Sample records for repair mechanisms radiosensibilidad

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

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


    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.

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

    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…



    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.

  4. DNA repair mechanisms in C. elegans

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


    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

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

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


    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

  6. Radiosensibilidad de semillas de soya a los rayos gamma 60Co

    C. de la Fé


    Full Text Available El presente estudio se desarrolló en las instalaciones del Instituto Nacional de Ciencias Agrícolas, con el objetivo de evaluar la radiosensibilidad de semillas de soya a los rayos gamma 60Co. Para su ejecución, se seleccionaron e irradiaron muestras de 50 semillas de la variedad Cubasoy-23, las que fueron sembradas en condiciones semicontroladas (macetas en la campaña de primavera, 1997. Las dosis de radiación fueron desde los 50 hasta los 480 Gy, con incrementos de 50 Gy entre las dosis de 50 y 200 Gy e incrementos de 40 Gy entre esta última y la dosis de 480 Gy. Las evaluaciones realizadas consistieron en porcentaje de semillas germinadas a los tres, seis y nueve días de la siembra, altura de las plantas a los 10, 20 y 50 días y número de pares de hojas emitidas a los 10 y 20 días de la siembra. El estudio realizado evidenció la ocurrencia de un efecto fuerte de las dosis aplicadas en el porcentaje de semillas germinadas, resultando las dosis próximas a los 280 Gy las de mayor efecto radioestimulador de la germinación. Desde el punto de vista de la altura de las plantas, el efecto de las dosis aplicadas se correspondió con el descrito para otros materiales biológicos irradiados, caracterizándose este por un aumento a dosis bajas seguido por una reducción cada vez mayor a medida que las dosis aplicadas se incrementaron. Por su parte, la emisión de hojas por las plantas mantuvo un comportamiento en correspondencia con la altura de las plantas. Los resultados del estudio permiten sugerir la aplicación de dosis próximas a los 360 Gy en los trabajos dirigidos a la creación de variabilidad genética en programas de mejora por inducción de mutaciones


    Hitesh Patadia


    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.

  8. Molecular mechanisms of DNA repair inhibition by caffeine

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


    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.

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

    Bonanno, Laura; Favaretto, Adolfo; Rosell, Rafael


    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.

  10. Mechanisms and functions of DNA mismatch repair

    Guo MinLi


    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.

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

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


    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.

  12. Self-repair networks a mechanism design

    Ishida, Yoshiteru


    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...

  13. An end-joining repair mechanism in Escherichia coli

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


    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

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

    De Felice F


    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

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

    Sarah C Shuck; Emily A Short; John J Turchi


    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.

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

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


    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.

  17. Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model

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


    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...

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

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


    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.

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

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


    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

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

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


    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.

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

    Stadelmann, Christine; Brück, Wolfgang


    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.

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

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


    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....

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

    Ru Wang


    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.

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

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


    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.

  5. Effects of scuba diving on vascular repair mechanisms.

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


    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

    Erhong Meng


    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

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


    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. Thermo-Mechanical Compatibility of Viscoelastic Mortars for Stone Repair

    Thibault Demoulin


    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.

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

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


    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

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

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz


    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.

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

    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…

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

    Kakarougkas, A; Jeggo, P A


    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.

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

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


    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.)

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

    Nony, Paul A; Schnellmann, Rick G


    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.

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

    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

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

    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.

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

    Rajesh P. Rastogi


    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.

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

    Kaysar Rahman


    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.

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

    D. Klobčar


    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.

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

    Sharad C.Paudyal; Zhongsheng You


    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.

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

    Jena, N R


    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.

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

    N R Jena


    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.

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

    Agnieszka Weinandy


    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.

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

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


    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.

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

    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.

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

    Daniel L. Jones


    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.

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

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


    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.

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

    Jungfer, Christina; Schwartz, Thomas; Obst, Ursula


    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.

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

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


    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.

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

    Li, Jingjing; Zhang, Siwei


    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.

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

    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...

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

    Faraji, Shirin; Dreuw, Andreas


    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.

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

    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)


    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

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

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


    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.

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

    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.


    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

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

    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: [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210 (United States)


    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

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

    Sergio B. Sesia


    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.

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

    Wendell Q Sun


    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

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

    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


    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.

  20. 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

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


    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)

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

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


    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.

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

    Kozmin, Stanislav G; Jinks-Robertson, Sue


    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.

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

    Agathi-Vasiliki Goula


    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.

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

    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.

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

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


    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

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

    Katona, Thomas R


    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.

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

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


    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.

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

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


    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.

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

    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...

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

    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))


    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.).

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



    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

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

    T. R. Rangaswamy


    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

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

    Lee, Andrew H.; Symington, Lorraine S.


    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

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

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


    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.

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

    Lu, Jing; Gao, Feng-Hou


    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

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

    Rahman, Md. Tawfiqur


    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.

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

    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…

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

    Alireza Saied


    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

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

    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.


    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

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

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


    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.

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

    Zhi-yuan Guo


    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.

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

    Ojini, Irene; Gammie, Alison


    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.

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

    Parnian Alizadeh Oskoee


    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.

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

    Saliou Fall

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

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

    Spampinato, Claudia P


    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.

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

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


    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...

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

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


    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.

  8. DNA repair. [UV radiation

    Setlow, R.


    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)

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

    Loupa, G


    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.

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

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


    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

  11. Motorcycle Repair.

    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…

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

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


    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)

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

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


    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.

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

    Benson Lee N


    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.

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

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


    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

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

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


    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

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

    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)


    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

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

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


    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...

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

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


    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.

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

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


    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

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

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


    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.

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

    Mafia Fousteri; Leon HF Mullenders


    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.

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

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


    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.

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

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


    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)

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

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


    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

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

    Victor D. Martinez


    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.

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

    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)


    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.

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

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


    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.

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

    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

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

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


    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.

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

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


    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.

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

    Terán, G., E-mail: [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: [Instituto Mexicano del Petróleo, Eje central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, México D.F. CP 07730, México (Mexico); Albiter, A., E-mail: [Instituto Mexicano del Petróleo, Eje central Lázaro Cárdenas 152, Col. San Bartolo Atepehuacan, México D.F. CP 07730, México (Mexico); Maldonado, C., E-mail: [Instituto de Investigaciones Metalúrgicas, UMSNH, PO Box 52-B, 58000, México (Mexico); Bracarense, A.Q., E-mail: [UFMG Departamento de Engeharia Mecánica Belo Horizonte, MG (Brazil)


    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

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

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


    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.

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

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


    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

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


    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



    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].

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


    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

    Wigard P. Kloosterman


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

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


    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.

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

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


    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.

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

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


    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.

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

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


    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.

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

    Peter Göttle


    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.

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

    Göttle, Peter; Küry, Patrick


    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.

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

    Tedeschi, Andrea; Omura, Takao; Costigan, Michael


    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.

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

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


    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.

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

    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.


    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

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

    Dierssen, Jan Willem Frederik


    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

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

    Medvedev, D; Stuchebrukhov, A A


    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.

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

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


    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.

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

    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.

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

    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…

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

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


    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.

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

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


    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.

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

    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.

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

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


    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.

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

    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


    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.

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

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


    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.

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

    Martin, P; Nunan, R


    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.

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

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


    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.

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

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


    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.

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

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


    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.

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

    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


    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.

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

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


    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.

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

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


    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

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

    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


    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.

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

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


    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.

  8. Optimality in DNA repair.

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


    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.

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

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


    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.

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

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


    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.

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

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


    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.

  12. 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

    Akbari, Mansour; Krokan, Hans E


    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...

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

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


    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.

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

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


    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

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

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


    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.

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

    Geroni Cristina


    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.

  17. Tendon repair

    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 ...

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

    赵刚; 贾琦


    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

  19. DNA repair protocols

    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...

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

    Jae-Woong Han


    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.

  1. 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.

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


    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.

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

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


    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.

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

    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.

  4. Bladder exstrophy repair

    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 ...

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

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


    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.

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

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


    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.

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

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


    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.


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


    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.

  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



      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

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


    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.


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


    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".

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


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



    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。

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

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


    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.

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

    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


    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: PMID:28092266

  16. 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.

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


    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.


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


    , 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.

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

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


    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.

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

    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.

  20. Nucleotide excision repair in yeast

    Eijk, Patrick van


    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

  1. Hypospadias repair

    ... 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 ...

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

    Wang, Hongjuan; Chen, Xuebo; Fang, Weihai


    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.

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

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


    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.

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

    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)


    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)

  5. Fix-It Careers: Jobs in Repair

    Torpey, Elka Maria


    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…

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

    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: [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China)


    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.

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

    M Sudha Swaraga; L Charitha; M Adinarayana


    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.

  8. Femoral hernia repair

    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 ...

  9. Undescended testicle repair

    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 ...

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

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


    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

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

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


    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

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

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


    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.

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

    Adeline Feri


    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.

  14. Intestinal obstruction repair

    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. ...

  15. Aortic aneurysm repair - endovascular

    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 ...

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

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


    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

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

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


    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.

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

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


    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

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

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


    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.

  20. Aircraft Propeller Hub Repair

    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)


    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.

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

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


    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.

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

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


    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.

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

    Rupp, W Dean


    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.

  4. Some aspects of RNA repair and editing

    Kovalchuk M. V.


    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.

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

    Zhang, Wen-Wei; Lypaczewski, Patrick


    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

  6. Bond strength of repaired amalgam restorations.

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi


    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.

  7. Eye muscle repair - discharge

    ... 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 ...

  8. Ventral hernia repair

    ... page: // Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  9. Brain aneurysm repair

    ... 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 ...

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

    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.

  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.

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


    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

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

    Margie eCastillo-Melendez


    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

  13. 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

    李龑鹏; 丁紫阳; 王腾飞


    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。

  14. Evaluation of the single radiosensitivity in patients subjected to medical exposure that show severe skin reactions; Evaluacion de la radiosensibilidad individual en pacientes sometidos a exposiciones medicas que manifiestan reacciones cutaneas severas

    Di Giorgio, M.; Vallerga, M.B. [Laboratorio de Dosimetria Biologica, Autoridad Regulatoria Nuclear, Av. Del Libertador 8250 (C1429BNP), Buenos Aires (Argentina); Portas, M. [Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Argentina); Perez, M.R. [Laboratorio de Radiopatologia, Autoridad Regulatoria Nuclear, Buenos Aires (Argentina)]. e-mail:


    The Burnt Hospital of the Buenos Aires City Government (HQGCBA) it is a hospital of reference of the Net of Medical Responses in Radiological Emergencies of the Argentine Republic. In the mark of an agreement among the HQGCBA and the Authority Regulatory Nuclear (ARN), it is in execution a study protocol for the one boarding diagnoses and therapeutic of radioinduced cutaneous leisure. They exist individual variations that can condition the response to the ionizing radiations (IR), so much in accidental exposures as having programmed (radiotherapy, radiology interventionist). In this context, the individual radiosensitivity is evaluated in the patients signed up in this protocol that presented sharp or late cutaneous reactions, with grades of severity 3-4 (approaches EORTC/RTOG). The capacity of repair of the DNA was evaluated in outlying blood lymphocytes irradiated in vitro (2 Gy, gamma of Co-60) by means of the micronucleus techniques and comet essay in alkaline conditions. In this work two cases in those that is applied this study protocol, the therapeutic answer and its correlate with the discoveries of the radiosensitivity tests is presented. Case 1: patient of feminine sex, subjected to external radiotherapy by a breast infiltrating ductal carcinoma; developed sharp cutaneous radiotoxicity grade 3 (confluent humid epithelitis) that motivate the interruption of the treatment. Case 2: patient of masculine sex, subjected to a coronary angioplasty (interventionist radiology); developed late cutaneous radiotoxicity grade 4 (ulceration in dorsal region). Both patients were treated with topical trolamine associated to systemic administration of pentoxiphiline and antioxidants. The therapeutic answer is evaluated by means of clinical pursuit, photographic serial register and complementary exams (thermography and ultrasonography of high frequency). In the case 1 the answer was very favorable, with precocious local improvement and complete remission of symptoms and

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

    A. Satoh


    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

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

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


    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.

  17. Base excision repair in sugarcane

    Agnez-Lima Lucymara F.


    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.

  18. 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

    陈雪曼; 孙胜祥


    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。

  19. Repairs the added value of being wrong

    Brandt, Patrick


    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

  20. Mammalian mismatch repair

    Pena Diaz, Javier; Jiricny, Josef


    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...

  1. DNA-Protein Crosslink Proteolysis Repair.

    Vaz, Bruno; Popovic, Marta; Ramadan, Kristijan


    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?

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


    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

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


    , 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. 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.

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


    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.

  5. Repair welding process of friction stir welding groove defect

    LIU Hui-jie; ZHANG Hui-jie


    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.

  6. Chromatin structure and DNA damage repair

    Dinant Christoffel


    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.

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

    Kaja Milanowska


    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.

  8. Changes in DNA repair during aging

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


    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

  9. 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

    白静; 白晓平; 赵巧艳


    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

  10. 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



    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.

  11. Pectus excavatum repair

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

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

    Lemaître, Charlène; Soutoglou, Evi


    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.

  13. 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

    曾理(综述); 丁群芳(审校)


    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。

  14. When "Other" Initiate Repair.

    Schegloff, Emanuel A.


    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)

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

    K. C. Summers


    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.

  16. Percutaneous mitral valve repair.

    Gillinov, A Marc; Liddicoat, John R


    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.

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

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


    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.

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

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


    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.

  19. Role of Deubiquitinating Enzymes in DNA Repair


    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.

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

    Johnson, Roger D.; Jasin, Maria


    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...

  1. Progress in patch repair of aerospace composite structures

    Hou, Weiguo; Zhang, Weifang; Tang, Qingyun


    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.

  2. 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

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


    .... 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...

  3. 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

    张明星; 杨垚; 程光权; 刘忠


    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.

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

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


    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

  5. Repairs of composite structures

    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

  6. Flexible Plug Repair for Shuttle Wing Leading Edge

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


    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.

  7. Exosomes and cardiac repair after myocardial infarction.

    Sahoo, Susmita; Losordo, Douglas W


    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.

  8. Workshop on DNA repair.

    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


    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

  9. Laparoscopic lumbar hernia repair.

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


    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.

  10. 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)

    Bauluz, C.


    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.

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

    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


    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

  12. 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

    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)


    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)

  13. 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

    侯懿烜; 柳满然; 张萍; 郑元义; 刘仁建; 唐成林


    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

  14. Salvage hypospadias repairs

    Sripathi V


    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.

  15. Repair and regeneration in endodontics.

    Lin, L M; Rosenberg, P A


    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.

  16. 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

    Akbari, Mansour; Krokan, Hans E


    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...

  17. Nucleotide excision repair in differentiated cells

    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:


    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.

  18. Elucidating the digital control mechanism for DNA damage repair with the p53-Mdm2 system: single cell data analysis and ensemble modelling.

    Ogunnaike, Babatunde A


    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.

  19. Macrophages in Tissue Repair, Regeneration, and Fibrosis.

    Wynn, Thomas A; Vannella, Kevin M


    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.

  20. A brief history of the DNA repair field.

    Friedberg, Errol C


    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.

  1. Nucleotide excision repair of DNA: The very early history.

    Friedberg, Errol C


    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.

  2. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    Y.M. Bastiaansen-Jenniskens (Yvonne)


    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

  3. A brief history of the DNA repair field

    Errol C Friedberg


    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.

  4. Haemophilus influenzae does not fit theories of postreplication repair

    Setlow, J K; Notani, N K


    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.

  5. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    Y.M. Bastiaansen-Jenniskens (Yvonne)


    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

  6. Progress of peripheral nerve repair



    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.

  7. Composite repairs qualification according to ISO/TS 24817

    Meniconi, Luiz C.M.; Perrut, Valber A. [Petroleo Brasileiro S.A. (PETROBRAS/CENPES), Rio de Janeiro, RJ (Brazil). Centro de Pesquisas


    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)

  8. Composite repairs qualification according to ISO/TS 24817

    Meniconi, Luiz C.M.; Perrut, Valber A. [Petroleo Brasileiro S.A. (PETROBRAS/CENPES), Rio de Janeiro, RJ (Brazil). Centro de Pesquisas


    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. Achilles tendon repair

    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 ...

  10. Diaphragmatic hernia repair - slideshow

    ... 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, ...

  11. Eye muscle repair - slideshow

    ... page: // 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. ...

  12. Tracheoesophageal fistula repair - slideshow

    ... page: // 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 ...

  13. Inguinal hernia repair - slideshow

    ... page: // 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 ...


    Robin Gordon; Bill Bruce; Ian Harris; Dennis Harwig; Nancy Porter; Mike Sullivan; Chris Neary


    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

  15. Pectus excavatum repair - slideshow

    ... this page: // 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 ...

  16. Hiatal hernia repair - slideshow

    ... 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 ...

  17. Repairing ceramic insulating tiles

    Dunn, B. R.; Laymance, E. L.


    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.

  18. Rotator cuff repair - slideshow

    ... this page: // 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 ...

  19. Cleft lip repair - slideshow

    ... this page: // 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 ...

  20. Grey Repairable System Analysis

    Renkuan Guo; Charles Ernie Love


    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.

  1. Repair of DNA Double-Strand Breaks

    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.

  2. Mechanisms of assembly of the enzyme-ssDNA complexes required for recombination-dependent DNA synthesis and repair in bacteriophage T4

    Morrical, S.; Hempstead, K.; Morrical, M. [Univ. of Vermont College of Medicine, Burlington, VT (United States)


    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.

  3. 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

    贺鹤鸣; 成耀荣


    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.

  4. Competition between replicative and translesion polymerases during homologous recombination repair in Drosophila.

    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.

  5. Mechanisms of larval midgut damage following exposure to phoxim and repair of phoxim-induced damage by cerium in Bombyx mori.

    Yu, Xiaohong; Sun, Qingqing; Li, Bing; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sheng, Lei; Sang, Xuezi; Gui, Suxin; Wang, Ling; Shen, Weide; Hong, Fashui


    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.

  6. 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



    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.

  7. DNA repair and gene targeting in plant end-joining mutants

    Jia, Qi


    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

  8. DNA repair and gene targeting in plant end-joining mutants

    Jia, Qi


    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

  9. Suppressed expression of non-DSB repair genes inhibits gamma-radiation-induced cytogenetic repair and cell cycle arrest.

    Zhang, Ye; Rohde, Larry H; Emami, Kamal; Hammond, Dianne; Casey, Rachael; Mehta, Satish K; Jeevarajan, Antony S; Pierson, Duane L; Wu, Honglu


    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.

  10. Valve radio and audio repair handbook



    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

  11. Chromatin challenges during DNA replication and repair

    Groth, Anja; Rocha, Walter; Verreault, Alain


    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...

  12. Histone displacement during nucleotide excision repair

    Dinant, C.; Bartek, J.; Bekker-Jensen, S.


    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...

  13. Mechanics, degradability, bioactivity, in vitro, and in vivo biocompatibility evaluation of poly(amino acid)/hydroxyapatite/calcium sulfate composite for potential load-bearing bone repair.

    Fan, Xiaoxia; Ren, Haohao; Luo, Xiaoman; Wang, Peng; Lv, Guoyu; Yuan, Huipin; Li, Hong; Yan, Yonggang


    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.

  14. Transactivation of repair genes by BRCA1.

    El-Deiry, Wafik S


    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.

  15. Detecting and Correcting Speech Repairs

    Heeman, P A; Heeman, Peter; Allen, James


    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.

  16. In utero repair of spina bifida.

    Moldenhauer, Julie S


    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.

  17. DNA repair responses in human skin cells

    Hanawalt, P.C.; Liu, S.C.; Parsons, C.S.


    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.

  18. Transcription-coupled repair: an update.

    Spivak, Graciela


    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.

  19. Thermo-radiosensitivity of the granulocyte and macrophage precursor cells of mice. I.-Development of the in vivo culture and effects induced by the hyperthermia; Termo-radiosensibilidad del precursor hematopoyetico que origina las series granulocitica y macrofaga de raton. I.- Desarrollo del cultivo in vivo y efectos producidos por la hipertermia

    Bueren, J. A.; Nieto, M.


    The present report shows the agar diffusion chamber technique for culturing granulocyte- macrophage precursor cells, obtained from mice bone marrow. Diffusion chambers containing the bone marrow suspension are implanted intraperitoneally Into mice and constitute a compartment which avoids the migration of cells, but allows the transit of the mouse biological fluxes, necessary for the cellular proliferation. By means of this technique, we studied the lethal effects of the hyperthermia on the precursors and their capacity to repair sublethal damage. (Author) 129 refs.

