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Sample records for distinct repair strategies

  1. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

    Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

  2. Language Repair Strategies in Bilingual Tutoring of Mathematics Word Problems

    ERIC Educational Resources Information Center

    Oliveira, Alandeom W.; Meskill, Carla; Judson, Darlene; Gregory, Karen; Rogers, Patterson; Imperial, Christopher J.; Casler-Failing, Shelli

    2015-01-01

    This study explores the "language repair strategies" (aimed at repairing communication problems) of two bilingual speakers during mathematics word problem tutoring sessions. Bilingual repair was shown to gradually shift from a linguistic to an epistemic focus during problem solving (i.e., communication became more conceptually focused…

  3. Strategies for cell engineering in tissue repair.

    PubMed

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

    1997-01-01

    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.

  4. Strategies for osteochondral repair: Focus on scaffolds

    PubMed Central

    Seo, Seog-Jin; Mahapatra, Chinmaya; Singh, Rajendra K; Knowles, Jonathan C

    2014-01-01

    Interest in osteochondral repair has been increasing with the growing number of sports-related injuries, accident traumas, and congenital diseases and disorders. Although therapeutic interventions are entering an advanced stage, current surgical procedures are still in their infancy. Unlike other tissues, the osteochondral zone shows a high level of gradient and interfacial tissue organization between bone and cartilage, and thus has unique characteristics related to the ability to resist mechanical compression and restoration. Among the possible therapies, tissue engineering of osteochondral tissues has shown considerable promise where multiple approaches of utilizing cells, scaffolds, and signaling molecules have been pursued. This review focuses particularly on the importance of scaffold design and its role in the success of osteochondral tissue engineering. Biphasic and gradient composition with proper pore configurations are the basic design consideration for scaffolds. Surface modification is an essential technique to improve the scaffold function associated with cell regulation or delivery of signaling molecules. The use of functional scaffolds with a controllable delivery strategy of multiple signaling molecules is also considered a promising therapeutic approach. In this review, we updated the recent advances in scaffolding approaches for osteochondral tissue engineering. PMID:25343021

  5. Alternative applications for distinct RNA sequencing strategies

    PubMed Central

    Han, Leng; Vickers, Kasey C.; Samuels, David C.

    2015-01-01

    Recent advances in RNA library preparation methods, platform accessibility and cost efficiency have allowed high-throughput RNA sequencing (RNAseq) to replace conventional hybridization microarray platforms as the method of choice for mRNA profiling and transcriptome analyses. RNAseq is a powerful technique to profile both long and short RNA expression, and the depth of information gained from distinct RNAseq methods is striking and facilitates discovery. In addition to expression analysis, distinct RNAseq approaches also allow investigators the ability to assess transcriptional elongation, DNA variance and exogenous RNA content. Here we review the current state of the art in transcriptome sequencing and address epigenetic regulation, quantification of transcription activation, RNAseq output and a diverse set of applications for RNAseq data. We detail how RNAseq can be used to identify allele-specific expression, single-nucleotide polymorphisms and somatic mutations and discuss the benefits and limitations of using RNAseq to monitor DNA characteristics. Moreover, we highlight the power of combining RNA- and DNAseq methods for genomic analysis. In summary, RNAseq provides the opportunity to gain greater insight into transcriptional regulation and output than simply miRNA and mRNA profiling. PMID:25246237

  6. Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways

    PubMed Central

    Gupta, Richa; Barkan, Daniel; Redelman-Sidi, Gil; Shuman, Stewart; Glickman, Michael S.

    2013-01-01

    Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double-strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in E. coli and constitute the major pathway of error free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error-prone pathway of DSB repair via nonhomologous end-joining (NHEJ) catalyzed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ, and a novel mechanism of single-strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA-independent SSA pathway. In contrast, the mycobacterial helicase-nuclease AdnAB participates in the RecA-dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways. PMID:21219454

  7. Biomaterial-mediated strategies targeting vascularization for bone repair.

    PubMed

    García, José R; García, Andrés J

    2016-04-01

    Repair of non-healing bone defects through tissue engineering strategies remains a challenging feat in the clinic due to the aversive microenvironment surrounding the injured tissue. The vascular damage that occurs following a bone injury causes extreme ischemia and a loss of circulating cells that contribute to regeneration. Tissue-engineered constructs aimed at regenerating the injured bone suffer from complications based on the slow progression of endogenous vascular repair and often fail at bridging the bone defect. To that end, various strategies have been explored to increase blood vessel regeneration within defects to facilitate both tissue-engineered and natural repair processes. Developments that induce robust vascularization will need to consolidate various parameters including optimization of embedded therapeutics, scaffold characteristics, and successful integration between the construct and the biological tissue. This review provides an overview of current strategies as well as new developments in engineering biomaterials to induce reparation of a functional vascular supply in the context of bone repair.

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

    PubMed Central

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

    2014-01-01

    SUMMARY MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection and signaling; yet, how its endo- and exonuclease activities regulate DSB repair by non-homologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here we employed structure-based design with a focused chemical library to discover specific MRE11 endo- or exonuclease inhibitors. With these inhibitors we examined repair pathway choice at DSBs generated in G2 following radiation exposure. Whilst endo- or exonuclease inhibition impairs radiation-induced RPA chromatin binding, suggesting diminished resection, the inhibitors surprisingly direct different repair outcomes. Endonuclease inhibition promotes NHEJ in lieu of HR, whilst exonuclease inhibition confers a repair defect. Collectively, the results describe nuclease-specific MRE11 inhibitors, define distinct nuclease roles in DSB repair, and support a mechanism whereby MRE11 endonuclease initiates resection, thereby licensing HR followed by MRE11 exo and EXO1/BLM bidirectional resection towards and away from the DNA end, which commits to HR. PMID:24316220

  9. Strategies of Repair in EFL Learners' Oral Discourse

    ERIC Educational Resources Information Center

    Rabab'ah, Ghaleb

    2013-01-01

    This study examines how EFL learners in the non-English speaking communities (Jordan and Germany) handle communication in story-retelling, and uncovers the repair strategies, which they deploy in order to overcome communication breakdowns and pass comprehensible messages to their interlocutors. The study also analyzes factors governing the EFL…

  10. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation.

    PubMed

    O'Connell, Grace D; Leach, J Kent; Klineberg, Eric O

    2015-01-01

    The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  11. Tissue Engineering a Biological Repair Strategy for Lumbar Disc Herniation

    PubMed Central

    O'Connell, Grace D.; Leach, J. Kent; Klineberg, Eric O.

    2015-01-01

    Abstract The intervertebral disc is a critical part of the intersegmental soft tissue of the spinal column, providing flexibility and mobility, while absorbing large complex loads. Spinal disease, including disc herniation and degeneration, may be a significant contributor to low back pain. Clinically, disc herniations are treated with both nonoperative and operative methods. Operative treatment for disc herniation includes removal of the herniated material when neural compression occurs. While this strategy may have short-term advantages over nonoperative methods, the remaining disc material is not addressed and surgery for mild degeneration may have limited long-term advantage over nonoperative methods. Furthermore, disc herniation and surgery significantly alter the mechanical function of the disc joint, which may contribute to progression of degeneration in surrounding tissues. We reviewed recent advances in tissue engineering and regenerative medicine strategies that may have a significant impact on disc herniation repair. Our review on tissue engineering strategies focuses on cell-based and inductive methods, each commonly combined with material-based approaches. An ideal clinically relevant biological repair strategy will significantly reduce pain and repair and restore flexibility and motion of the spine. PMID:26634189

  12. Repair Strategies Usage of Primary Elementary ESL Students: Implications for ESL Teachers

    ERIC Educational Resources Information Center

    Cho, Eun Hye; Larke, Patricia J.

    2010-01-01

    Repair strategies are the ways in which students resolve conversational problems in speaking, hearing and understanding. While there is a plethora of research on college and adult students' repair strategies usage, limited research has been done on the repair strategies usage of elementary school students, more specifically, English as a Second…

  13. National symbols and distinctiveness: rhetorical strategies in creating distinct national identities.

    PubMed

    Finell, Eerika; Liebkind, Karmela

    2010-06-01

    The purpose of this study is to examine qualitatively how respondents create national distinctiveness using rhetorical identity strategies in the context of four Finnish national symbols. The data consist of 127 essays written by Finnish secondary school students. Analysis revealed five different strategies used to distinguish between the in-group and the out-group. These strategies differ on two dimensions: the level of polarization, and the extent to which the in-group-out-group relationship is depicted as being active versus passive. Furthermore, the analysis showed that the two dimensions of nationalism, particularism and universalism, have an important role in the differentiation processes and therefore highlighted the importance of taking into consideration ideological issues while studying social identities. The meaning of the contents of national identity in the differentiation processes is also discussed. PMID:19558753

  14. Distinct Neurocognitive Strategies for Comprehensions of Human and Artificial Intelligence

    PubMed Central

    Ge, Jianqiao; Han, Shihui

    2008-01-01

    Although humans have inevitably interacted with both human and artificial intelligence in real life situations, it is unknown whether the human brain engages homologous neurocognitive strategies to cope with both forms of intelligence. To investigate this, we scanned subjects, using functional MRI, while they inferred the reasoning processes conducted by human agents or by computers. We found that the inference of reasoning processes conducted by human agents but not by computers induced increased activity in the precuneus but decreased activity in the ventral medial prefrontal cortex and enhanced functional connectivity between the two brain areas. The findings provide evidence for distinct neurocognitive strategies of taking others' perspective and inhibiting the process referenced to the self that are specific to the comprehension of human intelligence. PMID:18665211

  15. Strategies for Controlled Delivery of Biologics for Cartilage Repair

    PubMed Central

    Lam, Johnny; Lu, Steven; Kasper, F. Kurtis; Mikos, Antonios G.

    2014-01-01

    The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications. PMID:24993610

  16. Distinct fibroblast lineages determine dermal architecture in skin development and repair

    PubMed Central

    Driskell, Ryan R.; Simons, Ben D.; Charalambous, Marika; Ferron, Sacri R.; Herault, Yann; Pavlovic, Guillaume; Ferguson-Smith, Anne C.; Watt, Fiona M.

    2013-01-01

    Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibers of the extracellular matrix (ECM)1. Even within a single tissue fibroblasts exhibit remarkable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different environmental factors. Here we show, using transplantation assays and lineage tracing, that the fibroblasts of skin connective tissue arise from two distinct lineages. One forms the upper dermis, including the dermal papilla that regulates hair growth and the arrector pili muscle (APM), which controls piloerection. The other forms the lower dermis, including the reticular fibroblasts that synthesise the bulk of the fibrillar ECM, and the pre-adipocytes and adipocytes of the hypodermis. The upper lineage is required for hair follicle formation. In wounded adult skin, the initial wave of dermal repair is mediated by the lower lineage and upper dermal fibroblasts are recruited only during re-epithelialisation. Epidermal beta-catenin activation stimulates expansion of the upper dermal lineage, rendering wounds permissive for hair follicle formation. Our findings explain why wounding is linked to formation of ECM-rich scar tissue that lacks hair follicles2-4. They also form a platform for discovering fibroblast lineages in other tissues and for examining fibroblast changes in ageing and disease. PMID:24336287

  17. CHALLENGES AND STRATEGIES IN THE REPAIR OF RUPTURED ANNULUS FIBROSUS

    PubMed Central

    Guterl, Clare C.; See, Eugene Y.; Blanquer, Sebastien B.G.; Pandit, Abhay; Ferguson, Stephen J.; Benneker, Lorin M.; Grijpma, Dirk W.; Sakai, Daisuke; Eglin, David; Alini, Mauro; Iatridis, James C.; Grad, Sibylle

    2013-01-01

    Lumbar discectomy is the surgical procedure most frequently performed for patients suffering from low back pain and sciatica. Disc herniation as a consequence of degenerative or traumatic processes is commonly encountered as the underlying cause for the painful condition. While discectomy provides favourable outcome in a majority of cases, there are conditions where unmet requirements exist in terms of treatment, such as large disc protrusions with minimal disc degeneration; in these cases, the high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniations but otherwise minor degenerative changes. An attractive approach is a tissue-engineered implant that will enable/stimulate the repair of the ruptured annulus. The strategy is to develop three-dimensional scaffolds and activate them by seeding cells or by incorporating molecular signals that enable new matrix synthesis at the defect site, while the biomaterial provides immediate closure of the defect and maintains the mechanical properties of the disc. This review is structured into (1) introduction, (2) clinical problems, current treatment options and needs, (3) biomechanical demands, (4) cellular and extracellular components, (5) biomaterials for delivery, scaffolding and support, (6) pre-clinical models for evaluation of newly developed cell- and material-based therapies, and (7) conclusions. This article highlights that an interdisciplinary approach is necessary for successful development of new clinical methods for annulus fibrosus repair. This will benefit from a close collaboration between research groups with expertise in all areas addressed in this review. PMID:23283636

  18. Novel combination strategies to repair the injured mammalian spinal cord.

    PubMed

    Bunge, Mary Bartlett

    2008-01-01

    Due to the varied and numerous changes in spinal cord tissue following injury, successful treatment for repair may involve strategies combining neuroprotection (pharmacological prevention of some of the damaging intracellular cascades that lead to secondary tissue loss), axonal regeneration promotion (cell transplantation, genetic engineering to increase growth factors, neutralization of inhibitory factors, reduction in scar formation), and rehabilitation. Our goal has been to find effective combination strategies to improve outcome after injury to the adult rat thoracic spinal cord. Combination interventions tested have been implantation of Schwann cells (SCs) plus neuroprotective agents and growth factors administered in various ways, olfactory ensheathing cell (OEC) implantation, chondroitinase addition, or elevation of cyclic AMP. The most efficacious strategy in our hands for the acute complete transection/SC bridge model, including improvement in locomotion [Basso, Beattie, Bresnahan Scale (BBB)], is the combination of SCs, OECs, and chondroitinase administration (BBB 2.1 vs 6.6, 3 times more myelinated axons in the SC bridge, increased serotonergic axons in the bridge and beyond, and significant correlation between the number of bridge myelinated axons and functional improvement). We found the most successful combination strategy for a subacute spinal cord contusion injury (12.5-mm, 10-g weight, MASCIS impactor) to be SCs and elevation of cyclic AMP (BBB 10.4 vs 15, significant increases in white matter sparing, in myelinated axons in the implant, and in responding reticular formation and red and raphe nuclei, and a significant correlation between the number of serotonergic fibers and improvement in locomotion). Thus, in two injury paradigms, these combination strategies as well as others studied in our laboratory have been found to be more effective than SCs alone and suggest ways in which clinical application may be developed. PMID:18795474

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

    PubMed Central

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

    2006-01-01

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

  20. Cellular dynamics of regeneration reveals role of two distinct Pax7 stem cell populations in larval zebrafish muscle repair

    PubMed Central

    Pipalia, Tapan G.; Koth, Jana; Roy, Shukolpa D.; Hammond, Christina L.; Kawakami, Koichi

    2016-01-01

    ABSTRACT Heterogeneity of stem cells or their niches is likely to influence tissue regeneration. Here we reveal stem/precursor cell diversity during wound repair in larval zebrafish somitic body muscle using time-lapse 3D confocal microscopy on reporter lines. Skeletal muscle with incision wounds rapidly regenerates both slow and fast muscle fibre types. A swift immune response is followed by an increase in cells at the wound site, many of which express the muscle stem cell marker Pax7. Pax7+ cells proliferate and then undergo terminal differentiation involving Myogenin accumulation and subsequent loss of Pax7 followed by elongation and fusion to repair fast muscle fibres. Analysis of pax7a and pax7b transgenic reporter fish reveals that cells expressing each of the duplicated pax7 genes are distinctly localised in uninjured larvae. Cells marked by pax7a only or by both pax7a and pax7b enter the wound rapidly and contribute to muscle wound repair, but each behaves differently. Low numbers of pax7a-only cells form nascent fibres. Time-lapse microscopy revealed that the more numerous pax7b-marked cells frequently fuse to pre-existing fibres, contributing more strongly than pax7a-only cells to repair of damaged fibres. pax7b-marked cells are more often present in rows of aligned cells that are observed to fuse into a single fibre, but more rarely contribute to nascent regenerated fibres. Ablation of a substantial portion of nitroreductase-expressing pax7b cells with metronidazole prior to wounding triggered rapid pax7a-only cell accumulation, but this neither inhibited nor augmented pax7a-only cell-derived myogenesis and thus altered the cellular repair dynamics during wound healing. Moreover, pax7a-only cells did not regenerate pax7b cells, suggesting a lineage distinction. We propose a modified founder cell and fusion-competent cell model in which pax7a-only cells initiate fibre formation and pax7b cells contribute to fibre growth. This newly discovered cellular

  1. Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair

    PubMed Central

    Joyce, Eric F.; Pedersen, Michael; Tiong, Stanley; White-Brown, Sanese K.; Paul, Anshu; Campbell, Shelagh D.

    2011-01-01

    Ataxia telangiectasia–mutated (ATM) and ataxia telangiectasia–related (ATR) kinases are conserved regulators of cellular responses to double strand breaks (DSBs). During meiosis, however, the functions of these kinases in DSB repair and the deoxyribonucleic acid (DNA) damage checkpoint are unclear. In this paper, we show that ATM and ATR have unique roles in the repair of meiotic DSBs in Drosophila melanogaster. ATR mutant analysis indicated that it is required for checkpoint activity, whereas ATM may not be. Both kinases phosphorylate H2AV (γ-H2AV), and, using this as a reporter for ATM/ATR activity, we found that the DSB repair response is surprisingly dynamic at the site of DNA damage. γ-H2AV is continuously exchanged, requiring new phosphorylation at the break site until repair is completed. However, most surprising is that the number of γ-H2AV foci is dramatically increased in the absence of ATM, but not ATR, suggesting that the number of DSBs is increased. Thus, we conclude that ATM is primarily required for the meiotic DSB repair response, which includes functions in DNA damage repair and negative feedback control over the level of programmed DSBs during meiosis. PMID:22024169

  2. Interplay between Target Sequences and Repair Pathways Determines Distinct Outcomes of AID-Initiated Lesions.

    PubMed

    Chen, Zhangguo; Eder, Maxwell D; Elos, Mihret T; Viboolsittiseri, Sawanee S; Chen, Xiaomi; Wang, Jing H

    2016-03-01

    Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G mismatches, a rate-limiting step of Ab gene diversification. However, precise mechanisms regulating AID deamination frequency remain incompletely understood. Moreover, it is not known whether different sequence contexts influence the preferential access of mismatch repair or uracil glycosylase (UNG) to AID-initiated U:G mismatches. In this study, we employed two knock-in models to directly compare the mutability of core Sμ and VDJ exon sequences and their ability to regulate AID deamination and subsequent repair process. We find that the switch (S) region is a much more efficient AID deamination target than the V region. Igh locus AID-initiated lesions are processed by error-free and error-prone repair. S region U:G mismatches are preferentially accessed by UNG, leading to more UNG-dependent deletions, enhanced by mismatch repair deficiency. V region mutation hotspots are largely determined by AID deamination. Recurrent and conserved S region motifs potentially function as spacers between AID deamination hotspots. We conclude that the pattern of mutation hotspots and DNA break generation is influenced by sequence-intrinsic properties, which regulate AID deamination and affect the preferential access of downstream repair. Our studies reveal an evolutionarily conserved role for substrate sequences in regulating Ab gene diversity and AID targeting specificity.

  3. Parental Strategies for Knowledge of Adolescents' Friends: Distinct from Monitoring?

    ERIC Educational Resources Information Center

    Bourdeau, Beth; Miller, Brenda A.; Duke, Michael R.; Ames, Genevieve M.

    2011-01-01

    Parental monitoring is defined as a set of behaviors used to gain knowledge about an adolescent's whereabouts, friends and associates, and activities. However, can knowledge of adolescents' whereabouts/activities, and friends all be attained through the same strategies? Or do they require their own strategies? This study used qualitative…

  4. The Use of Non-Verbal Repair Strategies by Children with Autism

    ERIC Educational Resources Information Center

    Keen, Deb

    2005-01-01

    This study examined possible links between the occurrence of prosodic changes to vocalizations and gestures and the use of problem behaviors by children with autism when attempting to repair communication breakdowns. The repair strategies of six children with autism aged 2-5 years and with fewer than 10 words or signs were analyzed. Mother-child…

  5. Burden among male Alzheimer's caregivers: effects of distinct coping strategies.

    PubMed

    Geiger, Jennifer R; Wilks, Scott E; Lovelace, Lauren L; Chen, Zibei; Spivey, Christina A

    2015-05-01

    Focusing on the understudied, increasing population of male Alzheimer's disease (AD) caregivers, the purpose of this study was to identify their likelihood of utilizing 3 coping strategies (task focused, emotion focused, and avoidance focused) and to examine the effects of each coping strategy on caregiving burden. Data were collected from 138 male AD caregivers in southern United States, including geographically proportional representation of African Americans in the sample. Stepwise regression revealed effects of each coping strategy on caregiving burden, controlling for demographics. The sample reported high burden. Task focused was the highest reported coping strategy. Yet, regression models indicated no significant effect of task-focused coping on burden outcomes. Emotion-focused and avoidance-focused coping each showed significant proportional effects on burden. Implications suggest that emotion- and avoidance-focused coping among male AD caregivers may be maladaptive, that is, reinforcing burden. Male AD caregivers may benefit from more task-focused coping, such as planning and active problem solving. PMID:25267930

  6. Teaching VOCA Use as a Communicative Repair Strategy

    ERIC Educational Resources Information Center

    Sigafoos, Jeff; Drasgow, Eric; Halle, James W.; O'Reilly, Mark; Seely-York, Sue; Edrisinha, Chaturi; Andrews, Alonzo

    2004-01-01

    Students with developmental disabilities often rely on prelinguistic behavior (e.g., reaching, leading) to communicate. When listeners fail to attend to prelinguistic behaviors, students may benefit from responding with an alternative form of communication to repair the breakdown. In the present study, we taught two students with developmental…

  7. Multiple Learning Strategies Project. Small Engine Repair. Visually Impaired.

    ERIC Educational Resources Information Center

    Foster, Don; And Others

    This instructional package designed for visually impaired students, focuses on the vocational area of small engine repair. Contained in this document are forty learning modules organized into fourteen units: engine block; starters; fuel tank, lines, filters and pumps; carburetors; electrical; test equipment; motorcycle; machining; tune-ups; short…

  8. Whales use distinct strategies to counteract solar ultraviolet radiation.

    PubMed

    Martinez-Levasseur, Laura M; Birch-Machin, Mark A; Bowman, Amy; Gendron, Diane; Weatherhead, Elizabeth; Knell, Robert J; Acevedo-Whitehouse, Karina

    2013-01-01

    A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies. PMID:23989080

  9. Whales use distinct strategies to counteract solar ultraviolet radiation.

    PubMed

    Martinez-Levasseur, Laura M; Birch-Machin, Mark A; Bowman, Amy; Gendron, Diane; Weatherhead, Elizabeth; Knell, Robert J; Acevedo-Whitehouse, Karina

    2013-01-01

    A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies.

  10. Design of structurally distinct proteins using strategies inspired by evolution.

    PubMed

    Jacobs, T M; Williams, B; Williams, T; Xu, X; Eletsky, A; Federizon, J F; Szyperski, T; Kuhlman, B

    2016-05-01

    Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. We describe a computational protocol, called SEWING, which is inspired by this process and builds new proteins from connected or disconnected pieces of existing structures. Helical proteins designed with SEWING contain structural features absent from other de novo designed proteins and, in some cases, remain folded at more than 100°C. High-resolution structures of the designed proteins CA01 and DA05R1 were solved by x-ray crystallography (2.2 angstrom resolution) and nuclear magnetic resonance, respectively, and there was excellent agreement with the design models. This method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.

  11. Whales Use Distinct Strategies to Counteract Solar Ultraviolet Radiation

    PubMed Central

    Martinez-Levasseur, Laura M.; Birch-Machin, Mark A.; Bowman, Amy; Gendron, Diane; Weatherhead, Elizabeth; Knell, Robert J.; Acevedo-Whitehouse, Karina

    2013-01-01

    A current threat to the marine ecosystem is the high level of solar ultraviolet radiation (UV). Large whales have recently been shown to suffer sun-induced skin damage from continuous UV exposure. Genotoxic consequences of such exposure remain unknown for these long-lived marine species, as does their capacity to counteract UV-induced insults. We show that UV exposure induces mitochondrial DNA damage in the skin of seasonally sympatric fin, sperm, and blue whales and that this damage accumulates with age. However, counteractive molecular mechanisms are markedly different between species. For example, sperm whales, a species that remains for long periods at the sea surface, activate genotoxic stress pathways in response to UV exposure whereas the paler blue whale relies on increased pigmentation as the season progresses. Our study also shows that whales can modulate their responses to fluctuating levels of UV, and that different evolutionary constraints may have shaped their response strategies. PMID:23989080

  12. The behavioral correlates of overall and distinctive life history strategy.

    PubMed

    Sherman, Ryne A; Figueredo, Aurelio José; Funder, David C

    2013-11-01

    Life history (LH) theory provides an evolutionary theoretical framework for understanding individual differences in maturation, mating, reproduction, parenting, and social interaction. However, the psychometric assessment of human life history has been largely limited to generalized self-reports. Using template matching, this article examines the relationship between personality differences associated with slow-life history (slow-LH) and social behavior in 3 archival datasets. Two of these datasets include direct observations of behavior in the laboratory, and the 3rd provides self-reports of behavior in real life situations experienced within the preceding 24 hr. The results paint a consistent picture of the slow-LH individual as engaging in numerous adaptive social behaviors. However, when "normativeness" (the tendency for most people to be normal in both the statistical and evaluative sense) is statistically removed from the LH scores, a slightly different picture emerges. Both slow-LH and fast-LH persons display a number of behaviors that may be either adaptive or maladaptive in different contexts. Specifically, slow-LH individuals tended to behave in a manner that was considerate, kind, hard-working, and reliable but also socially awkward, insecure, and overcontrolling. Fast-LH individuals came across as talkative, socially skilled, dominant, and charming but also unpredictable, hostile, manipulative, and impulsive. These results are consistent with the evolutionary interpretation of LH strategies as being adapted to systematically different environments rather than better or worse approaches to reproductive fitness overall.

  13. Scaffold-based Anti-infection Strategies in Bone Repair

    PubMed Central

    Johnson, Christopher T.; García, Andrés J.

    2014-01-01

    Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field. PMID:25476163

  14. Scaffold-based anti-infection strategies in bone repair.

    PubMed

    Johnson, Christopher T; García, Andrés J

    2015-03-01

    Bone fractures and non-union defects often require surgical intervention where biomaterials are used to correct the defect, and approximately 10% of these procedures are compromised by bacterial infection. Currently, treatment options are limited to sustained, high doses of antibiotics and surgical debridement of affected tissue, leaving a significant, unmet need for the development of therapies to combat device-associated biofilm and infections. Engineering implants to prevent infection is a desirable material characteristic. Tissue engineered scaffolds for bone repair provide a means to both regenerate bone and serve as a base for adding antimicrobial agents. Incorporating anti-infection properties into regenerative medicine therapies could improve clinical outcomes and reduce the morbidity and mortality associated with biomaterial implant-associated infections. This review focuses on current animal models and technologies available to assess bone repair in the context of infection, antimicrobial agents to fight infection, the current state of antimicrobial scaffolds, and future directions in the field.

  15. Development of cost effective fenceline monitoring approaches to support advanced leak detection and repair strategies

    EPA Science Inventory

    Cost-effective fence line and process monitoring systems to support advanced leak detection and repair (LDAR) strategies can enhance protection of public health, facilitate worker safety, and help companies realize cost savings by reducing lost product. The U.S. EPA Office of Re...

  16. Short-Term Mood Repair through Art: Effects of Medium and Strategy

    ERIC Educational Resources Information Center

    Drake, Jennifer E.; Coleman, Katelyn; Winner, Ellen

    2011-01-01

    This study examined the effects of expressive media (drawing versus writing) and emotion regulation strategy (coping by venting versus coping by distraction) on short-term mood repair. After inducing a sad mood in 40 participants, the researchers randomly assigned them to one of two conditions: drawing or writing. Mood valence was assessed before…

  17. Relative effectiveness of three repair strategies on the visual-identification of misperceived words.

    PubMed

    Gagné, J P; Wyllie, K A

    1989-12-01

    Experimental videotapes were used to assess the effectiveness of three repair strategies: (1) repetitions, (2) synonyms, and (3) paraphrases. Three groups of normal-hearing adults viewed one of three videotapes. The same 50 test-words were used on each videotape. Each test-item consisted of three stimuli: a test-word, a stimulus that incorporated the repair strategy under investigation, and a repetition of the initial test-word. Each videotape displayed one of the three repair strategies under investigation. The subjects were required to identify test-words presented in a visual-only mode. The results indicated that the performance of the subjects who were provided with synonyms or paraphrases was significantly better than the performance of the subjects who were shown repetitions. Also, subjects who were shown paraphrases performed significantly better than those who were shown synonyms. These findings indicate that repair strategies that incorporate the use of substitute stimuli such as synonyms and paraphrases may be more effective than the simple repetition of the misperceived stimulus. PMID:2606287

  18. Total Oil Marine's Strategy for subsea pipe line repairs

    SciTech Connect

    Not Available

    1983-07-01

    Total oil marine has carried out an evaluation on methods of reducing risks in interrupting flow on a subsea gas pipe line and, in the event of an incident, how to minimize downtime. As a result of the evaluation, a contract has been awarded to Comex Houlder for the long-term lease of the Emergency Pipeline Repair Service (EPRS) equipment spread. Total Oil Marine operates the twin 354-km, 813-mm (220-mi, 32in.) natural gas transmission line connecting the Frigg field to St. Fergus, UK. These pipe lines transport about one-third of England's gas supply. Although rigorous procedures have been implemented for anchor deployment by floating installations near the lines, it was felt that additional insurance measures were necessary to prevent lengthy periods of downtime. The EPRS concept, developed jointly by Total and Comex Houlder, is based on the provision of a Seahorse underwater welding habitat and all associated equipment on permanent standby, together with the continuous availability of qualified diver/welder personnel.

