk calls contained 104 client questions. These show that clients seem tocall the helpdesk in order to repair a comprehension problem, to find specific information they mis

  14. Mechanisms and consequences of injury and repair in older organ transplants

    NARCIS (Netherlands)

    B.R. Slegtenhorst (Bendix); F.J.M.F. Dor (Frank); A. Elkhal (Abdala); H. Rodriguez (Hector); X. Yang (Xiaoyong); K. Edtinger (Karoline); R. Quante (Rainer); A.S. Chong (Anita); S.G. Tullius (Stefan)

    2014-01-01

    textabstractDonor organ scarcity remains a significant clinical challenge in transplantation. Older organs, increasingly utilized to meet the growing demand for donor organs, have been linked to inferior transplant outcomes. Susceptibility to organ injury, reduced repair capacity, and increased immu

  15. Dss1 interaction with Brh2 as a regulatory mechanism for recombinational repair

    DEFF Research Database (Denmark)

    Zhou, Qingwen; Kojic, Milorad; Cao, Zhimin;

    2007-01-01

    Brh2, the BRCA2 ortholog in Ustilago maydis, enables recombinational repair of DNA by controlling Rad51 and is in turn regulated by Dss1. Interplay with Rad51 is conducted via the BRC element located in the N-terminal region of the protein and through an unrelated domain, CRE, at the C terminus...

  16. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve A mechanical analysis*

    Institute of Scientific and Technical Information of China (English)

    Tao Yu; Changfu Zhao; Peng Li; Guangyao Liu; Min Luo

    2013-01-01

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study col ected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, fol owing which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) con-duit-repaired sciatic nerve fol owing tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Fol owing poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogen-ous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  17. Mechanical restoration and failure analyses of a hydrogel and scaffold composite strategy for annulus fibrosus repair

    NARCIS (Netherlands)

    Long, Rose G.; Buerki, Alexander; Zysset, Philippe; Eglin, David; Grijpma, Dirk W.; Blanquer, Sebastien B. G.; Hecht, Andrew C.; Iatridis, James C.

    2016-01-01

    Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of her

  18. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis.

    Science.gov (United States)

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min

    2013-07-25

    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  19. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects

    Institute of Scientific and Technical Information of China (English)

    Mafia Fousteri; Leon HF Mullenders

    2008-01-01

    The encounter of elongating RNA polymerase Ⅱ (RNAPIIo) with DNA lesions has severe consequences for the cell as this event provides a strong signal for P53-dependent apoptosis and cell cycle arrest. To counteract prolonged blockage of transcription, the cell removes the RNAPllo-hlocking DNA lesions by transcription-coupled repair (TC-NER), a specialized subpathway of nucleotide excision repair (NER). Exposure of mice to UVB light or chemicals has elucidated that TC-NER is a critical survival pathway protecting against acute toxic and long-term effects (cancer) of genotoxic exposure. Deficiency in TC-NER is associated with mutations in the CSA and CSB genes giving rise to the rare hu-man disorder Cockayne syndrome (CS). Recent data suggest that CSA and CSB play differential roles in mammalian TC-NER: CSB as a repair coupling factor to attract NER proteins, chromatin remodellers and the CSA- E3-ubiquitin iigase complex to the stalled RNAPI io. CSA is dispensable for attraction of NER proteins, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGNl and TFIIS. The emerging picture of TC-NER is complex: repair of transcription-blocking lesions occurs without displacement of the DNA damage-stalled RNAPIIo, and requires at least two essential assembly factors (CSA and CSB), the core NER factors (except for XPC-RAD23B), and TC-NER specific factors. These and yet unidentified proteins will accomplish not only efficient repair of transcrip-tion-blocking lesions, but are also likely to contribute to DNA damage signalling events.

  20. Effect of different mechanical and chemical surface treatments on the repaired bond strength of an indirect composite resin.

    Science.gov (United States)

    Kimyai, Soodabeh; Oskoee, Siavash Savadi; Mohammadi, Narmin; Rikhtegaran, Sahand; Bahari, Mahmoud; Oskoee, Parnian Alizadeh; Vahedpour, Hafez

    2015-02-01

    This study compared the effects of two mechanical surface preparation techniques, air abrasion and Nd:YAG laser, with the use of two adhesive systems, self-etch and etch and rinse, on the repair bond strengths of an indirect composite resin. One hundred fifty cylindrical samples of an indirect composite resin were prepared and randomly divided into six groups (n = 25). In groups 1-3, the composite resin surfaces were respectively prepared as follows: no roughening, roughening by air abrasion, and roughening by Nd:YAG laser, followed by application of an etch-and-rinse adhesive. In groups 4-6, the preparation techniques were respectively the same as those in groups 1-3, followed by application of a self-etch adhesive. Subsequently, a direct composite resin was added and repair bond strengths were measured. Data were analyzed with two-way ANOVA and post hoc Tukey's test. Mean bond strength value was significant based on the preparation technique (P composite resin with air abrasion and Nd:YAG laser resulted in a significant increase in the repair bond strength, with air abrasion being more effective. There were no significant differences in bond strength between the two adhesives.

  1. A Very Common Fallacy in Quantum Mechanics: Superposition, Delayed Choice, Quantum Erasers, Retrocausality, and All That

    CERN Document Server

    Ellerman, David

    2011-01-01

    There is a very common fallacy, here called the separation fallacy, that is involved in the interpretation of quantum experiments involving a certain type of separation such as the: double-slit experiments, which-way interferometer experiments, polarization analyzer experiments, Stern-Gerlach experiments, and quantum eraser experiments. It is the separation fallacy that leads not only to flawed textbook accounts of these experiments but to flawed inferences about retrocausality in the context of "delayed choice" versions of separation experiments.

  2. Mechanisms of DNA repair and radio-induced mutagenesis in higher eukaryotes; Mecanismes de reparation et mutagenese radio-induite chez les eucaryotes superieurs

    Energy Technology Data Exchange (ETDEWEB)

    Averbeck, D. [Centre Universitaire d' Orsay, Institut Curie, Section de Recherche, Lab. Raymond-Latarjet, UMR 2027 CNRS, 91 (France)

    2000-10-01

    Cells of higher eukaryotes possess several very efficient systems for the repair of radiation-induced lesions in DNA. Different strategies have been adopted at the cellular level to remove or even tolerate various types of lesions in order to assure survival and limit the mutagenic consequences. In mammalian cells, the main DNA repair systems comprise direct reversion of damage, excision of damage and exchange mechanisms with intact DNA. Among these, the direct ligation of single strand breaks (SSB) by a DNA ligase and the multi-enzymatic repair systems of mismatch repair, base and nucleotide excision repair as well as the repair of double strand breaks (DSB) by homologous recombination or non homologous end-joining are the most important systems. Most of these processes are error-free except the non homologous end-joining pathway used for the repair of DSB. Moreover, certain lesions can be tolerated by more or less accurately acting polymerases capable of performing trans-lesion DNA syntheses. The DNA repair systems are intimately integrated in the network of cellular regulation. Some of their components are DNA damage inducible. Radiation-induced mutagenesis is largely due to unrepaired DNA damage but also involves error-prone repair processes like the repair of DSB by non-homologous end-joining. Generally, mammalian cells are well prepared to repair radiation-induced lesions. However, some questions remain to be asked about mechanistic details and efficiencies of the systems for removing certain types of radiation-damage and about their order and timing of action. The answers to these questions would be important for radioprotection as well as radiotherapy. (author)

  3. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells

    Science.gov (United States)

    Sansone, Clementina; Galasso, Christian; Orefice, Ida; Nuzzo, Genoveffa; Luongo, Elvira; Cutignano, Adele; Romano, Giovanna; Brunet, Christophe; Fontana, Angelo; Esposito, Francesco; Ianora, Adrianna

    2017-01-01

    Green microalgae contain many active pigments such as carotenoids having antioxidant and protective activity on human cells. Here we investigate the biological activity of an ethanol/water extract of the marine green microalga Tetraselmis suecica containing high levels of carotenoids such as the xanthophylls lutein, violaxanthin, neoxanthin, antheraxanthin and loroxanthin esters. This extract has a strong antioxidant and repairing activity in the human lung cancer cell line (A549) as shown by the increased expression of dehydrocholesterol reductase-24 (DHCR24) and prostaglandin reductase 1 (PTGR1) genes and proteins. The extract also reduces prostaglandin E2 (PGE2) levels in cells damaged by H2O2 and has tissue repairing effects on reconstructed human epidermal tissue cells (EpiDermTM) indicating a potential cosmeceutical activity of this microalgal species. PMID:28117410

  4. Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

    Full Text Available Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM. Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

  5. A fracture mechanics analysis of bonded repaired skin/stiffener structures with inclined central crack

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Ki Hyun; Yang, Won Ho; Kim, Cheol; Heo, Sung Pil [Sungkyunkwan Univ., Seoul (Korea, Republic of); Ko, Myung Hoon [Daelim College, Anyang (Korea, Republic of)

    2001-07-01

    Composite patch repair of cracked aircraft structures has been accepted as one of improving fatigue life and attaining better structural integrity. Analysis for the stress intensity factor at the skin/stiffener structure with inclined central crack repaired by composite stiffened panels are developed. A numerical investigation was conducted to characterize the fracture behavior and crack growth behavior. In order to investigate the crack growth direction, Maximum Tangential Stress(MTS) criteria is used. The main objective of this research is the validation of the inclined crack patching design. In this paper, the reduction of stresses intensity factors at the crack-tip and prediction of crack growth direction are determined to evaluate the effects of various non-dimensional design parameter including; composite patch thickness and stiffener distance. The research on cracked structure subjected to mixed mode loading is accomplished and it is evident that more work using different approaches is necessary.

  6. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells.

    Science.gov (United States)

    Sansone, Clementina; Galasso, Christian; Orefice, Ida; Nuzzo, Genoveffa; Luongo, Elvira; Cutignano, Adele; Romano, Giovanna; Brunet, Christophe; Fontana, Angelo; Esposito, Francesco; Ianora, Adrianna

    2017-01-24

    Green microalgae contain many active pigments such as carotenoids having antioxidant and protective activity on human cells. Here we investigate the biological activity of an ethanol/water extract of the marine green microalga Tetraselmis suecica containing high levels of carotenoids such as the xanthophylls lutein, violaxanthin, neoxanthin, antheraxanthin and loroxanthin esters. This extract has a strong antioxidant and repairing activity in the human lung cancer cell line (A549) as shown by the increased expression of dehydrocholesterol reductase-24 (DHCR24) and prostaglandin reductase 1 (PTGR1) genes and proteins. The extract also reduces prostaglandin E2 (PGE2) levels in cells damaged by H2O2 and has tissue repairing effects on reconstructed human epidermal tissue cells (EpiDerm(TM)) indicating a potential cosmeceutical activity of this microalgal species.

  7. Regulation of DNA repair mechanism in human glioma xenograft cells both in vitro and in vivo in nude mice.

    Directory of Open Access Journals (Sweden)

    Shivani Ponnala

    Full Text Available BACKGROUND: Glioblastoma Multiforme (GBM is the most lethal form of brain tumor. Efficient DNA repair and anti-apoptotic mechanisms are making glioma treatment difficult. Proteases such as MMP9, cathepsin B and urokinase plasminogen activator receptor (uPAR are over expressed in gliomas and contribute to enhanced cancer cell proliferation. Non-homologous end joining (NHEJ repair mechanism plays a major role in double strand break (DSB repair in mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that silencing MMP9 in combination with uPAR/cathepsin B effects NHEJ repair machinery. Expression of DNA PKcs and Ku70/80 at both mRNA and protein levels in MMP9-uPAR (pMU and MMP9-cathepsin B (pMC shRNA-treated glioma xenograft cells were reduced. FACS analysis showed an increase in apoptotic peak and proliferation assays revealed a significant reduction in the cell population in pMU- and pMC-treated cells compared to untreated cells. We hypothesized that reduced NHEJ repair led to DSBs accumulation in pMU- and pMC-treated cells, thereby initiating cell death. This hypothesis was confirmed by reduced Ku70/Ku80 protein binding to DSB, increased comet tail length and elevated γH2AX expression in treated cells compared to control. Immunoprecipitation analysis showed that EGFR-mediated lowered DNA PK activity in treated cells compared to controls. Treatment with pMU and pMC shRNA reduced the expression of DNA PKcs and ATM, and elevated γH2AX levels in xenograft implanted nude mice. Glioma cells exposed to hypoxia and irradiation showed DSB accumulation and apoptosis after pMU and pMC treatments compared to respective controls. CONCLUSION/SIGNIFICANCE: Our results suggest that pMU and pMC shRNA reduce glioma proliferation by DSB accumulation and increase apoptosis under normoxia, hypoxia and in combination with irradiation. Considering the radio- and chemo-resistant cancers favored by hypoxia, our study provides important therapeutic potential

  8. The interplay among chromatin dynamics, cell cycle checkpoints and repair mechanisms modulates the cellular response to DNA damage.

    Science.gov (United States)

    Lazzaro, Federico; Giannattasio, Michele; Muzi-Falconi, Marco; Plevani, Paolo

    2007-06-01

    Cells are continuously under the assault of endogenous and exogenous genotoxic stress that challenges the integrity of DNA. To cope with such a formidable task cells have evolved surveillance mechanisms, known as checkpoints, and a variety of DNA repair systems responding to different types of DNA lesions. These lesions occur in the context of the chromatin structure and, as expected for all DNA transactions, the cellular response to DNA damage is going to be influenced by the chromatin enviroment. In this review, we will discuss recent studies implicating chromatin remodelling factors and histone modifications in the response to DNA double-strand breaks (DSBs) and in checkpoint activation in response to UV lesions.

  9. Dynamics and mechanism of UV-damaged DNA repair in indole-thymine dimer adduct: molecular origin of low repair quantum efficiency.

    Science.gov (United States)

    Guo, Xunmin; Liu, Zheyun; Song, Qinhua; Wang, Lijuan; Zhong, Dongping

    2015-02-26

    Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole-thymine dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.

  10. Characterization of the mechanical properties and structural integrity of T-welded connections repaired by grinding and wet welding

    Energy Technology Data Exchange (ETDEWEB)

    Terán, G., E-mail: gteran@imp.mx [Instituto Mexicano del Petróleo, Eje central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, México D.F. CP 07730, México (Mexico); Cuamatzi-Meléndez, R., E-mail: rcuamatzi@imp.mx [Instituto Mexicano del Petróleo, Eje central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, México D.F. CP 07730, México (Mexico); Albiter, A., E-mail: aalbiter@imp.mx [Instituto Mexicano del Petróleo, Eje central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, México D.F. CP 07730, México (Mexico); Maldonado, C., E-mail: cmzepeda@umich.mx [Instituto de Investigaciones Metalúrgicas, UMSNH, PO Box 52-B, 58000, México (Mexico); Bracarense, A.Q., E-mail: bracarense@ufmg.br [UFMG Departamento de Engeharia Mecánica Belo Horizonte, MG (Brazil)

    2014-04-01

    This paper presents an experimental methodology to characterize the structural integrity and mechanical properties of repaired T-welded connections using in fixed offshore structures. Grinding is employed to remove localized damage like cracking and corrosion and subsequent wet welding can be used to fill the grinded material. But it is important to define the grinding depth and profile in order to maintain structural integrity during the repair. Therefore, in this work different grinding depths were performed, for damage material removal, at the weld toe of the T-welded connections. The grinding was filled by wet welding in a hyperbaric chamber, simulating three different water depths: 50 m, 70 m and 100 m. The electrodes were coated with vinilic varnish, which is cheap and easy to apply. The characterization of the mechanical properties of the T-welded connections was done with standard tensile, hardness and Charpy tests; microstructure and porosity analysis were also performed. The samples were obtained from the welded connections in regions of the wet weld beads. The test results were compared with the mechanical properties of the T-welded connections welded in air conditions performed by other authors. The results showed that the wet welding technique performed in this work produced good mechanical properties of the repaired T-welded connection. The mechanical properties, measured in wet conditions, for 6 mm grinding depth, were similar for the 3 different water depths measured in air conditions. But for 10 mm grinding depth, the values of the mechanical properties measured in wet conditions were quite lower than that for air conditions for the 3 water depths. However a porosity analysis, performed with a Scanning Electronic Microscopy (SEM), showed that the level of porosity in the resulted wet weld beads is in the range of that published in the literature and some samples revealed lower level of porosity. The main resulting microstructure was polygonal

  11. Bacterial radiosensitivity to gamma and ultraviolet. Compositional dependence and repair mechanisms; Radiosensibilidad bacteriana frente a gamma y ultravioleta. Dependencia composicional y mecanismos de reparacion

    Energy Technology Data Exchange (ETDEWEB)

    Saez Angulo, R. M.; Davila, C. A.

    1974-07-01

    The gamma and ultraviolet radiosensitivity of several species of bacteria has been determined its dependence on DNAs composition and repair processes has been studied. Base composition are evaluated by chromatography, DNA melting temperature and isopycnic sedimentation on CsCl gradient. Repair capacity of gamma -and UV- lesions has been studied in two bacterial strains with same DMA base composition. It is concluded that the postulated correlation between radiosensitivity and base composition can not be generalized, the enzymatic repair mechanisms being of determining on radiosensitivity. (Author) 248 refs.

  12. Preparation, bioactivity and mechanism of nano-hydroxyapatite/sodium alginate/chitosan bone repair material.

    Science.gov (United States)

    Liao, Jianguo; Li, Yanqun; Li, Haiyan; Liu, Jingxian; Xie, Yufen; Wang, Jianping; Zhang, Yongxiang

    2017-08-11

    As the major inorganic component of natural bone, nano-hydroxyapatite (n-HA) on its own is limited in its use in bone repair, due to its brittleness. Chitosan (CS) and sodium alginate (SAL) are used to reduce its brittleness and tendency to degradation. However, the compressive strength of the composite is still low, and its biological performance needs further study. Nano-hydroxyapatite/sodium alginate/chitosan (n-HA/SAL/CS) composite was prepared via an in situ synthesis method. Further, we prepared the n-HA/SAL/CS self-setting bone repair material by mixing n-HA/SAL/CS powder with a curing liquid (20 wt.% citric acid). In addition, the in vitro bioactivity and cell cytotoxicity were also explored. Transmission electron microscopy photos revealed that the n-HA crystals were uniformly distributed throughout the polymer matrix. Infrared IR spectroscopy indicated that the HA interacted with the COO- of SAL and NH2- of CS. The compressive strength of the n-HA/SAL/CS bone cement was 34.3 MPa and matched the demands of weight-bearing bones. Soaking in vitro in simulated body fluid demonstrated that the composite material had reasonably good bioactivity, while cytotoxicity tests indicated that the n-HA/SAL/CS cement could promote cell proliferation and was biocompatible. Compressive strength of n-HA/SAL/CS can satisfy the needs of cancellous bone, and in vitro bioactivity and cytotoxicity tests results indicated that the n-HA/SAL/CS composite could act as an optimal bone repair material.

  13. Mechanical Design, Control Choices and first Return of Use of a Prosthetic Arm

    CERN Document Server

    Thomann, Guillaume

    2007-01-01

    In the world of upper limb prostheses, few companies dominate the majority of the market. They propose different kinds of hand, wrist and elbow prostheses but their control is often difficult to understand by the patients. We have decided to develop new myoelectric prosthetic arm (elbow, wrist and hand) by axing our development on the use of new technologies and facility of use for the patient. In this paper, we are explaining in details the different kinds of prostheses currently proposed to the amputees, their advantages and their drawbacks, the descriptions of the patients' needs and the possible improvements of the product. We will develop the designing choices of our prosthesis and the movements it can realize. Then we will explain the simplified control of the product by the patient and its first reactions. Finally, we will conclude by the news ideas and the next researches to concretize.

  14. Divergent impact of Toll-like receptor 2 deficiency on repair mechanisms in healthy muscle versus Duchenne muscular dystrophy.

    Science.gov (United States)

    Mojumdar, Kamalika; Giordano, Christian; Lemaire, Christian; Liang, Feng; Divangahi, Maziar; Qureshi, Salman T; Petrof, Basil J

    2016-05-01

    Injury to skeletal muscle, whether acute or chronic, triggers macrophage-mediated innate immunity in a manner which can be either beneficial or harmful for subsequent repair. Endogenous ligands for Toll-like receptor 2 (TLR2) are released by damaged tissues and might play an important role in activating the innate immune system following muscle injury. To test this hypothesis, we compared macrophage behaviour and muscle repair mechanisms in mice lacking TLR2 under conditions of either acute (cardiotoxin-induced) or chronic (mdx mouse genetic model of Duchenne muscular dystrophy; DMD) muscle damage. In previously healthy muscle subjected to acute damage, TLR2 deficiency reduced macrophage numbers in the muscle post-injury but did not alter the expression pattern of the prototypical macrophage polarization markers iNOS and CD206. In addition, there was abnormal persistence of necrotic fibres and impaired regeneration in TLR2-/- muscles after acute injury. In contrast, TLR2 ablation in chronically diseased muscles of mdx mice not only resulted in significantly reduced macrophage numbers but additionally modified their phenotype by shifting from inflammatory (iNOS(pos) CD206(neg) ) to more anti-inflammatory (iNOS(neg) CD206(pos) ) characteristics. This decrease in macrophage-mediated inflammation was associated with ameliorated muscle histopathology and improved force-generating capacity of the dystrophic muscle. Our results suggest that the role of TLR2 in macrophage function and skeletal muscle repair depends greatly upon the muscle injury context, and raise the possibility that inhibition of TLR2 could serve as a useful therapeutic measure in DMD.

  15. Relationship among the repair mechanisms and the genetic recombination; Relacion entre los mecanismos de reparacion y la recombinacion genetica

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    1987-12-15

    In accordance with the previous reports of the Project BZ87 of the Department of Radiobiology, a dependent stimulation of the system exists in E.coli SOS, of the recombination of the bacteriophage Lambda whose genetic material has not been damaged. This stimulation is not due to the increase of the cellular concentration of the protein RecA and the mechanism but probable for which we find that it is carried out, it is through a cooperation among the product of the gene rec N of E. coli and the system Net of recombination of Lambda. The gene recN belongs to the group of genes SOS and its expression is induced when damaging the bacterial DNA where it intervenes in the repair of breaks of the double helix of the molecule (Picksley et, 1984). If the repair of breaks of this type is a factor that limits the speed with which it happens the recombination among viral chromosomes, then the biggest readiness in the protein RecN, due to the induction of the functions SOS, would facilitate the repair of such ruptures. In this new project it is to enlarge the knowledge about this phenomenon, it was, on one hand of corroborating in a way but he/she specifies the relationship between the recombinogenic response of Lambda and the System SOS of E. coli and for the other one to determine the effect that has the inhibition of the duplication of the DNA on the stimulation of the viral recombination. Everything it with the idea of making it but evident and to be able to use it as a system of genotoxic agents detection in E. coli. (Author)

  16. Abstracts of the Conference on Mechanisms of DNA Repair and Mutagenesis on the 100. Anniversary of the Discovery of Polonium and Radium

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    The conference covered various aspects of mutagenesis and mechanisms of DNA repair. UV and ionizing radiation were use to induce DNA lesions in bacteria, yeast and cell cultures of higher organisms. This allows study of influence of mutations on particular processes in the cell. Mechanisms of resistance were also investigated. Biological investigations were performed using labelled compounds.

  17. [Research on effects of vitamin A palmitate on repair of mechanical corneal epithelial defects and conjunctival goblet cells in rabbits].

    Science.gov (United States)

    Qiu, Xiao-di; Gong, Lan; Chen, Min-jie

    2010-02-01

    Randomized controlled experimental study to investigate the influence of vitamin A palmitate and bovine recombinant basic fibroblast growth factor (bFGF) on repair of mechanical corneal epithelial defects, conjunctival epithelial cells and goblet cells in rabbits. One hundred and twenty New Zealand rabbits (all males) were selected to establish the mechanical corneal epithelial defects models (scratching out a round area with the diameter of 8 mm in the centre of cornea). Forty eight New Zealand rabbits were randomly divided into 4 groups: group A used lincomycin hydrochloride eye drops (LED) after the model had been established; group B used vitamin A palmitate eye gel and LED; group C used recombinant bFGF eye gel and LED; group D used vitamin A palmitate eye gel, bFGF eye gel and LED. Photo slit lamp examination and measurement of repaired area were performed on day 0, day 1, day 4 and day 7; transmission electron microscopy, histological microscope examination and impression cytology were performed on day 0, day 1, day 4 and day 7 to analysis the morphology and repairment of corneal epithelium, conjunctival epithelial cells and the goblet cells. The variants were tested using analysis of variance and Tukey's test. Statistic analysis showed that on day 1, the size of areas of repaired corneal epithelium was: group A(53.512 +/- 18.850) mm(2), group B (92.194 +/- 14.367) mm(2), group C (89.779 +/- 20.535) mm(2), group D (127.816 +/- 16.379) mm(2). The difference in size of repaired areas between different groups was statistically significant (F = 17.663, P = 0.000), with exception of the difference between groups B and C (P = 0.995). Conjunctival impression cytology showed that, the average number of conjunctival goblet cells per 740 microm x 550 microm at day 1 was decreased, group A (10.083 +/- 4.441), group B (10.667 +/- 3.551), group C (9.583 +/- 4.502), group D (9.167 +/- 5.606). The difference between these four groups was not significant (F = 0.239, P = 0

  18. Constitutional Chromothripsis Rearrangements Involve Clustered Double-Stranded DNA Breaks and Nonhomologous Repair Mechanisms

    Directory of Open Access Journals (Sweden)

    Wigard P. Kloosterman

    2012-06-01

    Full Text Available Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements.

  19. Evaluation of natural and engineered resistance mechanisms in potato against Colorado potato beetle in a no-choice field study.

    Science.gov (United States)

    Cooper, Susannah G; Douches, David S; Coombs, Joseph J; Grafius, Edward J

    2007-04-01

    The Colorado potato beetle, Leptinotarsa decemlineata Say, is the major insect pest of potato, Solanum tuberosum L., in eastern North America and is renowned for resistance development, currently resistant to >40 insecticides worldwide. Host plant resistance may assist in delaying in resistance development to insecticides. We evaluated natural host plant resistance mechanisms (glandular trichomes and Solanum chacoense Bitter-derived resistance) and engineered resistance mechanisms (Bacillus thuringiensis [Bt] Berliner cry3A and cry1Ia1) in a no-choice cage study. Six different potato lines representing four host plant resistance mechanisms were evaluated over 2 yr. Egg masses were placed in each cage (one egg mass per plant). Almost no feeding was observed in the Bt-cry3A lines, and only minor feeding was observed in the Bt-cry1Ia1 lines in either year. On the S. chacoense-derived line, there was significantly less defoliation than on either the susceptible line or the glandular trichome line in 2003. In 2004, there was significantly higher defoliation on the S. chacoense-derived line than on the susceptible line or glandular trichome line. The defoliation of the Solanum chacoense-derived line was largely due to larvae clipping the petioles, rather than consumption of the leaves. Defoliation on the glandular trichome line did not differ significantly from the defoliation of the susceptible line, suggesting glandular trichomes may not be effective in controlling larvae and preventing defoliation. This study suggested that Bt can provide high levels of resistance, but the natural resistance mechanisms tested here are variable for control of Colorado potato beetle larvae in no-choice situations.

  20. Introducing Mechanics: II. Towards a Justified Choice between Alternative Theories of Motion

    Science.gov (United States)

    Emmett, Katrina; Klaassen, Kees; Eijkelhof, Harrie

    2009-01-01

    In an earlier article we presented an innovative approach for introducing mechanics at upper secondary level based on the idea of tapping core causal knowledge, and we described the working of the first part of the module. In this article we describe the second part of the module, in which we make use of the students' intuitive plausibility…

  1. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

    Directory of Open Access Journals (Sweden)

    Francesca Marini

    2016-08-01

    Full Text Available Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2, the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs. Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles.

  2. Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations.

    Science.gov (United States)

    Allardyce, Benjamin J; Rajkhowa, Rangam; Dilley, Rodney J; Xie, Zhigang; Campbell, Luke; Keating, Adrian; Atlas, Marcus D; von Unge, Magnus; Wang, Xungai

    2016-12-01

    The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100μm) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing. These membranes were tested alongside animal cartilage, currently the strongest available myringoplasty graft as well as paper, which is commonly used for simpler procedures. Silk membranes showed resonant frequencies within the human hearing range and a higher vibrational amplitude than cartilage, suggesting that silk may offer good acoustic energy transfer characteristics. Silk membranes were also highly resistant to simulated pressure changes in the middle ear, suggesting they can resist retraction, a common cause of graft failure resulting from chronic negative pressures in the middle ear. Part of this strength can be explained by the substantially higher modulus of silk films compared with cartilage. This allows for the production of films that are much thinner than cartilage, with superior acoustic properties, but that still provide the same level of mechanical support as thicker cartilage. Together, these in vitro results suggest that silk membranes may provide good hearing outcomes while offering similar levels of mechanical support to the reconstructed middle ear.

  3. Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases.

    Science.gov (United States)

    Woods, Ryan D; O'Shea, Valerie L; Chu, Aurea; Cao, Sheng; Richards, Jody L; Horvath, Martin P; David, Sheila S

    2016-01-29

    MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new-for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer.

  4. Effects of suture position on left ventricular fluid mechanics under mitral valve edge-to-edge repair.

    Science.gov (United States)

    Du, Dongxing; Jiang, Song; Wang, Ze; Hu, Yingying; He, Zhaoming

    2014-01-01

    Mitral valve (MV) edge-to-edge repair (ETER) is a surgical procedure for the correction of mitral valve regurgitation by suturing the free edge of the leaflets. The leaflets are often sutured at three different positions: central, lateral and commissural portions. To study the effects of position of suture on left ventricular (LV) fluid mechanics under mitral valve ETER, a parametric model of MV-LV system during diastole was developed. The distribution and development of vortex and atrio-ventricular pressure under different suture position were investigated. Results show that the MV sutured at central and lateral in ETER creates two vortex rings around two jets, compared with single vortex ring around one jet of the MV sutured at commissure. Smaller total orifices lead to a higher pressure difference across the atrio-ventricular leaflets in diastole. The central suture generates smaller wall shear stresses than the lateral suture, while the commissural suture generated the minimum wall shear stresses in ETER.

  5. β1 integrin signaling in asymmetric migration of keratinocytes under mechanical stretch in a co-cultured wound repair model.

    Science.gov (United States)

    Lü, Dongyuan; Li, Zhan; Gao, Yuxin; Luo, Chunhua; Zhang, Fan; Zheng, Lu; Wang, Jiawen; Sun, Shujin; Long, Mian

    2016-12-28

    Keratinocyte (KC) migration in re-epithelization is crucial in repairing injured skin. But the mechanisms of how mechanical stimuli regulate the migration of keratinocytes have been poorly understood. Human immortalized keratinocyte HaCaT cells were co-cultured with skin fibroblasts on PDMS membranes and transferred to the static stretch device developed in-house for additional 6 day culture under mechanical stretch to mimic surface tension in skin. To detect the expression of proteins on different position at different time points and the effect of β1 integrin mechanotransduction on HaCaT migration, Immunofluorescence, Reverse transcription-polymerase chain reaction, Flow cytometry, Western blotting assays were applied. Mechanical receptor of β1 integrin that recognizes its ligand of collagen I was found to be strongly associated with migration of HaCaT cells since the knockdown of β1 integrin via RNA silence eliminated the key protein expression dynamically. Here the expression of vinculin was lower but that of Cdc42 was higher for the cells at outward edge than those at inward edge, respectively, supporting that the migration capability of keratinocytes is inversely correlated with the formation of focal adhesion complexes but positively related to the lamellipodia formation. This asymmetric expression feature was further confirmed by high or low expression of PI3K for outward- or inward-migrating cells. And ERK1/2 phosphorylation was up-regulated by mechanical stretch. We reported here, a novel mechanotransduction signaling pathways were β1 integrin-dependent pattern of keratinocytes migration under static stretch in an in vitro co-culture model. These results provided an insight into underlying molecular mechanisms of keratinocyte migration under mechanical stimuli.

  6. Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?

    Directory of Open Access Journals (Sweden)

    Peter Göttle

    2015-07-01

    Full Text Available A prominent feature of demyelinating diseases such as multiple sclerosis (MS is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC activation. These cells represent a widespread cell population within the adult central nervous system (CNS that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation-associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS.

  7. Intracellular Protein Shuttling: A Mechanism Relevant for Myelin Repair in Multiple Sclerosis?

    Science.gov (United States)

    Göttle, Peter; Küry, Patrick

    2015-07-03

    A prominent feature of demyelinating diseases such as multiple sclerosis (MS) is the degeneration and loss of previously established functional myelin sheaths, which results in impaired signal propagation and axonal damage. However, at least in early disease stages, partial replacement of lost oligodendrocytes and thus remyelination occur as a result of resident oligodendroglial precursor cell (OPC) activation. These cells represent a widespread cell population within the adult central nervous system (CNS) that can differentiate into functional myelinating glial cells to restore axonal functions. Nevertheless, the spontaneous remyelination capacity in the adult CNS is inefficient because OPCs often fail to generate new oligodendrocytes due to the lack of stimulatory cues and the presence of inhibitory factors. Recent studies have provided evidence that regulated intracellular protein shuttling is functionally involved in oligodendroglial differentiation and remyelination activities. In this review we shed light on the role of the subcellular localization of differentiation-associated factors within oligodendroglial cells and show that regulation of intracellular localization of regulatory factors represents a crucial process to modulate oligodendroglial maturation and myelin repair in the CNS.

  8. CNS repair and axon regeneration: Using genetic variation to determine mechanisms.

    Science.gov (United States)

    Tedeschi, Andrea; Omura, Takao; Costigan, Michael

    2017-01-01

    The importance of genetic diversity in biological investigation has been recognized since the pioneering studies of Gregor Johann Mendel and Charles Darwin. Research in this area has been greatly informed recently by the publication of genomes from multiple species. Genes regulate and create every part and process in a living organism, react with the environment to create each living form and morph and mutate to determine the history and future of each species. The regenerative capacity of neurons differs profoundly between animal lineages and within the mammalian central and peripheral nervous systems. Here, we discuss research that suggests that genetic background contributes to the ability of injured axons to regenerate in the mammalian central nervous system (CNS), by controlling the regulation of specific signaling cascades. We detail the methods used to identify these pathways, which include among others Activin signaling and other TGF-β superfamily members. We discuss the potential of altering these pathways in patients with CNS damage and outline strategies to promote regeneration and repair by combinatorial manipulation of neuron-intrinsic and extrinsic determinants. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Structural basis for a novel mechanism of DNA bridging and alignment in eukaryotic DSB DNA repair.

    Science.gov (United States)

    Gouge, Jérôme; Rosario, Sandrine; Romain, Félix; Poitevin, Frédéric; Béguin, Pierre; Delarue, Marc

    2015-04-15

    Eukaryotic DNA polymerase mu of the PolX family can promote the association of the two 3'-protruding ends of a DNA double-strand break (DSB) being repaired (DNA synapsis) even in the absence of the core non-homologous end-joining (NHEJ) machinery. Here, we show that terminal deoxynucleotidyltransferase (TdT), a closely related PolX involved in V(D)J recombination, has the same property. We solved its crystal structure with an annealed DNA synapsis containing one micro-homology (MH) base pair and one nascent base pair. This structure reveals how the N-terminal domain and Loop 1 of Tdt cooperate for bridging the two DNA ends, providing a templating base in trans and limiting the MH search region to only two base pairs. A network of ordered water molecules is proposed to assist the incorporation of any nucleotide independently of the in trans templating base. These data are consistent with a recent model that explains the statistics of sequences synthesized in vivo by Tdt based solely on this dinucleotide step. Site-directed mutagenesis and functional tests suggest that this structural model is also valid for Pol mu during NHEJ.

  10. Playful Mobility Choices: Motivating informed mobility decision making by applying game mechanics

    OpenAIRE

    2014-01-01

    Motivating people to change their mobility behaviour patterns towards more sustainable forms of mobility is one of the major challenges regarding climate change and quality of life. Recently, an increasing amount of attempts to use gamification for triggering such behavioural changes can be observed. However, little is known about the actual impact of using game elements. This contribution describes a concept for systematically analysing the group-specific effects of different game mechanics ...

  11. Mechanical Stress Changes the Complex Interplay Between HO-1, Inflammation and Fibrosis, During Excisional Wound Repair

    NARCIS (Netherlands)

    Cremers, N.A.J.; Suttorp, M.; Gerritsen, M.M.; Wong, R.J.; Run-van Breda, C. van; Dam, G.M. van; Brouwer, K.M.; Kuijpers-Jagtman, A.M.; Carels, C.E.L.; Lundvig, D.M.; Wagener, F.A.D.T.G.

    2015-01-01

    Mechanical stress following surgery or injury can promote pathological wound healing and fibrosis, and lead to functional loss and esthetic problems. Splinted excisional wounds can be used as a model for inducing mechanical stress. The cytoprotective enzyme heme oxygenase-1 (HO-1) is thought to orch

  12. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    NARCIS (Netherlands)

    Dierssen, Jan Willem Frederik

    2010-01-01

    This thesis describes molecular methods to distinguish separate colon tumour entities. Furthermore, it shows that distinct immune escape mechanisms, in particular distinct mechanisms of corrupting the HLA system, are operational in subsets of colon tumours. The apparent necessity of some colon tumou

  13. DNA repair activity in fish and interest in ecotoxicology: a review.

    Science.gov (United States)

    Kienzler, Aude; Bony, Sylvie; Devaux, Alain

    2013-06-15

    The knowledge of DNA repair in a target species is of first importance as it is the primary line of defense against genotoxicants, and a better knowledge of DNA repair capacity in fish could help to interpret genotoxicity data and/or assist in the choice of target species, developmental stage and tissues to focus on, both for environmental biomonitoring studies and DNA repair testing. This review focuses in a first part on what is presently known on a mechanistic basis, about the various DNA repair systems in fish, in vivo and in established cell lines. Data on base excision repair (BER), direct reversal with O⁶-alkylguanine transferase and double strand breaks repair, although rather scarce, are being reviewed, as well as nucleotide excision repair (NER) and photoreactivation repair (PER), which are by far the most studied repair mechanisms in fish. Most of these repair mechanisms seem to be strongly species and tissue dependent; they also depend on the developmental stage of the organisms. BER is efficient in vivo, although no data has been found on in vitro models. NER activity is quite low or even inexistent depending on the studies; however this lack is partly compensated by a strong PER activity, especially in early developmental stage. In a second part, a survey of the ecotoxicological studies integrating DNA repair as a parameter responding to single or mixture of contaminant is realized. Three main approaches are being used: the measurement of DNA repair gene expression after exposure, although it has not yet been clearly established whether gene expression is indicative of repair capacity; the monitoring of DNA damage removal by following DNA repair kinetics; and the modulation of DNA repair activity following exposure in situ, in order to assess the impact of exposure history on DNA repair capacity. Since all DNA repair processes are possible targets for environmental pollutants, we can also wonder at which extent such a modulation of repair capacities

  14. DNA repair mechanism by photolyase: electron transfer path from the photolyase catalytic cofactor FADH(-) to DNA thymine dimer.

    Science.gov (United States)

    Medvedev, D; Stuchebrukhov, A A

    2001-05-21

    Photolyase is an enzyme that catalyses photorepair of thymine dimers in UV damaged DNA by electron transfer reaction. The structure of the photolyase/DNA complex is unknown at present. Using crystal structure coordinates of the substrate-free enzyme from E. coli, we have recently built a computer molecular model of a thymine dimer docked to photolyase catalytic site and studied molecular dynamics of the system. In this paper, we present analysis of the electronic coupling and electron transfer pathway between the catalytic cofactor FADH(-) and the pyrimidine dimer by the method of interatomic tunneling currents. Electronic structure is treated in the extended Hückel approximation. The root mean square transfer matrix element is about 6 cm(-1), which is consistent with the experimentally determined rate of transfer. We find that electron transfer mechanism responsible for the repair utilizes an unusual folded conformation of FADH(-) in photolyases, in which the isoalloxazine ring of the flavin and the adenine are in close proximity, and the peculiar features of the docked orientation of the dimer. The tunneling currents show explicitly that despite of the close proximity between the donor and acceptor complexes, the electron transfer mechanism between the flavin and the thymine bases is not direct, but indirect, with the adenine acting as an intermediate. These calculations confirm the previously made conclusion based on an indirect evidence for such mechanism.