  20. Transcription factor EGR1 directs tendon differentiation and promotes tendon repair

    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


    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...

  1. Groin hernia repair in young males: mesh or sutured repair?

    Bisgaard, T; Bay-Nielsen, M; Kehlet, H


    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....

  2. Cleft lip and palate repair

    ... this page: // 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 ...

  3. Abdominal aortic aneurysm repair - open

    ... this page: // 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 ...

  4. 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)

    徐德峰; 赵谋明; 马忠华; 苏国万; 张婷


    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。

  5. Mystery of DNA repair: the role of the MRN complex and ATM kinase in DNA damage repair.

    Czornak, Kamila; Chughtai, Sanaullah; Chrzanowska, Krystyna H


    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.

  6. Regenerative endodontics: regeneration or repair?

    Simon, Stéphane R J; Tomson, Phillip L; Berdal, Ariane


    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.

  7. Nanomaterials promise better bone repair

    Qifei Wang; Jianhua Yan; Junlin Yang; Bingyun Li


    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...

  8. Laparoscopic repair of femoral hernia

    Yang, Xue-Fei; Liu, Jia-Lin


    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, ...

  9. Mechanics

    Hartog, J P Den


    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

  10. 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

    姜霁洋; 徐涵; 白雪婷; 程訸; 林艳玲; 凌震; 陈一村; 石刚刚


    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

  11. Heterogenous mismatch-repair status in colorectal cancer

    Joost, Patrick; Veurink, Nynke; Holck, Susanne;


    , 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...

  12. Nonhomologous Mechanisms of Repair of Chromosomal Breaks

    Haber, J. E.


    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.

  13. Differential repair of UV damage in Saccharomyces cerevisiae is cell cycle dependent.

    Terleth, C; Waters, R; Brouwer, J; van de Putte, P


    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.

  14. Potentials of Endogenous Neural Stem cells in Cortical Repair

    Bhaskar eSaha


    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.

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

    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.

  16. DNA repair: Dynamic defenders against cancer and aging

    Fuss, Jill O.; Cooper, Priscilla K.


    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

  17. Nanomaterials promise better bone repair

    Qifei Wang


    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.

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

    Kienzler, Aude; Bony, Sylvie; Devaux, Alain


    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

  19. Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats.

    Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M


    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

  20. Crack Repair in Aerospace Aluminum Alloy Panels by Cold Spray

    Cavaliere, P.; Silvello, A.


    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.

  1. Half-bead weld repairs for in-service applications

    Holz, P.P. Sr.


    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.

  2. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Lemontt, J F


    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.

  3. Genetic and physiological factors affecting repair and mutagenesis in yeast

    Lemontt, J F


    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.

  4. Electronic Pathways in Photoactivated Repair of UV Mutated DNA

    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.

  5. Use Of Phospho Magnesium Compounds as Concrete Repair


    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 ...

  6. PCNA Modifications for Regulation of Post-Replication Repair Pathways


    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 ...

  7. Laser cladding crack repair of austenitic stainless steel

    Van Rooyen, C


    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...

  8. Damage tolerance of bonded composite aircraft repairs for metallic structures

    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

  9. Mechanics

    Chester, W


    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...

  10. Aspects of DNA repair and nucleotide pool imbalance

    Holliday, R.


    Evidence that optimum repair depends on adequate pools of deoxynucleotide triphosphates (dNTPs) comes from the study of pyrimidine auxotrophs of Ustilago maydis. These strains are sensitive to UV light and X-rays, and for pyr1-1 it has been shown that the intracellular concentration of dTTP is reduced about 7-fold. The survival curve of pyr1-1 after UV-treatment, and split dose experiments with wild-type cells, provide evidence for an inducible repair mechanism, which probably depends on genetic recombination. Although inducible repair saves cellular resources, it has the disadvantage of becoming ineffective at doses which are high enough to inactivate the repressed structural gene(s) for repair enzymes. It is clear that a wide variety of repair mechanisms have evolved to remove lesions which arise either spontaneously or as a result of damage from external agents. Nevertheless, it would be incorrect to assume that all species require all possible pathways of repair. It is now well established that the accuracy of DNA and protein synthesis depends on proof-reading or editing mechanisms. Optimum accuracy levels will evolve from the balance between error avoidance in macromolecular synthesis and physiological efficiency in growth and propagation.

  11. DNA损伤修复机制——解读2015年诺贝尔化学奖%The Repair Mechanism for DNA Damage Understanding The 2015 Nobel Prize in Chemistry

    刘博雅; 杨鑫; 任梦梦; 陈帅怡; 罗建沅


    Tomas Lindahl,Paul Modrich和Aziz Sancar三位科学家因发现“DNA损伤修复机制”获得了2015年诺贝尔化学奖.Lindahl首次发现Escherichia Coli中参与碱基切除修复的第一个蛋白质——尿嘧啶-DNA糖基化酶(UNG);Modrich重建了错配修复的体外系统,从大肠杆菌到哺乳动物深入探究了错配修复的机制;Sancar利用纯化的UvrA、UvrB、UvrC重建了核苷酸切除修复的关键步骤,阐述了核苷酸切除修复的分子机制.DNA损伤是由生物所处体外环境和体内因素共同导致的,面对不同种类的损伤,机体启动多种不同的修复机制修复损伤,保护基因组稳定性.这些修复机制包括:光修复(light repairing);核苷酸切除修复(nucleotide excision repair,NER);碱基切除修复(base excision repair,BER);错配修复(mismatch repair,MMR);以及DNA双链断裂修复(DNA double strand breaks repair,DSBR).其中DNA双链断裂修复又分同源重组(homologous recombination,HR)和非同源末端连接(non-homologous end joining,NHEJ)两种方式.本文将对上述几种修复的机制进行总结与讨论.

  12. Effect of solution annealing on properties of used reformer centrifugally casted tubes prior to repair by welding

    B. Mateša


    Full Text Available The specimens of damaged tubes, ASTM A297 HK 40, are repaired by welding. Before repairing, solution annealing is used as a procedure for properties restitution. This paper explores the influence of used solution annealing procedure (1 050 şC / 2h on mechanical and micro-structural properties. The emphasis is put on specific procedures at repair by welding.

  13. A matter of life or death: modeling DNA damage and repair in bacteria.

    Karschau, Jens; de Almeida, Camila; Richard, Morgiane C; Miller, Samantha; Booth, Ian R; Grebogi, Celso; de Moura, Alessandro P S


    DNA damage is a hazard all cells must face, and evolution has created a number of mechanisms to repair damaged bases in the chromosome. Paradoxically, many of these repair mechanisms can create double-strand breaks in the DNA molecule which are fatal to the cell. This indicates that the connection between DNA repair and death is far from straightforward, and suggests that the repair mechanisms can be a double-edged sword. In this report, we formulate a mathematical model of the dynamics of DNA damage and repair, and we obtain analytical expressions for the death rate. We predict a counterintuitive relationship between survival and repair. We can discriminate between two phases: below a critical threshold in the number of repair enzymes, the half-life decreases with the number of repair enzymes, but becomes independent of the number of repair enzymes above the threshold. We are able to predict quantitatively the dependence of the death rate on the damage rate and other relevant parameters. We verify our analytical results by simulating the stochastic dynamics of DNA damage and repair. Finally, we also perform an experiment with Escherichia coli cells to test one of the predictions of our model.

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

    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.

  15. Endovascular repair of blunt popliteal arterial injuries

    Zhong, Shan; Zhang, Xiquan; Chen, Zhong; Zhu, Wei; Pan, Xiaolin [Dept. of nterventional Vascular, The 148th Hospital of Chinese People' s Liberation Army, Zibo (China); Dong, Peng; Sun, Yequan [Dept. of Medical Imaging, Weifang Medical University, Weifang (China); Qi, Deming [Dept. of Medical Imaging, Qilu Medical University, Zibo (China)


    To evaluate the feasibility and effectiveness of endovascular repair for blunt popliteal arterial injuries. A retrospective analysis of seven patients with clinical suspicion of popliteal arterial injuries that were confirmed by arteriography was performed from September 2009 to July 2014. Clinical data included demographics, mechanism of injury, type of injury, location of injury, concomitant injuries, time of endovascular procedures, time interval from trauma to blood flow restoration, instrument utilized, and follow-up. All patients were male (mean age of 35.9 ± 10.3 years). The type of lesion involved intimal injury (n = 1), partial transection (n = 2), complete transection (n = 2), arteriovenous fistula (n = 1), and pseudoaneurysm (n = 1). All patients underwent endovascular repair of blunt popliteal arterial injuries. Technical success rate was 100%. Intimal injury was treated with a bare-metal stent. Pseudoaneurysm and popliteal artery transections were treated with bare-metal stents. Arteriovenous fistula was treated with bare-metal stent and coils. No perioperative death and procedure-related complication occurred. The average follow-up was 20.9 ± 2.3 months (range 18–24 months). One patient underwent intra-arterial thrombolysis due to stent thrombosis at 18 months after the procedure. All limbs were salvaged. Stent migration, deformation, or fracture was not found during the follow-up. Endovascular repair seems to be a viable approach for patients with blunt popliteal arterial injuries, especially on an emergency basis. Endovascular repair may be effective in the short-term. Further studies are required to evaluate the long-term efficacy of endovascular repair.

  16. Study on the seismic flexural-shear damage mechanisms and rapid repair techniques for earthquake damaged bridge piers%钢筋混凝土桥墩地震弯剪破坏机理与震后快速修复技术研究

    司炳君; 孙治国; 杜修力; 王东升; 黄照南


    Quasi-static tests were conducted to study the seismic flexural-shear damage mechanisms and rapid repair techniques for earthquake damaged bridge piers.Six original pier specimens of circular cross sections were severely damaged under cyclic lateral force and constant axial load,and the damaged specimens were subsequently repaired using high-fluidity concrete with high early-strength and Carbon Fiber-Reinforced Polymer(CFRP),and then put into test again within a week.The failure pattern,strength,ductility and dissipated energy parameters and stiffness degradation of the repaired specimens were compared with the original ones.It is founded that the ultimate performance of bridge piers designed according to current seismic design codes of JTG/T B02-01—2008 and Caltrans with minimum confining reinforcement ratios may be dominated by shear failure in the plastic hinge zones.The repaired specimens show lower initial stiffness and larger yield displacement as a result of the pre-existing damage.But the failure for all of the repaired specimens was due to flexure,with higher strength,larger or the same ductility and dissipated energy parameters and recovered stiffness,which demonstrated the effectiveness of the proposed repair techniques.%为研究钢筋混凝土桥墩的地震弯剪破坏机理与震后快速修复技术,首先进行了6个圆形截面桥墩试件的拟静力试验,试件均发生严重弯剪破坏,然后利用高流动性早强混凝土和CFRP布对其进行快速修复并在1周内重新进行加载试验,将原桥墩与修复后试件的破坏形态、承载力、延性与耗能能力、刚度退化等进行了对比分析。研究表明:塑性铰区配箍满足我国《公路桥梁抗震设计细则》(JTG/T B02-01—2008)及美国Caltrans规范要求的钢筋混凝土桥墩试件,最终仍有可能因塑性铰区抗剪强度不足发生弯剪破坏。由于初始损伤的存在,震后修复

  17. Laparoscopic Repair of Morgagni Hernia

    ilker murat arer


    Full Text Available Morgagni hernia is a congenital herniation of abdominal contents into the thoracic cavity through a retrosternal diaphragmatic defect and make up about 1 % - 5 % of all types of congenital diaphragmatic hernias. Surgical repair of Morgagni hernias is usually indicated when patients are symptomatic and have a high risk of strangulation or incarceration of the contained viscera. 71-year-old male patient admitted to emergency department with a 2-day history of abdominal pain, vomiting and obstipation. Laparoscopic repair for Morgagni hernia was performed. Laparoscopic repair for Morgagni hernia with mesh repair is secure, satisfactory and easily performed. [Cukurova Med J 2015; 40(Suppl 1: 71-74

  18. Late repair of abductor avulsion after the transgluteal approach for hip arthroplasty.

    Miozzari, Hermes H; Dora, Claudio; Clark, John M; Nötzli, Hubert P


    The abductor release sometimes does not heal after a transgluteal approach for hip arthroplasty. Factors influencing the success of subsequent repair are unclear. We used magnetic resonance imaging (MRI) to compare the condition of the gluteus medius with clinical outcome after late repair of abductor dehiscence in 12 total hip patients. Evaluation included a pain rating, gait evaluation, Trendelenburg test, strength grading, and Harris Hip Score. Most had both prerepair and postrepair MRI studies to assess the repair and to grade abductor muscle fatty degeneration. Two repairs without MRI were explored surgically. Although average pain, limp, and strength scores improved significantly, rerupture occurred in 4 subjects and fatty degeneration in the gluteus medius did not improve, even with intact repair. Nine patients were satisfied; 7 of these had an intact repair. Magnetic resonance imaging and operative observations suggest that chronic degeneration in the abductor mechanism is the major impediment to successful repair.

  19. Double row repair: is it worth the hassle?

    Papalia, Rocco; Franceschi, Francesco; Del Buono, Angelo; Zampogna, Biagio; Maffulli, Nicola; Denaro, Vincenzo


    In the operative management of rotator cuff disease, comparable functional results have been reported after open or mini-open repair and arthroscopic fixation. Surgical repair aims to re-establish an anatomical configuration of the tendon-bone construct for restoring its mechanical performance. Single row repair is the most commonly used technique, but recently some authors have proposed to re-establish the rotator cuff footprint with 2 rows of suture anchors ("double row" repair). In regard to imaging assessment, at time zero double row repair results being more anatomic and allows for structurally sound restoration of the rotator cuff footprint. However, this does not seem to translate into superior clinical outcomes for the double row repair when evaluating all different sizes of rotator cuff tears as a whole. The scientific basis for recommending single or double row repair as preferred treatment for patients with rotator cuff tear is questionable, as minimal differences have been measured on clinical and functional rating scales.

  20. Combinatorial Reliability and Repair


    Press, Oxford, 1987. [2] G. Gordon and L. Traldi, Generalized activities and the Tutte polynomial , Discrete Math. 85 (1990), 167-176. [3] A. B. Huseby, A...particular, Satyanarayana and Tindell introduced a notion of (K,j)-domination in their study of a K-terminal version of the chromatic polynomial [6], and it...G)) graphs. He also intends to look into the properties of the polynomial that gives the expected number of needed repairs of a K-terminal network

  1. Conservative Repair of a Chromosomal Double-Strand Break by Single-Strand DNA through Two Steps of Annealing▿ †

    Storici, Francesca; Snipe, Joyce R.; Chan, Godwin K.; Dmitry A Gordenin; Michael A Resnick


    The repair of chromosomal double-strand breaks (DSBs) is essential to normal cell growth, and homologous recombination is a universal process for DSB repair. We explored DSB repair mechanisms in the yeast Saccharomyces cerevisiae using single-strand oligonucleotides with homology to both sides of a DSB. Oligonucleotide-directed repair occurred exclusively via Rad52- and Rad59-mediated single-strand annealing (SSA). Even the SSA domain of human Rad52 provided partial complementation for a null...

  2. DNA replication, repair, and repair tests. [Rat; human leukocytes

    Lambert, B.


    The rate of inhibition and recovery of DNA synthesis can be used in a rapid assay system to detect genotoxic potentials of chemicals. Also, the observation that an agent stimulates DNA repair in a test system indicates its ability to cause damage in DNA. Different experimental approaches to the study of repair synthesis are discussed.




    Hyperthermia specifically inhibits the repair of UV-induced DNA photolesions in transcriptionally active genes, To define more precisely which mechanisms underlie the heat-induced inhibition of repair of active genes, removal of cyclobutane pyrimidine dimers (CPDs) was studied in human fibroblasts w

  4. Biologics for tendon repair.

    Docheva, Denitsa; Müller, Sebastian A; Majewski, Martin; Evans, Christopher H


    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

  5. Kvitebjoern gas pipeline repair - baptism of remote pipeline repair system

    Gjertveit, Erling


    On the 1st of November 2007, severe anchor damage was discovered on the 30 inch Kvitebjoern gas export pipeline. The damage constituted a localised dent and a 17deg buckle, but no leakage. Statoil has invested in building an effective repair contingency structure for the large pipeline network on the Norwegian Continental shelf, with particular focus on the large gas export pipelines. The repair method for the Kvitebjoern pipeline was remotely operated using two Morgrip couplings and a spool. The installation used the purpose built Pipeline Repair System stored at Killingoey and couplings produced and tested back in 2005. This presentation will cover the initial damage investigations, the temporary operational phase, the repair preparations, the actual repair and lessons learned. (Author)

  6. DNA base excision repair nanosystem engineering: model development.

    Sokhansanj, B A


    DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity.

  7. Pain following the repair of an abdominal hernia

    Hansen, Mark Berner; Andersen, Kenneth Geving; Crawford, Michael Edward


    Pain and other types of discomfort are frequent symptoms following the repair of an abdominal hernia. After 1 year, the incidence of light to moderate pain following inguinal hernia repair is as high as 10% and 2% for severe disabling chronic pain. Postoperative chronic pain not only affects......, psychosocial characteristics, and surgical procedures) related to the postoperative pain conditions. Furthermore, the mechanisms for both acute and chronic pain are presented. We focus on inguinal hernia repair, which is the most frequent type of abdominal hernia surgery that leads to chronic pain. Finally...... the individual patient, but may also have a great impact on relatives and society, and may be a cause of concern for the responsible surgeon. This paper provides an overview of the anatomy, surgical procedures, and disposing factors (age, gender, ethnicity, genotype, previous hernia repair, pain prior to surgery...

  8. Automated Image Processing for the Analysis of DNA Repair Dynamics

    Riess, Thorsten; Tomas, Martin; Ferrando-May, Elisa; Merhof, Dorit


    The efficient repair of cellular DNA is essential for the maintenance and inheritance of genomic information. In order to cope with the high frequency of spontaneous and induced DNA damage, a multitude of repair mechanisms have evolved. These are enabled by a wide range of protein factors specifically recognizing different types of lesions and finally restoring the normal DNA sequence. This work focuses on the repair factor XPC (xeroderma pigmentosum complementation group C), which identifies bulky DNA lesions and initiates their removal via the nucleotide excision repair pathway. The binding of XPC to damaged DNA can be visualized in living cells by following the accumulation of a fluorescent XPC fusion at lesions induced by laser microirradiation in a fluorescence microscope. In this work, an automated image processing pipeline is presented which allows to identify and quantify the accumulation reaction without any user interaction. The image processing pipeline comprises a preprocessing stage where the ima...

  9. Polymer nanocomposites for high-temperature composite repair

    Sheng, Xia [Iowa State Univ., Ames, IA (United States)


    A novel repair agent for resin-injection repair of advanced high temperature composites was developed and characterized. The repair agent was based on bisphenol E cyanate ester (BECy) and reinforced with alumina nanoparticles. To ensure good dispersion and compatibility with the BECy matrix in nanocomposites, the alumina nanoparticles were functionalized with silanes. The BECy nanocomposites, containing bare and functionalized alumina nanoparticles, were prepared and evaluated for their thermal, mechanical, rheological, and viscoelastic properties. The monomer of BECy has an extremely low viscosity at ambient temperature, which is good for processability. The cured BECy polymer is a highly cross-linked network with excellent thermal mechanical properties, with a high glass transition temperature (Tg) of 270 C and decomposition temperature above 350 C. The incorporation of alumina nanoparticles enhances the mechanical and rheological properties of the BECy nanocomposites. Additionally, the alumina nanoparticles are shown to catalyze the cure of BECy. Characterization of the nanocomposites included dynamic mechanical analysis, differential scanning calorimetry, thermogravimetric analysis, rheological and rheokinetic evaluation, and transmission electron microscopy. The experimental results show that the BECy nanocomposite is a good candidate as repair agent for resin-injection repair applications.