  19. Strategies for Self-Repairing Shape Memory Alloy Actuators

    NASA Astrophysics Data System (ADS)

    Langbein, Sven; Czechowicz, Alexander Jaroslaw; Meier, Horst

    2011-07-01

    Shape memory alloys (SMAs) are thermally activated smart materials. Due to their ability to change into a previously imprinted actual shape by the means of thermal activation, they are suitable as actuators for microsystems and, within certain limitations, macroscopic systems. A commonly used shape memory actuator type is an alloy of nickel and titanium (NiTi), which starts to transform its inner phase from martensitic to austenitic structure at a certain austenite start temperature. Retransformation starts at martensitic start temperature after running a hysteresis cycle. Most SMA-systems use straight wire actuators because of their simple integration, the occurring cost reduction and the resulting miniaturization. Unfortunately, SMA-actuators are only seldom used by constructors and system developers. This is due to occurring functional fatigue effects which depend on boundary conditions like system loads, strains, and number of cycles. The actuating stroke does not reduce essentially during the first thousand cycles. Striking is the elongation of the wire while maintaining the stroke during cycling (walking). In order to create a system which adjusts and repairs itself, different concepts to solve this problem are presented. They vary from smart control methods to constructive solutions with calibration systems. The systems are analyzed due to their effective, life cycle, and system costs showing outstanding advantages in comparison to commonly used SMA actuators.

  20. Gene Delivery Strategies to Promote Spinal Cord Repair

    PubMed Central

    Walthers, Christopher M; Seidlits, Stephanie K

    2015-01-01

    Gene therapies hold great promise for the treatment of many neurodegenerative disorders and traumatic injuries in the central nervous system. However, development of effective methods to deliver such therapies in a controlled manner to the spinal cord is a necessity for their translation to the clinic. Although essential progress has been made to improve efficiency of transgene delivery and reduce the immunogenicity of genetic vectors, there is still much work to be done to achieve clinical strategies capable of reversing neurodegeneration and mediating tissue regeneration. In particular, strategies to achieve localized, robust expression of therapeutic transgenes by target cell types, at controlled levels over defined time periods, will be necessary to fully regenerate functional spinal cord tissues. This review summarizes the progress over the last decade toward the development of effective gene therapies in the spinal cord, including identification of appropriate target genes, improvements to design of genetic vectors, advances in delivery methods, and strategies for delivery of multiple transgenes with synergistic actions. The potential of biomaterials to mediate gene delivery while simultaneously providing inductive scaffolding to facilitate tissue regeneration is also discussed. PMID:25922572

  1. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair

    PubMed Central

    London, Anat; Cohen, Merav; Schwartz, Michal

    2013-01-01

    Functional macrophage heterogeneity is recognized outside the central nervous system (CNS), where alternatively activated macrophages can perform immune-resolving functions. Such functional heterogeneity was largely ignored in the CNS, with respect to the resident microglia and the myeloid-derived cells recruited from the blood following injury or disease, previously defined as blood-derived microglia; both were indistinguishably perceived detrimental. Our studies have led us to view the myeloid-derived infiltrating cells as functionally distinct from the resident microglia, and accordingly, to name them monocyte-derived macrophages (mo-MΦ). Although microglia perform various maintenance and protective roles, under certain conditions when they can no longer provide protection, mo-MΦ are recruited to the damaged CNS; there, they act not as microglial replacements but rather assistant cells, providing activities that cannot be timely performed by the resident cells. Here, we focus on the functional heterogeneity of microglia/mo-MΦ, emphasizing that, as opposed to the mo-MΦ, microglia often fail to timely acquire the phenotype essential for CNS repair. PMID:23596391

  2. Bourdieu's Distinction between Rules and Strategies and Secondary Principal Practice: A Review of Selected Literature

    ERIC Educational Resources Information Center

    Anderson, Karen

    2016-01-01

    This paper reviews a selection of literature on secondary principal practice from which to propose an approach for further research. The review demonstrates that applications of Bourdieu's theory of practice have contributed to understandings about secondary principal practice, and that the distinction he made between rules and strategies has the…

  3. Strategies in regenerative medicine for intervertebral disc repair using mesenchymal stem cells and bioscaffolds.

    PubMed

    Melrose, James

    2016-10-01

    The intervertebral disc (IVD) is a major weight bearing structure that undergoes degenerative changes with aging limiting its ability to dissipate axial spinal loading in an efficient manner resulting in the generation of low back pain. Low back pain is a number one global musculoskeletal disorder with massive socioeconomic impact. The WHO has nominated development of mesenchymal stem cells and bioscaffolds to promote IVD repair as primary research objectives. There is a clear imperative for the development of strategies to effectively treat IVD defects. Early preclinical studies with mesenchymal stem cells in canine and ovine models have yielded impressive results in IVD repair. Combinatorial therapeutic approaches encompassing biomaterial and cell-based therapies promise significant breakthroughs in IVD repair in the near future. PMID:27586197

  4. Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration

    PubMed Central

    Cao, Hung; Kang, Bong Jin; Lee, Chia-An; Shung, K. Kirk; Hsiai, Tzung K.

    2015-01-01

    Inadequate replacement of lost ventricular myocardium from myocardial infarction leads to heart failure. Investigating the regenerative capacity of mammalian hearts represents an emerging direction for tissue engineering and cell-based therapy. Recent advances in stem cells hold promise to restore cardiac functions. However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack functional phenotypes of the native myocardium, and transplanted tissues are not fully integrated for synchronized electrical and mechanical coupling with the host. In this context, this review highlights the mechanical and electrical strategies to promote cardiomyocyte maturation and integration, and to assess the functional phenotypes of regenerating myocardium. Simultaneous micro-electrocardiogram and high-frequency ultrasound techniques will also be introduced to assess electrical and mechanical coupling for small animal models of heart regeneration. PMID:25974948

  5. Vascular repair strategies in type 2 diabetes: novel insights

    PubMed Central

    Kuschnerus, Kira; Landmesser, Ulf

    2015-01-01

    Impaired functions of vascular cells are responsible for the majority of complications in patients with type 2 diabetes (T2D). Recently a better understanding of mechanisms contributing to development of vascular dysfunction and the role of systemic inflammatory activation and functional alterations of several secretory organs, of which adipose tissue has more recently been investigated, has been achieved. Notably, the progression of vascular disease within the context of T2D appears to be driven by a multitude of incremental signaling shifts. Hence, successful therapies need to target several mechanisms in parallel, and over a long time period. This review will summarize the latest molecular strategies and translational developments of cardiovascular therapy in patients with T2D. PMID:26543824

  6. Cell elimination as a strategy for repair in acute spinal cord injury.

    PubMed

    Kalderon, Nurit

    2005-01-01

    Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound healing (the third week after injury) triggering chronic inflammation and progressive tissue decay that is the characteristic pathology of spinal cord injury. Specific cell elimination within a critical time window after injury can lead to repair in the acutely injured spinal cord. Cell proliferation events can be manipulated/modified by x-irradiation. Clinically, numerous radiation protocols (i.e., radiation therapy) have been developed that specifically eliminate the rapidly dividing cells without causing any noticeable/significant damage to the tissue as a whole. Radiation therapy when applied within the critical time window after injury prevents the onset of chronic inflammation thus leading to repair of structure and function. Various aspects of the development of this cell-elimination strategy for repair in acute spinal cord injury by utilizing radiation therapy are being reviewed. Topics reviewed here: identifying the window of opportunity; and the beneficial repair effects of radiation therapy in a transection injury model and in a model relevant to human injury, the contusion injury model. The possible involvement of cellular components of the blood-spinal cord barrier as the trigger of chronic inflammation and/or target of the radiation therapy is discussed. PMID:15853680

  7. Failure-dependent test, repair, and shutdown strategies: Reducing the impact of common-cause failures

    SciTech Connect

    Uryasev, S.P.; Samanta, P.K.

    1996-11-01

    Failure-dependent testing implies a test of redundant components (or trains) when the failure of one component has been detected. The purpose of such testing is to detect any common-cause failures (CCFs) of multiple components so that a corrective action, such as repair or plant shutdown, can be taken to reduce the residence time of multiple failures. This type of testing focuses on reducing the conditional risk of CCFs. Formulas are developed for calculating the conditional failure probability of a two-train system with different test, repair, and shutdown strategies. A methodology is presented, with an example calculation, showing the risk effectiveness of failure-dependent strategies for emergency diesel generators in nuclear power plants. Four alternative actions after the identification of a failure of one component are analyzed: (a) not carrying out any additional testing, (b) testing the redundant components and shutting down the plant if a CCF is present, (c) emergency repair of the failed component in a given time (less than the allowed outage time), and (d) additional testing of redundant components after the repair of the failed component.

  8. Exploring the Effects of Conversational Repair as a Scaffolding Strategy to Promote Mathematics Explanations of Students with Learning Disabilities

    ERIC Educational Resources Information Center

    Liu, Jia

    2013-01-01

    Conversational repair often occurs in conversations when people attempt to address communicative breakdowns or inaccuracy by way of repeating what have been said or putting them in another way. The review of literature on conversational repair revealed that as an important concept in pragmatic aspect of language, it is an effective strategy to…

  9. Enabling a Prelinguistic Communicator with Autism to Use Picture Card as a Strategy for Repairing Listener Misunderstandings: A Case Study

    ERIC Educational Resources Information Center

    Ohtake, Yoshihisa; Wehmeyer, Michael; Uchida, Naomi; Nakaya, Akitaka; Yanagihara, Masafumi

    2010-01-01

    The purpose of this case study was to examine the effects of a time-delay prompting procedure on the acquisition of skills for repairing multiple listener misunderstandings. A prelinguistic student with autism was taught to use picture cards as a strategy to repair listener misunderstandings in a setting where the student had to ask the listener…

  10. DNA Repair in Human Pluripotent Stem Cells Is Distinct from That in Non-Pluripotent Human Cells

    PubMed Central

    Luo, Li Z.; Park, Sang-Won; Bates, Steven E.; Zeng, Xianmin; Iverson, Linda E.; O'Connor, Timothy R.

    2012-01-01

    The potential for human disease treatment using human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells (iPSCs), also carries the risk of added genomic instability. Genomic instability is most often linked to DNA repair deficiencies, which indicates that screening/characterization of possible repair deficiencies in pluripotent human stem cells should be a necessary step prior to their clinical and research use. In this study, a comparison of DNA repair pathways in pluripotent cells, as compared to those in non-pluripotent cells, demonstrated that DNA repair capacities of pluripotent cell lines were more heterogeneous than those of differentiated lines examined and were generally greater. Although pluripotent cells had high DNA repair capacities for nucleotide excision repair, we show that ultraviolet radiation at low fluxes induced an apoptotic response in these cells, while differentiated cells lacked response to this stimulus, and note that pluripotent cells had a similar apoptotic response to alkylating agent damage. This sensitivity of pluripotent cells to damage is notable since viable pluripotent cells exhibit less ultraviolet light-induced DNA damage than do differentiated cells that receive the same flux. In addition, the importance of screening pluripotent cells for DNA repair defects was highlighted by an iPSC line that demonstrated a normal spectral karyotype, but showed both microsatellite instability and reduced DNA repair capacities in three out of four DNA repair pathways examined. Together, these results demonstrate a need to evaluate DNA repair capacities in pluripotent cell lines, in order to characterize their genomic stability, prior to their pre-clinical and clinical use. PMID:22412831

  11. Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges.

    PubMed

    Pfister, Bryan J; Gordon, Tessa; Loverde, Joseph R; Kochar, Arshneel S; Mackinnon, Susan E; Cullen, D Kacy

    2011-01-01

    Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.

  12. Recurrence after composite repair of a giant hiatus hernia: 'the golf club' deformity is a distinctive clinical and radiological picture.

    PubMed

    Furtado, R V; Falk, G L; Vivian, S J

    2016-07-01

    Background Recurrence of a hiatus hernia after cardiopexy repair can obstruct the lower oesophagus but also provide characteristic radiographic images after a barium meal. Case History Two patients with recurrence of a hiatus hernia underwent repeat surgery. Here, we provide and discuss diagnostic imaging, surgical findings and outcome for these male and female patients. Conclusions Repeat surgery is indicated in patients with recurrence of a hiatus hernia after repair. PMID:27241603

  13. Drug delivery strategies to control macrophages for tissue repair and regeneration.

    PubMed

    Garash, Reham; Bajpai, Anamika; Marcinkiewicz, Brandon M; Spiller, Kara L

    2016-05-01

    Tissue repair and regeneration is a complex process. Our bodies have an excellent capacity to regenerate damaged tissues in many situations. However, tissue healing is impaired in injuries that exceed a critical size or are exacerbated by chronic inflammatory diseases like diabetes. In these instances, biomaterials and drug delivery strategies are often required to facilitate tissue regeneration by providing physical and biochemical cues. Inflammation is the body's response to injury. It is critical for wound healing and biomaterial integration and vascularization, as long as the timing is well controlled. For example, chronic inflammation is well known to impair healing in chronic wounds. In this review, we highlight the importance of a well-controlled inflammatory response, primarily mediated by macrophages in tissue repair and regeneration and discuss various strategies designed to promote regeneration by controlling macrophage behavior. These strategies include temporally controlled delivery of anti-inflammatory drugs, delivery of macrophages as cellular therapy, controlled release of cytokines that modulate macrophage phenotype, and the design of nanoparticles that exploit the inherent phagocytic behavior of macrophages. A clear outcome of this review is that a deeper understanding of the role and timing of complex macrophage phenotypes or activation states is required to fully harness their abilities with drug delivery strategies. PMID:27190256

  14. Oman India Pipeline: An operational repair strategy based on a rational assessment of risk

    SciTech Connect

    German, P.

    1996-12-31

    This paper describes the development of a repair strategy for the operational phase of the Oman India Pipeline based upon the probability and consequences of a pipeline failure. Risk analyses and cost benefit analyses performed provide guidance on the level of deepwater repair development effort appropriate for the Oman India Pipeline project and identifies critical areas toward which more intense development effort should be directed. The risk analysis results indicate that the likelihood of a failure of the Oman India Pipeline during its 40-year life is low. Furthermore, the probability of operational failure of the pipeline in deepwater regions is extremely low, the major proportion of operational failure risk being associated with the shallow water regions.

  15. Ecological and inhost factors promoting distinct parasite life-history strategies in Lyme borreliosis.

    PubMed

    Haven, James; Magori, Krisztian; Park, Andrew W

    2012-08-01

    Understanding the ecology and evolution of tick-borne parasites is the foundation for preventing and managing tick-borne diseases. Tick-borne diseases such as Lyme borreliosis, are an emerging health threat in America, Europe, and Asia. Certain strains of Borrelia burgdorferi (the etiological agent of Lyme borreliosis) sampled in nature appear to be rapidly cleared by murine hosts. These strains, unlike their inhost-persistent counterparts, are unlikely to manifest severe disease. Their emergence and abundance in North America is unclear. Understanding why strains adopt a persistent or rapid-clearing phenotype is a crucial question in Lyme biology. Using dynamic, data-driven infectivity profiles in a competitive, two-strain mathematical model, we show that these phenotypes are differentially favored under distinct ecological conditions (i.e. vector phenology). We argue these two phenotypes represent distinct parasite life-history strategies, impacting regional Lyme disease severity across North America.

  16. Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial

    PubMed Central

    Braithwaite, Bruce; Cheshire, Nicholas J.; Greenhalgh, Roger M.; Grieve, Richard; Hassan, Tajek B.; Hinchliffe, Robert; Howell, Simon; Moore, Fionna; Nicholson, Anthony A.; Soong, Chee V.; Thompson, Matt M.; Thompson, Simon G.; Ulug, Pinar; Heatley, Francine; Anjum, Aisha; Kalinowska, Gosia; Sweeting, Michael J.; Thompson, Simon G.; Gomes, Manuel; Grieve, Richard; Powell, Janet T.; Ashleigh, Ray; Gomes, Manuel; Greenhalgh, Roger M.; Grieve, Richard; Hinchliffe, Robert; Sweeting, Michael; Thompson, Matt M.; Thompson, Simon G.; Ulug, Pinar; Roberts, Ian; Bell, Peter R. F.; Cheetham, Anne; Stephany, Jenny; Warlow, Charles; Lamont, Peter; Moss, Jonathan; Tijssen, Jan; Braithwaite, Bruce; Nicholson, Anthony A.; Thompson, Matthew; Ashleigh, Ray; Thompson, Luke; Cheshire, Nicholas J.; Boyle, Jonathan R.; Serracino-Inglott, Ferdinand; Thompson, Matt M.; Hinchliffe, Robert J.; Bell, Rachel; Wilson, Noel; Bown, Matt; Dennis, Martin; Davis, Meryl; Ashleigh, Ray; Howell, Simon; Wyatt, Michael G.; Valenti, Domenico; Bachoo, Paul; Walker, Paul; MacSweeney, Shane; Davies, Jonathan N.; Rittoo, Dynesh; Parvin, Simon D.; Yusuf, Waquar; Nice, Colin; Chetter, Ian; Howard, Adam; Chong, Patrick; Bhat, Raj; McLain, David; Gordon, Andrew; Lane, Ian; Hobbs, Simon; Pillay, Woolagasen; Rowlands, Timothy; El-Tahir, Amin; Asquith, John; Cavanagh, Steve; Dubois, Luc; Forbes, Thomas L.; Ashworth, Emily; Baker, Sara; Barakat, Hashem; Brady, Claire; Brown, Joanne; Bufton, Christine; Chance, Tina; Chrisopoulou, Angela; Cockell, Marie; Croucher, Andrea; Dabee, Leela; Dewhirst, Nikki; Evans, Jo; Gibson, Andy; Gorst, Siobhan; Gough, Moira; Graves, Lynne; Griffin, Michelle; Hatfield, Josie; Hogg, Florence; Howard, Susannah; Hughes, Cían; Metcalfe, David; Lapworth, Michelle; Massey, Ian; Novick, Teresa; Owen, Gareth; Parr, Noala; Pintar, David; Spencer, Sarah; Thomson, Claire; Thunder, Orla; Wallace, Tom; Ward, Sue; Wealleans, Vera; Wilson, Lesley; Woods, Janet; Zheng, Ting

    2015-01-01

    Aims To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. Methods and results This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI −0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). Conclusion An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. Clinical trial registration ISRCTN 48334791. PMID:25855369

  17. Distinct genetic control of homologous recombination repair of Cas9-induced double-strand breaks, nicks and paired nicks.

    PubMed

    Vriend, Lianne E M; Prakash, Rohit; Chen, Chun-Chin; Vanoli, Fabio; Cavallo, Francesca; Zhang, Yu; Jasin, Maria; Krawczyk, Przemek M

    2016-06-20

    DNA double-strand breaks (DSBs) are known to be powerful inducers of homologous recombination (HR), but single-strand breaks (nicks) have also been shown to trigger HR. Both DSB- and nick-induced HR ((nick)HR) are exploited in advanced genome-engineering approaches based on the bacterial RNA-guided nuclease Cas9. However, the mechanisms of (nick)HR are largely unexplored. Here, we applied Cas9 nickases to study (nick)HR in mammalian cells. We find that (nick)HR is unaffected by inhibition of major damage signaling kinases and that it is not suppressed by nonhomologous end-joining (NHEJ) components, arguing that nick processing does not require a DSB intermediate to trigger HR. Relative to a single nick, nicking both strands enhances HR, consistent with a DSB intermediate, even when nicks are induced up to ∼1kb apart. Accordingly, HR and NHEJ compete for repair of these paired nicks, but, surprisingly, only when 5' overhangs or blunt ends can be generated. Our study advances the understanding of molecular mechanisms driving nick and paired-nick repair in mammalian cells and clarify phenomena associated with Cas9-mediated genome editing.

  18. Distinctive features of single nucleotide alterations in induced pluripotent stem cells with different types of DNA repair deficiency disorders

    PubMed Central

    Okamura, Kohji; Sakaguchi, Hironari; Sakamoto-Abutani, Rie; Nakanishi, Mahito; Nishimura, Ken; Yamazaki-Inoue, Mayu; Ohtaka, Manami; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali Abdullah; Higuchi, Akon; Hanaoka, Kazunori; Nakabayashi, Kazuhiko; Takada, Shuji; Hata, Kenichiro; Toyoda, Masashi; Umezawa, Akihiro

    2016-01-01

    Disease-specific induced pluripotent stem cells (iPSCs) have been used as a model to analyze pathogenesis of disease. In this study, we generated iPSCs derived from a fibroblastic cell line of xeroderma pigmentosum (XP) group A (XPA-iPSCs), a rare autosomal recessive hereditary disease in which patients develop skin cancer in the areas of skin exposed to sunlight. XPA-iPSCs exhibited hypersensitivity to ultraviolet exposure and accumulation of single-nucleotide substitutions when compared with ataxia telangiectasia-derived iPSCs that were established in a previous study. However, XPA-iPSCs did not show any chromosomal instability in vitro, i.e. intact chromosomes were maintained. The results were mutually compensating for examining two major sources of mutations, nucleotide excision repair deficiency and double-strand break repair deficiency. Like XP patients, XPA-iPSCs accumulated single-nucleotide substitutions that are associated with malignant melanoma, a manifestation of XP. These results indicate that XPA-iPSCs may serve a monitoring tool (analogous to the Ames test but using mammalian cells) to measure single-nucleotide alterations, and may be a good model to clarify pathogenesis of XP. In addition, XPA-iPSCs may allow us to facilitate development of drugs that delay genetic alteration and decrease hypersensitivity to ultraviolet for therapeutic applications. PMID:27197874

  19. Distinct genetic control of homologous recombination repair of Cas9-induced double-strand breaks, nicks and paired nicks

    PubMed Central

    Vriend, Lianne E.M.; Prakash, Rohit; Chen, Chun-Chin; Vanoli, Fabio; Cavallo, Francesca; Zhang, Yu; Jasin, Maria; Krawczyk, Przemek M.

    2016-01-01

    DNA double-strand breaks (DSBs) are known to be powerful inducers of homologous recombination (HR), but single-strand breaks (nicks) have also been shown to trigger HR. Both DSB- and nick-induced HR (nickHR) are exploited in advanced genome-engineering approaches based on the bacterial RNA-guided nuclease Cas9. However, the mechanisms of nickHR are largely unexplored. Here, we applied Cas9 nickases to study nickHR in mammalian cells. We find that nickHR is unaffected by inhibition of major damage signaling kinases and that it is not suppressed by nonhomologous end-joining (NHEJ) components, arguing that nick processing does not require a DSB intermediate to trigger HR. Relative to a single nick, nicking both strands enhances HR, consistent with a DSB intermediate, even when nicks are induced up to ∼1kb apart. Accordingly, HR and NHEJ compete for repair of these paired nicks, but, surprisingly, only when 5' overhangs or blunt ends can be generated. Our study advances the understanding of molecular mechanisms driving nick and paired-nick repair in mammalian cells and clarify phenomena associated with Cas9-mediated genome editing. PMID:27001513

  20. New strategies for repairing the injured spinal cord: the role of stem cells.

    PubMed

    Garbossa, D; Fontanella, M; Fronda, C; Benevello, C; Muraca, G; Ducati, A; Vercelli, A

    2006-07-01

    Thanks to advances in the stem cell biology of the central nervous system, the previously unconceivable regeneration of the damaged spinal cord is approaching reality. A number of potential strategies aim to optimize functional recovery after spinal cord injury. They include minimizing the progression of secondary injury, manipulating the inhibitory environment of the spinal cord, replacing lost tissue with transplanted cells or peripheral nerve grafts, remyelinating denuded axons and maximizing the intrinsic regenerative potential of endogenous progenitor cells. We review the application of stem cell transplantation to the spinal cord, emphasizing the use of embryonic stem cells for remyelinating damaged axons. Recent advancements in neural injury and repair, and the progress towards development of neuroprotective and regenerative interventions are discussed.

  1. Distinct coping strategies differentially predict urge levels and lapses in a smoking cessation attempt.

    PubMed

    Brodbeck, Jeannette; Bachmann, Monica S; Znoj, Hansjörg

    2013-06-01

    This study analysed mechanisms through which stress-coping and temptation-coping strategies were associated with lapses. Furthermore, we explored whether distinct coping strategies differentially predicted reduced lapse risk, lower urge levels, or a weaker association between urge levels and lapses during the first week of an unassisted smoking cessation attempt. Participants were recruited via the internet and mass media in Switzerland. Ecological momentary assessment (EMA) with mobile devices was used to assess urge levels and lapses. Online questionnaires were used to measure smoking behaviours and coping variables at baseline, as well as smoking behaviour at the three-month follow-up. The sample consisted of 243 individuals, aged 20 to 40, who reported 4199 observations. Findings of multilevel regression analyses show that coping was mainly associated with a reduced lapse risk and not with lower urge levels or a weaker association between urge levels and lapses. 'Calming down' and 'commitment to change' predicted a lower lapse risk and also a weaker relation between urge levels and lapses. 'Stimulus control' predicted a lower lapse risk and lower urge levels. Conversely, 'task-orientation' and 'risk assessment' were related to higher lapse risk and 'risk assessment' also to higher urge levels. Disengagement coping i.e. 'eating or shopping', 'distraction', and 'mobilising social support' did not affect lapse risk. Promising coping strategies during the initial stage of smoking cessation attempt are targeted directly at reducing the lapse risk and are characterised by engagement with the stressor or one's reactions towards the stressor and a focus on positive consequences instead of health risks. PMID:23501139

  2. Distinct coping strategies differentially predict urge levels and lapses in a smoking cessation attempt.

    PubMed

    Brodbeck, Jeannette; Bachmann, Monica S; Znoj, Hansjörg

    2013-06-01

    This study analysed mechanisms through which stress-coping and temptation-coping strategies were associated with lapses. Furthermore, we explored whether distinct coping strategies differentially predicted reduced lapse risk, lower urge levels, or a weaker association between urge levels and lapses during the first week of an unassisted smoking cessation attempt. Participants were recruited via the internet and mass media in Switzerland. Ecological momentary assessment (EMA) with mobile devices was used to assess urge levels and lapses. Online questionnaires were used to measure smoking behaviours and coping variables at baseline, as well as smoking behaviour at the three-month follow-up. The sample consisted of 243 individuals, aged 20 to 40, who reported 4199 observations. Findings of multilevel regression analyses show that coping was mainly associated with a reduced lapse risk and not with lower urge levels or a weaker association between urge levels and lapses. 'Calming down' and 'commitment to change' predicted a lower lapse risk and also a weaker relation between urge levels and lapses. 'Stimulus control' predicted a lower lapse risk and lower urge levels. Conversely, 'task-orientation' and 'risk assessment' were related to higher lapse risk and 'risk assessment' also to higher urge levels. Disengagement coping i.e. 'eating or shopping', 'distraction', and 'mobilising social support' did not affect lapse risk. Promising coping strategies during the initial stage of smoking cessation attempt are targeted directly at reducing the lapse risk and are characterised by engagement with the stressor or one's reactions towards the stressor and a focus on positive consequences instead of health risks.

  3. Targeting DNA repair, DNA metabolism and replication stress as anti-cancer strategies.

    PubMed

    Puigvert, Jordi Carreras; Sanjiv, Kumar; Helleday, Thomas

    2016-01-01

    Anti-cancer therapies targeting and damaging the DNA have been extensively used in the last 50 years since the discovery of nitrogen mustards, antimetabolites and platin agents. The use of these drugs is often limited by dose-limiting side effects related to their poor specificity. In recent years, much effort has been put on the discovery and development of compounds that would exploit defects in DNA repair in cancer cells such as Wee1, Chk1 or PARP1 inhibitors. However, not all cancers respond to these inhibitors. Recently, new developments towards specifically targeting broader characteristics of cancer such as replication stress (RS) and lost redox homeostasis have emerged. Oncogenes induce proliferation signals, which also result in replication-associated DNA damage, i.e. RS. Our knowledge into overall causes of RS, lesions produced and how these are signalled in cells to activate cell cycle checkpoints is evolving. Inhibition of ATR, which would normally keep non-deleterious levels of RS, induces intolerable RS levels for cancer cells. Interestingly, links between replication and transcription appear to underlie RS along with a reduction of the dNTP pool. Remarkably, sanitization of the dNTP pool by MutT homologue 1, impeding incorporation of oxidized dNTPs into the DNA, seems to be crucial for cancer cell survival. In this minireview we present an overview of current and novel strategies to target DNA repair and exploit DNA damage to treat cancer. We present the current models for cancer-associated RS as well as cancer phenotypic lethality. Both strategies are poised to better target cancer cells and reduce side effects. PMID:26507796

  4. Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL.

    PubMed

    Fukui, Kenji; Baba, Seiki; Kumasaka, Takashi; Yano, Takato

    2016-08-12

    In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the β-clamp-interacting motif (β motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with β-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until β clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the β motif. For example, the region corresponding to the β motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the β motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the β motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of β motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of β-clamp and that β-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a β motif-containing MutL, required β-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on β-clamp. PMID:27369079

  5. Distinct expression profiles of stress defense and DNA repair genes in Daphnia pulex exposed to cadmium, zinc, and quantum dots.

    PubMed

    Tang, Song; Wu, Yonggan; Ryan, Caitlin N; Yu, Shuangying; Qin, Guangqiu; Edwards, Donn S; Mayer, Gregory D

    2015-02-01

    The ever-increasing production and use of nanocrystaline semiconductors (Quantum dots; QDs) will inevitably result in increased appearance of these nanomaterials in the aquatic environment. However, the behavior and potential toxicity of heavy metal constituted nanoparticulates in aquatic invertebrates is largely unknown, especially with regard to molecular responses. The freshwater crustacean Daphnia pulex is a well-suited toxicological and ecological model to study molecular responses to environmental stressors. In this study, D. pulex were exposed for 48 h to sublethal doses of QDs (25% and 50% of LC50) with differing spectral properties (CdTe and CdSe/ZnS QDs) and Cd and Zn salts. Our data suggest that acute exposure to both CdSO4 and Cd-based QDs leads to Cd uptake in vivo, which was biologically supported by the observation of increased expression of metallothionein (MT-1). Furthermore, Cd, Zn, and CdSe/ZnS QDs induced different patterns of gene expression regarding stress defense and DNA repair, which furthers our knowledge regarding which response pathways are affected by nanoparticulate forms of metals versus ionic forms in aquatic crustaceans. PMID:25014899

  6. Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls.