  15. Deliberate choices or strong motives: Exploring the mechanisms underlying the bias of organic claims on leniency judgments.

    Science.gov (United States)

    Prada, Marília; Rodrigues, David; Garrido, Margarida V

    2016-08-01

    Organic claims can influence how a product is perceived in dimensions that are unrelated with the food production method (e.g., organic food is perceived as more healthful and less caloric than conventional food). Such claims can also bias how the consumers of organic food are perceived and how other people judge their behavior. Schuldt and Schwarz (2010) have shown that individuals evaluating a target with a weight-loss goal are more lenient in judging the target forgoing exercise when the target had an organic (vs. conventional) dessert. This impact of organic claims on leniency judgments has been interpreted either as a halo or a licensing effect. In the current research we aim to replicate and extend Schuldt and Schwarz's (2010) results by examining the mechanisms that are more likely to explain the observed leniency judgments. In Experiment 1, we observed that leniency towards a target that has consumed an organic meal is only observed when the target intentionally chooses such organic meal (vs. choice determined by the situation). These findings suggest that the impact of organic claims on leniency judgments is not merely based on a halo effect. Instead, a licensing account emerges as the most probable mechanism. In Experiment 2, we further found that stronger (vs. weaker) motives for forgoing exercise influenced leniency judgments to the same extent as having had an organic meal. Understanding the mechanisms that shape consumers' decisions may have important implications to prevent bias in their judgments about food and exercise.

  16. Mechanisms of weight loss, diabetes control and changes in food choices after gastrointestinal surgery.

    Science.gov (United States)

    Papamargaritis, Dimitrios; Panteliou, Eleftheria; Miras, Alexander D; le Roux, Carel W

    2012-12-01

    The long-term effects of lifestyle changes, diet and medical therapy on obesity are limited. Bariatric surgery is the most effective long-term treatment with the greatest chances for amelioration of obesity-associated complications, including type 2 diabetes mellitus (T2DM). There is increasing evidence in the literature that bariatric operations have a profound effect on human physiology, by reducing hunger, increasing satiety, paradoxically increasing energy expenditure, and even promoting healthy food preferences. Some of these operations improve glucose homeostasis in patients with T2DM independently of weight loss. Changes in the gut hormone levels of glucagon-like peptide 1, peptide YY and ghrelin have been proposed as some of the mediators implicated in changing physiology. The aim of this review is to critically explore the current knowledge on the putative mechanisms of the change in weight and improvement in T2DM glycaemic control after the most commonly performed bariatric operations.

  17. Cumulative asbestos exposure for US automobile mechanics involved in brake repair (circa 1950s-2000).

    Science.gov (United States)

    Finley, Brent L; Richter, Richard O; Mowat, Fionna S; Mlynarek, Steve; Paustenbach, Dennis J; Warmerdam, John M; Sheehan, Patrick J

    2007-11-01

    We analyzed cumulative lifetime exposure to chrysotile asbestos experienced by brake mechanics in the US during the period 1950-2000. Using Monte Carlo methods, cumulative exposures were calculated using the distribution of 8-h time-weighted average exposure concentrations for brake mechanics and the distribution of job tenure data for automobile mechanics. The median estimated cumulative exposures for these mechanics, as predicted by three probabilistic models, ranged from 0.16 to 0.41 fibers per cubic centimeter (f/cm(3)) year for facilities with no dust-control procedures (1970s), and from 0.010 to 0.012 f/cm(3) year for those employing engineering controls (1980s). Upper-bound (95%) estimates for the 1970s and 1980s were 1.96 to 2.79 and 0.07-0.10 f/cm(3) year, respectively. These estimates for US brake mechanics are consistent with, but generally slightly lower than, those reported for European mechanics. The values are all substantially lower than the cumulative exposure of 4.5 f/cm(3) year associated with occupational exposure to 0.1 f/cm(3) of asbestos for 45 years that is currently permitted under the current occupational exposure limits in the US. Cumulative exposures were usually about 100- to 1,000-fold less than those of other occupational groups with asbestos exposure for similar time periods. The cumulative lifetime exposure estimates presented here, combined with the negative epidemiology data for brake mechanics, could be used to refine the risk assessments for chrysotile-exposed populations.

  18. Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.

    Directory of Open Access Journals (Sweden)

    Dongyuan Lü

    Full Text Available Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.

  19. Farm and Ranch Mechanical Repair and VEH Farm and Ranch Maintenance. Curriculum Guide for Agribusiness 121. Agricultural Mechanics.

    Science.gov (United States)

    Texas A and M Univ., College Station. Dept. of Agricultural Education.

    This curriculum guide provides materials for teachers to use in developing a 1- or 2-year course in agricultural mechanics for at-risk and special education students. It is one of 28 semester courses in agricultural science and technology for Texas high schools. The program prepares low-achieving students with employability skills that are…

  20. A Protective Mechanism of Visible Red Light in Normal Human Dermal Fibroblasts: Enhancement of GADD45A-Mediated DNA Repair Activity.

    Science.gov (United States)

    Kim, Yeo Jin; Kim, Hyoung-June; Kim, Hye Lim; Kim, Hyo Jeong; Kim, Hyun Soo; Lee, Tae Ryong; Shin, Dong Wook; Seo, Young Rok

    2017-02-01

    The phototherapeutic effects of visible red light on skin have been extensively investigated, but the underlying biological mechanisms remain poorly understood. We aimed to elucidate the protective mechanism of visible red light in terms of DNA repair of UV-induced oxidative damage in normal human dermal fibroblasts. The protective effect of visible red light on UV-induced DNA damage was identified by several assays in both two-dimensional and three-dimensional cell culture systems. With regard to the protective mechanism of visible red light, our data showed alterations in base excision repair mediated by growth arrest and DNA damage inducible, alpha (GADD45A). We also observed an enhancement of the physical activity of GADD45A and apurinic/apyrimidinic endonuclease 1 (APE1) by visible red light. Moreover, UV-induced DNA damages were diminished by visible red light in an APE1-dependent manner. On the basis of the decrease in GADD45A-APE1 interaction in the activating transcription factor-2 (ATF2)-knockdown system, we suggest a role for ATF2 modulation in GADD45A-mediated DNA repair upon visible red light exposure. Thus, the enhancement of GADD45A-mediated base excision repair modulated by ATF2 might be a potential protective mechanism of visible red light. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Mechanism of repair of acrolein- and malondialdehyde-derived exocyclic guanine adducts by the α-ketoglutarate/Fe(II) dioxygenase AlkB.

    Science.gov (United States)

    Singh, Vipender; Fedeles, Bogdan I; Li, Deyu; Delaney, James C; Kozekov, Ivan D; Kozekova, Albena; Marnett, Lawrence J; Rizzo, Carmelo J; Essigmann, John M

    2014-09-15

    The structurally related exocyclic guanine adducts α-hydroxypropano-dG (α-OH-PdG), γ-hydroxypropano-dG (γ-OH-PdG), and M1dG are formed when DNA is exposed to the reactive aldehydes acrolein and malondialdehyde (MDA). These lesions are believed to form the basis for the observed cytotoxicity and mutagenicity of acrolein and MDA. In an effort to understand the enzymatic pathways and chemical mechanisms that are involved in the repair of acrolein- and MDA-induced DNA damage, we investigated the ability of the DNA repair enzyme AlkB, an α-ketoglutarate/Fe(II) dependent dioxygenase, to process α-OH-PdG, γ-OH-PdG, and M1dG in both single- and double-stranded DNA contexts. By monitoring the repair reactions using quadrupole time-of-flight (Q-TOF) mass spectrometry, it was established that AlkB can oxidatively dealkylate γ-OH-PdG most efficiently, followed by M1dG and α-OH-PdG. The AlkB repair mechanism involved multiple intermediates and complex, overlapping repair pathways. For example, the three exocyclic guanine adducts were shown to be in equilibrium with open-ring aldehydic forms, which were trapped using (pentafluorobenzyl)hydroxylamine (PFBHA) or NaBH4. AlkB repaired the trapped open-ring form of γ-OH-PdG but not the trapped open-ring of α-OH-PdG. Taken together, this study provides a detailed mechanism by which three-carbon bridge exocyclic guanine adducts can be processed by AlkB and suggests an important role for the AlkB family of dioxygenases in protecting against the deleterious biological consequences of acrolein and MDA.

  2. Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes.

    Directory of Open Access Journals (Sweden)

    Maria E Morales

    Full Text Available Heavy metals such as cadmium, arsenic and nickel are classified as carcinogens. Although the precise mechanism of carcinogenesis is undefined, heavy metal exposure can contribute to genetic damage by inducing double strand breaks (DSBs as well as inhibiting critical proteins from different DNA repair pathways. Here we take advantage of two previously published culture assay systems developed to address mechanistic aspects of DNA repair to evaluate the effects of heavy metal exposures on competing DNA repair outcomes. Our results demonstrate that exposure to heavy metals significantly alters how cells repair double strand breaks. The effects observed are both specific to the particular metal and dose dependent. Low doses of NiCl2 favored resolution of DSBs through homologous recombination (HR and single strand annealing (SSA, which were inhibited by higher NiCl2 doses. In contrast, cells exposed to arsenic trioxide preferentially repaired using the "error prone" non-homologous end joining (alt-NHEJ while inhibiting repair by HR. In addition, we determined that low doses of nickel and cadmium contributed to an increase in mutagenic recombination-mediated by Alu elements, the most numerous family of repetitive elements in humans. Sequence verification confirmed that the majority of the genetic deletions were the result of Alu-mediated non-allelic recombination events that predominantly arose from repair by SSA. All heavy metals showed a shift in the outcomes of alt-NHEJ repair with a significant increase of non-templated sequence insertions at the DSB repair site. Our data suggest that exposure to heavy metals will alter the choice of DNA repair pathway changing the genetic outcome of DSBs repair.

  3. Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms.

    Directory of Open Access Journals (Sweden)

    Elizabeth D Hutchins

    Full Text Available Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.

  4. Advanced self-healing asphalt composites in the pavement performance field: mechanisms at the nano level and new repairing methodologies.

    Science.gov (United States)

    Agzenai, Yahya; Pozuelo, Javier; Sanz, Javier; Perez, Ignacio; Baselga, Juan

    2015-01-01

    In an effort to give a global view of this field of research, in this mini-review we highlight the most recent publications and patents focusing on modified asphalt pavements that contain certain reinforcing nanoparticles which impart desirable thermal, electrical and mechanical properties. In response to the increasing cost of asphalt binder and road maintenance, there is a need to look for alternative technologies and new asphalt composites, able to self-repair, for preserving and renewing the existing pavements. First, we will focus on the self-healing property of asphalt, the evidences that support that healing takes place immediately after the contact between the faces of a crack, and how the amount of healing can be measured in both the laboratory and the field. Next we review the hypothetical mechanisms of healing to understand the material behaviour and establish models to quantify the damage-healing process. Thereafter, we outline different technologies, nanotechnologies and methodologies used for self-healing paying particular attention to embedded micro-capsules, new nano-materials like carbon nanotubes and nano-fibres, ionomers, and microwave and induction heating processes.

  5. Transcriptomic analysis of tail regeneration in the lizard Anolis carolinensis reveals activation of conserved vertebrate developmental and repair mechanisms.

    Science.gov (United States)

    Hutchins, Elizabeth D; Markov, Glenn J; Eckalbar, Walter L; George, Rajani M; King, Jesse M; Tokuyama, Minami A; Geiger, Lauren A; Emmert, Nataliya; Ammar, Michael J; Allen, April N; Siniard, Ashley L; Corneveaux, Jason J; Fisher, Rebecca E; Wade, Juli; DeNardo, Dale F; Rawls, J Alan; Huentelman, Matthew J; Wilson-Rawls, Jeanne; Kusumi, Kenro

    2014-01-01

    Lizards, which are amniote vertebrates like humans, are able to lose and regenerate a functional tail. Understanding the molecular basis of this process would advance regenerative approaches in amniotes, including humans. We have carried out the first transcriptomic analysis of tail regeneration in a lizard, the green anole Anolis carolinensis, which revealed 326 differentially expressed genes activating multiple developmental and repair mechanisms. Specifically, genes involved in wound response, hormonal regulation, musculoskeletal development, and the Wnt and MAPK/FGF pathways were differentially expressed along the regenerating tail axis. Furthermore, we identified 2 microRNA precursor families, 22 unclassified non-coding RNAs, and 3 novel protein-coding genes significantly enriched in the regenerating tail. However, high levels of progenitor/stem cell markers were not observed in any region of the regenerating tail. Furthermore, we observed multiple tissue-type specific clusters of proliferating cells along the regenerating tail, not localized to the tail tip. These findings predict a different mechanism of regeneration in the lizard than the blastema model described in the salamander and the zebrafish, which are anamniote vertebrates. Thus, lizard tail regrowth involves the activation of conserved developmental and wound response pathways, which are potential targets for regenerative medical therapies.

  6. Insights into the epigenetic mechanisms involving histone lysine methylation and demethylation in ischemia induced damage and repair has therapeutic implication.

    Science.gov (United States)

    Chakravarty, Sumana; Jhelum, Priya; Bhat, Unis Ahmad; Rajan, Wenson D; Maitra, Swati; Pathak, Salil S; Patel, Anant B; Kumar, Arvind

    2017-01-01

    Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/local administration of histone deacetylase inhibitors. However, the role of other epigenetic mechanisms such as histone lysine methylation and demethylation in stroke-induced damage and subsequent recovery process is elusive. Here, we established an Internal Carotid Artery Occlusion (ICAO) model in CD1 mouse that resulted in mild to moderate level of ischemic damage to the striatum, as suggested by magnetic resonance imaging (MRI), TUNEL and histopathological staining along with an evaluation of neurological deficit score (NDS), grip strength and rotarod performance. The molecular investigations show dysregulation of a number of histone lysine methylases (KMTs) and few of histone lysine demethylases (KDMs) post-ICAO with significant global attenuation in the transcriptionally repressive epigenetic mark H3K9me2 in the striatum. Administration of Dimethyloxalylglycine (DMOG), an inhibitor of KDM4 or JMJD2 class of histone lysine demethylases, significantly ameliorated stroke-induced NDS by restoring perturbed H3K9me2 levels in the ischemia-affected striatum. Overall, these results highlight the novel role of epigenetic regulatory mechanisms controlling the epigenetic mark H3K9me2 in mediating the stroke-induced striatal damage and subsequent repair following mild to moderate cerebral ischemia.

  7. Cellular and molecular mechanisms of repair in acute and chronic wound healing.

    Science.gov (United States)

    Martin, P; Nunan, R

    2015-08-01

    A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.

  8. A mathematical model of the process of ligament repair: effect of cold therapy and mechanical stress.

    Science.gov (United States)

    Cárdenas Sandoval, Rosy Paola; Garzón-Alvarado, Diego Alexander; Ramírez Martínez, Angélica Maria

    2012-06-07

    This article proposes a mathematical model that predicts the wound healing process of the ligament after a sprain, grade II. The model describes the swelling, expression of the platelet-derived growth factor (PDGF), formation and migration of fibroblasts into the injury area and the expression of collagen fibers. Additionally, the model can predict the effect of ice treatment in reducing inflammation and the action of mechanical stress in the process of remodeling of collagen fibers. The results obtained from computer simulation show a high concordance with the clinical data previously reported by other authors.

  9. Distinct mechanisms for opposite functions of homeoproteins Cdx2 and HoxB7 in double-strand break DNA repair in colon cancer cells.

    Science.gov (United States)

    Soret, Christine; Martin, Elisabeth; Duluc, Isabelle; Dantzer, Françoise; Vanier, Marie; Gross, Isabelle; Freund, Jean-Noël; Domon-Dell, Claire

    2016-05-01

    Homeobox genes, involved in embryonic development and tissues homeostasis in adults, are often deregulated in cancer, but their relevance in pathology is far from being fully elucidated. In colon cancers, we report that the homeoproteins HoxB7 and Cdx2 exhibit different heterogeneous patterns, Cdx2 being localized in moderately altered neoplasic glands in contrast to HoxB7 which predominates in poorly-differentiated areas; they are coexpressed in few cancer cells. In human colon cancer cells, both homeoproteins interact with the DNA repair factor KU70/80, but functional studies reveal opposite effects: HoxB7 stimulates DNA repair and cell survival upon etoposide treatment, whereas Cdx2 inhibits both processes. The stimulatory effect of HoxB7 on DNA repair requires the transactivation domain linked to the homeodomain involved in the interaction with KU70/80, whereas the transactivation domain of Cdx2 is dispensable for its inhibitory function, which instead needs the homeodomain to interact with KU70/80 and the C-terminal domain. Thus, HoxB7 and Cdx2 respectively use transcription-dependent and -independent mechanisms to stimulate and inhibit DNA repair. In addition, in cells co-expressing both homeoproteins, Cdx2 lessens DNA repair activity through a novel mechanism of inhibition of the transcriptional function of HoxB7, whereby Cdx2 forms a molecular complex with HoxB7 and prevents it to recognize its target in the chromatin. These results point out the complex interplay between the DSB DNA repair activity and the homeoproteins HoxB7 and Cdx2 in colon cancer cells, making the balance between these factors a determinant and a potential indicator of the efficacy of genotoxic drugs.

  10. The fluid mechanics of scleral buckling surgery for the repair of retinal detachment.

    Science.gov (United States)

    Foster, William Joseph; Dowla, Nadia; Joshi, Saurabh Y; Nikolaou, Michael

    2010-01-01

    Scleral buckling is a common surgical technique used to treat retinal detachments that involves suturing a radial or circumferential silicone element on the sclera. Although this procedure has been performed since the 1960s, and there is a reasonable experimental model of retinal detachment, there is still debate as to how this surgery facilitates the re-attachment of the retina. Finite element calculations using the COMSOL Multiphysics system are utilized to explain the influence of the scleral buckle on the flow of sub-retinal fluid in a physical model of retinal detachment. We found that, by coupling fluid mechanics with structural mechanics, laminar fluid flow and the Bernoulli effect are necessary for a physically consistent explanation of retinal reattachment. Improved fluid outflow and retinal reattachment are found with low fluid viscosity and rapid eye movements. A simulation of saccadic eye movements was more effective in removing sub-retinal fluid than slower, reading speed, eye movements in removing subretinal fluid. The results of our simulations allow us to explain the physical principles behind scleral buckling surgery and provide insight that can be utilized clinically. In particular, we find that rapid eye movements facilitate more rapid retinal reattachment. This is contradictory to the conventional wisdom of attempting to minimize eye movements.

  11. Mechanical evaluation of gradient electrospun scaffolds with 3D printed ring reinforcements for tracheal defect repair.

    Science.gov (United States)

    Ott, Lindsey M; Zabel, Taylor A; Walker, Natalie K; Farris, Ashley L; Chakroff, Jason T; Ohst, Devan G; Johnson, Jed K; Gehrke, Steven H; Weatherly, Robert A; Detamore, Michael S

    2016-04-21

    Tracheal stenosis can become a fatal condition, and current treatments include augmentation of the airway with autologous tissue. A tissue-engineered approach would not require a donor source, while providing an implant that meets both surgeons' and patients' needs. A fibrous, polymeric scaffold organized in gradient bilayers of polycaprolactone (PCL) and poly-lactic-co-glycolic acid (PLGA) with 3D printed structural ring supports, inspired by the native trachea rings, could meet this need. The purpose of the current study was to characterize the tracheal scaffolds with mechanical testing models to determine the design most suitable for maintaining a patent airway. Degradation over 12 weeks revealed that scaffolds with the 3D printed rings had superior properties in tensile and radial compression, with at least a three fold improvement and 8.5-fold improvement, respectively, relative to the other scaffold groups. The ringed scaffolds produced tensile moduli, radial compressive forces, and burst pressures similar to or exceeding physiological forces and native tissue data. Scaffolds with a thicker PCL component had better suture retention and tube flattening recovery properties, with the monolayer of PCL (PCL-only group) exhibiting a 2.3-fold increase in suture retention strength (SRS). Tracheal scaffolds with ring reinforcements have improved mechanical properties, while the fibrous component increased porosity and cell infiltration potential. These scaffolds may be used to treat various trachea defects (patch or circumferential) and have the potential to be employed in other tissue engineering applications.

  12. [Molecular repair mechanisms using the Intratissue Percutaneous Electrolysis technique in patellar tendonitis].

    Science.gov (United States)

    Abat, F; Valles, S L; Gelber, P E; Polidori, F; Stitik, T P; García-Herreros, S; Monllau, J C; Sanchez-Ibánez, J M

    2014-01-01

    To investigate the molecular mechanisms of tissue response after treatment with the Intratissue Percutaneous Electrolysis (EPI(®)) technique in collagenase-induced tendinopathy in Sprague-Dawley rats. Tendinopathy was induced by injecting 50 μg of type i collagenase into the patellar tendon of 24 Sprague Dawley rats of 7 months of age and weighting 300 g. The sample was divided into 4 groups: the control group, collagenase group, and two EPI(®) technique treatment groups of 3 and 6 mA, respectively. An EPI(®) treatment session was applied, and after 3 days, the tendons were analysed using immunoblotting and electrophoresis techniques. An analysis was also made of cytochrome C protein, Smac/Diablo, vascular endothelial growth factor and its receptor 2, as well as the nuclear transcription factor peroxisome proliferator-activated receptor gamma. A statistically significant increase, compared to the control group, was observed in the expression of cytochrome C, Smac/Diablo, vascular endothelial growth factor, its receptor 2 and peroxisome proliferator-activated receptor gamma in the groups in which the EPI(®) technique was applied. EPI(®) technique produces an increase in anti-inflammatory and angiogenic molecular mechanisms in collagenase-induced tendon injury in rats. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  13. Stimulation of bone repair with ultrasound: a review of the possible mechanic effects.

    Science.gov (United States)

    Padilla, Frédéric; Puts, Regina; Vico, Laurence; Raum, Kay

    2014-07-01

    In vivo and in vitro studies have demonstrated the positive role that ultrasound can play in the enhancement of fracture healing or in the reactivation of a failed healing process. We review the several options available for the use of ultrasound in this context, either to induce a direct physical effect (LIPUS, shock waves), to deliver bioactive molecules such as growth factors, or to transfect cells with osteogenic plasmids; with a main focus on LIPUS (or Low Intensity Pulsed Ultrasound) as it is the most widespread and studied technique. The biological response to LIPUS is complex as numerous cell types respond to this stimulus involving several pathways. Known to-date mechanotransduction pathways involved in cell responses include MAPK and other kinases signaling pathways, gap-junctional intercellular communication, up-regulation and clustering of integrins, involvement of the COX-2/PGE2, iNOS/NO pathways and activation of ATI mechanoreceptor. The mechanisms by which ultrasound can trigger these effects remain intriguing. Possible mechanisms include direct and indirect mechanical effects like acoustic radiation force, acoustic streaming, and propagation of surface waves, fluid-flow induced circulation and redistribution of nutrients, oxygen and signaling molecules. Effects caused by the transformation of acoustic wave energy into heat can usually be neglected, but heating of the transducer may have a potential impact on the stimulation in some in-vitro systems, depending on the coupling conditions. Cavitation cannot occur at the pressure levels delivered by LIPUS. In-vitro studies, although not appropriate to identify the overall biological effects, are of great interest to study specific mechanisms of action. The diversity of current experimental set-ups however renders this analysis very complex, as phenomena such as transducer heating, inhomogeneities of the sound intensity in the near field, resonances in the transmission and reflection through the culture

  14. Development of a novel sodium fusidate-loaded triple polymer hydrogel wound dressing: Mechanical properties and effects on wound repair.

    Science.gov (United States)

    Jin, Sung Giu; Kim, Kyeong Soo; Kim, Dong Wuk; Kim, Dong Shik; Seo, Youn Gee; Go, Toe Gyung; Youn, Yu Seok; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2016-01-30

    To develop a novel sodium fusidate-loaded triple polymer hydrogel dressing (TPHD), numerious polyvinyl alcohol-based (PVA) hydrogel dressings were prepared with various hydrophilic polymers using the freeze-thaw method, and their hydrogel dressing properties were assessed. Among the hydrophilic polymers tested, sodium alginate (SA) improved the swelling capacity the most, and polyvinyl pyrrolidone (PVP) provided the greatest improvement in bioadhesive stength and mechanical properties. Thus, PVA based-TPHDs were prepared using different ratios of PVP:SA. The effect of selected PVP:SA ratios on the swelling capacity, bioadhesive strength, mechanical properties, and drug release, permeation and deposition characteristics of sodium fusidate-loaded PVA-based TPHDs were assessed. As the ratio of PVP:SA increased in PVA-loaded TPHD, the swelling capacity, mechanical properties, drug release, permeation and deposition were improved. The TPHD containing PVA, PVP, SA and sodium fusidate at the weight ratio of 10/6/1/1 showed excellent hydrogel dressing properties, release, permeation and deposition of drug. Within 24h, 71.8 ± 1.3% of drug was released. It permeated 625.1 ± 81.2 μg/cm(2) through the skin and deposited of 313.8 ± 24.1 μg/cm(2) within 24h. The results of in vivo pharmacodynamic studies showed that sodium fusidate-loaded TPHD was more effective in improving the repair process than was a commercial product. Thus, this sodium fusidate-loaded TPHD could be a novel tool in wound care.

  15. Electrospun Matrices for Pelvic Floor Repair: Effect of Fiber Diameter on Mechanical Properties and Cell Behavior.

    Science.gov (United States)

    Vashaghian, Mahshid; Zandieh-Doulabi, Behrouz; Roovers, Jan-Paul; Smit, Theodoor Henri

    2016-12-01

    Electrospun matrices are proposed as an alternative for polypropylene meshes in reconstructive pelvic surgery. Here, we investigated the effect of fiber diameter on (1) the mechanical properties of electrospun poly (lactic-co-glycolic acid)-blended-poly(caprolactone) (PLGA/PCL) matrices; (2) cellular infiltration; and (3) the newly formed extracellular matrix (ECM) in vitro. We compared electrospun matrices with 1- and 8 μm fiber diameter and used nonporous PLGA/PCL films as controls. The 8-μm matrices were almost twice as stiff as the 1-μm matrices with 1.38 and 0.66 MPa, respectively. Matrices had the same ultimate tensile strength, but with 80% the 1-μm matrices were much more ductile than the 8-μm ones (18%). Cells infiltrated deeper into the matrices with larger pores, but cellular activity was comparable on both substrates. New ECM was deposited faster on the electrospun samples, but after 2 and 4 weeks the amount of collagen was comparable with that on nonporous films. The ECM deposited on the 1-μm matrices, and the nonporous film was about three times stiffer than the ECM found on the 8-μm matrices. Cell behavior in terms of myofibroblastic differentiation and remodeling was similar on the 1-μm matrices and nonporous films, in comparison to that on the 8-μm matrices. We conclude that electrospinning enhances the integration of host cells as compared with a nonporous film of the same material. The 1-μm matrices result in better mechanical behavior and qualitatively better matrix production than the 8-μm matrices, but with limited cellular infiltration. These data are useful for designing electrospun matrices for the pelvic floor.

  16. Optimality in DNA repair.

    Science.gov (United States)

    Richard, Morgiane; Fryett, Matthew; Miller, Samantha; Booth, Ian; Grebogi, Celso; Moura, Alessandro

    2012-01-07

    DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge.

  17. Skeletal myoblasts for heart regeneration and repair: state of the art and perspectives on the mechanisms for functional cardiac benefits.

    Science.gov (United States)

    Formigli, L; Zecchi-Orlandini, S; Meacci, E; Bani, D

    2010-01-01

    Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells in basic research and clinical trials of cell based therapy for cardiac repair and regeneration. Although SkMB engraftment into the post-infarcted heart has been consistently found to improve cardiac contractile function, the underlying therapeutic mechanisms remain still a matter of controversy and debate. This is basically because SkMBs do not attain a cardiac-like phenotype once homed into the diseased heart nor they form a contractile tissue functionally coupled with the surrounding viable myocardium. This issue of concern has generated the idea that the cardiotropic action of SkMBs may depend on the release of paracrine factors. However, the paracrine hypothesis still remains ill-defined, particularly concerning the identification of the whole spectrum of cell-derived soluble factors and details on their cardiac effects. In this context, the possibility to genetically engineering SkMBs to potentate their paracrine attitudes appears particularly attractive and is actually raising great expectation. Aim of the present review is not to cover all the aspects of cell-based therapy with SkMBs, as this has been the object of previous exhaustive reviews in this field. Rather, we focused on novel aspects underlying the interactions between SkMBs and the host cardiac tissues which may be relevant for directing the future basic and applied research on SkMB transplantation for post ischemic cardiac dysfunction.

  18. Mechanical behavior of colonic anastomosis in experimental settings as a measure of wound repair and tissue integrity

    Institute of Scientific and Technical Information of China (English)

    Konstantinos A Ekmektzoglou; Georgios C Zografos; Stavros K Kourkoulis; Ismene A Dontas; Panagiotis K Giannopoulos; Katerina A Marinou; Maria V Poulakou; Despina N Perrea

    2006-01-01

    AIM: To determine the mechanical properties of anastomotic colonic tissue in experimental settings and therefore give a measure of wound healing.METHODS: Thirty-six male Wistar rats were used as experimental models of anastomotic tissue integrity. On the 5th post-operative day, the tensile strength was measured by application of an axial force, providing a quantitative measure of anastomotic dehiscence and leakage.RESULTS: Diagrams of the load as a function of the time [P = P (t)] and of the displacement also as a function of time [△s = △s (t)] were recorded for each test,permitting the design of the load versus the displacement diagram and thus providing significant data about the critical values of anastomotic failure. Quantitative data were obtained concerning the anastomotic strength of both control specimens (healthy rats), as well as specimens from non-healthy rats for comparison.CONCLUSION: This experimental model provides an excellent method of measuring anastomotic strength.Despite the relative small number of specimens used,this method provides an accurate way of measuring wound repair. More experimental measurements need to be performed to correlate emerging tensile strength values to anastomotic failure.

  19. Porous alumina, zirconia and alumina/zirconia for bone repair: fabrication, mechanical and in vitro biological response.

    Science.gov (United States)

    Hadjicharalambous, Chrystalleni; Buyakov, Ales; Buyakova, Svetlana; Kulkov, Sergey; Chatzinikolaidou, Maria

    2015-04-23

    Zirconia (ZrO2) and alumina (Al2O3) based ceramics are widely used for load-bearing applications in bone repair due to their excellent mechanical properties and biocompatibility. They are often regarded as bioinert since no direct bone-material interface is created unless a porous structure intercedes, leading to better bone bonding. In this regard, investigating interactions between cells and porous ceramics is of great interest. In the present study, we report on the successful fabrication of sintered alumina A-61, zirconia Z-50 and zirconia/alumina composite ZA-60 ceramics with medium porosities of 61, 50 and 60%, respectively, indicating a bimodal pore size distribution and good interconnectivity. They exhibit elastic moduli of 3-10 GPa and compressive strength values of 60-240 MPa, similar to those of human cortical bone.We performed in vitro cell-material investigations comparing the adhesion, proliferation and differentiation of mouse pre-osteoblasts MC3T3-E1 on the three porous materials. While all three ceramics demonstrate a strong cell attachment, better cell spreading is observed on zirconia-containing substrates. Significantly higher cell growth was quantified on the latter ceramics, revealing an increased alkaline phosphatase activity, higher collagen production and increased calcium biomineralization compared to A-61. Hence, these porous zirconia-containing ceramics elicit superior biological responses over porous alumina of similar porosity, promoting enhanced biological interaction, with potential use as non-degradable bone grafts or as implant coatings.

  20. The effect of muscle repair on postoperative facial skeletal growth in children with bilateral cleft lip and palate.

    Science.gov (United States)

    Nagase, T; Januszkiewicz, J S; Keall, H J; de Geus, J J

    1998-12-01

    The effect of orbicularis muscle repair on postoperative facial skeletal growth in bilateral cleft lip and palate patients was studied by analysis of cephalometric radiographs and dental casts. Sixty-two patients operated on between 1961-1989 were selected for the study. They were divided into three groups, group 1a (muscle repair; n = 12), group 1b (failed attempt at muscle repair; n = 5), and group 2 (no attempt at muscle repair; n = 45). Comparison of the morphological measurements among these three groups showed that there was a trend towards crossbite in the muscle repair group, but this difference was not significant. Mechanisms by which muscle repair might influence maxillofacial skeletal growth include the possibility that the area around the nasal septum might be the growth centre. The choice of operative technique in bilateral cleft lip and palate should be important.

  1. Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei-Implications for comparative studies

    DEFF Research Database (Denmark)

    Akbari, Mansour; Krokan, Hans E

    2012-01-01

    The base excision repair (BER) pathway corrects many different DNA base lesions and is important for genomic stability. The mechanism of BER cannot easily be investigated in intact cells and therefore in vitro methods that reflect the in vivo processes are in high demand. Reconstitution of BER...... using purified proteins essentially mirror properties of the proteins used, and does not necessarily reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured cells have the capacity to carry out complete BER and can give important information on the mechanism. Furthermore...

  2. KAP1 Deacetylation by SIRT1 Promotes Non-Homologous End-Joining Repair.

    Directory of Open Access Journals (Sweden)

    Yi-Hui Lin

    Full Text Available Homologous recombination and non-homologous end joining are two major DNA double-strand-break repair pathways. While HR-mediated repair requires a homologous sequence as the guiding template to restore the damage site precisely, NHEJ-mediated repair ligates the DNA lesion directly and increases the risk of losing nucleotides. Therefore, how a cell regulates the balance between HR and NHEJ has become an important issue for maintaining genomic integrity over time. Here we report that SIRT1-dependent KAP1 deacetylation positively regulates NHEJ. We show that up-regulation of KAP1 attenuates HR efficiency while promoting NHEJ repair. Moreover, SIRT1-mediated KAP1 deacetylation further enhances the effect of NHEJ by stabilizing its interaction with 53BP1, which leads to increased 53BP1 focus formation in response to DNA damage. Taken together, our study suggests a SIRT1-KAP1 regulatory mechanism for HR-NHEJ repair pathway choice.

  3. The mechanics of PLGA nanofiber scaffolds with biomimetic gradients in mineral for tendon-to-bone repair.

    Science.gov (United States)

    Lipner, J; Liu, W; Liu, Y; Boyle, J; Genin, G M; Xia, Y; Thomopoulos, S

    2014-12-01

    along the length of the scaffolds, and Raman spectroscopic analysis revealed that the mineral produced was hydroxylapatite. Mechanical testing showed that the stiffness gradient using the new method was significantly steeper. By analyzing the scaffolds using micromechanical modeling techniques and extrapolating from our experimental results, we present evidence that the new mineralization protocol has the potential to achieve levels of stiffness adequate to contribute to enhanced repair of tendon-to-bone attachments.

  4. Potential of human γD-crystallin for hair damage repair: insights into the mechanical properties and biocompatibility.

    Science.gov (United States)

    Ribeiro, A; Matamá, T; Cruz, C F; Gomes, A C; Cavaco-Paulo, A M

    2013-10-01

    The objective of this work was to develop a new strategy to physically 'repair' chemically damaged hair. Hence the human eye γD-crystallin, a protein from the superfamily characterized structurally by the Greek key motif, was studied. The human γD-crystallin was chosen based on the ability of proteins belonging to this superfamily to be involved in the coating of specific structures. Two crystallins were used on the study, the wild type (Protein Data Bank ID: 1HK0) and the mutant protein. The mutant form was intended to induce a strong and quick protein polymerization as well to have new possible points of anchorage to hair. The ability of both crystallins to bind to damaged hair and even penetrate into its cortex was checked by fluorescence microscopy, confocal microscopy and scanning electron microscopy. Furthermore the reinforcement of hair mechanical resistance, the potential cytotoxic/inflammatory effect of crystallins were studied in order to have a fully comprehension about the protein based formulation. Although the chemical over-bleaching treatment induced a decrease of 20% on the resistance of the hair, the crystallins which bind and penetrate the hair fibre were able to recover and even to improve its mechanical properties when compared to the virgin hair. Moreover none of the crystallins displayed a toxic effect in fibroblasts for all the range of tested concentrations upon 72 h of exposure. The active aggregation process of mutant crystallin induced an inflammatory response in fibroblasts in the first 24 h of contact, measured by the amount of released pro-inflammatory cytokine IL-6 to the medium. In contrast contact with wild type crystallin did not lead to significant inflammation. Outcome from protein formulation characterization supports the hypothesis that the γD-crystallin it is able to recover and improve the mechanical properties of chemical damaged hair. Therefore it can be considered as a very promising strengthening agent for the

  5. Plants Possess a Cyclic Mitochondrial Metabolic Pathway similar to the Mammalian Metabolic Repair Mechanism Involving Malate Dehydrogenase and l-2-Hydroxyglutarate Dehydrogenase.

    Science.gov (United States)

    Hüdig, Meike; Maier, Alexander; Scherrers, Isabell; Seidel, Laura; Jansen, Erwin E W; Mettler-Altmann, Tabea; Engqvist, Martin K M; Maurino, Veronica G

    2015-09-01

    Enzymatic side reactions can give rise to the formation of wasteful and toxic products that are removed by metabolite repair pathways. In this work, we identify and characterize a mitochondrial metabolic repair mechanism in Arabidopsis thaliana involving malate dehydrogenase (mMDH) and l-2-hydroxyglutarate dehydrogenase (l-2HGDH). We analyze the kinetic properties of both A. thaliana mMDH isoforms, and show that they produce l-2-hydroxyglutarate (l-2HG) from 2-ketoglutarate (2-KG) at low rates in side reactions. We identify A. thaliana l-2HGDH as a mitochondrial FAD-containing oxidase that converts l-2HG back to 2-KG. Using loss-of-function mutants, we show that the electrons produced in the l-2HGDH reaction are transferred to the mitochondrial electron transport chain through the electron transfer protein (ETF). Thus, plants possess the biochemical components of an l-2HG metabolic repair system identical to that found in mammals. While deficiencies in the metabolism of l-2HG result in fatal disorders in mammals, accumulation of l-2HG in plants does not adversely affect their development under a range of tested conditions. However, orthologs of l-2HGDH are found in all examined genomes of viridiplantae, indicating that the repair reaction we identified makes an essential contribution to plant fitness in as yet unidentified conditions in the wild.

  6. Investigating glutamatergic mechanism in attention and impulse control using rats in a modified 5-choice serial reaction time task.