  10. Mononuclear Cells and Vascular Repair in HHT

    Calinda eDingenouts


    Full Text Available Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease is a rare genetic vascular disorder known for its endothelial dysplasia causing arteriovenous malformations and severe bleedings. HHT-1 and HHT-2 are the most prevalent variants and are caused by heterozygous mutations in endoglin and ALK1, respectively. An undervalued aspect of the disease is that HHT patients experience persistent inflammation. Although endothelial and mural cells have been the main research focus trying to unravel the mechanism behind the disease, wound healing is a process with a delicate balance between inflammatory and vascular cells. Inflammatory cells are part of the mononuclear cells (MNCs fraction, and can, next to eliciting an immune response, also have angiogenic potential. This biphasic effect of MNC can hold a promising mechanism to further elucidate treatment strategies for HHT patients. Before MNC are able to contribute to repair, they need to home to and retain in ischemic and damaged tissue. Directed migration (homing of mononuclear cells following tissue damage is regulated by the stromal cell derived factor 1 (SDF1. MNCs that express the C-X-C chemokine receptor 4 (CXCR4 migrate towards the tightly regulated gradient of SDF1. This directed migration of monocytes and lymphocytes can be inhibited by dipeptidyl peptidase 4 (DPP4. Interestingly, MNC of HHT patients express elevated levels of DPP4 and show impaired homing towards damaged tissue. Impaired homing capacity of the MNCs might therefore contribute to the impaired angiogenesis and tissue repair observed in HHT patients. This review summarizes recent studies regarding the role of MNCs in the etiology of HHT and vascular repair, and evaluates the efficacy of DPP4 inhibition in tissue integrity and repair.

  11. Handbook of adhesive bonded structural repair

    Wegman, Raymond F


    Provides repair methods for adhesive bonded and composite structures; identifies suitable materials and equipment for repairs; describes damage evaluation criteria and techniques, and methods of inspection before and after repair.

  12. Clamp wins pipe repair prize



    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  13. The journey of DNA repair

    Saini, Natalie


    21 years ago, the DNA Repair Enzyme was declared “Molecule of the Year”. Today, we are celebrating another “year of repair”, with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways.

  14. Transcript RNA supports precise repair of its own DNA gene.

    Keskin, Havva; Meers, Chance; Storici, Francesca


    The transfer of genetic information from RNA to DNA is considered an extraordinary process in molecular biology. Despite the fact that cells transcribe abundant amount of RNA with a wide range of functions, it has been difficult to uncover whether RNA can serve as a template for DNA repair and recombination. An increasing number of experimental evidences suggest a direct role of RNA in DNA modification. Recently, we demonstrated that endogenous transcript RNA can serve as a template to repair a DNA double-strand break (DSB), the most harmful DNA lesion, not only indirectly via formation of a DNA copy (cDNA) intermediate, but also directly in a homology driven mechanism in budding yeast. These results point out that the transfer of genetic information from RNA to DNA is more general than previously thought. We found that transcript RNA is more efficient in repairing a DSB in its own DNA (in cis) than in a homologous but ectopic locus (in trans). Here, we summarize current knowledge about the process of RNA-driven DNA repair and recombination, and provide further data in support of our model of DSB repair by transcript RNA in cis. We show that a DSB is precisely repaired predominately by transcript RNA and not by residual cDNA in conditions in which formation of cDNA by reverse transcription is inhibited. Additionally, we demonstrate that defects in ribonuclease (RNase) H stimulate precise DSB repair by homologous RNA or cDNA sequence, and not by homologous DNA sequence carried on a plasmid. These results highlight an antagonistic role of RNase H in RNA-DNA recombination. Ultimately, we discuss several questions that should be addressed to better understand mechanisms and implications of RNA-templated DNA repair and recombination.

  15. Rethinking transcription coupled DNA repair.

    Kamarthapu, Venu; Nudler, Evgeny


    Nucleotide excision repair (NER) is an evolutionarily conserved, multistep process that can detect a wide variety of DNA lesions. Transcription coupled repair (TCR) is a subpathway of NER that repairs the transcribed DNA strand faster than the rest of the genome. RNA polymerase (RNAP) stalled at DNA lesions mediates the recruitment of NER enzymes to the damage site. In this review we focus on a newly identified bacterial TCR pathway in which the NER enzyme UvrD, in conjunction with NusA, plays a major role in initiating the repair process. We discuss the tradeoff between the new and conventional models of TCR, how and when each pathway operates to repair DNA damage, and the necessity of pervasive transcription in maintaining genome integrity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Microvesicle shedding and lysosomal repair fulfill divergent cellular needs during the repair of streptolysin O-induced plasmalemmal damage.

    Alexander P Atanassoff

    Full Text Available Pathogenic bacteria secrete pore-forming toxins that permeabilize the plasma membrane of host cells. Nucleated cells possess protective mechanisms that repair toxin-damaged plasmalemma. Currently two putative repair scenarios are debated: either the isolation of the damaged membrane regions and their subsequent expulsion as microvesicles (shedding or lysosome-dependent repair might allow the cell to rid itself of its toxic cargo and prevent lysis. Here we provide evidence that both mechanisms operate in tandem but fulfill diverse cellular needs. The prevalence of the repair strategy varies between cell types and is guided by the severity and the localization of the initial toxin-induced damage, by the morphology of a cell and, most important, by the incidence of the secondary mechanical damage. The surgically precise action of microvesicle shedding is best suited for the instant elimination of individual toxin pores, whereas lysosomal repair is indispensable for mending of self-inflicted mechanical injuries following initial plasmalemmal permeabilization by bacterial toxins. Our study provides new insights into the functioning of non-immune cellular defenses against bacterial pathogens.

  17. Reward optimization of a repairable system

    Castro, I.T. [Departamento de Matematicas, Facultad de Veterinaria, Universidad de Extremadura, Avenida de la Universidad, s/n. 10071 Caceres (Spain)]. E-mail:; Perez-Ocon, R. [Departamento de Estadistica e Investigacion Operativa, Facultad de Ciencias, Universidad de Granada, Avenida de Severo Ochoa, s/n. 18071 Granada (Spain)]. E-mail:


    This paper analyzes a system subject to repairable and non-repairable failures. Non-repairable failures lead to replacement of the system. Repairable failures, first lead to repair but they lead to replacement after a fixed number of repairs. Operating and repair times follow phase type distributions (PH-distributions) and the pattern of the operating times is modelled by a geometric process. In this context, the problem is to find the optimal number of repairs, which maximizes the long-run average reward per unit time. To this end, the optimal number is determined and it is obtained by efficient numerical procedures.

  18. Wound repair in Pocillopora

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo


    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  19. Groin hernia repair

    Kehlet, Henrik; Aasvang, Eske


    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...

  20. 摩擦焊接及形变热处理技术在外加厚油管修复中的应用%Application of Friction Welding and Thermal-mechanical Treatment Technology in the External Upset Tubing Repairing

    张朋举; 魏晓娟; 张永红; 王语; 殷志杰; 张仙文; 魏芳


    通过对外加厚油管的修复工艺展开分析, 设计了摩擦焊接及形变热处理为关键技术的修复工艺, 并且选择了系列修复设备和辅助设施. 在此基础上以准73.02 mm×5.5 mm规格油管为样品进行工程试验, 检测了接头的微观组织和力学性能. 结果表明, 在一定的摩擦焊接参数条件下,准73.02 mm×5.5 mm规格油管焊缝性能可达到API SPEC 5CT规定的力学性能要求. 通过工程试验,认为该技术在油管修复上的应用是可行的, 并且可以成为外加厚油管生产的一种新方法.%In this article,the analysis on the repair technology of the external upset tubing was carried out,the key technology repair process of friction welding and thermal-mechanical treatment was designed, and chose a series of repair equipment and auxiliary facilities. On this basis, taking 准73.02 mm × 5.5 mm tubing as engineering test samples, the microstructure and mechanical properties of joint were detected. The results showed that the performance of tubing with size of 准73.02 mm × 5.5 mm can reach the mechanical performance requirements specified in API SPEC 5CT, under certain conditions of friction welding parameters. Through the engineering test, it considered that the technology application in tubing repair is feasible, and can become a new method for external upset tubing production.

  1. Nucleotide Excision Repair in Caenorhabditis elegans

    Hannes Lans


    Full Text Available Nucleotide excision repair (NER plays an essential role in many organisms across life domains to preserve and faithfully transmit DNA to the next generation. In humans, NER is essential to prevent DNA damage-induced mutation accumulation and cell death leading to cancer and aging. NER is a versatile DNA repair pathway that repairs many types of DNA damage which distort the DNA helix, such as those induced by solar UV light. A detailed molecular model of the NER pathway has emerged from in vitro and live cell experiments, particularly using model systems such as bacteria, yeast, and mammalian cell cultures. In recent years, the versatility of the nematode C. elegans to study DNA damage response (DDR mechanisms including NER has become increasingly clear. In particular, C. elegans seems to be a convenient tool to study NER during the UV response in vivo, to analyze this process in the context of a developing and multicellular organism, and to perform genetic screening. Here, we will discuss current knowledge gained from the use of C. elegans to study NER and the response to UV-induced DNA damage.

  2. Low molecular weight heparin impairs tendon repair.

    Virchenko, O; Aspenberg, P; Lindahl, T L


    Thrombin has many biological properties similar to those of growth factors. In a previous study, we showed that thrombin improves healing of the rat tendo Achillis. Low molecular weight heparin (LMWH) inhibits the activity and the generation of thrombin. We therefore considered that LMWH at a thromboprophylactic dose might inhibit tendon repair. Transection of the tendo Achillis was carried out in 86 rats and the healing tested mechanically. Low molecular weight heparin (dalateparin) was either injected a few minutes before the operation and then given continuously with an osmotic mini pump for seven days, or given as one injection before the operation. In another experiment ,we gave LMWH or a placebo by injection twice daily. The anti-factor Xa activity was analysed. Continuous treatment with LMWH impaired tendon healing. After seven days, this treatment caused a 33% reduction in force at failure, a 20% reduction in stiffness and a 67% reduction in energy uptake. However, if injected twice daily, LMWH had no effect on tendon healing. Anti-factor Xa activity was increased by LMWH treatment, but was normal between intermittent injections. Low molecular weight heparin delays tendon repair if given continuously, but not if injected intermittently, probably because the anti-factor Xa activity between injections returns to normal, allowing sufficient thrombin stimulation for repair. These findings indicate the need for caution in the assessment of long-acting thrombin and factor Xa inhibitors.

  3. How to repair an episiotomy.

    Steen, Mary; Cummins, Bernie


    Rationale and key points Skilful repair of an episiotomy is an important aspect of maternal health care. It is essential that midwives and doctors have the knowledge and skills to undertake this procedure in a safe and effective manner. ▶ An episiotomy should be repaired promptly to reduce blood loss and prevent infection. ▶ Repair of an episiotomy is undertaken in three stages: repair of the vaginal mucosa, repair of the muscle layer and repair of the skin layer. ▶ Adequate pain relief should be provided before suturing. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. Why a rectal examination is recommended before and following repair of an episiotomy. 2. What you would do to improve your suturing skills. 3. The factors that may prevent or delay an episiotomy from healing. Subscribers can upload their reflective accounts at .

  4. DNA repair in Chromobacterium violaceum.

    Duarte, Fábio Teixeira; Carvalho, Fabíola Marques de; Bezerra e Silva, Uaska; Scortecci, Kátia Castanho; Blaha, Carlos Alfredo Galindo; Agnez-Lima, Lucymara Fassarella; Batistuzzo de Medeiros, Silvia Regina


    Chromobacterium violaceum is a Gram-negative beta-proteobacterium that inhabits a variety of ecosystems in tropical and subtropical regions, including the water and banks of the Negro River in the Brazilian Amazon. This bacterium has been the subject of extensive study over the last three decades, due to its biotechnological properties, including the characteristic violacein pigment, which has antimicrobial and anti-tumoral activities. C. violaceum promotes the solubilization of gold in a mercury-free process, and has been used in the synthesis of homopolyesters suitable for the production of biodegradable polymers. The complete genome sequence of this organism has been completed by the Brazilian National Genome Project Consortium. The aim of our group was to study the DNA repair genes in this organism, due to their importance in the maintenance of genomic integrity. We identified DNA repair genes involved in different pathways in C. violaceum through a similarity search against known sequences deposited in databases. The phylogenetic analyses were done using programs of the PHILYP package. This analysis revealed various metabolic pathways, including photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, recombinational repair, and the SOS system. The similarity between the C. violaceum sequences and those of Neisserie miningitidis and Ralstonia solanacearum was greater than that between the C. violaceum and Escherichia coli sequences. The peculiarities found in the C. violaceum genome were the absence of LexA, some horizontal transfer events and a large number of repair genes involved with alkyl and oxidative DNA damage.

  5. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...


    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a... killing or growth inhibition of repair deficient bacteria in a set of repair proficient and deficient...

  6. DNA repair: a changing geography? (1964-2008).

    Maisonobe, Marion; Giglia-Mari, Giuseppina; Eckert, Denis


    This article aims to explain the current state of DNA Repair studies' global geography by focusing on the genesis of the community. Bibliometric data is used to localize scientific activities related to DNA Repair at the city level. The keyword "DNA Repair" was introduced first by American scientists. It started to spread after 1964 that is to say, after P. Howard-Flanders (Yale University), P. Hanawalt (Stanford University) and R. Setlow (Oak Ridge Laboratories) found evidence for Excision Repair mechanisms. It was the first stage in the emergence of an autonomous scientific community. In this article, we will try to assess to what extent the geo-history of this scientific field is determinant in understanding its current geography. In order to do so, we will localize the places where the first "DNA Repair" publications were signed fifty years ago and the following spatial diffusion process, which led to the current geography of the field. Then, we will focus on the evolution of the research activity of "early entrants" in relation to the activity of "latecomers". This article is an opportunity to share with DNA Repair scientists some research results of a dynamic field in Science studies: spatial scientometrics.

  7. Bone repair and stem cells.

    Ono, Noriaki; Kronenberg, Henry M


    Bones are an important component of vertebrates; they grow explosively in early life and maintain their strength throughout life. Bones also possess amazing capabilities to repair-the bone is like new without a scar after complete repair. In recent years, a substantial progress has been made in our understanding on mammalian bone stem cells. Mouse genetic models are powerful tools to understand the cell lineage, giving us better insights into stem cells that regulate bone growth, maintenance and repair. Recent findings about these stem cells raise new questions that require further investigations.

  8. Repairing and Upgrading Your PC

    Thompson, Robert


    Repairing and Upgrading Your PC delivers start-to-finish instructions, simple enough for even the most inexperienced PC owner, for troubleshooting, repairing, and upgrading your computer. Written by hardware experts Robert Bruce Thompson and Barbara Fritchman Thompson, this book covers it all: how to troubleshoot a troublesome PC, how to identify which components make sense for an upgrade, and how to tear it all down and put it back together. This book shows how to repair and upgrade all of your PC's essential components.

  9. Laparoscopic repair of incisional hernia.

    Lau, H; Lee, F; Patil, N G


    A 75-year-old man developed an incisional hernia over the upper abdomen following a wedge resection of a gastric stromal tumour in 1996. This is the first published report of a successful repair of an incisional hernia via a laparoscopic intraperitoneal on-lay technique using GORE-TEX DualMesh material in Hong Kong. Compared with conventional open repair of incisional hernia, long incisions and wound tension are avoided using the laparoscopic approach. This translates into a reduced risk of wound-related complications and facilitates recovery. In selected cases, minimally invasive surgery is a safe technique for the repair of incisional hernias.

  10. [Inguinal and femoral hernia repair].

    Geissler, B; Anthuber, M


    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.

  11. Identification of novel DNA repair proteins via primary sequence, secondary structure, and homology

    Akutsu Tatsuya


    Full Text Available Abstract Background DNA repair is the general term for the collection of critical mechanisms which repair many forms of DNA damage such as methylation or ionizing radiation. DNA repair has mainly been studied in experimental and clinical situations, and relatively few information-based approaches to new extracting DNA repair knowledge exist. As a first step, automatic detection of DNA repair proteins in genomes via informatics techniques is desirable; however, there are many forms of DNA repair and it is not a straightforward process to identify and classify repair proteins with a single optimal method. We perform a study of the ability of homology and machine learning-based methods to identify and classify DNA repair proteins, as well as scan vertebrate genomes for the presence of novel repair proteins. Combinations of primary sequence polypeptide frequency, secondary structure, and homology information are used as feature information for input to a Support Vector Machine (SVM. Results We identify that SVM techniques are capable of identifying portions of DNA repair protein datasets without admitting false positives; at low levels of false positive tolerance, homology can also identify and classify proteins with good performance. Secondary structure information provides improved performance compared to using primary structure alone. Furthermore, we observe that machine learning methods incorporating homology information perform best when data is filtered by some clustering technique. Analysis by applying these methodologies to the scanning of multiple vertebrate genomes confirms a positive correlation between the size of a genome and the number of DNA repair protein transcripts it is likely to contain, and simultaneously suggests that all organisms have a non-zero minimum number of repair genes. In addition, the scan result clusters several organisms' repair abilities in an evolutionarily consistent fashion. Analysis also identifies several

  12. Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

    Gao, Min; Wei, Wei; Li, Ming Hua


    DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute...... (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian...

  13. Functions and Dynamics of DNA Repair Proteins in Mitosis and Meiosis

    E.J. Uringa


    textabstractMy PhD project encompassed studies on the functions of several different proteins, all involved in DNA repair, in somatic and germ-line cells. Hr6b and Rad18Sc are involved in a DNA repair mechanism called ‘Replicative Damage Bypass’ (RDB), and function as ubiquitin conjugating enzym

  14. Cloning and characterization of the human DNA-excision repair gene ERCC-1

    M. van Duin (Michel)


    textabstractIt is the aim of the work described in this thesis to isolate and characterize human genes involved DNA excision repair. This will facilitate the understanding of the mechanism of this repair process whereas it also provides an important step to better understand the relationship

  15. Cloning and characterization of the human DNA-excision repair gene ERCC-1

    M. van Duin (Michel)


    textabstractIt is the aim of the work described in this thesis to isolate and characterize human genes involved DNA excision repair. This will facilitate the understanding of the mechanism of this repair process whereas it also provides an important step to better understand the relationship between

  16. Large myelomeningocele repair

    Farideh Nejat


    Full Text Available Background: Wound closure is accomplished in most cases of myelomeningocele (MMC by undermining of the skin edges surrounding the defect. However, large defects cannot be closed reliably by this simple technique. Due to the technical challenge associated with large MMC, surgeons have devised different methods for repairing large defects. In this paper, we report our experience of managing large defects, which we believe bears a direct relationship to decrease the incidence of wound complications. Materials and Methods: Forty children with large MMCs underwent surgical repair and represent our experience. We recommend using all hairy skin around the defect as a way to decrease the tension on the edges of the wound and the possible subsequent necrosis. It is our experience that vertical incision on one or two flanks parallel to the midline can decrease the tension of the wound. Moreover, ventriculo-peritoneal shunting for children who developed hydrocephalus was performed simultaneously, which constitutes another recommendation for preventing fluid collection and build up of pressure on the wound. Results: Patients in this study were in the age range of 2 days to 8 years. The most common location of MMC was in the thoracolumbar area. All but four patients had severe weakness in lower extremities. We used as much hairy skin around the MMC sac as possible in all cases. Vertical incisions on one or both flanks and simultaneous shunt procedure were performed in 36 patients. We treated children with large MMC defects with acceptable tension-free closure. Nonetheless, three patients developed superficial skin infection and partial wound dehiscence, and they were managed conservatively. Conclusions: We recommend using all hairy skin around the MMC defect for closure of large defects. In cases that were expected to be at a higher risk to develop dehiscence release incisions on one or two flanks towards the fascia were found to be useful. Simultaneous

  17. Parametric studies on self-repairing approaches for resin infused composites subjected to low velocity impact

    Motuku, M.; Vaidya, U. K.; Janowski, G. M.


    Low velocity impact response of glass reinforced polymer composites, which have the potential to self-repair both micro- and macro-damage, has been investigated. This class of material falls under the category of passive smart polymer composites. The self-repairing mechanism is achieved through the incorporation of hollow fibers in addition to the normal solid reinforcing fibers. The hollow fibers store the damage-repairing solution or chemicals that are released into the matrix or damaged zone upon fiber failure. Plain-weave S-2 glass fabric reinforcement, vinyl ester 411-C50 and EPON-862 epoxy resin systems were considered for this study. Different tubing materials were investigated for potential use as storage materials for the repairing chemicals instead of the actual hollow repair fibers and included borosilicate glass micro-capillary pipets, flint glass pasteur pipets, copper tubing and aluminum tubing. composite panels were fabricated by using a vacuum assisted resin transfer molding process. The present investigation addressed fabrication of self-repairing composite panels and some of the parameters that influence the response of self-repairing composites to impact loading. Specific issues addressed by this study include: the processing quality; the selection of storage material for the repairing solution; release and transportation of the repairing solution; the effect of the number, type and spatial distribution of the repairing tubes, specimen thickness, matrix material and impact energy level.