    PubMed

    Leininger, Elizabeth C; Kelley, Darcy B

    2013-04-01

    Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors. PMID:23407829

  7. Distinct neural and neuromuscular strategies underlie independent evolution of simplified advertisement calls

    PubMed Central

    Leininger, Elizabeth C.; Kelley, Darcy B.

    2013-01-01

    Independent or convergent evolution can underlie phenotypic similarity of derived behavioural characters. Determining the underlying neural and neuromuscular mechanisms sheds light on how these characters arose. One example of evolutionarily derived characters is a temporally simple advertisement call of male African clawed frogs (Xenopus) that arose at least twice independently from a more complex ancestral pattern. How did simplification occur in the vocal circuit? To distinguish shared from divergent mechanisms, we examined activity from the calling brain and vocal organ (larynx) in two species that independently evolved simplified calls. We find that each species uses distinct neural and neuromuscular strategies to produce the simplified calls. Isolated  Xenopus borealis brains produce fictive vocal patterns that match temporal patterns of actual male calls; the larynx converts nerve activity faithfully into muscle contractions and single clicks. In contrast, fictive patterns from isolated Xenopus boumbaensis brains are short bursts of nerve activity; the isolated larynx requires stimulus bursts to produce a single click of sound. Thus, unlike X. borealis, the output of the X. boumbaensis hindbrain vocal pattern generator is an ancestral burst-type pattern, transformed by the larynx into single clicks. Temporally simple advertisement calls in genetically distant species of Xenopus have thus arisen independently via reconfigurations of central and peripheral vocal neuroeffectors. PMID:23407829

  8. Different Cold Spray Deposition Strategies: Single- and Multi-layers to Repair Aluminium Alloy Components

    NASA Astrophysics Data System (ADS)

    Rech, Silvano; Trentin, Andrea; Vezzù, Simone; Vedelago, Enrico; Legoux, Jean-Gabriel; Irissou, Eric

    2014-12-01

    Cold spraying is increasingly being used for reconstruction or repair of damaged aluminium alloy components, especially in the aviation industry. Both thin (<0.5 mm) and thick (up to 1 cm) coatings are necessary to achieve dimensional recovery of such components. Thin and above all thick coatings can be deposited in a single pass (single layer) or in several passes (multi-pass), resulting in different thermal and stress effects in the component and the coating itself. The thermal input, the amount and type of residual stresses and the porosity affect various characteristics such as adhesion, crack propagation and mechanical properties of the coating. In this study, two sets (single- and multi-pass) of aluminium alloy (AA6061) coatings with different thicknesses (0.5 mm to 2 mm) were deposited onto AA6061 substrates and compared using metallographic and fractographic analyses, four-point bending testing, residual stress analysis and Vickers microhardness indentation. Finally, the coating adhesion and cohesion were measured using the standard ASTM-C633 adhesion test and tubular coating tensile test. This study demonstrates that the single-layer strategy results in greater adhesion and lower porosity, while multilayer coatings have higher elastic modulus. Independent of the strategy, the compressive residual stress decreases as a function of coating thickness.

  9. Strategies to Stimulate Mobilization and Homing of Endogenous Stem and Progenitor Cells for Bone Tissue Repair

    PubMed Central

    Herrmann, Marietta; Verrier, Sophie; Alini, Mauro

    2015-01-01

    The gold standard for the treatment of critical-size bone defects is autologous or allogenic bone graft. This has several limitations including donor site morbidity and the restricted supply of graft material. Cell-based tissue engineering strategies represent an alternative approach. Mesenchymal stem cells (MSCs) have been considered as a source of osteoprogenitor cells. More recently, focus has been placed on the use of endothelial progenitor cells (EPCs), since vascularization is a critical step in bone healing. Although many of these approaches have demonstrated effectiveness for bone regeneration, cell-based therapies require time consuming and cost-expensive in vitro cell expansion procedures. Accordingly, research is becoming increasingly focused on the homing and stimulation of native cells. The stromal cell-derived factor-1 (SDF-1) – CXCR4 axis has been shown to be critical for the recruitment of MSCs and EPCs. Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and has been targeted in many studies. Here, we present an overview of the different approaches for delivering homing factors to the defect site by absorption or incorporation to biomaterials, gene therapy, or via genetically manipulated cells. We further review strategies focusing on the stimulation of endogenous cells to support bone repair. Finally, we discuss the major challenges in the treatment of critical-size bone defects and fracture non-unions. PMID:26082926

  10. Tissue-engineering strategies to repair joint tissue in osteoarthritis: nonviral gene-transfer approaches.

    PubMed

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

    Loss of articular cartilage is a common clinical consequence of osteoarthritis (OA). In the past decade, substantial progress in tissue engineering, nonviral gene transfer, and cell transplantation have provided the scientific foundation for generating cartilaginous constructs from genetically modified cells. Combining tissue engineering with overexpression of therapeutic genes enables immediate filling of a cartilage defect with an engineered construct that actively supports chondrogenesis. Several pioneering studies have proved that spatially defined nonviral overexpression of growth-factor genes in constructs of solid biomaterials or hydrogels is advantageous compared with gene transfer or scaffold alone, both in vitro and in vivo. Notably, these investigations were performed in models of focal cartilage defects, because advanced cartilage-repair strategies based on the principles of tissue engineering have not advanced sufficiently to enable resurfacing of extensively degraded cartilage as therapy for OA. These studies serve as prototypes for future technological developments, because they raise the possibility that cartilage constructs engineered from genetically modified chondrocytes providing autocrine and paracrine stimuli could similarly compensate for the loss of articular cartilage in OA. Because cartilage-tissue-engineering strategies are already used in the clinic, combining tissue engineering and nonviral gene transfer could prove a powerful approach to treat OA.

  11. Distinct Discrimination Learning Strategies and Their Relation with Spatial Memory and Attentional Control in 4- to 14-Year-Olds

    ERIC Educational Resources Information Center

    Schmittmann, Verena D.; van der Maas, Han L. J.; Raijmakers, Maartje E. J.

    2012-01-01

    Behavioral, psychophysiological, and neuropsychological studies have revealed large developmental differences in various learning paradigms where learning from positive and negative feedback is essential. The differences are possibly due to the use of distinct strategies that may be related to spatial working memory and attentional control. In…

  12. Distinct discrimination learning strategies and their relation with spatial memory and attentional control in 4- to 14-year-olds.

    PubMed

    Schmittmann, Verena D; van der Maas, Han L J; Raijmakers, Maartje E J

    2012-04-01

    Behavioral, psychophysiological, and neuropsychological studies have revealed large developmental differences in various learning paradigms where learning from positive and negative feedback is essential. The differences are possibly due to the use of distinct strategies that may be related to spatial working memory and attentional control. In this study, strategies in performing a discrimination learning task were distinguished in a cross-sectional sample of 302 children from 4 to 14 years of age. The trial-by-trial accuracy data were analyzed with mathematical learning models. The best-fitting model revealed three learning strategies: hypothesis testing, slow abrupt learning, and nonlearning. The proportion of hypothesis-testing children increased with age. Nonlearners were present only in the youngest age group. Feature preferences for the irrelevant dimension had a detrimental effect on performance in the youngest age group. The executive functions spatial working memory and attentional control significantly predicted posterior learning strategy probabilities after controlling for age.

  13. Development of cost effective fenceline monitoring methods to support advanced leak detection and repair strategies

    EPA Science Inventory

    Improved mitigation of fugitive emissions of hazardous air pollutants (HAPs), volatile organic compounds (VOCs), and greenhouse gas (GHG) emissions is an important emerging topic in many industrial sectors. Efficacious leak detection and repair (LDAR) programs of the future yiel...

  14. Hierarchical decision processes that operate over distinct timescales underlie choice and changes in strategy.

    PubMed

    Purcell, Braden A; Kiani, Roozbeh

    2016-08-01

    Decision-making in a natural environment depends on a hierarchy of interacting decision processes. A high-level strategy guides ongoing choices, and the outcomes of those choices determine whether or not the strategy should change. When the right decision strategy is uncertain, as in most natural settings, feedback becomes ambiguous because negative outcomes may be due to limited information or bad strategy. Disambiguating the cause of feedback requires active inference and is key to updating the strategy. We hypothesize that the expected accuracy of a choice plays a crucial rule in this inference, and setting the strategy depends on integration of outcome and expectations across choices. We test this hypothesis with a task in which subjects report the net direction of random dot kinematograms with varying difficulty while the correct stimulus-response association undergoes invisible and unpredictable switches every few trials. We show that subjects treat negative feedback as evidence for a switch but weigh it with their expected accuracy. Subjects accumulate switch evidence (in units of log-likelihood ratio) across trials and update their response strategy when accumulated evidence reaches a bound. A computational framework based on these principles quantitatively explains all aspects of the behavior, providing a plausible neural mechanism for the implementation of hierarchical multiscale decision processes. We suggest that a similar neural computation-bounded accumulation of evidence-underlies both the choice and switches in the strategy that govern the choice, and that expected accuracy of a choice represents a key link between the levels of the decision-making hierarchy. PMID:27432960

  15. Hierarchical decision processes that operate over distinct timescales underlie choice and changes in strategy.

    PubMed

    Purcell, Braden A; Kiani, Roozbeh

    2016-08-01

    Decision-making in a natural environment depends on a hierarchy of interacting decision processes. A high-level strategy guides ongoing choices, and the outcomes of those choices determine whether or not the strategy should change. When the right decision strategy is uncertain, as in most natural settings, feedback becomes ambiguous because negative outcomes may be due to limited information or bad strategy. Disambiguating the cause of feedback requires active inference and is key to updating the strategy. We hypothesize that the expected accuracy of a choice plays a crucial rule in this inference, and setting the strategy depends on integration of outcome and expectations across choices. We test this hypothesis with a task in which subjects report the net direction of random dot kinematograms with varying difficulty while the correct stimulus-response association undergoes invisible and unpredictable switches every few trials. We show that subjects treat negative feedback as evidence for a switch but weigh it with their expected accuracy. Subjects accumulate switch evidence (in units of log-likelihood ratio) across trials and update their response strategy when accumulated evidence reaches a bound. A computational framework based on these principles quantitatively explains all aspects of the behavior, providing a plausible neural mechanism for the implementation of hierarchical multiscale decision processes. We suggest that a similar neural computation-bounded accumulation of evidence-underlies both the choice and switches in the strategy that govern the choice, and that expected accuracy of a choice represents a key link between the levels of the decision-making hierarchy.

  16. Four different strategies for repair of aortic coarctation accompanied by cardiac lesions

    PubMed Central

    Ugur, Murat; Alp, Ibrahim; Arslan, Gokhan; Temizkan, Veysel; Ucak, Alper; Yilmaz, Ahmet Turan

    2013-01-01

    OBJECTIVES Coarctation accompanied by cardiac lesions is a complex clinical situation due to the presence of two different pathologies that necessitate surgical treatment. An individual strategy, according to the severity of the disease, is important to reduce perioperative mortality and morbidity. METHODS We report here on 25 patients with coarctation accompanied by cardiac lesions who were treated by various surgical approaches. Coarctation and associated disease were treated in 14 patients in a single stage by an ascending-to-descending bypass (n = 11) or by a hybrid procedure (n = 3). The remaining 11 patients underwent a two-stage operation for their treatment. Six of these 11 patients who had coronary artery disease or signs of congestive heart failure were first operated for their cardiac disease, whereas in the remaining five patients, who did not have any congestive signs, coarctation repair was performed first. RESULTS All the patients were male, between the ages of 20 and 24 years, except for one 45-year-old woman. The mean cross-clamp times, cardiopulmonary bypass times and operation times were 52 ± 14.5, 102.3 ± 28.5 and 174 ± 24.8 min in the extra-anatomical bypass group; 29.8 ± 11.7, 55.5 ± 17.6 and 116 ± 22 min in the two-stage groups and 49 ± 19.8, 63 ± 18.7 and 159 ± 21.3 min in the hybrid patients, respectively. One patient who underwent extra-anatomical bypass died on the 14th postoperative day. There were no events during the follow-up period for the other patients. Also, there were no gradients between the extremities and no graft-related complications. CONCLUSIONS As a consequence of the progress in the development of endovascular techniques, hybrid treatment is becoming a more popular option for the treatment of coarctation accompanied by cardiac diseases. Two-stage procedures and extra-anatomical bypass might be alternative techniques if endovascular procedures are contraindicated or failing. PMID:23744896

  17. Seismic design repair and retrofit strategies for steel roof deck diaphragms

    NASA Astrophysics Data System (ADS)

    Franquet, John-Edward

    Structural engineers will often rely on the roof diaphragm to transfer lateral seismic loads to the bracing system of single-storey structures. The implementation of capacity-based design in the NBCC 2005 has caused an increase in the diaphragm design load due to the need to use the probable capacity of the bracing system, thus resulting in thicker decks, closer connector patterns and higher construction costs. Previous studies have shown that accounting for the in-plane flexibility of the diaphragm when calculating the overall building period can result in lower seismic forces and a more cost-efficient design. However, recent studies estimating the fundamental period of single storey structures using ambient vibration testing showed that the in-situ approximation was much shorter than that obtained using analytical means. The difference lies partially in the diaphragm stiffness characteristics which have been shown to decrease under increasing excitation amplitude. Using the diaphragm as the energy-dissipating element in the seismic force resisting system has also been investigated as this would take advantage of the diaphragm's ductility and limited overstrength; thus, lower capacity based seismic forces would result. An experimental program on 21.0m by 7.31m diaphragm test specimens was carried out so as to investigate the dynamic properties of diaphragms including the stiffness, ductility and capacity. The specimens consisted of 20 and 22 gauge panels with nailed frame fasteners and screwed sidelap connections as well a welded and button-punch specimen. Repair strategies for diaphragms that have previously undergone inelastic deformations were devised in an attempt to restitute the original stiffness and strength and were then experimentally evaluated. Strength and stiffness experimental estimations are compared with those predicted with the Steel Deck Institute (SDI) method. A building design comparative study was also completed. This study looks at the

  18. High resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies

    PubMed Central

    Rabani, Michal; Raychowdhury, Raktima; Jovanovic, Marko; Rooney, Michael; Stumpo, Deborah J.; Hacohen, Nir; Schier, Alexander F.; Blackshear, Perry J.; Friedman, Nir; Amit, Ido; Regev, Aviv

    2014-01-01

    Summary Cells control dynamic transitions in transcript levels by regulating transcription, processing and/or degradation through an integrated regulatory strategy. Here, we combine RNA metabolic labeling, rRNA-depleted RNA-seq, and DRiLL, a novel computational framework, to quantify the level, editing sites, and transcription, processing and degradation rates of each transcript at a splice junction resolution during the LPS response of mouse dendritic cells. Four key regulatory strategies, dominated by RNA transcription changes, generate most temporal gene expression patterns. Non-canonical strategies that also employ dynamic posttranscriptional regulation control only a minority of genes, but provide unique signal processing features. We validate Tristetraprolin (TTP) as a major regulator of RNA degradation in one non-canonical strategy. Applying DRiLL to the regulation of non-coding RNAs and to zebrafish embryogenesis demonstrates its broad utility. Our study provides a new quantitative approach to discover transcriptional and post-transcriptional events that control dynamic changes in transcript levels using RNA-Seq data. PMID:25497548

  19. Understanding Strategies in Foreign Language Learning: Are Integrative and Intrinsic Motives Distinct Predictors?

    ERIC Educational Resources Information Center

    Bonney, Christina Rhee; Cortina, Kai S.; Smith-Darden, Joanne P.; Fiori, Katherine L.

    2008-01-01

    This study examines the relation between the motivational structure and use of learning strategies of high school foreign language students. Students in 36 foreign language classrooms (French, German, Latin, and Spanish; first- through fifth-years) from a large Midwestern high school participated in the study (N=694). As predicted, correlation and…

  20. Evaluating random search strategies in three mammals from distinct feeding guilds.

    PubMed

    Auger-Méthé, Marie; Derocher, Andrew E; DeMars, Craig A; Plank, Michael J; Codling, Edward A; Lewis, Mark A

    2016-09-01

    Searching allows animals to find food, mates, shelter and other resources essential for survival and reproduction and is thus among the most important activities performed by animals. Theory predicts that animals will use random search strategies in highly variable and unpredictable environments. Two prominent models have been suggested for animals searching in sparse and heterogeneous environments: (i) the Lévy walk and (ii) the composite correlated random walk (CCRW) and its associated area-restricted search behaviour. Until recently, it was difficult to differentiate between the movement patterns of these two strategies. Using a new method that assesses whether movement patterns are consistent with these two strategies and two other common random search strategies, we investigated the movement behaviour of three species inhabiting sparse northern environments: woodland caribou (Rangifer tarandus caribou), barren-ground grizzly bear (Ursus arctos) and polar bear (Ursus maritimus). These three species vary widely in their diets and thus allow us to contrast the movement patterns of animals from different feeding guilds. Our results showed that although more traditional methods would have found evidence for the Lévy walk for some individuals, a comparison of the Lévy walk to CCRWs showed stronger support for the latter. While a CCRW was the best model for most individuals, there was a range of support for its absolute fit. A CCRW was sufficient to explain the movement of nearly half of herbivorous caribou and a quarter of omnivorous grizzly bears, but was insufficient to explain the movement of all carnivorous polar bears. Strong evidence for CCRW movement patterns suggests that many individuals may use a multiphasic movement strategy rather than one-behaviour strategies such as the Lévy walk. The fact that the best model was insufficient to describe the movement paths of many individuals suggests that some animals living in sparse environments may use

  1. Novel Cannulation Strategy for Repair of an Ascending Aortic Pseudoaneurysm in a 2.8-kg Infant.

    PubMed

    Venkataraman, Rajesh; Thangavelu, Periyasamy; Muthukumar, Sivasubramanian; Jayavelan, Ramkumar; Pyrra, Dheeraj; Karthekeyan, Baskar Ranjith; Vakamudi, Mahesh; Rathinasamy, Jebaraj

    2015-10-01

    Pseudoaneurysm of the ascending aorta is rare in infants, with few cases reported in the literature. These aneurysms are usually mycotic, occurring after cardiac surgery, or caused by mediastinitis. They have high risk of spontaneous rupture. Surgery is usually complex because of the need for peripheral cannulation in small infants. We report an ascending aortic pseudoaneurysm in a less than 3-month-old infant that occurred within a month after repair of type 2 truncus arteriosus and was managed successfully with a modified cardiopulmonary bypass strategy.

  2. Multiple Learning Strategies Project. Small Engine Repair Service. Low Reader-Educable Mentally Impaired. [Vol. 1.

    ERIC Educational Resources Information Center

    Pitts, Jim; And Others

    This instructional package, one of two designed for low reader-educable mentally impaired students, focuses on the vocational area of small engine repair service. (Low readers are identified as those reading at a 3-6 grade level.) Contained in this document are forty-three learning modules organized into nine units: engine block; air cleaner;…

  3. Multiple Learning Strategies Project. Small Engine Repair Service. Regular Vocational. [Vol. 1.

    ERIC Educational Resources Information Center

    Pitts, Jim; And Others

    This instructional package is one of two designed for use by regular vocational students in the vocational area of small engine repair service. Contained in this document are forty-four learning modules organized into ten units: engine block; air cleaner; starters; fuel tanks; lines, filters, and pumps; carburetors; electrical; magneto systems;…

  4. Multiple Learning Strategies Project. Small Engine Repair Service. [Regular Vocational. Vol. 2.

    ERIC Educational Resources Information Center

    Pitts, Jim; And Others

    This instructional package is one of two designed for use by regular vocational students in the vocational area of small engine repair service. Contained in this document are forty-nine learning modules organized into eleven units: test equipment; motorcycle; engine removal and replacement; machining; tune-ups; short blocks; storage; filling out…

  5. Multiple Learning Strategies Project. Small Engine Repair Service. Low Reader-Educable Mentally Impaired. [Vol. 2.

    ERIC Educational Resources Information Center

    White, Debi; And Others

    This instructional package, one of two designed for low reader-educable mentally impaired students, focuses on the vocational area of small engine repair service. (Low readers are identified as those at a reading level of grades 3-6.) Contained in this document are fifty learning modules organized into twelve units: sharpening and grinding mowers;…

  6. Evaluation of mask repair strategies via focused electron, helium, and neon beam induced processing for EUV applications

    NASA Astrophysics Data System (ADS)

    Gonzalez, C. M.; Slingenbergh, W.; Timilsina, R.; Noh, J.-H.; Stanford, M. G.; Lewis, B. B.; Klein, K. L.; Liang, T.; Fowlkes, J. D.; Rack, P. D.

    2014-04-01

    One critical area for EUV lithography is the development of appropriate mask repair strategies. To this end, we have explored etching repair strategies for nickel absorber layers and focused electron beam induced deposition of ruthenium capping layers. Nickel has higher EUV absorption than the standard TaN absorber layer and thus thinner films and improved optical quality can be realized. A thin (2.5 nm) ruthenium film is commonly used as a protective capping layer on the Mo-Si EUV multi-layer mirror which mechanically and chemically protects the multi-layers during standard mask-making procedures. The gas field ion (GFIS) microscope was used to investigate helium and neon ion beam induced etching (IBIE) of nickel as a candidate technique for EUV lithography mask editing. No discernable nickel etching was observed for helium, however transmission electron microscopy (TEM) revealed subsurface damage to the underlying Mo-Si multilayers. Subsequently, neon beam induced etching at 30 keV was investigated and successfully removed the 50 nm nickel absorber film. TEM imaging also revealed subsurface damage in the underlying Mo-Si multilayer. Two damage regimes were apparent, namely: 1) beam induced mixing of the Mo-Si layers and 2) nanobubble formation. Monte Carlo simulations were performed and the observed damage regimes were correlated to: 1) the nuclear energy loss and 2) a critical implant concentration. Electron beam induced deposition (EBID) was explored to deposit ruthenium capping/protective layers. Several ruthenium precursors were screened and so far liquid bis(ethylcyclopentyldienyl)ruthenium(II) was successful. The purity of the as-deposited nanodeposits was estimated to be 10% Ru and 90% C. We demonstrate a new chemically assisted electron beam purification process to remove carbon by-products and show that high-fidelity nanoscale ruthenium repairs can be realized.

  7. A novel strategy to enhance mesenchymal stem cell migration capacity and promote tissue repair in an injury specific fashion.

    PubMed

    Xinaris, C; Morigi, M; Benedetti, V; Imberti, B; Fabricio, A S; Squarcina, E; Benigni, A; Gagliardini, E; Remuzzi, G

    2013-01-01

    Mesenchymal stem cells (MSCs) of bone marrow origin appear to be an attractive candidate for cell-based therapies. However, the major barrier to the effective implementation of MSC-based therapies is the lack of specific homing of exogenously infused cells and overall the inability to drive them to the diseased or damaged tissue. In order to circumvent these limitations, we developed a preconditioning strategy to optimize MSC migration efficiency and potentiate their beneficial effect at the site of injury. Initially, we screened different molecules by using an in vitro injury-migration setting, and subsequently, we evaluated the effectiveness of the different strategies in mice with acute kidney injury (AKI). Our results showed that preconditioning of MSCs with IGF-1 before infusion improved cell migration capacity and restored normal renal function after AKI. The present study demonstrates that promoting migration of MSCs could increase their therapeutic potential and indicates a new therapeutic paradigm for organ repair.

  8. Behavioral coping strategies in response to social stress are associated with distinct neuroendocrine, monoaminergic and immune response profiles in mice.

    PubMed

    De Miguel, Zurine; Vegas, Oscar; Garmendia, Larraitz; Arregi, Amaia; Beitia, Garikoitz; Azpiroz, Arantza

    2011-12-01

    Individual variation in behavioral coping strategies to stress implies that animals may have a distinct physiological adaptation to stress; these differences may underlie differences in vulnerability to stress-related diseases. This study was designed to test the hypothesis that different behavioral coping strategies (active vs. passive) are stable over time and that they would be associated with differences in hypothalamic-pituitary-adrenal (HPA) and sympathetic-adreno-medular (SAM) axes, and monoaminergic and immune activity. Male mice were subjected to social stress. Twelve days after the first social interaction, mice were subjected to a second identical social stress interaction. Behavior was videotaped and assessed during both sessions. One hour after the final social interaction, serum was collected for corticosterone and adrenaline concentrations and brains were collected for hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression. Monoaminergic system activity was determined by mRNA expression of serotonin, dopamine and noradrenaline synthetic enzymes in the brain stem. Immune system activity was determined by mRNA expression of hypothalamic interleukin-1β (IL-1β) and splenic IL-1β and interleukin-2 (IL-2). Mice engaging in a passive strategy had higher serum corticosterone and lower serum adrenaline concentrations than the active group. The passive group showed lower hypothalamic mRNA expression of IL-1β and CRH and lower splenic mRNA expression of IL-2 and IL-1β relative to mice in the active group. An active strategy was associated with higher expression of the dopaminergic synthetic enzyme, while a passive strategy was associated with decreased expression of the serotonergic synthetic enzyme. These findings indicate that individual coping strategies are stable over time and are related to differences in the physiological stress response and immune activity. PMID:21864582

  9. Comparison of phylogenetically distinct Histoplasma strains reveals evolutionarily divergent virulence strategies.

    PubMed

    Sepúlveda, Victoria E; Williams, Corinne L; Goldman, William E

    2014-01-01

    Infection with the dimorphic fungus Histoplasma capsulatum results from the inhalation of contaminated soil. Disease outcome is variable and depends on the immune status of the host, number of organisms inhaled, and the H. capsulatum strain. H. capsulatum is divided into seven distinct clades based on phylogenetic analyses, and strains from two separate clades have been identified in North America (denoted as NAm strains). We characterized an H. capsulatum isolate (WU24) from the NAm 1 lineage in relation to two other well-characterized Histoplasma isolates, the Panamanian strain G186A and the NAm 2 strain G217B. We determined that WU24 is a chemotype II strain and requires cell wall α-(1,3)-glucan for successful in vitro infection of macrophages. In a mouse model of histoplasmosis, WU24 exhibited a disease profile that was very similar to that of strain G186A at a high sublethal dose; however, at this dose G217B had markedly different kinetics. Surprisingly, infection with a lower dose mitigated many of the differences during the course of infection. The observed differences in fungal burden, disease kinetics, symptomology, and cytokine responses all indicate that there is a sophisticated relationship between host and fungus that drives the development and progression of histoplasmosis. Importance: Histoplasmosis has a wide range of clinical manifestations, presenting as mild respiratory distress, acute respiratory infection, or a life-threatening disseminated disease most often seen in immunocompromised patients. Additionally, the outcome appears to be dependent on the amount and strain of fungus inhaled. In this study, we characterized a recent clinical H. capsulatum isolate that was collected from an HIV(+) individual in North America. In contrast to other isolates from the same lineage, this strain, WU24, infected both macrophages and wild-type mice. We determined that in contrast to many other North American strains, WU24 infection of macrophages is

  10. Dual promoters of the major catalase (KatA) govern distinct survival strategies of Pseudomonas aeruginosa

    PubMed Central

    Chung, In-Young; Kim, Bi-o; Jang, Hye-Jeong; Cho, You-Hee

    2016-01-01

    KatA is the major catalase required for hydrogen peroxide (H2O2) resistance and acute virulence in Pseudomonas aeruginosa PA14, whose transcription is driven from the promoter (katAp1) located at 155 nucleotide (nt) upstream of the start codon. Here, we identified another promoter (katAp2), the +1 of which was mapped at the 51 nt upstream of the start codon, which was responsible for the basal transcription during the planktonic culture and down-regulated upon H2O2 treatment under the control by the master regulator of anaerobiosis, Anr. To dissect the roles of the dual promoters in conditions involving KatA, we created the promoter mutants for each -10 box (p1m, p2m, and p1p2m) and found that katAp1 is required for the function of KatA in the logarithmic growth phase during the planktonic culture as well as in acute virulence, whereas katAp2 is required for the function of KatA in the stationary phase as well as in the prolonged biofilm culture. This dismantling of the dual promoters of katA sheds light on the roles of KatA in stress resistance in both proliferative and growth-restrictive conditions and thus provides an insight into the regulatory impacts of the major catalase on the survival strategies of P. aeruginosa. PMID:27491679

  11. Dual promoters of the major catalase (KatA) govern distinct survival strategies of Pseudomonas aeruginosa.

    PubMed

    Chung, In-Young; Kim, Bi-O; Jang, Hye-Jeong; Cho, You-Hee

    2016-08-05

    KatA is the major catalase required for hydrogen peroxide (H2O2) resistance and acute virulence in Pseudomonas aeruginosa PA14, whose transcription is driven from the promoter (katAp1) located at 155 nucleotide (nt) upstream of the start codon. Here, we identified another promoter (katAp2), the +1 of which was mapped at the 51 nt upstream of the start codon, which was responsible for the basal transcription during the planktonic culture and down-regulated upon H2O2 treatment under the control by the master regulator of anaerobiosis, Anr. To dissect the roles of the dual promoters in conditions involving KatA, we created the promoter mutants for each -10 box (p1m, p2m, and p1p2m) and found that katAp1 is required for the function of KatA in the logarithmic growth phase during the planktonic culture as well as in acute virulence, whereas katAp2 is required for the function of KatA in the stationary phase as well as in the prolonged biofilm culture. This dismantling of the dual promoters of katA sheds light on the roles of KatA in stress resistance in both proliferative and growth-restrictive conditions and thus provides an insight into the regulatory impacts of the major catalase on the survival strategies of P. aeruginosa.