    Directory of Open Access Journals (Sweden)

    Abigail Benn

    Full Text Available The 5-choice serial reaction time task (5CSRTT has been widely used to study attention and impulse control in rodents. In order to mimic cognitive impairments in psychiatry, one approach has been to use acute administration of NMDA antagonists. This disruption in glutamatergic transmission leads to impairments in accuracy, omissions, and premature responses although findings have been inconsistent. In this study, we further investigated glutamatergic mechanisms using a novel version of the 5CSRTT, which we have previously shown to be more sensitive to cognitive enhancers. We first investigated the effects of systemic treatment with NMDA antagonists. We also carried out a preliminary investigation using targeted medial prefrontal cortex infusions of a NMDA antagonist (MK801, mGluR2/3 antagonist (LY341495, and mGluR7 negative allosteric modulator (MMPIP. Acute systemic administration of the different NMDA antagonists had no specific effects on accuracy. At higher doses PCP, ketamine, and memantine, increased omissions and affected other measures suggesting a general disruption in task performance. Only MK801 increased premature responses, and reduced omissions at lower doses suggesting stimulant like effects. None of the NMDA antagonists affected accuracy or any other measures when tested using a short stimulus challenge. Infusions of MK801 had no effect on accuracy but increased premature responses following infralimbic, but not prelimbic infusion. LY341495 had no effects in either brain region but a decrease in accuracy was observed following prelimbic infusion of MMPIP. Contrary to our hypothesis, disruptions to glutamate transmission using NMDA antagonists did not induce any clear deficits in accuracy in this modified version of the 5CSRTT. We also found that the profile of effects for MK801 differed from those observed with PCP, ketamine, and memantine. The effects of MK801 in the infralimbic cortex add to the literature indicating this brain

  7. Down-regulation of the Nucleotide Excision Repair gene XPG as a new mechanism of drug resistance in human and murine cancer cells

    Directory of Open Access Journals (Sweden)

    Geroni Cristina

    2010-09-01

    Full Text Available Abstract Background Drug resistance is one of the major obstacles limiting the activity of anticancer agents. Activation of DNA repair mechanism often accounts for increase resistance to cancer chemotherapy. Results We present evidence that nemorubicin, a doxorubicin derivative currently in clinical evaluation, acts through a mechanism of action different from classical anthracyclines, requiring an intact nucleotide excision repair (NER system to exert its activity. Cells made resistant to nemorubicin show increased sensitivity to UV damage. We have analysed the mechanism of resistance and discovered a previously unknown mechanism resulting from methylation-dependent silencing of the XPG gene. Restoration of NER activity through XPG gene transfer or treatment with demethylating agents restored sensitivity to nemorubicin. Furthermore, we found that a significant proportion of ovarian tumors present methylation of the XPG promoter. Conclusions Methylation of a NER gene, as described here, is a completely new mechanism of drug resistance and this is the first evidence that XPG gene expression can be influenced by an epigenetic mechanism. The reported methylation of XPG gene could be an important determinant of the response to platinum based therapy. In addition, the mechanism of resistance reported opens up the possibility of reverting the resistant phenotype using combinations with demethylating agents, molecules already employed in the clinical setting.

  8. DSB (Im)mobility and DNA repair compartmentalization in mammalian cells.

    Science.gov (United States)

    Lemaître, Charlène; Soutoglou, Evi

    2015-02-13

    Chromosomal translocations are considered as causal in approximately 20% of cancers. Therefore, understanding their mechanisms of formation is crucial in the prevention of carcinogenesis. The first step of translocation formation is the concomitant occurrence of double-strand DNA breaks (DSBs) in two different chromosomes. DSBs can be repaired by different repair mechanisms, including error-free homologous recombination (HR), potentially error-prone non-homologous end joining (NHEJ) and the highly mutagenic alternative end joining (alt-EJ) pathways. Regulation of DNA repair pathway choice is crucial to avoid genomic instability. In yeast, DSBs are mobile and can scan the entire nucleus to be repaired in specialized DNA repair centers or if they are persistent, in order to associate with the nuclear pores or the nuclear envelope where they can be repaired by specialized repair pathways. DSB mobility is limited in mammals; therefore, raising the question of whether the position at which a DSB occurs influences its repair. Here, we review the recent literature addressing this question. We first present the reports describing the extent of DSB mobility in mammalian cells. In a second part, we discuss the consequences of non-random gene positioning on chromosomal translocations formation. In the third part, we discuss the mobility of heterochromatic DSBs in light of our recent data on DSB repair at the nuclear lamina, and finally, we show that DSB repair compartmentalization at the nuclear periphery is conserved from yeast to mammals, further pointing to a role for gene positioning in the outcome of DSB repair. When regarded as a whole, the different studies reviewed here demonstrate the importance of nuclear architecture on DSB repair and reveal gene positioning as an important parameter in the study of tumorigenesis.

  9. Tendon repair

    Science.gov (United States)

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  10. A Study of the Repair Mechanism in Japanese Conversation%日语会话的修正机制研究

    Institute of Scientific and Technical Information of China (English)

    赵刚; 贾琦

    2012-01-01

    本文主要考察日语会话中常见的修正现象,探讨了修正机制和特征。首先在Schegloff,Jefferson&Sacks(1977)的基础上,对修正的定义和结构特征进行了补充。对桥内(1999)的修正内容分类进行了完善,提出了“信息补充修正”这一分类,首次从阻碍源和修正的照应关系,以及从会话管理的视点等方面对修正进行了详细的分类和深入的考察,明确了修正在互动行为中的功能和作用。%This paper mainly focuses on the repair phenomenon which is most common in Japanese daily conversation, discussing the repair mechanism and its features. Firstly, the paper takes its basis from the research of Schegloff, Jefferson & Sacks (1977) and supplements the definition of repair and its structural characteristics. In addition, we perfect the repair content classification system put forward by Hashiuchi (1999) and describe a new classification system called "information supplement repair". Moreover, this paper details the classification system from the aspect of the source of trouble and deeply examines the revision of the anaphoric relationship and conversation management for the first time. Thus, the function of repair in interactive behavior is made clear through the above analysis

  11. Psychological Mechanism Underlying Preference Reversals in Intertemporal Choice%跨期选择中偏好反转的心理机制

    Institute of Scientific and Technical Information of China (English)

    陈海贤; 何贵兵

    2012-01-01

    通过直接测量近期和远期选择中备选项激活的情绪、间隔的时间知觉及对备选项金额差异和时间间隔的重视程度,以探究跨期选择中偏好反转产生的心理机制。结果表明:(1)近期选择中,备选项激活的情绪强度差异显著,而远期选择中两者的差异不显著;(2)近期和远期选择中,情绪强度差异和时间知觉差异能够预测偏好反转的发生。研究结果支持了偏好反转的情绪激活差异假说和时间知觉差异假说。%Preference reversals in intertemporal choice refer to the tendency of a decision maker to prefer alternative SS(Sooner-Smaller) to LL(Larger-Later) when the outcomes are near but prefer alternative LL to SS when the outcomes are distant.Preference reversals cast doubts on the DU(Discounting Utility) model,which assumed stationary preferences across time. There are three main theories about psychological mechanism underlying preference reversals.The first theory hypothesized that choices between the immediate outcome and the distant outcome activated stronger impulsive affection than choices between distant outcomes. Different impulsive affection caused reversals(Loewenstein,1996;Metcalfe Mischel,1999).The second theory hypothesized that the subject interval perception was longer in near choices than in distant choices,even though the object interval between alternatives was the same(Takahashi,Oonob, Radfordb,2008;Zauberman,Kim,Malkoc, Bettman,2009).Different interval perception caused different value discounting,which caused reversals.The third theory hypothesized that the magnitude of money (high-level construal) were more weighted whereas interval(low-level construal) was less weighted as psychology distance increased, and the varing weight of money and interval in near and distant choices caused reversals(Trope Liberman,2003,2010). The purpose of this study was to test these theories.We hypothesized that the psychological variables underlying

  12. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  13. Mechanical and Permeability Characteristics of Latex-Modified Pre-Packed Pavement Repair Concrete as a Function of the Rapid-Set Binder Content

    Directory of Open Access Journals (Sweden)

    Jae-Woong Han

    2015-10-01

    Full Text Available We evaluated the strength and durability characteristics of latex-polymer-modified, pre-packed pavement repair concrete (LMPPRC with a rapid-set binder. The rapid-set binder was a mixture of rapid-set cement and silica sand, where the fluidity was controlled using a latex polymer. The resulting mix exhibited a compressive strength of ¥21 MPa and a flexural strength of ¥3.5 MPa after 4 h of curing (i.e., the traffic opening term for emergency repairs of pavement. The ratio of latex polymer to rapid-set binder material was varied through 0.40, 0.33, 0.29, and 0.25. Mechanical characterization revealed that the mechanical performance, permeability, and impact resistance increased as the ratio of latex polymer to rapid-set binder decreased. The mixture exhibited a compressive strength of ¥21 MPa after 4 h when the ratio of latex polymer to rapid-set binder material was ¤0.29. The mixture exhibited a flexural strength of ¥3.5 MPa after 4 h when the ratio of latex polymer to rapid-set binder material was ¤0.33. The permeability resistance to chloride ions satisfied 2000 C after 7 days of curing for all ratios. The ratio of latex polymer to rapid-set binder material that satisfied all conditions for emergency pavement repair was ¤0.29.

  14. 游离肩胛皮瓣移植修复头皮大面积缺损合并骨外露%Free scapular flaps become a choice for repairing large-area scalp defect and skull exposure

    Institute of Scientific and Technical Information of China (English)

    鲍世威; 马小兵; 赵红艺; 钱文江; 杨明勇

    2014-01-01

    背景:游离肩胛皮瓣具有可提供面积大、皮瓣色泽好、质地优良、薄厚适中、皮瓣易于切取、血管恒定、供区隐蔽等特点,适合作为大面积头皮缺损伴有骨外露的首选皮瓣之一。  目的:回顾性分数应用肩胛皮瓣游离移植修复复杂的大面积头皮缺损合并颅骨外露的方法及经验。  方法:对8例头皮大面积缺损合并颅骨外露患者,采用切取游离肩胛皮瓣,将旋肩胛动静脉与颞浅动静脉或面动静脉吻合方法修复大面积缺损及骨外露。随访6-12个月,观察游离肩胛皮瓣移植后皮瓣感染情况,游离肩胛皮瓣成活情况,供皮区处理及愈合结果及不良反应。  结果与结论:全部8例肩胛皮瓣均一期成活,2例出现静脉回流不畅,给予针刺放血及拆除远端部分缝线后好转;术后随访期间,皮瓣血运良好,头部局部外形好,未见并发症。结果提示游离肩胛皮瓣血管恒定,血运可靠,皮瓣色泽质地优良,可切取面积大,对供区影响小,可作为修复大面积头皮缺损的选择方法之一。%BACKGROUND:The local flap and expanded flap cannot repair the large area scalp defect, especialy for patients with skul exposure and infection. The free flap is suitable for this kind of cases. The free scapular flap shows many advantages: constant vessel site, stable blood supply, supporting the amount and variability of tissue types available for harvest and minor deformity of the donor site. It is one of the most excelent choices for large-area scalp defects and skul exposure. OBJECTIVE:To retrospectively analyze the method and experience of repairing the large area scalp defect and skul exposure by free scapular flaps. METHODS: Free scapular flaps were used to repair the large-area scalp defects and skul exposure in eight patients. The circumflex scapular vessel was anastomosed with superficial temporal vessel or facial vessel

  15. Collagen insulated from tensile damage by domains that unfold reversibly: in situ X-ray investigation of mechanical yield and damage repair in the mussel byssus.

    Science.gov (United States)

    Harrington, Matthew J; Gupta, Himadri S; Fratzl, Peter; Waite, J Herbert

    2009-07-01

    The byssal threads of the California mussel, Mytilus californianus, are highly hysteretic, elastomeric fibers that collectively perform a holdfast function in wave-swept rocky seashore habitats. Following cyclic loading past the mechanical yield point, threads exhibit a damage-dependent reduction in mechanical performance. However, the distal portion of the byssal thread is capable of recovering initial material properties through a time-dependent healing process in the absence of active cellular metabolism. Byssal threads are composed almost exclusively of multi-domain hybrid collagens known as preCols, which largely determine the mechanical properties of the thread. Here, the structure-property relationships that govern thread mechanical performance are further probed. The molecular rearrangements that occur during yield and damage repair were investigated using time-resolved in situ wide-angle X-ray diffraction (WAXD) coupled with cyclic tensile loading of threads and through thermally enhanced damage-repair studies. Results indicate that the collagen domains in byssal preCols are mechanically protected by the unfolding of sacrificial non-collagenous domains that refold on a slower time-scale. Time-dependent healing is primarily attributed to stochastic recoupling of broken histidine-metal coordination complexes.

  16. Plants as concept generators for biomimetic light-weight structures with variable stiffness and self-repair mechanisms

    Institute of Scientific and Technical Information of China (English)

    Thomas Speck; Tom Masselter; Bettina Prüm; Olga Speck; Rolf Luchsinger; Siegfried Fink

    2004-01-01

    Plants possess many structural and functional properties that have a high potential to serve as concept generators for the production of biomimetic technical materials and structures. We present data on two features of plants (variable stiffness due to pressure changes in cellular structures and rapid self-repair functions) that may be used as models for biomimetic projects.

  17. Left ventricular mechanics in repaired tetralogy of Fallot with and without pulmonary valve replacement: analysis by three-dimensional speckle tracking echocardiography.

    Directory of Open Access Journals (Sweden)

    Shu-Na Li

    Full Text Available BACKGROUND: Altered septal curvature and left ventricular (LV geometry secondary to right ventricular (RV dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF patients. The novel three-dimensional (3D speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics. METHODS AND RESULTS: Seventy-six patients aged 23.6 ± 8.3 years, 55 with isolated repair (group I and 21 with subsequent pulmonary valve replacement (group II, and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI, twist, twist gradient (twist/LV length, and ejection fraction. A global performance index was calculated as (global 3D strain•twist gradient/SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI (all p<0.05. All but the four apical LV segments in patients had reduced regional 3D strain compared with controls (all p<0.05. Septal curvature correlated with LV global 3D strain (r=0.41, p<0.001, average septal strain (r=0.38, p<0.001, twist (r=0.32, p<0.001, twist gradient (r=0.33, p<0.001, and global performance index (r=0.43, p<0.001. CONCLUSIONS: Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement.

  18. [Inguinal and femoral hernia repair].

    Science.gov (United States)

    Geissler, B; Anthuber, M

    2011-05-01

    With an incidence of 200,000 new cases per year in Germany, inguinal hernia has a significant socioeconomic impact. The 2009 guidelines from the European Hernia Society established treatment recommendations. Hernia repair is based on reinforcing the posterior wall of the inguinal canal by suture or mesh repair by an anterior or posterior approach. Lightweight mesh reduces recurrence rates and is the treatment of choice even in primary hernias. Laparoscopic hernia repair is associated with specific risks but is superior in postoperative pain and earlier return to work.

  19. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  20. Effects of Repair Weld of Reactor Pressure Vessel Upper Head Control Rod Drive Mechanism Penetration Nozzle on J-Groove Weldment Using Finite Element Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ju Hee; Yoo, Sam Hyeon [Korea Military Academy, Seoul (Korea, Republic of); Kim, Yun Jae [Korea University, Seoul (Korea, Republic of)

    2014-06-15

    In pressurized water reactors, the upper head of the reactor pressure vessel (RPV) contains numerous control rod drive mechanism (CRDM) nozzles. These nozzles are fabricated by welding after being inserted into the RPV head with a room temperature shrink fit. The tensile residual stresses caused by this welding are a major factor in primary water stress corrosion cracking (PWSCC). Over the last 15 years, the incidences of cracking in alloy 600 CRDM nozzles have increased significantly. These cracks are caused by PWSCC and have been shown to be driven by the welding residual stresses and operational stresses in the weld region. Various measures are being sought to overcome these problems. The defects resulting from the welding process are often the cause of PWSCC acceleration. Therefore, any weld defects found in the RPV manufacturing process are immediately repaired by repair welding. Detailed finite element simulations for the Korea Nuclear Reactor Pressure Vessel were conducted in order to predict the magnitudes of the repair weld residual stresses in the tube materials.

  1. The spliceosome U2 snRNP factors promote genome stability through distinct mechanisms; transcription of repair factors and R-loop processing.

    Science.gov (United States)

    Tanikawa, M; Sanjiv, K; Helleday, T; Herr, P; Mortusewicz, O

    2016-12-19

    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress.

  2. Psychology of fragrance use: perception of individual odor and perfume blends reveals a mechanism for idiosyncratic effects on fragrance choice.

    Science.gov (United States)

    Lenochová, Pavlína; Vohnoutová, Pavla; Roberts, S Craig; Oberzaucher, Elisabeth; Grammer, Karl; Havlíček, Jan

    2012-01-01

    Cross-culturally, fragrances are used to modulate body odor, but the psychology of fragrance choice has been largely overlooked. The prevalent view is that fragrances mask an individual's body odor and improve its pleasantness. In two experiments, we found positive effects of perfume on body odor perception. Importantly, however, this was modulated by significant interactions with individual odor donors. Fragrances thus appear to interact with body odor, creating an individually-specific odor mixture. In a third experiment, the odor mixture of an individual's body odor and their preferred perfume was perceived as more pleasant than a blend of the same body odor with a randomly-allocated perfume, even when there was no difference in pleasantness between the perfumes. This indicates that fragrance use extends beyond simple masking effects and that people choose perfumes that interact well with their own odor. Our results provide an explanation for the highly individual nature of perfume choice.

  3. Evidence for repair of ultraviolet light-damaged herpes virus in human fibroblasts by a recombination mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Hall, J.D.; Featherston, J.D.; Almy, R.E.

    1980-09-01

    Human cells were either singly or multiply infected with herpes simplex virus (HSV-1) damaged by ultraviolet (uv) light, and the fraction of cells able to produce infectious virus was measured. The fraction of virus-producing cells was considerably greater for multiply infected cells than for singly infected cells at each uv dose examined. These high survival levels of uv-irradiated virus in multiply infected cells demonstrated that multiplicity-dependent repair, possibly due to genetic exchanges between damaged HSV-1 genomes, was occurring in these cells. To test whether uv light is recombinogenic for HSV-1, the effect of uv irradiation on the yield of temperature-resistant viral recombinants in cells infected with pairs of temperature-sensitive mutants was also investigated. The results of these experiments showed that the defective functions in these mutant host cells are not required for multiplicity-dependent repair or uv-stimulated viral recombination in herpes-infected cells.

  4. "Choice" and destiny: the substrate composition and mechanical stability of settlement structures can mediate coral recruit fate in post-bleached reefs

    Science.gov (United States)

    Yadav, Shreya; Rathod, Pooja; Alcoverro, Teresa; Arthur, Rohan

    2016-03-01

    Increasingly frequent and intense ocean warming events seriously test the buffer and recovery capacities of tropical coral reefs. Post-disturbance, available settlement structures on a reef (often dead coral skeletons) vary considerably in their mechanical stability and substrate composition, critically influencing coral recruit settlement choice and fate. In the wake of a coral mass mortality in the Lakshadweep archipelago, we examine (1) the relative availability of recruit settlement structures (from stable to unstable: reef platform, dead massive coral, consolidated rubble, dead corymbose coral, dead tabular coral, and unconsolidated rubble) in 12 recovering reefs across three atolls in the archipelago, (2) the substrate composition [crustose coralline algae (CCA), mixed turf, macroalgae] of these structural forms, and (3) whether the choice and fate of young coral are mediated by the substrate and stability of different structural forms. For this, we measured the abundance and distribution of recruit (corals of 24 common coral genera. Four years after the mass mortality, reefs differed considerably in composition of settlement structures. The structures themselves varied significantly in substrate cover with dead tables largely covered in CCA [60 ± 6.05 % (SE)] and dead corymbose coral dominated by mixed turf (61.83 ± 3.8 %). The youngest visible recruits (coral choice, the mechanical stability of settlement structures is critical in determining post-settlement coral survival. The composition and availability of settlement structures on a reef may serve as a characteristic signature of its recovery potential, aiding in assessments of reef resilience.

  5. Improving the effectiveness of nutritional information policies: assessment of unconscious pleasure mechanisms involved in food-choice decisions.

    Science.gov (United States)

    Jacquier, Caroline; Bonthoux, Françoise; Baciu, Monica; Ruffieux, Bernard

    2012-02-01

    The rise in obesity in many countries has led to the emergence of nutritional information policies that aim to change people's diets. Changing an individual's diet is an ambitious goal, since numerous factors influence a person's food-choice decisions, many of which are made unconsciously. These frequently subconscious processes should not be underestimated in food-choice behavior, as they play a major role in food diet composition. In this review, research in cognitive experimental psychology and neuroscience provides the basis for a critical analysis of the role of pleasure in eating behaviors. An assessment of the main characteristics of nutritional policies is provided, followed by recent findings showing that food choices are guided primarily by automatic emotional processes. Neuroimaging and behavioral studies, which provide new insights into the relationships between emotions and food both in lean persons and in persons with eating disorders, are reported as well. Lastly, the argument is presented that future nutritional policies can be more effective if they associate healthy food with eating pleasure.

  6. 社会网络对会计政策选择作用机理研究%Influencing mechanism of social network on accounting policy choice

    Institute of Scientific and Technical Information of China (English)

    韩鹤

    2014-01-01

    会计政策选择研究是实证会计研究的核心。会计政策选择如同公司的其他决策一样,也是在社会网络情境下做出的。在中国上市公司现有制度背景下,依据社会网络理论,从企业连接强度和位置、网络弱连接、结构空洞、网络制度环境、企业网络结构的约束行为以及企业网络锁入效应等方面研究了社会网络对会计政策选择行为的作用机理。从社会网络新视角研究了企业会计政策选择过程,扩展了会计政策选择研究的理论视野。%Accounting policy choice is the core of empirical accounting research .Accounting policy choice , like other companies decision , also made in the context of social networks . Based on social network theory ,social network accounting policy choice behavior mechanism was discussed in the background of the existing system of Chinese listed companies .From the position, link strength, network weak link, structural voids, network institutional environ-ment, the behavior of the enterprise network infrastructure constraints .Accounting policy choice was discussed from the perspective of the social network , expanding the view of ac-counting policy choice influencing factors theory .

  7. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Bill Bruce; Nancy Porter; George Ritter; Matt Boring; Mark Lozev; Ian Harris; Bill Mohr; Dennis Harwig; Robin Gordon; Chris Neary; Mike Sullivan

    2005-07-20

    liners, indicating that this type of liner is only marginally effective at restoring the pressure containing capabilities of pipelines. Failure pressures for larger diameter pipe repaired with a semi-circular patch of carbon fiber-reinforced composite lines were also marginally greater than that of a pipe section with un-repaired simulated damage without a liner. These results indicate that fiber reinforced composite liners have the potential to increase the burst pressure of pipe sections with external damage Carbon fiber based liners are viewed as more promising than glass fiber based liners because of the potential for more closely matching the mechanical properties of steel. Pipe repaired with weld deposition failed at pressures lower than that of un-repaired pipe in both the virgin and damaged conditions, indicating that this repair technology is less effective at restoring the pressure containing capability of pipe than a carbon fiber-reinforced liner repair. Physical testing indicates that carbon fiber-reinforced liner repair is the most promising technology evaluated to-date. In lieu of a field installation on an abandoned pipeline, a preliminary nondestructive testing protocol is being developed to determine the success or failure of the fiber-reinforced liner pipeline repairs. Optimization and validation activities for carbon-fiber repair methods are ongoing.

  8. Groin hernia repair

    DEFF Research Database (Denmark)

    Kehlet, Henrik; Aasvang, Eske

    2005-01-01

    The choice of anesthesia for groin hernia repair is between general, regional (epidural or spinal), and local anesthesia. Existing data from large consecutive patient series and randomized studies have shown local anesthesia to be the method of choice because it can be performed by the surgeon......, does not necessarily require an attending anesthesiologist, translates into the shortest recovery (bypassing the postanesthesia care unit), has the lowest cost, and has the lowest postoperative morbidity regarding risk of urinary retention. Spinal anesthesia has no documented benefits for this small...... scientific data to support the choice of anesthesia, large epidemiologic and nationwide information from databases show an undesirable high (about 10-20%) use of spinal anesthesia and low (about 10%) use of local infiltration anesthesia. Surgeons and anesthesiologists should therefore adjust their anesthesia...

  9. 机械式清除冰雪机械的保养和检修%Discussion on maintenance and repair of mechanical snow removing machinery

    Institute of Scientific and Technical Information of China (English)

    张健

    2013-01-01

      由于我国的气候原因,很多城市在冬季来临时道路上会积下很多冰雪,影响道路安全。机械除雪的方法因为基本没有副作用,所以被广泛使用,而对机械式清除冰雪机械的保养和检修也越来越被人们所重视。%  Because of climate in our country, many cities in the winter comes, accumulated a lot of snow and ice on roads, impact on road safety. Mechanical snow removal method for basic have no side effects, so widely used, and the me-chanical removal of snow and ice mechanical maintenance and repair is becoming more and more attention by people.

  10. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  11. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-12-31

    liners, indicating that this type of liner is only marginally effective at restoring the pressure containing capabilities of pipelines. Failure pressures for larger diameter pipe repaired with a semi-circular patch of carbon fiber-reinforced composite lines were also marginally greater than that of a pipe section with un-repaired simulated damage without a liner. These results indicate that fiber reinforced composite liners have the potential to increase the burst pressure of pipe sections with external damage Carbon fiber based liners are viewed as more promising than glass fiber based liners because of the potential for more closely matching the mechanical properties of steel. Pipe repaired with weld deposition failed at pressures lower than that of un-repaired pipe in both the virgin and damaged conditions, indicating that this repair technology is less effective at restoring the pressure containing capability of pipe than a carbon fiber-reinforced liner repair. Physical testing indicates that carbon fiber-reinforced liner repair is the most promising technology evaluated to-date. The first round of optimization and validation activities for carbon-fiber repairs are complete. Development of a comprehensive test plan for this process is recommended for use in the field trial portion of this program.

  12. CRISPR Technology Reveals RAD(51)-ical Mechanisms of Repair in Roundworms: An Educational Primer for Use with "Promotion of Homologous Recombination by SWS-1 in Complex with RAD-51 Paralogs in Caenorhabditis elegans".

    Science.gov (United States)

    Turcotte, Carolyn A; Andrews, Nicolas P; Sloat, Solomon A; Checchi, Paula M

    2016-11-01

    The mechanisms cells use to maintain genetic fidelity via DNA repair and the accuracy of these processes have garnered interest from scientists engaged in basic research to clinicians seeking improved treatment for cancer patients. Despite the continued advances, many details of DNA repair are still incompletely understood. In addition, the inherent complexity of DNA repair processes, even at the most fundamental level, makes it a challenging topic. This primer is meant to assist both educators and students in using a recent paper, "Promotion of homologous recombination by SWS-1 in complex with RAD-51 paralogs in Caenorhabditis elegans," to understand mechanisms of DNA repair. The goals of this primer are to highlight and clarify several key techniques utilized, with special emphasis on the clustered, regularly interspaced, short palindromic repeats technique and the ways in which it has revolutionized genetics research, as well as to provide questions for deeper in-class discussion.

  13. 53BP1 regulates DSB repair using Rif1 to control 5' end resection.

    Science.gov (United States)

    Zimmermann, Michal; Lottersberger, Francisca; Buonomo, Sara B; Sfeir, Agnel; de Lange, Titia

    2013-02-08

    The choice between double-strand break (DSB) repair by either homology-directed repair (HDR) or nonhomologous end joining (NHEJ) is tightly regulated. Defects in this regulation can induce genome instability and cancer. 53BP1 is critical for the control of DSB repair, promoting NHEJ, and inhibiting the 5' end resection needed for HDR. Using dysfunctional telomeres and genome-wide DSBs, we identify Rif1 as the main factor used by 53BP1 to impair 5' end resection. Rif1 inhibits resection involving CtIP, BLM, and Exo1; limits accumulation of BRCA1/BARD1 complexes at sites of DNA damage; and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in Brca1-deficient cells. These data establish Rif1 as an important contributor to the control of DSB repair by 53BP1.

  14. 浅谈现代煤炭企业机电设备维修%On Modern Coal Enterprises of Mechanical and Electrical Equipment Repairing

    Institute of Scientific and Technical Information of China (English)

    吕皋鸣

    2015-01-01

    In recent years,China's coal industry has been rapid developed,in order to ensure the safe production of coal enterprises to improve economic efficiency and electromechanical equipment can work stably, therefore, electrical and mechanical equipment repair management is becoming more and more important. This article from the electrical and mechanical equipment maintenance and coal play an important role in the production of each link, modify the equipment repair plan, deepen the staff technical training, to improve the equipment maintenance personnel business level as a priority task, strict implementation of equipment inspection system, to ensure the safe and stable operation of electrical equipment, the implementation of professional repair, improve the quality of maintenance etc, discusses reform measures of the modern coal enterprises in the production of electrical and mechanical equipment repair work.%近年来,我国煤炭产业得到快速发展,为了确保煤炭企业得以安全生产并提高经济效益,需要机电设备可以稳定工作,因此,机电设备的维修管理工作正变得越来越重要。从几个方面探讨了现代煤炭企业在生产中机电设备维修工作的改革措施:发挥煤炭机电设备的维护在生产各个环节的重要作用,修改设备维修方案;深化员工技术培训工作,把提高设备维护人员业务水平作为重点工作来抓;严格执行设备检查制度,来保障机电设备安全稳定运行;施行专业化维修,提高检修质量。

  15. A Neural Mechanism of Strategic Social Choice under Sanction-Induced Norm Compliance1,2,3

    Science.gov (United States)

    Makwana, Aidan; Grön, Georg; Fehr, Ernst

    2015-01-01

    Abstract In recent years, much has been learned about the representation of subjective value in simple, nonstrategic choices. However, a large fraction of our daily decisions are embedded in social interactions in which value guided decisions require balancing benefits for self against consequences imposed by others in response to our choices. Yet, despite their ubiquity, much less is known about how value computation takes place in strategic social contexts that include the possibility of retribution for norm violations. Here, we used functional magnetic resonance imaging (fMRI) to show that when human subjects face such a context connectivity increases between the temporoparietal junction (TPJ), implicated in the representation of other peoples’ thoughts and intentions, and regions of ventromedial prefrontal cortex (vmPFC) that are associated with value computation. In contrast, we find no increase in connectivity between these regions in social nonstrategic cases where decision-makers are immune from retributive monetary punishments from a human partner. Moreover, there was also no increase in TPJ-vmPFC connectivity when the potential punishment was performed by a computer programmed to punish fairness norm violations in the same manner as a human would. Thus, TPJ-vmPFC connectivity is not simply a function of the social or norm enforcing nature of the decision, but rather occurs specifically in situations where subjects make decisions in a social context and strategically consider putative consequences imposed by others. PMID:26464981

  16. Choice experiments

    Science.gov (United States)

    Thomas P Holmes; Wiktor L Adamawicz; Fredrik Carlsson

    2017-01-01

    There has been an explosion of interest during the past two decades in a class of nonmarket stated-preference valuation methods known as choice experiments. The overall objective of a choice experiment is to estimate economic values for characteristics (or attributes) of an environmental good that is the subject of policy analysis, where...

  17. Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from Coxsackievirus B3-induced myocarditis.

    Science.gov (United States)

    Yao, Hai-Lan; Song, Juan; Sun, Peng; Song, Qin-Qin; Sheng, Lin-Jun; Chi, Miao-Miao; Han, Jun

    2016-02-02

    To investigate the innate immune injury and repair mechanism during recovery from Coxsackievirus B3 (CVB3) induced myocarditis, we established an acute viral myocarditis recovery model by infecting BALB/c mice with CVB3. Histopathological examination of cardiac tissues after infection showed a gradual increase of myocardial injury to the maximum degree at 8 dpi (days post infection), followed by a recovery process with reduced viral replication. We also measured expression changes of innate immune genes in heart after 4, 8 and 12 days of infection using innate immune real-time PCR array. The results showed expression alterations in many Pattern Recognition Receptors (PRRs) genes upon CVB3 infection, which activated multiple important signaling pathways during recovery process. The expression of TLRs, RLRs, PKR and cytokines were strongly induced and reached the peak at 4 dpi in early myocarditis stage, followed by a gradual reduction in recovery stage, during which the levels were even lower than normal at 12 dpi. The strong correlation between cardiac histopathology score and chemokine expression level suggested that the chemokines might play a role in pathological changes during early myocarditis stage. In addition, we also found that both cell survival signaling pathways (AKT1, p38MAPK) and antiviral signaling pathways (IKKα/β/ε) were activated and promoted the recovery during late myocarditis stage. Altogether, our observations improved the understanding of formation and progression of the pathological lesions, as well as the repair mechanism for acute viral myocarditis.

  18. TGF-β reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24− cancer cells

    Science.gov (United States)

    Pal, Debjani; Pertot, Anja; Shirole, Nitin H; Yao, Zhan; Anaparthy, Naishitha; Garvin, Tyler; Cox, Hilary; Chang, Kenneth; Rollins, Fred; Kendall, Jude; Edwards, Leyla; Singh, Vijay A; Stone, Gary C; Schatz, Michael C; Hicks, James; Hannon, Gregory J; Sordella, Raffaella

    2017-01-01

    Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+/CD24− cell surface marker profile. Here, we report that human CD44+/CD24− cancer cells are genetically highly unstable because of intrinsic defects in their DNA-repair capabilities. In fact, in CD44+/CD24− cells, constitutive activation of the TGF-beta axis was both necessary and sufficient to reduce the expression of genes that are crucial in coordinating DNA damage repair mechanisms. Consequently, we observed that cancer cells that reside in a CD44+/CD24− state are characterized by increased accumulation of DNA copy number alterations, greater genetic diversity and improved adaptability to drug treatment. Together, these data suggest that the transition into a CD44+/CD24− cell state can promote intra-tumor genetic heterogeneity, spur tumor evolution and increase tumor fitness. DOI: http://dx.doi.org/10.7554/eLife.21615.001 PMID:28092266

  19. Effect of glenohumeral abduction angle on the mechanical interaction between the supraspinatus and infraspinatus tendons for the intact, partial-thickness torn, and repaired supraspinatus tendon conditions.

    Science.gov (United States)

    Andarawis-Puri, Nelly; Kuntz, Andrew F; Ramsey, Matthew L; Soslowsky, Louis J

    2010-07-01

    Rotator cuff tears are difficult to manage because of the structural and mechanical inhomogeneity of the supraspinatus tendon. Previously, we showed that with the arm at the side, the supraspinatus and infraspinatus tendons mechanically interact such that conditions that increase supraspinatus tendon strain, such as load or full-thickness tears, also increase infraspinatus tendon strain. This suggests that the infraspinatus tendon may shield the supraspinatus tendon from further injury while becoming at increased risk of injury itself. In this study, the effect of glenohumeral abduction angle on the interaction between the two tendons was evaluated for supraspinatus tendon partial-thickness tears and two repair techniques. Principal strains were quantified in both tendons for 0 degrees , 30 degrees , and 60 degrees of glenohumeral abduction. Results showed that interaction between the two tendons is interrupted by an increase in abduction angle for all supraspinatus tendon conditions evaluated. Infraspinatus tendon strain was lower at 30 degrees and 60 degrees than at 0 degrees abduction angle. In conclusion, interaction between the supraspinatus and infraspinatus tendons is interrupted with increase in abduction angle. Additionally, 30 degrees abduction should be further evaluated for management of rotator cuff tears and repairs as it is the angle at which both supraspinatus and infraspinatus tendon strain is decreased.

  20. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; George Ritter; Bill Mohr; Matt Boring; Nancy Porter; Mike Sullivan; Chris Neary

    2004-08-17

    , indicating that this type of liner is only marginally effective at restoring the pressure containing capabilities of pipelines. Failure pressures for larger diameter pipe repaired with a semi-circular patch of carbon fiber-reinforced composite lines were also marginally greater than that of a pipe section with un-repaired simulated damage without a liner. These results indicate that fiber reinforced composite liners have the potential to increase the burst pressure of pipe sections with external damage Carbon fiber based liners are viewed as more promising than glass fiber based liners because of the potential for more closely matching the mechanical properties of steel. Pipe repaired with weld deposition failed at pressures lower than that of un-repaired pipe in both the virgin and damaged conditions, indicating that this repair technology is less effective at restoring the pressure containing capability of pipe than a carbon fiber-reinforced liner repair. Physical testing indicates that carbon fiber-reinforced liner repair is the most promising technology evaluated to-date. Development of a comprehensive test plan for this process is recommended for use in the field trial portion of this program.

  1. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin.

    Science.gov (United States)

    Herrero, Ana B; Martín-Castellanos, Cristina; Marco, Esther; Gago, Federico; Moreno, Sergio

    2006-08-15

    Trabectedin (Yondelis) is a potent antitumor drug that has the unique characteristic of killing cells by poisoning the DNA nucleotide excision repair (NER) machinery. The basis for the NER-dependent toxicity has not yet been elucidated but it has been proposed as the major determinant for the drug's cytotoxicity. To study the in vivo mode of action of trabectedin and to explore the role of NER in its cytotoxicity, we used the fission yeast Schizosaccharomyces pombe as a model system. Treatment of S. pombe wild-type cells with trabectedin led to cell cycle delay and activation of the DNA damage checkpoint, indicating that the drug causes DNA damage in vivo. DNA damage induced by the drug is mostly caused by the NER protein, Rad13 (the fission yeast orthologue to human XPG), and is mainly repaired by homologous recombination. By constructing different rad13 mutants, we show that the DNA damage induced by trabectedin depends on a 46-amino acid region of Rad13 that is homologous to a DNA-binding region of human nuclease FEN-1. More specifically, an arginine residue in Rad13 (Arg961), conserved in FEN1 (Arg314), was found to be crucial for the drug's cytotoxicity. These results lead us to propose a model for the action of trabectedin in eukaryotic cells in which the formation of a Rad13/DNA-trabectedin ternary complex, stabilized by Arg961, results in cell death.

  2. PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors.

    Directory of Open Access Journals (Sweden)

    Hiroto Iwasaki

    Full Text Available RATIONALE: Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM cells, recent clinical trials have revealed less benefit from these therapies than expected. OBJECTIVE: We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF, a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity. METHODS AND RESULTS: Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+/Lin(- (SL BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage. CONCLUSIONS: Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.

  3. Nucleotide excision repair in yeast

    NARCIS (Netherlands)

    Eijk, Patrick van

    2012-01-01

    Nucleotide Excision Repair (NER) is a conserved DNA repair pathway capable of removing a broad spectrum of DNA damage. In human cells a defect in NER leads to the disorder Xeroderma pigmentosum (XP). The yeast Saccharomyces cerevisiae is an excellent model organism to study the mechanism of NER. The

  4. Hypospadias repair

    Science.gov (United States)

    ... the problem. If the repair is not done, problems may occur later on such as: Difficulty controlling and directing urine stream A curve in the penis during erection Decreased fertility Embarrassment about appearance of penis Surgery ...

  5. Excited-state proton coupled electron transfer between photolyase and the damaged DNA through water wire: a photo-repair mechanism.

    Science.gov (United States)

    Wang, Hongjuan; Chen, Xuebo; Fang, Weihai

    2014-12-14

    The photolyase enzyme absorbs blue light to repair damaged DNA through a cyclic electron transfer reaction. A description of the underlying mechanism has proven to be a challenging issue for both experimental and theoretical studies. In the present work, combined CASPT2//CASSCF/AMBER (QM/MM) calculations have been performed for damaged DNA in photolyase. A proton-coupled electron transfer (PCET) mechanism has been determined for restoring cyclobutane pyrimidine dimer (CPD) to two normal thymine bases by irradiation of photolyase. A well-defined water wire between FADH(-) and CPD was determined as a bridge to assist the PCET process within FADH(-) and thereby trigger the forward electron transfer to CPD. The subsequent CPD splitting and the alternation of the H-bond pattern proceed in a concerted way, which makes the productive backward electron transfer occur on an ultrafast timescale. A local minimum of SCT((1)ππ*)-LMin was identified on the pathway of the futile backward electron transfer (BET), which is stabilized by the strong H-bond interaction between the water wire and CPD. As a result, the futile BET process is endothermic by ∼18.0 kcal mol(-1), which is responsible for a 2.4 ns timescale inferred experimentally for the futile BET process. Besides the unbiased interpretation for the majority of the experimental findings, the present study provides a new excited-state PCET mechanism, which leads to a significant step toward a deeper understanding of the photo-repair process of damaged-DNA by the photolyase enzyme.

  6. Editor's choice

    DEFF Research Database (Denmark)

    Larzon, T; Roos, H; Gruber, G

    2015-01-01

    OBJECTIVES: The aim was to investigate whether the fascia suture technique (FST) can reduce access closure time and procedural costs compared with the Prostar technique (Prostar) in patients undergoing endovascular aortic repair and to evaluate the short- and mid-term outcomes of both techniques...

  7. Impaired mechanical response of an EDMD mutation leads to motility phenotypes that are repaired by loss of prenylation.