  18. Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

    Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki


    Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability.

  19. A Two-Unit Cold Standby Repairable System with One Replaceable Repair Facility and Delay Repair:Some Reliability Problems

    WEI Ying-yuan; TANG Ying-hui


    This paper considers a two-unit same cold standby repairable system with a replaceable repair facility and delay repair .The failure time of unit is assumed to follow exponential distribution , and the repair time and delay time of failed unit are assumed to follow arbitrary distributions , whereas the failure and replacement time distributions of the repair facility are exponential and arbitrary . By using the Markov renewal process theory, some primary reliability quantities of the system are obtained.

  20. 40 CFR 63.1024 - Leak repair.


    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical, but not later than 15...

  1. 40 CFR 65.105 - Leak repair.


    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Leak repair. 65.105 Section 65.105... FEDERAL AIR RULE Equipment Leaks § 65.105 Leak repair. (a) Leak repair schedule. The owner or operator shall repair each leak detected as soon as practical but not later than 15 calendar days after it...

  2. 40 CFR 63.1005 - Leak repair.


    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Leak repair. 63.1005 Section 63.1005... Standards for Equipment Leaks-Control Level 1 § 63.1005 Leak repair. (a) Leak repair schedule. The owner...

  3. Excision repair of UV radiation-induced DNA damage in Caenorhabditis elegans

    Hartman, P.S.; Hevelone, J.; Dwarakanath, V.; Mitchell, D.L. (Texas Christian Univ., Fort Worth (USA))


    Radioimmunoassays were used to monitor the removal of antibody-binding sites associated with the two major UV radiation-induced DNA photoproducts (cyclobutane dimers and (6-4) photoproducts). Unlike with cultured human cells, where (6-4) photoproducts are removed more rapidly than cyclobutane dimers, the kinetics of repair were similar for both lesions. Repair capacity in wild type diminished throughout development. The radioimmunoassays were also employed to confirm the absence of photoreactivation in C. elegans. In addition, three radiation-sensitive mutants (rad-1, rad-2, rad-7) displayed normal repair capacities. An excision defect was much more pronounced in larvae than embryos in the fourth mutant tested (rad-3). This correlates with the hypersensitivity pattern of this mutant and suggests that DNA repair may be developmentally regulated in C. elegans. The mechanism of DNA repair in C. elegans as well as the relationship between the repair of specific photoproducts and UV radiation sensitivity during development are discussed.

  4. Combinations of resting RSA and RSA reactivity impact maladaptive mood repair and depression symptoms

    Yaroslavsky, Ilya; Bylsma, Lauren M.; Rottenberg, Jonathan; Kovacs, Maria


    We examined whether the combined indices of respiratory sinus arrhythmia at rest (resting RSA) and in response to a sad film (RSA reactivity) predict effective and ineffective responses to reduce sadness (adaptive vs. maladaptive mood repair) in women with histories of juvenile-onset depression (n = 74) and no history of major mental disorders (n = 75). Structural equation models were used to estimate latent resting RSA, depression, and adaptive and maladaptive mood repair and to test the study hypotheses. Results indicated that combinations of resting RSA+RSA reactivity (RSA patterns) predicted maladaptive mood repair, which in turn, mediated the effects of RSA pattern on depression. Further, RSA patterns moderated the depressogenic effects of maladaptive mood repair. RSA patterns were unrelated to adaptive mood repair. Our findings suggest that mood repair is one mechanism through which physiological vulnerabilities adversely affect mental health. PMID:23827087

  5. Current advances in DNA repair: regulation of enzymes and pathways involved in maintaining genomic stability.

    Neher, Tracy M; Turchi, John J


    Novel discoveries in the DNA repair field have lead to continuous and rapid advancement of our understanding of not only DNA repair but also DNA replication and recombination. Research in the field transcends numerous areas of biology, biochemistry, physiology, and medicine, making significant connections across these broad areas of study. From early studies conducted in bacterial systems to current analyses in eukaryotic systems and human disease, the innovative research into the mechanisms of repair machines and the consequences of ineffective DNA repair has impacted a wide scientific community. This Forum contains a select mix of primary research articles in addition to a number of timely reviews covering a subset of DNA repair pathways where recent advances and novel discoveries are improving our understanding of DNA repair, its regulation, and implications to human disease.

  6. Do all hemolytic anemias that occur after mitral valve repair require surgical treatment?

    Gungunes, Askin; Akpinar, Ibrahim; Dogan, Mehmet; Baser, Kazim; Yildirim, Ismail Safa; Haznedaroglu, Ibrahim C


    We report on a 29-year-old woman with severe hemolytic anemia following mitral valve annuloplasty. Although hemolysis due to mechanical prosthetic mitral valve is well recognized, hemolytic anemia associated with mitral valve repair is an uncommon condition. Reoperation may be considered if the patient has serious and persistent anemia. Although valve replacement is suggested to be a unique intervention, it may not be the solution every time because of mechanical effects. Various mechanisms of hemolysis related to mitral valve repair were suggested, but sufficient and precise data is not available. In this case, we tried to emphasize whether all hemolytic anemias that occur after mitral valve repair require surgical treatment.

  7. DNA repair deficiency in neurodegeneration

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.


    : homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage......Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...

  8. Analysis of DNA double-strand break repair pathways in mice

    Brugmans, Linda [Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, PO Box 1738, Rotterdam 3015GE (Netherlands); Kanaar, Roland [Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, PO Box 1738, Rotterdam 3015GE (Netherlands); Department of Radiation Oncology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam (Netherlands); Essers, Jeroen [Department of Cell Biology and Genetics, Erasmus MC, Dr. Molewaterplein 50, PO Box 1738, Rotterdam 3015GE (Netherlands) and Department of Radiation Oncology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam (Netherlands)]. E-mail:


    During the last years significant new insights have been gained into the mechanism and biological relevance of DNA double-strand break (DSB) repair in relation to genome stability. DSBs are a highly toxic DNA lesion, because they can lead to chromosome fragmentation, loss and translocations, eventually resulting in cancer. DSBs can be induced by cellular processes such as V(D)J recombination or DNA replication. They can also be introduced by exogenous agents DNA damaging agents such as ionizing radiation or mitomycin C. During evolution several pathways have evolved for the repair of these DSBs. The most important DSB repair mechanisms in mammalian cells are nonhomologous end-joining and homologous recombination. By using an undamaged repair template, homologous recombination ensures accurate DSB repair, whereas the untemplated nonhomologous end-joining pathway does not. Although both pathways are active in mammals, the relative contribution of the two repair pathways to genome stability differs in the different cell types. Given the potential differences in repair fidelity, it is of interest to determine the relative contribution of homologous recombination and nonhomologous end-joining to DSB repair. In this review, we focus on the biological relevance of DSB repair in mammalian cells and the potential overlap between nonhomologous end-joining and homologous recombination in different tissues.

  9. Construction, repair and maintenance

    Hinger, R. [Terasen Pipelines, Calgary, AB (Canada); Wong, P. [KC Integrity Corp., Calgary, AB (Canada); Yeomans, M.; Glover, A. [TransCanada PipeLines Ltd., Calgary, AB (Canada)


    The presentations by Working Group 4 focused on construction, repair and maintenance of pipelines with particular reference to high-strength steels and their applications for natural gas transmission pipelines. Discussions focused on how technology can be used to provide cost-effective design and construction solutions for long distance pipelines in a manner that does not compromise safety and reliability. The role that carbon plays in increasing the toughness of steel was also discussed. A few fundamental changes in steel production technology and a reduction in carbon content can result in a simultaneous increase in strength and toughness of steels. The cost impact of this technology was summarized. It was concluded that high strength steels offer effective solutions to deliver cost-effective pipelines to transport natural gas from northern basins. This session also presented pipeline routes that transport diluted bitumens from the Athabasca Oil Sands Project and the Muskeg River Mine to upgrader facilities in Alberta. Construction issues included design conservatism, water course crossings, winter construction, winter ditching, and public consultation. Examples of high strength steel pipe applications were also included with reference to experience gained by TransCanada and Corridor Pipeline. tabs., figs.

  10. Laparoscopic repair of postoperative perineal hernia.

    Ryan, Stephen


    Perineal hernias are infrequent complications following abdominoperineal operations. Various approaches have been described for repair of perineal hernias including open transabdominal, transperineal or combined abdominoperineal repairs. The use of laparoscopic transabdominal repair of perineal hernias is not well-described. We present a case report demonstrating the benefits of laparoscopic repair of perineal hernia following previous laparoscopic abdominoperineal resection (APR) using a nonabsorbable mesh to repair the defect. We have demonstrated that the use of laparoscopy with repair of the pelvic floor defect using a non absorbable synthetic mesh offers an excellent alternative with many potential advantages over open transabdominal and transperineal repairs.

  11. Umbilical and epigastric hernia repair.

    Muschaweck, Ulrike


    The repair of umbilical and epigastric hernias still represents a challenge to surgeons. Although a common and relatively simple procedure, there is no exact protocol today on how the repair should be done. The Mayo technique and its alterations could not stand the test of time: a recurrence rate of 20% and higher is not acceptable for any surgical procedure. Although there is no consensus opinion, one thing is clear: the importance of an anatomic repair without tension and without an artificial enlargement of the defect. In 1987 Lichtenstein reported on 6321 cases of herniorraphy with a tension free repair, and in 1994 Stuart reemphasized that special importance in his editorial in the Lancet. A newer study from Brancato and coworkers in Italy also states the advantage of a tension-free prosthetic repair in 16 patients with epigastric hernia. We have gone even further and recommend a tailored-to-the-patient repair using a customized polypropylene mesh and a one-layer running suture. The advantages should be obvious: no artificial creation of an even bigger than original defect, a completely tension-free repair, and little to no recurrence of the hernia. Our results clearly prove that assumption. Moreover, the procedure is extremely safe and complications are very rare and minor. We conclude that using a mesh plug in a customized tension-free repair of umbilical and epigastric hernia shows many advantages over the commonly used methods. And we finally conclude with the words of Albert Einstein: "The only source of knowledge is experience."

  12. Repair Types, Procedures - Part 1


    New Jersey, USA. Repair Types, Procedures – Part I RTO-EN-AVT-156 9 - 19 [5] Drieker R, Botello C, MacBeth S, and Grody J, “Aircraft Battle... MacBeth S, and Grody J, “Aircraft Battle Damage Assessment and Repair (ABDAR), Vol. III: Field Test Report,” AFRL-HE-WP-TR-2002-0039, July 2000. [8

  13. Hand function after nerve repair.

    Lundborg, Göran; Rosén, Birgitta


    Treatment of injuries to major nerve trunks in the hand and upper extremity remains a major and challenging reconstructive problem. Such injuries may cause long-lasting disabilities in terms of lost fine sensory and motor functions. Nowadays there is no surgical repair technique that can ensure recovery of tactile discrimination in the hand of an adult patient following nerve repair while very young individuals usually regain a complete recovery of functional sensibility. Post-traumatic nerve...

  14. Cobbler's technique for Iridodialysis repair

    Surinder Singh Pandav


    Full Text Available We describe a novel “Cobbler's technique” for iridodialysis repair in the right eye of a patient aged 18 years, with a traumatic iridodialysis secondary to open globe injury with an iron rod. Our technique is simple with easy surgical maneuvers, that is, effective for repairing iridodialysis. The “Cobbler's technique” allows a maximally functional and cosmetic result for iridodialysis.

  15. Rehabilitation after Rotator Cuff Repair.

    Nikolaidou, Ourania; Migkou, Stefania; Karampalis, Christos


    Rotator cuff tears are a very common condition that is often incapacitating. Whether non-surgical or surgical, successful management of rotator cuff disease is dependent on appropriate rehabilitation. If conservative management is insufficient, surgical repair is often indicated. Postsurgical outcomes for patients having had rotator cuff repair can be quite good. A successful outcome is much dependent on surgical technique as it is on rehabilitation. Numerous rehabilitation protocols for the management of rotator cuff disease are based primarily on clinical experience and expert opinion. This article describes the different rehabilitation protocols that aim to protect the repair in the immediate postoperative period, minimize postoperative stiffness and muscle atrophy. A review of currently available literature on rehabilitation after arthroscopic rotator cuff tear repair was performed to illustrate the available evidence behind various postoperative treatment modalities. There were no statistically significant differences between a conservative and an accelerated rehabilitation protocol . Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. The currently available literature did not identify any significant differences in functional outcomes and relative risks of re-tears between delayed and early motion in patients undergoing arthroscopic rotator cuff repairs. A gentle rehabilitation protocol with limits in range of motion and exercise times after arthroscopic rotator cuff repair would be better for tendon healing without taking any substantial risks. A close communication between the surgeon, the patient and the physical therapy team is important and should continue throughout the whole recovery process.

  16. Repairing Learned Knowledge Using Experience


    It necessar and Identify by’ 6109h nii be) learning precedent-based learning knowledge repair explanation-based learning near - miss groups 20. ABSTRACT...can a program use explanations to repair a recollection, preventing further misapplication? Near - Miss Groups Isolate Suspicious Relations If a metal...pail differs from a porcelain cup only in the position of handle attachment, then we would say that the pail is a near miss . Unfortunately, there are

  17. Aircraft Metal Skin Repair and Honeycomb Structure Repair; Sheet Metal Work 3: 9857.02.

    Dade County Public Schools, Miami, FL.

    The course helps students determine types of repairs, compute repair sizes, and complete the repair through surface protection. Course content includes goals, specific objectives, protection of metals, repairs to metal skin, and honeycomb structure repair. A bibliography and post-test are appended. A prerequisite for this course is mastery of the…

  18. Scarf Repair of Composite Laminates

    Xie Zonghong


    Full Text Available The use of composite materials, such as carbon-fiber reinforced plastic (CFRP composites, aero-structures has led to an increased need of advanced assembly joining and repair technologies. Adhesive bonded repairs as an alternative to recover full or part of initial strength were investigated. Tests were conducted with the objective of evaluating the effectiveness of techniques used for repairing damage fiber reinforced laminated composites. Failure loads and failure modes were generated and compared with the following parameters: scarf angles, roughness of grind tool and number of external plies. Results showed that scarf angle was the critical parameter and the largest tensile strength was observed with the smallest scarf angle. Besides, the use of external plies at the outer surface could not increase the repairs efficiency for large scarf angle. Preparing the repair surfaces by sanding them with a sander ranging from 60 to 100 grit number had significant effect on the failure load. These results allowed the proposal of design principles for repairing CFRP structures.

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

    Lemaître, Charlène; Soutoglou, Evi


    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.

  20. Aging and DNA repair capability. [Review

    Tice, R R


    A review of the literature on DNA repair processes in relation to aging is presented under the following headings: DNA repair processes; age-related occurrence of unrepaired DNA lesions; DNA repair capability as a function of age; tissue-specific DNA repair capability; acceleration of the aging process by exposure to DNA damaging agents; human genetic syndromes; and longevity and DNA repair processes. (HLW)

  1. Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

    Lavínia Almeida Cruz


    Full Text Available Eukaryotic cells have developed mechanisms to prevent genomic instability, such as DNA damage detection and repair, control of cell cycle progression and cell death induction. The bifunctional compound furocumarin 8-methoxy-psoralen (8-MOP is widely used in the treatment of various inflammatory skin diseases. In this review, we summarize recent data about the role of chromatin remodeling in the repair of DNA damage induced by treatment with 8-methoxypsoralen plus UVA (8-MOP+UVA, focusing on repair proteins in budding yeast Saccharomyces cerevisiae, an established model system for studying DNA repair pathways. The interstrand crosslinks (ICL formed by the 8-MOP+UVA treatment are detrimental lesions that can block transcription and replication, leading to cell death if not repaired. Current data show the involvement of different pathways in ICL processing, such as nucleotide excision repair (NER, base excision repair (BER, translesion repair (TLS and double-strand break repair. 8-MOP+UVA treatment in yeast enhances the expression of genes involved in the DNA damage response, double strand break repair by homologous replication, as well as genes related to cell cycle regulation. Moreover, alterations in the expression of subtelomeric genes and genes related to chromatin remodeling are consistent with structural modifications of chromatin relevant to DNA repair. Taken together, these findings indicate a specific profile in 8-MOP+UVA responses related to chromatin remodeling and DNA repair.

  2. Insights on accelerated skeletal repair in Cushing's disease

    So-Young Kim


    In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.

  3. Industrial Machinery Maintenance and Repair. Florida Vocational Program Guide.

    University of South Florida, Tampa. Dept. of Adult and Vocational Education.

    This vocational program guide is intended to assist in the organization, operation, and evaluation of a program in industrial machinery maintenance and repair in school districts, area vocational centers, and community colleges. The following topics are covered: job duties of millwrights, maintenance mechanics, and machinery erectors; program…

  4. Thermosetting Polymer-Matrix Composites for Strucutral Repair Applications

    Goertzen, William Kirby [Iowa State Univ., Ames, IA (United States)


    Several classes of thermosetting polymer matrix composites were evaluated for use in structural repair applications. Initial work involved the characterization and evaluation of woven carbon fiber/epoxy matrix composites for structural pipeline repair. Cyanate ester resins were evaluated as a replacement for epoxy in composites for high-temperature pipe repair applications, and as the basis for adhesives for resin infusion repair of high-temperature composite materials. Carbon fiber/cyanate ester matrix composites and fumed silica/cyanate ester nanocomposites were evaluated for their thermal, mechanical, viscoelastic, and rheological properties as they relate to their structure, chemistry, and processing characteristics. The bisphenol E cyanate ester under investigation possesses a high glass transition temperature, excellent mechanical properties, and unique ambient temperature processability. The incorporate of fumed silica served to enhance the mechanical and rheological properties of the polymer and reduce thermal expansion without sacrificing glass transition or drastically altering curing kinetics. Characterization of the composites included dynamic mechanical analysis, thermomechanical analysis, differential scanning calorimetry, thermogravimetric analysis, rheological and rheokinetic evaluation, and transmission electron microscopy.

  5. Selective targeting of homologous DNA recombination repair by gemcitabine

    Wachters, FM; van Putten, JWG; Maring, JG; Zdzienicka, MZ; Groen, HJM; Kampinga, HH


    Purpose: Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) is a potent radiosensitizer. The mechanism of dFdC-mediated radiosensitization is yet poorly understood. We recently excluded inhibition of DNA double-strand break (DSB) repair by nonhomologous end-joining (NHEJ) as a means of

  6. Production, Purification, and Characterization of 15N-Labeled DNA Repair Proteins as Internal Standards for Mass Spectrometric Measurements

    Jaruga, Pawel; Nelson, Bryant C.; Lowenthal, Mark S.; Jemth, Ann-Sofie; Loseva, Olga; Coskun, Erdem; Helleday, Thomas


    Oxidatively induced DNA damage is caused in living organisms by a variety of damaging agents, resulting in the formation of a multiplicity of lesions, which are mutagenic and cytotoxic. Unless repaired by DNA repair mechanisms before DNA replication, DNA lesions can lead to genomic instability, which is one of the hallmarks of cancer. Oxidatively induced DNA damage is mainly repaired by base excision repair pathway with the involvement of a plethora of proteins. Cancer tissues develop greater DNA repair capacity than normal tissues by overexpressing DNA repair proteins. Increased DNA repair in tumors that removes DNA lesions generated by therapeutic agents before they became toxic is a major mechanism in the development of therapy resistance. Evidence suggests that DNA repair capacity may be a predictive biomarker of patient response. Thus, knowledge of DNA–protein expressions in disease-free and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. Our laboratory has developed methodologies that use mass spectrometry with isotope dilution for the measurement of expression of DNA repair proteins in human tissues and cultured cells. For this purpose, full-length 15N-labeled analogs of a number of human DNA repair proteins have been produced and purified to be used as internal standards for positive identification and accurate quantification. This chapter describes in detail the protocols of this work. The use of 15N-labeled proteins as internal standards for the measurement of several DNA repair proteins in vivo is also presented. PMID:26791985

  7. 49 CFR 1242.42 - Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired...