  12. Root and leaf traits reflect distinct resource acquisition strategies in tropical lianas and trees.

    PubMed

    Collins, Courtney G; Wright, S Joseph; Wurzburger, Nina

    2016-04-01

    In Neotropical forests, lianas are increasing in abundance relative to trees. This increased species richness may reflect a positive response to global change factors including increased temperature, atmospheric CO2, habitat fragmentation, and drought severity; however, questions remain as to the specific mechanisms facilitating the response. Previous work suggests that lianas may gain an ecological advantage over trees through leaf functional traits that offer a quick return on investment of resources, although it is unknown whether this pattern extends to root traits and relationships with fungal or bacterial symbionts belowground. We sampled confamilial pairs of liana and tree species and quantified morphological and chemical traits of leaves and fine roots, as well as root symbiont abundance, to determine whether functional traits associated with resource acquisition differed between the two. Compared to trees, lianas possessed higher specific leaf area, specific root length, root branching intensity, and root nitrogen (N) and phosphorus (P) concentrations, and lower leaf and root tissue density, leaf and root carbon (C), root diameter, root C:P and N:P, and mycorrhizal colonization. Our study provides new evidence that liana leaf and root traits are characterized by a rapid resource acquisition strategy relative to trees. These liana functional traits may facilitate their response to global change, raising questions about how increased liana dominance might affect ecosystem processes of Neotropical forests.

  13. Mechanistic Strategies for Catalysis Adopted by Evolutionary Distinct Family 43 Arabinanases*

    PubMed Central

    Santos, Camila R.; Polo, Carla C.; Costa, Maria C. M. F.; Nascimento, Andrey F. Z.; Meza, Andreia N.; Cota, Junio; Hoffmam, Zaira B.; Honorato, Rodrigo V.; Oliveira, Paulo S. L.; Goldman, Gustavo H.; Gilbert, Harry J.; Prade, Rolf A.; Ruller, Roberto; Squina, Fabio M.; Wong, Dominic W. S.; Murakami, Mário T.

    2014-01-01

    Arabinanases (ABNs, EC 3.2.1.99) are promising catalysts for environmentally friendly biomass conversion into energy and chemicals. These enzymes catalyze the hydrolysis of the α-1,5-linked l-arabinofuranoside backbone of plant cell wall arabinans releasing arabino-oligosaccharides and arabinose, the second most abundant pentose in nature. In this work, new findings about the molecular mechanisms governing activation, functional differentiation, and catalysis of GH43 ABNs are presented. Biophysical, mutational, and biochemical studies with the hyperthermostable two-domain endo-acting ABN from Thermotoga petrophila (TpABN) revealed how some GH43 ABNs are activated by calcium ions via hyperpolarization of the catalytically relevant histidine and the importance of the ancillary domain for catalysis and conformational stability. On the other hand, the two GH43 ABNs from rumen metagenome, ARN2 and ARN3, presented a calcium-independent mechanism in which sodium is the most likely substituent for calcium ions. The crystal structure of the two-domain endo-acting ARN2 showed that its ability to efficiently degrade branched substrates is due to a larger catalytic interface with higher accessibility than that observed in other ABNs with preference for linear arabinan. Moreover, crystallographic characterization of the single-domain exo-acting ARN3 indicated that its cleavage pattern producing arabinose is associated with the chemical recognition of the reducing end of the substrate imposed by steric impediments at the aglycone-binding site. By structure-guided rational design, ARN3 was converted into a classical endo enzyme, confirming the role of the extended Arg203–Ala230 loop in determining its action mode. These results reveal novel molecular aspects concerning the functioning of GH43 ABNs and provide new strategies for arabinan degradation. PMID:24469445

  14. Mechanistic strategies for catalysis adopted by evolutionary distinct family 43 arabinanases.

    PubMed

    Santos, Camila R; Polo, Carla C; Costa, Maria C M F; Nascimento, Andrey F Z; Meza, Andreia N; Cota, Junio; Hoffmam, Zaira B; Honorato, Rodrigo V; Oliveira, Paulo S L; Goldman, Gustavo H; Gilbert, Harry J; Prade, Rolf A; Ruller, Roberto; Squina, Fabio M; Wong, Dominic W S; Murakami, Mário T

    2014-03-14

    Arabinanases (ABNs, EC 3.2.1.99) are promising catalysts for environmentally friendly biomass conversion into energy and chemicals. These enzymes catalyze the hydrolysis of the α-1,5-linked L-arabinofuranoside backbone of plant cell wall arabinans releasing arabino-oligosaccharides and arabinose, the second most abundant pentose in nature. In this work, new findings about the molecular mechanisms governing activation, functional differentiation, and catalysis of GH43 ABNs are presented. Biophysical, mutational, and biochemical studies with the hyperthermostable two-domain endo-acting ABN from Thermotoga petrophila (TpABN) revealed how some GH43 ABNs are activated by calcium ions via hyperpolarization of the catalytically relevant histidine and the importance of the ancillary domain for catalysis and conformational stability. On the other hand, the two GH43 ABNs from rumen metagenome, ARN2 and ARN3, presented a calcium-independent mechanism in which sodium is the most likely substituent for calcium ions. The crystal structure of the two-domain endo-acting ARN2 showed that its ability to efficiently degrade branched substrates is due to a larger catalytic interface with higher accessibility than that observed in other ABNs with preference for linear arabinan. Moreover, crystallographic characterization of the single-domain exo-acting ARN3 indicated that its cleavage pattern producing arabinose is associated with the chemical recognition of the reducing end of the substrate imposed by steric impediments at the aglycone-binding site. By structure-guided rational design, ARN3 was converted into a classical endo enzyme, confirming the role of the extended Arg(203)-Ala(230) loop in determining its action mode. These results reveal novel molecular aspects concerning the functioning of GH43 ABNs and provide new strategies for arabinan degradation.

  15. The DNA Repair Inhibitor DT01 as a Novel Therapeutic Strategy for Chemosensitization of Colorectal Liver Metastasis.

    PubMed

    Herath, Nirmitha I; Devun, Flavien; Lienafa, Marie-Christine; Herbette, Aurélie; Denys, Alban; Sun, Jian-Sheng; Dutreix, Marie

    2016-01-01

    Metastatic liver disease from colorectal cancer is a significant clinical problem. This is mainly attributed to nonresectable metastases that frequently display low sensitivities to available chemotherapies and develop drug resistance partly via hyperactivation of some DNA repair functions. Combined therapies have shown some disease control; however, there is still a need for more efficient chemotherapies to achieve eradication of colorectal cancer liver metastasis. We investigated the tolerance and efficacy of a novel class of DNA repair inhibitors, Dbait, in association with conventional chemotherapy. Dbait mimics double-strand breaks and activates damage signaling, consequently inhibiting single- and double-stranded DNA repair enzyme recruitment. In vitro, Dbait treatment increases sensitivity of HT29 and HCT116 colorectal cancer cell lines. In vivo, the pharmacokinetics, biodistribution and the efficacy of the cholesterol-conjugated clinical form of Dbait, DT01, were assessed. The chemosensitizing abilities of DT01 were evaluated in association with oxaliplatin and 5-fluorouracil in intrahepatic HT29 xenografted mice used as a model for colorectal cancer liver metastasis. The high uptake of DT01 indicates that the liver is a specific target. We demonstrate significant antitumor efficacy in a liver metastasis model with DT01 treatment in combination with oxaliplatin and 5-fluorouracil (mean: 501 vs. 872 mm(2), P = 0.02) compared to chemotherapy alone. The decrease in tumor volume is further associated with significant histologic changes in necrosis, proliferation, angiogenesis and apoptosis. Repeated cycles of DT01 do not increase chemotherapy toxicity. Combining DT01 with conventional chemotherapy may prove to be a safe and effective therapeutic strategy in the treatment of metastatic liver cancer.

  16. In situ strategy for bone repair by facilitated endogenous tissue engineering.

    PubMed

    Chen, Jingdi; Zhang, Yujue; Pan, Panpan; Fan, Tiantang; Chen, Mingmao; Zhang, Qiqing

    2015-11-01

    Traditional tissue engineering procedures are expensive and time consuming. Facilitated endogenous tissue engineering (FETE) provides a solution that can avoid the ex vivo culture of autologous cells and initiate in situ reparative endogenous repair processes in vivo. This method involves fabricating a porous scaffold that mimics the environment present during the bone formation process, consisting of components that provide biomimetic interfacial interactions to cells. After the scaffold is implanted, progenitor cells provided by autologous bone marrow and surrounding tissues then differentiate to bone cells under the direction of the in situ scaffold. This paper reports a biomimetic method to prepare a hierarchically structured hybrid scaffold. Bone-like nano hydroxyapatite (HA) was crystallized from a collagen and chitosan (CC) matrix to form a porous scaffold. The in vivo study demonstrates that this nanohybrid scaffold supports excellent bone repair. This means that the FETE approach, in which the cell culture portion of traditional tissue engineering takes place in vivo, can promote the intrinsic regenerative potential of endogenous tissues.

  17. Strategies for endogenous spinal cord repair: HPMA hydrogel to recruit migrating endogenous stem cells.

    PubMed

    Espinosa-Jeffrey, Araceli; Oregel, Karlos; Wiggins, Laurent; Valera, Remelyn; Bosnoyan, Kathrin; Agbo, Chioma; Awosika, Oluwole; Zhao, Paul M; de Vellis, Jean; Woerly, Stéphane

    2012-01-01

    Injury to the spinal cord disrupts ascending and descending axonal pathways and causes tissue damage with a subsequent limited cellular regeneration. Successful treatment would encompass the restoration of the cytoarchitecture, homeostasis and function all in dear need. Transplantation-based treatments using exogenous cells are the most favoured approach. Yet, with the advent of the stem cell concept and continuous progress in the field it became clear that the endogenous potential for repair is greater than previously thought. As an alternative to neural grafting, we and other researchers have aimed at understanding what are the elements needed for a successful repair with self progenitors that would give rise to the cell types needed to restore function of the central nervous system. Some studies involve both scaffolds and cell grafts. Here we describe studies on spinal cord repair using what we call "endogenous tissue engineering for regenerative medicine". The approach involves a hydrogel that mimics the natural milieu where endogenous pre-existing and newly formed cells populate the gel progressively allowing for the integration of CNS self populations leading to a successful recovery of function. Highlight aspects learned from this type of studies are that: Endogenous reconstruction of the injured spinal cord is possible by using the adequate support. The contribution of nestin-expressing progenitors to spinal cord regeneration is continuous and substantial both, in the reconstructed segment as well as, along the distal and caudal segments of the reconstructed spinal cord. Most of these cells appear to have been in a quiescent state until the injury occurred and only a small fraction of these neural progenitors was produced via cell proliferation. The hydrogel combined with exercise was necessary and sufficient to restore locomotor function in cats that underwent spinal transaction followed by reconstructive surgery. This recovery of function was first seen

  18. Strategies for tissue engineering cardiac constructs to affect functional repair following myocardial infarction.

    PubMed

    Ye, Kathy Yuan; Black, Lauren Deems

    2011-10-01

    Tissue-engineered cardiac constructs are a high potential therapy for treating myocardial infarction. These therapies have the ability to regenerate or recreate functional myocardium following the infarction, restoring some of the lost function of the heart and thereby preventing congestive heart failure. Three key factors to consider when developing engineered myocardial tissue include the cell source, the choice of scaffold, and the use of biomimetic culture conditions. This review details the various biomaterials and scaffold types that have been used to generate engineered myocardial tissues as well as a number of different methods used for the fabrication and culture of these constructs. Specific bioreactor design considerations for creating myocardial tissue equivalents in vitro, such as oxygen and nutrient delivery as well as physical stimulation, are also discussed. Lastly, a brief overview of some of the in vivo studies that have been conducted to date and their assessment of the functional benefit in repairing the injured heart with engineered myocardial tissue is provided.

  19. Advances in mesenchymal stem cell-based strategies for cartilage repair and regeneration.

    PubMed

    Toh, Wei Seong; Foldager, Casper Bindzus; Pei, Ming; Hui, James Hoi Po

    2014-10-01

    Significant research efforts have been undertaken in the last decade in the development of stem cell-based therapies for cartilage repair. Among the various stem cell sources, mesenchymal stem cells (MSCs) demonstrate great promise and clinical efficacy in cartilage regeneration. With a deeper understanding of stem cell biology, new therapeutics and new bioengineering approaches have emerged and showed potential for further developments. Of note, there has been a paradigm shift in applying MSCs for tissue regeneration from the use of stem cells for transplantation to the use of stem cell-derived matrix and secretome components as therapeutic tools and agents for cartilage regeneration. In this review, we will discuss the emerging role of MSCs in cartilage regeneration and the most recent advances in development of stem cell-based therapeutics for cartilage regeneration.

  20. Visualization of DNA double-strand break repair in live bacteria reveals dynamic recruitment of Bacillus subtilis RecF, RecO and RecN proteins to distinct sites on the nucleoids.

    PubMed

    Kidane, Dawit; Sanchez, Humberto; Alonso, Juan C; Graumann, Peter L

    2004-06-01

    We have found that SMC-like RecN protein, RecF and RecO proteins that are involved in DNA recombination play an important role in DNA double-strand break (DSB) repair in Bacillus subtilis. Upon induction of DNA DSBs, RecN, RecO and RecF localized as a discrete focus on the nucleoids in a majority of cells, whereas two or three foci were rarely observed. RecN, RecO and RecF co-localized to the induced foci, with RecN localizing first, while RecO localized later, followed by RecF. Thus, three repair proteins were differentially recruited to distinct sites on the nucleoids, potentially constituting active DSB repair centres (RCs). RecF did not form regular foci in the absence of RecN and failed to form any foci in recO cells, demonstrating a central role for RecN and RecO in initializing the formation of RCs. RecN/O/F foci were detected in recA, recG or recU mutant cells, indicating that the proteins act upstream of proteins involved in synapsis or post-synapsis. In the absence of exogenous DNA damage, RCs were rare, but they accumulated in recA and recU cells, suggesting that DSBs occur frequently in the absence of RecA or RecU. The results suggest a model in which RecN that forms multimers in solution and high-molecular-weight complexes in cells containing DSBs initiates the formation of RCs that mediate DSB repair with the homologous sister chromosome, which presents a novel concept for DSB repair in prokaryotes. PMID:15186413

  1. Distinct physiological strategies are used to cope with constant hypoxia and intermittent hypoxia in killifish (Fundulus heteroclitus).

    PubMed

    Borowiec, Brittney G; Darcy, Kimberly L; Gillette, Danielle M; Scott, Graham R

    2015-04-15

    Many fish encounter hypoxia on a daily cycle, but the physiological effects of intermittent hypoxia are poorly understood. We investigated whether acclimation to constant (sustained) hypoxia or to intermittent diel cycles of nocturnal hypoxia (12 h normoxia:12 h hypoxia) had distinct effects on hypoxia tolerance or on several determinants of O2 transport and O2 utilization in estuarine killifish. Adult killifish were acclimated to normoxia, constant hypoxia, or intermittent hypoxia for 7 or 28 days in brackish water (4 ppt). Acclimation to both hypoxia patterns led to comparable reductions in critical O2 tension and resting O2 consumption rate, but only constant hypoxia reduced the O2 tension at loss of equilibrium. Constant (but not intermittent) hypoxia decreased filament length and the proportion of seawater-type mitochondrion-rich cells in the gills (which may reduce ion loss and the associated costs of active ion uptake), increased blood haemoglobin content, and reduced the abundance of oxidative fibres in the swimming muscle. In contrast, only intermittent hypoxia augmented the oxidative and gluconeogenic enzyme activities in the liver and increased the capillarity of glycolytic muscle, each of which should facilitate recovery between hypoxia bouts. Neither exposure pattern affected muscle myoglobin content or the activities of metabolic enzymes in the brain or heart, but intermittent hypoxia increased brain mass. We conclude that the pattern of hypoxia exposure has an important influence on the mechanisms of acclimation, and that the optimal strategies used to cope with intermittent hypoxia may be distinct from those for coping with constant hypoxia.

  2. Distinct Roles of Ape1 Protein, an Enzyme Involved in DNA Repair, in High or Low Linear Energy Transfer Ionizing Radiation-induced Cell Killing*

    PubMed Central

    Wang, Hongyan; Wang, Xiang; Chen, Guangnan; Zhang, Xiangming; Tang, Xiaobing; Park, Dongkyoo; Cucinotta, Francis A.; Yu, David S.; Deng, Xingming; Dynan, William S.; Doetsch, Paul W.; Wang, Ya

    2014-01-01

    High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy. PMID:25210033

  3. Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.

    PubMed

    Zheng, Li-zhen; Cao, Hui-juan; Chen, Shi-hui; Tang, Tao; Fu, Wei-min; Huang, Le; Chow, Dick Ho Kiu; Wang, Yi-xiang; Griffith, James Francis; He, Wei; Zhou, Hong; Zhao, De-wei; Zhang, Ge; Wang, Xin-luan; Qin, Ling

    2015-11-01

    Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (μCT)-based trabecular architecture with finite element analysis (FEA), μCT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D μCT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy. PMID:25917347

  4. Bidirectional thermotaxis in Caenorhabditis elegans is mediated by distinct sensorimotor strategies driven by the AFD thermosensory neurons

    PubMed Central

    Luo, Linjiao; Cook, Nathan; Venkatachalam, Vivek; Martinez-Velazquez, Luis A.; Zhang, Xiaodong; Calvo, Ana C.; Hawk, Josh; MacInnis, Bronwyn L.; Frank, Michelle; Ng, Jia Hong Ray; Klein, Mason; Gershow, Marc; Hammarlund, Marc; Goodman, Miriam B.; Colón-Ramos, Daniel A.; Zhang, Yun; Samuel, Aravinthan D. T.

    2014-01-01

    The nematode Caenorhabditis elegans navigates toward a preferred temperature setpoint (Ts) determined by long-term temperature exposure. During thermotaxis, the worm migrates down temperature gradients at temperatures above Ts (negative thermotaxis) and performs isothermal tracking near Ts. Under some conditions, the worm migrates up temperature gradients below Ts (positive thermotaxis). Here, we analyze positive and negative thermotaxis toward Ts to study the role of specific neurons that have been proposed to be involved in thermotaxis using genetic ablation, behavioral tracking, and calcium imaging. We find differences in the strategies for positive and negative thermotaxis. Negative thermotaxis is achieved through biasing the frequency of reorientation maneuvers (turns and reversal turns) and biasing the direction of reorientation maneuvers toward colder temperatures. Positive thermotaxis, in contrast, biases only the direction of reorientation maneuvers toward warmer temperatures. We find that the AFD thermosensory neuron drives both positive and negative thermotaxis. The AIY interneuron, which is postsynaptic to AFD, may mediate the switch from negative to positive thermotaxis below Ts. We propose that multiple thermotactic behaviors, each defined by a distinct set of sensorimotor transformations, emanate from the AFD thermosensory neurons. AFD learns and stores the memory of preferred temperatures, detects temperature gradients, and drives the appropriate thermotactic behavior in each temperature regime by the flexible use of downstream circuits. PMID:24550307

  5. Normoxia vs. Hyperoxia: Impact of Oxygen Tension Strategies on Outcomes for Patients Receiving Cardiopulmonary Bypass for Routine Cardiac Surgical Repair

    PubMed Central

    Brown, D. Mark; Holt, David W.; Edwards, Jeff T.; Burnett, Robert J.

    2006-01-01

    Abstract: Oxygen pressure field theory (OPFT) was originally described in the early 1900s by Danish physiologist, Dr. August Krogh. This revolutionary theory described microcirculation of blood gases at the capillary level using a theoretical cylindrical tissue model commonly referred to as the Krogh cylinder. In recent years, the principles and benefits of OPFT in long-term extracorporeal circulatory support (ECMO) have been realized. Cardiac clinicians have successfully mastered OPFT fundamentals and incorporated them into their clinical practice. These clinicians have experienced significantly improved survival rates as a result of OPFT strategies. The objective of this study was to determine if a hyperoxic strategy can lead to equally beneficial outcomes for short-term support as measured by total ventilator time and total length of stay in intensive care unit (ICU) in the cardiopulmonary bypass (CPB) patient at a private institution. Patients receiving traditional blood gas management while on CPB (group B, n = 17) were retrospectively compared with hyperoxic patients (group A, n = 19). Hyperoxic/OPFT management was defined as paO2 values of 300–350 mmHg and average VSAT > 75%. Traditional blood gas management was defined as paO2 values of 150–250 mmHg and average VSAT < 75%. No significant differences between treatment groups were found for patient weight, CPB/AXC times, BSA, pre/post Hgb, pre/post-platelet (PLT) counts, pre/post-creatinine levels, pre/post-BUN, UF volumes, or CPB urine output. Additionally, no significant statistical differences were found between treatment groups for total time in ICU (T-ICU) or total time on ventilator (TOV). Hyperoxic management strategies provided no conclusive evidence of outcome improvement for patients receiving CPB for routine cardiac surgical repair. Additional studies into the impact of hyperoxia in short-term extracorporeal circulatory support are needed. PMID:17089511

  6. New strategies to improve results of mesh surgeries for vaginal prolapses repair – an update

    PubMed Central

    Dias, Fernando Goulart Fernandes; Dias, Paulo Henrique Goulart Fernandes; Prudente, Alessandro; Riccetto, Cassio

    2015-01-01

    ABSTRACT The use of meshes has become the first option for the treatment of soft tissue disorders as hernias and stress urinary incontinence and widely used in vaginal prolapse's treatment. However, complications related to mesh issues cannot be neglected. Various strategies have been used to improve tissue integration of prosthetic meshes and reduce related complications. The aim of this review is to present the state of art of mesh innovations, presenting the whole arsenal which has been studied worldwide since composite meshes, coated meshes, collagen's derived meshes and tissue engineered prostheses, with focus on its biocompatibility and technical innovations, especially for vaginal prolapse surgery. PMID:26401853

  7. Tissue engineering-based therapeutic strategies for vocal fold repair and regeneration.

    PubMed

    Li, Linqing; Stiadle, Jeanna M; Lau, Hang K; Zerdoum, Aidan B; Jia, Xinqiao; Thibeault, Susan L; Kiick, Kristi L

    2016-11-01

    Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

  8. Nonpulsed sinusoidal electromagnetic fields as a noninvasive strategy in bone repair: the effect on human mesenchymal stem cell osteogenic differentiation.

    PubMed

    Ledda, Mario; D'Emilia, Enrico; Giuliani, Livio; Marchese, Rodolfo; Foletti, Alberto; Grimaldi, Settimio; Lisi, Antonella

    2015-02-01

    In vivo control of osteoblast differentiation is an important process needed to maintain the continuous supply of mature osteoblast cells for growth, repair, and remodeling of bones. The regulation of this process has also an important and significant impact on the clinical strategies and future applications of cell therapy. In this article, we studied the effect of nonpulsed sinusoidal electromagnetic field radiation tuned at calcium-ion cyclotron frequency of 50 Hz exposure treatment for bone differentiation of human mesenchymal stem cells (hMSCs) alone or in synergy with dexamethasone, their canonical chemical differentiation agent. Five days of continuous exposure to calcium-ion cyclotron resonance affect hMSC proliferation, morphology, and cytoskeletal actin reorganization. By quantitative real-time polymerase chain reaction, we also observed an increase of osteoblast differentiation marker expression such as Runx2, alkaline phosphatase (ALP), osteocalcin (OC), and osteopontin (OPN) together with the osteoprotegerin mRNA modulation. Moreover, in these cells, the increase of the protein expression of OPN and ALP was also demonstrated. These results demonstrate bone commitment of hMSCs through a noninvasive and biocompatible differentiating physical agent treatment and highlight possible applications in new regenerative medicine protocols. PMID:25087470

  9. Generation of human secondary cardiospheres as a potent cell processing strategy for cell-based cardiac repair.

    PubMed

    Cho, Hyun-Jai; Lee, Ho-Jae; Chung, Yeon-Ju; Kim, Ju-Young; Cho, Hyun-Ju; Yang, Han-Mo; Kwon, Yoo-Wook; Lee, Hae-Young; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

    2013-01-01

    Cell therapy is a promising approach for repairing damaged heart. However, there are large rooms to be improved in therapeutic efficacy. We cultured a small quantity (5-10 mg) of heart biopsy tissues from 16 patients who received heart transplantation. We produced primary and secondary cardiospheres (CSs) using repeated three-dimensional culture strategy and characterized the cells. Approximately 5000 secondary CSs were acquired after 45 days. Genetic analysis confirmed that the progenitor cells in the secondary CSs originated from the innate heart, but not from extra-cardiac organs. The expressions of Oct4 and Nanog were significantly induced in secondary CSs compared with adherent cells derived from primary CSs. Those expressions in secondary CSs were higher in a cytokine-deprived medium than in a cytokine-supplemented one, suggesting that formation of the three-dimensional structure was important to enhance stemness whereas supplementation with various cytokines was not essential. Signal blocking experiments showed that the ERK and VEGF pathways are indispensable for sphere formation. To optimize cell processing, we compared four different methods of generating spheres. Method based on the hanging-drop or AggreWell™ was superior to that based on the poly-d-lysine-coated dish or Petri dish with respect to homogeneity of the product, cellular potency and overall simplicity of the process. When transplanted into the ischemic myocardium of immunocompromised mice, human secondary CSs differentiated into cardiomyocytes and endothelial cells. These results demonstrate that generation of secondary CSs from a small quantity of adult human cardiac tissue is a feasible and effective cell processing strategy to improve the therapeutic efficacy of cell therapy.

  10. Generation of human secondary cardiospheres as a potent cell processing strategy for cell-based cardiac repair.

    PubMed

    Cho, Hyun-Jai; Lee, Ho-Jae; Chung, Yeon-Ju; Kim, Ju-Young; Cho, Hyun-Ju; Yang, Han-Mo; Kwon, Yoo-Wook; Lee, Hae-Young; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

    2013-01-01

    Cell therapy is a promising approach for repairing damaged heart. However, there are large rooms to be improved in therapeutic efficacy. We cultured a small quantity (5-10 mg) of heart biopsy tissues from 16 patients who received heart transplantation. We produced primary and secondary cardiospheres (CSs) using repeated three-dimensional culture strategy and characterized the cells. Approximately 5000 secondary CSs were acquired after 45 days. Genetic analysis confirmed that the progenitor cells in the secondary CSs originated from the innate heart, but not from extra-cardiac organs. The expressions of Oct4 and Nanog were significantly induced in secondary CSs compared with adherent cells derived from primary CSs. Those expressions in secondary CSs were higher in a cytokine-deprived medium than in a cytokine-supplemented one, suggesting that formation of the three-dimensional structure was important to enhance stemness whereas supplementation with various cytokines was not essential. Signal blocking experiments showed that the ERK and VEGF pathways are indispensable for sphere formation. To optimize cell processing, we compared four different methods of generating spheres. Method based on the hanging-drop or AggreWell™ was superior to that based on the poly-d-lysine-coated dish or Petri dish with respect to homogeneity of the product, cellular potency and overall simplicity of the process. When transplanted into the ischemic myocardium of immunocompromised mice, human secondary CSs differentiated into cardiomyocytes and endothelial cells. These results demonstrate that generation of secondary CSs from a small quantity of adult human cardiac tissue is a feasible and effective cell processing strategy to improve the therapeutic efficacy of cell therapy. PMID:23103158

  11. Industrial motor repair in the United States

    SciTech Connect

    Schueler, V.; Leistner, P.; Douglass, J.

    1994-09-01

    This report characterizes the motor repair industry in the United States; summarizes current motor repair and testing practice; and identifies barriers to energy motor repair practice and recommends strategies for overcoming those barriers.

  12. Distinct kinetics of human DNA ligases I, IIIalpha, IIIbeta, and IV reveal direct DNA sensing ability and differential physiological functions in DNA repair

    SciTech Connect

    Chen, Xi; Ballin, Jeff D.; Della-Maria, Julie; Tsai, Miaw-Sheue; White, Elizabeth J.; Tomkinson, Alan E.; Wilson, Gerald M.

    2009-05-11

    The three human LIG genes encode polypeptides that catalyze phosphodiester bond formation during DNA replication, recombination and repair. While numerous studies have identified protein partners of the human DNA ligases (hLigs), there has been little characterization of the catalytic properties of these enzymes. In this study, we developed and optimized a fluorescence-based DNA ligation assay to characterize the activities of purified hLigs. Although hLigI joins DNA nicks, it has no detectable activity on linear duplex DNA substrates with short, cohesive single-strand ends. By contrast, hLigIII{beta} and the hLigIII{alpha}/XRCC1 and hLigIV/XRCC4 complexes are active on both nicked and linear duplex DNA substrates. Surprisingly, hLigIV/XRCC4, which is a key component of the major non-homologous end joining (NHEJ) pathway, is significantly less active than hLigIII on a linear duplex DNA substrate. Notably, hLigIV/XRCC4 molecules only catalyze a single ligation event in the absence or presence of ATP. The failure to catalyze subsequent ligation events reflects a defect in the enzyme-adenylation step of the next ligation reaction and suggests that, unless there is an in vivo mechanism to reactivate DNA ligase IV/XRCC4 following phosphodiester bond formation, the cellular NHEJ capacity will be determined by the number of adenylated DNA ligaseIV/XRCC4 molecules.

  13. Shaping Vulnerable Bodies at the Thin Boundary between Environment and Organism: Skin, DNA Repair, and a Genealogy of DNA Care Strategies.

    PubMed

    von Schwerin, Alexander

    2015-09-01

    This paper brings together the history of risk and the history of DNA repair, a biological phenomenon that emerged as a research field in between molecular biology, genetics, and radiation research in the 1960s. The case of xeroderma pigmentosum (XP), an inherited hypersensitivity to UV light and, hence, a disposition to skin cancer will be the starting point to argue that, in the 1970s and 1980s, DNA repair became entangled in the creation of new models of the human body at risk - what is here conceptually referred to as the vulnerability aspect of body history - and new attempts at cancer prevention and enhancement of the body associated with the new flourishing research areas of antimutagenesis and anticarcinogenesis. The aim will be to demonstrate that DNA repair created special attempts at disease prevention: molecular enhancement, seeking to identify means to increase the self-repair abilities of the body at the molecular level. Prevention in this sense meant enhancing the body's ability to cope with the environmental hazards of an already toxic world. This strategy has recently been adopted by the beauty industry, which introduced DNA care as a new target for skin care research and anti-aging formulas. PMID:26256506

  14. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    NASA Astrophysics Data System (ADS)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  15. Distinct molecular strategies for Hox-mediated limb suppression in Drosophila: from cooperativity to dispensability/antagonism in TALE partnership.