    Science.gov (United States)

    Zuela, Noam; Zwerger, Monika; Levin, Tal; Medalia, Ohad; Gruenbaum, Yosef

    2016-05-01

    There are roughly 14 distinct heritable autosomal dominant diseases associated with mutations in lamins A/C, including Emery-Dreifuss muscular dystrophy (EDMD). The mechanical model proposes that the lamin mutations change the mechanical properties of muscle nuclei, leading to cell death and tissue deterioration. Here, we developed an experimental protocol that analyzes the effect of disease-linked lamin mutations on the response of nuclei to mechanical strain in living Caenorhabditis elegans We found that the EDMD mutation L535P disrupts the nuclear mechanical response specifically in muscle nuclei. Inhibiting lamin prenylation rescued the mechanical response of the EDMD nuclei, reversed the muscle phenotypes and led to normal motility. The LINC complex and emerin were also required to regulate the mechanical response of C. elegans nuclei. This study provides evidence to support the mechanical model and offers a potential future therapeutic approach towards curing EDMD.

  8. Total Extraperitoneal Preperitoneal Laparoscopic Hernia Repair Using Spinal Anesthesia

    OpenAIRE

    Molinelli, Bruce M.; Tagliavia, Alfonso; Bernstein, David

    2006-01-01

    Background: Laparoscopic herniorrhaphy is a well-debated approach to inguinal hernia repair. Multiple technical and outcome variables have been compared with those of traditional open inguinal hernia repairs. One of these variables is the choice of anesthesia. To date, no reports describe the use of spinal anesthesia for laparoscopic hernia repairs. We present herein a review of our experience with spinal anesthesia for the total extraperitoneal preperitoneal laparoscopic hernia repair (TEP)....

  9. Total Extraperitoneal Preperitoneal Laparoscopic Hernia Repair Using Spinal Anesthesia

    OpenAIRE

    2006-01-01

    Background: Laparoscopic herniorrhaphy is a well-debated approach to inguinal hernia repair. Multiple technical and outcome variables have been compared with those of traditional open inguinal hernia repairs. One of these variables is the choice of anesthesia. To date, no reports describe the use of spinal anesthesia for laparoscopic hernia repairs. We present herein a review of our experience with spinal anesthesia for the total extraperitoneal preperitoneal laparoscopic hernia repair (TEP)....

  10. Mechanical behavior of pre tensioned metallic sleeves for pipeline repair; Comportamento mecanico de luvas metalicas pre tensionadas para reparo de dutos terrestres

    Energy Technology Data Exchange (ETDEWEB)

    Meniconi, Luiz C.M.; Paes, Marcelo T. Piza [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas; Frainer, Vitor [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Dept. de Metalurgia. Lab. de Metalurgia Fisica (LAMEF); Souza Filho, Byron G. de [PETROBRAS Transportes S.A. (TRANSPETRO), Rio de Janeiro, RJ (Brazil); Patricio, Wagner [Foxoil do Brasil Ltda., Macae, RJ (Brazil)

    2005-07-01

    Two different methods for pre-tensioning of metallic sleeves for pipeline repair were appraised: mechanic, by means of hydraulic jacks, and thermal, trough the use of oxyacetylene torches. Hydraulic jacks promote an 'in situ' forming of the sleeves, once they impose loads rather than displacements. There is no need of a perfect match between the external diameter of the pipe and the internal diameter of the sleeve. The thermal method, on the other hand, needs a tight fit between the sleeve and the pipe to assure that thermal expansion will turn into elastic deformation. Test specimens were built with four different defect types: crack, dent, gouged dent and thickness loss due to corrosion. The use of pre-tensioned sleeves led to failure pressures 39% above the hydro test pressure, at least. All the specimen failures occurred outside the reinforced area. (author)

  11. Fix-It Careers: Jobs in Repair

    Science.gov (United States)

    Torpey, Elka Maria

    2010-01-01

    From auto mechanic to HVAC technicians, many occupations require repair skills. For jobseekers with the right skills, there are many advantages to a repair career. Repair work provides millions of jobs throughout the United States. Wages are often higher than average. And in many occupations, the employment outlook is bright. Plus, most repair…

  12. Mate choice, sexual imprinting, and speciation: a test of a one-allele isolating mechanism in sympatric sticklebacks.

    Science.gov (United States)

    Albert, Arianne Y K

    2005-04-01

    One-allele isolating mechanisms should make the evolution of reproductive isolation between potentially hybridizing taxa easier than two-allele mechanisms, but the generality of one-allele mechanisms in nature has yet to be established. A potentially important one-allele mechanism is sexual imprinting, where the mate preferences of individuals are based on the phenotype of their parents. Here I test the possibility that sexual imprinting promotes reproductive isolation using sympatric species of threespine sticklebacks (Gasterosteus aculeatus). Sympatric species of sticklebacks consist of large benthic species and small limnetic species that are reproductively isolated and adapted to feeding in different environments. I fostered families of F1 hybrids between the species to males of both species. Preferences of these fostered females for males of either type revealed little or no effect of sexual imprinting on assortative mating. However, F1 females showed preferences for males that were similar to themselves in length, suggesting that size-assortative mating may be more important than sexual imprinting for promoting reproductive isolation between species pairs of threespine sticklebacks.

  13. Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xuan; Liu, Yang; Li, Weichang; Long, Kai; Wang, Lin; Liu, Sa; Wang, Yingjun [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China)

    2015-10-01

    Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)–citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The results showed that the Col–CA films had necessary optical performance, water content. The collagenase resistance of CA crosslinked films was superior to that of EDC crosslinked films. And CA5 film (Col:CA:EDC:NHS = 60:3:10:10) had the best mechanical properties. Cell experiments showed that CA5 film was non-cytotoxic and human corneal epithelial cells could proliferate well on the films. Lamellar keratoplasty showed that the CA5 film could be sutured in the rabbit eyes and was epithelialized completely in about 10 days, and the transparency was restored quickly in 30 ± 5 days. No inflammation and corneal neovascularization were observed at 6 months. Corneal stroma had been repaired; stromal cells and neo-stroma could be seen in the area of operation from the hematoxylin–eosin stained histologic sections and anterior segment optical coherence tomography images. These results indicated that Col–CA films were highly promising biomaterials that could be used in corneal tissue engineering and a variety of other tissue engineering applications. - Highlights: • Adding different amounts of citric acid could change the properties of films. • The crosslinked films had better mechanical property than non-modified films. • Crosslinked collagen–citric acid films could tolerate suture during operation. • The films showed good ability of epithelial and stromal repair.

  14. Mechanism of protection of adenosine from sulphate radical anion and repair of adenosine radicals by caffeic acid in aqueous solution

    Indian Academy of Sciences (India)

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

    The photooxidation of adenosine in presence of peroxydisulphate (PDS) has been studied by spectrophotometrically measuring the absorbance of adenosine at 260 nm. The rates of oxidation of adenosine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in [caffeic acid] is found to decrease the rate of oxidation of adenosine suggesting that caffeic acid acts as an efficient scavenger of $SO_{4}^{\\bullet-}$ and protects adenosine from it. Sulphate radical anion competes for adenosine as well as for caffeic acid. The quantum yields of photooxidation of adenosine have been calculated from the rates of oxidation of adenosine and the light intensity absorbed by PDS at 254 nm, the wavelength at which PDS is activated to sulphate radical anion. From the results of experimentally determined quantum yields (exptl) and the quantum yields calculated (cal) assuming caffeic acid acting only as a scavenger of $SO_{4}^{\\bullet-}$ show that exptl values are lower than cal values. The ' values, which are experimentally found quantum yield values at each caffeic acid concentration and corrected for $SO_{4}^{\\bullet-}$ scavenging by caffeic acid, are also found to be greater than exptl values. These observations suggest that the transient adenosine radicals are repaired by caffeic acid in addition to scavenging of sulphate radical anions.

  15. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  16. Undescended testicle repair

    Science.gov (United States)

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  17. Cognitive and Neural Mechanisms of Intertemporal Choice%跨期选择的认知机制与神经基础

    Institute of Scientific and Technical Information of China (English)

    刘雷; 赵伟华; 冯廷勇

    2012-01-01

    less steeply discounts all delayed rewards and is active in both now and not-now trials. The single-valuation account assumes that at least one location in the human brain encodes the hyperbolically discounted value of all rewards, both on now and not-now trials, and that the option with the higher discounted value is then chosen. However, the single- and dual-valuation accounts agree that the choice of an option results directly from the comparison of their valuations, without additional intervening processes such as self-control. In contrast, the self-control account assumes that preference expressed by evaluation judgments and choice can be discrepant, because neural valuations reflected by valuation judgments can be overridden in choice. Choice is determined not by valuation processes alone, but also involves self-control processes, and especially, the areas of DLPFC may involve self-control process. What has been reviewed above suggests that we are just beginning to gain insight into the nature of temporal decision-making. Much of this work has sought to explore the phenomenon of delay discounting; compared with current or recent gains (or losses), people always give less weight on future gains (or losses). We have pointed to several places where there is currently ambiguity in the treatment of temporal choice: how to perceive time, the neural mechanisms of intertemporal choice, e.g. correlates of patience (self-control) vs. subjective value signals. With the clinical and public policy implications of temporal decision-making as well as the sheer scientific potential in psychology, neuroscience, and economics, further studies should more closely exam the application of intertemporal choice and give more attention from an evolutionary perspective.%跨期选择是现实生活中一个极为普遍的决策现象。本文首先介绍跨期选择的几种经典心理效应,重点分析了跨期选择的认知机制:计算模型和认知成分模型,然

  18. Diverse Responses to UV-B Radiation and Repair Mechanisms of Bacteria Isolated from High-Altitude Aquatic Environments▿

    Science.gov (United States)

    Fernández Zenoff, V.; Siñeriz, F.; Farías, M. E.

    2006-01-01

    Acinetobacter johnsonii A2 isolated from the natural community of Laguna Azul (Andean Mountains at 4,560 m above sea level), Serratia marcescens MF42, Pseudomonas sp. strain MF8 isolated from the planktonic community, and Cytophaga sp. strain MF7 isolated from the benthic community from Laguna Pozuelos (Andean Puna at 3,600 m above sea level) were subjected to UV-B (3,931 J m−2) irradiation. In addition, a marine Pseudomonas putida strain, 2IDINH, and a second Acinetobacter johnsonii strain, ATCC 17909, were used as external controls. Resistance to UV-B and kinetic rates of light-dependent (UV-A [315 to 400 nm] and cool white light [400 to 700 nm]) and -independent reactivation following exposure were determined by measuring the survival (expressed as CFU) and accumulation of cyclobutane pyrimidine dimers (CPD). Significant differences in survival after UV-B irradiation were observed: Acinetobacter johnsonii A2, 48%; Acinetobacter johnsonii ATCC 17909, 20%; Pseudomonas sp. strain MF8, 40%; marine Pseudomonas putida strain 2IDINH, 12%; Cytophaga sp. strain MF7, 20%; and Serratia marcescens, 21%. Most bacteria exhibited little DNA damage (between 40 and 80 CPD/Mb), except for the benthic isolate Cytophaga sp. strain MF7 (400 CPD/Mb) and Acinetobacter johnsonii ATCC 17909 (160 CPD/Mb). The recovery strategies through dark and light repair were different in all strains. The most efficient in recovering were both Acinetobacter johnsonii A2 and Cytophaga sp. strain MF7; Serratia marcescens MF42 showed intermediate recovery, and in both Pseudomonas strains, recovery was essentially zero. The UV-B responses and recovery abilities of the different bacteria were consistent with the irradiation levels in their native environment. PMID:17056692

  19. The energetics and mechanics of level and gradient skipping: Preliminary results for a potential gait of choice in low gravity environments.

    Science.gov (United States)

    Minetti, Alberto E.; Pavei, Gaspare; Biancardi, Carlo M.

    2012-12-01

    Walking and running in low gravity cannot be used at useful speeds, while 'skipping', a gait displayed by kids and spontaneously adopted by astronauts of Apollo missions, proved to have the potential to become the gait of choice in that condition. In this paper the previous biomechanical and metabolic analysis of level skipping is extended to positive and negative gradients, in normal gravity. The results confirm at all gradients the higher (average) ground reaction force during the contact phase, with respect to running at the same speed, which would allow confidently facing the Lunar surface where the dust and regoliths affect, in addition to a lower gravity, the locomotion dynamics. Metabolic data, other gait variables related to the mechanical work done and the locomotor/respiratory coupling have also been investigated.

  20. Analysis of Repair Mechanisms following an Induced Double-Strand Break Uncovers Recessive Deleterious Alleles in the Candida albicans Diploid Genome

    Science.gov (United States)

    Feri, Adeline; Loll-Krippleber, Raphaël; Commere, Pierre-Henri; Maufrais, Corinne; Sertour, Natacha; Schwartz, Katja; Sherlock, Gavin; Bougnoux, Marie-Elisabeth

    2016-01-01

    ABSTRACT The diploid genome of the yeast Candida albicans is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH) events. To provide a deeper understanding of the mechanisms leading to LOH, we investigated the repair of a unique DNA double-strand break (DSB) in the laboratory C. albicans SC5314 strain using the I-SceI meganuclease. Upon I-SceI induction, we detected a strong increase in the frequency of LOH events at an I-SceI target locus positioned on chromosome 4 (Chr4), including events spreading from this locus to the proximal telomere. Characterization of the repair events by single nucleotide polymorphism (SNP) typing and whole-genome sequencing revealed a predominance of gene conversions, but we also observed mitotic crossover or break-induced replication events, as well as combinations of independent events. Importantly, progeny that had undergone homozygosis of part or all of Chr4 haplotype B (Chr4B) were inviable. Mining of genome sequencing data for 155 C. albicans isolates allowed the identification of a recessive lethal allele in the GPI16 gene on Chr4B unique to C. albicans strain SC5314 which is responsible for this inviability. Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. Our results demonstrate that recessive lethal alleles in the genomes of C. albicans isolates prevent the occurrence of specific extended LOH events. While these and other recessive lethal and deleterious alleles are likely to accumulate in C. albicans due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the C. albicans species. PMID:27729506

  1. Analysis of Repair Mechanisms following an Induced Double-Strand Break Uncovers Recessive Deleterious Alleles in the Candida albicans Diploid Genome.

    Science.gov (United States)

    Feri, Adeline; Loll-Krippleber, Raphaël; Commere, Pierre-Henri; Maufrais, Corinne; Sertour, Natacha; Schwartz, Katja; Sherlock, Gavin; Bougnoux, Marie-Elisabeth; d'Enfert, Christophe; Legrand, Mélanie

    2016-10-11

    The diploid genome of the yeast Candida albicans is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH) events. To provide a deeper understanding of the mechanisms leading to LOH, we investigated the repair of a unique DNA double-strand break (DSB) in the laboratory C. albicans SC5314 strain using the I-SceI meganuclease. Upon I-SceI induction, we detected a strong increase in the frequency of LOH events at an I-SceI target locus positioned on chromosome 4 (Chr4), including events spreading from this locus to the proximal telomere. Characterization of the repair events by single nucleotide polymorphism (SNP) typing and whole-genome sequencing revealed a predominance of gene conversions, but we also observed mitotic crossover or break-induced replication events, as well as combinations of independent events. Importantly, progeny that had undergone homozygosis of part or all of Chr4 haplotype B (Chr4B) were inviable. Mining of genome sequencing data for 155 C. albicans isolates allowed the identification of a recessive lethal allele in the GPI16 gene on Chr4B unique to C. albicans strain SC5314 which is responsible for this inviability. Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. Our results demonstrate that recessive lethal alleles in the genomes of C. albicans isolates prevent the occurrence of specific extended LOH events. While these and other recessive lethal and deleterious alleles are likely to accumulate in C. albicans due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the C. albicans species.

  2. Analysis of Repair Mechanisms following an Induced Double-Strand Break Uncovers Recessive Deleterious Alleles in the Candida albicans Diploid Genome

    Directory of Open Access Journals (Sweden)

    Adeline Feri

    2016-10-01

    Full Text Available The diploid genome of the yeast Candida albicans is highly plastic, exhibiting frequent loss-of-heterozygosity (LOH events. To provide a deeper understanding of the mechanisms leading to LOH, we investigated the repair of a unique DNA double-strand break (DSB in the laboratory C. albicans SC5314 strain using the I-SceI meganuclease. Upon I-SceI induction, we detected a strong increase in the frequency of LOH events at an I-SceI target locus positioned on chromosome 4 (Chr4, including events spreading from this locus to the proximal telomere. Characterization of the repair events by single nucleotide polymorphism (SNP typing and whole-genome sequencing revealed a predominance of gene conversions, but we also observed mitotic crossover or break-induced replication events, as well as combinations of independent events. Importantly, progeny that had undergone homozygosis of part or all of Chr4 haplotype B (Chr4B were inviable. Mining of genome sequencing data for 155 C. albicans isolates allowed the identification of a recessive lethal allele in the GPI16 gene on Chr4B unique to C. albicans strain SC5314 which is responsible for this inviability. Additional recessive lethal or deleterious alleles were identified in the genomes of strain SC5314 and two clinical isolates. Our results demonstrate that recessive lethal alleles in the genomes of C. albicans isolates prevent the occurrence of specific extended LOH events. While these and other recessive lethal and deleterious alleles are likely to accumulate in C. albicans due to clonal reproduction, their occurrence may in turn promote the maintenance of corresponding nondeleterious alleles and, consequently, heterozygosity in the C. albicans species.

  3. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  4. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  5. Habitat Choice and Speciation

    Directory of Open Access Journals (Sweden)

    Sophie E. Webster

    2012-01-01

    Full Text Available The role of habitat choice in reproductive isolation and ecological speciation has often been overlooked, despite acknowledgement of its ability to facilitate local adaptation. It can form part of the speciation process through various evolutionary mechanisms, yet where habitat choice has been included in models of ecological speciation little thought has been given to these underlying mechanisms. Here, we propose and describe three independent criteria underlying ten different evolutionary scenarios in which habitat choice may promote or maintain local adaptation. The scenarios are the result of all possible combinations of the independent criteria, providing a conceptual framework in which to discuss examples which illustrate each scenario. These examples show that the different roles of habitat choice in ecological speciation have rarely been effectively distinguished. Making such distinctions is an important challenge for the future, allowing better experimental design, stronger inferences and more meaningful comparisons among systems. We show some of the practical difficulties involved by reviewing the current evidence for the role of habitat choice in local adaptation and reproductive isolation in the intertidal gastropod Littorina saxatilis, a model system for the study of ecological speciation, assessing whether any of the proposed scenarios can be reliably distinguished, given current research.

  6. The Role of Satisfaction and Emotional Response in the Choice Mechanisms of Suburban Natural-Areas Users

    Science.gov (United States)

    Lopez-Mosquera, Natalia; Sanchez, Mercedes

    2012-01-01

    The unique observations and experiences of users of suburban natural areas lead them to perceive their surroundings in a manner associated with their personal values. It follows that every individual has a unique cognitive decision-making structure. This paper examines users' affective and cognitive evaluation of a particular suburban natural area by applying the means-end chain method to reveal the cognitive mechanism by which users link the attributes and benefits of an environmental public good with their own personal values. Analysis of a survey conducted of visitors to a Spanish suburban natural area (park) reveals the main attributes to be the opportunity to practice sports and proximity of the park and the main potential benefits to be the improvement of physical and psychological well-being. The desired personal values include fun, quality of life and self-fulfillment at the individual level and improved social relationships at the collective level. The paper also tests for cross-group, cognitive-structure differences in visitor groups, segmented by level of satisfaction and reported range of emotions, and finds that perceived physical and psychological health improvements and individual and social awareness increase with higher levels of satisfaction and emotional response. Therefore, the recommendations for natural area management suggested by these findings include enhancing the scenic beauty and peacefulness of suburban natural areas in order to improve the affective state of visitors because this could contribute to reducing social costs (including health care) within the area of influence of the natural area.

  7. Models of the behaviour of (thermally stressed) microbial spores in foods: Tools to study mechanisms of damage and repair

    NARCIS (Netherlands)

    ter Beek, A.; Hornstra, L.M.; Pandey, R.; Kallemeijn, W.W.; Smelt, J.P.P.M.; Manders, E.M.M.; Brul, S.

    2011-01-01

    The ‘Omics’ revolution has brought a wealth of new mechanistic insights in many fields of biology. It offers options to base predictions of microbial behaviour on mechanistic insight. As the cellular mechanisms involved often turn out to be highly intertwined it is crucial that model development aim

  8. Turbine repair process, repaired coating, and repaired turbine component

    Energy Technology Data Exchange (ETDEWEB)

    Das, Rupak; Delvaux, John McConnell; Garcia-Crespo, Andres Jose

    2015-11-03

    A turbine repair process, a repaired coating, and a repaired turbine component are disclosed. The turbine repair process includes providing a turbine component having a higher-pressure region and a lower-pressure region, introducing particles into the higher-pressure region, and at least partially repairing an opening between the higher-pressure region and the lower-pressure region with at least one of the particles to form a repaired turbine component. The repaired coating includes a silicon material, a ceramic matrix composite material, and a repaired region having the silicon material deposited on and surrounded by the ceramic matrix composite material. The repaired turbine component a ceramic matrix composite layer and a repaired region having silicon material deposited on and surrounded by the ceramic matrix composite material.

  9. Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism

    Science.gov (United States)

    Jing, Da; Zhai, Mingming; Tong, Shichao; Xu, Fei; Cai, Jing; Shen, Guanghao; Wu, Yan; Li, Xiaokang; Xie, Kangning; Liu, Juan; Xu, Qiaoling; Luo, Erping

    2016-01-01

    Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/β-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and β-catenin protein expressions. In vivo results via μCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/β-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/β-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect. PMID:27555216

  10. 资产专用性对诚信行为选择的作用机理%Action Mechanism of Asset Specificity to Good Faith Behavior Choice

    Institute of Scientific and Technical Information of China (English)

    孙葆春

    2015-01-01

    Through the discussion on the action mechanism of asset specificity to good faith behavior choice, we have conclusion that the asset specificity can produce certain sanction against good faith behavior choice. At the same time, if the asset specificity has different degree of sanction against economic individual, one with the lower degree has the larger initiative right and decisive power. The primary influencing factors of asset specificity playing the role are dealing frequency and information asymmetry. The measures and suggestions to construct the honesty and credit trading environment had been put forward on the base of that analysis.%对资产专用性影响诚信行为选择的作用机理进行探讨的结果显示,资产专用性的投入对经济主体的诚信行为选择具有一定的约束力,资产专用性程度投入水平较低的交易方具有较大的主动权和决定权,影响资产专用性作用发挥的主要因素包括交易频率和信息不对称。为了构建诚信交易环境,需要适度提高专用性资产投入水平、加强市场监管力度、降低信息不对称程度、培养交易主体的诚信意识等。

  11. Systems biology approaches to understanding stem cell fate choice.

    Science.gov (United States)

    Peltier, J; Schaffer, D V

    2010-01-01

    Stem cells have the capability to self-renew and maintain their undifferentiated state or to differentiate into one or more specialised cell types. Stem cell expansion and manipulation ex vivo is a promising approach for engineering cell replacement therapies, and endogenous stem cells represent potential drugable targets for tissue repair. Before we can harness stem cells' therapeutic potential, we must first understand the intracellular mechanisms controlling their fate choices. These mechanisms involve complex signal transduction and gene regulation networks that feature, for example, intricate feed-forward loops, feedback loops and cross-talk between multiple signalling pathways. Systems biology applies computational and experimental approaches to investigate the emergent behaviour of collections of molecules and strives to explain how these numerous components interact to regulate molecular, cellular and organismal behaviour. Here we review systems biology, and in particular computational, efforts to understand the intracellular mechanisms of stem cell fate choice. We first discuss deterministic and stochastic models that synthesise molecular knowledge into mathematical formalism, enable simulation of important system behaviours and stimulate further experimentation. In addition, statistical analyses such as Bayesian networks and principal components analysis (PCA)/partial least squares (PLS) regression can distill large datasets into more readily managed networks and principal components that provide insights into the critical aspects and components of regulatory networks. Collectively, integrating modelling with experimentation has strong potential for enabling a deeper understanding of stem cell fate choice and thereby aiding the development of therapies to harness stem cells' therapeutic potential.

  12. Models of the behaviour of (thermally stressed) microbial spores in foods: tools to study mechanisms of damage and repair.

    Science.gov (United States)

    Ter Beek, Alex; Hornstra, Luc M; Pandey, Rachna; Kallemeijn, Wouter W; Smelt, Jan P P M; Manders, Erik M M; Brul, Stanley

    2011-06-01

    The 'Omics' revolution has brought a wealth of new mechanistic insights in many fields of biology. It offers options to base predictions of microbial behaviour on mechanistic insight. As the cellular mechanisms involved often turn out to be highly intertwined it is crucial that model development aims at identifying the level of complexity that is relevant to work at. For the prediction of microbiologically stable foods insight in the behaviour of bacterial spore formers is crucial. Their chances of germination and likelihood of outgrowth are major food stability indicators, as well as the transition from outgrowth to first cell division and vegetative growth. Current available technology to assess these parameters in a time-resolved manner at the single spore level will be discussed. Tools to study molecular processes operative in heat induced damage will be highlighted.

  13. Choice & Consequence

    DEFF Research Database (Denmark)

    Khan, Azam

    between cause and effect in complex systems complicates decision making. To address this issue, we examine the central role that data-driven decision making could play in critical domains such as sustainability or medical treatment. We developed systems for exploratory data analysis and data visualization...... of data analysis and instructional interface design, to both simulation systems and decision support interfaces. We hope that projects such as these will help people to understand the link between their choices and the consequences of their decisions....

  14. Choice & Consequence

    DEFF Research Database (Denmark)

    Khan, Azam

    between cause and effect in complex systems complicates decision making. To address this issue, we examine the central role that data-driven decision making could play in critical domains such as sustainability or medical treatment. We developed systems for exploratory data analysis and data visualization...... of data analysis and instructional interface design, to both simulation systems and decision support interfaces. We hope that projects such as these will help people to understand the link between their choices and the consequences of their decisions....

  15. Aircraft Propeller Hub Repair

    Energy Technology Data Exchange (ETDEWEB)

    Muth, Thomas R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Peter, William H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-02-13

    The team performed a literature review, conducted residual stress measurements, performed failure analysis, and demonstrated a solid state additive manufacturing repair technique on samples removed from a scrapped propeller hub. The team evaluated multiple options for hub repair that included existing metal buildup technologies that the Federal Aviation Administration (FAA) has already embraced, such as cold spray, high velocity oxy-fuel deposition (HVOF), and plasma spray. In addition the team helped Piedmont Propulsion Systems, LLC (PPS) evaluate three potential solutions that could be deployed at different stages in the life cycle of aluminum alloy hubs, in addition to the conventional spray coating method for repair. For new hubs, a machining practice to prevent fretting with the steel drive shaft was recommended. For hubs that were refurbished with some material remaining above the minimal material condition (MMC), a silver interface applied by an electromagnetic pulse additive manufacturing method was recommended. For hubs that were at or below the MMC, a solid state additive manufacturing technique using ultrasonic welding (UW) of thin layers of 7075 aluminum to the hub interface was recommended. A cladding demonstration using the UW technique achieved mechanical bonding of the layers showing promise as a viable repair method.

  16. Effect of low-level mechanical vibration on osteogenesis and osseointegration of porous titanium implants in the repair of long bone defects

    Science.gov (United States)

    Jing, Da; Tong, Shichao; Zhai, Mingming; Li, Xiaokang; Cai, Jing; Wu, Yan; Shen, Guanghao; Zhang, Xuhui; Xu, Qiaoling; Guo, Zheng; Luo, Erping

    2015-11-01

    Emerging evidence substantiates the potential of porous titanium alloy (pTi) as an ideal bone-graft substitute because of its excellent biocompatibility and structural properties. However, it remains a major clinical concern for promoting high-efficiency and high-quality osseointegration of pTi, which is beneficial for securing long-term implant stability. Accumulating evidence demonstrates the capacity of low-amplitude whole-body vibration (WBV) in preventing osteopenia, whereas the effects and mechanisms of WBV on osteogenesis and osseointegration of pTi remain unclear. Our present study shows that WBV enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton of primary osteoblasts in pTi. WBV upregulated osteogenesis-associated gene and protein expression in primary osteoblasts, including OCN, Runx2, Wnt3a, Lrp6 and β-catenin. In vivo findings demonstrate that 6-week and 12-week WBV stimulated osseointegration, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defects via μCT, histological and histomorphometric analyses. WBV induced higher ALP, OCN, Runx2, BMP2, Wnt3a, Lrp6 and β-catenin, and lower Sost and RANKL/OPG gene expression in rabbit femora. Our findings demonstrate that WBV promotes osteogenesis and osseointegration of pTi via its anabolic effect and potential anti-catabolic activity, and imply the promising potential of WBV for enhancing the repair efficiency and quality of pTi in osseous defects.

  17. Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2

    Energy Technology Data Exchange (ETDEWEB)

    Schellenberg, Matthew J; Appel, C Denise; Adhikari, Sanjay; Robertson, Patrick D; Ramsden, Dale A; Williams, R Scott [NIH; (Georgetown); (UNC)

    2012-10-28

    The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl–linked topo II–DNA adducts. Here, X-ray structures of mouse Tdp2–DNA complexes reveal that Tdp2 β–2-helix–β DNA damage–binding 'grasp', helical 'cap' and DNA lesion–binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove. The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing. Structural, mutational and functional analyses support a single–metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase (EEP) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs.

  18. Early days of DNA repair: discovery of nucleotide excision repair and homology-dependent recombinational repair.

    Science.gov (United States)

    Rupp, W Dean

    2013-12-13

    The discovery of nucleotide excision repair in 1964 showed that DNA could be repaired by a mechanism that removed the damaged section of a strand and replaced it accurately by using the remaining intact strand as the template. This result showed that DNA could be actively metabolized in a process that had no precedent. In 1968, experiments describing postreplication repair, a process dependent on homologous recombination, were reported. The authors of these papers were either at Yale University or had prior Yale connections. Here we recount some of the events leading to these discoveries and consider the impact on further research at Yale and elsewhere.

  19. Some aspects of RNA repair and editing

    Directory of Open Access Journals (Sweden)

    Kovalchuk M. V.

    2010-11-01

    Full Text Available All cellular RNA molecules are damaged at the scale of DNA molecules, or even more. In the present review the RNA damaging agents, some mechanisms of RNA repair and editing, their difference from DNA repair mechanisms have been discussed.

  20. Biodegradable Materials for Bone Repair and Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Zeeshan Sheikh

    2015-08-01

    Full Text Available This review discusses and summarizes the recent developments and advances in the use of biodegradable materials for bone repair purposes. The choice between using degradable and non-degradable devices for orthopedic and maxillofacial applications must be carefully weighed. Traditional biodegradable devices for osteosynthesis have been successful in low or mild load bearing applications. However, continuing research and recent developments in the field of material science has resulted in development of biomaterials with improved strength and mechanical properties. For this purpose, biodegradable materials, including polymers, ceramics and magnesium alloys have attracted much attention for osteologic repair and applications. The next generation of biodegradable materials would benefit from recent knowledge gained regarding cell material interactions, with better control of interfacing between the material and the surrounding bone tissue. The next generations of biodegradable materials for bone repair and regeneration applications require better control of interfacing between the material and the surrounding bone tissue. Also, the mechanical properties and degradation/resorption profiles of these materials require further improvement to broaden their use and achieve better clinical results.

  1. Optimized CRISPR-Cas9 Genome Editing for Leishmania and Its Use To Target a Multigene Family, Induce Chromosomal Translocation, and Study DNA Break Repair Mechanisms

    Science.gov (United States)

    Zhang, Wen-Wei; Lypaczewski, Patrick

    2017-01-01

    of the miltefosine transporter gene and serial transfections of an oligonucleotide donor significantly eased isolation of edited mutants. This cotargeting strategy was efficiently used to delete all 11 members of the A2 virulence gene family. This technical advancement is valuable, since there are many gene clusters and supernumerary chromosomes in the various Leishmania species and isolates. We simplified this CRISPR system by developing a gRNA and Cas9 coexpression vector which could be used to delete genes in various Leishmania species. This CRISPR system could also be used to generate specific chromosomal translocations, which will help in the study of Leishmania gene expression and transcription control. This study also provides new information about double-strand DNA break repair mechanisms in Leishmania. PMID:28124028

  2. Bond strength of repaired amalgam restorations.

    Science.gov (United States)

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi

    2015-01-01

    This in vitro study investigated the interfacial flexural strength (FS) of amalgam repairs and the optimal combination of repair materials and mechanical retention required for a consistent and durable repair bond. Amalgam bricks were created, each with 1 end roughened to expose a fresh surface before repair. Four groups followed separate repair protocols: group 1, bonding agent with amalgam; group 2, bonding agent with composite resin; group 3, mechanical retention (slot) with amalgam; and group 4, slot with bonding agent and amalgam. Repaired specimens were stored in artificial saliva for 1, 10, 30, 120, or 360 days before being loaded to failure in a 3-point bending test. Statistical analysis showed significant changes in median FS over time in groups 2 and 4. The effect of the repair method on the FS values after each storage period was significant for most groups except the 30-day storage groups. Amalgam-amalgam repair with adequate condensation yielded the most consistent and durable bond. An amalgam bonding agent could be beneficial when firm condensation on the repair surface cannot be achieved or when tooth structure is involved. Composite resin can be a viable option for amalgam repair in an esthetically demanding region, but proper mechanical modification of the amalgam surface and selection of the proper bonding system are essential.

  3. Robotic repair of retrocaval ureter: A case series

    Directory of Open Access Journals (Sweden)

    B. Nayak

    2012-09-01

    Conclusions: Robotic retrocaval ureter repair without excision of the retrocaval segment is feasible and an effective alternative to open or laparoscopic retrocaval ureter repair with good anatomical and functional outcome. It may become the procedure of choice along with laparoscopic surgery for retrocaval ureter.

  4. Brain repair: cell therapy in stroke

    Directory of Open Access Journals (Sweden)

    Kalladka D

    2014-02-01

    Full Text Available Dheeraj Kalladka, Keith W Muir Institute of Neuroscience and Psychology, University of Glasgow, Southern General Hospital, Glasgow, United Kingdom Abstract: Stroke affects one in every six people worldwide, and is the leading cause of adult disability. Some spontaneous recovery is usual but of limited extent, and the mechanisms of late recovery are not completely understood. Endogenous neurogenesis in humans is thought to contribute to repair, but its extent is unknown. Exogenous cell therapy is promising as a means of augmenting brain repair, with evidence in animal stroke models of cell migration, survival, and differentiation, enhanced endogenous angiogenesis and neurogenesis, immunomodulation, and the secretion of trophic factors by stem cells from a variety of sources, but the potential mechanisms of action are incompletely understood. In the animal models of stroke, both mesenchymal stem cells (MSCs and neural stem cells (NSCs improve functional recovery, and MSCs reduce the infarct volume when administered acutely, but the heterogeneity in the choice of assessment scales, publication bias, and the possible confounding effects of immunosuppressants make the comparison of effects across cell types difficult. The use of adult-derived cells avoids the ethical issues around embryonic cells but may have more restricted differentiation potential. The use of autologous cells avoids rejection risk, but the sources are restricted, and culture expansion may be necessary, delaying treatment. Allogeneic cells offer controlled cell numbers and immediate availability, which may have advantages for acute treatment. Early clinical trials of both NSCs and MSCs are ongoing, and clinical safety data are emerging from limited numbers of selected patients. Ongoing research to identify prognostic imaging markers may help to improve patient selection, and the novel imaging techniques may identify biomarkers of recovery and the mechanism of action for cell

  5. Randomized trial comparing the Prolene Hernia System, mesh plug repair and Lichtenstein method for open inguinal hernia repair.

    NARCIS (Netherlands)

    Nienhuijs, S.W.; Oort, I.M. van; Keemers-Gels, M.E.; Strobbe, L.J.; Rosman, C.

    2005-01-01

    BACKGROUND: Most surgeons favour the use of a mesh for open inguinal hernia repair as it has a low recurrence rate. Procedures used most frequently are the Lichtenstein method, mesh plug repair and the Prolene Hernia System. The choice of technique may be influenced by the effects on postoperative p

  6. Eye muscle repair - discharge

    Science.gov (United States)

    ... Lazy eye repair - discharge; Strabismus repair - discharge; Extraocular muscle surgery - discharge ... You or your child had eye muscle repair surgery to correct eye muscle ... term for crossed eyes is strabismus. Children most often ...

  7. Ventral hernia repair

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007661.htm Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  8. Brain aneurysm repair

    Science.gov (United States)

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  9. Sesbania mosaic virus (SeMV infectious clone: possible mechanism of 3' and 5' end repair and role of polyprotein processing in viral replication.

    Directory of Open Access Journals (Sweden)

    Kunduri Govind

    Full Text Available Sesbania mosaic virus (SeMV is a positive stranded RNA virus belonging to the genus Sobemovirus. Construction of an infectious clone is an essential step for deciphering the virus gene functions in vivo. Using Agrobacterium based transient expression system we show that SeMV icDNA is infectious on Sesbania grandiflora and Cyamopsis tetragonoloba plants. The efficiency of icDNA infection was found to be significantly high on Cyamopsis plants when compared to that on Sesbania grandiflora. The coat protein could be detected within 6 days post infiltration in the infiltrated leaves. Different species of viral RNA (double stranded and single stranded genomic and subgenomic RNA could be detected upon northern analysis, suggesting that complete replication had taken place. Based on the analysis of the sequences at the genomic termini of progeny RNA from SeMV icDNA infiltrated leaves and those of its 3' and 5' terminal deletion mutants, we propose a possible mechanism for 3' and 5' end repair in vivo. Mutation of the cleavage sites in the polyproteins encoded by ORF 2 resulted in complete loss of infection by the icDNA, suggesting the importance of correct polyprotein processing at all the four cleavage sites for viral replication. Complementation analysis suggested that ORF 2 gene products can act in trans. However, the trans acting ability of ORF 2 gene products was abolished upon deletion of the N-terminal hydrophobic domain of polyprotein 2a and 2ab, suggesting that these products necessarily function at the replication site, where they are anchored to membranes.

  10. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells.

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    In the research, clinical, and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however, this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical, and logistical considerations, together with the propensity for native cells to form teratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs), or umbilical cord blood (UCB) stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  11. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    Directory of Open Access Journals (Sweden)

    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  12. 基于数控等离子耐磨技术的综采中部槽修复%Fully mechanized coal mining central trough repair based on numerical control plasma wear resistance technology

    Institute of Scientific and Technical Information of China (English)

    李龑鹏; 丁紫阳; 王腾飞

    2015-01-01

    in order to solve the problem of mechanized coal mining central trough easy to wear and short life, numerical control plasma wear resistance technology was used to repair central trough of fully mechanized coal mining. and numerical control plasma wear resistance technology and equipment are studied and applied. The results showed that numerical control plasma wear resistance technology is suitable for the repair mechanized coal mining central trough, and this method to repair the central trough can increase the life about 2 times. Moreover, it has a good economic and social beneifts.%为了解决煤矿综采中部槽易磨损、使用寿命短的问题,采用数控等离子耐磨技术修复综采中部槽,通过对数控等离子耐磨技术及设备进行研究并应用。结果表明:数控等离子耐磨技术适合于综采中部槽的修复,且该方法修复后中部槽使用寿命提高了约2倍,具有较好的经济效益和社会效益。

  13. Improvement of adhesion performance of mortar-repair interface with inducing crack path into repair

    Directory of Open Access Journals (Sweden)

    A. Satoh

    2015-10-01

    Full Text Available The most important performance for repair materials is adhesion to the substrate. The authors experimentally find out that high modulus fine aggregates in repair material enhance strength of it as well as the strength of the interface repaired with it, compared to the ordinary repair without fine aggregates. This paper elaborates the mechanisms for that with fractographic observation and FEM analysis based on the results of experiment. Also the authors discuss the ways for enhancing the strength and ductility of the repaired mortar

  14. Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

    Science.gov (United States)

    Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

    2007-02-01

    Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

  15. Biomimetic Scaffold Design for Functional and Integrative Tendon Repair

    Science.gov (United States)

    Zhang, Xinzhi; Bogdanowicz, Danielle; Erisken, Cevat; Lee, Nancy M.; Lu, Helen H.