    ... 49 Transportation 9 2010-10-01 2010-10-01 false Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits, other casualties and insurance... maintenance, machinery repair, equipment damaged, dismantling retired property, fringe benefits,...

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

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


    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.

  9. Protein damage and repair controlling seed vigor and longevity.

    Ogé, Laurent; Broyart, Caroline; Collet, Boris; Godin, Béatrice; Jallet, Denis; Bourdais, Gildas; Job, Dominique; Grappin, Philippe


    The formation of abnormal isoaspartyl residues derived from aspartyl or asparaginyl residues is a major source of spontaneous protein misfolding in cells. The repair enzyme protein L: -isoaspartyl methyltransferase (PIMT) counteracts such damage by catalyzing the conversion of abnormal isoaspartyl residues to their normal aspartyl forms. Thus, this enzyme contributes to the survival of many organisms, including plants. Analysis of the accumulation of isoaspartyl-containing proteins and its modulation by the PIMT repair pathway, using germination tests, immunodetection, enzymatic assays, and HPLC analysis, gives new insights in understanding controlling mechanisms of seed longevity and vigor.

  10. Inducible repair of oxidative DNA damage in Escherichia coli.

    Demple, B; Halbrook, J

    Hydrogen peroxide is lethal to many cell types, including the bacterium Escherichia coli. Peroxides yield transient radical species that can damage DNA and cause mutations. Such partially reduced oxygen species are occasionally released during cellular respiration and are generated by lethal and mutagenic ionizing radiation. Because cells live in an environment where the threat of oxidative DNA damage is continual, cellular mechanisms may have evolved to avoid and repair this damage. Enzymes are known which evidently perform these functions. We report here that resistance to hydrogen peroxide toxicity can be induced in E. coli, that this novel induction is specific and occurs, in part, at the level of DNA repair.

  11. Vascular smooth muscle progenitor cells: building and repairing blood vessels.

    Majesky, Mark W; Dong, Xiu Rong; Regan, Jenna N; Hoglund, Virginia J


    Molecular pathways that control the specification, migration, and number of available smooth muscle progenitor cells play key roles in determining blood vessel size and structure, capacity for tissue repair, and progression of age-related disorders. Defects in these pathways produce malformations of developing blood vessels, depletion of smooth muscle progenitor cell pools for vessel wall maintenance and repair, and aberrant activation of alternative differentiation pathways in vascular disease. A better understanding of the molecular mechanisms that uniquely specify and maintain vascular smooth muscle cell precursors is essential if we are to use advances in stem and progenitor cell biology and somatic cell reprogramming for applications directed to the vessel wall.

  12. In Vivo Shoulder Function After Surgical Repair of a Torn Rotator Cuff

    Bey, Michael J.; Peltz, Cathryn D.; Ciarelli, Kristin; Kline, Stephanie K.; Divine, George W.; van Holsbeeck, Marnix; Muh, Stephanie; Kolowich, Patricia A.; Lock, Terrence R.; Moutzouros, Vasilios


    Background Surgical repair of a torn rotator cuff is based on the belief that repairing the tear is necessary to restore normal glenohumeral joint (GHJ) mechanics and achieve a satisfactory clinical outcome. Hypothesis Dynamic joint function is not completely restored by rotator cuff repair, thus compromising shoulder function and potentially leading to long-term disability. Study Design Controlled laboratory study and Case series; Level of evidence, 4. Methods Twenty-one rotator cuff patients and 35 control participants enrolled in the study. Biplane radiographic images were acquired bilaterally from each patient during coronal-plane abduction. Rotator cuff patients were tested at 3, 12, and 24 months after repair of a supraspinatus tendon tear. Control participants were tested once. Glenohumeral joint kinematics and joint contact patterns were accurately determined from the biplane radiographic images. Isometric shoulder strength and patient-reported outcomes were measured at each time point. Ultrasound imaging assessed rotator cuff integrity at 24 months after surgery. Results Twenty of 21 rotator cuff repairs appeared intact at 24 months after surgery. The humerus of the patients’ repaired shoulder was positioned more superiorly on the glenoid than both the patients’ contralateral shoulder and the dominant shoulder of control participants. Patient-reported outcomes improved significantly over time. Shoulder strength also increased over time, although strength deficits persisted at 24 months for most patients. Changes over time in GHJ mechanics were not detected for either the rotator cuff patients’ repaired or contralateral shoulders. Clinical outcome was associated with shoulder strength but not GHJ mechanics. Conclusion Surgical repair of an isolated supraspinatus tear may be sufficient to keep the torn rotator cuff intact and achieve satisfactory patient-reported outcomes, but GHJ mechanics and shoulder strength are not fully restored with current

  13. Transcript-RNA-templated DNA recombination and repair.

    Keskin, Havva; Shen, Ying; Huang, Fei; Patel, Mikir; Yang, Taehwan; Ashley, Katie; Mazin, Alexander V; Storici, Francesca


    Homologous recombination is a molecular process that has multiple important roles in DNA metabolism, both for DNA repair and genetic variation in all forms of life. Generally, homologous recombination involves the exchange of genetic information between two identical or nearly identical DNA molecules; however, homologous recombination can also occur between RNA molecules, as shown for RNA viruses. Previous research showed that synthetic RNA oligonucleotides can act as templates for DNA double-strand break (DSB) repair in yeast and human cells, and artificial long RNA templates injected in ciliate cells can guide genomic rearrangements. Here we report that endogenous transcript RNA mediates homologous recombination with chromosomal DNA in yeast Saccharomyces cerevisiae. We developed a system to detect the events of homologous recombination initiated by transcript RNA following the repair of a chromosomal DSB occurring either in a homologous but remote locus, or in the same transcript-generating locus in reverse-transcription-defective yeast strains. We found that RNA-DNA recombination is blocked by ribonucleases H1 and H2. In the presence of H-type ribonucleases, DSB repair proceeds through a complementary DNA intermediate, whereas in their absence, it proceeds directly through RNA. The proximity of the transcript to its chromosomal DNA partner in the same locus facilitates Rad52-driven homologous recombination during DSB repair. We demonstrate that yeast and human Rad52 proteins efficiently catalyse annealing of RNA to a DSB-like DNA end in vitro. Our results reveal a novel mechanism of homologous recombination and DNA repair in which transcript RNA is used as a template for DSB repair. Thus, considering the abundance of RNA transcripts in cells, RNA may have a marked impact on genomic stability and plasticity.

  14. Potential of bacteria-based repair solution as healing agent for porous network concrete

    Wiktor, V.A.C.; Sangadji, S.; Jonkers, H.M.; Schlangen, H.E.J.G.


    Bacterially induced calcium carbonate precipitation has received considerable attention for its potential application in enforcing or repairing construction material. The mechanism of bacterially mediated calcite precipitation in those studies is primarily based on the enzymatic hydrolysis of urea.

  15. Potential of bacteria-based repair solution as healing agent for porous network concrete

    Wiktor, V.A.C.; Sangadji, S.; Jonkers, H.M.; Schlangen, H.E.J.G.


    Bacterially induced calcium carbonate precipitation has received considerable attention for its potential application in enforcing or repairing construction material. The mechanism of bacterially mediated calcite precipitation in those studies is primarily based on the enzymatic hydrolysis of urea.

  16. Dorsal variant blister aneurysm repair.

    Couldwell, William T; Chamoun, Roukoz


    Dorsal variant proximal carotid blister aneurysms are treacherous lesions to manage. It is important to recognize this variant on preoperative angiographic imaging, in anticipation of surgical strategies for their treatment. Strategies include trapping the involved segment and revascularization if necessary. Other options include repair of the aneurysm rupture site directly. Given that these are not true berry aneurysms, repair of the rupture site involves wrapping or clip-grafting techniques. The case presented here was a young woman with a subarachnoid hemorrhage from a ruptured dorsal variant blister aneurysm. The technique used is demonstrated in the video and is a modified clip-wrap technique using woven polyester graft material. The patient was given aspirin preoperatively as preparation for the clip-wrap technique. It is the authors' current protocol to attempt a direct repair with clip-wrapping and leaving artery sacrifice with or without bypass as a salvage therapy if direct repair is not possible. Assessment of vessel patency after repair is performed by intraoperative Doppler and indocyanine green angiography. Intraoperative somatosensory and motor evoked potential monitoring is performed in all cases. The video can be found here:

  17. Occupational injuries in automobile repair workers.

    Vyas, Heer; Das, Subir; Mehta, Shashank


    Mechanics are exposed to varied work stressors such as hot noisy environments, strenuous postures, improperly designed tools and machinery and poor psycho-social environments which may exert an influence on their health and safety. The study aimed to examine the occupational injury patterns and identify work stressors associated with injury amongst automobile mechanics. A descriptive ergonomic checklist and questionnaire on general health and psycho-social issues were administered to male workers (N=153). The relative risk factors and correlation statistics were used to identify the work stressors associated with occupational injury. 63% of the workers reported injuries. Cuts were the chief injuries being reported. Poor work environment, machinery and tool characteristics, suffering from poor health and psycho-social stressors were associated with injury occurrence amongst automobile repair workers.

  18. Ancient bacteria show evidence of DNA repair

    Johnson, Sarah Stewart; Hebsgaard, Martin B; Christensen, Torben R


    Recent claims of cultivable ancient bacteria within sealed environments highlight our limited understanding of the mechanisms behind long-term cell survival. It remains unclear how dormancy, a favored explanation for extended cellular persistence, can cope with spontaneous genomic decay over......-term survival of bacteria sealed in frozen conditions for up to one million years. Our results show evidence of bacterial survival in samples up to half a million years in age, making this the oldest independently authenticated DNA to date obtained from viable cells. Additionally, we find strong evidence...... that this long-term survival is closely tied to cellular metabolic activity and DNA repair that over time proves to be superior to dormancy as a mechanism in sustaining bacteria viability....

  19. Rapid repair of severely earthquake-damaged bridge piers with flexural-shear failure mode

    Sun, Zhiguo; Wang, Dongsheng; Du, Xiuli; Si, Bingjun


    An experimental study was conducted to investigate the feasibility of a proposed rapid repair technique for severely earthquake-damaged bridge piers with flexural-shear failure mode. Six circular pier specimens were first tested to severe damage in flexural-shear mode and repaired using early-strength concrete with high-fluidity and carbon fiber reinforced polymers (CFRP). After about four days, the repaired specimens were tested to failure again. The seismic behavior of the repaired specimens was evaluated and compared to the original specimens. Test results indicate that the proposed repair technique is highly effective. Both shear strength and lateral displacement of the repaired piers increased when compared to the original specimens, and the failure mechanism of the piers shifted from flexural-shear failure to ductile flexural failure. Finally, a simple design model based on the Seible formulation for post-earthquake repair design was compared to the experimental results. It is concluded that the design equation for bridge pier strengthening before an earthquake could be applicable to seismic repairs after an earthquake if the shear strength contribution of the spiral bars in the repaired piers is disregarded and 1.5 times more FRP sheets is provided.

  20. 干细胞在中枢神经系统疾病修复中的机制及应用价值%Mechanism and applied values of neural stem cells in repair of central nevous system diseases

    雷霆; 王煜


    Neural stem cells,which exist in the central nervous system,have the ability of selfrenewal and the potential of multi differentiation.They have broad application prospects in the repair of central nervous system diseases.In this text,the researches and articles about neural stem cells from both at home and abroad in the past few years are summarized.In the field of basic researches,many breakthroughs have been made,such as the characteristics of stem cells,drawing and directional induction differentiation,transplantation and nerve repair functions.With the increasing intention at home on the stem cells application prospect,more and more major basic research project is gradually expanded.In the aspect of clinical studies,due to the cost,market standardization and other causes of many aspects,so in many aspects,domestic research relatively lags in other foreign countries.However,with the development of neural stem cells interest and research in China,a further breakthrough of the clinical transformation and promotion of stem cells therapy will be made.%神经干细胞是存在于中枢神经系统,具有自我更新能力和多向分化潜能的细胞,其在中枢神经系统疾病的修复有着广阔的应用前景.本文就近几年国内外针对神经干细胞的相关研究及文章进行总结,在基础研究方面,干细胞的特性、取材、定向诱导分化、移植以及神经功能修复功能已有很多突破,随着国内对干细胞应用前景的关注,越来越多的重大基础研究项目正逐步展开;在临床研究方面,由于费用、市场规范化等多方面原因,国内研究相对滞后于国外.但是,随着国内对于神经干细胞兴趣及研究不断深入,干细胞的治疗的临床转化及推广将有更进一步突破.

  1. Failure analyses and weld repair of boiler feed water pumps

    Vulpen, R. van [KemaPower Generation, Arnhem (Netherlands)


    During a regular inspection of the Boiler Auxiliaries at one of the Dutch Electricity Production Companies serious cracks were found in the cover and casings of the feed water circulation pumps in two units after 108.000 and 122.000 hours of boiler operation. Kema Laboratories carried out Failure analyses on boat samples at the cracked areas. Corrosion fatigue cracking was found on the inner side of the GS-24CrNiMo325 casing. Shop Weld repairs were carried out using a newly developed mechanized Plasma Welding Technique. The repaired feed water circulation pumps showed no problems alter several years of operation. The costs of repair were substantially lower than the costs of replacement. (orig.) 3 refs.

  2. Repair works at coke ovens lined with refractory mixtures

    Beckmann, R.; Friebe, G.


    The wear characteristics of the usual refractory mixtures are strongly dependent upon the prevailing operating conditions, the location of use within the oven and the temperature range to be expected. As exemplified by typical deteriorations, the suitability of refractory mixtures of aluminium sulphate, water glass, clay, aluminous cement and phosphate basis for various applications is discussed. Structure and bonding mechanisms of the repair mixtures are decisive for application, service time and temperature behaviour. Also pretreatment of the base and proper selection of the application method are important for the success of the repair. The application methods: dusting, spraying, pressure spraying, casting and ramming, are compared based on operating experience. Pressure spraying proved to be a simple and less expensive method for repairing large deteriorations. With sufficient care good success is ensured.

  3. Properties shaping and repair of selected types of cast iron

    J. Szajnar


    Full Text Available The paper presents research results of twofold use of TIG - Tungsten Inert Gas also known as GTA - Gas Tungsten Arc. First is surfacing by welding on cold and hot-cold to repair chromium cast iron with chromium content about 15%. Second is remelting with electric arc of selected gray (with pearlitic matrix and ductile (with ferritic-pearlitic matrix cast iron. Repair of cast iron elements was realized in order to cut out a casting defects. Defects decrease a usability of castings for constructional application and increase a manufacturing costs. Application of surface heat treatment guarantees mechanical properties i.e. hardness and wear resistance improvement. The result of investigations show possibility of castings repair by put on defects a good quality padding welds, which have comparable properties with base material. Use of electric arc surface heat treatment resulted in increase of hardness and wear resistance, which was measured on the basis of ASTM G 65 - 00 standard.

  4. Teaching of direct composite restoration repair in undergraduate dental schools in the United Kingdom and Ireland.

    Blum, I R; Lynch, C D; Wilson, N H F


    To investigate aspects of the teaching of restoration repair as a minimally invasive alternative to the replacement of defective direct composite restorations in teaching programmes in undergraduate curricula in dental schools in the United Kingdom and Ireland. An online questionnaire which sought information in relation to the current teaching of composite restoration repair was developed and distributed to the 17 established UK and Irish dental schools with undergraduate teaching programmes in Spring 2010. Completed responses were received from all 17 schools (response rate= 100%). Fifteen schools reported that they included teaching of repair techniques for defective direct composite restorations in their programme. Of the two remaining schools, one indicated that it would introduce teaching of repair techniques during the next five years. The most common indication for a composite repair was that of 'tooth substance preservation' (15 schools). The defects in restorations considered appropriate for repair rather than replacement by the largest number of schools included partial loss of restoration (13 schools) and marginal defects (12 schools). The most commonly taught surface treatment when performing a repair was mechanical roughening of the existing composite with removal of the surface layer (14 schools). Thirteen schools taught etching and the application of an adhesive bonding agent to the prepared surfaces, while the most commonly taught material for completing the repair was a hybrid composite resin (12 schools). Popular finishing implements included diamond finishing instruments (13 schools) and finishing discs (11 schools). Not withstanding reluctance amongst general dental practitioners, the teaching of repair of a defective composite restoration, rather than total restoration replacement, is firmly established within UK and Irish dental school programmes. Repair techniques have clear advantages for patients, not least including a minimally invasive

  5. Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma

    Koji eYoshimoto


    Full Text Available Many conventional chemotherapeutic drugs exert their cytotoxic function by inducing DNA damage in the tumor cell. Therefore, a cell-inherent DNA repair pathway, which reverses the DNA-damaging effect of the cytotoxic drugs, can mediate therapeutic resistance to chemotherapy. The monofunctional DNA-alkylating agent temozolomide (TMZ is a commonly used chemotherapeutic drug and the gold standard treatment for glioblastoma. Although the activity of DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT has been described as the main modulator to determine the sensitivity of glioblastoma to TMZ, a subset of glioblastoma does not respond despite MGMT inactivation, suggesting that another DNA repair mechanism may also modulate the tolerance to TMZ. Considerable interest has focused on MGMT, mismatch repair (MMR, and the base-excision repair (BER pathway in the mechanism of mediating TMZ resistance, but emerging roles for the DNA strand-break repair pathway have been demonstrated. In the first part of this review article, we briefly review the significant role of MGMT, MMR, and the BER pathway in the tolerance to TMZ; in the last part, we review the recent publications that demonstrate possible roles of DNA strand-break repair pathways, such as single-strand break (SSB repair and double-strand break (DSB repair, as well as the Fanconi anemia pathway in the repair process after alkylating agent-based therapy. It is possible that all of these repair pathways have a potential to modulate the sensitivity to TMZ and aid in overcoming the therapeutic resistance in the clinic.

  6. Repair of sciatic nerve defects using tissue engineered nerves*

    Caishun Zhang; Gang Lv


    In this study, we constructed tissue-engineered nerves with acel ular nerve al ografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cel s of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tis-sue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acel ular nerve al ografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle;regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acel ular nerve al ografts. The hind limb motor function at the affected side was significantly improved, indicating that acel ular nerve al ografts combined with bone marrow me-senchymal stem cel bridging could promote functional recovery of rats with sciatic nerve defects.

  7. Repair integrity monitoring of composite aerostructures using thermographic imaging

    Grammatikos, S.; Kordatos, E.; Barkoula, N.-M.; Matikas, T.; Paipetis, A.


    Bonded repair offers significant advantages over mechanically fastened repair schemes as it eliminates local stress concentrations and seals the interface between the mother structure and the patch. However, it is particularly difficult to assess the efficiency of the bonded repair as well as its performance during service loads. Thermography is a particularly attractive technique for the particular application as it is a non-contact, wide field non destructive method. Phase thermography is also offering the advantage of depth discrimination in layered structures such as in typical patch repairs particularly in the case where composites are used. Lock-in thermography offers the additional advantage of on line monitoring of the loaded structure and subsequently the real time evolution of any progressive debonding which may lead to critical failure of the patched repair. In this study composite systems (CFRP plates) with artificially introduced defects (PTFE) were manufactured. The aforementioned methods were employed in order to assess the efficiency of the thermographic technique. The obtained results were compared with typical C-scans.

  8. Regulation of tissue repair and regeneration by electric fields

    WANG En-tong; ZHAO Min


    Endogenous electric fields(Efs)have been detected at wounds and damaged tissues.The potential roles of Efs in tissue repair and regeneration have been an intriguing topic for centuries.Recent researches have provided significant insights into how naturally occurring Efs may participate in the control of tissue repair and regeneration.Applied Efs equivalent to the size of fields measured in vivo direct cell migration,cell proliferation and nerve sprouting at wounds.More remarkably,physiological Efs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation,wound void,contact inhibition release,population pressure and chemotaxis.Efs activate many intracellular signaling pathways in a directional manner.Modulation of endogenous wound Efs affects epithelial cell migration,cell proliferation,and nerve growth at cornea wounds in vivo.Electric stimulation is being tested clinically for the treatments of bone fracture,wound healing and spinal cord injury.Efs thus may represent a novel type of signaling paradigm in tissue repair and regeneration.Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration.This review introduces experimental evidence for the existence of endogenous Efs and discusses their roles in tissue repair and regeneration.