    PubMed

    Sambrani, Nagraj; Hudry, Bruno; Maurel-Zaffran, Corinne; Zouaz, Amel; Mishra, Rakesh; Merabet, Samir; Graba, Yacine

    2013-01-01

    The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution. Sequence divergence of paralogous proteins accounts for functional specialization, promoting axial morphological diversification in bilaterian animals. Yet functionally specialized paralogous Hox proteins also continue performing ancient common functions. In this study, we investigate how highly divergent Hox proteins perform an identical function. This was achieved by comparing in Drosophila the mode of limb suppression by the central (Ultrabithorax and AbdominalA) and posterior class (AbdominalB) Hox proteins. Results highlight that Hox-mediated limb suppression relies on distinct modes of DNA binding and a distinct use of TALE cofactors. Control of common functions by divergent Hox proteins, at least in the case studied, relies on evolving novel molecular properties. Thus, changes in protein sequences not only provide the driving force for functional specialization of Hox paralogue proteins, but also provide means to perform common ancient functions in distinct ways.

  16. Comparison between antegrade and retrograde cerebral perfusion or profound hypothermia as brain protection strategies during repair of type A aortic dissection

    PubMed Central

    Rausch, Laura A.; Kouchoukos, Nicholas T.; Lobdell, Kevin W.; Khabbaz, Kamal; Murphy, Edward; Hagberg, Robert C.

    2016-01-01

    Background The goal of this study was to compare early postoperative outcomes and actuarial-free survival between patients who underwent repair of acute type A aortic dissection by the method of cerebral perfusion used. Methods A total of 324 patients from five academic medical centers underwent repair of acute type A aortic dissection between January 2000 and December 2010. Of those, antegrade cerebral perfusion (ACP) was used for 84 patients, retrograde cerebral perfusion (RCP) was used for 55 patients, and deep hypothermic circulatory arrest (DHCA) was used for 184 patients during repair. Major morbidity, operative mortality, and 5-year actuarial survival were compared between groups. Multivariate logistic regression was used to determine predictors of operative mortality and Cox Regression hazard ratios were calculated to determine the predictors of long term mortality. Results Operative mortality was not influenced by the type of cerebral protection (19% for ACP, 14.5% for RCP and 19.1% for DHCA, P=0.729). In multivariable logistic regression analysis, hemodynamic instability [odds ratio (OR) =19.6, 95% confidence intervals (CI), 0.102–0.414, P<0.001] and CPB time >200 min(OR =4.7, 95% CI, 1.962–1.072, P=0.029) emerged as independent predictors of operative mortality. Actuarial 5-year survival was unchanged by cerebral protection modality (48.8% for ACP, 61.8% for RCP and 66.8% for no cerebral protection, log-rank P=0.844). Conclusions During surgical repair of type A aortic dissection, ACP, RCP or DHCA are safe strategies for cerebral protection in selected patients with type A aortic dissection. PMID:27563545

  17. EUVL Mask Blank Repair

    SciTech Connect

    Barty, A; Mirkarimi, P; Stearns, D G; Sweeney, D; Chapman, H N; Clift, M; Hector, S; Yi, M

    2002-05-22

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

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

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

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

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

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

    The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer. PMID:27183258

  20. Human DNA repair genes.

    PubMed

    Wood, R D; Mitchell, M; Sgouros, J; Lindahl, T

    2001-02-16

    Cellular DNA is subjected to continual attack, both by reactive species inside cells and by environmental agents. Toxic and mutagenic consequences are minimized by distinct pathways of repair, and 130 known human DNA repair genes are described here. Notable features presently include four enzymes that can remove uracil from DNA, seven recombination genes related to RAD51, and many recently discovered DNA polymerases that bypass damage, but only one system to remove the main DNA lesions induced by ultraviolet light. More human DNA repair genes will be found by comparison with model organisms and as common folds in three-dimensional protein structures are determined. Modulation of DNA repair should lead to clinical applications including improvement of radiotherapy and treatment with anticancer drugs and an advanced understanding of the cellular aging process. PMID:11181991

  1. Biodegradation of cis-1,4-Polyisoprene Rubbers by Distinct Actinomycetes: Microbial Strategies and Detailed Surface Analysis

    PubMed Central

    Linos, Alexandros; Berekaa, Mahmoud M.; Reichelt, Rudolf; Keller, Ulrike; Schmitt, Jürgen; Flemming, Hans-Curt; Kroppenstedt, Reiner M.; Steinbüchel, Alexander

    2000-01-01

    Several actinomycetes isolated from nature were able to use both natural rubber (NR) and synthetic cis-1,4-polyisoprene rubber (IR) as a sole source of carbon. According to their degradation behavior, they were divided into two groups. Representatives of the first group grew only in direct contact to the rubber substrate and led to considerable disintegration of the material during cultivation. The second group consisted of weaker rubber decomposers that did not grow adhesively, as indicated by the formation of clear zones (translucent halos) around bacterial colonies after cultivation on NR dispersed in mineral agar. Taxonomic analysis of four selected strains based on 16S rRNA similarity examinations revealed two Gordonia sp. strains, VH2 and Kb2, and one Mycobacterium fortuitum strain, NF4, belonging to the first group as well as one Micromonospora aurantiaca strain, W2b, belonging to the second group. Schiff's reagent staining tests performed for each of the strains indicated colonization of the rubber surface, formation of a bacterial biofilm, and occurrence of compounds containing aldehyde groups during cultivation with NR latex gloves. Detailed analysis by means of scanning electron microscopy yielded further evidence for the two different microbial strategies and clarified the colonization efficiency. Thereby, strains VH2, Kb2, and NF4 directly adhered to and merged into the rubber material, while strain W2b produced mycelial corridors, especially on the surface of IR. Fourier transform infrared spectroscopy comprising the attenuated total reflectance technique was applied on NR latex gloves overgrown by cells of the Gordonia strains, which were the strongest rubber decomposers. Spectra demonstrated the decrease in number of cis-1,4 double bonds, the formation of carbonyl groups, and the change of the overall chemical environment, indicating that an oxidative attack at the double bond is the first metabolic step of the biodegradation process. PMID:10742254

  2. Clubfoot repair

    MedlinePlus

    ... release; Talipes equinovarus - repair; Tibialis anterior tendon transfer Images Clubfoot repair - series References Kelly DM. Congenital Anomalies ... provided herein should not be used during any medical emergency or for the diagnosis or treatment of ...

  3. Tendon repair

    MedlinePlus

    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 ...

  4. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

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

    2005-07-20

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated 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. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal 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 when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  5. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

    The concept of using gene transfer strategies for cartilage repair originates from the idea of transferring genes encoding therapeutic factors into the repair tissue, resulting in a temporarily and spatially defined delivery of therapeutic molecules to sites of cartilage damage. This review focuses on the potential benefits of using gene therapy approaches for the repair of articular cartilage and meniscal fibrocartilage, including articular cartilage defects resulting from acute trauma, osteochondritis dissecans, osteonecrosis, and osteoarthritis. Possible applications for meniscal repair comprise meniscal lesions, meniscal sutures, and meniscal transplantation. Recent studies in both small and large animal models have demonstrated the applicability of gene-based approaches for cartilage repair. Chondrogenic pathways were stimulated in the repair tissue and in osteoarthritic cartilage using genes for polypeptide growth factors and transcription factors. Although encouraging data have been generated, a successful translation of gene therapy for cartilage repair will require an ongoing combined effort of orthopedic surgeons and of basic scientists. PMID:26069580

  6. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

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

    2004-12-31

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated 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. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal 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 when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without

  7. A high throughput screening strategy to identify protein-protein interaction inhibitors that block the Fanconi anemia DNA repair pathway

    PubMed Central

    Voter, Andrew F.; Manthei, Kelly A.

    2016-01-01

    Induction of the Fanconi anemia (FA) DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies. Proper execution of the FA pathway requires interaction between the FA complementation group M protein (FANCM) and the RecQ-mediated genome instability protein (RMI) complex, and mutations that disrupt FANCM/RMI interactions sensitize cells to DNA crosslinking agents. Inhibitors that block FANCM/RMI complex formation could be useful therapeutics for re-sensitizing tumors that have acquired chemotherapeutic resistance. To identify such inhibitors, we have developed and validated high-throughput fluorescence polarization and proximity assays that are sensitive to inhibitors that disrupt interactions between the RMI complex and its binding site on FANCM (a peptide referred to as MM2). A pilot screen of 74,807 small molecules was performed using the fluorescence polarization assay. Hits from the primary screen were further tested using the proximity assay and an orthogonal proximity assay was used to assess inhibitor selectivity. Direct physical interaction between the RMI complex and the most selective inhibitor identified through the screening process was measured by surface plasmon resonance and isothermal titration calorimetry. Observation of direct binding by this small molecule validates the screening protocol. PMID:26962873

  8. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

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

    2004-08-17

    The two broad categories of fiber-reinforced composite liner repair and deposited weld metal repair technologies were reviewed and evaluated 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. Principal conclusions from a survey of natural gas transmission industry pipeline operators can be summarized in terms of the following performance requirements for internal repair: (1) Use of internal repair is most attractive for river crossings, under other bodies of water, in difficult soil conditions, under highways, under congested intersections, and under railway. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling when a new bore must be created to solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) The most common size range for 80% to 90% of operators surveyed is 508 mm (20 in.) to 762 mm (30 in.), with 95% using 558.8 mm (22 in.) pipe. Evaluation trials were conducted on pipe sections with simulated corrosion damage repaired with glass fiber-reinforced composite liners, carbon fiber-reinforced composite liners, and weld deposition. Additional un-repaired pipe sections were evaluated in the virgin condition and with simulated damage. Hydrostatic failure pressures for pipe sections repaired with glass fiber-reinforced composite liner were only marginally greater than that of pipe sections without liners

  9. Postexercise Dietary Protein Strategies to Maximize Skeletal Muscle Repair and Remodeling in Masters Endurance Athletes: A Review.

    PubMed

    Doering, Thomas M; Reaburn, Peter R; Phillips, Stuart M; Jenkins, David G

    2016-04-01

    Participation rates of masters athletes in endurance events such as long-distance triathlon and running continue to increase. Given the physical and metabolic demands of endurance training, recovery practices influence the quality of successive training sessions and, consequently, adaptations to training. Research has suggested that, after muscle-damaging endurance exercise, masters athletes experience slower recovery rates in comparison with younger, similarly trained athletes. Given that these discrepancies in recovery rates are not observed after non-muscle-damaging exercise, it is suggested that masters athletes have impairments of the protein remodeling mechanisms within skeletal muscle. The importance of postexercise protein feeding for endurance athletes is increasingly being acknowledged, and its role in creating a positive net muscle protein balance postexercise is well known. The potential benefits of postexercise protein feeding include elevating muscle protein synthesis and satellite cell activity for muscle repair and remodeling, as well as facilitating muscle glycogen resynthesis. Despite extensive investigation into age-related anabolic resistance in sedentary aging populations, little is known about how anabolic resistance affects postexercise muscle protein synthesis and thus muscle remodeling in aging athletes. Despite evidence suggesting that physical training can attenuate but not eliminate age-related anabolic resistance, masters athletes are currently recommended to consume the same postexercise dietary protein dose (approximately 20 g or 0.25 g/kg/meal) as younger athletes. Given the slower recovery rates of masters athletes after muscle-damaging exercise, which may be due to impaired muscle remodeling mechanisms, masters athletes may benefit from higher doses of postexercise dietary protein, with particular attention directed to the leucine content of the postexercise bolus.

  10. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

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

    2004-04-12

    solve a leak or other problem. (3) Typical travel distances can be divided into three distinct groups: up to 305 m (1,000 ft.); between 305 m and 610 m (1,000 ft. and 2,000 ft.); and beyond 914 m (3,000 ft.). All three groups require pig-based systems. A despooled umbilical system would suffice for the first two groups which represents 81% of survey respondents. The third group would require an onboard self-contained power unit for propulsion and welding/liner repair energy needs. (4) Pipe diameter sizes range from 50.8 mm (2 in.) through 1,219.2 mm (48 in.). The most common size range for 80% to 90% of operators surveyed is 508 mm to 762 mm (20 in. to 30 in.), with 95% using 558.8 mm (22 in.) pipe. An evaluation of potential repair methods clearly indicates that the project should continue to focus on the development of a repair process involving the use of GMAW welding and on the development of a repair process involving the use of fiber-reinforced composite liners.

  11. Craniosynostosis repair

    MedlinePlus

    ... will be asleep and will not feel pain. Traditional surgery is called open repair. It includes these ... helps keep the swelling down. Talking, singing, playing music, and telling stories may help soothe your child. ...

  12. Minimally disruptive schedule repair for MCM missions

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    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.

  13. Pectus excavatum repair

    MedlinePlus

    Funnel chest repair; Chest deformity repair; Sunken chest repair; Cobbler's chest repair; Nuss repair; Ravitch repair ... There are two types of surgery to repair this condition -- open surgery ... surgery is done while the child is in a deep sleep and pain- ...

  14. Femoral hernia repair

    MedlinePlus

    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 ...

  15. Undescended testicle repair

    MedlinePlus

    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 ...

  16. Cell lineages, growth and repair of the mouse heart.

    PubMed

    Lescroart, Fabienne; Meilhac, Sigolène M

    2012-01-01

    The formation of the heart involves diversification of lineages which differentiate into distinct cardiac cell types or contribute to different regions such as the four cardiac chambers. The heart is the first organ to form in the embryo. However, in parallel with the growth of the organism, before or after birth, the heart has to adapt its size to maintain pumping efficiency. The adult heart has only a mild regeneration potential; thus, strategies to repair the heart after injury are based on the mobilisation of resident cardiac stem cells or the transplantation of external sources of stem cells. We discuss current knowledge on these aspects and raise questions for future research.

  17. Intestinal obstruction repair

    MedlinePlus

    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. ...

  18. Motorcycle Repair.

    ERIC Educational Resources Information Center

    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…

  19. Outboard Repair.

    ERIC Educational Resources Information Center

    Hardway, Jack

    This consortium-developed instructor's manual for small engine repair (with focus on outboard motors) consists of the following nine instructional units: electrical remote control assembly, mechanical remote control assembly, tilt assemblies, exhaust housing, propeller and trim tabs, cooling system, mechanical gearcase, electrical gearcase, and…

  20. Snowmobile Repair.

    ERIC Educational Resources Information Center

    Helbling, Wayne

    This guide is designed to provide and/or improve instruction for occupational training in the area of snowmobile repair, and includes eight areas. Each area consists of one or more units of instruction, with each instructional unit including some or all of the following basic components: Performance objectives, suggested activities for teacher and…

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

    SciTech Connect

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

    2015-11-03

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

  2. Molecular inhibitors of DNA repair: searching for the ultimate tumor killing weapon.

    PubMed

    Nikitaki, Zacharenia; Michalopoulos, Ioannis; Georgakilas, Alexandros G

    2015-08-01

    DNA repair (DR) inhibitors are small molecules that interact with DR proteins in order to disrupt their function and induce a 'strike' to the high fidelity of the mammalian DNA repair systems. Many anticancer therapies aim to harm the DNA of the usually highly proliferative cancer cell, causing it to undergo apoptosis. In response to this, cancer cells attempt to fix the induced lesion and reconstitute its genomic integrity, in turn reducing the efficacy of treatment. To overcome this, DR inhibitors suppress DNA repair proteins' function, increasing the potency and tumor killing effect of chemotherapy or radiotherapy. In this review, we discuss clinically applied novel inhibitors under translational investigation and we apply bioinformatic tools in order to identify repair proteins implicated in more than two phenomenically distinct DNA repair pathways (e.g., base excision repair and nonhomologous end joining), that is, the concept of 'synthetic lethality'. Our study can aid towards the optimization of this therapeutic strategy and, therefore, maximizing treatment effectiveness like in the case of radiation therapy.

  3. Conversational Repair Strategies in Response to Requests for Clarification in Typically Developing Jordanian Children Ages 4;0-6;0 Years

    ERIC Educational Resources Information Center

    Kamal, Sana M.; Haj-Tas, Maisa A.

    2014-01-01

    Conversational repairs are an important pragmatic language skill. We identified types of responses to requests for clarification and their frequencies in typically developing 4;0-6;0-year-old Jordanian children. This study was motivated by the fact that there are no Arabic data regarding this issue and by the limited range of forms of requests for…

  4. [Mechanisms of repair after renal injury].

    PubMed

    Menè, P; Polci, R; Festuccia, F

    2003-01-01

    Recovery from kidney injury through repair mechanisms often linked to inflammation is conditioned by nature and severity of the insult. In the assessment of kidney repair, functional recovery should be kept distinct from structural repair: compensatory hypertrophy/function of intact nephrons often masks the inability of the kidney to heal or replace damaged structures. The mechanisms of repair reflect three degrees of injury, differently handled by the kidney. First, repair of DNA damage is accomplished through proofreading DNA polymerases, along with other controls for sequence misalignment / nucleotide replacement. If DNA cannot be repaired, cells carrying mutation(s) are disposed of through apoptosis, which is also critical to clearing damaged kidney cells and infiltrating leukocytes in acute and chronic ischemic, immunological, or chemical damage. A second mechanism of repair is linked to proliferation of surviving cells. At least 5 types of reparative proliferation are known to occur, some of which implicate stem cell immigration from distant reservoirs, followed by in situ differentiation. A third mode of repair could be referred to as structural repair, indeed limited in the human kidney by the absence of postnatal nephrogenesis. Recovery from acute tubular necrosis involves remodelling of the proximal tubule, with a strict requirement for integrity of the basement membrane. Contrary to the current dogma that only acute injury can be repaired, whereas chronic damage leads to irreversible loss of nephrons, evidence is emerging that some degree of renal remodelling occurs even in chronic renal disease, despite the occurrence of stabilized structural changes.

  5. Mitral valve repair in acquired dextrocardia.

    PubMed

    Elmistekawy, Elsayed; Chan, Vincent; Hynes, Mark; Mesana, Thierry

    2015-10-01

    Surgical correction of valvular heart disease in patients with dextrocardia is extremely rare. We report a surgical case of mitral valve repair in a patient with acquired dextrocardia. Successful mitral valve repair was performed through a right lateral thoracotomy. We describe our surgical strategy and summarize the literature.

  6. New Partnerships for New Jersey: A Financial Strategy for Academic Distinction. Report of the Committee on Future Financing of Rutgers, The State University of New Jersey.

    ERIC Educational Resources Information Center

    Rutgers, The State Univ., New Brunswick, NJ.

    A financial plan to help Rutgers, The State University of New Jersey achieve national stature is considered. Fundamental principles of the financial strategy include: as New Jersey's only comprehensive public research university, Rutgers is in a position to advance the development of New Jersey; the state should provide the university with the…

  7. Scaffold devices for rotator cuff repair.

    PubMed

    Ricchetti, Eric T; Aurora, Amit; Iannotti, Joseph P; Derwin, Kathleen A

    2012-02-01

    Rotator cuff tears affect 40% or more of those aged older than 60 years, and repair failure rates of 20% to 70% remain a significant clinical challenge. Hence, there is a need for repair strategies that can augment the repair by mechanically reinforcing it, while at the same time biologically enhancing the intrinsic healing potential of the tendon. Tissue engineering strategies to improve rotator cuff repair healing include the use of scaffolds, growth factors, and cell seeding, or a combination of these approaches. Currently, scaffolds derived from mammalian extracellular matrix, synthetic polymers, and a combination thereof, have been cleared by the U.S. Food and Drug Administration and are marketed as medical devices for rotator cuff repair in humans. Despite the growing clinical use of scaffold devices for rotator cuff repair, there are numerous questions related to their indication, surgical application, safety, mechanism of action, and efficacy that remain to be clarified or addressed. This article reviews the current basic science and clinical understanding of commercially available synthetic and extracellular matrix scaffolds for rotator cuff repair. Our review will emphasize the host response and scaffold remodeling, mechanical and suture-retention properties, and preclinical and clinical studies on the use of these scaffolds for rotator cuff repair. We will discuss the implications of these data on the future directions for use of these scaffolds in tendon repair procedures.

  8. The Use of Conversational Repairs by African American Preschoolers

    ERIC Educational Resources Information Center

    Stockman, Ida J.; Karasinski, Laura; Guillory, Barbara

    2008-01-01

    Purpose: This study aimed to describe the types and frequency of conversational repairs used by African American (AA) children in relationship to their geographic locations and levels of performance on commonly used speech-language measures. Method: The strategies used to initiate repairs and respond to repair requests were identified in…

  9. Dorsal variant blister aneurysm repair.

    PubMed

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

    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: http://youtu.be/crUreWGQdGo.

  10. Brain aneurysm repair

    MedlinePlus

    ... 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 ...

  11. Repairing native defects on EUV mask blanks

    NASA Astrophysics Data System (ADS)

    Lawliss, Mark; Gallagher, Emily; Hibbs, Michael; Seki, Kazunori; Isogawa, Takeshi; Robinson, Tod; LeClaire, Jeff

    2014-10-01

    Mask defectivity is a serious problem for all lithographic masks, but especially for EUV masks. Defects in the EUV blank are particularly challenging because their elimination is beyond control of the mask fab. If defects have been identified on a mask blank, patterns can be shifted to place as many blank defects as possible in regions where printing impact will be eliminated or become unimportant. For those defects that cannot be mitigated through pattern shift, repair strategies must be developed. Repairing defects that occur naturally in the EUV blank is challenging because the printability of these defects varies widely. This paper describes some types of native defects commonly found and begins to outline a triage strategy for defects that are identified on the blank. Sample defects best suited to nanomachining repair are treated in detail: repairs are attempted, characterized using mask metrology and then tested for printability. Based on the initial results, the viability of repairing EUV blank native defects is discussed.

  12. Reprogramming Cells for Brain Repair

    PubMed Central

    Guarino, Alyx T.; McKinnon, Randall D.

    2013-01-01

    At present there are no clinical therapies that can repair traumatic brain injury, spinal cord injury or degenerative brain disease. While redundancy and rewiring of surviving circuits can recover some lost function, the brain and spinal column lack sufficient endogenous stem cells to replace lost neurons or their supporting glia. In contrast, pre-clinical studies have demonstrated that exogenous transplants can have remarkable efficacy for brain repair in animal models. Mesenchymal stromal cells (MSCs) can provide paracrine factors that repair damage caused by ischemic injury, and oligodendrocyte progenitor cell (OPC) grafts give dramatic functional recovery from spinal cord injury. These studies have progressed to clinical trials, including human embryonic stem cell (hESC)-derived OPCs for spinal cord repair. However, ESC-derived allografts are less than optimal, and we need to identify a more appropriate donor graft population. The cell reprogramming field has developed the ability to trans-differentiate somatic cells into distinct cell types, a technology that has the potential to generate autologous neurons and glia which address the histocompatibility concerns of allografts and the tumorigenicity concerns of ESC-derived grafts. Further clarifying how cell reprogramming works may lead to more efficient direct reprogram approaches, and possibly in vivo reprogramming, in order to promote brain and spinal cord repair. PMID:24961526

  13. Techniques in Endovascular Aneurysm Repair

    PubMed Central

    Phade, Sachin V.; Garcia-Toca, Manuel; Kibbe, Melina R.

    2011-01-01

    Endovascular repair of infrarenal abdominal aortic aneurysms (EVARs) has revolutionized the treatment of aortic aneurysms, with over half of elective abdominal aortic aneurysm repairs performed endoluminally each year. Since the first endografts were placed two decades ago, many changes have been made in graft design, operative technique, and management of complications. This paper summarizes modern endovascular grafts, considerations in preoperative planning, and EVAR techniques. Specific areas that are addressed include endograft selection, arterial access, sheath delivery, aortic branch management, graft deployment, intravascular ultrasonography, pressure sensors, management of endoleaks and compressed limbs, and exit strategies. PMID:22121487

  14. A sequential bioorthogonal dual strategy: ManNAl and SiaNAl as distinct tools to unravel sialic acid metabolic pathways.

    PubMed

    Gilormini, P A; Lion, C; Vicogne, D; Levade, T; Potelle, S; Mariller, C; Guérardel, Y; Biot, C; Foulquier, F

    2016-02-01

    Recent methodological developments in metabolic oligosaccharide engineering (MOE) pave the way for tremendous advances in glycobiology. Herein, we propose a Sequential Bioorthogonal Dual Strategy (SBDS) combining the use of two unprotected alkyne-tagged monosaccharide reporters (ManNAl and SiaNAl) with the bioligation of fluorescent probes by copper-catalysed azide-alkyne cycloaddition (CuAAC). With SBDS, we are able to shed light on trafficking and cellular uptake mechanisms of sialic acid. Using their corresponding analogues, we visualized that SiaNAl enters via endocytosis, whereas its biosynthetic intermediate ManNAl uptake is mediated by a yet unknown but specific plasma membrane transporter. Sialin, a lysosomal protein, is shown to be crucial for the export of exogenous sialic acid from lysosomes to the cytosol. Metabolic labeling with alkyne-tagged derivatives of N-acetylneuraminic acid (Neu5Ac) or N-acetylmannosamine (ManNAc) could thus be used to follow endocytosis in physiological vs. pathological conditions. PMID:26727964

  15. Book Repair Manual.

    ERIC Educational Resources Information Center

    Milevski, Robert J.

    1995-01-01

    This book repair manual developed for the Illinois Cooperative Conservation Program includes book structure and book problems, book repair procedures for 4 specific problems, a description of adhesive bindings, a glossary, an annotated list of 11 additional readings, book repair supplies and suppliers, and specifications for book repair kits. (LRW)

  16. Oxidative DNA Damage and Nucleotide Excision Repair

    PubMed Central

    Melis, Joost P.M.; Luijten, Mirjam

    2013-01-01

    Abstract Significance: Oxidative DNA damage is repaired by multiple, overlapping DNA repair pathways. Accumulating evidence supports the hypothesis that nucleotide excision repair (NER), besides base excision repair (BER), is also involved in neutralizing oxidative DNA damage. Recent Advances: NER includes two distinct sub-pathways: transcription-coupled NER (TC-NER) and global genome repair (GG-NER). The CSA and CSB proteins initiate the onset of TC-NER. Recent findings show that not only CSB, but also CSA is involved in the repair of oxidative DNA lesions, in the nucleus as well as in mitochondria. The XPG protein is also of importance for the removal of oxidative DNA lesions, as it may enhance the initial step of BER. Substantial evidence exists that support a role for XPC in NER and BER. XPC deficiency not only results in decreased repair of oxidative lesions, but has also been linked to disturbed redox homeostasis. Critical Issues: The role of NER proteins in the regulation of the cellular response to oxidative (mitochondrial and nuclear) DNA damage may be the underlying mechanism of the pathology of accelerated aging in Cockayne syndrome patients, a driving force for internal cancer development in XP-A and XP-C patients, and a contributor to the mixed exhibited phenotypes of XP-G patients. Future Directions: Accumulating evidence indicates that DNA repair factors can be involved in multiple DNA repair pathways. However, the distinct detailed mechanism and consequences of these additional functions remain to be elucidated and can possibly shine a light on clinically related issues. Antioxid. Redox Signal. 18, 2409–2419. PMID:23216312

  17. Rapid road repair vehicle

    DOEpatents

    Mara, L.M.

    1998-05-05

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find at the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was not heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past. 2 figs.

  18. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1998-01-01

    Disclosed is a rapid road repair vehicle capable of moving over a surface to be repaired at near normal posted traffic speeds to scan for and find an the high rate of speed, imperfections in the pavement surface, prepare the surface imperfection for repair by air pressure and vacuum cleaning, applying a correct amount of the correct patching material to effect the repair, smooth the resulting repaired surface, and catalog the location and quality of the repairs for maintenance records of the road surface. The rapid road repair vehicle can repair surface imperfections at lower cost, improved quality, at a higher rate of speed than was was heretofor possible, with significantly reduced exposure to safety and health hazards associated with this kind of road repair activities in the past.

  19. A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.

    PubMed

    Voter, Andrew F; Manthei, Kelly A; Keck, James L

    2016-07-01

    Induction of the Fanconi anemia (FA) DNA repair pathway is a common mechanism by which tumors evolve resistance to DNA crosslinking chemotherapies. Proper execution of the FA pathway requires interaction between the FA complementation group M protein (FANCM) and the RecQ-mediated genome instability protein (RMI) complex, and mutations that disrupt FANCM/RMI interactions sensitize cells to DNA crosslinking agents. Inhibitors that block FANCM/RMI complex formation could be useful therapeutics for resensitizing tumors that have acquired chemotherapeutic resistance. To identify such inhibitors, we have developed and validated high-throughput fluorescence polarization and proximity assays that are sensitive to inhibitors that disrupt interactions between the RMI complex and its binding site on FANCM (a peptide referred to as MM2). A pilot screen of 74,807 small molecules was performed using the fluorescence polarization assay. Hits from the primary screen were further tested using the proximity assay, and an orthogonal proximity assay was used to assess inhibitor selectivity. Direct physical interaction between the RMI complex and the most selective inhibitor identified through the screening process was measured by surface plasmon resonance and isothermal titration calorimetry. Observation of direct binding by this small molecule validates the screening protocol.

  20. Wnt Signaling and Injury Repair

    PubMed Central

    Whyte, Jemima L.; Smith, Andrew A.; Helms, Jill A.

    2012-01-01

    Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. In this review we summarize recent data elucidating the roles that the Wnt pathway plays in the injury repair process. These data provide a foundation for potential Wnt-based therapeutic strategies aimed at stimulating tissue regeneration. PMID:22723493

  1. The immune system and cardiac repair

    PubMed Central

    Frangogiannis, Nikolaos G.

    2008-01-01

    Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the

  2. DNA Mismatch Repair

    PubMed Central

    MARINUS, M. G.