    2012-01-01

    Rotator cuff tears represent the most common shoulder injuries in the United States. The debilitating effect of this degenerative condition coupled with the high incidence of failure associated with existing graft choices underscore the clinical need for alternative grafting solutions. The two critical design criteria for the ideal tendon graft would require the graft to not only exhibit physiologically relevant mechanical properties but also be able to facilitate functional graft integration by promoting the regeneration of the native tendon-to-bone interface. Centered on these design goals, this review will highlight current approaches to functional and integrative tendon repair. In particular, the application of biomimetic design principles through the use of nanofiber- and nanocomposite-based scaffolds for tendon tissue engineering will be discussed. This review will begin with nanofiber-based approaches to functional tendon repair, followed by a section highlighting the exciting research on tendon-to-bone interface regeneration, with an emphasis on implementation of strategic biomimicry in nanofiber scaffold design and the concomitant formation of graded multi-tissue systems for integrative soft tissue repair. This review will conclude with a summary and future directions section. PMID:22244070

  16. Base excision repair in sugarcane

    Directory of Open Access Journals (Sweden)

    Agnez-Lima Lucymara F.

    2001-01-01

    Full Text Available DNA damage can be induced by a large number of physical and chemical agents from the environment as well as compounds produced by cellular metabolism. This type of damage can interfere with cellular processes such as replication and transcription, resulting in cell death and/or mutations. The low frequency of mutagenesis in cells is due to the presence of enzymatic pathways which repair damaged DNA. Several DNA repair genes (mainly from bacteria, yeasts and mammals have been cloned and their products characterized. The high conservation, especially in eukaryotes, of the majority of genes related to DNA repair argues for their importance in the maintenance of life on earth. In plants, our understanding of DNA repair pathways is still very poor, the first plant repair genes having only been cloned in 1997 and the mechanisms of their products have not yet been characterized. The objective of our data mining work was to identify genes related to the base excision repair (BER pathway, which are present in the database of the Sugarcane Expressed Sequence Tag (SUCEST Project. This search was performed by tblastn program. We identified sugarcane clusters homologous to the majority of BER proteins used in the analysis and a high degree of conservation was observed. The best results were obtained with BER proteins from Arabidopsis thaliana. For some sugarcane BER genes, the presence of more than one form of mRNA is possible, as shown by the occurrence of more than one homologous EST cluster.

  17. Price auditing research of equipment repair based on the price formation mechanism of target price%目标价格形成机制下的装备修理价格审核研究

    Institute of Scientific and Technical Information of China (English)

    陈雪曼; 孙胜祥

    2011-01-01

    In order to promote the development of the price aduting of equipment repair and increase the beneficial cost of equipment repair based on the analysis of the target price, this paper explains how to use the price formation mechanism of target price during the price management of equipment repair, discusses the change of price aduiting work, and last bring forward some suggestions on how to put the price formation mechanism of target price into effect.%为促进装备修理价格审核工作的发展,提高装备修理费用的使用效益,通过对目标价格的相关分析,说明了如何在装备修理价格管理中运用目标价格的价格形成机制,并对新的价格机制下审价工作的改变进行了研究,提出了实施目标价格的价格形成机制的几点建议。

  18. Repairs the added value of being wrong

    CERN Document Server

    Brandt, Patrick

    2013-01-01

    Grammatical structures connect systems of thought and articulation, the conditions of which hardly seem to fit each other. Repairs are productive mechanisms that solve translation problems between modules or levels by adapting derivations or representations to requirements that have to be met unconditionally. Compensating for derivational and interpretive defects, repairs

  19. Mammalian mismatch repair

    DEFF Research Database (Denmark)

    Pena Diaz, Javier; Jiricny, Josef

    2012-01-01

    A considerable surge of interest in the mismatch repair (MMR) system has been brought about by the discovery of a link between Lynch syndrome, an inherited predisposition to cancer of the colon and other organs, and malfunction of this key DNA metabolic pathway. This review focuses on recent...... advances in our understanding of the molecular mechanisms of canonical MMR, which improves replication fidelity by removing misincorporated nucleotides from the nascent DNA strand. We also discuss the involvement of MMR proteins in two other processes: trinucleotide repeat expansion and antibody maturation...

  20. Modeling damage complexity-dependent non-homologous end-joining repair pathway.

    Directory of Open Access Journals (Sweden)

    Yongfeng Li

    Full Text Available Non-homologous end joining (NHEJ is the dominant DNA double strand break (DSB repair pathway and involves several repair proteins such as Ku, DNA-PKcs, and XRCC4. It has been experimentally shown that the choice of NHEJ proteins is determined by the complexity of DSB. In this paper, we built a mathematical model, based on published data, to study how NHEJ depends on the damage complexity. Under an appropriate set of parameters obtained by minimization technique, we can simulate the kinetics of foci track formation in fluorescently tagged mammalian cells, Ku80-EGFP and DNA-PKcs-YFP for simple and complex DSB repair, respectively, in good agreement with the published experimental data, supporting the notion that simple DSB undergo fast repair in a Ku-dependent, DNA-PKcs-independent manner, while complex DSB repair requires additional DNA-PKcs for end processing, resulting in its slow repair, additionally resulting in slower release rate of Ku and the joining rate of complex DNA ends. Based on the numerous experimental descriptions, we investigated several models to describe the kinetics for complex DSB repair. An important prediction of our model is that the rejoining of complex DSBs is through a process of synapsis formation, similar to a second order reaction between ends, rather than first order break filling/joining. The synapsis formation (SF model allows for diffusion of ends before the synapsis formation, which is precluded in the first order model by the rapid coupling of ends. Therefore, the SF model also predicts the higher number of chromosomal aberrations observed with high linear energy transfer (LET radiation due to the higher proportion of complex DSBs compared to low LET radiation, and an increased probability of misrejoin following diffusion before the synapsis is formed, while the first order model does not provide a mechanism for the increased effectiveness in chromosomal aberrations observed.

  1. DNA-Protein Crosslink Proteolysis Repair.

    Science.gov (United States)

    Vaz, Bruno; Popovic, Marta; Ramadan, Kristijan

    2017-06-01

    Proteins that are covalently bound to DNA constitute a specific type of DNA lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles to the progression of DNA replication. If not repaired, DPCs cause stalling of DNA replication forks that consequently leads to DNA double-strand breaks, the most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of DPC repair was unclear until now. Recent work unveiled that DPC repair is orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis repair as a separate DNA repair pathway for genome stability and protection from accelerated aging and cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Cortical Button Fixation: A Better Patellar Tendon Repair?

    Science.gov (United States)

    Ode, Gabriella E; Piasecki, Dana P; Habet, Nahir A; Peindl, Richard D

    2016-10-01

    Patellar tendon ruptures require surgical repair to optimize outcomes, but no consensus exists regarding the ideal repair technique. Cortical button fixation is a secure method for tendon repair that has not been studied in patellar tendons. Cortical button repair is biomechanically superior to the standard transpatellar repair and biomechanically equivalent to suture anchor repair. Controlled laboratory study. Twenty-three fresh-frozen cadaveric knees were used to compare 3 techniques of patellar tendon repair after a simulated rupture at the inferior pole of the patella. Repairs were performed at 45° of flexion using a standard transpatellar suture repair (n = 7), polyetheretherketone (PEEK) suture anchor repair (n = 8), or cortical button repair (n = 8). All specimens were tested on a custom apparatus to simulate cyclic open kinetic chain quadriceps contraction from extension to 90(o) of flexion. Outcomes of gap formation up to 250 cycles, maximum load to failure, and mode of failure were evaluated. Cortical button repair had significantly less gap formation than anchor repair after 1 cycle (P button repair sustained significantly higher loads to failure than anchor repair and suture repair (P button repairs either failed through the suture (n = 5), secondary failure of the patellar tendon (n = 2), or subsidence of the button through the anterior cortex of the patella (n = 1). Patellar tendon repair using cortical button fixation demonstrated mechanical advantages over suture repair and anchor repair in cadaveric specimens. Cortical button fixation showed less cyclic gap formation and withstood at least twice the load to failure of the construct. The biomechanical superiority of cortical button fixation may impart clinical advantages in accelerating postoperative rehabilitation. © 2016 The Author(s).

  3. Nuclear translocation contributes to regulation of DNA excision repair activities

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne;

    2009-01-01

    , it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA.......T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also...

  4. Mate choice turns cognitive.

    Science.gov (United States)

    Miller, G F; Todd, P M

    1998-05-01

    Evolutionary psychology has revolutionized research on human mate choice and sexual attraction in recent years, combining a rigorous Darwinian framework based on sexual selection theory with a loosely cognitivist orientation to task analysis and mechanism modelling. This hard Darwinian, soft computational approach has been most successful at revealing the adaptive logic behind physical beauty, demonstrating that many sexual cues computed from face and body shape are not arbitrary, but function as reliable indicators of phenotypic and genetic quality. The same approach could be extended from physical to psychological cues if evolutionary psychology built stronger ties with personality psychology, psychometrics and behavioral genetics. A major challenge for mate choice research is to develop more explicit computational models at three levels, specifying: (1) the perceptual adaptations that register sexual cues given sensory input, (2) the judgment adaptations that integrate multiple cues into assessments of overall attractiveness, and (3) the search strategies that people follow in trying to form mutually attracted pairs. We describe both recent efforts and possible extensions in these directions. The resulting confluence between evolutionary principles, cognitive models and game-theoretic insights can put mate choice research at the vanguard of an emerging `evolutionary cognitive science' more concerned with domain-specific mental adaptations than with domain-general intelligence.

  5. Emergency inguinal hernia repair under local anesthesia: a 5-year experience in a teaching hospital

    OpenAIRE

    2016-01-01

    Background Local anesthesia (LA) has been reported to be the best choice for elective open inguinal hernia repair because it is cost efficient, with less post-operative pain and enables more rapid recovery. However, the role of LA in emergency inguinal hernia repair is still controversial. The aim of this study is to investigate the safety and effectiveness of LA in emergency inguinal hernia repair. Methods All patients underwent emergency inguinal hernia repair in our hospital between Januar...

  6. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair.

    Science.gov (United States)

    Sasaki, T; Akagi, R; Akatsu, Y; Fukawa, T; Hoshi, H; Yamamoto, Y; Enomoto, T; Sato, Y; Nakagawa, R; Takahashi, K; Yamaguchi, S; Sasho, T

    2017-03-01

    of MSCs in a rabbit model.Cite this article: T. Sasaki, R. Akagi, Y. Akatsu, T. Fukawa, H. Hoshi, Y. Yamamoto, T. Enomoto, Y. Sato, R. Nakagawa, K. Takahashi, S. Yamaguchi, T. Sasho. The effect of systemic administration of G-CSF on a full-thickness cartilage defect in a rabbit model MSC proliferation as presumed mechanism: G-CSF for cartilage repair. Bone Joint Res 2017;6:123-131. DOI: 10.1302/2046-3758.63.BJR-2016-0083. © 2017 Sasho et al.

  7. Repair welding process of friction stir welding groove defect

    Institute of Scientific and Technical Information of China (English)

    LIU Hui-jie; ZHANG Hui-jie

    2009-01-01

    The groove defect formed in the friction stir welding dramatically deteriorates weld appearances and mechanical properties of the joints owing to its larger size and penetration. Therefore, the friction stir repair welding was utilized to remove such a groove defect, and the focus was placed on the mechanical properties and microstructural characteristics of the repair joints so as to obtain an optimum repair welding process. The experimental results indicate that the groove defect can be removed by friction stir repair welding, and the offset repair welding process is superior to the symmetrical repair welding process. In the symmetrical repair welding process, a large number of fine cavity defects and an obvious aggregation of hard-brittle phase Al2Cu occur, accordingly the mechanical properties of the repair joint are weakened, and the fracture feature of repair joint is partially brittle and partially plastic. A good-quality repair joint can be obtained by the offset repair welding process, and the repair joint is fractured near the interface between the weld nugget zone and thermal-mechanically affected zone.

  8. Choice certainty in Discrete Choice Experiments

    DEFF Research Database (Denmark)

    Uggeldahl, Kennet; Jacobsen, Catrine; Lundhede, Thomas Hedemark;

    2016-01-01

    In this study, we conduct a Discrete Choice Experiment (DCE) using eye tracking technology to investigate if eye movements during the completion of choice sets reveal information about respondents’ choice certainty. We hypothesise that the number of times that respondents shift their visual...... attention between the alternatives in a choice set reflects their stated choice certainty. Based on one of the largest samples of eye tracking data in a DCE to date, we find evidence in favor of our hypothesis. We also link eye tracking observations to model-based choice certainty through parameterization...... of the scale function in a random parameters logit model. We find that choices characterized by more frequent gaze shifting do indeed exhibit a higher degree of error variance, however, this effects is insignificant once response time is controlled for. Overall, findings suggest that eye tracking can provide...

  9. Chromatin structure and DNA damage repair

    Directory of Open Access Journals (Sweden)

    Dinant Christoffel

    2008-11-01

    Full Text Available Abstract The integrity of the genome is continuously challenged by both endogenous and exogenous DNA damaging agents. These damaging agents can induce a wide variety of lesions in the DNA, such as double strand breaks, single strand breaks, oxidative lesions and pyrimidine dimers. The cell has evolved intricate DNA damage response mechanisms to counteract the genotoxic effects of these lesions. The two main features of the DNA damage response mechanisms are cell-cycle checkpoint activation and, at the heart of the response, DNA repair. For both damage signalling and repair, chromatin remodelling is most likely a prerequisite. Here, we discuss current knowledge on chromatin remodelling with respect to the cellular response to DNA damage, with emphasis on the response to lesions resolved by nucleotide excision repair. We will discuss the role of histone modifications as well as their displacement or exchange in nucleotide excision repair and make a comparison with their requirement in transcription and double strand break repair.

  10. Databases and Bioinformatics Tools for the Study of DNA Repair

    Directory of Open Access Journals (Sweden)

    Kaja Milanowska

    2011-01-01

    Full Text Available DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER and nucleotide excision repair (NER or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS. There are also other mechanisms of DNA repair such as homologous recombination repair (HRR, nonhomologous end-joining repair (NHEJ, or DNA damage response system (DDR. This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

  11. Non-consensus heptamer sequences destabilize the RAG post-cleavage complex, making ends available to alternative DNA repair pathways.

    Science.gov (United States)

    Arnal, Suzzette M; Holub, Abigail J; Salus, Sandra S; Roth, David B

    2010-05-01

    V(D)J recombination entails double-stranded DNA cleavage at the antigen receptor loci by the RAG1/2 proteins, which recognize conserved recombination signal sequences (RSSs) adjoining variable (V), diversity (D) and joining (J) gene segments. After cleavage, RAG1/2 remain associated with the coding and signal ends (SE) in a post-cleavage complex (PCC), which is critical for their proper joining by classical non-homologous end joining (NHEJ). Certain mutations in RAG1/2 destabilize the PCC, allowing DNA ends to access inappropriate repair pathways such as alternative NHEJ, an error-prone pathway implicated in chromosomal translocations. The PCC is thus thought to discourage aberrant rearrangements by controlling repair pathway choice. Since interactions between RAG1/2 and the RSS heptamer element are especially important in forming the RAG-SE complex, we hypothesized that non-consensus heptamer sequences might affect PCC stability. We find that certain non-consensus heptamers, including a cryptic heptamer implicated in oncogenic chromosomal rearrangements, destabilize the PCC, allowing coding and SEs to be repaired by non-standard pathways, including alternative NHEJ. These data suggest that some non-consensus RSS, frequently present at chromosomal translocations in lymphoid neoplasms, may promote genomic instability by a novel mechanism, disabling the PCC's ability to restrict repair pathway choice.

  12. Changes in DNA repair during aging

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei; Mao, Zhiyong; Hine, Christpher

    2007-01-01

    DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old. PMID:17913742

  13. EGFR相关的DNA修复及放射抗拒机制研究现状%Relativity of EGFR signal as a regulatory mechanism to DNA repair and radiation resistance

    Institute of Scientific and Technical Information of China (English)

    白静; 白晓平; 赵巧艳

    2012-01-01

    目的:总结国外关于表皮生长因子受体(EGFR)通过各种信号通路调节DNA修复导致辐射抗拒相关机制的研究进展.方法:应用PubMed数据库系统,以“表皮生长因子受体、信号通路、DNA损伤修复、放射抗拒”为关键词检索2005-01-2011-12的相关文献,共检索到英文文献198篇.纳入标准:1)EGFR的表达;2)辐射抗拒和DNA损伤修复机制;3)EGFR和辐射诱导的DNA损伤修复;4)EGFR信号通路调控DNA损伤修复导致放射抗拒的可能机制.根据纳入标准,纳入分析22篇文献.结果:EGFR过表达与放化疗抗拒相关.它可以通过联接DNA蛋白激酶催化亚单位(DNA-PKcs)来调节放疗诱导的DNA损伤的修复.EGFR及其对DNA修复能力之间的分子连接可能通过该受体的一个或多个下游信号通路介导.结论:EGFR作为调节DNA损伤修复机制的信号通路与放射抗拒之间存在相关性,靶向于其中激活的信号通路可以为改善放射抗拒提供新的治疗思路.%OBJECTIVE:To sum up the articles related to improvement that epidermal growth factor receptor (EGFR) modulate DNA repair after radiation-induced damage through many signal pathways. METHODS: Epidermal growth factor receptor,signal pathway ,DNA-damage repair and radiation resistance were searched as key words by Pubmed database system from 2005-01 to 2011-12, Altogether 198 English literatures were obtained. Enrolled criteria: 1, EGFR expression; 2. mechanism of DNA repair and radiation resistances 3, EGFR and radiation resistances 4, EGFR signal as a regulatory mechanism to DNA repair and radiation resistance. By extraction according to enrolled criteria, among roughing hundreds of relative articles,46 papers were selected, and 22 papers were finally analyzed. RESULTS: EGFR Overexpres-sion is associated with resistance to chemotherapy and radiotherapy. It modulates DNA repair after radiation-induced damage through association with the catalytic subunit of DNA protein

  14. Origin of Online Metaphor Misunderstanding and Its Repair Mechanism from CBT Perspective%CBT观照下的在线隐喻误解根源及修正机制探究

    Institute of Scientific and Technical Information of China (English)

    李运河

    2012-01-01

    将概念合成理论用于隐喻构建和理解的构想模型,较为合理地解释了部分隐喻的运作机制,这为隐喻误解根源的探究和误解修正机制的假设提供了研究视角。认知图式的差异是在线隐喻误解的重要根源之一,施喻者的补救和受喻者的求同构成误解的修正机制。%The conceived model under the Conceptual Blending Theory (CBT) reasonably explains the operation mechanism of some online metaphors, and the study provides a new perspective for the origin of metaphor misunderstanding and the hypothesis of the repair mechanism. Cognitive schema differences are one of the key sources of the online metaphor misunderstanding. The repair mechanism is realized by the remedy of the metaphor provider and the identification of the metaphor recipient.

  15. Choice Probability Generating Functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel L; Bierlaire, Michel

    This paper considers discrete choice, with choice probabilities coming from maximization of preferences from a random utility field perturbed by additive location shifters (ARUM). Any ARUM can be characterized by a choice-probability generating function (CPGF) whose gradient gives the choice...

  16. Choice Probability Generating Functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel L; Bierlaire, Michel

    This paper considers discrete choice, with choice probabilities coming from maximization of preferences from a random utility field perturbed by additive location shifters (ARUM). Any ARUM can be characterized by a choice-probability generating function (CPGF) whose gradient gives the choice...

  17. Choice probability generating functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel; Bierlaire, Michel

    2013-01-01

    This paper considers discrete choice, with choice probabilities coming from maximization of preferences from a random utility field perturbed by additive location shifters (ARUM). Any ARUM can be characterized by a choice-probability generating function (CPGF) whose gradient gives the choice...

  18. Pectus excavatum repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002949.htm Pectus excavatum repair To use the sharing features on this page, please enable JavaScript. Pectus excavatum repair is surgery to correct pectus excavatum . This ...

  19. Double strand break (DSB) repair in heterochromatin and heterochromatin proteins in DSB repair.

    Science.gov (United States)

    Lemaître, Charlène; Soutoglou, Evi

    2014-07-01

    Chromosomal translocations are a hallmark of cancer cells and they represent a major cause of tumorigenesis. To avoid chromosomal translocations, faithful repair of DNA double strand breaks (DSBs) has to be ensured in the context of high ordered chromatin structure. However, chromatin compaction is proposed to represent a barrier for DSB repair. Here we review the different mechanisms cells use to alleviate the heterochromatic barrier for DNA repair. At the same time, we discuss the activating role of heterochromatin-associated proteins in this process, therefore proposing that chromatin structure, more than being a simple barrier, is a key modulator of DNA repair.

  20. DNA损伤修复机制和糖尿病造成的动脉粥样硬化%Advances in the Relationship between DNA Damage Repair Mechanism and Diabetic Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    曾理(综述); 丁群芳(审校)

    2015-01-01

    Atherosclerosis and the subsequent cardiovascular complications such as myocardial infarc-tion,stroke,and coronary atherosclerotic heart disease are major causes of death among the elderly. DNA damage is the cause of the activation of the DNA damage repair pathway resulting in cell senescence,and the evidence that DNA damage and DNA damage repair mechanism participate in the process of atherosclerosis has been found in some studies. Diabetes,as a risk factor of cardiovascular disease,can lead to DNA damage, so as to accelerate the aging of blood vessels. Here is to make a review of the research development of DNA damage and DNA double strand damage repair mechanism,to provide a new method to prevent and treat ath-erosclerosis.%动脉粥样硬化及其所引起的心肌梗死、脑卒中、冠状动脉粥样硬化性心脏病(冠心病)等是导致老年人病死率增加的重要原因。 DNA损伤是激活DNA损伤修复路径导致细胞早衰的重要原因,而动脉粥样硬化中存在DNA损伤及DNA损伤修复机制参与的证据。糖尿病作为心血管疾病危险因素具有导致DNA损伤,从而加速血管老化的作用。该文综述了动脉粥样硬化疾病中DNA损伤和DNA双链损伤修复机制的研究进展,从而为防治动脉粥样硬化疾病提供新的思路。

  1. Posthysterectomy vault prolapse of vaginal walls: Choice of operating procedure

    Directory of Open Access Journals (Sweden)

    Argirović Rajka

    2012-01-01

    Full Text Available Post-hysterectomy vaginal vault prolapse is a common complication following different types of hysterectomy with a negative impact on the woman’s quality of life due to associated urinary, anorectal and sexual dysfunction. A clear understanding of the supporting mechanisms for the uterus and vagina is important in order to make the right choice of the corrective procedure and also to minimize the risk of posthysterectomy occurrence of vault prolapse. Preexisting pelvic floor defect prior to hysterectomy is the single most important risk factor for vault prolapse. Various surgical techniques have been advanced in hysterectomy to prevent vault prolapse. Vaginal vault repair can be carried out abdominally or vaginally. Sacrospinous fixation and abdominal sacrocolpopexy are the commonly performed procedures. The vaginal approach for vault prolapse is superior to the abdominal approach in terms of complication rates, blood loss, postoperative discomfort, length of hospital stay and costeffectiveness. Moreover, it allows the simultaneous repair of all coexistent pelvic floor defects, such as cystocele, enterocele and rectocele. Abdominal sacrocolpopexy is associated with a lower rate of recurrent vault prolapse and dyspareunia than the vaginal sacrospinous colpopexy. Other less commonly performed procedures include uterosacral ligament suspension and illeococcygeal fixation with a high risk of ureteric injury. Surgical mesh of non-absorbent material is gaining in popularity and preliminary data from vaginal mesh procedures is encouraging.

  2. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  3. Phosphorylation: The Molecular Switch of Double-Strand Break Repair

    Directory of Open Access Journals (Sweden)

    K. C. Summers

    2011-01-01

    Full Text Available Repair of double-stranded breaks (DSBs is vital to maintaining genomic stability. In mammalian cells, DSBs are resolved in one of the following complex repair pathways: nonhomologous end-joining (NHEJ, homologous recombination (HR, or the inclusive DNA damage response (DDR. These repair pathways rely on factors that utilize reversible phosphorylation of proteins as molecular switches to regulate DNA repair. Many of these molecular switches overlap and play key roles in multiple pathways. For example, the NHEJ pathway and the DDR both utilize DNA-PK phosphorylation, whereas the HR pathway mediates repair with phosphorylation of RPA2, BRCA1, and BRCA2. Also, the DDR pathway utilizes the kinases ATM and ATR, as well as the phosphorylation of H2AX and MDC1. Together, these molecular switches regulate repair of DSBs by aiding in DSB recognition, pathway initiation, recruitment of repair factors, and the maintenance of repair mechanisms.

  4. Social defaults : Observed choices become choice defaults

    NARCIS (Netherlands)

    Huh, Young Eun; Vosgerau, J.; Morewedge, C.K.

    2014-01-01

    Defaults effects can be created by social contexts. The observed choices of others can become social defaults, increasing their choice share. Social default effects are a novel form of social influence not due to normative or informational influence: participants were more likely to mimic observed

  5. Mitral Valve Repair: The Chordae Tendineae

    Directory of Open Access Journals (Sweden)

    Carlos-A Mestres

    2015-10-01

    Full Text Available Repair of the mitral valve is the treatment of choice for mitral valve regurgitation when the anatomy is favorable. It is well known that mitral valve repair enjoys better clinical and functional results than any other type of valve substitute. This fact is beyond doubt regardless of the etiology of the valve lesion and is of particular importance in degenerative diseases.This review analyzes the most important advances in the knowledge of the anatomy, pathophysiology, and chordal function of the mitral valve as well as the different alternatives in the surgical repair and clinical results of the most prevalent diseases of the mitral valve. An attempt has been made to organize the acquired information available in a practical way.

  6. Alternative end-joining and classical nonhomologous end-joining pathways repair different types of double-strand breaks during class-switch recombination.

    Science.gov (United States)

    Cortizas, Elena M; Zahn, Astrid; Hajjar, Maurice E; Patenaude, Anne-Marie; Di Noia, Javier M; Verdun, Ramiro E

    2013-12-01

    Classical nonhomologous end-joining (C-NHEJ) and alternative end-joining (A-EJ) are the main DNA double-strand break (DSB) repair pathways when a sister chromatid is not available. However, it is not clear how one pathway is chosen over the other to process a given DSB. To address this question, we studied in mouse splenic B cells and CH12F3 cells how C-NHEJ and A-EJ repair DSBs initiated by the activation-induced deaminase during IgH (Igh) class-switch recombination (CSR). We show in this study that lowering the deamination density at the Igh locus increases DSB resolution by microhomology-mediated repair while decreasing C-NHEJ activity. This process occurs without affecting 53BP1 and γH2AX levels during CSR. Mechanistically, lowering deamination density increases exonuclease I recruitment and single-stranded DNA at the Igh locus and promotes C-terminal binding protein interacting protein and MSH2-dependent DSB repair during CSR. Indeed, reducing activation-induced deaminase levels increases CSR efficiency in C-NHEJ-defective cells, suggesting enhanced use of an A-EJ pathway. Our results establish a mechanism by which C-NHEJ and this C-terminal binding protein interacting protein/MSH2-dependent pathway that relies on microhomology can act concurrently but independently to repair different types of DSBs and reveal that the density of DNA lesions influences the choice of DSB repair pathway during CSR.

  7. The Determinants of Food Choice

    DEFF Research Database (Denmark)

    Leng, Gareth; Adan, Roger A. H.; Belot, Michele

    2017-01-01

    , we need to be able to make valid predictions about the consequences of proposed interventions, and for this, we need a better understanding of the determinants of food choice. These determinants include dietary components (e.g. highly palatable foods and alcohol), but also diverse cultural and social...... pressures, cognitive-affective factors (perceived stress, health attitude, anxiety and depression), and familial, genetic and epigenetic influences on personality characteristics. In addition, our choices are influenced by an array of physiological mechanisms, including signals to the brain from...

  8. The effects of a technology-enhanced, flexible choice science program on achievement, self-efficacy and the scale learner progression mechanism in science

    Science.gov (United States)

    Grace, Lori

    A mixed methods comparative case study of two DRG I urban high schools was used to determine the effectiveness of the Flexible Choice Science Program (FCSP) at producing equitable learning outcomes in students. FCSP recognized both 'among and within learner' differences, while allowing the teacher the semblance of a single lesson. Program sequencing, a differentiated technology platform and allowances for student control and creativity, allowed learners to progress from novice to master at their own pace. Results showed that holistic participation in FCSP by School A students led to significant positive learning effects, particularly for low ability learners. Results of this study challenge current educational grouping techniques that have resulted in inequity, by demonstrating that when students group themselves, their success increases by more than 100%. Results of this research also challenge common notion that cognition most defines student potential by demonstrating that student affect most influences learning.

  9. The New Technology of Composite Materials Repairing by Light Wave

    Institute of Scientific and Technical Information of China (English)

    ZHAO Zhi-min; CHEN Yu-ming; YU Xiao-lei; WANG Le-xin

    2004-01-01

    The repairing of damaged composite materials becomes a hot research subject in the late 1990s.In this paper a new technology of repairing composite materials is given on the basis of our previous research.The light wave of 675nm transmitted by optical fiber is used as repairing light source,special repairable adhesive which can be stimulated by the light is adopted.By comparing the stiffness of the composite material before and after being damaged,it can be concluded that the mechanical property will not be changed with the feasible repairing technology.

  10. This mood is familiar and I don't deserve to feel better anyway: mechanisms underlying self-esteem differences in motivation to repair sad moods.

    Science.gov (United States)

    Wood, Joanne V; Heimpel, Sara A; Manwell, Laurie A; Whittington, Elizabeth J

    2009-02-01

    Why are people with low self-esteem (LSE) less motivated than people with high self-esteem (HSE) to improve sad moods? The present research examined whether feelings of personal deservingness contribute to this difference. Four experiments with undergraduate participants involved a sad mood induction, a manipulation of personal deservingness, or both. Results suggested that (a) LSEs feel less deserving of positive outcomes and of positive moods than do HSEs, (b) feelings of personal deservingness can vary with the situation, and be lowered through reminders of social rejection and personal flaws, and (c) feeling relatively undeserving dampens LSEs', but not HSEs', motivation to repair sad moods. These results have implications for the emotion regulation, self-esteem, and social justice literatures.

  11. 连锁董事连结对会计政策选择的影响机理%Mechanism of interlocking directorates coupling influencing on accounting policy choice

    Institute of Scientific and Technical Information of China (English)

    韩鹤

    2015-01-01

    现有文献大都关注正式契约对会计政策选择的影响,但作为非正式契约的董事联结关系对会计政策选择的影响却被忽视.运用社会网络分析方法,站在社会网络这一视角研究企业会计政策的选择机制.从连锁董事的行为受到董事网络的影响、连锁董事联结是具有影响力的信息通道、连锁董事联结使公司间会计政策选择趋于同质化方面分析了连锁董事网络对会计政策选择的影响;从内外部连锁董事联结强弱关系、外部连锁董事联结更能为公司决策提供有价值的信息分析了内外部连锁董事连结对会计政策选择的影响;从间接连锁董事联结及个体角色间相似性含义、间接连锁董事联结使企业间会计政策选择具有相似性方面分析了间接连锁董事联结对会计政策选择的影响.%The existing literature are mostly focused on the influence of formal contract' s on the accounting policy choice, but the influence of director coupling relation as informal con-tract on accounting policy choice is ignored.In this paper, enterprise accounting policy choice mechanism was studied using social network analysis method from the perspective of social network.From interlocking directorates' behavior being affected by the director net-work, interlocking directorates coupling is influential information channel, analysis of inter-locking director network influencing on accounting policy choice in perspective of interlocking directorates coupling making accounting policy choices tend to be more homogeneous between the companies.Analysis of internal and external interlocking directorates coupling influen-cing on an accounting policy choice in perspective of internal and external interlocking direc-torates coupling strength relation, external interlocking directorates coupling can provide more valuable information for companiy decision-making.Analysis of indirect interlocking directorates coupling

  12. Role of Deubiquitinating Enzymes in DNA Repair

    OpenAIRE

    2016-01-01

    Both proteolytic and nonproteolytic functions of ubiquitination are essential regulatory mechanisms for promoting DNA repair and the DNA damage response in mammalian cells. Deubiquitinating enzymes (DUBs) have emerged as key players in the maintenance of genome stability. In this minireview, we discuss the recent findings on human DUBs that participate in genome maintenance, with a focus on the role of DUBs in the modulation of DNA repair and DNA damage signaling.

  13. Primary repair of colon injuries: clinical study of nonselective approach

    Directory of Open Access Journals (Sweden)

    Krivokapic Zoran V

    2010-12-01

    Full Text Available Abstract Background This study was designed to determine the role of primary repair and to investigate the possibility of expanding indications for primary repair of colon injuries using nonselective approach. Methods Two groups of patients were analyzed. Retrospective (RS group included 30 patients managed by primary repair or two stage surgical procedure according to criteria published by Stone (S/F and Flint (Fl. In this group 18 patients were managed by primary repair. Prospective (PR group included 33 patients with primary repair as a first choice procedure. In this group, primary repair was performed in 30 cases. Results Groups were comparable regarding age, sex, and indexes of trauma severity. Time between injury and surgery was shorter in PR group, (1.3 vs. 3.1 hours. Stab wounds were more frequent in PR group (9:2, and iatrogenic lesions in RS group (6:2. Associated injuries were similar, as well as segmental distribution of colon injuries. S/F criteria and Flint grading were similar. In RS group 15 primary repairs were successful, while in two cases relaparotomy and colostomy was performed due to anastomotic leakage. One patient died. In PR group, 25 primary repairs were successful, with 2 immediate and 3 postoperative (7-10 days deaths, with no evidence of anastomotic leakage. Conclusions Results of this study justify more liberal use of primary repair in early management of colon injuries. Trial registration Current Controlled Trials ISRCTN94682396

  14. Aortoenteric Fistula as a Complication of Open Reconstruction and Endovascular Repair of Abdominal Aorta

    Directory of Open Access Journals (Sweden)

    Marek Tagowski

    2014-01-01

    Full Text Available The paper intends to present a review of imaging characteristics of secondary aortoenteric fistula (AEF. Mechanical injury, infection, and adherence of a bowel segment to the aorta or aortic graft are major etiologic factors of AEF after open aortic repair. The pathogenesis of AEF formation after endovascular abdominal aortic repair is related to mechanical failure of the stent-graft, to stent graft infection, and to persistent pressurization of the aneurysmal sac. The major clinical manifestations of AEF comprise haematemesis, melaena, abdominal pain, sepsis, and fever. CT is the initial diagnostic modality of choice in a stable patient. However, the majority of reported CT appearances are not specific. In case of equivocal CT scans and clinical suspicion of AEF, scintigraphy, 67Ga citrate scans or 18F-FDG PET/CT is useful. Diagnostic accuracy of endoscopy in evaluation of AEF is low; nevertheless it allows to evaluate other than AEF etiologies of gastrointestinal bleeding. Without adequate therapy, AEF is lethal. Conventional surgical treatment is associated with high morbidity and mortality. The endovascular repair may be an option in hemodynamically unstable and high-risk surgical patients. We also illustrate an example of a secondary AEF with highly specific albeit rare radiologic picture from our institution.

  15. Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells

    OpenAIRE

    Johnson, Roger D.; Jasin, Maria

    2000-01-01

    In mammalian cells, repair of DNA double-strand breaks (DSBs) occurs by both homologous and non-homologous mechanisms. By definition, homologous recombination requires a template with sufficient sequence identity to the damaged molecule in order to direct repair. We now show that the sister chromatid acts as a repair template in a substantial proportion of DSB repair events. The outcome of sister chromatid repair is primarily gene conversion unassociated with reciprocal exchange. This contras...

  16. Progress in patch repair of aerospace composite structures

    Science.gov (United States)

    Hou, Weiguo; Zhang, Weifang; Tang, Qingyun

    2012-04-01

    With the rapid application of the composite structure in the aerospace industry, more load-bearing structures and components are used with composites instead of conventional engineering materials. However, the composite structures are inevitably suffered damages in the complex environment, the composites structures repair become more important in the airplane maintenance. This paper describes the composites patch repair progress. Firstly, the flaws and damages concerned to composite structures are concluded, and also the repair principles are presented. Secondly, the advantages and disadvantages for different repair methods are analyzed, as well as the different bonded repair and their applicability to different structures is discussed. According the recent research in theory and experiment, the scarf repair effects under different parameters are analyzed. Finally, the failure mechanisms of repair structure are discussed, and some prospects are put forward.

  17. Effect of glenohumeral abduction angle on the mechanical interaction between the supraspinatus and infraspinatus tendons for the intact, partial-thickness torn, and repaired supraspinatus tendon conditions

    National Research Council Canada - National Science Library

    Andarawis-Puri, Nelly; Kuntz, Andrew F; Ramsey, Matthew L; Soslowsky, Louis J

    2010-01-01

    .... Previously, we showed that with the arm at the side, the supraspinatus and infraspinatus tendons mechanically interact such that conditions that increase supraspinatus tendon strain, such as load...

  18. 目标网络分层描述与自修复机制研究∗%Analysis of Hierarchical Models of Target Network and Self Repairing Mechanisms

    Institute of Scientific and Technical Information of China (English)

    张明星; 杨垚; 程光权; 刘忠

    2016-01-01

    针对目标网络分层建模与自修复机制问题展开研究。首先建立了分层次的作战目标网络模型,在此基础上提出六种维度的指标以评价作战目标网络在攻击前后能力的变化情况;其次,从预警网络层、火力网络层、指控网络层分析探索作战目标体系在遭受攻击后的最优自修复策略;最后,通过模拟攻击实验仿真分析上述自修复机制的可行性。实验结果表明该目标网络的自修复机制相比传统方法,能够更好地发挥剩余节点的作战效能。%This paper researches the hierarchical models of the target operation network and the self repairing mechanisms. First, it builds the hierarchical models of the target operation network and proposes six measures to quantify the different a⁃bilities variations of target operation network before and after attacks. Then, it analyzes the best strategies for different types of nodes after attacks from the perspectives of intelligence level, force network level, command and control level. Last, it an⁃alyzes the feasibility of the self repairing mechanism through the simulation experiment. Theoretical analysis and simulation results confirms that our methods is better than the traditional ones on which it can better utilize the left nodes� effects.

  19. Bundles of spider silk, braided into sutures, resist basic cyclic tests: potential use for flexor tendon repair.

    Directory of Open Access Journals (Sweden)

    Kathleen Hennecke

    Full Text Available Repair success for injuries to the flexor tendon in the hand is often limited by the in vivo behaviour of the suture used for repair. Common problems associated with the choice of suture material include increased risk of infection, foreign body reactions, and inappropriate mechanical responses, particularly decreases in mechanical properties over time. Improved suture materials are therefore needed. As high-performance materials with excellent tensile strength, spider silk fibres are an extremely promising candidate for use in surgical sutures. However, the mechanical behaviour of sutures comprised of individual silk fibres braided together has not been thoroughly investigated. In the present study, we characterise the maximum tensile strength, stress, strain, elastic modulus, and fatigue response of silk sutures produced using different braiding methods to investigate the influence of braiding on the tensile properties of the sutures. The mechanical properties of conventional surgical sutures are also characterised to assess whether silk offers any advantages over conventional suture materials. The results demonstrate that braiding single spider silk fibres together produces strong sutures with excellent fatigue behaviour; the braided silk sutures exhibited tensile strengths comparable to those of conventional sutures and no loss of strength over 1000 fatigue cycles. In addition, the braiding technique had a significant influence on the tensile properties of the braided silk sutures. These results suggest that braided spider silk could be suitable for use as sutures in flexor tendon repair, providing similar tensile behaviour and improved fatigue properties compared with conventional suture materials.