  9. Regulation of tissue repair and regeneration by electric fields.

    Wang, En-tong; Zhao, Min


    Endogenous electric fields (EFs) have been detected at wounds and damaged tissues. The potential roles of EFs in tissue repair and regeneration have been an intriguing topic for centuries. Recent researches have provided significant insights into how naturally occurring EFs may participate in the control of tissue repair and regeneration. Applied EFs equivalent to the size of fields measured in vivo direct cell migration, cell proliferation and nerve sprouting at wounds. More remarkably, physiological EFs are a guidance cue that directs cell migration which overrides other well accepted directional signals including initial injury stimulation, wound void, contact inhibition release, population pressure and chemotaxis. EFs activate many intracellular signaling pathways in a directional manner. Modulation of endogenous wound EFs affects epithelial cell migration, cell proliferation, and nerve growth at cornea wounds in vivo. Electric stimulation is being tested clinically for the treatments of bone fracture, wound healing and spinal cord injury. EFs thus may represent a novel type of signaling paradigm in tissue repair and regeneration. Combination of the electric stimulation and other well understood biochemical regulatory mechanisms may offer powerful and effective therapies for tissue repair and regeneration. This review introduces experimental evidence for the existence of endogenous EFs and discusses their roles in tissue repair and regeneration.

  10. Molecular Understanding of Efficient DNA Repair Machinery of Photolyase

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


    Photolyases repair the UV-induced pyrimidine dimers in damage DNA with high efficiency, through a cylic light-driven electron transfer radical mechanism. We report here our systematic studies of the repair dynamics in E. coli photolyase with mutation of five active-site residues. The significant loss of repair efficiency by the mutation indicates that those active-site residues play an important role in the DNA repair by photolyase. To understand how the active-site residues modulate the efficiency, we mapped out the entire evolution of each elementary step during the repair in those photolyase mutants with femtosecond resolution. We completely analyzed the electron transfer dynamics using the Sumi-Marcus model. The results suggest that photolyase controls the critical electron transfer and the ring-splitting of pyrimidine dimer through modulation of the redox potentials and reorganization energies, and stabilization of the anionic intermediates, maintaining the dedicated balance of all the reaction steps and achieving the maximum function activity.

  11. Electrosleeve process for in-situ nuclear steam generator repair

    Barton, R.A. [Ontario Hydro Technologies, Toronto, ON (Canada); Moran, T.E. [Framatome Technologies Inc., Lynchburg, VA (United States); Renaud, E. [Babcock and Wilcox Industries Ltd., Cambridge, ON (Canada)


    Degradation of steam generator (SG) tubing by localized corrosion is a widespread problem in the nuclear industry that can lead to costly forced out-ages, unit de-rating, SG replacement or even the permanent shutdown of a reactor. In response to the onset of SG tubing degradation at Ontario Hydro's Pickering Nuclear Generating Station (PNGS) Unit 5, and the determined unsuitability of conventional repair methods (mechanically expanded or welded sleeves) for Alloy 400, an alternative repair technology was developed. Electrosleeve is a non-intrusive, low-temperature process that involves the electrodeposition of a nanocrystalline nickel microalloy forming a continuously bonded, structural layer over the internal diameter of the degraded region. This technology is designed to provide a long-term pressure boundary repair, fully restoring the structural integrity of the damaged region to its original state. This paper describes the Electrosleeve process for SG tubing repair and the unique properties of the advanced sleeve material. The successful installation of Electrosleeves that have been in service for more than three years in Alloy 400 SG tubing at the Pickering-5 CANDU unit, the more recent extension of the technology to Alloy 600 and its demonstration in a U.S. pressurized water reactor (PWR), is presented. A number of PWR operators have requested plant operating technical specification changes to permit Electrosleeve SG tube repair. Licensing of the Electrosleeve by the U.S. Nuclear Regulatory Commission (NRC) is expected imminently. (author)

  12. Suture anchor repair of quadriceps tendon rupture after total knee arthroplasty.

    Kim, Tae Won B; Kamath, Atul F; Israelite, Craig L


    Disruption of the extensor mechanism after total knee arthroplasty (TKA) is a devastating complication, usually requiring surgical repair. Although suture anchor fixation is well described for repair of the ruptured native knee quadriceps tendon, no study has discussed the use of suture anchors in quadriceps repair after TKA. We present an illustrative case of successful suture anchor fixation of the quadriceps mechanism after TKA. The procedure has been performed in a total of 3 patients. A surgical technique and brief review of the literature follows. Suture anchor fixation of the quadriceps tendon is a viable option in the setting of rupture after TKA.

  13. ERCC1-XPF endonuclease facilitates DNA double-strand break repair.

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


    ERCC1-XPF endonuclease is required for nucleotide excision repair (NER) of helix-distorting DNA lesions. However, mutations in ERCC1 or XPF in humans or mice cause a more severe phenotype than absence of NER, prompting a search for novel repair activities of the nuclease. In Saccharomyces cerevisiae, orthologs of ERCC1-XPF (Rad10-Rad1) participate in the repair of double-strand breaks (DSBs). Rad10-Rad1 contributes to two error-prone DSB repair pathways: microhomology-mediated end joining (a Ku86-independent mechanism) and single-strand annealing. To determine if ERCC1-XPF participates in DSB repair in mammals, mutant cells and mice were screened for sensitivity to gamma irradiation. ERCC1-XPF-deficient fibroblasts were hypersensitive to gamma irradiation, and gammaH2AX foci, a marker of DSBs, persisted in irradiated mutant cells, consistent with a defect in DSB repair. Mutant mice were also hypersensitive to irradiation, establishing an essential role for ERCC1-XPF in protecting against DSBs in vivo. Mice defective in both ERCC1-XPF and Ku86 were not viable. However, Ercc1(-/-) Ku86(-/-) fibroblasts were hypersensitive to gamma irradiation compared to single mutants and accumulated significantly greater chromosomal aberrations. Finally, in vitro repair of DSBs with 3' overhangs led to large deletions in the absence of ERCC1-XPF. These data support the conclusion that, as in yeast, ERCC1-XPF facilitates DSB repair via an end-joining mechanism that is Ku86 independent.

  14. Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

    Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.


    Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095

  15. 富血小板血浆修复骨缺损的机制研究进展%Research progress of the mechanism of repairing bone defect with PRP

    陈帅; 张宁; 陈维善; 吴永平


    富血小板血浆(platelet-rich plasma,PRP)是含有高浓度血小板的血浆,其中含丰富的生长因子,广泛应用于口腔颌面外科、骨科,用于骨组织、软骨组织和软组织的修复,其中生长因子对骨修复的多个阶段和多个方面都起作用,以血小板衍化生长因子(PDGF)和转化生长因子-β(TGF-β)的作用最为显著,机制研究也较为透彻.%Platelet-rich plasma (PRP) is a kind of plasma with high concentration of platelet, which includes a lot of growth factors. It was widely used in oral and maxillofacial surgery and orthopedics,for the repairing of bone,cartilage and soft tissues. The growth factors .especially PDGF and TGF-(3,plays an important role in different stages and aspects.

  16. Pulmonary function in automobile repair workers

    Chattopadhyay O


    Full Text Available Background : Automobile repair shop is a place where workers are exposed to harmful chemicals and toxic substances. Objective : To study the occurrence of obstructive and restrictive pulmonary impairment among automobile garage workers. Methods : A cross sectional study involving 151 automobile garage workers from 14 randomly selected garages of urban Kolkata. The study variables were Forced Expiratory Volume in 1 second (FEV 1 , Forced Vital Capacity (FVC, Peak Expiratory Flow Rate (PE FR, age, smoking habit, duration of work, type of work, and respiratory symptoms. The study was analysed using Regression equations, and Chi-square test. Results : All the workers were male. Obstructive impairment was seen in 25.83% of the workers whereas restrictive impairment was seen in 21.19% of the workers. Mixed obstructive and restrictive impairment was seen in 10.6% of the workers. The frequency of obstructive impairment was higher in older workers. In the age group of less than 20 years, 13.6% of the workers had obstructive impairment while 42.86% of workers above 40 years of age had obstructive impairment. Obstructive impairment was more frequently observed in battery repair workers (58.33% and spray painters (37.5% while 16.67% of the body repair workers and 30.19% of the engine mechanics had obstructive impairment. Obstructive impairment was more frequently observed in smokers (53.1 % as compared to ex-smokers (33.3% and non-smokers (6.4%. Obstructive impairment was more frequently observed in workers who had been working for a longer duration. Conclusion: Nearly 36.4% of the automobile garage workers had some form of pulmonary function impairment; obstructive and/or restrictive. The use of personal protective equipment, worker education, and discontinuation of the use of paints containing toxic pigments are recommended.

  17. Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression.

    Yaroslavsky, Ilya; Rottenberg, Jonathan; Bylsma, Lauren M; Jennings, J Richard; George, Charles; Baji, Ildikó; Benák, István; Dochnal, Roberta; Halas, Kitti; Kapornai, Krisztina; Kiss, Enikő; Makai, Attila; Varga, Hedvig; Vetró, Ágnes; Kovacs, Maria


    Depressive disorders that onset in the juvenile years have been linked to far-reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n = 210) and emotionally healthy peers (n = 161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair.

  18. 基于SSA修复机制和特异性核酸酶活性检测的双荧光报告载体系统的开发及应用%Development and application of dual-fluorescence reporter systems for measuring specific nuclease activity based on SSA repair mechanism

    韩芙蓉; 王令; 徐坤; 张智英; 王昕


    报告载体系统因构建快捷、改造简单、操作容易、经济有效,并且能通过介导筛选核酸酶阳性细胞富集基因组修饰的阳性细胞克隆,而成为特异性核酸酶活性检测的重要手段。基于非同源末端连接(Non-homologous end joining,NHEJ)修复机制的报告系统在引入DNA双链断裂(Double strand breaks,DSBs)后,经过优化最高也只有2/3的概率实现报告基因的修复;而单链退火(Single strand annealing,SSA)修复机制在引入DSBs后,理论上可以实现报告基因100%的修复,具有更高的灵敏度,有利于活性较低的特异性核酸酶活性的检测,为基因组修饰研究中特异性核酸酶活性的检测提供了有效的手段。本研究设计并构建了3套基于 SSA 修复机制的双荧光报告载体系统,并应用mRFP-eGFP系统检测了3对ZFNs的有效活性,其活性检测结果分别为8.9%、9.3%和5.0%,该研究为核酸酶活性的检测提供了有效的手段。%Reporter vector system has become an important method for measuring activity of specific nucleas-es because of its fast construction, simple modification, easy operation, economic effectiveness as well as its role in enriching positive cells with genomic modification through mediating screen of specific nucleases positive cells. After in-troducing double strand breaks (DSBs), a reporter system based on non-homologous end joining (NHEJ)-mediated repair can only repair maximally two thirds of reporter genes after optimization, while single strand annealing (SSA)-mediated repair can repair all reporter genes theoretically which has higher sensitivity and facilitates the de-tection of specific nuclease with low activity and provides an effective way to detect specific nuclease activity in genome modification studies. In this study, we designed and constructed three sets of dual-fluorescence reporter systems based on SSA repair mechanism and applied the mRFP-eGFP system in

  19. Nucleotide excision repair in the test tube.

    N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan)


    textabstractThe eukaryotic nucleotide excision-repair pathway has been reconstituted in vitro, an achievement that should hasten the full enzymological characterization of this highly complex DNA-repair pathway.

  20. Biological Augmentation of Rotator Cuff Tendon Repair

    Kovacevic, David; Rodeo, Scott A


    A histologically normal insertion site does not regenerate following rotator cuff tendon-to-bone repair, which is likely due to abnormal or insufficient gene expression and/or cell differentiation at the repair site...

  1. Cleft lip and palate repair - discharge

    ... this page: // Cleft lip and palate repair - discharge To use the sharing ... Elsevier Saunders; 2015:chap 8. Read More Cleft lip and palate Cleft lip and palate repair Review Date 5/9/ ...

  2. Abdominal aortic aneurysm repair - open - discharge

    ... this page: // Abdominal aortic aneurysm repair - open - discharge To use the sharing features ... References Orandi BJ, Black JH. Open repair of abdominal aortic aneurysms. In: Cameron JL, Cameron AM, eds. Current Surgical ...

  3. Biomolecular Simulation of Base Excision Repair and Protein Signaling

    Straatsma, TP; McCammon, J A; Miller, John H; Smith, Paul E; Vorpagel, Erich R; Wong, Chung F; Zacharias, Martin W


    The goal of the Biomolecular Simulation of Base Excision Repair and Protein Signaling project is to enhance our understanding of the mechanism of human polymerase-β, one of the key enzymes in base excision repair (BER) and the cell-signaling enzymes cyclic-AMP-dependent protein kinase. This work used molecular modeling and simulation studies to specifically focus on the • dynamics of DNA and damaged DNA • dynamics and energetics of base flipping in DNA • mechanism and fidelity of nucleotide insertion by BER enzyme human polymerase-β • mechanism and inhibitor design for cyclic-AMP-dependent protein kinase. Molecular dynamics simulations and electronic structure calculations have been performed using the computer resources at the Molecular Science Computing Facility at the Environmental Molecular Sciences Laboratory.

  4. Stem cells for brain repair and recovery after stroke.

    Gutiérrez-Fernández, María; Rodríguez-Frutos, Berta; Ramos-Cejudo, Jaime; Otero-Ortega, Laura; Fuentes, Blanca; Díez-Tejedor, Exuperio


    Stroke is a major worldwide cause of death and disability. Currently, intravenous thrombolysis and reperfusion therapies, but not the so-called neuroprotectant drugs, have been shown to be effective for acute ischemic stroke. Thus, new strategies to promote brain plasticity are necessary. Stem cell administration is an attractive future therapeutic approach. Brain protection and repair mechanisms are activated after stroke. This article is focused on the capacity of stem cell-based therapy to enhance this postinfarct brain plasticity and recovery. Future therapeutic considerations and prospects for stroke are discussed. Although cell therapy is promising in stroke treatment, mechanisms of action need to be characterized in detail. Further, the different mechanisms of axonal plasticity and remodeling involucrated in brain repair, not only in the gray but also in white matter, must be investigated through noninvasive techniques, and a multidisciplinary approach is fundamental in this.

  5. ROCLA robots repaired after tough times


    The team of five welders and five mechanics, represented by Pascal Mésenge (right) and Fabrice Multon (left), worked during two week-ends to repair the two ROCLA. At the centre, Oliver Boettcher, technical manager for the robot. The two LHC magnet transport robots ROCLA have recently been repaired after cracks were found in the welds of their load-bearing structure. The Safety Commission suspended the use of one robot and limited the operation conditions of the other. These vehicles are used intensively for the transport of the LHC cryodipoles between the test and the assembly facilities SM18 and SMA18. As a consequence, a speedy solution had to be implemented to minimize the potential disruption to the LHC schedule. Appropriate CERN resources were immediately focused on the problem. As soon as TS/MME had designed a reinforced gantry support, the necessary raw material was ordered. Less than 10 days were required to get the two ROCLA robots operating again. This included 2 full weekends, many extra hours a...

  6. Autonomic Self-Repairing Glassy Materials

    Coillot, D.; Mear, F.O.; Montagne, L. [Univ Lille Nord France, CNRS, Unite Catalyse and Chim Solide, UMR 8181, F-59652 Villeneuve Dascq (France); Podor, R. [CEA Marcoule, CNRS UM2 ENSCM, Inst Chim Separat Marcoule, UMR 5257, 30 (France)


    A new process that enables glassy materials to self-repair from mechanical damage is presented in this paper. Contrary to intrinsic self-healing, which involves overheating to enable crack healing by glass softening, this process is based on an extrinsic effect produced by vanadium boride (VB) particles dispersed within the glass matrix. Self-repair is obtained through the oxidation of VB particles, and thus without the need to increase the operating temperature. The VB healing agent is selected for its capacity to oxidize at a lower temperature than the softening point of the glass. Thermogravimetric analyses indeed show that VB oxidation is rapid and occurs below the glass transition temperature. Solid-state nuclear magnetic resonance spectroscopy indicates that VB is oxidized into V{sub 2}O{sub 5} and B{sub 2}O{sub 3}, which enable the local formation of glass. The autonomic self-healing effect is demonstrated by an in situ experiment visualized using an environmental scanning electron microscope. It is shown that a crack could be healed by the VB oxidation products. (authors)

  7. Strategies for cell engineering in tissue repair.

    Brown, R A; Smith, K D; Angus McGrouther, D


    Cellular and tissue engineering are new areas of research, currently attracting considerable interest because of the remarkable potential they have for clinical application. Some claims have indeed been dramatic, including the possibility of growing complete, artificial organs, such as the liver. However, amid such long-term aspirations there is the very real possibility that small tissues (artificial grafts) may be fabricated in the near future for use in reconstructive surgery. Logically, we should focus on how it is possible to produce modest, engineered tissues for tissue repair. It is evident that strategies to date either depend on innate information within implanted cells, to reform the target tissue or aim to provide appropriate environmental cues or guidance to direct cell behavior. It is argued here that present knowledge of tissue repair biology points us toward the latter approach, providing external cues which will direct how cells should organize the new tissue. This will be particularly true where we need to reproduce microscopic and ultrastructural features of the original tissue architecture. A number of such cues have been identified, and methods are already available, including substrate chemistry, substrate contact guidance, mechanical loading, and biochemical mediators to provide these cues. Examples of these are already being used with some success to control the formation of tissue structures.

  8. Brain repair: cell therapy in stroke

    Kalladka D


    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

  9. Bonded repair of composite aircraft structures: A review of scientific challenges and opportunities

    Katnam, K. B.; Da Silva, L. F. M.; Young, T. M.


    Advanced composite materials have gained popularity in high-performance structural designs such as aerospace applications that require lightweight components with superior mechanical properties in order to perform in demanding service conditions as well as provide energy efficiency. However, one of the major challenges that the aerospace industry faces with advanced composites - because of their inherent complex damage behaviour - is structural repair. Composite materials are primarily damaged by mechanical loads and/or environmental conditions. If material damage is not extensive, structural repair is the only feasible solution as replacing the entire component is not cost-effective in many cases. Bonded composite repairs (e.g. scarf patches) are generally preferred as they provide enhanced stress transfer mechanisms, joint efficiencies and aerodynamic performance. With an increased usage of advanced composites in primary and secondary aerospace structural components, it is thus essential to have robust, reliable and repeatable structural bonded repair procedures to restore damaged composite components. But structural bonded repairs, especially with primary structures, pose several scientific challenges with the current existing repair technologies. In this regard, the area of structural bonded repair of composites is broadly reviewed - starting from damage assessment to automation - to identify current scientific challenges and future opportunities.

  10. Transvesicoscopic Repair of Vesicovaginal Fistula

    R. B. Nerli


    Full Text Available Introduction. Vesicovaginal fistula has been a social and surgical problem for centuries. Many surgical techniques have been developed to correct this abnormality, including transabdominal, transvaginal, and endoscopic approaches. The best approach is probably the one with which the surgeon feels most experienced and comfortable. Laparoscopy has become increasingly popular in urology, reducing the invasiveness of treatment and shortening the period of convalescence. We report our results of transvesicoscopic approach for VVF repair. Materials and Methods. Patients with VVF were offered repair using the transvesicoscopic route. With the patient under general anaesthesia and in modified lithotomy position cystoscopy was performed with gas insufflation. Under cystoscopic guidance the bladder was fixed to anterior abdominal wall and ports inserted into the bladder. The fistula was repaired under endoscopic vision. Results. Four women, who had VVF following abdominal hysterectomy, underwent this procedure. The operating time ranged from 175 to 235 minutes. There was minimal bleeding. Post operative complications included ileus in one and fever in another. No recurrence of VVF was noted in any patient. Conclusions. Transvesicoscopic repair of VVF is feasible, safe, and results in lower morbidity and quicker recovery time.