    2014-01-01

    DNA mismatch repair functions to correct replication errors in newly synthesized DNA and to prevent recombination between related, but not identical (homeologous), DNA sequences. The mechanism of mismatch repair is best understood in Escherichia coli and is the main focus of this review. The early genetic studies of mismatch repair are described as a basis for the subsequent biochemical characterization of the system. The effects of mismatch repair on homologous and homeologous recombination are described. The relationship of mismatch repair to cell toxicity induced by various drugs is included. The VSP (Very Short Patch) repair system is described in detail. PMID:26442827

  3. Animal models of cartilage repair

    PubMed Central

    Cook, J. L.; Hung, C. T.; Kuroki, K.; Stoker, A. M.; Cook, C. R.; Pfeiffer, F. M.; Sherman, S. L.; Stannard, J. P.

    2014-01-01

    Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94. PMID:24695750

  4. Laparoscopic Inguinal Hernia Repair

    MedlinePlus

    ... Some hernia repairs are performed using a small telescope known as a laparoscope. If your surgeon has ... in the abdominal wall (muscle) using small incisions, telescopes and a patch (mesh). Laparoscopic repair offers a ...

  5. Eye muscle repair - discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000111.htm Eye muscle repair - discharge To use the sharing features on ... enable JavaScript. You or your child had eye muscle repair surgery to correct eye muscle problems that ...

  6. Hydrocele repair - series (image)

    MedlinePlus

    ... vaginalis into the scrotum. This is called an inguinal hernia. If a hydrocele persists past the first six ... months of life, it should be surgically repaired. Inguinal hernia in infants is usually repaired within the first ...

  7. Optimal inventories for overhaul of repairable redundant systems - A Markov decision model

    NASA Technical Reports Server (NTRS)

    Schaefer, M. K.

    1984-01-01

    A Markovian decision model was developed to calculate the optimal inventory of repairable spare parts for an avionics control system for commercial aircraft. Total expected shortage costs, repair costs, and holding costs are minimized for a machine containing a single system of redundant parts. Transition probabilities are calculated for each repair state and repair rate, and optimal spare parts inventory and repair strategies are determined through linear programming. The linear programming solutions are given in a table.

  8. Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

    PubMed

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient.

  9. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  10. Dental materials for cleft palate repair.

    PubMed

    Sharif, Faiza; Ur Rehman, Ihtesham; Muhammad, Nawshad; MacNeil, Sheila

    2016-04-01

    Numerous bone and soft tissue grafting techniques are followed to repair cleft of lip and palate (CLP) defects. In addition to the gold standard surgical interventions involving the use of autogenous grafts, various allogenic and xenogenic graft materials are available for bone regeneration. In an attempt to discover minimally invasive and cost effective treatments for cleft repair, an exceptional growth in synthetic biomedical graft materials have occurred. This study gives an overview of the use of dental materials to repair cleft of lip and palate (CLP). The eligibility criteria for this review were case studies, clinical trials and retrospective studies on the use of various types of dental materials in surgical repair of cleft palate defects. Any data available on the surgical interventions to repair alveolar or palatal cleft, with natural or synthetic graft materials was included in this review. Those datasets with long term clinical follow-up results were referred to as particularly relevant. The results provide encouraging evidence in favor of dental and other related biomedical materials to fill the gaps in clefts of lip and palate. The review presents the various bones and soft tissue replacement strategies currently used, tested or explored for the repair of cleft defects. There was little available data on the use of synthetic materials in cleft repair which was a limitation of this study. In conclusion although clinical trials on the use of synthetic materials are currently underway the uses of autologous implants are the preferred treatment methods to date.

  11. When is rumination an adaptive mood repair strategy? Day-to-day rhythms of life in combat veterans with and without posttraumatic stress disorder.

    PubMed

    Kashdan, Todd B; Young, Kevin C; McKnight, Patrick E

    2012-10-01

    Prior research suggests that rumination and chronic negative emotions serve to maintain emotional disorders. However, some evidence suggests that pondering the nature and meaning of negative experiences can be adaptive. To better understand the function of this dimension of rumination, we studied the use of this strategy in response to negative emotions as they unfold from day to day in veterans with (n=27) and without (n=27) post traumatic stress disorder (PTSD). For two weeks, veterans completed daily questions about when they experienced a bad mood and how often they used rumination to feel differently. It was hypothesized that rumination would attenuate negative emotional reactions in veterans without PTSD, but that rigid, intense negative emotions would persist in veterans with PTSD. Using multilevel modeling, we found that on the same day, rumination was positively associated with negative affect. Because covariation fails to address directionality, we also examined lagged effects from one occasion to the next. For veterans without PTSD, more frequent use of rumination predicted less intense negative affect the next day; there was no support for a model with negative affect predicting rumination the next day. For veterans with PTSD, the prior day's intensity of negative affect was the only predictor of intensity of negative affect the next day. Results support the value of distinguishing within-day and across day effects, and the presence of PTSD, to clarify contexts when rumination is adaptive.

  12. Photosystem II repair in marine diatoms with contrasting photophysiologies.

    PubMed

    Lavaud, Johann; Six, Christophe; Campbell, Douglas A

    2016-02-01

    Skeletonema costatum and Phaeodactylum tricornutum are model marine diatoms with differing strategies for non-photochemical dissipation of excess excitation energy within photosystem II (PSII). We showed that S. costatum, with connectivity across the pigment bed serving PSII, and limited capacity for induction of sustained non-photochemical quenching (NPQ), maintained a large ratio of [PSII(Total)]/[PSII(Active)] to buffer against fluctuations in light intensity. In contrast, P. tricornutum, with a larger capacity to induce sustained NPQ, could maintain a lower [PSII(Total)]/[PSII(Active)]. Induction of NPQ was correlated with an active PSII repair cycle in both species, and inhibition of chloroplastic protein synthesis with lincomycin leads to run away over-excitation of remaining PSII(Active), particularly in S. costatum. We discuss these distinctions in relation to the differing capacities, induction and relaxation rates for NPQ, and as strain adaptations to the differential light regimes of their originating habitats. The present work further confirms the important role for the light-dependent fast regulation of photochemistry by NPQ interacting with PSII repair cycle capacity in the ecophysiology of both pennate and centric diatoms. PMID:26156125

  13. Global genome nucleotide excision repair is organized into domains that promote efficient DNA repair in chromatin

    PubMed Central

    Yu, Shirong; Evans, Katie; Bennett, Mark; Webster, Richard M.; Leadbitter, Matthew; Teng, Yumin; Waters, Raymond

    2016-01-01

    The rates at which lesions are removed by DNA repair can vary widely throughout the genome, with important implications for genomic stability. To study this, we measured the distribution of nucleotide excision repair (NER) rates for UV-induced lesions throughout the budding yeast genome. By plotting these repair rates in relation to genes and their associated flanking sequences, we reveal that, in normal cells, genomic repair rates display a distinctive pattern, suggesting that DNA repair is highly organized within the genome. Furthermore, by comparing genome-wide DNA repair rates in wild-type cells and cells defective in the global genome–NER (GG-NER) subpathway, we establish how this alters the distribution of NER rates throughout the genome. We also examined the genomic locations of GG-NER factor binding to chromatin before and after UV irradiation, revealing that GG-NER is organized and initiated from specific genomic locations. At these sites, chromatin occupancy of the histone acetyl-transferase Gcn5 is controlled by the GG-NER complex, which regulates histone H3 acetylation and chromatin structure, thereby promoting efficient DNA repair of UV-induced lesions. Chromatin remodeling during the GG-NER process is therefore organized into these genomic domains. Importantly, loss of Gcn5 significantly alters the genomic distribution of NER rates; this has implications for the effects of chromatin modifiers on the distribution of mutations that arise throughout the genome. PMID:27470111

  14. Optimality in DNA repair.

    PubMed

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

    2012-01-01

    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. PMID:21945337

  15. Nerve repair and cable grafting for facial paralysis.

    PubMed

    Humphrey, Clinton D; Kriet, J David

    2008-05-01

    Facial nerve injury and facial paralysis are devastating for patients. Although imperfect, primary repair is currently the best option to restore facial nerve function. Cable, or interposition, nerve grafting is an acceptable alternative when primary repair is not possible. Several donor nerves are at the surgeon's disposal. Great auricular, sural, or medial and lateral antebrachial cutaneous nerves are all easily obtained. Both primary repair and interposition grafting typically result in better facial function than do other dynamic and static rehabilitation strategies. Proficient anastomotic technique and, when necessary, selection of an appropriate interposition graft will optimize patient outcomes. Promising research is under way that will enhance future nerve repair and grafting efforts.

  16. Variation in Base Excision Repair Capacity

    PubMed Central

    Wilson, David M.; Kim, Daemyung; Berquist, Brian R.; Sigurdson, Alice J.

    2010-01-01

    The major DNA repair pathway for coping with spontaneous forms of DNA damage, such as natural hydrolytic products or oxidative lesions, is base excision repair (BER). In particular, BER processes mutagenic and cytotoxic DNA lesions such as non-bulky base modifications, abasic sites, and a range of chemically distinct single-strand breaks. Defects in BER have been linked to cancer predisposition, neurodegenerative disorders, and immunodeficiency. Recent data indicate a large degree of sequence variability in DNA repair genes and several studies have associated BER gene polymorphisms with disease risk, including cancer of several sites. The intent of this review is to describe the range of BER capacity among individuals and the functional consequences of BER genetic variants. We also discuss studies that associate BER deficiency with disease risk and the current state of BER capacity measurement assays. PMID:21167187

  17. Repair of Electronics for Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Pettegrew, Richard D.; Easton, John; Struk, Peter

    2007-01-01

    To reduce mission risk, long duration spaceflight and exploration activities will require greater degrees of self-sufficiency with regards to repair capability than have ever been employed before in space exploration. The current repair paradigm of replacing Orbital Replacement Units (ORUs) of malfunctioning avionics and electronic hardware will be impractical, since carrying all of the spares that could possibly be needed for a long duration mission would require upmass and volume at unprecedented and unacceptable levels. A strategy of component-level repair for electronics, however, could significantly reduce the mass and volume necessary for spares and enhance mission safety via a generic contingency capability. This approach is already used to varying degrees by the U.S. Navy, where vessels at sea experience some similar constraints such as the need for self sufficiency for moderately long time periods, and restrictions on volume of repair spares and infrastructure. The concept of conducting component-level repairs of electronics in spacecraft requires the development of design guidelines for future avionics (to enable repair), development of diagnostic techniques to allow an astronaut to pinpoint the faulty component aboard a vastly complex vehicle, and development of tools and methodologies for dealing with the physical processes of replacing the component. This physical process includes tasks such as conformal coating removal and replacement, component removal, replacement, and alignment--all in the difficulty of a reduced gravity environment. Further, the gravitational effects on the soldering process must be characterized and accounted for to ensure reliability of the newly repaired components. The Component-Level Electronics-Assembly Repair (CLEAR) project under the NASA Supportability program was established to develop and demonstrate the practicality of this repair approach. CLEAR involves collaborative efforts between NASA s Glenn Research Center

  18. DNA repair meets the RNA world.

    PubMed

    Lee, Chow H

    2014-02-01

    The ability to repair damaged DNA and to maintain genome stability is the utmost importance for the survival of any species. Hence, it is not surprising to find that DNA repair mechanisms are evolutionarily conserved and are expected to evolve to maintain the existence of species. In the last few years, there has been an exponential increase in the evidence linking RNA processing with DNA repair programs. For instance, the well-studied DNA base excision repair (BER) enzyme apurinic/apyrimidinic endonuclease 1 can cleave RNA molecules, regulate mRNA levels, and associate physically with proteins involved in RNA processing. It is now clear that not only the expression of noncoding RNAs are changed upon DNA damage, they can modulate the expression of genes involved in the genome stability programs. The five reviews in this Forum provide the up-to-date knowledge on DNA repair, with a focus on BER, and a perspective on how the two ancient biochemical pathways are linked. The contributions demonstrate the complexity of such interactions, but also pointed out the opportunities for new therapeutic interventions. Future in vivo studies on the link between DNA repair processes and RNA metabolism should contribute to our basic understanding of physiology, disease, and treatment strategies.

  19. Laparoscopic lumbar hernia repair.

    PubMed

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

    2006-04-01

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

  20. Snowmobile Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Hennessy, Stephen S.; Conrad, Rex

    This teacher's guide contains 14 units on snowmobile repair: (1) introduction to snowmobile repair; (2) skis, front suspension, and steering; (3) drive clutch; (4) drive belts; (5) driven clutch; (6) chain drives; (7) jackshafts and axles; (8) rear suspension; (9) tracks; (10) shock absorbers; (11) brakes; (12) engines; (13) ignition and…

  1. Through-focus EUV multilayer defect repair with nanomachining

    NASA Astrophysics Data System (ADS)

    McIntyre, Gregory; Gallagher, Emily; Robinson, Tod; Smith, Adam C.; Lawliss, Mark; LeClaire, Jeffrey; Bozak, Ron; White, Roy; Archuletta, Michael

    2013-04-01

    Defects within the multilayer mirrors of EUV photomasks have been a leading challenge for EUV lithography for quite some time. By creating non-planar surfaces, they distort both the amplitude and phase of reflected light. Amplitude errors generally create a CD error on wafer, whereas phase errors tend to cause asymmetric printing through focus. Since defect-free mask blanks are not expected to be available for initial high volume EUV manufacturing, defect mitigation, compensation, and repair strategies are essential. This paper describes a technique to repair both the amplitude and phase effects of multilayer defects. For a bump defect, the phase effect (i.e. tilted Bossung curve behavior) is corrected by removing multilayer material in the vicinity of the defect. This creates a phase effect opposite to that of the defect and the two effects cancel. The amplitude error (i.e. CD error) caused by both the defect and by the phase repair is then corrected by modifying the surrounding absorber pattern. The repairs in this paper are performed by nanomachining with an AFM repair tool. The concept is validated by a combination of simulation and experimental studies with data from the Actinic Inspection Tool (AIT) at the Lawrence Berkeley National Laboratories, the EUV Alpha Demo Tool (ADT) in Albany, New York, and an AFM repair tool. The process for a complete multilayer repair is described using an example native defect repair. Encouraging results indicate that nanomachining is capable of creating the complex nano-scale three dimensional topographies required for the repair. Repair strategies for both bump and pit defects are addressed. Multiple simulation studies are used to understand the requirements for such a repair and what type of repairs may be possible.

  2. The role of DNA repair in brain related disease pathology.

    PubMed

    Canugovi, Chandrika; Misiak, Magdalena; Ferrarelli, Leslie K; Croteau, Deborah L; Bohr, Vilhelm A

    2013-08-01

    Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease.

  3. Repair in the central nervous system.

    PubMed

    Fitzgerald, J; Fawcett, J

    2007-11-01

    The subject of central nervous system damage includes a wide variety of problems, from the slow selective 'picking off' of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system. PMID:17998174

  4. Biomimetic strategies for bone repair and regeneration.

    PubMed

    Raucci, Maria G; Guarino, Vincenzo; Ambrosio, Luigi

    2012-01-01

    The osseointegration rate of implants is related to their composition and surface roughness. Implant roughness favors both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate (Ca-P) coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. It has been clearly shown in many publications that Ca-P coating accelerates bone formation around the implant. This review discusses two main routes for the manufacturing of polymer-based osteoconductive scaffolds for tissue engineering, namely the incorporation of bioceramic particles in the scaffold and the coating of a scaffold with a thin layer of apatite through a biomimetic process.

  5. Biomimetic Strategies for Bone Repair and Regeneration

    PubMed Central

    Raucci, Maria G.; Guarino, Vincenzo; Ambrosio, Luigi

    2012-01-01

    The osseointegration rate of implants is related to their composition and surface roughness. Implant roughness favors both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate (Ca-P) coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. It has been clearly shown in many publications that Ca-P coating accelerates bone formation around the implant. This review discusses two main routes for the manufacturing of polymer-based osteoconductive scaffolds for tissue engineering, namely the incorporation of bioceramic particles in the scaffold and the coating of a scaffold with a thin layer of apatite through a biomimetic process. PMID:24955638

  6. Rapid road repair vehicle

    SciTech Connect

    Mara, L.M.

    1999-09-07

    Disclosed are improvements to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  7. Rapid road repair vehicle

    DOEpatents

    Mara, Leo M.

    1999-01-01

    Disclosed are improvments to a rapid road repair vehicle comprising an improved cleaning device arrangement, two dispensing arrays for filling defects more rapidly and efficiently, an array of pre-heaters to heat the road way surface in order to help the repair material better bond to the repaired surface, a means for detecting, measuring, and computing the number, location and volume of each of the detected surface imperfection, and a computer means schema for controlling the operation of the plurality of vehicle subsystems. The improved vehicle is, therefore, better able to perform its intended function of filling surface imperfections while moving over those surfaces at near normal traffic speeds.

  8. Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair.

    PubMed

    Heymer, Andrea; Haddad, Daniel; Weber, Meike; Gbureck, Uwe; Jakob, Peter M; Eulert, Jochen; Nöth, Ulrich

    2008-04-01

    For the development of new therapeutical cell-based strategies for articular cartilage repair, a reliable cell monitoring technique is required to track the cells in vivo non-invasively and repeatedly. We present a systematic and detailed study on the performance and biological impact of a simple and efficient labelling protocol for human mesenchymal stem cells (hMSCs). Commercially available very small superparamagnetic iron oxide particles (VSOPs) were used as magnetic resonance (MR) contrast agent. Iron uptake via endocytosis was confirmed histologically with prussian blue staining and quantified by mass spectrometry. Compared with unlabelled cells, VSOP-labelling did neither influence the viability nor the proliferation potential of hMSCs. Furthermore, iron incorporation did not affect hMSCs in undergoing adipogenic, osteogenic or chondrogenic differentiation, as demonstrated histologically and by gene expression analyses. The efficiency of the labelling protocol was assessed with high-resolution MR imaging at 11.7T. VSOP-labelled hMSCs were visualised in a collagen type I hydrogel, which is in clinical use for matrix-based articular cartilage repair. The presence of VSOP-labelled hMSCs was indicated by distinct hypointense spots in the MR images, as a result of iron specific loss of signal intensity. In summary, this labelling technique has great potential to visualise hMSCs and track their migration after transplantation for articular cartilage repair with MR imaging.

  9. Learning to improve iterative repair scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte; Davis, Eugene

    1992-01-01

    This paper presents a general learning method for dynamically selecting between repair heuristics in an iterative repair scheduling system. The system employs a version of explanation-based learning called Plausible Explanation-Based Learning (PEBL) that uses multiple examples to confirm conjectured explanations. The basic approach is to conjecture contradictions between a heuristic and statistics that measure the quality of the heuristic. When these contradictions are confirmed, a different heuristic is selected. To motivate the utility of this approach we present an empirical evaluation of the performance of a scheduling system with respect to two different repair strategies. We show that the scheduler that learns to choose between the heuristics outperforms the same scheduler with any one of two heuristics alone.

  10. Repairing Thermal Tiles

    NASA Technical Reports Server (NTRS)

    Mccain, C. R., Jr.; Feiler, C. W.

    1984-01-01

    Small chips and depression in surfaces of surface insulation tiles repaired using Ludox colloidal silica solution and silica powder. No waiting time necessary between mixing filler and using it. Patch cures quickly without heat being applied.

  11. Easily repairable networks

    NASA Astrophysics Data System (ADS)

    Fink, Thomas

    2015-03-01

    We introduce a simple class of distribution networks which withstand damage by being repairable instead of redundant. Instead of asking how hard it is to disconnect nodes through damage, we ask how easy it is to reconnect nodes after damage. We prove that optimal networks on regular lattices have an expected cost of reconnection proportional to the lattice length, and that such networks have exactly three levels of structural hierarchy. We extend our results to networks subject to repeated attacks, in which the repairs themselves must be repairable. We find that, in exchange for a modest increase in repair cost, such networks are able to withstand any number of attacks. We acknowledge support from the Defense Threat Reduction Agency, BCG and EU FP7 (Growthcom).

  12. Imperforate anus repair - slideshow

    MedlinePlus

    ... presentations/100030.htm Imperforate anus repair - series—Normal anatomy To use the sharing features on this page, ... of 4 Overview In individuals with a normal anatomy, the large intestine (colon) empties into a pouch- ...

  13. Timpani Repair and Maintenance.

    ERIC Educational Resources Information Center

    Combs, F. Michael

    1980-01-01

    Rather than focusing on specific brands of timpani, these guidelines for repair cover mechanical problems of a general nature: pedals, dents, unclear tone, and squeaking. Preventive maintenance is discussed. (Author/SJL)

  14. Eye muscle repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100062.htm Eye muscle repair - series—Normal anatomy To use the sharing ... the eyeball to the eye socket. The external muscles of the eye are found behind the conjunctiva. ...

  15. Laparoscopic Ventral Hernia Repair

    MedlinePlus

    ... the likelihood of a hernia including persistent coughing, difficulty with bowel movements or urination, or frequent need for straining. What are the Advantages of Laparoscopic Ventral Hernia Repair? Keep reading... Page 1 of 2 1 2 » Brought to ...

  16. Planning Maintenance and Repairs.

    ERIC Educational Resources Information Center

    Fitzemeyer, Ted

    2001-01-01

    Discusses the use of school facility design as an aid to efficiently repairing and maintaining facility systems. Also presents details on facility design's influence in properly maintaining mechanical and electrical systems. (GR)

  17. Patent urachus repair

    MedlinePlus

    Patent urachal tube repair ... belly. Next, the surgeon will find the urachal tube and remove it. The bladder opening will be ... surgeon uses the tools to remove the urachal tube and close off the bladder and area where ...

  18. Achilles tendon repair

    MedlinePlus

    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 ...

  19. Repairing ceramic insulating tiles

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

    Fused-silica tiles containing large voids or gauges are repaired without adhesives by plug insertion method. Tiles are useful in conduits for high-temperature gases, in furnaces, and in other applications involving heat insulation.

  20. Ontology Alignment Repair through Modularization and Confidence-Based Heuristics.

    PubMed

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

    2015-01-01

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

  1. Ontology Alignment Repair through Modularization and Confidence-Based Heuristics

    PubMed Central

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

    2015-01-01

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

  2. Repairing Foam Insulation

    NASA Technical Reports Server (NTRS)

    Corbin, J.; Buras, D.

    1986-01-01

    Large holes in polyurethane foam insulation repaired reliably by simple method. Little skill needed to apply method, used for overhead repairs as well as for those in other orientations. Plug positioned in hole to be filled and held in place with mounting fixture. Fresh liquid foam injected through plug to bond it in place. As foam cures and expands, it displaces plug outward. Protrusion later removed.

  3. Robotic inguinal hernia repair.

    PubMed

    Escobar Dominguez, Jose E; Gonzalez, Anthony; Donkor, Charan

    2015-09-01

    Inguinal hernias have been described throughout the history of medicine with many efforts to achieve the cure. Currently, with the advantages of minimally invasive surgery, new questions arise: what is going to be the best approach for inguinal hernia repair? Is there a real benefit with the robotic approach? Should minimally invasive hernia surgery be the standard of care? In this report we address these questions by describing our experience with robotic inguinal hernia repair. PMID:26153353

  4. Emergent properties of neural repair: elemental biology to therapeutic concepts

    PubMed Central

    2016-01-01

    Stroke is the leading cause of adult disability. The past decade has seen advances in basic science research of neural repair in stroke. The brain forms new connections after stroke, which have a causal role in recovery of function. Brain progenitors, including neuronal and glial progenitors, respond to stroke and initiate a partial formation of new neurons and glial cells. The molecular systems that underlie axonal sprouting, neurogenesis, and gliogenesis after stroke have recently been identified. Importantly, tractable drug targets exist within these molecular systems that might stimulate tissue repair. These basic science advances have taken the field to its first scientific milestone; the elemental principles of neural repair in stroke have been identified. The next stages in this field involve understanding how these elemental principles of recovery interact in the dynamic cellular systems of the repairing brain. Emergent principles arise out of the interaction of the fundamental or elemental principles in a system. In neural repair, the elemental principles of brain reorganization after stroke interact to generate higher order and distinct concepts of regenerative brain niches in cellular repair, neuronal networks in synaptic plasticity, and the distinction of molecular systems of neuroregeneration. Many of these emergent principles directly guide the development of new therapies, such as the necessity for spatial and temporal control in neural repair therapy delivery and the overlap of cancer and neural repair mechanisms. This review discusses the emergent principles of neural repair in stroke as they relate to scientific and therapeutic concepts in this field. Ann Neurol 2016;79:895–906 PMID:27043816

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

    PubMed Central

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

    2015-01-01

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

  6. DNA Damage, DNA Repair, Aging, and Neurodegeneration.

    PubMed

    Maynard, Scott; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Croteau, Deborah L; Bohr, Vilhelm A

    2015-09-18

    Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span.

  7. Complications of Endovascular Repair of Abdominal Aortic Aneurysms: A Review

    SciTech Connect

    Katzen, Barry T. MacLean, Alexandra A.

    2006-12-15

    The endovascular procedure for repair of abdominal aortic aneurysms has had an enormous impact on the treatment of this challenging disease. Complications, however, do occur and it is important to have a thorough understanding of the array of complications and appropriate management strategies. In this review of endovascular complications, we describe early and late complications paying particular attention to preventive, treatment and surveillance strategies.

  8. Myelin repair is accelerated by inactivating CXCR2 on non-hematopoietic cells

    PubMed Central

    Liu, LiPing; Darnall, Lindsey; Hu, Taofang; Choi, Karen; Ransohoff, Richard M.

    2010-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) and remyelination in MS ultimately fails. Although strategies to promote myelin repair are eagerly sought, mechanisms underlying remyelination in vivo have been elusive. CXCR2 is expressed on neutrophils and oligodendrocyte lineage cells in the central nervous system (CNS). CXCR2 positive neutrophils facilitate inflammatory demyelination in demyelination models such as experimental autoimmune encephalomyelitis (EAE) and cuprizone intoxication. Systemic injection of a small molecule CXCR2 antagonist at the onset of EAE decreased demyelinated lesions. These results left the cellular target of the CXCR2 antagonist uncertain, and did not clarify whether CXCR2 blockade prevented demyelination or promoted remyelination. Here, we show that the actions of CXCR2 on non-hematopoietic cells unexpectedly delay myelin repair. Bone marrow chimeric mice (Cxcr2+/−→Cxcr2−/− and Cxcr2+/−→Cxcr2+/+) were subjected to two distinct models of myelin injury. In all cases, myelin repair was more efficient in Cxcr2+/−→Cxcr2−/− animals. Oligodendrocyte progenitor cells (OPCs) in demyelinated lesions of Cxcr2+/−→Cxcr2−/− mice proliferated earlier and more vigorously than in tissues from Cxcr2+/−→Cxcr2+/+ animals. In vitro demyelinated CNS slice cultures also showed better myelin repair when CXCR2 was blocked with neutralizing antibodies, or was genetically deleted. Our results suggest that CXCR2 inactivation permits optimal spatiotemporal positioning of OPCs in demyelinating lesions to receive local proliferative and differentiating signals. Given that CXCR2 exerts dual functions which promote demyelination and decrease remyelination by actions towards hematopoietic cells and non-hematopoietic cells respectively, our findings identify CXCR2 as a promising drug target for clinical demyelinating disorders. PMID:20610741

  9. Signaling Pathways in Cartilage Repair

    PubMed Central

    Mariani, Erminia; Pulsatelli, Lia; Facchini, Andrea

    2014-01-01

    In adult healthy cartilage, chondrocytes are in a quiescent phase characterized by a fine balance between anabolic and catabolic activities. In ageing, degenerative joint diseases and traumatic injuries of cartilage, a loss of homeostatic conditions and an up-regulation of catabolic pathways occur. Since cartilage differentiation and maintenance of homeostasis are finely tuned by a complex network of signaling molecules and biophysical factors, shedding light on these mechanisms appears to be extremely relevant for both the identification of pathogenic key factors, as specific therapeutic targets, and the development of biological approaches for cartilage regeneration. This review will focus on the main signaling pathways that can activate cellular and molecular processes, regulating the functional behavior of cartilage in both physiological and pathological conditions. These networks may be relevant in the crosstalk among joint compartments and increased knowledge in this field may lead to the development of more effective strategies for inducing cartilage repair. PMID:24837833

  10. Radiological assessment of steam generator repair and replacement

    SciTech Connect

    Parkhurst, M.A.; Rathbun, L.A.; Murphy, D.W.

    1983-12-01

    Previous analyses of the radiological impact of removing and replacing corroded steam generators have been updated based on experience at Surry Units 1 and 2 and Turkey Point Units 3 and 4. The sleeving repairs of degraded tubes at San Onofre Unit 1, Point Beach Unit 2, and R.E. Ginna are also analyzed. Actual occupational doses incurred during application of the various technologies used in repairs have been included, along with radioactive waste quantities and constituents. Considerable progress has been made in improving radiation protection and reducing worker dose by the development of remotely controlled equipment and the implementation of dose reduction strategies that have been successful in previous repair operations.

  11. DNA repair mechanisms in cancer development and therapy

    PubMed Central

    Torgovnick, Alessandro; Schumacher, Björn

    2015-01-01

    DNA damage has been long recognized as causal factor for cancer development. When erroneous DNA repair leads to mutations or chromosomal aberrations affecting oncogenes and tumor suppressor genes, cells undergo malignant transformation resulting in cancerous growth. Genetic defects can predispose to cancer: mutations in distinct DNA repair systems elevate the susceptibility to various cancer types. However, DNA damage not only comprises a root cause for cancer development but also continues to provide an important avenue for chemo- and radiotherapy. Since the beginning of cancer therapy, genotoxic agents that trigger DNA damage checkpoints have been applied to halt the growth and trigger the apoptotic demise of cancer cells. We provide an overview about the involvement of DNA repair systems in cancer prevention and the classes of genotoxins that are commonly used for the treatment of cancer. A better understanding of the roles and interactions of the highly complex DNA repair machineries will lead to important improvements in cancer therapy. PMID:25954303

  12. Nucleotide excision repair: new tricks with old bricks.

    PubMed

    Kamileri, Irene; Karakasilioti, Ismene; Garinis, George A

    2012-11-01

    Nucleotide excision repair (NER) is a major DNA repair pathway that ensures that the genome remains functionally intact and is faithfully transmitted to progeny. However, defects in NER lead, in addition to cancer and aging, to developmental abnormalities whose clinical heterogeneity and varying severity cannot be fully explained by the DNA repair deficiencies. Recent work has revealed that proteins in NER play distinct roles, including some that go well beyond DNA repair. NER factors are components of protein complexes known to be involved in nucleosome remodeling, histone ubiquitination, and transcriptional activation of genes involved in nuclear receptor signaling, stem cell reprogramming, and postnatal mammalian growth. Together, these findings add new pieces to the puzzle for understanding NER and the relevance of NER defects in development and disease.