  20. Bundles of Spider Silk, Braided into Sutures, Resist Basic Cyclic Tests: Potential Use for Flexor Tendon Repair

    Science.gov (United States)

    Hennecke, Kathleen; Redeker, Joern; Kuhbier, Joern W.; Strauss, Sarah; Allmeling, Christina; Kasper, Cornelia; Reimers, Kerstin; Vogt, Peter M.

    2013-01-01

    Repair success for injuries to the flexor tendon in the hand is often limited by the in vivo behaviour of the suture used for repair. Common problems associated with the choice of suture material include increased risk of infection, foreign body reactions, and inappropriate mechanical responses, particularly decreases in mechanical properties over time. Improved suture materials are therefore needed. As high-performance materials with excellent tensile strength, spider silk fibres are an extremely promising candidate for use in surgical sutures. However, the mechanical behaviour of sutures comprised of individual silk fibres braided together has not been thoroughly investigated. In the present study, we characterise the maximum tensile strength, stress, strain, elastic modulus, and fatigue response of silk sutures produced using different braiding methods to investigate the influence of braiding on the tensile properties of the sutures. The mechanical properties of conventional surgical sutures are also characterised to assess whether silk offers any advantages over conventional suture materials. The results demonstrate that braiding single spider silk fibres together produces strong sutures with excellent fatigue behaviour; the braided silk sutures exhibited tensile strengths comparable to those of conventional sutures and no loss of strength over 1000 fatigue cycles. In addition, the braiding technique had a significant influence on the tensile properties of the braided silk sutures. These results suggest that braided spider silk could be suitable for use as sutures in flexor tendon repair, providing similar tensile behaviour and improved fatigue properties compared with conventional suture materials. PMID:23613793

  1. Speakers' choice of frame in binary choice

    Directory of Open Access Journals (Sweden)

    Marc van Buiten

    2009-02-01

    Full Text Available A distinction is proposed between extit{recommending for} preferred choice options and extit{recommending against} non-preferred choice options. In binary choice, both recommendation modes are logically, though not psychologically, equivalent. We report empirical evidence showing that speakers recommending for preferred options predominantly select positive frames, which are less common when speakers recommend against non-preferred options. In addition, option attractiveness is shown to affect speakers' choice of frame, and adoption of recommendation mode. The results are interpreted in terms of three compatibility effects, (i extit{recommendation mode---valence framing compatibility}: speakers' preference for positive framing is enhanced under extit{recommending for} and diminished under extit{recommending against} instructions, (ii extit{option attractiveness---valence framing compatibility}: speakers' preference for positive framing is more pronounced for attractive than for unattractive options, and (iii extit{recommendation mode---option attractiveness compatibility}: speakers are more likely to adopt a extit{recommending for} approach for attractive than for unattractive binary choice pairs.

  2. Dose- and time-dependent effects of genipin crosslinking on cell viability and tissue mechanics - toward clinical application for tendon repair

    NARCIS (Netherlands)

    Fessel, Gion; Cadby, Jennifer; Wunderli, Stefania; Snedeker, Jess G; van Weeren, René

    2014-01-01

    The crosslinking agent genipin is increasingly invoked for the mechanical augmentation of collagen tissues and implants, and has previously been demonstrated to arrest mechanical damage accumulation in various tissues. This study established an in vitro dose-response baseline for the effects of geni

  3. Repairs of composite structures

    Science.gov (United States)

    Roh, Hee Seok

    Repair on damaged composite panels was conducted. To better understand adhesively bonded repair, the study investigates the effect of design parameters on the joint strength. The design parameters include bondline length, thickness of adherend and type of adhesive. Adhesives considered in this study were tested to measure their tensile material properties. Three types of adhesively bonded joints, single strap, double strap, and single lap joint were considered under changing bondline lengths, thickness of adherend and type of adhesive. Based on lessons learned from bonded joints, a one-sided patch repair method for composite structures was conducted. The composite patch was bonded to the damaged panel by either film adhesive FM-73M or paste adhesive EA-9394 and the residual strengths of the repaired specimens were compared under varying patch sizes. A new repair method using attachments has been suggested to enhance the residual strength. Results obtained through experiments were analyzed using finite element analysis to provide a better repair design and explain the experimental results. It was observed that the residual strength of the repaired specimen was affected by patch length. Method for rapid repairs of damaged composite structures was investigated. The damage was represented by a circular hole in a composite laminated plate. Pre-cured composite patches were bonded with a quick-curing commercial adhesive near (rather than over) the hole. Tensile tests were conducted on specimens repaired with various patch geometries. The test results showed that, among the methods investigated, the best repair method restored over 90% of the original strength of an undamaged panel. The interfacial stresses in the adhesive zone for different patches were calculated in order to understand the efficiencies of the designs of these patch repairs. It was found that the composite patch that yielded the best strength had the lowest interfacial peel stress between the patch and

  4. Informed Food Choice

    DEFF Research Database (Denmark)

    Coff, Christian

    2014-01-01

    Food production and consumption influence health, the environment, social structures, etc. For this reason consumers are increasingly interested in information about these effects. Disclosure of information about the consequences of food production and consumption is essential for the idea...... of informed food choice. An informed food choice is an enlightened food choice made by the individual based on the information made available. Food choices are made when shopping for food or when eating/drinking, and information is believed to give clarity to the options by increasing market transparency......, supporting rationality (the best choice), consumers’ self-governance (autonomy) and life coherence (integrity). On a practical level, informed food choice remains an ideal to strive for, as information on food often is inadequate....

  5. Informed food choice

    DEFF Research Database (Denmark)

    Coff, Christian Eyde

    2014-01-01

    Food production and consumption influence health, the environment, social structures, etc. For this reason consumers are increasingly interested in information about these effects. Disclosure of information about the consequences of food production and consumption is essential for the idea...... of informed food choice. An informed food choice is an enlightened food choice made by the individual based on the information made available. Food choices are made when shopping for food or when eating/drinking, and information is believed to give clarity to the options by increasing market transparency......, supporting rationality (the best choice), consumers’ self-governance (autonomy) and life coherence (integrity). On a practical level, informed food choice remains an ideal to strive for, as information on food often is inadequate....

  6. Informed Food Choice

    DEFF Research Database (Denmark)

    Coff, Christian

    2014-01-01

    of informed food choice. An informed food choice is an enlightened food choice made by the individual based on the information made available. Food choices are made when shopping for food or when eating/drinking, and information is believed to give clarity to the options by increasing market transparency......, supporting rationality (the best choice), consumers’ self-governance (autonomy) and life coherence (integrity). On a practical level, informed food choice remains an ideal to strive for, as information on food often is inadequate.......Food production and consumption influence health, the environment, social structures, etc. For this reason consumers are increasingly interested in information about these effects. Disclosure of information about the consequences of food production and consumption is essential for the idea...

  7. Promoting educated consumer choices

    DEFF Research Database (Denmark)

    Edinger, Wieke Willemijn Huizing

    2016-01-01

    Contemporary EU food information legislation combines and balances two main consumer interests, i.e., a consumer right to information and the freedom of choice, into one single protective standard: informed choice. Although the recent legislative measures quite openly establish a link between...... informed choice and the rather abstract societal norm of “what is good for the consumer,” this does not justify the conclusion that food information legislation has become overly meddlesome in relation to EU consumers and their choice of food. Rather, there has been a gradual maturing of the EU legislator......’s perception of its task from the mere provision of food information to ensuring educated consumer choices. This development is a logical and necessary consequence of the growing complexity of food choices....

  8. Flexible Plug Repair for Shuttle Wing Leading Edge

    Science.gov (United States)

    Camarda, Charles J.; Sikora, Joseph; Smith, Russel; Rivers, H.; Scotti, Stephen J.; Fuller, Alan M.; Klacka, Robert; Reinders, Martin; Schwind, Francis; Sullivan, Brian; hide

    2012-01-01

    In response to the Columbia Accident Investigation Board report, a plug repair kit has been developed to enable astronauts to repair the space shuttle's wing leading edge (WLE) during orbit. The plug repair kit consists of several 17.78- cm-diameter carbon/silicon carbide (C/SiC) cover plates of various curvatures that can be attached to the refractory carbon-carbon WLE panels using a TZM refractory metal attach mechanism. The attach mechanism is inserted through the damage in the WLE panel and, as it is tightened, the cover plate flexes to conform to the curvature of the WLE panel within 0.050 mm. An astronaut installs the repair during an extravehicular activity (EVA). After installing the plug repair, edge gaps are checked and the perimeter of the repair is sealed using a proprietary material, developed to fill cracks and small holes in the WLE.

  9. Exosomes and cardiac repair after myocardial infarction.

    Science.gov (United States)

    Sahoo, Susmita; Losordo, Douglas W

    2014-01-17

    Myocardial infarction is a leading cause of death among all cardiovascular diseases. The analysis of molecular mechanisms by which the ischemic myocardium initiates repair and remodeling indicates that secreted soluble factors are key players in communication to local and distant tissues, such as bone marrow. Recently, actively secreted membrane vesicles, including exosomes, are being recognized as new candidates with important roles in intercellular and tissue-level communication. In this review, we critically examine the emerging role of exosomes in local and distant microcommunication mechanisms after myocardial infarction. A comprehensive understanding of the role of exosomes in cardiac repair after myocardial infarction could bridge a major gap in knowledge of the repair mechanism after myocardial injury.

  10. Workshop on DNA repair.

    NARCIS (Netherlands)

    A.R. Lehmann (Alan); J.H.J. Hoeijmakers (Jan); A.A. van Zeeland (Albert); C.M.P. Backendorf (Claude); B.A. Bridges; A. Collins; R.P.D. Fuchs; G.P. Margison; R. Montesano; E. Moustacchi; A.T. Natarajan; M. Radman; A. Sarasin; E. Seeberg; C.A. Smith; M. Stefanini (Miria); L.H. Thompson; G.P. van der Schans; C.A. Weber (Christine); M.Z. Zdzienika

    1992-01-01

    textabstractA workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic C

  11. Laparoscopic lumbar hernia repair.

    Science.gov (United States)

    Madan, Atul K; Ternovits, Craig A; Speck, Karen E; Pritchard, F Elizabeth; Tichansky, David S

    2006-04-01

    Lumbar hernias are rare clinical entities that often pose a challenge for repair. Because of the surrounding anatomy, adequate surgical herniorraphy is often difficult. Minimally invasive surgery has become an option for these hernias. Herein, we describe two patients with lumbar hernias (one with a recurrent traumatic hernia and one with an incisional hernia). Both of these hernias were successfully repaired laparoscopically.

  12. Choice Neighborhood Grantees

    Data.gov (United States)

    Department of Housing and Urban Development — Choice Neighborhoods grants transform distressed neighborhoods, public and assisted projects into viable and sustainable mixed-income neighborhoods by linking...

  13. Princess takamatsu symposium on DNA repair and human cancers.

    Science.gov (United States)

    Loeb, Lawrence A; Nishimura, Susumu

    2010-06-01

    The 40th International Symposium of the Princess Takamatsu Cancer Research Fund, entitled "DNA Repair and Human Cancers," was held on November 10-12, 2009 at Hotel Grand Palace, Tokyo, Japan. The meeting focused on the role of DNA repair in preventing mutations by endogenous and exogenous DNA damage and increasing the efficacy of chemotherapeutic agents by interfering with DNA repair. The 14 presentations by the speakers from the United States, four from the United Kingdom, one each from Italy, The Netherlands, and France, and 13 from Japan, covered most aspects of DNA repair, spanning DNA damage, molecular structures of repair enzymes, and clinical studies on inhibition of DNA repair processes. Extensive time was reserved for discussions with the active participation of the 150 invited Japanese scientists. The choice of a symposium on DNA repair in human cancers resulted in part from the excellent basic and clinical studies that have been carried out for many years in Japan, and the general lack of recognition versus the importance of DNA repair in understanding carcinogenesis. Copyright 2010 AACR.

  14. Mechanisms involved in repairing the lesions induced in pBR 322 by PUVA treatment (8-Methoxypsoralen + ultraviolet A light). Mecanismos implicados en la reparacion de las lesiones inducidas en pBR322 por tratamiento Puva (8-metoxipsoraleno + luz ultravioleta A)

    Energy Technology Data Exchange (ETDEWEB)

    Bauluz, C.

    1988-07-01

    This work deals with the genotoxic effects derived from damaging pBR322 DNA through PUVA treatment (8-Methoxypsoralen plus UVA light), both with respect to the lethality and mutagenicity of the lesions produced by the treatment. The mechanisms involved in the repair of the plasmid lesions have been investigated by transforming several strains of E. coli differing in their DNA-repair capacities. The frequency, distribution and type of mutations occurring in a restriction fragment of the damaged plasmid were determined in order to establish the mutagenic features of the PUVA treatment. Damages produced by PUVA have a strong lethal effect on plasmid survival; however, partial recovery is possible through some of the bacterial DNA repair pathways, namely excision repair, SOS-repair and a third mechanism which appears to be independent from the analyzed genes and is detected at high density of lesions per plasmid molecule. PUVA treatment produces a high increase in plasmid mutagenesis; however, the contribution of such an increase to the whole plasmid survival is negligible. Only punctual mutations were detected and consisted mainly in base-pair substitutions. Some mutation-prone regions were found inside the investigated DNA fragment, although their existence is more likely to be related with the structure acquired by the damaged DNA than with the type of damaging agent.

  15. THE UNEXPECTED YARD OF SHIP REPAIR INDUSTRY COSCO ZHOUSHAN Shipyard

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ It was July 8th 2004 when the email on screen showing one of my company tankers was strutted by another tanker at the waterway outside of Quanzhou, without any other choices, followed by one of the underwriters'suggestion, the vessel was tugged to COSCO (Zhoushan) Shipyard, a brand new shipyard for repairing.

  16. A singular choice for multiple choice

    DEFF Research Database (Denmark)

    Frandsen, Gudmund Skovbjerg; Schwartzbach, Michael Ignatieff

    2006-01-01

    How should multiple choice tests be scored and graded, in particular when students are allowed to check several boxes to convey partial knowledge? Many strategies may seem reasonable, but we demonstrate that five self-evident axioms are sufficient to determine completely the correct strategy. We ...

  17. Screening of biochemical and molecular mechanisms of secondary injury and repair in the brain after experimental blast-induced traumatic brain injury in rats.

    Science.gov (United States)

    Kochanek, Patrick M; Dixon, C Edward; Shellington, David K; Shin, Samuel S; Bayır, Hülya; Jackson, Edwin K; Kagan, Valerian E; Yan, Hong Q; Swauger, Peter V; Parks, Steven A; Ritzel, David V; Bauman, Richard; Clark, Robert S B; Garman, Robert H; Bandak, Faris; Ling, Geoffrey; Jenkins, Larry W

    2013-06-01

    Abstract Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. Injury produced ∼25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2'-AMP [adenosine monophosphate], and 5'-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1α, IL-6, IL-10, and macrophage inflammatory protein 1 alpha [MIP-1α]) were increased; by 24 h, only MIP-1α remained elevated. ATP was not depleted, and adenosine correlated with 2'-cyclic AMP (cAMP), and not 5'-cAMP. Our data reveal (1) gene-array alterations similar to disorders of

  18. Mechanical analyses of pipeline repair and reinforcement with use of composite functionally graded materials; Analise mecanica de reforco de dutos submarinos com materiais compositos com gradacao funcional

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcos S.M. [Sondotecnica Engenharia de Solos S.A., Rio de Janeiro, RJ (Brazil); Roehl, Deane de Mesquita [Pontificia Universidade Catolica do Rio de Janeiro (PUC-Rio), RJ (Brazil)

    2008-07-01

    This work presents a methodology for design of stiffener sleeve constituted by functionally graded composite materials in offshore pipelines located in extreme-deep waters, where high mechanical resistance allied to an efficient system of thermal isolation is necessary, in view of the excellent thermomechanical behavior of composites. For the case of FGMs, due to continuous variation in its featuring, is necessary to employ an adapted model, based on a model typically adopted for conventional composites (Rule of Mixture), as the model idealized by Tamura, Tomato e Ozawa, the TTO model. In this report, the influence of geometric and materials parameters in mechanical behavior of pipelines under propagating collapse is analyzed. (author)

  19. Competitive repair by naturally dispersed repetitive DNA during non-allelic homologous recombination

    Energy Technology Data Exchange (ETDEWEB)

    Hoang, Margaret L.; Tan, Frederick J.; Lai, David C.; Celniker, Sue E.; Hoskins, Roger A.; Dunham, Maitreya J.; Zheng, Yixian; Koshland, Douglas

    2010-08-27

    Genome rearrangements often result from non-allelic homologous recombination (NAHR) between repetitive DNA elements dispersed throughout the genome. Here we systematically analyze NAHR between Ty retrotransposons using a genome-wide approach that exploits unique features of Saccharomyces cerevisiae purebred and Saccharomyces cerevisiae/Saccharomyces bayanus hybrid diploids. We find that DNA double-strand breaks (DSBs) induce NAHR-dependent rearrangements using Ty elements located 12 to 48 kilobases distal to the break site. This break-distal recombination (BDR) occurs frequently, even when allelic recombination can repair the break using the homolog. Robust BDR-dependent NAHR demonstrates that sequences very distal to DSBs can effectively compete with proximal sequences for repair of the break. In addition, our analysis of NAHR partner choice between Ty repeats shows that intrachromosomal Ty partners are preferred despite the abundance of potential interchromosomal Ty partners that share higher sequence identity. This competitive advantage of intrachromosomal Tys results from the relative efficiencies of different NAHR repair pathways. Finally, NAHR generates deleterious rearrangements more frequently when DSBs occur outside rather than within a Ty repeat. These findings yield insights into mechanisms of repeat-mediated genome rearrangements associated with evolution and cancer.

  20. Consumer choice behaviour

    DEFF Research Database (Denmark)

    Hansen, Flemming; Percy, Larry; Hallum Hansen, Morten

    2004-01-01

    The paper is concerned with the measurement of emotions and the study of the role ofemotions in consumer choice. Contemporary neurological findings suggest that emotionsmay play a role in its own right, quite different from the way in which they have beenconsidered in traditional consumer choice...

  1. Making Smart Food Choices

    Science.gov (United States)

    ... turn JavaScript on. Feature: Healthy Aging Making Smart Food Choices Past Issues / Winter 2015 Table of Contents Everyday ... NIH www.nia.nih.gov/Go4Life Making Smart Food Choices To maintain a healthy weight, balance the calories ...

  2. School Choice Marches forward

    Science.gov (United States)

    Butcher, Jonathan

    2013-01-01

    One year ago, the "Wall Street Journal" dubbed 2011 "the year of school choice," opining that "this year is shaping up as the best for reformers in a very long time." School-choice laws took great strides in 2011, both in the number of programs that succeeded across states and also in the size and scope of the adopted…

  3. Empirical social choice

    DEFF Research Database (Denmark)

    Kurrild-Klitgaard, Peter

    2014-01-01

    applications. Special attention is given to three phenomena and their possible empirical manifestations: The instability of social choice in the form of (1) the possibility of majority cycles, (2) the non-robustness of social choices given alternative voting methods, and (3) the possibility of various forms...

  4. Crime Location Choice

    NARCIS (Netherlands)

    Bernasco, Wim; Ruiter, Stijn

    2014-01-01

    Most behavior of interest to social scientists is choice behavior: actions people commit while they could also have done something else. In geographical and environmental criminology, a new framework has emerged for analyzing individual crime location choice. It is based on the principle of random u

  5. Tough and easy choices

    DEFF Research Database (Denmark)

    Olsen, Søren Bøye; Lundhede, Thomas; Jacobsen, Jette Bredahl

    2011-01-01

    Respondents in Stated Preference studies may be uncertain about their preferences for the good presented to them. Inspired by Wang (J Environ Econ Manag 32:219–232, 1997) we hypothesize that respondents’ stated certainty in choice increases with the utility difference between the alternative chosen...... and the best alternative to that. We test this hypothesis using data from two independent Choice Experiments both focusing on nature values. In modelling respondents’ self-reported certainty in choice, we find evidence that the stated level of certainty increases significantly as utility difference in choice...... sets increases. In addition, stated certainty increases with income. Furthermore, there is some evidence that male respondents are inherently more certain in their choices than females, and a learning effect may increase stated certainty. We find evidence of this in the first study where the good...

  6. Tough and easy choices

    DEFF Research Database (Denmark)

    Olsen, Søren Bøye; Lundhede, Thomas; Jacobsen, Jette Bredahl

    2011-01-01

    Respondents in Stated Preference studies may be uncertain about their preferences for the good presented to them. Inspired by Wang (J Environ Econ Manag 32:219–232, 1997) we hypothesize that respondents’ stated certainty in choice increases with the utility difference between the alternative chosen...... and the best alternative to that. We test this hypothesis using data from two independent Choice Experiments both focusing on nature values. In modelling respondents’ self-reported certainty in choice, we find evidence that the stated level of certainty increases significantly as utility difference in choice...... sets increases. In addition, stated certainty increases with income. Furthermore, there is some evidence that male respondents are inherently more certain in their choices than females, and a learning effect may increase stated certainty. We find evidence of this in the first study where the good...

  7. Physiological and Biochemical Mechanism of Massage on Repairing of Injury Skeletal Muscle%骨骼肌损伤修复的生理生化机制研究

    Institute of Scientific and Technical Information of China (English)

    侯懿烜; 柳满然; 张萍; 郑元义; 刘仁建; 唐成林

    2011-01-01

    To understand the physiological and biochemical mechanism of massage on the repair of rabbit damaged skeletal muscle and its motor endplate (MEP). Methods 30 of New Zealand rabbits were randomly divided into 3 groups, which were normal group, self-repairing group (including 7-day (3 rabbits) , 14-day, 21-day injury subgroup (6 rabbits/subgroup)) and massage group (including 7-day, 14-day subgroup, 6 rabbits/subgroup). The quadriceps femoris injured models were established with self-made lead hitter. H&E staining and Choline copper method were employed todetect the pathologic change or activity of AchE and MEPs in the quadriceps femoris tissue derived from massage therapeutic and self-repairing rabbits. Results The obvious broken muscular fibers, muscle atrophy were found in self-repairing tissue contrasted to the tissue from massage-rabbits. No obvious histological change was found in the normal tissue with average 9.1 M Eps/field and its average size of 91.6μm2. In the massaged rabbits, muscle atrophy was found to be hindered, and higher activity of AchE was detected in the recovering skeletal muscle. The average numbers of MEPs were 6. 3 (about 72μm2) and 8.9 (about 89μm2) in massage-rabbits for 7 days and 14 days respectively. However, these parameters were 3.0 (about 31μm2) in rabbits injured for 7 days, 3. 8 (about 53μm2) in 14 days' self-repairing rabbits and 5.9 (about 74 u,m2) in 21 days' self-repairing rabbits. Conclusion Massage can prompt the repair of injured quadriceps femoris through enhancing muscular AchE activity and recovery of MEPs, thus prevent the degenerative muscle atrophy.%为探讨新西兰兔股四头肌损伤修复过程中,按摩对骨骼肌和运动终板(MEP)损伤修复的生理生化机制,将30只雄性新西兰大白兔随机分成正常组、自然恢复组(损伤后7d(3只)、14 d和21 d三个亚组(各6只))和按摩治疗组(按摩7d和14d两个亚组(各6只)).重物打击法制作兔股四头肌急性损伤模型,H&E染

  8. Ceramic restoration repair: report of two cases

    Directory of Open Access Journals (Sweden)

    Luís Henrique Araújo Raposo

    2009-04-01

    Full Text Available The esthetic and functional rehabilitation of patients with multiple missing teeth can be performed with several techniques and materials. Ceramic restorations provide reliable masticatory function and good esthetics. However, fracture can occur in some cases due to their brittle behavior. In some cases, the replacement of an extensive prosthesis is a problem due to the high treatment cost. In this paper, two cases are presented, in which fractures occurred in extensive metal-ceramic fixed partial dentures, and their replacement was not possible. Ceramic repair was chosen and the sequences of treatment with and without presence of the ceramic fragment are also discussed. The cases illustrate that, in some situations, fractured metal-ceramic partial dentures can be successfully repaired when prosthetic replacement is not a choice. Prosthodontists must use alternatives that allow a reliable repair to extensive metal-ceramic fixed partial dentures. Surface preparation of the ceramic with hydrofluoric acid in conjunction with a silane coupling agent is essential for a predictable bonding of composite resin. The repair performed with composite resin is an esthetic and functional alternative when extensive fixed partial dentures cannot be replaced.

  9. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available 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.

  10. Repair and regeneration in endodontics.

    Science.gov (United States)

    Lin, L M; Rosenberg, P A

    2011-10-01

    The ideal objective of treatment of established diseases, including irreversible pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can result in repair or regeneration. The ultimate goal of wound healing is to restore the original architecture and biological function of the injured tissue or organ. Although humans are equipped with powerful innate and adaptive immune defence mechanisms, many intrinsic and extrinsic factors can affect wound healing. Complete regeneration following injury in humans can occur only in the pre-natal foetus within 24 weeks of gestation. Post-natal wounds including irreversible pulpitis or apical periodontitis always heal by repair or by a combination of repair and regeneration. Somatic cells, such as fibroblasts, macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues have limited potential for regeneration following injury and lack of telomerase. Wound healing of irreversible pulpitis and apical periodontitis requires recruitment and differentiation of progenitor/stem cells into tissue-committed somatic cells. Stem cell differentiation is regulated by intrinsic factors and extrinsic micro-environmental cues. Functionality of stem cells appears to show an age-related decline because of the change in intrinsic properties and diminished signals within the extrinsic local and systemic environment that modulate the function of stem cells or their progeny. Infection induces an immuno-inflammatory response and tissue destruction, which hinders the potential of tissue regeneration. Therefore, prevention, early detection and treatment of inflammation/infection of pulpal and periapical disease can enhance regeneration and minimize the repair of pulpal and periapical tissues after endodontic therapy. © 2011 International Endodontic Journal.

  11. A Quantum of Solace: Guzman on the Classical Mechanics of International Law - Book Review: Andrew Guzman, How International Law Works. A Rational Choice Theory (2008

    Directory of Open Access Journals (Sweden)

    Matthias Goldmann

    2009-02-01

    class="ArticleText">Compared to the discipline of international law, scholars of physics are blessed. While the principles of classical mechanics were theorized several centuries ago, quantum theory and the theory of relativity offer supplementary ways for describing how material objects and energy interact where classical mechanics does not provide an explanation. Thus, even in the absence of an all-comprising “world theory”, physicists have a wide array of workable theories at their service. By contrast, the “classical mechanics” of international law, i.e. the explanation of the most basic causal relationships between international legal norms and the behaviour of states as the main subjects of international law, are still subject to deep theoretical controversies. International legal doctrine presupposes that international law does have an impact and does not aim at questioning or further explaining this assumption. Traditional legal theories that see the essence of legal normativity in the possibility to trigger mechanisms of physical constraint often come to the conclusion that international law, in the absence of central enforcement mechanisms, is at best a primitive form of law. More recent enquiries into international legal theory from very different theoretical angles come to even less uplifting conclusions. Some argue that international legal norms are either entirely devoid of content because of their inherent indeterminacy and therefore prone to be captured by special interests. Others consider international law to be merely epiphenomenal because rational states would only consent to legal norms if, and as long as, they describe a behaviour they would choose anyway because it promises higher payoffs. In particular the latter critique put forward so forcefully by Jack Goldsmith and Eric Posner sent considerable shock waves through the invisible college of international lawyers. This is the background that needs to be kept

  12. Unbounded evidence accumulation characterizes subjective visual vertical (SVV) forced-choice perceptual choice and confidence.

    Science.gov (United States)

    Lim, Koeun; Wang, Wei; Merfeld, Daniel M

    2017-07-26

    Humans can subjectively yet quantitatively assess choice confidence based on perceptual precision even when a perceptual decision is made without an immediate reward or feedback. However, surprisingly little is known about choice confidence. Here we investigate the dynamics of choice confidence by merging two parallel conceptual frameworks of decision-making, signal detection theory and sequential analyses (i.e., drift diffusion modeling). Specifically, in order to capture end-point statistics of binary choice and confidence, we built on a previous study that defined choice confidence in terms of psychophysics derived from signal detection theory. At the same time, we augmented this mathematical model to include accumulator dynamics of a drift-diffusion model to characterize the time-dependency of the choice behaviors in a standard forced-choice paradigm in which stimulus duration is controlled by the operator. Human subjects performed a subjective visual vertical task, simultaneously reporting binary orientation choice and probabilistic confidence. Both binary choice and confidence experimental data displayed statistics and dynamics consistent with both signal detection theory and evidence accumulation, respectively. Specifically, the computational simulations showed that the unbounded evidence accumulator model fits the confidence data better than the classical bounded model, while bounded and unbounded models were indistinguishable for binary choice data. These results suggest that the brain can utilize mechanisms consistent with signal detection theory - especially when judging confidence without time pressure. Copyright © 2017, Journal of Neurophysiology.

  13. Laparoscopic repair for vesicouterine fistulae

    Directory of Open Access Journals (Sweden)

    Rafael A. Maioli

    2015-10-01

    . Discussion: Laparoscopy has advantages over open surgery in that it is associated with less pain, shorter length of hospital stay, better cosmesis, quicker recovery, and equal efficacy. Although cases of VUF are rarely noted, the laparoscopic skill obtained through other urological procedures suggest, that laparoscopic repair may be the procedure of choice for such cases (2. The reported operative time for the laparoscopic repair of VUF in the literature varies between 140 and 220 min (3. However, laparoscopic techniques should be considered as a mode of abdominal access and should not influence the method of surgical repair. Surgical success should depend on the adherence to good technique rather than the approach. Hence, this method appears to be a viable alternative for surgeons experienced with laparoscopic suturing techniques. Conclusion: Laparoscopic repair appears to be a viable alternative for surgeons experienced with laparoscopic suturing techniques.

  14. Balanitis xerotica obliterans complicating hypospadias repair.

    Science.gov (United States)

    Kumar, M V; Harris, D L

    1999-01-01

    We review the literature and report a series of eight cases of balanitis xerotica obliterans (BXO) developing in patients following primary hypospadias repair. The ages of these patients ranged from 8 to 25 years with BXO developing from 1 to 16 years postoperatively. Six patients were treated by excision of the BXO tissue and two-stage urethroplasties with full-thickness grafts. Three of these patients had further recurrence of BXO and had re-do urethroplasty using a combination of bladder and buccal mucosa. The last two patients in this series had re-do urethroplasty using bladder mucosa only and bladder-buccal mucosa technique, respectively, as first choice for BXO complicating their hypospadias repair.

  15. Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei-Implications for comparative studies

    DEFF Research Database (Denmark)

    Akbari, Mansour; Krokan, Hans E

    2012-01-01

    using purified proteins essentially mirror properties of the proteins used, and does not necessarily reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured cells have the capacity to carry out complete BER and can give important information on the mechanism. Furthermore......, candidate proteins in extracts can be inhibited or depleted in a controlled way, making defined extracts an important source for mechanistic studies. The major drawback is that there is no standardized method of preparing nuclear extract for BER studies, and it does not appear to be a topic given much...... attention. Here we have examined BER activity of nuclear cell extracts from HeLa cells, using as substrate a circular DNA molecule with either uracil or an AP-site in a defined position. We show that BER activity of nuclear extracts from the same batch of cells varies inversely with the volume of nuclear...

  16. Nucleotide excision repair in differentiated cells

    Energy Technology Data Exchange (ETDEWEB)

    Wees, Caroline van der [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Jansen, Jacob [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Laarse, Arnoud van der [Department of Cardiology, Leiden University Medical Center, Leiden (Netherlands); Zeeland, Albert van [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Mullenders, Leon [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands)]. E-mail: l.mullenders@lumc.nl

    2007-01-03

    Nucleotide excision repair (NER) is the principal pathway for the removal of a wide range of DNA helix-distorting lesions and operates via two NER subpathways, i.e. global genome repair (GGR) and transcription-coupled repair (TCR). Although detailed information is available on expression and efficiency of NER in established mammalian cell lines, little is known about the expression of NER pathways in (terminally) differentiated cells. The majority of studies in differentiated cells have focused on repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4-photoproducts (6-4PP) because of the high frequency of photolesions at low level of toxicity and availability of sensitive technologies to determine photolesions in defined regions of the genome. The picture that emerges from these studies is blurred and rather complex. Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression. This repair phenotype is clearly different from human terminal differentiated neurons. Furthermore, both cell types were found to carry out TCR of CPD, thus mimicking the repair phenotype of established rodent cell lines. In contrast, in intact rat spermatogenic cells repair was very inefficient at the genome overall level and in transcriptionally active genes indicating that GGR and TCR are non-functional. Also, non-differentiated mouse embryonic stem (ES) cells exhibit low levels of NER after UV irradiation. However, the mechanisms that lead to low NER activity are clearly different: in differentiated spermatogenic cells differences in chromatin compaction and sequestering of NER proteins may underlie the lack of NER activity in pre-meiotic cells, whereas in non-differentiated ES cells NER is impaired by a strong apoptotic response.

  17. Elucidating the digital control mechanism for DNA damage repair with the p53-Mdm2 system: single cell data analysis and ensemble modelling.

    Science.gov (United States)

    Ogunnaike, Babatunde A

    2006-02-22

    Recent experimental evidence about DNA damage response using the p53-Mdm2 system has raised some fundamental questions about the control mechanism employed. In response to DNA damage, an ensemble of cells shows a damped oscillation in p53 expression whose amplitude increases with increased DNA damage--consistent with 'analogue' control. Recent experimental results, however, show that the single cell response is a series of discrete pulses in p53; and with increase in DNA damage, neither the height nor the duration of the pulses change, but the mean number of pulses increase--consistent with 'digital' control. Here we present a system engineering model that uses published data to elucidate this mechanism and resolve the dilemma of how digital behaviour at the single cell level can manifest as analogue ensemble behaviour. First, we develop a dynamic model of the p53-Mdm2 system that produces non-oscillatory responses to a stress signal. Second, we develop a probability model of the distribution of pulses in a cell population, and combine the two with the simplest digital control algorithm to show how oscillatory responses whose amplitudes grow with DNA damage can arise from single cell behaviour in which each single pulse response is independent of the extent of DNA damage. A stochastic simulation of the hypothesized control mechanism reproduces experimental observations remarkably well.

  18. Macrophages in Tissue Repair, Regeneration, and Fibrosis.

    Science.gov (United States)

    Wynn, Thomas A; Vannella, Kevin M

    2016-03-15

    Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.

  19. A brief history of the DNA repair field.

    Science.gov (United States)

    Friedberg, Errol C

    2008-01-01

    The history of the repair of damaged DNA can be traced to the mid-1930s. Since then multiple DNA repair mechanisms, as well as other biological responses to DNA damage, have been discovered and their regulation has been studied. This article briefly recounts the early history of this field.

  20. Nucleotide excision repair of DNA: The very early history.

    Science.gov (United States)

    Friedberg, Errol C

    2011-07-15

    This article, taken largely from the book Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms, summarizes the very early history of the discovery of nucleotide excision repair. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne)

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in

  2. A brief history of the DNA repair field

    Institute of Scientific and Technical Information of China (English)

    Errol C Friedberg

    2008-01-01

    The history of the repair of damaged DNA can be traced to the mid-1930s. Since then multiple DNA repair mecha-nisms, as well as other biological responses to DNA damage, have been discovered and their regulation has been studied. This article briefly recounts the early history of this field.

  3. Haemophilus influenzae does not fit theories of postreplication repair

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, J K; Notani, N K

    1980-01-01

    Studies with Escherichia coli have provided all the initial insights into the molecular bases of repair processes. It is the thesis of this article that especially if we believe that there are some general mechanisms in nature, it is important to consider more than one microorganism in arriving at an understanding of the biology of repair of DNA.

  4. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne)

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in repai

  5. Irrational choice and the value of information

    OpenAIRE

    Marco Vasconcelos; Tiago Monteiro; Alex Kacelnik

    2015-01-01

    Irrational decision making in humans and other species challenges the use of optimality in behavioural biology. Here we show that such observations are in fact powerful tools to understand the adaptive significance of behavioural mechanisms. We presented starlings choices between probabilistic alternatives, receiving or not information about forthcoming, delayed outcomes after their choices. Subjects could not use this information to alter the outcomes. Paradoxically, outcome information indu...

  6. 选择与竞争:英国国民医疗服务体系的准市场机制改革%Choice and Competition: Analysis on Quasi-market Mechanism Reform of British NHS System

    Institute of Scientific and Technical Information of China (English)

    王向澄

    2015-01-01

    The quality, efficiency, responsiveness, and equity of service management are the indicators for the public health care system. International experiences show that the provision of public medical and health services in general has four modes: namely, trust-based mode, command and control mode, opinion expression mode, and choice and competition mode. Each mode has its own advantage, as well as disadvantage. Existing theories and empirical studies suggest that the choice and competition mode in most cases is superior to other modes. Since the 21st century, the British National Health Service (NHS) system carried through a quasi-market mechanism reform based on the principle of choice and competition. As a result, its medical service in terms of quality, efficiency, responsiveness, and equity made significant improvement. Meanwhile, the related management institutions and policy have the necessity to get well-arranged and redesign in order to cope with potential problems and challenges.%服务管理的质量、效率、回应性与公平性是公立医疗卫生体系注重的指标.国际经验显示,公立医疗卫生服务的提供包括信任模式、指挥与控制模式、表达模式、选择与竞争模式,每种模式各有利弊.理论与实证分析认为,选择与竞争模式多数情况下优于其他模式.本世纪以来,英国国民医疗服务体系进行的是基于选择与竞争的准市场机制改革.目前已在医疗服务的质量、效率、回应性及公平性等方面取得显著的提升.但同时,相关的管理与政策有必要加以完善,以应对潜在的问题与挑战.对英国国民医疗服务体系改革的模式选择与实践经验的学习与分析,将对我国的医疗改革在一定程度上有借鉴意义,有利于进一步明晰改革的方向并实现改革的稳步推进.

  7. Progress of peripheral nerve repair

    Institute of Scientific and Technical Information of China (English)

    陈峥嵘

    2002-01-01

    Study on repair of peripheral nerve injury has been proceeding over a long period of time. With the use of microsurgery technique since 1960s,the quality of nerve repair has been greatly improved. In the past 40 years, with the continuous increase of surgical repair methods, more progress has been made on the basic research of peripheral nerve repair.

  8. Composite repairs qualification according to ISO/TS 24817

    Energy Technology Data Exchange (ETDEWEB)

    Meniconi, Luiz C.M.; Perrut, Valber A. [Petroleo Brasileiro S.A. (PETROBRAS/CENPES), Rio de Janeiro, RJ (Brazil). Centro de Pesquisas

    2009-07-01

    Composite repairs for metallic pipes from three different suppliers were evaluated according to ISO Technical Specification TS 24817. The intended application scenarios are offshore production plants, but the design methodology is also applicable to onshore pipelines and pipework. The evaluation covered all the relevant mechanical properties and established the maximum application temperatures for each repair system. The tests also considered the application of composite repair sleeves to metallic pipes with through thickness defects, by measuring the strain energy release rates of the composite-metal interfaces. The test campaigns aimed to verify the applicability of the recently published ISO document, and to implement it as the routine procedure for composite repairs evaluation within PETROBRAS. The tests also addressed the influence of metallic pipe surface preparation on the final properties of the repair sleeves, especially in relation to the long term behavior of leaking pipes repaired by means of composite materials. (author)

  9. Composite repairs qualification according to ISO/TS 24817

    Energy Technology Data Exchange (ETDEWEB)

    Meniconi, Luiz C.M.; Perrut, Valber A. [Petroleo Brasileiro S.A. (PETROBRAS/CENPES), Rio de Janeiro, RJ (Brazil). Centro de Pesquisas

    2009-07-01

    Composite repairs for metallic pipes from three different suppliers were evaluated according to ISO Technical Specification TS 24817. The intended application scenarios are offshore production plants, but the design methodology is also applicable to onshore pipelines and pipework. The evaluation covered all the relevant mechanical properties and established the maximum application temperatures for each repair system. The tests also considered the application of composite repair sleeves to metallic pipes with through thickness defects, by measuring the strain energy release rates of the composite-metal interfaces. The test campaigns aimed to verify the applicability of the recently published ISO document, and to implement it as the routine procedure for composite repairs evaluation within PETROBRAS. The tests also addressed the influence of metallic pipe surface preparation on the final properties of the repair sleeves, especially in relation to the long term behavior of leaking pipes repaired by means of composite materials. (author)

  10. Achilles tendon repair

    Science.gov (United States)

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large cut ...