  11. Small Crater Expedient Repair Test.


    Force Base, New Mexico , October 1975. 3. Rollings, Raymond S., Laboratory Evaluation of Expedient Pavement Repair Materials, CEEDO-TR-7-44, Civil and...blank) APPENDIX A EQUIPMENT PERFORMANCE SP6WCIFICATIONS Performance specit’ications are included i.n tl is appe udi \\ tor the following equipment: 1

  12. Outcome of quadriceps tendon repair.

    Puranik, Gururaj S; Faraj, Adnan


    Complete rupture of the quadriceps tendon is a well-described injury. There is a scarcity of literature relating to the outcome of patients with this injury after surgery. We undertook a retrospective analysis of patients who had surgical repair of their quadriceps tendon at our institution over a 13-year period, totalling 21 patients. Males were more commonly affected, with a male/female ratio of 4:1. The peak incidence was in the sixth decade of life. Assessment consisted of the completion of a functional knee questionnaire and a clinical examination. Symptomatic outcome following surgical repair was good with a mean symptom score generated of 19.16 out of a maximum of 25 using the Rougraff et al scoring system. Most of the patients returned to their pre-injury level of activity. Five degrees deficit and extension lag was present in three patients; these patients had the quadriceps repaired using transosseous sutures. Patients who had direct repair of the tendon using the Bunnell technique had lower Rougraff scores than the rest.

  13. How the Brain Repairs Stuttering

    Kell, Christian A.; Neumann, Katrin; von Kriegstein, Katharina; Posenenske, Claudia; von Gudenberg, Alexander W.; Euler, Harald; Giraud, Anne-Lise


    Stuttering is a neurodevelopmental disorder associated with left inferior frontal structural anomalies. While children often recover, stuttering may also spontaneously disappear much later after years of dysfluency. These rare cases of unassisted recovery in adulthood provide a model of optimal brain repair outside the classical windows of…

  14. Microwave Oven Repair. Teacher Edition.

    Smreker, Eugene

    This competency-based curriculum guide for teachers addresses the skills a technician will need to service microwave ovens and to provide customer relations to help retain the customer's confidence in the product and trust in the service company that performs the repair. The guide begins with a task analysis, listing 20 cognitive tasks and 5…

  15. Pure robotic retrocaval ureter repair

    Ashok k. Hemal


    Full Text Available PURPOSE: To demonstrate the feasibility of pure robotic retrocaval ureter repair. MATERIALS AND METHODS: A 33 year old female presented with right loin pain and obstruction on intravenous urography with the classical "fish-hook" appearance. She was counseled on the various methods of repair and elected to have a robot assisted repair. The following steps are performed during a pure robotic retrocaval ureter repair. The patient is placed in a modified flank position, pneumoperitoneum created and ports inserted. The colon is mobilized to expose the retroperitoneal structures: inferior vena cava, right gonadal vein, right ureter, and duodenum. The renal pelvis and ureter are mobilized and the renal pelvis transected. The ureter is transposed anterior to the inferior vena cava and a pyelopyelostomy is performed over a JJ stent. RESULTS: This patient was discharged on postoperative day 3. The catheter and drain tube were removed on day 1. Her JJ stent was removed at 6 weeks postoperatively. The postoperative intravenous urography at 3 months confirmed normal drainage of contrast medium. CONCLUSION: Pure robotic retrocaval ureter is a feasible procedure; however, there does not appear to be any great advantage over pure laparoscopy, apart from the ergonomic ease for the surgeon as well the simpler intracorporeal suturing.

  16. [Complications of inguinal hernia repair].

    Forte, A; D'Urso, A; Gallinaro, L S; Lo Storto, G; Bosco, M R; Vietri, F; Beltrami, V


    It's shown by literature and confirmed by Author's experience that, on account of the excellent results, prosthetic repair of inguinal hernia is more effective than "conventional" (Bassini, Mc Vay, Shouldice). Between January 1993 and December 2000 were observed 875 patients with inguinal hernia (814 monolateral, 61 bilateral); all patients underwent a Lichtenstein repair both in the primary version and in its variations (internal ring plastic, trasversalis plicate, plug repair). The patients were discharged from hospital within 24 hours after surgery in 90% of cases. No important intraoperative complications were observed; the patients restarting work varied from 3 to 15 days after the discharging in relation to patient anxiety, onset of complications and to the type of work. The complications observed were: urine retention (1.6%), superficial haematoma (1.3%), superficial infection (1%), wound suppuration (0.5%), serous effusion (0.7%), postsurgery pain (2.1%), scrotal edema (1.7%), persistent inguinal neuralgia (0.6), local hypoesthesia (4.3%), ischemical orchitis (0.1%), recurrence (0.2%). In conclusion Authors assert that "tension free" repair allows optimal results both for the surgery point (easiness of the technique, repeatability, less invasivity, scanty incident of recurrences, low frequency of postoperative complications) and in economic terms, allowing an early mobilization of the patients. A further improvement would be obtained with more care in surgical and patient management, with more excellent results.

  17. UV exposed electronically activated damage and photoreactivation repair

    Bohr, Henrik; Malik, Bary


    An investigation of the possible physics underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism is presented in this study. An electronic pathway starting from the initial damage to the final repair process is proposed. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of the thymine 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. Due to energy balance, the process has to involve an electronic excited state (s). The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process, that is, is a radiationless process.

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

    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.

  19. 30 CFR 57.6801 - Vehicle repair.


    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 57.6801 Section 57.6801 Mineral... and Underground § 57.6801 Vehicle repair. Vehicles containing explosive material and oxidizers shall not be taken into a repair garage or shop....

  20. Nationwide prevalence of groin hernia repair

    Burcharth, Jakob; Pedersen, Michael; Bisgaard, Thue;


    Groin hernia repair is a commonly performed surgical procedure in the western world but large-scaled epidemiologic data are sparse. Large-scale data on the occurrence of groin hernia repair may provide further understanding to the pathophysiology of groin hernia development. This study was undert...... was undertaken to investigate the age and gender dependent prevalence of groin hernia repair....

  1. Hand function after nerve repair.

    Lundborg, G; Rosén, B


    Treatment of injuries to major nerve trunks in the hand and upper extremity remains a major and challenging reconstructive problem. Such injuries may cause long-lasting disabilities in terms of lost fine sensory and motor functions. Nowadays there is no surgical repair technique that can ensure recovery of tactile discrimination in the hand of an adult patient following nerve repair while very young individuals usually regain a complete recovery of functional sensibility. Post-traumatic nerve regeneration is a complex biological process where the outcome depends on multiple biological and environmental factors such as survival of nerve cells, axonal regeneration rate, extent of axonal misdirection, type of injury, type of nerve, level of the lesion, age of the patient and compliance to training. A major problem is the cortical functional reorganization of hand representation which occurs as a result of axonal misdirection. Although protective sensibility usually occurs following nerve repair, tactile discriminative functions seldom recover--a direct result of cortical remapping. Sensory re-education programmes are routinely applied to facilitate understanding of the new sensory patterns provided by the hand. New trends in hand rehabilitation focus on modulation of central nervous processes rather than peripheral factors. Principles are being evolved to maintain the cortical hand representation by using the brain capacity for visuo-tactile and audio-tactile interaction for the initial phase following nerve injury and repair (phase 1). After the start of the re-innervation of the hand (phase 2), selective de-afferentation, such as cutaneous anaesthesia of the forearm of the injured hand, allows expansion of the nerve-injured cortical hand representation, thereby enhancing the effects of sensory relearning. Recent data support the view that training protocols specifically addressing the relearning process substantially increase the possibilities for improved

  2. Observation of tendon repair in animal model using second-harmonic-generation microscopy

    Hase, Eiji; Minamikawa, Takeo; Sato, Katsuya; Takahashi, Mitsuhiko; Yasui, Takashi


    Tendon rupture is a trauma difficult to recover the condition before injury. In previous researches, tensile test and staining method have been widely used to elucidate the mechanism of the repair process from the viewpoints of the mechanical property and the histological findings. However, since both methods are destructive and invasive, it is difficult to obtain both of them for the same sample. If both the mechanical property and the histological findings can be obtained from the same sample, one may obtain new findings regarding mechanisms of tendon repairing process. In this paper, we used second-harmonic-generation (SHG) microscopy, showing high selectivity and good image contrast to collagen molecules as well as high spatial resolution, optical three-dimensional sectioning, deep penetration, and without additional staining. Since SHG light intensity sensitively reflects the structural maturity of collagen molecule and its aggregates, it will be a good indicator for the repairing degree of the ruptured tendon. From comparison of SHG images between the 4-weeks-repaired tendon and the sound tendon in the animal model, we confirmed that SHG light intensity of the repaired tendon was significantly lower than that of the sound tendon, indicating that the collagen structure in the repaired tendon is still immature. Furthermore, we performed both SHG imaging and the tensile test for the same sample, and confirmed a correlation between them. This result shows a potential of SHG light for an indicator of the histological and mechanical recovery of the ruptured tendon.


    V. M. Bubnov


    Full Text Available Purpose. The volume of cargo transportation demands the introduction of a new generation of cars that would be able to provide all the needs of carriers. But this is impossible without the implementation of renovation repair facilities with the introduction of new technologies and modernization of the repair process. Repair of rolling stock is a key factor that must proceed with the establishment of new cars, as not all of the inventions may be repaired in car-repair depots, most of which are obsolete. The purpose is to analyze the possibility of increasing the efficiency of the repair process by introducing new repair technologies or improving the existing ones. It will improve not only the quality of the repair, but also its rate. Methodology. Works on improving the designs of freight cars are held by many design organizations in almost all industrialized countries. It makes repair organizations (depots and car-repair plants to upgrade the repair process. Achievements of-this goal is possible by improving the technology renovation and reorganization through the use of flexible flow technologies, which to date are the most effective in the repair of rolling stock. Findings. When performing the analysis it was determined that there are different designs of cars. More of cars are all-purpose and their repair does not cause difficulties for car-repair business. However, the number of specialized cars is also significant, and the technology of their repair should be improved. One of the reasons is that many models, such as tank wagons for the carriage of sulfur, are intended for the carriage of dangerous goods and their failure at the time of motion is not permitted. Originality. Firstly the authors have defined direction at improving technologies of repair specialized cars. Practical value. Actual improvement in the construction of cars is to improve the existing repair facilities. In addition, the repair technology using nowadays when repairing

  4. Targeted gene repair: the ups and downs of a promising gene therapy approach.

    de Semir, David; Aran, Josep M


    As a novel form of molecular medicine based on direct actions over the genes, targeted gene repair has raised consideration recently above classical gene therapy strategies based on genetic augmentation or complementation. Targeted gene repair relies on the local induction of the cell's endogenous DNA repair mechanisms to attain a therapeutic gene conversion event within the genome of the diseased cell. Successful repair has been achieved both in vitro and in vivo with a variety of corrective molecules ranging from oligonucleotides (chimeraplasts, modified single-stranded oligonucleotides, triplex-forming oligonucleotides), to small DNA fragments (small fragment homologous replacement (SFHR)), and even viral vectors (AAV-based). However, controversy on the consistency and lack of reproducibility of early experiments regarding frequencies and persistence of targeted gene repair, particularly for chimeraplasty, has flecked the field. Nevertheless, several hurdles such as inefficient nuclear uptake of the corrective molecules, and misleading assessment of targeted repair frequencies have been identified and are being addressed. One of the key bottlenecks for exploiting the overall potential of the different targeted gene repair modalities is the lack of a detailed knowledge of their mechanisms of action at the molecular level. Several studies are now focusing on the assessment of the specific repair pathway(s) involved (homologous recombination, mismatch repair, etc.), devising additional strategies to increase their activity (using chemotherapeutic drugs, chimeric nucleases, etc.), and assessing the influence of the cell cycle in the regulation of the repair process. Until therapeutic correction frequencies for single gene disorders are reached both in cellular and animal models, precision and undesired side effects of this promising gene therapy approach will not be thoroughly evaluated.

  5. Self-repairable polymeric networks: Synthesis and network design

    Ghosh, Biswajit

    This dissertation describes the design, synthesis and development of a new class of polymeric networks that exhibit self-repairing properties under UV exposure. It consists of two parts: (a) modification and synthesis of oxetane (OXE), and oxolane (OXO) substituted chitosan (CHI) macromonomer, and (b) design, and synthesis of self-repairing polyurethane (PUR) networks consisting of modified chitosan. Unmodified CHI consisting of acetamide (-NHCOCH3), primary hydroxyl (-OH), and amine (-NH2) functional groups were reacted with OXE or OXO compounds under basic conditions in order to substitute the 1° --OH groups, and at the same time, convert -NHCOCH 3 functionalities into -NH2 groups, while maintaining their un-reacted form to generate OXE/OXO-substituted CHI macromonomer. These substituted CHI macromonomers were incorporated within the PUR backbone by reacting with trifunctional isocyanate in the presence of polyethylene glycol (PEG) and dibutyl tin dilaurate catalyst (DBTDL). Utilizing spectroscopic analysis combined with optical microscopy, these studies showed that the kinetics of self-repair depends on the stoichiometry of the individual entities as well as the time required for self-repairing to occur decrease with increasing OXE quantity within the network. Internal reflection infrared imaging (IRIRI) of OXE/OXO-CHI-PUR networks as well as Raman and Fourier transform IR (FT-IR) studies of OXE/OXO-CHI macromonomers revealed that cationic OXE/OXO ring opening, free radical polyurea (PUA)-to-PUR conversion, along with chair-to-boat conformational changes of CHI backbone are responsible for repairing the damaged network. The network remodeling process, investigated by utilizing micro-thermal analyzer (muTA), revealed that mechanical damage generates small fragments or oligomers within the scratch, therefore glass transition temperature (Tg) decreases, and under UV exposure cross-linking reactions propagate from the bottom of the scratch to the top resulting in

  6. Studies on bleomycin-induced repair DNA synthesis in permeable mouse ascites sarcoma cells.



    Full Text Available To study the mechanism of DNA excision repair, a DNA repair system employing permeable mouse sarcoma (SR-C3H/He cells was established and characterized. SR-C3H/He cells were permeabilized with a 0.0175% Triton X-100 solution. The permeable cells were treated with 1 mM ATP and 0.11 mM bleomycin, and then washed thoroughly to remove ATP and bleomycin. Repair DNA synthesis occurred in the bleomycin-damaged, permeable SR-C3H/He cells when incubated with ATP and four deoxyribonucleoside triphosphates. The repair nature of the DNA synthesis was confirmed by the BrdUMP density shift technique, and by the reduced sensitivity of the newly synthesized DNA to Escherichia coli exonuclease III. The DNA synthesis was optimally enhanced by addition of 0.08 M NaCl. Studies using selective inhibitors of DNA synthesis showed that aphidicolin-sensitive DNA polymerase (DNA polymerase alpha and/or delta and DNA polymerase beta were involved in the repair process. The present DNA repair system is thought to be useful to study nuclear DNA damage by bleomycin, removal of the damaged ends by an exonuclease, repair DNA synthesis by DNA polymerases and repair patch ligation by DNA ligase(s.

  7. Deletion-bias in DNA double-strand break repair differentially contributes to plant genome shrinkage.

    Vu, Giang T H; Cao, Hieu X; Reiss, Bernd; Schubert, Ingo


    In order to prevent genome instability, cells need to be protected by a number of repair mechanisms, including DNA double-strand break (DSB) repair. The extent to which DSB repair, biased towards deletions or insertions, contributes to evolutionary diversification of genome size is still under debate. We analyzed mutation spectra in Arabidopsis thaliana and in barley (Hordeum vulgare) by PacBio sequencing of three DSB-targeted loci each, uncovering repair via gene conversion, single strand annealing (SSA) or nonhomologous end-joining (NHEJ). Furthermore, phylogenomic comparisons between A. thaliana and two related species were used to detect naturally occurring deletions during Arabidopsis evolution. Arabidopsis thaliana revealed significantly more and larger deletions after DSB repair than barley, and barley displayed more and larger insertions. Arabidopsis displayed a clear net loss of DNA after DSB repair, mainly via SSA and NHEJ. Barley revealed a very weak net loss of DNA, apparently due to less active break-end resection and easier copying of template sequences into breaks. Comparative phylogenomics revealed several footprints of SSA in the A. thaliana genome. Quantitative assessment of DNA gain and loss through DSB repair processes suggests deletion-biased DSB repair causing ongoing genome shrinking in A. thaliana, whereas genome size in barley remains nearly constant.

  8. 1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report



    This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conference sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.

  9. Future application of e-beam repair tool beyond 3X generation

    Kanamitsu, Shingo; Hirano, Takashi


    Currently, repair technology is one of the key factors in mask making process regarding TAT reduction and yield level enhancement. Since its commercial release EB repair tool has been commonly used for production line and contributed to high quality repair. But it is not guaranteed whether those conventional machines can keep up with future pattern reduction trend or not. In 2Xnm generation node some advanced exposure techniques seem to be adopted and that will inevitably require higher specification of repair machine. A simple lithography simulation predicts 5nm of indispensable repair accuracy for 2Xnm generation pattern. This number implies the necessity of upper class machine. Generally, the error budget of EB repair tool is composed of three to four components, stated another way mechanical stability, electrical (charging) uniformity, process stability, and graphical quality including software ability. If errors from those components are reduced, overall repair accuracy could be better. A suggestion which can improve those errors was issued last year from tool vender including new machine concept. We have conducted several kind of experiment in order to confirm the performance of new machine. In this paper, we will report the result of experiment and consider which part can effectively contribute to repair accuracy. And we have also evaluated its practical utility value for 2Xnm node by verifying actual application of some 3Xnm production masks.


    V. V. Myamlin


    Full Text Available Purpose. The article is aimed to improve the methods of car repair organization using the search of rational structures of flexible flows. Methodology. For operation analyses of the car repair flows the simulation modeling was used. The initial data for random value generation of cars repair duration are the statistical data. They were collected at the existing car repair enterprises. Findings. Obtained results show that at the same amount of modules the flexible repair flow is more efficient. Flexible flow increases the working capacity, improves the removal of cars from one module and reduces car detention time in repair. Originality. There were identified the mechanisms, which allow establishing links between the different structural variants of flexible flow and their operational performance. Concrete data that give a fresh look to the organization of car repair production were obtained. Practical value. These results can be used in designing the new perspective enterprises for car repair and also under reconstruction or expansion of existing enterprises in order to transfer them to the flexible flow. It is recommended to incorporate the obtained results and try to put them into production during designing and construction of new car enterprises.

  11. A symphony on C : orchestrating DNA repair for gene expression via cytosine modification The 2012 IMB Conference: DNA Demethylation, Repair and Beyond Institute of Molecular Biology, Mainz, Germany, 18-21 October 2012

    Rots, Marianne G.; Petersen-Mahrt, Svend K.


    Headline-grabbing attention has been given to DNA demethylation pathways as new epigenetic mechanisms, with reviews and hypotheses outnumbering research papers. As candidate proteins for DNA demethylation include well-known DNA repair enzymes, it was timely to join epigenetics and DNA repair experts

  12. 脊髓发育和损伤修复过程中巢蛋白的作用及机制****%Effect and mechanism of nestin in the spinal cord development and injury repair process

    王诗韵; 张若煜; 刘学红


      背景:巢蛋白作为一种神经元特异标记物,其表达活性在一定程度上反映了脊髓神经细胞增殖、分化、迁移的演变规律。目的:综述巢蛋白的分子结构、生物学功能及其在脊髓发育及损伤修复中的表达分布规律,进而为脊髓损伤后神经干细胞的移植治疗提供前期研究基础。方法:应用计算机检索1990至2012年维普、万方数据库相关文章,检索词为“脊髓,巢蛋白”,并限定文章语言种类为中文。同时计算机检索1990至2012年PubMed和Springer外文电子期刊及电子图书(全文)数据库相关文章,检索词为“spinal cord,nestin”,并限定文章语言种类为English。共检索到文献343篇,最终纳入符合标准的文献35篇。结果与结论:作为神经干细胞的分子标记物之一,巢蛋白在胚胎期呈现时空性表达,与神经前体细胞的发育成熟程度呈反相关,即随着神经细胞分化发育的不断成熟,其表达强度则会逐渐减弱甚至消失。在脊髓损伤等病理情况下,受损组织区内巢蛋白的表达强度和数量能够反映损伤脊髓组织的修复能力。故脊髓组织发育过程中巢蛋白的表达强度、数量及分布现已作为判断脊髓神经细胞发育的一项重要指标,为临床脊髓损伤治疗提供重要前期研究基础。%  BACKGROUND: As a specific marker of neurons, expression activity of Nestin to a certain extent reflects the evolution law of spinal cord nerve cel s’s proliferation, differentiation and migration. OBJECTIVE: To review the molecular structure, biological function, and expression and distribution law of Nestin in spinal cord development and damage repair, then to provide previous research foundation in the transplantation of neural stem cel s after spinal cord injury. METHODS: VIP and Wanfang databases (1990/2012) were retrieved by computer with the key words of “spinal cord, Nestin” in

  13. Age-related neuronal degeneration: complementary roles of nucleotide excision repair and transcription-coupled repair in preventing neuropathology.