  13. Rescheduling with iterative repair

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  14. Bone fracture repair - series (image)

    MedlinePlus

    The three main treatment options for bone fractures are: Casting Open reduction, and internal fixation- this involves a surgery to repair the fracture-frequently, metal rods, screws or plates are used to repair the ...

  15. Cleft lip and palate repair

    MedlinePlus

    Orofacial cleft; Craniofacial birth defect repair; Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty ... these conditions at birth. Most times, cleft lip repair is done when the child is 6 to ...

  16. Electric motor model repair specifications

    SciTech Connect

    1995-08-01

    These model repair specifications list the minimum requirements for repair and overhaul of polyphase AC squireel cage induction motors. All power ranges, voltages, and speeds of squirrel cage motors are covered.

  17. Repair of proboscis lateralis.

    PubMed

    Uğurlu, Kemal; Karşidag, Semra; Ozçelik, Derya; Sadikoğlu, Buğra; Baş, Lütfü

    2005-01-01

    We report an 8-year-old girl presented with a proboscis on the right nasal nostril, right heminasal hypoplasia, hypertelorism, and cleft lip and palate on the other side. After repair of the cleft lip and palate and the hypertelorism, we successfully reconstructed the heminose with a V-Y advancement flap containing the proboscis tube. PMID:16019753

  18. Repairing cracked glass

    NASA Technical Reports Server (NTRS)

    Helman, D. D.; Holt, J. W.; Smiser, L. V.

    1979-01-01

    Filing procedure consisting of machined lightweight fused-silica tiles coated with thin-layer of borosilicate glass produces homogeneous seal in thin glass. Procedure is useful in repairing glass envelopes, X-ray tub windows, Dewar flasks, and similar thin glass objects.

  19. Automotive Body Repair Competencies.

    ERIC Educational Resources Information Center

    D'Armond, Jack; And Others

    Designed to provide a model curriculum and guidelines, this manual presents tasks that were identified by employers, employees, and teachers as important in a postsecondary auto body repair curriculum. The tasks are divided into ten major component areas of instruction: metalworking and fiberglass, painting, frame and suspension, glass and trim,…

  20. Patent urachus repair - slideshow

    MedlinePlus

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair - series—Normal anatomy URL of this ...

  1. Aircraft Propeller Hub Repair

    SciTech Connect

    Muth, Thomas R.; Peter, William H.

    2015-02-13

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

  2. Basic Book Repair Methods.

    ERIC Educational Resources Information Center

    Schechter, Abraham A.

    This book addresses some common preservation techniques that invariably become necessary in library and archival collections of any size. The procedures are described in chronological sequence, and photographs show the techniques from the viewpoint of the person actually doing the work. The recommended repair methods can be accomplished using…

  3. Comprehensive Small Engine Repair.

    ERIC Educational Resources Information Center

    Hires, Bill; And Others

    This curriculum guide contains the basic information needed to repair all two- and four-stroke cycle engines. The curriculum covers four areas, each consisting of one or more units of instruction that include performance objectives, suggested activities for teacher and students, information sheets, assignment sheets, job sheets, visual aids,…

  4. Targeting Nuclear Envelope Repair.

    PubMed

    2016-06-01

    Migrating cancer cells undergo repeated rupture of the protective nuclear envelope as they squeeze through small spaces in the surrounding tissue, compromising genomic integrity. Inhibiting both general DNA repair and the mechanism that seals these tears may enhance cell death and curb metastasis. PMID:27130435

  5. DNA repair, immunosuppression, and skin cancer.

    PubMed

    Yarosh, Daniel B

    2004-11-01

    UV radiation (UVR) produces erythema within the first 24 hours of exposure, suppression of the immune system within the first 10 days, and, for many people, over the course of decades, skin cancer. Although UVR damages many skin targets, DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) is an important mediator of these sequelae. The action spectrum for erythema parallels the action spectrum for CPD formation in skin, and in the absence of repair, as in the genetic disease xeroderma pigmentosum (XP), skin cancer rates are dramatically increased. DNA repair in skin can be enhanced by the delivery of DNA repair enzymes encapsulated in liposomes. Used in this way, photoreactivation of CPDs greatly diminishes erythema and the suppression of contact hypersensitivity (CHS). UV endonucleases delivered by liposomes also prevent UV-induced suppression of delayed-type hypersensitivity. In a clinical study of patients with XP, T4 endonuclease V (T4N5) liposome lotion applied for one year reduced the rates of actinic keratosis (AK) and skin cancer compared with placebo. These results showed that strategies to increase sun protection should include measures to reduce DNA damage and increase the rate of DNA repair.

  6. Repairing Holes in Pressure Walls

    NASA Technical Reports Server (NTRS)

    Mori, Paul Bruce Y.; Capriloa, Laurie J.; Corocado, Alexander R.; Gibbins, Martin N.; Horne, Robert B.

    1987-01-01

    Patches and easy-to-use tools yield pressure-tight seal. Repairer lifts patch from repair kit with hook-and-pile-tipped tool and positions it over puncture hole. With tool, even gloved repairer easily manipulates patch without damaging it.

  7. Lawn and Garden Equipment Repair.

    ERIC Educational Resources Information Center

    Hardway, Jack; And Others

    This publication is designed to supplement the Comprehensive Small Engine Rapair guide by covering in detail all aspects of lawn and garden equipment repair not included in general engine repair or the repair of other small engines. It consists of instructional materials for both teachers and students, written in terms of student performance using…

  8. Cleft lip repair - series (image)

    MedlinePlus

    ... the middle of the upper lip. A cleft palate is an opening in the roof of the mouth (palate). ... Cleft lip repair and cleft palate repair are indicated for: Repair of physical deformity Nursing, feeding, or speech problems resulting from cleft lip or palate

  9. Automotive Engine Maintenance and Repair.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

    This correspondence course, originally developed for the Marine Corps, is designed to provide students with an understanding of automotive engine maintenance and repair. The course contains six study units covering automotive engine maintenance and repair; design classification; engine malfunction, diagnosis, and repair; engine disassembly; engine…

  10. Electronic Repair Concepts for Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Easton, John; Pettegrew, Richard D.; Struk, Peter M.

    2007-01-01

    Constraints on the mass and volume that can be allocated for electronics spares and repair equipment on long-duration space missions mean that NASA must look at repair strategies beyond the traditional approach, which has been to replace faulty subsystems in a modular form, termed Orbital Replacement Units or Line Replacement Units. Other possible strategies include component and board-level replacement, modular designs that allow reprogramming of less-critical systems to take the place of more critical failed systems, and a blended approach which uses elements of each of these approaches, along with a limited number of Line Replacement Units. This paper presents some of the constraints and considerations that affect the decision on how to approach electronics repair for long duration space missions, and discusses the benefits and limitations of each of the previously mentioned strategies.

  11. Base Excision Repair and Cancer

    PubMed Central

    Wallace, Susan S.; Murphy, Drew L.; Sweasy, Joann B.

    2012-01-01

    Base excision repair is the system used from bacteria to man to remove the tens of thousands of endogenous DNA damages produced daily in each human cell. Base excision repair is required for normal mammalian development and defects have been associated with neurological disorders and cancer. In this paper we provide an overview of short patch base excision repair in humans and summarize current knowledge of defects in base excision repair in mouse models and functional studies on short patch base excision repair germ line polymorphisms and their relationship to cancer. The biallelic germ line mutations that result in MUTYH-associated colon cancer are also discussed. PMID:22252118

  12. DNA repair: Dynamic defenders against cancer and aging

    SciTech Connect

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

    You probably weren't thinking about your body's cellular DNA repair systems the last time you sat on the beach in the bright sunshine. Fortunately, however, while you were subjecting your DNA to the harmful effects of ultraviolet light, your cells were busy repairing the damage. The idea that our genetic material could be damaged by the sun was not appreciated in the early days of molecular biology. When Watson and Crick discovered the structure of DNA in 1953 [1], it was assumed that DNA is fundamentally stable since it carries the blueprint of life. However, over 50 years of research have revealed that our DNA is under constant assault by sunlight, oxygen, radiation, various chemicals, and even our own cellular processes. Cleverly, evolution has provided our cells with a diverse set of tools to repair the damage that Mother Nature causes. DNA repair processes restore the normal nucleotide sequence and DNA structure of the genome after damage [2]. These responses are highly varied and exquisitely regulated. DNA repair mechanisms are traditionally characterized by the type of damage repaired. A large variety of chemical modifications can alter normal DNA bases and either lead to mutations or block transcription if not repaired, and three distinct pathways exist to remove base damage. Base excision repair (BER) corrects DNA base alterations that do not distort the overall structure of the DNA helix such as bases damaged by oxidation resulting from normal cellular metabolism. While BER removes single damaged bases, nucleotide excision repair (NER) removes short segments of nucleotides (called oligonucleotides) containing damaged bases. NER responds to any alteration that distorts the DNA helix and is the mechanism responsible for repairing bulky base damage caused by carcinogenic chemicals such as benzo [a]pyrene (found in cigarette smoke and automobile exhaust) as well as covalent linkages between adjacent pyrimidine bases resulting from the ultraviolet (UV

  13. The ups and downs of DNA repair biomarkers for PARP inhibitor therapies

    PubMed Central

    Wang, XiaoZhe; Weaver, David T

    2011-01-01

    PARP inhibitors are emerging as a valuable new drug class in the treatment of cancer. Recent discoveries make a compelling case for the complexity of DNA repair biomarker evaluation and underscore the need to examine at multiple biomarkers in a relational manner. This review updates the current trends in DNA repair biomarker strategies in use for the PARP inhibitors and describes the impact of many DNA repair biomarkers on PARP inhibitor benefit in the cancer clinic. PMID:21968427

  14. Carbon nanotubes in neuroregeneration and repair.

    PubMed

    Fabbro, Alessandra; Prato, Maurizio; Ballerini, Laura

    2013-12-01

    In the last decade, we have experienced an increasing interest and an improved understanding of the application of nanotechnology to the nervous system. The aim of such studies is that of developing future strategies for tissue repair to promote functional recovery after brain damage. In this framework, carbon nanotube based technologies are emerging as particularly innovative tools due to the outstanding physical properties of these nanomaterials together with their recently documented ability to interface neuronal circuits, synapses and membranes. This review will discuss the state of the art in carbon nanotube technology applied to the development of devices able to drive nerve tissue repair; we will highlight the most exciting findings addressing the impact of carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal differentiation, growth and network reconstruction. PMID:23856411

  15. Semi-Automated Diagnosis, Repair, and Rework of Spacecraft Electronics

    NASA Technical Reports Server (NTRS)

    Struk, Peter M.; Oeftering, Richard C.; Easton, John W.; Anderson, Eric E.

    2008-01-01

    NASA's Constellation Program for Exploration of the Moon and Mars places human crews in extreme isolation in resource scarce environments. Near Earth, the discontinuation of Space Shuttle flights after 2010 will alter the up- and down-mass capacity for the International Space Station (ISS). NASA is considering new options for logistics support strategies for future missions. Aerospace systems are often composed of replaceable modular blocks that minimize the need for complex service operations in the field. Such a strategy however, implies a robust and responsive logistics infrastructure with relatively low transportation costs. The modular Orbital Replacement Units (ORU) used for ISS requires relatively large blocks of replacement hardware even though the actual failed component may really be three orders of magnitude smaller. The ability to perform in-situ repair of electronics circuits at the component level can dramatically reduce the scale of spares and related logistics cost. This ability also reduces mission risk, increases crew independence and improves the overall supportability of the program. The Component-Level Electronics Assembly Repair (CLEAR) task under the NASA Supportability program was established to demonstrate the practicality of repair by first investigating widely used soldering materials and processes (M&P) performed by modest manual means. The work will result in program guidelines for performing manual repairs along with design guidance for circuit reparability. The next phase of CLEAR recognizes that manual repair has its limitations and some highly integrated devices are extremely difficult to handle and demand semi-automated equipment. Further, electronics repairs require a broad range of diagnostic capability to isolate the faulty components. Finally repairs must pass functional tests to determine that the repairs are successful and the circuit can be returned to service. To prevent equipment demands from exceeding spacecraft volume

  16. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  17. Nucleosomes determine their own patch size in base excision repair.

    PubMed

    Meas, Rithy; Smerdon, Michael J

    2016-01-01

    Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2-12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in 'designed' nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase β and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER. PMID:27265863

  18. Active DNA demethylation by DNA repair: Facts and uncertainties.

    PubMed

    Schuermann, David; Weber, Alain R; Schär, Primo

    2016-08-01

    Pathways that control and modulate DNA methylation patterning in mammalian cells were poorly understood for a long time, although their importance in establishing and maintaining cell type-specific gene expression was well recognized. The discovery of proteins capable of converting 5-methylcytosine (5mC) to putative substrates for DNA repair introduced a novel and exciting conceptual framework for the investigation and ultimate discovery of molecular mechanisms of DNA demethylation. Against the prevailing notion that DNA methylation is a static epigenetic mark, it turned out to be dynamic and distinct mechanisms appear to have evolved to effect global and locus-specific DNA demethylation. There is compelling evidence that DNA repair, in particular base excision repair, contributes significantly to the turnover of 5mC in cells. By actively demethylating DNA, DNA repair supports the developmental establishment as well as the maintenance of DNA methylation landscapes and gene expression patterns. Yet, while the biochemical pathways are relatively well-established and reviewed, the biological context, function and regulation of DNA repair-mediated active DNA demethylation remains uncertain. In this review, we will thus summarize and critically discuss the evidence that associates active DNA demethylation by DNA repair with specific functional contexts including the DNA methylation erasure in the early embryo, the control of pluripotency and cellular differentiation, the maintenance of cell identity, and the nuclear reprogramming. PMID:27247237

  19. Nucleosomes determine their own patch size in base excision repair

    PubMed Central

    Meas, Rithy; Smerdon, Michael J.

    2016-01-01

    Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2–12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in ‘designed’ nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase β and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER. PMID:27265863

  20. A review of DNA repair and possible DNA-repair adjuvants and selected natural anti-oxidants.

    PubMed

    Emanuel, Patrick; Scheinfeld, Noah

    2007-01-01

    Few other organs have the environmental exposure-neoplasia relationship that has been observed between epithelial cutaneous malignancy and UVB exposure. A significant DNA type of defective linking of DNA nucleotides involves pyrimidine dimers. Important insight into the molecular processes that affect the response of cells to UVB have been provided by the study of rare inherited diseases characterized by DNA repair defects. Nucleotide excision repair is the best characterized of these and its importance is illustrated by the disease, xeroderma pigmentosum. This heterogenous disorder clinically characterized by malignant tumor development and molecularly by distinct alterations in the nucleotide excision repair apparatus. More recently, other DNA mechanisms have been shown to have some role in skin cancer, such as DNA-mismatch repair and double-stranded DNA breaks. Herein, we discuss the DNA-repair adjuvants a aqueous extract of Urcaria tomentosa (AC-11, Optigenex, Inc.), and T4 endonuclease V that is prepared in a liposome lotion (Dimericine, Applied Genetics Inc. Dermatics). The positive effects on the integrity DNA of other substances (from nature, heat shock proteins and cytokines) including IL-12, Polypodium leucotomos, and ubiquitin are also reviewed. Understanding DNA repair mechanisms is far from complete; further understanding will provide insight into the pathogenesis of cancer and pave the way for efficacious therapeutic agents.

  1. Open aortic surgery after thoracic endovascular aortic repair.

    PubMed

    Coselli, Joseph S; Spiliotopoulos, Konstantinos; Preventza, Ourania; de la Cruz, Kim I; Amarasekara, Hiruni; Green, Susan Y

    2016-08-01

    In the last decade, thoracic endovascular aortic aneurysm repair (TEVAR) has emerged as an appealing alternative to the traditional open aortic aneurysm repair. This is largely due to generally improved early outcomes associated with TEVAR, including lower perioperative mortality and morbidity. However, it is relatively common for patients who undergo TEVAR to need a secondary intervention. In select circumstances, these secondary interventions are performed as an open procedure. Although it is difficult to assess the rate of open repairs after TEVAR, the rates in large series of TEVAR cases (>300) have ranged from 0.4 to 7.9 %. Major complications of TEVAR that typically necessitates open distal aortic repair (i.e., repair of the descending thoracic or thoracoabdominal aorta) include endoleak (especially type I), aortic fistula, endograft infection, device collapse or migration, and continued expansion of the aneurysm sac. Conversion to open repair of the distal aorta may be either elective (as for many endoleaks) or emergent (as for rupture, retrograde complicated dissection, malperfusion, and endograft infection). In addition, in select patients (e.g., those with a chronic aortic dissection), unrepaired sections of the aorta may progressively dilate, resulting in the need for multiple distal aortic repairs. Open repairs after TEVAR can be broadly classified as full extraction, partial extraction, or full salvage of the stent-graft. Although full and partial stent-graft extraction imply failure of TEVAR, such failure is generally absent in cases where the stent-graft can be fully salvaged. We review the literature regarding open repair after TEVAR and highlight operative strategies.

  2. Examining Communication Repairs of 2 Young Children with Autism Spectrum Disorder: The Influence of the Environment

    ERIC Educational Resources Information Center

    Meadan, Hedda; Halle, James W.; Watkins, Ruth V.; Chadsey, Janis G.

    2006-01-01

    Purpose: The purpose of this study was to examine the repair strategies of 2 young children with autism spectrum disorder from an environmental rather than a developmental perspective. Method: A scripted protocol that included opportunities for requests and repair was followed. The environmental variables investigated were activity type (e.g.,…

  3. DNA repair in cultured keratinocytes.

    PubMed

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

    1983-07-01

    Most of our understanding of DNA repair mechanisms in human cells has come from the study of these processes in cultured fibroblasts. The unique properties of keratinocytes and their pattern of terminal differentiation led us to a comparative examination of their DNA repair properties. We have examined the relative repair capabilities of the basal cells and the differentiated epidermal keratinocytes as well as possible correlations of DNA repair capacity with respect to age of the donor. In addition, since portions of human skin are chronically exposed to sunlight, we have assessed the repair response to ultraviolet (UV) irradiation (254 nm) when the cells are conditioned by chronic low-level UV irradiation. The methods of Liu and Karasek were used to grow pure keratinocytes on collagen gels following their isolation from abdominal skin of newborns and adults at autopsy. Density labeling with 5-bromodeoxyuridine was used to resolve repair replication from the semiconservative mode. We found similar repair characteristics in human epidermal keratinocytes to those previously reported for cultured fibroblasts. However, the DNA repair response in basal cells was much greater than that in differentiated cells from the same skin preparation. Our comparative studies of DNA repair in keratinocytes from infant and aged donors have revealed no significant age-related differences for repair of UV-induced damage to DNA. Sublethal UV conditioning of cells from infant skin had no appreciable effect on either the repair or normal replication response to higher, challenge doses of UVL. However, such conditioning resulted in attenuated repair in keratinocytes from adult skin after UV doses above 25 J/m2. In addition, a surprising enhancement in replication was seen in conditioned cells from adult following challenge UV doses.

  4. Endovascular abdominal aortic aneurysm repair

    PubMed Central

    Norwood, M G A; Lloyd, G M; Bown, M J; Fishwick, G; London, N J; Sayers, R D

    2007-01-01

    The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique. PMID:17267674

  5. DNA repair in cultured keratinocytes

    SciTech Connect

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

    1983-07-01

    Most of our understanding of DNA repair mechanisms in human cells has come from the study of these processes in cultured fibroblasts. The unique properties of keratinocytes and their pattern of terminal differentiation led us to a comparative examination of their DNA repair properties. The relative repair capabilities of the basal cells and the differentiated epidermal keratinocytes as well as possible correlations of DNA repair capacity with respect to age of the donor have been examined. In addition, since portions of human skin are chronically exposed to sunlight, the repair response to ultraviolet (UV) irradiation (254 nm) when the cells are conditioned by chronic low-level UV irradiation has been assessed. The comparative studies of DNA repair in keratinocytes from infant and aged donors have revealed no significant age-related differences for repair of UV-induced damage to DNA. Sublethal UV conditioning of cells from infant skin had no appreciable effect on either the repair or normal replication response to higher, challenge doses of UVL. However, such conditioning resulted in attenuated repair in keratinocytes from adult skin after UV doses above 25 J/m2. In addition, a surprising enhancement in replication was seen in conditioned cells from adult following challenge UV doses.

  6. Mutagenic roles of DNA "repair" proteins in antibody diversity and disease-associated trinucleotide repeat instability.

    PubMed

    Slean, Meghan M; Panigrahi, Gagan B; Ranum, Laura P; Pearson, Christopher E

    2008-07-01

    While DNA repair proteins are generally thought to maintain the integrity of the whole genome by correctly repairing mutagenic DNA intermediates, there are cases where DNA "repair" proteins are involved in causing mutations instead. For instance, somatic hypermutation (SHM) and class switch recombination (CSR) require the contribution of various DNA repair proteins, including UNG, MSH2 and MSH6 to mutate certain regions of immunoglobulin genes in order to generate antibodies of increased antigen affinity and altered effector functions. Another instance where "repair" proteins drive mutations is the instability of gene-specific trinucleotide repeats (TNR), the causative mutations of numerous diseases including Fragile X mental retardation syndrome (FRAXA), Huntington's disease (HD), myotonic dystrophy (DM1) and several spinocerebellar ataxias (SCAs) all of which arise via various modes of pathogenesis. These healthy and deleterious mutations that are induced by repair proteins are distinct from the genome-wide mutations that arise in the absence of repair proteins: they occur at specific loci, are sensitive to cis-elements (sequence context and/or epigenetic marks) and transcription, occur in specific tissues during distinct developmental windows, and are age-dependent. Here we review and compare the mutagenic role of DNA "repair" proteins in the processes of SHM, CSR and TNR instability.

  7. 49 CFR 193.2617 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Repairs. 193.2617 Section 193.2617 Transportation...: FEDERAL SAFETY STANDARDS Maintenance § 193.2617 Repairs. (a) Repair work on components must be performed... repaired. (b) For repairs made while a component is operating, each operator shall include in...

  8. Skeletal myoblasts for cardiac repair

    PubMed Central

    Durrani, Shazia; Konoplyannikov, Mikhail; Ashraf, Muhammad; Haider, Khawaja Husnain

    2011-01-01

    Stem cells provide an alternative curative intervention for the infarcted heart by compensating for the cardiomyocyte loss subsequent to myocardial injury. The presence of resident stem and progenitor cell populations in the heart, and nuclear reprogramming of somatic cells with genetic induction of pluripotency markers are the emerging new developments in stem cell-based regenerative medicine. However, until safety and feasibility of these cells are established by extensive experimentation in in vitro and in vivo experimental models, skeletal muscle-derived myoblasts, and bone marrow cells remain the most well-studied donor cell types for myocardial regeneration and repair. This article provides a critical review of skeletal myoblasts as donor cells for transplantation in the light of published experimental and clinical data, and indepth discussion of the advantages and disadvantages of skeletal myoblast-based therapeutic intervention for augmentation of myocardial function in the infarcted heart. Furthermore, strategies to overcome the problems of arrhythmogenicity and failure of the transplanted skeletal myoblasts to integrate with the host cardiomyocytes are discussed. PMID:21082891

  9. Neonatal Repair in a Patient With Heterotaxy, Truncus Arteriosus, Pulmonary Artery Sling, and Tracheal Stenosis.

    PubMed

    Anagnostopoulos, Petros V; Kenny, Eugene C; Peterson, Amy L H; Hagen, Scott A; McMurray, J Scott

    2015-12-01

    We present a newborn with heterotaxy features, multiple congenital anomalies, truncus arteriosus with long segment tracheal stenosis, and a left pulmonary artery sling. The patient had complete neonatal repair with slide tracheoplasty and repair of the left pulmonary artery sling with anterior translocation of the pulmonary artery. The truncus was repaired with a transventricular ventricular septal defect closure with a patch and right ventricle to pulmonary artery conduit. Complete repair of complex cardiac neonatal lesions with critical tracheal stenosis is feasible and should be the strategy of choice in these complex patients. PMID:26652536

  10. Therapeutic ultrasound for dental tissue repair.

    PubMed

    Scheven, B A A; Shelton, R M; Cooper, P R; Walmsley, A D; Smith, A J

    2009-10-01

    Dental disease affects human health and the quality of life of millions worldwide. Tooth decay (caries) and diseases of the dental pulp result in loss of tooth vitality and function requiring invasive treatment to restore the tooth to health. "Therapeutic" low intensity pulsed ultrasound has been shown to accelerate bone fracture healing indicating that ultrasound may be used as a tool to facilitate hard tissue regeneration. We have shown recently that low frequency ultrasound is able to exert biological effects on odontoblast-like cells. In this paper, we postulate that low frequency, low intensity ultrasound may stimulate endogenous coronal tooth repair by stimulating dentine formation from existing odontoblasts or by activating dental pulp stem cells to differentiate into new reparative dentine-producing cells. Ultrasound therapy promoting dentine formation and repair may also have the potential benefit of alleviating dentine hypersensitivity by inducing occlusion of dentinal tubules. It is envisaged that therapeutic ultrasound may be used in future to facilitate dental tissue engineering and stem cell therapy applications for dental tissue regeneration. Further research is warranted in this clinically important area and we envisage that novel strategies in dental therapy will be realised that may ultimately lead to the development of novel non-invasive, multifunctional ultrasound devices for dental diagnostics, repair and regeneration.

  11. Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

    PubMed Central

    Zuliani-Alvarez, Lorena; Midwood, Kim S.

    2015-01-01

    Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing. PMID:26005593

  12. Pectoralis Major Tendon Repair

    PubMed Central

    Cordasco, Frank A.; Degen, Ryan; Mahony, Gregory Thomas; Tsouris, Nicholas

    2016-01-01

    Objectives: Systematic reviews of the literature have identified 365 reported cases of Pectoralis Major Tendon (PMT) injuries. While surgical treatment has demonstrated improved outcomes compared to non-operative treatment, there is still relatively limited data on the functional outcome, return to sport and need for 2nd surgery in athletes following PMT repair. This study comprises the largest series of athletes following PMT repair reported to date. The Objective is to report on the functional outcomes, return to sport and need for 2nd surgery in a consecutive series of PMT tears. Methods: From 2009, 81 patients with PMT tears were enrolled in this prospective series. Baseline evaluation included patient demographics, mechanism of injury, physical examination and PMT specific MRI for confirmation of the diagnosis and analysis of the extent of injury. Each patient underwent surgical repair by the senior author utilizing a previously published surgical technique. Patients were then followed at 2 weeks, 6 weeks, 3 months and 6 months and further follow-up was conducted annually thereafter with functional outcome scores and adduction strength testing. The return to sport and incidence of 2nd surgery data were recorded. This study includes the first 40 athletes to reach the 2-year post-operative period. Results: All athletes were male, with an average age of 34.4 years (range 23-59). The patient cohort consisted of 4 professional NFL players and 36 recreational athletes. Average follow-up duration was 2.5 years (range 2 - 6.0 years). The most common mechanisms of injury occurred during the bench press (n=26) and contact sport participation (n=14). Sixteen injuries were complete avulsions involving both the clavicular and sternocostal heads, while 24 were isolated sternocostal head avulsions. Average pre-injury bench press of 396 lbs (range 170-500 lbs) was restored to 241 lbs post-operatively (range 140-550 lbs). Single Assessment Numeric Evaluation (SANE) scores

  13. Recommendations for Enabling Manual Component Level Electronic Repair for Future Space Missions

    NASA Technical Reports Server (NTRS)

    Struk, Peter M.; Easton, John W.; Funk, Gregory P.; Latta, Gary S.; Ganster, Andrew W.; Estes, Brett E.

    2011-01-01

    Long duration missions to the Moon and Mars pose a number of challenges to mission designers, controllers, and the crews. Among these challenges are planning for corrective maintenance actions which often require a repair. Current repair strategies on the International Space Station (ISS) rely primarily on the use of Orbital Replacement Units (ORUs), where a faulty unit is replaced with a spare, and the faulty unit typically returns to Earth for analysis and possible repair. The strategy of replace to repair has posed challenges even for the ISS program. Repairing faulty hardware at lower levels such as the component level can help maintain system availability in situations where no spares exist and potentially reduce logistic resupply mass.This report provides recommendations to help enable manual replacement of electronics at the component-level for future manned space missions. The recommendations include hardware, tools, containment options, and crew training. The recommendations are based on the work of the Component Level Electronics Assembly Repair (CLEAR) task of the Exploration Technology Development Program from 2006 to 2009. The recommendations are derived based on the experience of two experiments conducted by the CLEAR team aboard the International Space Station as well as a group of experienced Miniature/Microminiature (2M) electronics repair technicians and instructors from the U.S. Navy 2M Project Office. The emphasis of the recommendations is the physical repair. Fault diagnostics and post-repair functional test are discussed in other CLEAR reports.