  11. Diaphragmatic hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100014.htm Diaphragmatic hernia repair - series—Normal anatomy To use the sharing ... Overview The chest cavity includes the heart and lungs. The abdominal cavity includes the liver, the stomach, ...

  12. Eye muscle repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  13. Tracheoesophageal fistula repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100103.htm Tracheoesophageal fistula repair - series—Normal anatomy To use the sharing ... Editorial team. Related MedlinePlus Health Topics Esophagus Disorders Fistulas Tracheal Disorders A.D.A.M., Inc. is ...

  14. Inguinal hernia repair - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100027.htm Inguinal hernia repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview A hernia occurs when part of an organ protrudes through ...

  15. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary

    2004-04-12

    The two broad categories of deposited weld metal repair and fiber-reinforced composite liner repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repair and for fiber-reinforced composite liner repair. Evaluation trials have been conducted using a modified fiber-reinforced composite liner provided by RolaTube and pipe sections without liners. All pipe section specimens failed in areas of simulated damage. Pipe sections containing fiber-reinforced composite liners failed at pressures marginally greater than the pipe sections without liners. The next step is to evaluate a liner material with a modulus of elasticity approximately 95% of the modulus of elasticity for steel. Preliminary welding parameters were developed for deposited weld metal repair in preparation of the receipt of Pacific Gas & Electric's internal pipeline welding repair system (that was designed specifically for 559 mm (22 in.) diameter pipe) and the receipt of 559 mm (22 in.) pipe sections from Panhandle Eastern. The next steps are to transfer welding parameters to the PG&E system and to pressure test repaired pipe sections to failure. A survey of pipeline operators was conducted to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. Completed surveys contained the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway crossings. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created

  16. Pectus excavatum repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100035.htm Pectus excavatum repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Pectus excavatum is a deformity of the front of the ...

  17. Hiatal hernia repair - slideshow

    Science.gov (United States)

    ... presentations/100028.htm Hiatal hernia repair - series—Normal anatomy To use the sharing features on ... Overview The esophagus runs through the diaphragm to the stomach. It functions to carry food from the mouth ...

  18. Repairing ceramic insulating tiles

    Science.gov (United States)

    Dunn, B. R.; Laymance, E. L.

    1980-01-01

    Fused-silica tiles containing large voids or gauges are repaired without adhesives by plug insertion method. Tiles are useful in conduits for high-temperature gases, in furnaces, and in other applications involving heat insulation.

  19. Rotator cuff repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100229.htm Rotator cuff repair - series—Normal anatomy To use the sharing ... to slide 4 out of 4 Overview The rotator cuff is a group of muscles and tendons that ...

  20. Cleft lip repair - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100010.htm Cleft lip repair - series—Normal anatomy To use the sharing ... abnormal opening in the middle of the upper lip. A cleft palate is an opening in the roof of ...

  1. Choices after Graduation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    正From the above table,we can see that the students of this university have three main choices after graduation.Of these choices,the students who have found a job only take up 50%.In contrast,students who pursue further study by taking the postgraduate entrance exam or going abroad have increased greatly than before, with the total percentage of 47%.Indeed,this phenomenon is also quite common in other universities. The following factors can account for the choices of graduates.Above all,with the enrollment extension of universities,college graduates are facing the severe em-

  2. Choice probability generating functions

    DEFF Research Database (Denmark)

    Fosgerau, Mogens; McFadden, Daniel; Bierlaire, Michel

    2010-01-01

    This paper establishes that every random utility discrete choice model (RUM) has a representation that can be characterized by a choice-probability generating function (CPGF) with specific properties, and that every function with these specific properties is consistent with a RUM. The choice...... probabilities from the RUM are obtained from the gradient of the CPGF. Mixtures of RUM are characterized by logarithmic mixtures of their associated CPGF. The paper relates CPGF to multivariate extreme value distributions, and reviews and extends methods for constructing generating functions for applications...

  3. The axiom of choice

    CERN Document Server

    Jech, Thomas J

    2008-01-01

    Comprehensive in its selection of topics and results, this self-contained text examines the relative strengths and consequences of the axiom of choice. Each chapter contains several problems, graded according to difficulty, and concludes with some historical remarks.An introduction to the use of the axiom of choice is followed by explorations of consistency, permutation models, and independence. Subsequent chapters examine embedding theorems, models with finite supports, weaker versions of the axiom, and nontransferable statements. The final sections consider mathematics without choice, cardin

  4. Grey Repairable System Analysis

    Institute of Scientific and Technical Information of China (English)

    Renkuan Guo; Charles Ernie Love

    2006-01-01

    In this paper, we systematically discuss the basic concepts of grey theory, particularly the grey differential equation and its mathematical foundation, which is essentially unknown in the reliability engineering community. Accordingly,we propose a small-sample based approach to estimate repair improvement effects by partitioning system stopping times into intrinsic functioning times and repair improvement times. An industrial data set is used for illustrative purposes in a stepwise manner.

  5. Repair of DNA Double-Strand Breaks

    Science.gov (United States)

    Falk, Martin; Lukasova, Emilie; Kozubek, Stanislav

    The genetic information of cells continuously undergoes damage induced by intracellular processes including energy metabolism, DNA replication and transcription, and by environmental factors such as mutagenic chemicals and UV and ionizing radiation. This causes numerous DNA lesions, including double strand breaks (DSBs). Since cells cannot escape this damage or normally function with a damaged genome, several DNA repair mechanisms have evolved. Although most "single-stranded" DNA lesions are rapidly removed from DNA without permanent damage, DSBs completely break the DNA molecule, presenting a real challenge for repair mechanisms, with the highest risk among DNA lesions of incorrect repair. Hence, DSBs can have serious consequences for human health. Therefore, in this chapter, we will refer only to this type of DNA damage. In addition to the biochemical aspects of DSB repair, which have been extensively studied over a long period of time, the spatio-temporal organization of DSB induction and repair, the importance of which was recognized only recently, will be considered in terms of current knowledge and remaining questions.

  6. Mechanisms of assembly of the enzyme-ssDNA complexes required for recombination-dependent DNA synthesis and repair in bacteriophage T4

    Energy Technology Data Exchange (ETDEWEB)

    Morrical, S.; Hempstead, K.; Morrical, M. [Univ. of Vermont College of Medicine, Burlington, VT (United States)

    1994-12-31

    During late stages of bacteriophage T4 infection in E. coli, the initiation of phage DNA replication is dependent on the homologous recombination activity of the T4 uvsX protein. In vitro, uvsX protein initiates DNA synthesis on a duplex template by inserting the 3{prime} end of a homologous ssDNA molecule into the duplex. The resulting D-loop structure serves as a primer-template junction for the assembly of the T4 replication fork. Two key steps in this initiation process are (A) the assembly of uvsX-ssDNA complexes necessary for recombination activity and for the priming of lead-strand DNA synthesis, and (B) the assembly of the T4 primosome (gp41 helicase/gp61 primase complex) onto the single-stranded template for lagging-strand synthesis. Our laboratory is focusing on the mechanisms of these two different but related enzyme-ssDNA assembly processes. In this extended abstract, we describe recent efforts in our laboratory to elucidate the mechanism by which the gp41 helicase enzyme is assembled onto gp32-covered ssDNA, a process requiring the activity of a special helicase assembly factor, the T4 gp59 protein.

  7. Research on supply chain repair mechanism based on directed weighted complex network%基于有向加权复杂网络的供应链修复机制研究

    Institute of Scientific and Technical Information of China (English)

    贺鹤鸣; 成耀荣

    2016-01-01

    为从整体效率出发确定供应链受损后的修复方案,通过调节供应链网络的连边权重来模拟其受损状况,对有限修复资源进行分配,以供应链网络效率为指标寻找最优方案。以BBV(Barrat-Barthelemy-Vespignani)模型为基础,结合企业之间的当量物流量和空间距离计算连边权重,从有向加权复杂网络的角度建立供应链网络模型。结合连接阻力对最短路径公式进行改进,设计出基于节点间平均最小合作阻力的供应链网络效率指标。分别从全局受损和某节点受损进行供应链的修复研究,并且找到效率最优方案。研究结果表明:由于供应链网络的节点、连边之间相互影响,不同的节点、连边组合会产生不同的效果,从供应链网络效率角度考虑修复方案更具全局意义。%In order to study the repair mechanism of damaged supply chain from the perspective of overall effi-ciency,the weight of the supply chain links was adjusted to simulate the damage of the supply chain,allocate limited repair resources,and find the optimal solution with supply chain network efficiency as the index.Logistics volume and spatial distance were combined to calculate the weight of links,and a directed weighted supply chain network model was established on the basis of BBV.The formula of the shortest path combined with connection resistance was improved,and the efficiency index of supply chain network was designed based on the average min-imum cooperation resistance between nodes.Supply chain repair mechanism was studied from the global damage and the damage of one node,and the optimal efficiency scheme was found.Results show that due to the mutual in-fluence existing between nodes and links,different combinations of nodes and links can produce different effects, while the restoration scheme has more global significance from the point of the efficiency of supply chain network.

  8. Make Better Food Choices

    Science.gov (United States)

    10 tips Nutrition Education Series make better food choices 10 tips for women’s health Fruits Grains Dairy Vegetables Protein Make yourself a priority and take time to care for yourself. ChooseMyPlate. gov ...

  9. Veterans Choice Program

    Data.gov (United States)

    Department of Veterans Affairs — If you are already enrolled in VA health care, the Choice Program allows you to receive health care within your community. Using this program does NOT impact your...

  10. Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila.

    Directory of Open Access Journals (Sweden)

    Daniel P Kane

    Full Text Available In metazoans, the mechanism by which DNA is synthesized during homologous recombination repair of double-strand breaks is poorly understood. Specifically, the identities of the polymerase(s that carry out repair synthesis and how they are recruited to repair sites are unclear. Here, we have investigated the roles of several different polymerases during homologous recombination repair in Drosophila melanogaster. Using a gap repair assay, we found that homologous recombination is impaired in Drosophila lacking DNA polymerase zeta and, to a lesser extent, polymerase eta. In addition, the Pol32 protein, part of the polymerase delta complex, is needed for repair requiring extensive synthesis. Loss of Rev1, which interacts with multiple translesion polymerases, results in increased synthesis during gap repair. Together, our findings support a model in which translesion polymerases and the polymerase delta complex compete during homologous recombination repair. In addition, they establish Rev1 as a crucial factor that regulates the extent of repair synthesis.

  11. Mechanisms of larval midgut damage following exposure to phoxim and repair of phoxim-induced damage by cerium in Bombyx mori.

    Science.gov (United States)

    Yu, Xiaohong; Sun, Qingqing; Li, Bing; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sheng, Lei; Sang, Xuezi; Gui, Suxin; Wang, Ling; Shen, Weide; Hong, Fashui

    2015-04-01

    Bombyx mori is an important economic animal for silk production. However, it is liable to be infected by organophosphorus pesticide that can contaminate its food and growing environment. It has been known that organophosphorus pesticide including phoxim exposure may damage the digestive systems, produce oxidative stress and neurotoxicity in silkworm B. mori, whereas cerium treatment has been demonstrated to relieve phoxim-induced toxicity in B. mori. However, very little is known about the molecular mechanisms of midgut injury due to phoxim exposure and B. mori protection after cerium pretreatment. The aim of this study was to evaluate the midgut damage and its molecular mechanisms, and the protective role of cerium in B. mori following exposure to phoxim. The results showed that phoxim exposure led to severe midgut damages and oxidative stress; whereas cerium relieved midgut damage and oxidative stress caused by phoxim in B. mori. Furthermore, digital gene expression suggested that phoxim exposure led to significant up-regulation of 94 genes and down-regulation of 52 genes. Of these genes, 52 genes were related with digestion and absorption, specifically, the significant alterations of esterase, lysozyme, amylase 48, and lipase expressions. Cerium pretreatment resulted in up-regulation of 116 genes, and down-regulation of 29 genes, importantly, esterase 48, lipase, lysozyme, and α-amylase were up-regulated. Treatment with Phoxim + CeCl3 resulted in 66 genes up-regulation and 39 genes down-regulation; specifically, levels of esterase 48, lipase, lysozyme, and α-amylase expression in the midgut of silkworms were significantly increased. Therefore, esterase 48, lipase, lysozyme, and α-amylase may be potential biomarkers of midgut toxicity caused by phoxim exposure. These findings may expand the application of rare earths in sericulture. Copyright © 2013 Wiley Periodicals, Inc.

  12. China’s Sports Public Service System:the Pattern Choice and Mechanism Construction%中国公共体育服务体系:模式选择与机制建设

    Institute of Scientific and Technical Information of China (English)

    李燕领; 王家宏; 蒋玉红

    2015-01-01

    公共体育服务体系建设是“十二五”时期中国全面建成小康社会的重大战略举措。研究认为:兼顾效率与公平的包容型公共体育服务模式是市场经济体制下中国公共体育服务发展的现实选择,其实质性内核主要包括“公共财政为主,社会资金参与”的公共体育服务支出模式,“广覆盖、适度水平、兼顾公平与效率”的公共体育服务消费模式和“政府主导、多元协同”的公共体育服务供给模式。公共体育服务体系机制建设需要效率机制、公平机制、监督机制、评价机制与问责机制协调运作,以保证公共体育服务的效率和公平,确保公共体育服务提供的稳定性、有效性和持续性。%Public Sports service system construction is a major strategic initiative of building a moderately prosperous society during“The 12th five - year - plan”period. The research believes that the inclusive public sports serv-ice pattern with both efficiency and equity is a realistic choice under market economy,with the substantive core including the “public finance - based,social funds - participated?”spending patterns ,the“wide coverage,a moderate level,both fair and efficient”public sports service consumption patterns and the “government - led, multi - collaborative”public sports service supply pattern. The mechanism construction for sports public service system needs an efficient mechanism,a fair mechanism,a supervision mechanism,an evaluation mechanism and an accountability mechanism to cooperate,to ensure efficiency and equity of public sports services,to en-sure the stability of public sports services,effectiveness and sustainability.

  13. Controversies in laparoscopic repair of incisional hernia

    Directory of Open Access Journals (Sweden)

    Sarela Abeezar

    2006-01-01

    Full Text Available Background: Incisional hernias can be a significant problem after open abdominal surgery. Laparoscopic incisional hernia repair (LIHR is conceptually appealing: a large, abdominal wall re-incision with potential wound-related ill effects is avoided and an intra-peritoneal onlay mesh is expected to provide security that is equivalent to open, retro-muscular mesh repair. As such, LIHR has gained substantial popularity despite sparse, randomised clinical data to compare with conventional, open repair. Aim: To enumerate and discuss important, controversial issues in patient-selection, technique and early post-operative care for LIHR. Materials and Methods: Pragmatic summary of comprehensive review of English language literature, discussion with experts and personal experience. Outcomes: Six important areas of some dispute were identified: 1. Size of abdominal-wall defect that is suitable for LIHR: Generally, defect-diameter > 10 cm is better served by open retromuscular repair with tension-free re-approximation of the edges of the defect. 2. Extent of adhesiolysis: Complete division of adhesions to the anterior abdominal wall may identify sub-clinical "Swiss-cheese" defects but incurs some risk of additional complications. 3. Intra-operative recognition of enterotomy: Possible options are either laparoscopic suture of bowel injury and simultaneous completion of LIHR, or staged LIHR or conversion to open suture-repair. 4. Choice of mesh: "Composite" meshes are regarded as the current standard of care but there is paucity of data regarding potential dangers of intra-peritoneal polypropylene mesh. 5. Technique of mesh-fixation: Trans-parietal sutures are more secure than tacks, with limited data to correlate with post-operative pain. 6. Alarm over post-operative pain: Unlike other advanced laparoscopic operations, the specificity of pain as a marker of intra-abdominal sepsis after LIHR remains unclear. Conclusion : Recognition of and attention to

  14. A quantum delayed choice experiment

    CERN Document Server

    Peruzzo, Alberto; Brunner, Nicolas; Popescu, Sandu; O'Brien, Jeremy L

    2012-01-01

    Quantum systems exhibit particle-like or wave-like behaviour depending on the experimental apparatus they are confronted by. This wave-particle duality is at the heart of quantum mechanics, and is fully captured in Wheeler's famous delayed choice gedanken experiment. In this variant of the double slit experiment, the observer chooses to test either the particle or wave nature of a photon after it has passed through the slits. Here we report on a quantum delayed choice experiment, based on a quantum controlled beam-splitter, in which both particle and wave behaviours can be investigated simultaneously. The genuinely quantum nature of the photon's behaviour is tested via a Bell inequality, which here replaces the delayed choice of the observer. We observe strong Bell inequality violations, thus showing that no model in which the photon knows in advance what type of experiment it will be confronted by, hence behaving either as a particle or as wave, can account for the experimental data.

  15. The repair mechanisms and protection strategy of hyperoxia-induced lung injury in neonatal%新生儿高氧肺损伤的肺修复机制与保护策略

    Institute of Scientific and Technical Information of China (English)

    邹新艳

    2010-01-01

    Hyperoxia-induced lung injury in neonatal is a common complication after the clinical high oxygen therapy. There is not specific and effective prevention and treatment. Recent research suggests that many factor play an important role in the repair and protection of hyperoxia-induced lung injury in neonatal, such as growth factor, bone marrow mesenchymal stem cells,erythropoietin, anti-chemokine and anti-oxidation. The article reviews the molecular systems mechanisms in the pathologic process of hyperroxia-induced lung injury in neonatal.%新生儿高氧肺损伤是临床高氧治疗后较常见的并发症,目前尚无特异有效的防治方法.最近研究表明生长因子、骨髓间充质干细胞、促红细胞生成素、抗炎及抗氧化剂在新生儿高氧肺损伤的肺修复及保护中发挥了重要作用.该文综述以上分子系统在延缓和逆转新生儿高氧肺损伤病理过程中的作用机制.

  16. DNA repair and gene targeting in plant end-joining mutants

    NARCIS (Netherlands)

    Jia, Qi

    2011-01-01

    DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR) or by non-homologous end joining (NHEJ). The latter mechanism is the major route for DSB repair in the somatic cells of higher eukaryotes, including plants. If we could manipulate the balance of the DSB repair pathways

  17. DNA repair and gene targeting in plant end-joining mutants

    NARCIS (Netherlands)

    Jia, Qi

    2011-01-01

    DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR) or by non-homologous end joining (NHEJ). The latter mechanism is the major route for DSB repair in the somatic cells of higher eukaryotes, including plants. If we could manipulate the balance of the DSB repair pathways

  18. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Science.gov (United States)

    Zhang, Ye; Rohde, Larry H; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish K; Jeevarajan, Antony S; Pierson, Duane L; Wu, Honglu

    2008-11-01

    successful DSB repair requires both DSB repair mechanisms and non-DSB repair systems. These results reveal that many genes play previously unrecognized roles in multiple DNA repair responses, all of which are required for successful repair of IR-induced damage.

  19. Mode choice model parameters estimation

    OpenAIRE

    Strnad, Irena

    2010-01-01

    The present work focuses on parameter estimation of two mode choice models: multinomial logit and EVA 2 model, where four different modes and five different trip purposes are taken into account. Mode choice model discusses the behavioral aspect of mode choice making and enables its application to a traffic model. Mode choice model includes mode choice affecting trip factors by using each mode and their relative importance to choice made. When trip factor values are known, it...

  20. Valve radio and audio repair handbook

    CERN Document Server

    MILLER, CHAS

    2000-01-01

    This book is not only an essential read for every professional working with antique radio and gramophone equipment, but also dealers, collectors and valve technology enthusiasts the world over. The emphasis is firmly on the practicalities of repairing and restoring, so technical content is kept to a minimum, and always explained in a way that can be followed by readers with no background in electronics. Those who have a good grounding in electronics, but wish to learn more about the practical aspects, will benefit from the emphasis given to hands-on repair work, covering mechanical as

  1. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

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

  2. Histone displacement during nucleotide excision repair

    DEFF Research Database (Denmark)

    Dinant, C.; Bartek, J.; Bekker-Jensen, S.

    2012-01-01

    Nucleotide excision repair (NER) is an important DNA repair mechanism required for cellular resistance against UV light and toxic chemicals such as those found in tobacco smoke. In living cells, NER efficiently detects and removes DNA lesions within the large nuclear macromolecular complex called...... of histone variants and histone displacement (including nucleosome sliding). Here we review current knowledge, and speculate about current unknowns, regarding those chromatin remodeling activities that physically displace histones before, during and after NER. © 2012 by the authors; licensee MDPI, Basel...

  3. Mechanics, degradability, bioactivity, in vitro, and in vivo biocompatibility evaluation of poly(amino acid)/hydroxyapatite/calcium sulfate composite for potential load-bearing bone repair.

    Science.gov (United States)

    Fan, Xiaoxia; Ren, Haohao; Luo, Xiaoman; Wang, Peng; Lv, Guoyu; Yuan, Huipin; Li, Hong; Yan, Yonggang

    2016-03-01

    A ternary composite of poly(amino acid), hydroxyapatite, and calcium sulfate (PAA/HA/CS) was prepared using in situ melting polycondensation method and evaluated in terms of mechanical strengths, in vitro degradability, bioactivity, as well as in vitro and in vivo biocompatibility. The results showed that the ternary composite exhibited a compressive strength of 147 MPa, a bending strength of 121 MPa, a tensile strength of 122 MPa, and a tensile modulus of 4.6 GPa. After immersion in simulated body fluid, the compressive strength of the composite decreased from 147 to 98 MPa for six weeks and the bending strength decreased from 121 to 75 MPa for eight weeks, and both of them kept stable in the following soaking period. The composite could be slowly degraded with 7.27 wt% loss of initial weight after soaking in phosphate buffered solution for three weeks when started to keep stable weight in the following days. The composite was soaked in simulated body fluid solution and the hydroxyapatite layer, as flower-like granules, formed on the surface of the composite samples, showing good bioactivity. Moreover, it was found that the composite could promote proliferation of MG-63 cells, and the cells with normal phenotype extended and spread well on the composite surface. The implantation of the composite into the ulna of sheep confirmed that the composite was biocompatible and osteoconductive in vivo, and offered the PAA/HA/CS composite promising material for load-bearing bone substitutes for clinical application.

  4. Irrational choice and the value of information.

    Science.gov (United States)

    Vasconcelos, Marco; Monteiro, Tiago; Kacelnik, Alex

    2015-09-09

    Irrational decision making in humans and other species challenges the use of optimality in behavioural biology. Here we show that such observations are in fact powerful tools to understand the adaptive significance of behavioural mechanisms. We presented starlings choices between probabilistic alternatives, receiving or not information about forthcoming, delayed outcomes after their choices. Subjects could not use this information to alter the outcomes. Paradoxically, outcome information induced loss-causing preference for the lower probability option. The effect depended on time under uncertainty: information given just after each choice caused strong preference for lower probability, but information just before the outcome did not. A foraging analysis shows that these preferences would maximize gains if post-choice information were usable, as when predators abandon a chase when sure of the prey escaping. Our study illustrates how experimentally induced irrational behaviour supports rather than weakens the evolutionary optimality approach to animal behaviour.

  5. Strategy application, observability, and the choice combinator.

    Energy Technology Data Exchange (ETDEWEB)

    Winter, Victor Lono (University of Nebraska at Omaha)

    2004-03-01

    In many strategic systems, the choice combinator provides a powerful mechanism for controlling the application of rules and strategies to terms. The ability of the choice combinator to exercise control over rewriting is based on the premise that the success and failure of strategy application can be observed. In this paper we present a higher-order strategic framework with the ability to dynamically construct strategies containing the choice combinator. To this framework, a combinator called hide is introduced that prevents the successful application of a strategy from being observed by the choice combinator. We then explore the impact of this new combinator on a real-world problem involving a restricted implementation of the Java Virtual Machine.

  6. Sexual Orientation and Choice

    Directory of Open Access Journals (Sweden)

    Ayala Saray

    2017-07-01

    Full Text Available Is there a choice in sexual orientation? [Wilkerson, William S. (2009: “Is It a Choice? Sexual Orientation as Interpretation”. In: Journal of Social Philosophy 40. No. 1, p. 97–116] argues that sexual desires require interpretation in order to be fully constituted, and therefore sexual orientation is at least partially constituted by choice. [Díaz-León, Esa (2017: “Sexual Orientation as Interpretation? Sexual Desires, Concepts, and Choice”; In: Journal of Social Ontology] critically assesses Wilkerson’s argument, concluding that we still lack a good argument for the claim that choice plays a role in sexual orientation. Here I examine Díaz-León’s response to Wilkerson. I introduce what I call the conceptual act theory of sexual orientation, and argue that even if interpretation were not necessary to constitute sexual desires, it is a necessary element to constitute what we call sexual orientation. However, I conclude that even if we agree that interpretation is involved in sexual orientation, it does not follow that there is a choice involved.

  7. Predicting affective choice.

    Science.gov (United States)

    Suri, Gaurav; Sheppes, Gal; Gross, James J

    2013-08-01

    Affect is increasingly recognized as central to decision making. However, it is not clear whether affect can be used to predict choice. To address this issue, we conducted 4 studies designed to create and test a model that could predict choice from affect. In Study 1, we used an image rating task to develop a model that predicted approach-avoidance motivations. This model quantified the role of two basic dimensions of affect--valence and arousal--in determining choice. We then tested the predictive power of this model for two types of decisions involving images: preference based selections (Study 2) and risk-reward trade-offs (Study 3). In both cases, the model derived in Study 1 predicted choice and outperformed competing models drawn from well-established theoretical views. Finally, we showed that this model has ecological validity: It predicted choices between news articles on the basis of headlines (Study 4). These findings have implications for diverse fields, including neuroeconomics and judgment and decision making. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. Choice of initial therapy

    Directory of Open Access Journals (Sweden)

    Manuel Battegay

    2014-11-01

    Full Text Available Current international and national treatment guidelines such as EACS, BHIVA, DHHS or IAS update regularly recommendations on the choice of initial combination antiretroviral treatment (cART regimens. Preferred cART regimens include a backbone with two nucleoside (nucleotide reverse transcriptase inhibitors combined either with one non-nucleoside reverse transcriptase inhibitor or one ritonavir boosted protease inhibitor or more recently one integrase inhibitor. Response rates according to viral load measurements increased in recent years, in particular due to better tolerability. The choice of initial therapy is flexible and influenced by several factors such as height of viral load, genotypic resistance testing, CD4 cell count, co-morbidities, interactions, potential adverse events, (potential for pregnancy, convenience, adherence, costs as well as physician's and patient's preferences. Diverse highly potent initial cART regimens exist. Following the many possibilities, the choice of a regimen is based on a mixture of evidence-informed data and individualized concepts, some of the latter only partly supported by strong evidence. For example, different perceptions and personal experiences exist about boosted protease inhibitors compared to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors and vice versa which may influence the initial choice. This lecture will discuss choices of initial cART in view of international guidelines and the evidence for individualization of initial HIV therapy.

  9. The impact of choice context on consumers' choice heuristics

    DEFF Research Database (Denmark)

    Mueller Loose, Simone; Scholderer, Joachim; Corsi, Armando M.

    2012-01-01

    Context effects in choice settings have received recent attention but little is known about the impact of context on choice consistency and the extent to which consumers apply choice heuristics. The sequence of alternatives in a choice set is examined here as one specific context effect. We compa...

  10. Transactivation of repair genes by BRCA1.

    Science.gov (United States)

    El-Deiry, Wafik S

    2002-01-01

    Recent studies have identified a link between the BRCA1 tumor suppressor and transcriptional regulation of a group of genes involved in nucleotide excision repair. There is some controversy regarding the precise mechanism of upregulation of XPE DDB2 or XPC by BRCA1, with some evidence suggesting that p53 is involved in their regulation. Some evidence suggests BRCA1 may stabilize p53 and direct regulation of DNA repair genes, although how BRCA1 stabilizes p53 remains unclear and whether BRCA1 can upregulate DNA repair genes in a p53-independent manner remains a possibility. A transcriptional component to the action of BRCA1 and involvement of XP genes brings up new and interesting questions about breast cancer development and therapy.

  11. Detecting and Correcting Speech Repairs

    CERN Document Server

    Heeman, P A; Heeman, Peter; Allen, James

    1994-01-01

    Interactive spoken dialog provides many new challenges for spoken language systems. One of the most critical is the prevalence of speech repairs. This paper presents an algorithm that detects and corrects speech repairs based on finding the repair pattern. The repair pattern is built by finding word matches and word replacements, and identifying fragments and editing terms. Rather than using a set of prebuilt templates, we build the pattern on the fly. In a fair test, our method, when combined with a statistical model to filter possible repairs, was successful at detecting and correcting 80\\% of the repairs, without using prosodic information or a parser.

  12. In utero repair of spina bifida.

    Science.gov (United States)

    Moldenhauer, Julie S

    2014-08-01

    Open spina bifida or myelomeningocele (MMC) is the most common congenital malformation of the central nervous system compatible with long-term survival and is associated with significant lifelong disabilities. Postnatal care of MMC involves covering the exposed spinal cord, infection prevention, and ventricular shunting for hydrocephalus. The aim of postnatal MMC surgery is not to reverse or prevent the neurologic injury seen in MMC, but to palliate. The neurologic defects result from primary incomplete neurulation and secondary chronic in utero damage to the exposed neural elements through mechanical and chemical trauma-the two-hit hypothesis. With the ability to accurately diagnose spina bifida prenatally and the concept of the two-hit hypothesis, in utero repair to decrease exposure and alter the antenatal course of neurologic destruction was conceived. Through animal models and human pilot studies, the feasibility of fetal spina bifida repair was demonstrated. Subsequently, the prospective randomized multicenter Management of Myelomeningocele Study (MOMS trial) revealed a decreased need for shunting, reversal of hindbrain herniation, and preservation of neurologic function, making in utero repair an accepted care alternative for select women carrying a fetus with spina bifida. This article will highlight the background and rationale for in utero repair, and the progression to becoming an alternative standard of care. The future directions of fetal spina bifida repair will also be addressed.

  13. DNA repair responses in human skin cells

    Energy Technology Data Exchange (ETDEWEB)

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.

    1981-07-01

    Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xeroderma pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of crosslinks while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.

  14. Transcription-coupled repair: an update.

    Science.gov (United States)

    Spivak, Graciela

    2016-11-01

    Nucleotide excision repair (NER) is a versatile pathway that removes helix-distorting DNA lesions from the genomes of organisms across the evolutionary scale, from bacteria to humans. The serial steps in NER involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. Transcription-coupled repair (TCR) is a subpathway of NER dedicated to the repair of lesions that, by virtue of their location on the transcribed strands of active genes, encumber elongation by RNA polymerases. In this review, I report on recent findings that contribute to the elucidation of TCR mechanisms in the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae and human cells. I review general models for the biochemical pathways and how and when cells might choose to utilize TCR or other pathways for repair or bypass of transcription-blocking DNA alterations.

  15. Choosing health, constrained choices.

    Science.gov (United States)

    Chee Khoon Chan

    2009-12-01

    In parallel with the neo-liberal retrenchment of the welfarist state, an increasing emphasis on the responsibility of individuals in managing their own affairs and their well-being has been evident. In the health arena for instance, this was a major theme permeating the UK government's White Paper Choosing Health: Making Healthy Choices Easier (2004), which appealed to an ethos of autonomy and self-actualization through activity and consumption which merited esteem. As a counterpoint to this growing trend of informed responsibilization, constrained choices (constrained agency) provides a useful framework for a judicious balance and sense of proportion between an individual behavioural focus and a focus on societal, systemic, and structural determinants of health and well-being. Constrained choices is also a conceptual bridge between responsibilization and population health which could be further developed within an integrative biosocial perspective one might refer to as the social ecology of health and disease.

  16. Complex Strategic Choices

    DEFF Research Database (Denmark)

    Leleur, Steen

    . Complex Strategic Choices provides clear principles and methods which can guide and support strategic decision making to face the many current challenges. By considering ways in which planning practices can be renewed and exploring the possibilities for acquiring awareness and tools to add value...... and students in the field of planning and decision analysis as well as practitioners dealing with strategic analysis and decision making. More broadly, Complex Strategic Choices acts as guide for professionals and students involved in complex planning tasks across several fields such as business...... to strategic decision making, Complex Strategic Choices presents a methodology which is further illustrated by a number of case studies and example applications. Dr. Techn. Steen Leleur has adapted previously established research based on feedback and input from various conferences, journals and students...

  17. Effect of Various Surface Treatment on Repair Strength of Composite Resin

    Directory of Open Access Journals (Sweden)

    Y. Alizade

    2004-12-01

    Full Text Available Statement of Problem: In some clinical situations, repair of composite restorations is treatment of choice. Improving the bond strength between one new and old composite usually requires increased surface roughness to promote mechanical interlocking sincechemical bonding might not be adequate. Similarly, the treatment of a laboratory fabricated resin composite restoration involves the same procedures, and there is a need to create the strongest possible bond of a resin cement to a previously polymerized composite.Purpose: The aim of this study was to evaluate the effect of various surface treatments on the shear bond strength of repaired to aged composite resin.Materials and Methods: Eighty four cylindrical specimens of a composite resin were fabricated and stored in distilled water for 100 days prior to surface treatment. Surface treatment of old composite was done in 6 groups as follow:1- Air abrasion with CoJet sand particles with micoretcher + silane + dentin bonding agent2- Air abrasion with 50μm Al2O3 particles+ phosphoric acid+ silane+ dentin bonding agent3- Air abrasion with 50μm Al2O3 particles + phosphoric acid + dentin bonding agent4- Diamond bur + phosphoric acid + silane + dentin bonding agent5- Diamond bur + phosphoric acid + dentin bonding agent6- Diamond bur + phosphoric acid + composite activator + dentin bonding agentThen fresh composite resin was bonded to treated surfaces. Twelve specimens were also fabricated as control group with the same diameter but with the height twice as much as other specimens. All of the specimens were thermocycled prior to testing for shear bondstrength. The bond strength data were analyzed statistically using one way ANOVA test, t test and Duncan's grouping test.Results: One-way ANOVA indicated no significant difference between 7 groups (P=0.059. One-way ANOVA indicated significant difference between the three diamond bur groups (P=0.036. Silane had a significant effect on the repair bond

  18. Exchange rate regime choice

    Directory of Open Access Journals (Sweden)

    Beker Emilija

    2006-01-01

    Full Text Available The choice of an adequate exchange rate regime proves to be a highly sensitive field within which the economic authorities present and confirm themselves. The advantages and disadvantages of fixed and flexible exchange rate regimes, which have been quite relativized from the conventional point of view, together with simultaneous, but not synchronized effects of structural and external factors, remain permanently questioned throughout a complex process of exchange rate regime decision making. The paper reflects the attempt of critical identification of the key exchange rate performances with emphasis on continuous non-uniformity and (uncertainty of shelf life of a relevant choice.

  19. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

    National Research Council Canada - National Science Library

    Guerquin, Marie-Justine; Charvet, Benjamin; Nourissat, Geoffroy; Havis, Emmanuelle; Ronsin, Olivier; Bonnin, Marie-Ange; Ruggiu, Mathilde; Olivera-Martinez, Isabel; Robert, Nicolas; Lu, Yinhui; Kadler, Karl E; Baumberger, Tristan; Doursounian, Levon; Berenbaum, Francis; Duprez, Delphine

    2013-01-01

    Tendon formation and repair rely on specific combinations of transcription factors, growth factors, and mechanical parameters that regulate the production and spatial organization of type I collagen...

  20. Groin hernia repair in young males: mesh or sutured repair?

    DEFF Research Database (Denmark)

    Bisgaard, T; Bay-Nielsen, M; Kehlet, H

    2010-01-01

    Large-scale data for the optimal inguinal hernia repair in younger men with an indirect hernia is not available. We analysed nationwide data for risk of reoperation in younger men after a primary repair using a Lichtenstein operation or a conventional non-mesh hernia repair....

  1. Variation in male mate choice in Drosophila melanogaster.

    Science.gov (United States)

    Edward, Dominic A; Chapman, Tracey

    2013-01-01

    Male mate choice has been reported in the fruit fly, Drosophila melanogaster, even though males of this species were previously thought to maximise their fitness by mating with all available females. To understand the evolution of male mate choice it is important to understand variation in male mating preferences. Two studies, using different stock populations and different methods, have reported contrasting patterns of variation in male mate choice in D. melanogaster. Two possible explanations are that there are evolved differences in each stock population or that the methods used to measure choice could have biased the results. We investigated these hypotheses here by repeating the methods used in one study in which variable male mate choice was found, using the stock population from the other study in which choice was not variable. The results showed a significant resource-independent male preference for less fecund, smaller females, which contrasts with previous observations of male mate choice. This indicates that different selection pressures between populations have resulted in evolved differences in the expression of male mate choice. It also reveals phenotypic plasticity in male mate choice in response to cues encountered in each choice environment. The results highlight the importance of variation in male mate choice, and of identifying mechanisms in order to understand the evolution of mate choice under varying ecological conditions.

  2. Variation in male mate choice in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Dominic A Edward

    Full Text Available Male mate choice has been reported in the fruit fly, Drosophila melanogaster, even though males of this species were previously thought to maximise their fitness by mating with all available females. To understand the evolution of male mate choice it is important to understand variation in male mating preferences. Two studies, using different stock populations and different methods, have reported contrasting patterns of variation in male mate choice in D. melanogaster. Two possible explanations are that there are evolved differences in each stock population or that the methods used to measure choice could have biased the results. We investigated these hypotheses here by repeating the methods used in one study in which variable male mate choice was found, using the stock population from the other study in which choice was not variable. The results showed a significant resource-independent male preference for less fecund, smaller females, which contrasts with previous observations of male mate choice. This indicates that different selection pressures between populations have resulted in evolved differences in the expression of male mate choice. It also reveals phenotypic plasticity in male mate choice in response to cues encountered in each choice environment. The results highlight the importance of variation in male mate choice, and of identifying mechanisms in order to understand the evolution of mate choice under varying ecological conditions.

  3. Cleft lip and palate repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002979.htm Cleft lip and palate repair To use the sharing features on this page, please enable JavaScript. Cleft lip and cleft palate repair is surgery to fix birth defects ...

  4. Abdominal aortic aneurysm repair - open

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007392.htm Abdominal aortic aneurysm repair - open To use the sharing features on this page, please enable JavaScript. Open abdominal aortic aneurysm repair is surgery to fix a widened part ...

  5. 酒精性脑损伤的突触机制及其修复策略述评%Synaptic Mechanism and Repairing Strategies for Alcoholic Recognition Impairment (review)

    Institute of Scientific and Technical Information of China (English)

    徐德峰; 赵谋明; 马忠华; 苏国万; 张婷

    2015-01-01

    Alcoholic dementia is increasingly becoming both a severe medical issue and a social problem;the unknown overall mecha-nism is the bottleneck for effective intervention and treatment of alcoholic brain injury. As the primary structure for the release, transmission of neurotransmitter and information integration between neurons, synapse plays a significant role in performing the advanced function of brain, such as learning and memory. Based on the neurobiological principles of synaptic structure and function, the changes in process and efficiency of synaptic transmission and information integration stressed by alcoholic molecular were reviewed in comparison with the nor-mal process. The molecular mechanisms for alcoholic brain damage in learning and memory abilities were systematically discussed from the levels of synaptic morphology, material components, and signal transduction, respectively, and the repairing strategies for the damaged syn-aptic structure were proposed accordingly. Hopefully, this review could provide a deep insight into understanding the molecular mechanism of alcoholic brain damage, and draw ideas for the memory-enhancing peptides development.%酒精性痴呆日益成为严峻的医学和社会问题,整体机制不明是目前酒精性脑损伤干预和治疗的瓶颈。突触作为神经元之间递质释放与跨膜信息传递及整合的核心结构,对于学习记忆等脑的高级功能具有决定性作用。本文基于突触传递的神经生物学基础,围绕酒精分子胁迫下突触传递过程和效率的变化,分别从突触形态结构、物质基础、信号转导等层面,系统评述了酒精性脑损伤的突触机制及其修复策略,以期为酒精性脑损伤的深入研究和益智类保健食品开发提供思路借鉴。

  6. Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.