    Dick Jaarsma


    Full Text Available Neuronal degeneration is a hallmark of many DNA repair syndromes. Yet, how DNA damage causes neuronal degeneration and whether defects in different repair systems affect the brain differently is largely unknown. Here, we performed a systematic detailed analysis of neurodegenerative changes in mouse models deficient in nucleotide excision repair (NER and transcription-coupled repair (TCR, two partially overlapping DNA repair systems that remove helix-distorting and transcription-blocking lesions, respectively, and that are associated with the UV-sensitive syndromes xeroderma pigmentosum (XP and Cockayne syndrome (CS. TCR-deficient Csa(-/- and Csb(-/- CS mice showed activated microglia cells surrounding oligodendrocytes in regions with myelinated axons throughout the nervous system. This white matter microglia activation was not observed in NER-deficient Xpa(-/- and Xpc(-/- XP mice, but also occurred in Xpd(XPCS mice carrying a point mutation (G602D in the Xpd gene that is associated with a combined XPCS disorder and causes a partial NER and TCR defect. The white matter abnormalities in TCR-deficient mice are compatible with focal dysmyelination in CS patients. Both TCR-deficient and NER-deficient mice showed no evidence for neuronal degeneration apart from p53 activation in sporadic (Csa(-/-, Csb(-/- or highly sporadic (Xpa(-/-, Xpc(-/- neurons and astrocytes. To examine to what extent overlap occurs between both repair systems, we generated TCR-deficient mice with selective inactivation of NER in postnatal neurons. These mice develop dramatic age-related cumulative neuronal loss indicating DNA damage substrate overlap and synergism between TCR and NER pathways in neurons, and they uncover the occurrence of spontaneous DNA injury that may trigger neuronal degeneration. We propose that, while Csa(-/- and Csb(-/- TCR-deficient mice represent powerful animal models to study the mechanisms underlying myelin abnormalities in CS, neuron

  14. Current Biomechanical Concepts for Rotator Cuff Repair


    For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471

  15. Ultrasound determination of rotator cuff tear repairability

    Tse, Andrew K; Lam, Patrick H; Walton, Judie R; Hackett, Lisa


    Background Rotator cuff repair aims to reattach the torn tendon to the greater tuberosity footprint with suture anchors. The present study aimed to assess the diagnostic accuracy of ultrasound in predicting rotator cuff tear repairability and to assess which sonographic and pre-operative features are strongest in predicting repairability. Methods The study was a retrospective analysis of measurements made prospectively in a cohort of 373 patients who had ultrasounds of their shoulder and underwent rotator cuff repair. Measurements of rotator cuff tear size and muscle atrophy were made pre-operatively by ultrasound to enable prediction of rotator cuff repairability. Tears were classified following ultrasound as repairable or irreparable, and were correlated with intra-operative repairability. Results Ultrasound assessment of rotator cuff tear repairability has a sensitivity of 86% (p rotator cuff repairability were tear size (p rotator cuff tear. Conclusions Ultrasound assessment is accurate in predicting rotator cuff tear repairability. Tear size or anteroposterior tear length and age were the best predictors of repairability. PMID:27582996

  16. Minimally disruptive schedule repair for MCM missions

    Molineaux, Matthew; Auslander, Bryan; Moore, Philip G.; Gupta, Kalyan M.


    Mine countermeasures (MCM) missions entail planning and operations in very dynamic and uncertain operating environments, which pose considerable risk to personnel and equipment. Frequent schedule repairs are needed that consider the latest operating conditions to keep mission on target. Presently no decision support tools are available for the challenging task of MCM mission rescheduling. To address this capability gap, we have developed the CARPE system to assist operation planners. CARPE constantly monitors the operational environment for changes and recommends alternative repaired schedules in response. It includes a novel schedule repair algorithm called Case-Based Local Schedule Repair (CLOSR) that automatically repairs broken schedules while satisfying the requirement of minimal operational disruption. It uses a case-based approach to represent repair strategies and apply them to new situations. Evaluation of CLOSR on simulated MCM operations demonstrates the effectiveness of case-based strategy. Schedule repairs are generated rapidly, ensure the elimination of all mines, and achieve required levels of clearance.

  17. Mechanistic Modelling and Bayesian Inference Elucidates the Variable Dynamics of Double-Strand Break Repair


    DNA double-strand breaks are lesions that form during metabolism, DNA replication and exposure to mutagens. When a double-strand break occurs one of a number of repair mechanisms is recruited, all of which have differing propensities for mutational events. Despite DNA repair being of crucial importance, the relative contribution of these mechanisms and their regulatory interactions remain to be fully elucidated. Understanding these mutational processes will have a profound impact on our knowledge of genomic instability, with implications across health, disease and evolution. Here we present a new method to model the combined activation of non-homologous end joining, single strand annealing and alternative end joining, following exposure to ionising radiation. We use Bayesian statistics to integrate eight biological data sets of double-strand break repair curves under varying genetic knockouts and confirm that our model is predictive by re-simulating and comparing to additional data. Analysis of the model suggests that there are at least three disjoint modes of repair, which we assign as fast, slow and intermediate. Our results show that when multiple data sets are combined, the rate for intermediate repair is variable amongst genetic knockouts. Further analysis suggests that the ratio between slow and intermediate repair depends on the presence or absence of DNA-PKcs and Ku70, which implies that non-homologous end joining and alternative end joining are not independent. Finally, we consider the proportion of double-strand breaks within each mechanism as a time series and predict activity as a function of repair rate. We outline how our insights can be directly tested using imaging and sequencing techniques and conclude that there is evidence of variable dynamics in alternative repair pathways. Our approach is an important step towards providing a unifying theoretical framework for the dynamics of DNA repair processes. PMID:27741226

  18. A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

    Pontier, D.B.; Tijsterman, M.


    To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ) o

  19. A robust network of double-strand break repair pathways governs genome integrity during C. elegans development.

    Pontier, D.B.; Tijsterman, M.


    To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ)

  20. Fabrication Flaw Density and Distribution In Repairs to Reactor Pressure Vessel and Piping Welds

    GJ Schuster, FA Simonen, SR Doctor


    The Pacific Northwest National Laboratory is developing a generalized fabrication flaw distribution for the population of nuclear reactor pressure vessels and for piping welds in U.S. operating reactors. The purpose of the generalized flaw distribution is to predict component-specific flaw densities. The estimates of fabrication flaws are intended for use in fracture mechanics structural integrity assessments. Structural integrity assessments, such as estimating the frequency of loss-of-coolant accidents, are performed by computer codes that require, as input, accurate estimates of flaw densities. Welds from four different reactor pressure vessels and a collection of archived pipes have been studied to develop empirical estimates of fabrication flaw densities. This report describes the fabrication flaw distribution and characterization in the repair weld metal of vessels and piping. This work indicates that large flaws occur in these repairs. These results show that repair flaws are complex in composition and sometimes include cracks on the ends of the repair cavities. Parametric analysis using an exponential fit is performed on the data. The relevance of construction records is established for describing fabrication processes and product forms. An analysis of these records shows there was a significant change in repair frequency over the years when these components were fabricated. A description of repair flaw morphology is provided with a discussion of fracture mechanics significance. Fabrication flaws in repairs are characterized using optimized-access, high-sensitivity nondestructive ultrasonic testing. Flaw characterizations are then validated by other nondestructive evaluation techniques and complemented by destructive testing.

  1. Myosin II does not contribute to wound repair in Dictyostelium cells

    Shigehiko Yumura


    Full Text Available Cells are always subjected to mechanical stresses, resulting in wounds of the cell membrane, but cells are able to repair and reseal their wounded membrane. Previous reports have shown that actin and myosin II accumulate around the wound and that the constriction of this purse-string closes the membrane pore. Here, we developed a microsurgical wound assay to assess wound repair in Dictyostelium cells. Fluorescent dye that had been incorporated into the cells leaked out for only 2–3 sec after wounding, and a GFP-derived, fluorescent Ca2+ sensor showed that intracellular Ca2+ transiently increased immediately after wounding. In the absence of external Ca2+, the cell failed to repair itself. During the repair process, actin accumulated at the wounded sites but myosin II did not. The wounds were repaired even in myosin II null cells to a comparable degree as the wild-type cells, suggesting that myosin II does not contribute to wound repair. Thus, the actomyosin purse-string constriction model is not a common mechanism for wound repair in eukaryotic cells, and this discrepancy may arise from the difference in cell size.

  2. Methods of repairing a substrate

    Riedell, James A. (Inventor); Easler, Timothy E. (Inventor)


    A precursor of a ceramic adhesive suitable for use in a vacuum, thermal, and microgravity environment. The precursor of the ceramic adhesive includes a silicon-based, preceramic polymer and at least one ceramic powder selected from the group consisting of aluminum oxide, aluminum nitride, boron carbide, boron oxide, boron nitride, hafnium boride, hafnium carbide, hafnium oxide, lithium aluminate, molybdenum silicide, niobium carbide, niobium nitride, silicon boride, silicon carbide, silicon oxide, silicon nitride, tin oxide, tantalum boride, tantalum carbide, tantalum oxide, tantalum nitride, titanium boride, titanium carbide, titanium oxide, titanium nitride, yttrium oxide, zirconium boride, zirconium carbide, zirconium oxide, and zirconium silicate. Methods of forming the ceramic adhesive and of repairing a substrate in a vacuum and microgravity environment are also disclosed, as is a substrate repaired with the ceramic adhesive.

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

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


    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.

  4. Context-sensitivity in Conversation. Eye gaze and the German Repair Initiator ‘bitte?’ (´pardon?´)

    Egbert, Maria


    Just as turn-taking has been found to be both context-free and context-sensitive (Sacks, Schegloff & Jefferson 1974), the organization of repair is also shown here to be both context-free and context-sensitive. In a comparison of American and German conversation, repair can be shown to be context......-free in that, basically, the same mechanism can be found across these two languages. However, repair is also sensitive to the linguistic inventory of a given language; in German, morphological marking, syntactic constraints, and grammatical congruity across turns are used as interactional resources....... In addition, repair is sensitive to certain characteristics of social situations. The selection of a particular repair initiator, German bitte? ‘pardon?’, indexes that there is no mutual gaze between interlocutors; i.e., there is no common course of action. The selection of bitte? not only initiates repair...

  5. Disruption of microtubule integrity initiates mitosis during CNS repair.

    Bossing, Torsten; Barros, Claudia S; Fischer, Bettina; Russell, Steven; Shepherd, David


    Mechanisms of CNS repair have vital medical implications. We show that traumatic injury to the ventral midline of the embryonic Drosophila CNS activates cell divisions to replace lost cells. A pilot screen analyzing transcriptomes of single cells during repair pointed to downregulation of the microtubule-stabilizing GTPase mitochondrial Rho (Miro) and upregulation of the Jun transcription factor Jun-related antigen (Jra). Ectopic Miro expression can prevent midline divisions after damage, whereas Miro depletion destabilizes cortical β-tubulin and increases divisions. Disruption of cortical microtubules, either by chemical depolymerization or by overexpression of monomeric tubulin, triggers ectopic mitosis in the midline and induces Jra expression. Conversely, loss of Jra renders midline cells unable to replace damaged siblings. Our data indicate that upon injury, the integrity of the microtubule cytoskeleton controls cell division in the CNS midline, triggering extra mitosis to replace lost cells. The conservation of the identified molecules suggests that similar mechanisms may operate in vertebrates.

  6. Suture anchor repair of patellar tendon rupture after total knee arthroplasty.

    Kamath, Atul F; Shah, Roshan P; Summers, Nathan; Israelite, Craig L


    Extensor mechanism disruption after total knee arthroplasty (TKA) is a complex problem that often requires surgical repair for functional deficits. We present a brief technical note on suture anchor fixation of a patellar tendon rupture after TKA. A surgical technique and literature review follows. Although suture anchor fixation is well described for tendinous repairs in other areas of orthopedic surgery, no study has discussed the use of suture anchors in patellar tendon repair after TKA. The technique must be evaluated in more patients with longer follow-up before adoption.

  7. Recent progress with the DNA repair mutants of Chinese hamster ovary cells

    Thompson, L.H.; Salazar, E.P.; Brookman, K.W.; Collins, C.C.; Stewart, S.A.; Busch, D.B.; Weber, C.A.


    Repair deficient mutants of Chinese hamster ovary (CHO) cells are being used to identify human genes that correct the repair defects and to study mechanisms of DNA repair and mutagenesis. Five independent tertiary DNA transformants were obtained from the EM9 mutant. In these clones a human DNA sequence was identified that correlated with the resistance of the cells to CldUrd. After Eco RI digestion, Southern transfer, and hybridization of transformant DNAs with the BLUR-8 Alu family sequence, a common fragment of 25 to 30 kb was present. 37 refs., 4 figs., 3 tabs.

  8. Large Extremity Peripheral Nerve Repair


    IL, Kochevar IE, Redmond RW. Large extremity peripheral nerve repair. Military Health System Research Symposium (MHSRS) Fort Lauderdale, FL. August...some notable discoveries that may impact military health care in the near future. There is a clear need in military medicine to improve outcomes in...membranes or “caul” intact was considered extremely lucky. Children were gifted with life-long happiness , the ability to see spirits, and protection

  9. Shelf Stable Epoxy Repair Adhesive


    manufacturing operations are more efficient , discarding less expired film. Commercial and military aircraft repair operations at Boeing experience very similar...successfully encapsulated at concentrations greater than 50 wt% within four N N = CC Infoscitex Corporation Shelf Stable Epoxy Resin Adhesive WP-1763 8...affects the composition of the encapsulant , which in turn affects the ability of the encapsulant to wet the core phase, the barrier properties of the

  10. Pain after groin hernia repair

    Callesen, T; Bech, K; Nielsen, R


    BACKGROUND: The purpose of the study was to provide a detailed description of postoperative pain after elective day-case open inguinal hernia repair under local anaesthesia. METHODS: This was a prospective consecutive case series study. After 500 hernia operations in 466 unselected patients aged 18...... between types of surgery or hernia. CONCLUSION: Pain remained a problem despite the pre-emptive use of opioids, non-steroidal anti-inflammatory drugs and local anaesthesia, irrespective of surgical technique....

  11. Biologics for tendon repair


    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately,...

  12. Large Extremity Peripheral Nerve Repair


    71. Burman S, Tejwani S, Vemuganti GK. Ophthalmic applications of preserved human amniotic membrane: a review of current indications. Cell Tissue Bank...segmental nerve deficit repair using isograft show the best performing wrap/ fixation method to be sutureless photochemical tissue bonding with the...crosslinked amnion wrap. Autograft is often unavailable in wounded warriors, due to extensive tissue damage and amputation and, importantly, we also

  13. Application of Interfacial Propagation and Kinking Crack Concept to ECC/Concrete Overlay Repair System

    Yaw ChiaHwan


    Full Text Available Research on the application of ultraductile engineered cementitious composite (ECC as overlay in the repair of deteriorated concrete structures is performed in this paper. Also, interfacial crack kinking and trapping mechanism experimentally observed in ECC/concrete overlay repair system are described by comparison of toughness and energy release rate. The mechanism involves cycles of extension, kinking, and arrest of interfacial crack into the overlay. Experimental testing of overlay repair system reveals significant improvements in load carrying capacity and ductility over conventional concrete overlay. The commonly observed overlay system failure mode of delamination or spalling is eliminated when ECC is applied. These failure modes are suppressed when ECC is used as an ideal and durable candidate overlay repair material.

  14. Theoretical study on the detailed repair of O6-methyl guanine to guanine by cysteine

    Ali Ebrahimi; Mostafa Habibi-Khorasani; Shiva Rezazadeh; Roya Behazin; Abolfazl Azizi


    The repair process of O6-methylguanine (O6mG) by cysteine (Cys145) has been studied using the quantum mechanical calculations in the presence of solvent water molecules and also using the polarizable continuum model (PCM). The proton transfer from Cys145 to O6mG, directly and mediated by bridged water molecules, has been considered to investigate the role and the sequence of the proton transfer on the repair process. In both models, the energy barrier of the methyl transfer is reduced when the proton is initially transferred from O6mG to Cys145. In addition, the protonation of N3 and N7 sites of O6mG in the acidic environment facilitates the repair process. Results of this study help to understand repair mechanisms of damaged DNA bases better on the basis of proton transfer between that and nucleic acids.

  15. Revisional laparoscopic parastomal hernia repair.

    Zacharakis, Emmanouil; Shalhoub, Joseph; Selvapatt, Nowlan; Darzi, Ara; Ziprin, Paul


    We herein report a laparoscopically performed re-do operation on a patient who had previously undergone a laparoscopic parastomal hernia repair. We describe the case of a 71-year-old patient who presented within 3 months of her primary laparoscopic parastomal hernia repair with recurrence. On relaparoscopy, dense adhesions to the mesh were found, and the mesh had migrated into the hernia sac. This had allowed loops of small bowel to herniate into the sac. The initial part of the procedure involved the lysis of adhesions. A piece of Gore-Tex DualMesh with a central keyhole and a radial slit was cut so that it could provide at least 3 cm to 5 cm of overlap of the fascial defect. The tails of the mesh were wrapped around the bowel, and the mesh was secured to the margins of the hernia with circumferential metal tacking and 4 transfascial sutures. The patient remains in satisfactory condition and no recurrence or any surgery-related problem has been observed during 8 months of follow-up. Revisional laparoscopic repair of parastomal hernias seems feasible and has been shown to be safe and effective in this case. The success of this approach depends on longer follow-up reports and standardization of the technical elements.

  16. Augmented Reality Repair Guidance System

    Sidharth Bhatia


    Full Text Available The daily life of a common man revolves around various forms of appliances/gadgets he uses throughout the day such as a mobile phone, laptop, printer, microwave oven, washing machine, etc. Although these appliances/gadgets are taken by most of the people for granted, the problem occurs when any of these things do not work as they are expected to. Getting them to the repair shops for every small glitch is expensive as well as time consuming. Although most of the companies which produce these appliances/gadgets do supply them with basic manuals, which deal with how to solve these minor issues, but reading them and at the same time repairing the corresponding appliance/gadget can be a frustrating task at times. These problems can be reduced to a large extent if some kind of live guidance is available. In this paper we propose a method to do so with the help of an augmented reality based system that will guide the user to carry out small scale repair jobs on these gadgets. All that is required is a decent webcam and a computing device, with a processor of 1 GHz or more and a display screen.

  17. Direct Repair without Augmentation of Patellar Tendon Avulsion following TKA

    Ravi Mittal


    Full Text Available Complications involving the extensor mechanism after TKA are potentially disastrous. We are reporting a case of patellar tendon rupture from tibial tuberosity following total knee arthroplasty. We managed it by direct repair with fiberwire using Krackow suture technique without augmentation. Our long term result has been very encouraging. Our method is a safe and better method of management of patellar tendon avulsion following TKA when it happens without any tissue loss.

  18. Direct Repair without Augmentation of Patellar Tendon Avulsion following TKA


    Complications involving the extensor mechanism after TKA are potentially disastrous. We are reporting a case of patellar tendon rupture from tibial tuberosity following total knee arthroplasty. We managed it by direct repair with fiberwire using Krackow suture technique without augmentation. Our long term result has been very encouraging. Our method is a safe and better method of management of patellar tendon avulsion following TKA when it happens without any tissue loss.

  19. Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor Tendon Repairs.

    Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A


    The aim of the study was to compare biomechanical strength, repair times, and repair values for zone II core flexor tendon repairs. A total of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index through small finger and randomized into one of 5 repair groups: 4-stranded cross-stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double-stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided suture). Repairs were measured in situ and their repair times were measured. Tendons were linearly loaded to failure and multiple biomechanical values were measured. The repair value was calculated based on operating room costs, repair times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc statistical analysis were used to compare repair data. The braided cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the 4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to perform. The total repair value was the highest for braided cruciate ( P > .05) compared with all other repairs. Barbed suture did not outperform any repairs in any categories. The braided cruciate was the strongest of the tested flexor tendon repairs. The 2-mm gapping and maximum load to failure for this repair approached similar historical strength of other 6- and 8-stranded repairs. In this study, suture cost was negligible in the overall repair cost and should be not a determining factor in choosing a repair.

  20. Aberrant repair and fibrosis development in skeletal muscle

    Mann Christopher J


    Full Text Available Abstract The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.