    Science.gov (United States)

    Czornak, Kamila; Chughtai, Sanaullah; Chrzanowska, Krystyna H

    2008-01-01

    Genomes are subject to a number of exogenous or endogenous DNA-damaging agents that cause DNA double-strand breaks (DSBs). These critical DNA lesions can result in cell death or a wide variety of genetic alterations, including deletions, translocations, loss of heterozygosity, chromosome loss, or chromosome fusions, which enhance genome instability and can trigger carcinogenesis. The cells have developed an efficient mechanism to cope with DNA damages by evolving the DNA repair machinery. There are 2 major DSB repair mechanisms: nonhomologous end joining (NHEJ) and homologous recombination (HR). One element of the repair machinery is the MRN complex, consisting of MRE11, RAD50 and NBN (previously described as NBS1), which is involved in DNA replication, DNA repair, and signaling to the cell cycle checkpoints. A number of kinases, like ATM (ataxia-telangiectasia mutated), ATR (ataxia-telangiectasia and Rad-3-related), and DNA PKcs (DNA protein kinase catalytic subunit), phosphorylate various protein targets in order to repair the damage. If the damage cannot be repaired, they direct the cell to apoptosis. The MRN complex as well as repair kinases are also involved in telomere maintenance and genome stability. The dysfunction of particular elements involved in the repair mechanisms leads to genome instability disorders, like ataxia telangiectasia (A-T), A-T-like disorder (ATLD) and Nijmegen breakage syndrome (NBS). The mutated genes responsible for these disorders code for proteins that play key roles in the process of DNA repair. Here we present a detailed review of current knowledge on the MRN complex, kinases engaged in DNA repair, and genome instability disorders.

  7. Regenerative endodontics: regeneration or repair?

    Science.gov (United States)

    Simon, Stéphane R J; Tomson, Phillip L; Berdal, Ariane

    2014-04-01

    Recent advances in biotechnology and translational research have made it possible to provide treatment modalities that protect the vital pulp, allow manipulation of reactionary and reparative dentinogenesis, and, more recently, permit revascularization of an infected root canal space. These approaches are referred to as regenerative procedures. The method currently used to determine the origin of the tissue secreted during the repair/regeneration process is largely based on the identification of cellular markers (usually proteins) left by cells that were responsible for this tissue production. The presence of these proteins in conjunction with other indicators of cellular behavior (especially biomineralization) and analysis of the structure of the newly generated tissue allow conclusions to be made of how it was formed. Thus far, it has not been possible to truly establish the biological mechanism controlling tertiary dentinogenesis. This article considers current therapeutic techniques to treat the dentin-pulp complex and contextualize them in terms of reparative and regenerative processes. Although it may be considered a semantic argument rather than a biological one, the definitions of regeneration and repair are explored to clarify our position in this era of regenerative endodontics. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  8. Choices, Not Circumstances.

    Science.gov (United States)

    National Education Association, Washington, DC. Div. of Instruction and Professional Development.

    Following a brief account of the circumstances of migrant workers and the status of migrant education in the United States, this pamphlet describes how the National Education Association (NEA) has impacted and will continue to impact the process of providing educational choices for migrant students. The NEA has consistently testified before…

  9. Households' portfolio choices

    NARCIS (Netherlands)

    Hochgürtel, S.

    1998-01-01

    This thesis presents four topics on households' portfolio choices. Empirically, households do not hold well-diversified wealth portfolios. In particular, they refrain from putting their savings into risky assets. We explore several ways that might help explaining this observation. Using Dutch

  10. Career choice, influence

    African Journals Online (AJOL)

    Information Impact | Journal of Information and Knowledge Management

    Keywords: Career choice, influence, students, academic performance. Introduction ... Sharma (2012) also included that grade, attendance, standard test and .... outgoing. A student's personality must be a self-motivated type”. ..... Mercy Arodovwe Igere is a lecturer at the Department of Library and Information. Science.

  11. Single-basined choice

    NARCIS (Netherlands)

    Bossert, W.; Peters, H.J.M.

    2013-01-01

    Single-basined preferences generalize single-dipped preferences by allowing for multiple worst elements. These preferences have played an important role in areas such as voting, strategy-proofness and matching problems. We examine the notion of single-basinedness in a choice-theoretic setting. In co

  12. Deterministic Walks with Choice

    Energy Technology Data Exchange (ETDEWEB)

    Beeler, Katy E.; Berenhaut, Kenneth S.; Cooper, Joshua N.; Hunter, Meagan N.; Barr, Peter S.

    2014-01-10

    This paper studies deterministic movement over toroidal grids, integrating local information, bounded memory and choice at individual nodes. The research is motivated by recent work on deterministic random walks, and applications in multi-agent systems. Several results regarding passing tokens through toroidal grids are discussed, as well as some open questions.

  13. A Matter of Choice

    Science.gov (United States)

    Vriend, John

    1973-01-01

    Since the goal of helping the client make wise decisions is at the core of counseling, it is suggested that existentialism as a state of mind may give the contemporary counselor an outlook most conducive to achieving that goal. The entire role of choice must be dealt with by the counselor in light of the reality of current events. (Author)

  14. Angelina′s choice

    Directory of Open Access Journals (Sweden)

    Nishu Singh Goel

    2013-01-01

    Full Text Available This is an opinion piece on how a celebrity′s personal choice to undergo prophylactic mastectomy on discovery of an aberrant gene, when publicly promoted, carries in itself the power to influence and impact healthcare trends and decisions. When celebrities advocate causes that are universally and uniformly acceptable and indisputable as the best in the realm of healthcare and cure (e.g. no smoking, it creates well-being and awareness in society at large. But those which are personal choices made out of a repertoire of other available and effective options may, because of celebrity preference, don the mantle of a norm. They thus run the danger of being blindly replicated by others without proper awareness and knowledge of the true potential of disease, risk factors, and other existing remedial or risk-reducing measures. Society should thus be encouraged to question, debate, and understand the validity, authenticity, and reason of the choices, especially those with a medical basis. This tempering of information with intelligence and rationale and making informed choices based on facts will serve humanity as a whole.

  15. The Choice for Learning

    Science.gov (United States)

    Bennett, Scott

    2006-01-01

    We are building conventional library space without making the paradigm shift our digital environment requires. The chief obstacles to change lie in our conception of readers as information consumers, in our allegiance to library operations as the drivers of library design, and in the choice made between foundational and non-foundational views of…

  16. Nanomaterials promise better bone repair

    OpenAIRE

    Qifei Wang; Jianhua Yan; Junlin Yang; Bingyun Li

    2016-01-01

    Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture rep...

  17. Laparoscopic repair of femoral hernia

    OpenAIRE

    Yang, Xue-Fei; Liu, Jia-Lin

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. Femoral hernia could be repaired through the laparoscopic procedures for inguinal hernia. These procedures have clear anatomic view in the operation and preoperatively undiagnosed femoral hernia could be confirmed and treated. Lower recurrence ratio was reported in laparoscopic procedures compared with open procedures for repair of femoral hernia. The technical details of laparoscopic repair of femoral hernia, ...

  18. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  19. 朱槿花苞提取物治疗皮肤疖痈溃疡及其机制研究%Research in skin healing and repair function and mechanism of Hibiscus rosa-sinensis Linn bud extract

    Institute of Scientific and Technical Information of China (English)

    姜霁洋; 徐涵; 白雪婷; 程訸; 林艳玲; 凌震; 陈一村; 石刚刚

    2015-01-01

    目的:研究朱槿花苞提取物对小鼠皮肤疖痈溃疡模型的治疗作用,并对其可能作用机制进行探讨。方法将昆明小鼠分为模型组、阳性药组和朱槿花苞正丁醇萃取物( HrBN)组,采用小鼠疖痈模型,观察给药后实验结果。将昆明小鼠分为模型组、阳性药组和HrBN低、中、高剂量组,采用小鼠全层切除模型,观察给药后实验结果。通过体外抗菌实验检测朱槿花苞提取物抗菌MIC和抑菌圈。通过碳粒廓清实验测定朱槿花苞提取物对小鼠巨噬细胞廓清作用的影响,计算 K 和α值。结果 HrBN 对疖痈溃疡修复效果明显,并呈现量效关系。 HrBN、朱槿花苞乙酸乙酯萃取物( HrBE)及AB-8树脂体积分数0.3乙醇段、0.6乙醇段的抗菌作用明显。 HrBN及朱槿花苞乙醇提物( HrBA)高剂量能够增加K和α值。结论 HrBN在动物实验中体现了良好的皮肤疖痈溃疡修复作用,其疗效与抗菌活性和免疫增强作用可能有关。%Aim To test the skin healing and repairing efficacy and the mechanism of Hibiscus rosa-sinensis L bud extract by using the animal models. Methods KM mice were randomly divided into three groups:the model group, the positive control group, and the n-bu-tyl alcohol extract ( HrBN) group. Using the boils and carbuncles model, the healing condition of all the animals were observed. KM mice were kept in the SPF condition room and divided into five groups: the model group, the positive control group, and the low, middle, high dose groups. Using the full-thickness loss model, the repairing results of all the mice were ob-served. Through the antimicrobial test, the results of MIC and inhibition zone were obtained. The carbon clearance test was used to collect the blood at the time 5min and 15min, and get the liver and spleen, and the results of K andαwere obtained. Results In vivo ex-periments showed there was significant difference be-tween groups;the Hr

  20. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne;

    2014-01-01

    , heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative...... expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. RESULTS: Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations....... CONCLUSIONS: Heterogenous mismatch repair status can be demonstrated in colorectal cancer. Though rare, attention to this phenomenon is recommended since it corresponds to differences in mismatch repair status that are relevant for correct classification. VIRTUAL SLIDES: The virtual slide(s) for this article...

  1. Social Networks and Choice Set Formation in Discrete Choice Models

    Directory of Open Access Journals (Sweden)

    Bruno Wichmann

    2016-10-01

    Full Text Available The discrete choice literature has evolved from the analysis of a choice of a single item from a fixed choice set to the incorporation of a vast array of more complex representations of preferences and choice set formation processes into choice models. Modern discrete choice models include rich specifications of heterogeneity, multi-stage processing for choice set determination, dynamics, and other elements. However, discrete choice models still largely represent socially isolated choice processes —individuals are not affected by the preferences of choices of other individuals. There is a developing literature on the impact of social networks on preferences or the utility function in a random utility model but little examination of such processes for choice set formation. There is also emerging evidence in the marketplace of the influence of friends on choice sets and choices. In this paper we develop discrete choice models that incorporate formal social network structures into the choice set formation process in a two-stage random utility framework. We assess models where peers may affect not only the alternatives that individuals consider or include in their choice sets, but also consumption choices. We explore the properties of our models and evaluate the extent of “errors” in assessment of preferences, economic welfare measures and market shares if network effects are present, but are not accounted for in the econometric model. Our results shed light on the importance of the evaluation of peer or network effects on inclusion/exclusion of alternatives in a random utility choice framework.

  2. Nonhomologous Mechanisms of Repair of Chromosomal Breaks

    Energy Technology Data Exchange (ETDEWEB)

    Haber, J. E.

    2001-12-19

    Discovered three new proteins involved in DNA damage assessment. Interestingly they are all proteins involved in recombination, but they have very different roles in that process and other proteins that might be expected to be equivalently involved are not. This is developing into a very significant area of research.

  3. Differential repair of UV damage in Saccharomyces cerevisiae is cell cycle dependent.

    Science.gov (United States)

    Terleth, C; Waters, R; Brouwer, J; van de Putte, P

    1990-09-01

    In the yeast Saccharomyces cerevisiae the transcriptionally active MAT alpha locus is repaired preferentially to the inactive HML alpha locus after UV irradiation. Here we analysed the repair of both loci after irradiating yeast cells at different stages of the mitotic cell cycle. In all stages repair of the active MAT alpha locus occurs at a rate of 30% removal of dimers per hour after a UV dose of 60 J/m2. The inactive HML alpha is repaired as efficiently as MAT alpha following irradiation in G2 whereas repair of HML alpha is less efficient in the other stages. Thus differential repair is observed in G1 and S but not in G2. Apparently, in G2 a chromatin structure exists in which repair does not discriminate between transcriptionally active and inactive DNA or, alternatively, an additional repair mechanism might exist which is only operational during G2.

  4. Potentials of Endogenous Neural Stem cells in Cortical Repair

    Directory of Open Access Journals (Sweden)

    Bhaskar eSaha

    2012-04-01

    Full Text Available In the last few decades great thrust has been put in the area of regenerative neurobiology research to combat brain injuries and neurodegenerative diseases. The recent discovery of neurogenic niches in the adult brain has led researchers to study how to mobilize these cells to orchestrate an endogenous repair mechanism. The brain can minimize injury-induced damage by means of an immediate glial response and by initiating repair mechanisms that involve the generation and mobilization of new neurons to the site of injury where they can integrate into the existing circuit. This review highlights the current status of research in this field. Here, we discuss the changes that take place in the neurogenic milieu following injury. We will focus, in particular, on the cellular and molecular controls that lead to increased proliferation in the Sub ventricular Zone (SVZ as well as neurogenesis. We will also concentrate on how these cellular and molecular mechanisms influence the migration of new cells to the affected area and their differentiation into neuronal/glial lineage that initiate the repair mechanism. Next, we will discuss some of the different factors that limit/retard the repair process and highlight future lines of research that can help to overcome these limitations. A clear understanding of the underlying molecular mechanisms and physiological changes following brain damage and the subsequent endogenous repair should help us develop better strategies to repair damaged brains.

  5. Does Challenge by Choice Increase Participation?

    Science.gov (United States)

    Chase, Daniel L.

    2015-01-01

    Challenge by choice (CBC) has been regarded as a foundational principle for challenge ropes course programs. Although CBC is widely accepted as the primary mechanism for facilitating intended ropes course outcomes, especially a participant's involvement, until recently it had remained an untested assumption. This study explored the role of CBC as…

  6. When incentives backfire: Spillover effects in food choice

    OpenAIRE

    Angelucci, Manuela; Prina, Silvia; Royer, Heather; Samek, Anya

    2016-01-01

    Little is known about how peers influence the impact of incentives. We investigate two mechanisms by which these effects can occur: through peers' actions and peers' incentives. In a field experiment on snack choice in the school lunchroom (choice of grapes versus cookies), we randomize who receives incentives, the fraction of peers incentivized, and whether or not it can be observed that peers' choices are incentivized. We show that, while peers' actions - picking grapes - have a positive sp...

  7. Choice of getting elements for different mining and geology conditions; Dobor organow urabiajacych dla roznych warunkow gorniczo-geologicznych

    Energy Technology Data Exchange (ETDEWEB)

    Krauze, K. [Akademia Gorniczo-Hutnicza, Cracow (Poland); Skrzypiec, A. [Zabrzanskie Zaklady Naprawcze Przemyslu Weglowego S.A. (Poland)

    1995-12-01

    One of the basic conditions of proper operation of longwall cutter-loader is a right choice of getting elements which meet the user`s requirements. The presented choice and design procedure of milling worm elements, using computer technique, allows to reduce time of choice decision as well as design time of the elements for the required mining and geology conditions. This method and computer programs were implemented in the Zabrze Coal Industry Repair Workshops at Zabrze. (author). 6 refs., 9 figs.

  8. DNA repair: Dynamic defenders against cancer and aging

    Energy Technology Data Exchange (ETDEWEB)

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet

  9. Prediction of economic choice by primate amygdala neurons.

    Science.gov (United States)

    Grabenhorst, Fabian; Hernádi, István; Schultz, Wolfram

    2012-11-13

    The amygdala is a key structure of the brain's reward system. Existing theories view its role in decision-making as restricted to an early valuation stage that provides input to decision mechanisms in downstream brain structures. However, the extent to which the amygdala itself codes information about economic choices is unclear. Here, we report that individual neurons in the primate amygdala predict behavioral choices in an economic decision task. We recorded the activity of amygdala neurons while monkeys chose between saving liquid reward with interest and spending the accumulated reward. In addition to known value-related responses, we found that activity in a group of amygdala neurons predicted the monkeys' upcoming save-spend choices with an average accuracy of 78%. This choice-predictive activity occurred early in trials, even before information about specific actions associated with save-spend choices was available. For a substantial number of neurons, choice-differential activity was specific for free, internally generated economic choices and not observed in a control task involving forced imperative choices. A subgroup of choice-predictive neurons did not show relationships to value, movement direction, or visual stimulus features. Choice-predictive activity in some amygdala neurons was preceded by transient periods of value coding, suggesting value-to-choice transitions and resembling decision processes in other brain systems. These findings suggest that the amygdala might play an active role in economic decisions. Current views of amygdala function should be extended to incorporate a role in decision-making beyond valuation.

  10. Fuzzy social choice theory

    CERN Document Server

    B Gibilisco, Michael; E Albert, Karen; N Mordeson, John; J Wierman, Mark; D Clark, Terry

    2014-01-01

    This book offers a comprehensive analysis of the social choice literature and shows, by applying fuzzy sets, how the use of fuzzy preferences, rather than that of strict ones, may affect the social choice theorems. To do this, the book explores the presupposition of rationality within the fuzzy framework and shows that the two conditions for rationality, completeness and transitivity, do exist with fuzzy preferences. Specifically, this book examines: the conditions under which a maximal set exists; the Arrow’s theorem;  the Gibbard-Satterthwaite theorem; and the median voter theorem.  After showing that a non-empty maximal set does exists for fuzzy preference relations, this book goes on to demonstrating the existence of a fuzzy aggregation rule satisfying all five Arrowian conditions, including non-dictatorship. While the Gibbard-Satterthwaite theorem only considers individual fuzzy preferences, this work shows that both individuals and groups can choose alternatives to various degrees, resulting in a so...

  11. Endovascular aneurysm repair: state-of-art imaging techniques for preoperative planning and surveillance

    DEFF Research Database (Denmark)

    Truijers, M; Resch, T; Van Den Berg, J C

    2009-01-01

    Endovascular aneurysm repair (EVAR) represents one of the greatest advances in vascular surgery over the past 50 years. In contrast to conventional aneurysm repair, EVAR requires accurate preoperative imaging and stringent postoperative surveillance. Duplex ultrasound (DUS), transesophageal...... echocardiography, intravascular ultrasound, computed tomography (CT) and magnetic resonance (MR), each provide useful information for patient selection, choice of endograft type and surveillance. Today most interventionists and surgeons will rely on CT or MR to assess aortic morphology, evaluate access artery...

  12. Nanomaterials promise better bone repair

    Directory of Open Access Journals (Sweden)

    Qifei Wang

    2016-10-01

    Full Text Available Nanomaterials mimicking the nano-features of bones and offering unique smart functions are promising for better bone fracture repair. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone fracture repair. This review begins with a brief introduction of bone fracture repair processes, then discusses the importance of vascularization, the role of growth factors in bone fracture repair, and the failure of bone fracture repair. Next, the review discusses the applications of nanomaterials for bone fracture repair, with a focus on the recent breakthroughs such as nanomaterials leading to precise immobilization of growth factors at the molecular level, promoting vascularization without the use of growth factors, and re-loading therapeutic agents after implantation. The review concludes with perspectives on challenges and future directions for developing nanomaterials for improved bone fracture repair.

  13. Mate choice on leks.

    Science.gov (United States)

    Balmford, A

    1991-03-01

    In lek-breeding animals, males defend tiny territories clustered into arenas, where females come to mate. Typically, most lek males secure relatively few copulations while a small number are highly successful. Recent studies suggest that the skewed distribution of matings seen at leks may be the result of females using a variety of criteria to select particular mating partners. Nevertheless, the possible benefits to females of mate choice at leks, where males offer neither resources nor paternal care, remain obscure.

  14. How Happiness Affects Choice

    OpenAIRE

    Cassie Mogilner; Jennifer Aaker; Sepandar D. Kamvar

    2012-01-01

    Consumers want to be happy, and marketers are increasingly trying to appeal to consumers' pursuit of happiness. However, the results of six studies reveal that what happiness means varies, and consumers' choices reflect those differences. In some cases, happiness is defined as feeling excited, and in other cases, happiness is defined as feeling calm. The type of happiness pursued is determined by one's temporal focus, such that individuals tend to choose more exciting options when focused on ...

  15. Food choices during Ramadan

    Directory of Open Access Journals (Sweden)

    Thamina Rashid

    2017-03-01

    Full Text Available Few studies have assessed the dietary Practices of people with diabetes during Ramadan (1. A sub study of Ramadan prospective diabetes study (2 which was conducted at the outpatient department of Baqai Institute of Diabetology and endocrinology, Karachi Pakistan in 2009 analyzed the food choices of patients with diabetes during Ramadan. Several irregularities regarding dietary intake and food choices were noted among the study participants. Although, the patients were counseled regarding diet before Ramadan, many did not follow the dietary advice. All patients had taken food at Iftar but majority of them preferred fried items like samosas, pakoras (fried snack, chicken rolls etc. these deeply fried items can lead to post Iftar hyperglycemia. Patients were also opted for fruit chat, dahibara and chanachaat at Iftar, higher load of these items can also worsen glycemic control. The striking finding was almost absence of meat (protein intake at Iftar but study from India showed increment of all three macronutrients during Ramadan (3. This may result in higher intake of items from carbohydrate and fat groups resulting in hyperglycemia after iftar. Intake of vegetables at Iftar was also negligible and hence the diet was not well balanced. The food choices at sahoor included roti, paratha (fried bread, slices, khajla, pheni, meat, egg and milk. Though it is advisable to take complex carbohydrates, protein and fat at sahoor as these are slowly digestible and can prevent hypoglycemia during fasting but khajla pheni are extremely rich in fat and carbohydrate content and should be avoided (4. However, paratha in 2 teaspoon of oil can be taken at sahoor.Patients with diabetes who fast during the month of Ramadan should have pre Ramadan dietary guidance and counseling session in order to modify their food preferences and choices during the holy month of Ramadan (4.

  16. Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats.

    Science.gov (United States)

    Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M

    2015-10-01

    Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Controlled laboratory study. Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro-computed tomography. All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered

  17. Topological social choice

    CERN Document Server

    1997-01-01

    The origins of this volume can be traced back to a conference on "Ethics, Economic and Business" organized by Columbia Busi­ ness School in March of 1993, and held in the splendid facilities of Columbia's Casa Italiana. Preliminary versions of several of the papers were presented at that meeting. In July 1994 the Fields Institute of Mathematical Sciences sponsored a workshop on "Geometry, Topology and Markets": additional papers and more refined versions of the original papers were presented there. They were published in their present versions in Social Choice and Wel­ fare, volume 14, number 2, 1997. The common aim of these workshops and this volume is to crystallize research in an area which has emerged rapidly in the last fifteen years, the area of topological approaches to social choice and the theory of games. The area is attracting increasing interest from social choice theorists, game theorists, mathematical econ­ omists and mathematicians, yet there is no authoritative collection of papers in the a...

  18. The choice that disappeared

    DEFF Research Database (Denmark)

    Gjerris, Mickey; Saxe, Henrik

    2013-01-01

    This article criticise the notion that ethical consumerism can solve the ethical issues related to sustainability and food production through an analysis of the complexity of the concept of sustainability as related to food choices. The current trend of leaving the political discussion and regula......This article criticise the notion that ethical consumerism can solve the ethical issues related to sustainability and food production through an analysis of the complexity of the concept of sustainability as related to food choices. The current trend of leaving the political discussion...... and regulation of the food area to the political consumer is shown to be problematic as shopping for sustainability might be much harder than initially believed due to the conflicting considerations entailed in the concept. Thus political consumerism may give way to fatalism as the complexity of choices become...... apparent and acts of citizenship increasingly are reduced to ethical consumerism supposed to be performed while shopping. The suggested solution is to let food policies be decided to a much higher degree through the political process engaging humans as citizens rather than consumers in the process....

  19. Crack Repair in Aerospace Aluminum Alloy Panels by Cold Spray

    Science.gov (United States)

    Cavaliere, P.; Silvello, A.

    2017-02-01

    The cold-spray process has recently been recognized as a very useful tool for repairing metallic sheets, achieving desired adhesion strengths when employing optimal combinations of material process parameters. We present herein the possibility of repairing cracks in aluminum sheets by cold spray. A 2099 aluminum alloy panel with a surface 30° V notch was repaired by cold spraying of 2198 and 7075 aluminum alloy powders. The crack behavior of V-notched sheets subjected to bending loading was studied by finite-element modeling (FEM) and mechanical experiments. The simulations and mechanical results showed good agreement, revealing a remarkable K factor reduction, and a consequent reduction in crack nucleation and growth velocity. The results enable prediction of the failure initiation locus in the case of repaired panels subjected to bending loading and deformation. The stress concentration was quantified to show how the residual stress field and failure are affected by the mechanical properties of the sprayed materials and by the geometrical and mechanical properties of the interface. It was demonstrated that the crack resistance increases more than sevenfold in the case of repair using AA2198 and that cold-spray repair can contribute to increased global fatigue life of cracked structures.

  20. Half-bead weld repairs for in-service applications

    Energy Technology Data Exchange (ETDEWEB)

    Holz, P.P. Sr.

    1978-01-01

    Successful half- or temper-bead technique weld repairs performed to Section XI of the American Society of Mechanical Engineers Boiler and Pressure Vessel Code guidelines were made to two Heavy-Section Steel Technology Program vessels and a qualification prolongation. Intermediate sized vessels, equivalent in thickness to nuclear pressure vessels, were repair welded and subsequently flawed and pressure tested to approximately 2/sup 1///sub 4/ times design pressure before leakage occurred. Discussed are the standards and procedures used with half-bead repairs, resultant induced metallurgical and stress effects, flaw test criterion, pressure test details and results, and recommendations for further development work for a speedier application process.

  1. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Lemontt, J F

    1979-01-01

    Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis.

  2. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Energy Technology Data Exchange (ETDEWEB)

    Lemontt, J F

    1979-01-01

    Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis.

  3. Electronic Pathways in Photoactivated Repair of UV Mutated DNA

    Science.gov (United States)

    Bohr, Henrik; Jalkanen, K. J.; Bary Malik, F.

    An investigation of the physics, underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism, is presented in this study. Electronic pathways, starting from the initial damage to the final repair process, are presented. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of a dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light, interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Density functional theoretical calculations supporting the theory are presented. The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process. Recent experimental data are compatible with this theory.

  4. Composite mesh and gluteal fasciocutaneous rotation flap for perineal hernia repair after abdominoperineal resection: a novel technique.

    Science.gov (United States)

    Papadakis, Marios; Hübner, Gunnar; Bednarek, Marzena; Arafkas, Mohamed

    2017-03-01

    Perineal hernia is an uncommon complication following abdominoperineal rectum resection. Several surgical procedures have been proposed for perineal hernia repair, including perineal, laparoscopic and abdominal approaches. Repair techniques can be classified into primary suture techniques, mesh placements and repairs with autogenous tissue. We report a 68-year-old man with a perineal hernia, who underwent a pelvic floor reconstruction with a transperineal composite mesh and a gluteal fasciocutaneous rotation flap. We conclude that a combined approach with transperineal mesh reconstruction and gluteal fasciocutaneous flap could be an alternative choice in perineal hernia repair after abdominoperineal resection.

  5. Occupational Choice and Student Values

    Science.gov (United States)

    McSweeney, R. V.

    1973-01-01

    Article attempts to set out a way of measuring determination, the element capable of making students' occupational choice' a reality not just an ideal, by exploration of the part played by the value system in relation to occupational choice. (Author)

  6. Promotion of Dental Pulp Cell Migration and Pulp Repair by a Bioceramic Putty Involving FGFR-mediated Signaling Pathways.

    Science.gov (United States)

    Zhang, J; Zhu, L X; Cheng, X; Lin, Y; Yan, P; Peng, B

    2015-06-01

    Mineral trioxide aggregate is the currently recommended material of choice for clinical pulp repair despite several disadvantages, including handling inconvenience. Little is known about the signaling mechanisms involved in bioceramic-mediated dental pulp repair-particularly, dental pulp cell (DPC) migration. This study evaluated the effects of iRoot BP Plus, a novel ready-to-use nanoparticulate bioceramic putty, on DPC migration in vitro and pulp repair in vivo, focusing on possible involvement of fibroblast growth factor receptor (FGFR)-related signaling, including mitogen-activated protein kinase and Akt pathways. Treatment with iRoot BP Plus extracts enhanced horizontal and vertical migration of DPCs, which was comparable with the effects induced by mineral trioxide aggregate extracts. The DPCs exposed to iRoot BP Plus extracts demonstrated no evident apoptosis. Importantly, treatment with iRoot BP Plus extracts resulted in rapid activation of FGFR, p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), and Akt signaling in DPCs. Confocal immunofluorescence staining revealed that iRoot BP Plus stimulated focal adhesion formation and stress fiber assembly in DPCs, in addition to upregulating the expression of focal adhesion molecules, including p-focal adhesion kinase, p-paxillin, and vinculin. Moreover, activation of FGFR, ERK, JNK, and Akt were found to mediate the upregulated expression of focal adhesion molecules, stress fiber assembly, and enhanced DPC migration induced by iRoot BP Plus. Consistent with the in vitro results, we observed induction of homogeneous dentin bridge formation and expression of p-focal adhesion kinase, p-FGFR, p-ERK 1/2, p-JNK, and p-Akt near injury sites by iRoot BP Plus in an in vivo pulp repair model. These data demonstrate that iRoot BP Plus can promote DPC migration and pulp repair involving the FGFR-mediated ERK 1/2, JNK, and Akt pathways. These findings provide

  7. Channel Choice: A Literature Review

    DEFF Research Database (Denmark)

    Østergaard Madsen, Christian; Kræmmergaard, Pernille

    2015-01-01

    The channel choice branch of e-government studies citizens’ and businesses’ choice of channels for interacting with government, and how government organizations can integrate channels and migrate users towards the most cost-efficient channels. In spite of the valuable contributions offered no sys...... no systematic overview exist of channel choice. We present a literature review of channel choice studies in government to citizen context identifying authors, countries, methods, concepts, units of analysis, and theories, and offer suggestionsfor future studies....

  8. Serotonergic genotypes, neuroticism, and financial choices.

    Directory of Open Access Journals (Sweden)

    Camelia M Kuhnen

    Full Text Available Life financial outcomes carry a significant heritable component, but the mechanisms by which genes influence financial choices remain unclear. Focusing on a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR, we found that individuals possessing the short allele of this gene invested less in equities, were less engaged in actively making investment decisions, and had fewer credit lines. Short allele carriers also showed higher levels of the personality trait neuroticism, despite not differing from others with respect to cognitive skills, education, or wealth. Mediation analysis suggested that the presence of the 5-HTTLPR short allele decreased real life measures of financial risk taking through its influence on neuroticism. These findings show that 5-HTTLPR short allele carriers avoid risky and complex financial choices due to negative emotional reactions, and have implications for understanding and managing individual differences in financial choice.

  9. Use Of Phospho Magnesium Compounds as Concrete Repair

    OpenAIRE

    2008-01-01

    International audience; Phospho magnesium compounds are tested to repair different typologies of concrete elements prepared with different surface roughness. Mechanical tests (flexion tests) show that rupture is logically conditioned by the type of preparation. SEM observations are realised along the rupture plan. The phosphate binder crystallized phases at the interface are very dense. When repaired surface is rough , the adhesion between the two phases (phosphate binder and Portland cement ...

  10. PCNA Modifications for Regulation of Post-Replication Repair Pathways

    OpenAIRE

    2008-01-01

    Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is ...

  11. Laser cladding crack repair of austenitic stainless steel

    CSIR Research Space (South Africa)

    Van Rooyen, C

    2009-06-01

    Full Text Available . Simulated crack repair and overlay cladding with 316L is shown in Fig. 6. Three small leaking pores were observed in the first layer, indicated by arrows. Hammer peening was applied to the first layer to mechanically seal the leaking pores prior... scenario for a three axis gantry manipulation system that could typically be used to repair pipes or water storage vessels. Powder efficiency should ideally be as high as possible and effective deposition rate should be maximised. Increased cladding...

  12. STUDY OF THE PARAMETERS OF EFFICIENCY IN CENTRES FOR REPAIR OF AGRICULTURAL MACHINERY

    Directory of Open Access Journals (Sweden)

    Natalia Stoyanova

    2015-06-01

    Full Text Available The paper makes a thorough study of the parameters of efficiency in the centers for the repair of agricultural machinery, considering production and technological structure, the basic principles for design of the process of service, the quantitative indicators for servicing. It presents a theoretical model for the management of services in the service business, taking into account the basic system requirements for maintenance of agricultural machinery, the main elements of the standards of customer service, choice of forms for maintenance of agricultural machinery. Opportunities are proposed for the optimization of repair activities in the centers for repair of agricultural machinery.

  13. Search, Memory, and Choice Error: An Experiment.

    Directory of Open Access Journals (Sweden)

    Adam Sanjurjo

    Full Text Available Multiple attribute search is a central feature of economic life: we consider much more than price when purchasing a home, and more than wage when choosing a job. An experiment is conducted in order to explore the effects of cognitive limitations on choice in these rich settings, in accordance with the predictions of a new model of search memory load. In each task, subjects are made to search the same information in one of two orders, which differ in predicted memory load. Despite standard models of choice treating such variations in order of acquisition as irrelevant, lower predicted memory load search orders are found to lead to substantially fewer choice errors. An implication of the result for search behavior, more generally, is that in order to reduce memory load (thus choice error a limited memory searcher ought to deviate from the search path of an unlimited memory searcher in predictable ways-a mechanism that can explain the systematic deviations from optimal sequential search that have recently been discovered in peoples' behavior. Further, as cognitive load is induced endogenously (within the task, and found to affect choice behavior, this result contributes to the cognitive load literature (in which load is induced exogenously, as well as the cognitive ability literature (in which cognitive ability is measured in a separate task. In addition, while the information overload literature has focused on the detrimental effects of the quantity of information on choice, this result suggests that, holding quantity constant, the order that information is observed in is an essential determinant of choice failure.

  14. Evoked Emotions Predict Food Choice

    NARCIS (Netherlands)

    Dalenberg, Jelle R.; Gutjar, Swetlana; ter Horst, Gert J.; de Graaf, Kees; Renken, Remco J.; Jager, Gerry

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments.

  15. Ethics and Challenge by Choice.

    Science.gov (United States)

    Nussbaum, Gary

    1996-01-01

    An experiential practitioner discusses the foundations of his ethical perspective on challenge by choice--participant choice within adventure activities. These foundations include existential and experiential philosophy, leisure theory, and the adventure-based counseling model. The ethics of choice and informed consent is discussed in relation to…

  16. Evoked Emotions Predict Food Choice

    NARCIS (Netherlands)

    Dalenberg, J.R.; Gutjar, S.; Horst, ter G.J.; Graaf, de C.; Renken, R.; Jager, G.

    2014-01-01

    In the current study we show that non-verbal food-evoked emotion scores significantly improve food choice prediction over merely liking scores. Previous research has shown that liking measures correlate with choice. However, liking is no strong predictor for food choice in real life environments. Th

  17. Damage tolerance of bonded composite aircraft repairs for metallic structures

    Science.gov (United States)

    Clark, Randal John

    This thesis describes the development and validation of methods for damage tolerance substantiation of bonded composite repairs applied to cracked plates. This technology is used to repair metal aircraft structures, offering improvements in fatigue life, cost, manufacturability, and inspectability when compared to riveted repairs. The work focuses on the effects of plate thickness and bending on repair life, and covers fundamental aspects of fracture and fatigue of cracked plates and bonded joints. This project falls under the UBC Bonded Composite Repair Program, which has the goal of certification and widespread use of bonded repairs in civilian air transportation. This thesis analyses the plate thickness and transverse stress effects on fracture of repaired plates and the related problem of induced geometrically nonlinear bending in unbalanced (single-sided) repairs. The author begins by developing a classification scheme for assigning repair damage tolerance substantiation requirements based upon stress-based adhesive fracture/fatigue criteria and the residual strength of the original structure. The governing equations for bending of cracked plates are then reformulated and line-spring models are developed for linear and nonlinear coupled bending and extension of reinforced cracks. The line-spring models were used to correct the Wang and Rose energy method for the determination of the long-crack limit stress intensity, and to develop a new interpolation model for repaired cracks of arbitrary length. The analysis was validated using finite element models and data from mechanical tests performed on hybrid bonded joints and repair specimens that are representative of an in-service repair. This work will allow designers to evaluate the damage tolerance of the repaired plate, the adhesive, and the composite patch, which is an airworthiness requirement under FAR (Federal Aviation Regulations) 25.571. The thesis concludes by assessing the remaining barriers to

  18. Current developments in hernia repair; meshes, adhesives, and tacking.

    Science.gov (United States)

    Powell, Benjamin S; Voeller, Guy R

    2010-10-01

    Open and laparoscopic hernia surgery continues to evolve with new products allowing surgeons multiple choices in treating their patients. The evolution towards tension-free techniques in dealing with hernias requires that today's surgeons know the options available in meshes as well as fixation methods in order to have the best outcomes. In recent years, there has been a rapid expansion in the number of meshes available. Currently, there are numerous uncoated, coated, and biologic meshes in production that can be used in hernia repair. This paper will focus on the latest developments in coated meshes that allow for intra-abdominal placement as well as the different types of biologic meshes and their typical uses. Tacking devices for laparoscopic hernia repair now come in titanium as well as absorbable devices. AbsorbaTack™ (Covidien, Norwalk, CT) and Sorbafix™ (Davol, Warwick, RI) are two of the newest absorbable tacking devices thought to possibly benefit patients with decreased pain and long-term complications as compared with their titanium counterparts. Adhesives continue to be used more and more for hernia repair, especially in inguinal and paraesophageal hernia repairs. Tissucol™/Tisseel™ (Baxter, Deerfield, IL) and Evicel™ (Ethicon, Somerville, NJ) are two types of fibrin glues that are available for use in hernia repair. Practitioners using these biologic adhesives think there is less pain compared with tacking.

  19. Endovascular repair of para-anastomotic aortoiliac aneurysms.

    LENUS (Irish Health Repository)

    Tsang, Julian S

    2009-11-01

    The purpose of this study is to evaluate the use of endovascular stent grafts in the treatment of para-anastomotic aneurysms (PAAs) as an alternative to high-risk open surgical repair. We identified all patients with previous open aortic aneurysm repair who underwent infrarenal endovascular aneurysm repair (EVAR) at our institution from June 1998 to April 2007. Patient demographics, previous surgery, and operative complications were recorded. One hundred forty-eight patients underwent EVAR during the study period and 11 patients had previous aortic surgery. Of these 11 redo patients, the mean age was 62 years at initial surgery and 71 years at EVAR. All patients were male. Initial open repair was for rupture in five (45%) patients. The average time between initial and subsequent reintervention was 9 years. All patients were ASA Grade III or IV. Fifty-five percent of the PAAs involved the iliac arteries, 36% the abdominal aorta, and 9% were aortoiliac. Ten patients had endovascular stent-grafts inserted electively, and one patient presented with a contained leak. Aorto-uni-iliac stent-grafts were deployed in seven patients, and bifurcated stent-grafts in four patients. A 100% successful deployment rate was achieved. Perioperative mortality was not seen and one patient needed surgical reintervention to correct an endoleak. Endovascular repair of PAAs is safe and feasible. It is a suitable alternative and has probably now become the treatment of choice in the management of PAAs.

  20. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...