  14. DNA repair in cancer: emerging targets for personalized therapy

    PubMed Central

    Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

    2014-01-01

    Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repair is a major driver for carcinogenesis and could promote aggressive cancer biology. Interestingly, in established tumors, DNA repair activity is required to counteract oxidative DNA damage that is prevalent in the tumor microenvironment. Emerging clinical data provide compelling evidence that overexpression of DNA repair factors may have prognostic and predictive significance in patients. More recently, DNA repair inhibition has emerged as a promising target for anticancer therapy. Synthetic lethality exploits intergene relationships where the loss of function of either of two related genes is nonlethal, but loss of both causes cell death. Exploiting this approach by targeting DNA repair has emerged as a promising strategy for personalized cancer therapy. In the current review, we focus on recent advances with a particular focus on synthetic lethality targeting in cancer. PMID:24600246

  15. DNA repair of oxidative DNA damage in human carcinogenesis

    PubMed Central

    Paz-Elizur, Tamar; Sevilya, Ziv; Leitner-Dagan, Yael; Elinger, Dalia; Roisman, Laila; Livneh, Zvi

    2008-01-01

    Efficient DNA repair mechanisms comprise a critical component in the protection against human cancer, as indicated by the high predisposition to cancer of individuals with germ-line mutations in DNA repair genes. This includes biallelic germ-line mutations in the MUYH gene, encoding a DNA glycosylase that is involved in the repair of oxidative DNA damage, which strongly predispose humans to a rare hereditary form of colorectal cancer. Extensive research efforts including biochemical, enzymological and genetic studies in model organisms established that the oxidative DNA lesion 8-oxoguanine is mutagenic, and that several DNA repair mechanisms operate to prevent its potentially mutagenic and carcinogenic outcome. Epidemiological studies on the association with sporadic cancers of single nucleotide polymorphisms in genes such as OGG1, involved in the repair of 8-oxoguanine yielded conflicting results, and suggest a minor effect at best. A new approach based on the functional analysis of DNA repair enzymatic activity showed that reduced activity of 8-oxoguanine DNA glycosylase (OGG) is a risk factor in lung and head and neck cancer. Moreover, the combination of smoking and low OGG activity was associated with a higher risk, suggesting a potential strategy for risk assessment and prevention of lung cancer, as well as other types of cancer. PMID:18374480

  16. Mononuclear cells and vascular repair in HHT

    PubMed Central

    Dingenouts, Calinda K. E.; Goumans, Marie-José; Bakker, Wineke

    2015-01-01

    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 activin receptor-like kinase 1, 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 MNCs 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 toward 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 toward 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. PMID:25852751

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

    PubMed

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

    2007-11-01

    Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies. PMID:17586107

  18. Membrane Repair: Mechanisms and Pathophysiology

    PubMed Central

    Cooper, Sandra T.; McNeil, Paul L.

    2015-01-01

    Eukaryotic cells have been confronted throughout their evolution with potentially lethal plasma membrane injuries, including those caused by osmotic stress, by infection from bacterial toxins and parasites, and by mechanical and ischemic stress. The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity. Calcium has been identified as the key trigger to activate an effective membrane repair response that utilizes exocytosis and endocytosis to repair a membrane tear, or remove a membrane pore. We here review what is known about the cellular and molecular mechanisms of membrane repair, with particular emphasis on the relevance of repair as it relates to disease pathologies. Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Yet to be fully understood is whether core membrane repair machinery exists in all cells, or whether evolutionary adaptation has resulted in multiple compensatory repair pathways that specialize in different tissues and cells within our body. PMID:26336031

  19. Cobbler's Technique for Iridodialysis Repair

    PubMed Central

    Pandav, Surinder Singh; Gupta, Parul Chawla; Singh, Rishi Raj; Das, Kalpita; Kaushik, Sushmita; Raj, Srishti; Ram, Jagat

    2016-01-01

    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. PMID:26957855

  20. Cobbler's Technique for Iridodialysis Repair.

    PubMed

    Pandav, Surinder Singh; Gupta, Parul Chawla; Singh, Rishi Raj; Das, Kalpita; Kaushik, Sushmita; Raj, Srishti; Ram, Jagat

    2016-01-01

    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. PMID:26957855

  1. Laparoscopic paracolostomy hernia mesh repair.

    PubMed

    Virzí, Giuseppe; Giuseppe, Virzí; Scaravilli, Francesco; Francesco, Scaravilli; Ragazzi, Salvatore; Salvatore, Ragazzi; Piazza, Diego; Diego, Piazza

    2007-12-01

    Paracolostomy hernia is a common occurrence, representing a late complication of stoma surgery. Different surgical techniques have been proposed to repair the wall defect, but the lowest recurrence rates are associated with the use of mesh. We present the case report of a patient in which laparoscopic paracolostomy hernia mesh repair has been successfully performed. PMID:18097321

  2. Major Appliance Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Smreker, Eugene; Calvert, King

    This module is a comprehensive text on basic appliance repair, designed to prepare students for entry-level jobs in this growing field. Ensuring a firm grounding in electrical knowledge, the module contains 13 instructional units that cover the following topics: (1) major appliance repair orientation; (2) safety and first aid; (3) fundamentals of…

  3. Instructional Guide for Autobody Repair.

    ERIC Educational Resources Information Center

    Virginia Polytechnic Inst. and State Univ., Blacksburg. Dept. of Education.

    The curriculum guide was developed to serve as a statewide model for Virginia auto body repair programs. The guide is designed to 1,080 hours of instruction in eleven blocks: orientation, introduction, welding and cutting, techniques of shaping metal, body filler and fiberglass repairs, body and frame, removing and replacing damaged parts, basic…

  4. Communication Repair and Response Classes

    ERIC Educational Resources Information Center

    Meadan, Hedda; Halle, James W.

    2004-01-01

    A communicative repair has been defined as the ability to persist in communication and to modify, repeat, or revise a signal when the initial communication attempt failed. From an operant perspective, initial communicative acts and communicative repairs can be considered members of a response class in which each response produces the same outcome.…

  5. Pipe inspection and repair system

    NASA Technical Reports Server (NTRS)

    Schempf, Hagen (Inventor); Mutschler, Edward (Inventor); Chemel, Brian (Inventor); Boehmke, Scott (Inventor); Crowley, William (Inventor)

    2004-01-01

    A multi-module pipe inspection and repair device. The device includes a base module, a camera module, a sensor module, an MFL module, a brush module, a patch set/test module, and a marker module. Each of the modules may be interconnected to construct one of an inspection device, a preparation device, a marking device, and a repair device.

  6. Cycling with BRCA2 from DNA repair to mitosis

    SciTech Connect

    Lee, Hyunsook

    2014-11-15

    Genetic integrity in proliferating cells is guaranteed by the harmony of DNA replication, appropriate DNA repair, and segregation of the duplicated genome. Breast cancer susceptibility gene BRCA2 is a unique tumor suppressor that is involved in all three processes. Hence, it is critical in genome maintenance. The functions of BRCA2 in DNA repair and homology-directed recombination (HDR) have been reviewed numerous times. Here, I will briefly go through the functions of BRCA2 in HDR and focus on the emerging roles of BRCA2 in telomere homeostasis and mitosis, then discuss how BRCA2 exerts distinct functions in a cell-cycle specific manner in the maintenance of genomic integrity. - Highlights: • BRCA2 is a multifaceted tumor suppressor and is crucial in genetic integrity. • BRCA2 exerts distinct functions in cell cycle-specific manner. • Mitotic kinases regulate diverse functions of BRCA2 in mitosis and cytokinesis.

  7. Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

    PubMed Central

    Dewan, Ashvin K.; Gibson, Matthew A.; Elisseeff, Jennifer H.; Trice, Michael E.

    2014-01-01

    Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI) and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient's knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients. PMID:25210707

  8. A new nucleotide-excision-repair gene associated with the disorder trichothiodystrophy

    SciTech Connect

    Stefanini, M.; Giliani, S. ); Vermuelen, W.; Weeda, G.; Hoeijmakers, H.J.; Mezzina, M.; Sarasin, A.; Harper, J.I.; Arlett, C.F.; Lehmann, A.R.

    1993-10-01

    The sun-sensitive, cancer-prone genetic disorder xeroderma pigmentosum (XP) is associated in most cases with a defect in the ability to carry out excision repair of UV damage. Seven genetically distinct complementation groups (i.e., A-G) have been identified. A large proportion of patients with the unrelated disorder trichothiodystrophy (TTD), which is characterized by hair-shaft abnormalities, as well as by physical and mental retardation, are also deficient in excision repair of UV damage. In most of these cases the repair deficiency is in the same complementation group as is XP group D. The authors report here on cells from a patient, TTD1BR, in which the repair defect complements all known XP groups (including XP-D). Furthermore, microinjection of various cloned human repair genes fails to correct the repair defect in this cell strain. The defect in TTD1BR cells is therefore in a new gene involved in excision repair in human cells. The finding of a second DNA repair gene that is associated with the clinical features of TTD argues strongly for an involvement of repair proteins in hair-shaft development. 20 refs., 2 figs., 1 tab.

  9. Integrating Multi-omics Data to Dissect Mechanisms of DNA repair Dysregulation in Breast Cancer

    PubMed Central

    Liu, Chao; Rohart, Florian; Simpson, Peter T.; Khanna, Kum Kum; Ragan, Mark A.; Lê Cao, Kim-Anh

    2016-01-01

    DNA repair genes and pathways that are transcriptionally dysregulated in cancer provide the first line of evidence for the altered DNA repair status in tumours, and hence have been explored intensively as a source for biomarker discovery. The molecular mechanisms underlying DNA repair dysregulation, however, have not been systematically investigated in any cancer type. In this study, we performed a statistical analysis to dissect the roles of DNA copy number alteration (CNA), DNA methylation (DM) at gene promoter regions and the expression changes of transcription factors (TFs) in the differential expression of individual DNA repair genes in normal versus tumour breast samples. These gene-level results were summarised at pathway level to assess whether different DNA repair pathways are affected in distinct manners. Our results suggest that CNA and expression changes of TFs are major causes of DNA repair dysregulation in breast cancer, and that a subset of the identified TFs may exert global impacts on the dysregulation of multiple repair pathways. Our work hence provides novel insights into DNA repair dysregulation in breast cancer. These insights improve our understanding of the molecular basis of the DNA repair biomarkers identified thus far, and have potential to inform future biomarker discovery. PMID:27666291

  10. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  11. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  12. Timing of traumatic lumbar hernia repair: is delayed repair safe? Report of two cases and review of the literature.

    PubMed

    Bathla, L; Davies, E; Fitzgibbons, R J; Cemaj, S

    2011-04-01

    Fewer than 100 cases of traumatic lumbar hernias are described in the English literature. The herniation has been described as a consequence of a combination of local tangential shearing forces combined with an acute increase in intra-abdominal pressure secondary to sudden deceleration sustained during blunt abdominal trauma. Delayed diagnosis is not uncommon, as nearly a quarter of these are missed at initial presentation. These hernias are best managed by operative intervention; however, there is no well-defined treatment strategy regarding either the timing or the type of repair. Several approaches, including laparoscopy, have been described to repair these defects. Various techniques, including primary repair, musculoaponeurotic reconstruction, and prosthetic mesh repair, have been described. These repairs are usually complicated because of the lack of musculoaponeurotic tissue inferiorly near the iliac crest. We describe here two cases of traumatic lumbar hernia managed by initial watchful waiting and subsequent elective repair using a combined laparoscopic and open technique and one with and one without bone anchor fixation.

  13. Optimal Distinctiveness Signals Membership Trust.

    PubMed

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

    According to optimal distinctiveness theory, sufficiently small minority groups are associated with greater membership trust, even among members otherwise unknown, because the groups are seen as optimally distinctive. This article elaborates on the prediction's motivational and cognitive processes and tests whether sufficiently small minorities (defined by relative size; for example, 20%) are associated with greater membership trust relative to mere minorities (45%), and whether such trust is a function of optimal distinctiveness. Two experiments, examining observers' perceptions of minority and majority groups and using minimal groups and (in Experiment 2) a trust game, revealed greater membership trust in minorities than majorities. In Experiment 2, participants also preferred joining minorities over more powerful majorities. Both effects occurred only when minorities were 20% rather than 45%. In both studies, perceptions of optimal distinctiveness mediated effects. Discussion focuses on the value of relative size and optimal distinctiveness, and when membership trust manifests. PMID:27140657

  14. Progress in Neuroprotective Strategies for Preventing Epilepsy

    PubMed Central

    Acharya, Munjal M.; Hattiangady, Bharathi; Shetty, Ashok K.

    2008-01-01

    Neuroprotection is increasingly considered as a promising therapy for preventing and treating temporal lobe epilepsy (TLE). The development of chronic TLE, also termed as epileptogenesis, is a dynamic process. An initial precipitating injury (IPI) such as the status epilepticus (SE) leads to neurodegeneration, abnormal reorganization of the brain circuitry and a significant loss of functional inhibition. All of these changes likely contribute to the development of chronic epilepsy, characterized by spontaneous recurrent motor seizures (SRMS) and learning and memory deficits. The purpose of this review is to discuss the current state of knowledge pertaining to neuroprotection in epileptic conditions, and to highlight the efficacy of distinct neuroprotective strategies for preventing or treating chronic TLE. Although the administration of certain conventional and new generation antiepileptic drugs is effective for primary neuroprotection such as reduced neurodegeneration after acute seizures or the SE, their competence for preventing the development of chronic epilepsy after an IPI is either unknown or not promising. On the other hand, alternative strategies such as the ketogenic diet therapy, administration of distinct neurotrophic factors, hormones or antioxidants seem useful for preventing and treating chronic TLE. However, long term studies on the efficacy of these approaches introduced at different time-points after the SE or an IPI are lacking. Additionally, grafting of fetal hippocampal cells at early time-points after an IPI holds considerable promise for preventing TLE, though issues regarding availability of donor cells, ethical concerns, timing of grafting after SE, and durability of graft-mediated seizure suppression need to be resolved for further advances with this approach. Overall, from the studies performed so far, there is consensus that neuroprotective strategies need to be employed as quickly as possible after the onset of the SE or an IPI for

  15. Developing miRNA therapeutics for cardiac repair in ischemic heart disease

    PubMed Central

    Zhu, Kai; Liu, Dingqian; Lai, Hao

    2016-01-01

    MicroRNAs (miRNAs) families have been found to be powerful regulators in a wide variety of diseases, which enables the possible use of miRNAs in therapeutic strategies for cardiac repair after ischemic heart disease. This review provides some general insights into miRNAs modulation for development of current molecular and cellular therapeutics in cardiac repair, including endogenous regeneration, endogenous repair, stem cells transplantation, and reprogramming. We also review the delivery strategies for miRNAs modulation, and briefly summarize the current bench and clinical efforts that are being made to explore miRNAs as the future therapeutic target. PMID:27747027

  16. Wound repair in Pocillopora.

    PubMed

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry Martin; Calderon-Aguilera, Luis Eduardo

    2016-09-01

    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 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). 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. PMID:27397755

  17. Wound repair in Pocillopora

    USGS Publications Warehouse

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

    2016-01-01

    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.

  18. Wound repair in Pocillopora.

    PubMed

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry Martin; Calderon-Aguilera, Luis Eduardo

    2016-09-01

    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 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). 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. Coal bunker repairs

    SciTech Connect

    Emmons, M.H.; Hoffman, M.G. )

    1992-01-01

    Detroit Edison's St. Clair Power Plant (STCPP) Units 1 through 4 are 1950's vintage fossil fueled units with an average capacity of 163 megawatt per unit. Each unit had identical 2190 ton bunkers. The Unit No. 1 bunker had been experiencing noticeable exterior deterioration at the lower level internal support system. An internal bunker inspection revealed large deflections in the network of beams supporting the bunker side walls. A complete collapse of the internal support beams was imminent. Failure of these beams would have transferred the coal pressure loads to the bunker skin and external stiffeners which were not capable of sustaining the load and were also showing signs of distress. This paper presents the temporary repair installed immediately after inspection, the redesign of the lower internal support system and construction procedures involved in bringing the bunker back into operating condition.

  20. TPS Inspection and Repair

    NASA Technical Reports Server (NTRS)

    Parazynski, Scott

    2012-01-01

    Dr. Scott Parazynski provided a retrospective on the EVA tools and procedures efforts NASA went through in the aftermath of Columbia for the Shuttle Thermal Protection System (TPS) inspection and repair. He describes his role as the lead astronaut on this effort, and covered all of the Neutral Buoyancy Lab (NBL), KC 135 (reduced gravity aircraft), Precision Air Bearing Floor (PABF), vacuum chamber and 1 G testing that was done in order to develop the tools and techniques that were flown. Parazynski also discusses how the EVA community worked together to resolve a huge safety issue, and how his work in the spacesuit was critical to overcoming a design limitation of the Space Shuttle.

  1. Preclinical Models for Translating Regenerative Medicine Therapies for Rotator Cuff Repair

    PubMed Central

    Baker, Andrew Ryan; Iannotti, Joseph P.; McCarron, Jesse A.

    2010-01-01

    Despite improvements in the understanding of rotator cuff pathology and advances in surgical treatment options, repairs of chronic rotator cuff tears often re-tear or fail to heal after surgery. Hence, there is a critical need for new regenerative repair strategies that provide effective mechanical reinforcement of rotator cuff repair as well as stimulate and enhance the patient's intrinsic healing potential. This article will discuss and identify appropriate models for translating regenerative medicine therapies for rotator cuff repair. Animal models are an essential part of the research and development pathway; however, no one animal model reproduces all of the features of the human injury condition. The rat shoulder is considered the most appropriate model to investigate the initial safety, mechanism, and efficacy of biologic treatments aimed to enhance tendon-to-bone repair. Whereas large animal models are considered more appropriate to investigate the surgical methods, safety and efficacy of the mechanical—or combination biologic/mechanical—strategies are ultimately needed for treating human patients. The human cadaver shoulder model, performed using standard-of-care repair techniques, is considered the best for establishing the surgical techniques and mechanical efficacy of various repair strategies at time zero. While preclinical models provide a critical aspect of the translational pathway for engineered tissues, controlled clinical trials and postmarketing surveillance are also needed to define the efficacy, proper indications, and the method of application for each new regenerative medicine strategy. PMID:19663651

  2. Conservatism and new technology: the impact on abdominal aortic aneurysm repair.

    PubMed

    Bush, Ruth L; Najibi, Sasan; Lin, Peter H; Lumsden, Alan B; Dodson, Thomas F; Salam, Atef A; Smith, Robert B; Chaikof, Elliot L; Weiss, Victor L

    2002-01-01

    The last decade has represented a time of fundamental change in the treatment of abdominal aortic aneurysms (AAAs). Potentially, vascular surgeons will either acquire catheter-based skills or relinquish the care for many patients with infrarenal AAA. We investigated AAA referral patterns and method of AAA repair after the establishment of an endovascular AAA program at our institution. We conducted a retrospective review of elective AAA repairs after the initiation of an endovascular AAA program in April 1994. Six vascular surgeons performed all procedures with a clear distinction between the surgeons (n=3) who performed traditional AAA repair only and those (n=3) who managed AAAs by means of either endovascular or traditional treatment. From April 1994 through December 2000, 740 elective AAA repairs were performed. During this time the mean number of AAA repairs has been 106/year ranging from 75 to 155/year. More notable however is the steady increase in the percentage of endovascular AAA repairs from 6 per cent of all AAA repairs in 1994 to 61 per cent in 2000. During this time traditional surgeons have experienced a plateau in total AAA repairs performed per year with their number of open repairs decreasing by 36 per cent. At the same time endovascular surgeons have seen a progressive rise in total AAA cases including an increase of 200 per cent in open repairs and of 1367 per cent in endovascular repairs. Our vascular surgeons who repair AAA utilizing both endovascular and open techniques have experienced an increase in aneurysm referrals since the advent of an endovascular AAA program. Those who have not adopted endovascular skills have seen a decline in their aneurysm practice. The larger question about whether or not to embrace new technology before the availability of long-term follow-up remains unanswered. PMID:12467319

  3. Is forebrain neurogenesis a potential repair mechanism after stroke?

    PubMed

    Inta, Dragos; Gass, Peter

    2015-07-01

    The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ generates predominantly calretinin (CR)-expressing GABAergic interneurons, which cannot replace the broad spectrum of neuronal subtypes damaged by stroke. Therefore, SVZ neurogenesis may represent a repair mechanism only after genetic manipulation redirecting its differentiation.

  4. Is forebrain neurogenesis a potential repair mechanism after stroke?

    PubMed Central

    Inta, Dragos; Gass, Peter

    2015-01-01

    The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ generates predominantly calretinin (CR)-expressing GABAergic interneurons, which cannot replace the broad spectrum of neuronal subtypes damaged by stroke. Therefore, SVZ neurogenesis may represent a repair mechanism only after genetic manipulation redirecting its differentiation. PMID:25966955

  5. Microvascular Repair: Post-Angiogenesis Vascular Dynamics

    PubMed Central

    LeBlanc, Amanda J.; Krishnan, Laxminarayanan; Sullivan, Christopher J.; Williams, Stuart K.; Hoying, James B.

    2013-01-01

    Vascular compromise and the accompanying perfusion deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures thereby establishing more competent microcirculatory beds. Growing evidence indicates that an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation and includes vascular guidance and inosculation, vessel maturation, pruning, arterio-venous specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation. While many of the mechanisms regulating angiogenesis have been detailed, a thorough understanding of the mechanisms driving post-angiogenesis activities specific to neovascularization has yet to be fully realized, but is necessary in order to develop effective therapeutic strategies for repairing compromised microcirculations as a means to treat disease. PMID:22734666

  6. Language Learning Strategies and Communication Strategies: A Synthesis

    ERIC Educational Resources Information Center

    Husain, Kausar

    2006-01-01

    Since Selinker's (1972) historic invocation of language learning strategies (LLS) and communication strategies (CS) as two distinct processes involved in the development of interlanguage, it has become customary in SLA literature to distinguish the strategies of learning from the strategies of communication. It has been argued in this article that…

  7. DNA repair in Chromobacterium violaceum.

    PubMed

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

    2004-03-31

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

  8. Novel DNA mismatch repair activity involving YB-1 in human mitochondria

    PubMed Central

    de Souza-Pinto, Nadja C.; Mason, Penelope A.; Hashiguchi, Kazunari; Weissman, Lior; Tian, Jingyan; Guay, David; Lebel, Michel; Stevnsner, Tinna V.; Rasmussen, Lene Juel; Bohr, Vilhelm A.

    2009-01-01

    Maintenance of the mitochondrial genome (mtDNA) is essential for proper cellular function. The accumulation of damage and mutations in the mtDNA leads to diseases, cancer, and aging. Mammalian mitochondria have proficient base excision repair, but the existence of other DNA repair pathways is still unclear. Deficiencies in DNA mismatch repair (MMR), which corrects base mismatches and small loops, are associated with DNA microsatellite instability, accumulation of mutations, and cancer. MMR proteins have been identified in yeast and coral mitochondria; however, MMR proteins and function have not yet been detected in human mitochondria. Here we show that human mitochondria have a robust mismatch-repair activity, which is distinct from nuclear MMR. Key nuclear MMR factors were not detected in mitochondria, and similar mismatch-binding activity was observed in mitochondrial extracts from cells lacking MSH2, suggesting distinctive pathways for nuclear and mitochondrial MMR. We identified the repair factor YB-1 as a key candidate for a mitochondrial mismatch-binding protein. This protein localizes to mitochondria in human cells, and contributes significantly to the mismatch-binding and mismatch-repair activity detected in HeLa mitochondrial extracts, which are significantly decreased when the intracellular levels of YB-1 are diminished. Moreover, YB-1 depletion in cells increases mitochondrial DNA mutagenesis. Our results show that human mitochondria contain a functional MMR repair pathway in which YB-1 participates, likely in the mismatch binding and recognition steps. PMID:19272840

  9. DNA repair in Mycoplasma gallisepticum

    PubMed Central

    2013-01-01

    Background DNA repair is essential for the maintenance of genome stability in all living beings. Genome size as well as the repertoire and abundance of DNA repair components may vary among prokaryotic species. The bacteria of the Mollicutes class feature a small genome size, absence of a cell wall, and a parasitic lifestyle. A small number of genes make Mollicutes a good model for a “minimal cell” concept. Results In this work we studied the DNA repair system of Mycoplasma gallisepticum on genomic, transcriptional, and proteomic levels. We detected 18 out of 22 members of the DNA repair system on a protein level. We found that abundance of the respective mRNAs is less than one per cell. We studied transcriptional response of DNA repair genes of M. gallisepticum at stress conditions including heat, osmotic, peroxide stresses, tetracycline and ciprofloxacin treatment, stationary phase and heat stress in stationary phase. Conclusions Based on comparative genomic study, we determined that the DNA repair system M. gallisepticum includes a sufficient set of proteins to provide a cell with functional nucleotide and base excision repair and mismatch repair. We identified SOS-response in M. gallisepticum on ciprofloxacin, which is a known SOS-inducer, tetracycline and heat stress in the absence of established regulators. Heat stress was found to be the strongest SOS-inducer. We found that upon transition to stationary phase of culture growth transcription of DNA repair genes decreases dramatically. Heat stress does not induce SOS-response in a stationary phase. PMID:24148612

  10. Retinoschisis transposition following a retinal detachment repair

    PubMed Central

    McVeigh, Katherine; Keller, Johannes; Haynes, Richard J.

    2015-01-01

    Objective: The authors have observed this phenomenon of translocation of the schisis cavity in a few previous cases and aim to report this unusual finding. Method: A patient with known superotemporal retinoschisis developed a distinctly separate inferotemporal retinal detachment in his left eye. This was repaired with a vitrectomy, cryotherapy and C2F6 tamponade under local anaesthetic. Following surgery, the retinoschisis was found in the inferonasal quadrant of the eye and remained stable as the gas dispersed. Result: We hypothesise that the tamponading agent compressed the viscous fluid within the area of schisis, displacing the area of schisis circumferentially. Conclusion: This case emphasises that as long as the retinal breaks are properly sealed, no intervention is required with the schisis during rhegmatogenous retinal detachment surgery.

  11. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  12. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair.

    PubMed

    Rey-Rico, Ana; Madry, Henning; Cucchiarini, Magali

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  13. Error-Prone Repair of DNA Double-Strand Breaks.

    PubMed

    Rodgers, Kasey; McVey, Mitch

    2016-01-01

    Preserving the integrity of the DNA double helix is crucial for the maintenance of genomic stability. Therefore, DNA double-strand breaks represent a serious threat to cells. In this review, we describe the two major strategies used to repair double strand breaks: non-homologous end joining and homologous recombination, emphasizing the mutagenic aspects of each. We focus on emerging evidence that homologous recombination, long thought to be an error-free repair process, can in fact be highly mutagenic, particularly in contexts requiring large amounts of DNA synthesis. Recent investigations have begun to illuminate the molecular mechanisms by which error-prone double-strand break repair can create major genomic changes, such as translocations and complex chromosome rearrangements. We highlight these studies and discuss proposed models that may explain some of the more extreme genetic changes observed in human cancers and congenital disorders.

  14. Iterative Repair Planning for Spacecraft Operations Using the Aspen System

    NASA Technical Reports Server (NTRS)

    Rabideau, G.; Knight, R.; Chien, S.; Fukunaga, A.; Govindjee, A.

    2000-01-01

    This paper describes the Automated Scheduling and Planning Environment (ASPEN). ASPEN encodes complex spacecraft knowledge of operability constraints, flight rules, spacecraft hardware, science experiments and operations procedures to allow for automated generation of low level spacecraft sequences. Using a technique called iterative repair, ASPEN classifies constraint violations (i.e., conflicts) and attempts to repair each by performing a planning or scheduling operation. It must reason about which conflict to resolve first and what repair method to try for the given conflict. ASPEN is currently being utilized in the development of automated planner/scheduler systems for several spacecraft, including the UFO-1 naval communications satellite and the Citizen Explorer (CX1) satellite, as well as for planetary rover operations and antenna ground systems automation. This paper focuses on the algorithm and search strategies employed by ASPEN to resolve spacecraft operations constraints, as well as the data structures for representing these constraints.

  15. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair.

  16. Cellular Encapsulation Enhances Cardiac Repair

    PubMed Central

    Levit, Rebecca D.; Landázuri, Natalia; Phelps, Edward A.; Brown, Milton E.; García, Andrés J.; Davis, Michael E.; Joseph, Giji; Long, Robert; Safley, Susan A.; Suever, Jonathan D.; Lyle, Alicia N.; Weber, Collin J.; Taylor, W. Robert

    2013-01-01

    Background Stem cells for cardiac repair have shown promise in preclinical trials, but lower than expected retention, viability, and efficacy. Encapsulation is one potential strategy to increase viable cell retention while facilitating paracrine effects. Methods and Results Human mesenchymal stem cells (hMSC) were encapsulated in alginate and attached to the heart with a hydrogel patch in a rat myocardial infarction (MI) model. Cells were tracked using bioluminescence (BLI) and cardiac function measured by transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR). Microvasculature was quantified using von Willebrand factor staining and scar measured by Masson's Trichrome. Post‐MI ejection fraction by CMR was greatly improved in encapsulated hMSC‐treated animals (MI: 34±3%, MI+Gel: 35±3%, MI+Gel+hMSC: 39±2%, MI+Gel+encapsulated hMSC: 56±1%; n=4 per group; P<0.01). Data represent mean±SEM. By TTE, encapsulated hMSC‐treated animals had improved fractional shortening. Longitudinal BLI showed greatest hMSC retention when the cells were encapsulated (P<0.05). Scar size at 28 days was significantly reduced in encapsulated hMSC‐treated animals (MI: 12±1%, n=8; MI+Gel: 14±2%, n=7; MI+Gel+hMSC: 14±1%, n=7; MI+Gel+encapsulated hMSC: 7±1%, n=6; P<0.05). There was a large increase in microvascular density in the peri‐infarct area (MI: 121±10, n=7; MI+Gel: 153±26, n=5; MI+Gel+hMSC: 198±18, n=7; MI+Gel+encapsulated hMSC: 828±56 vessels/mm2, n=6; P<0.01). Conclusions Alginate encapsulation improved retention of hMSCs and facilitated paracrine effects such as increased peri‐infarct microvasculature and decreased scar. Encapsulation of MSCs improved cardiac function post‐MI and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases. PMID:24113327

  17. Role of biomechanics on intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair?

    PubMed Central

    Iatridis, James C.; Nicoll, Steven B.; Michalek, Arthur J.; Walter, Benjamin A.; Gupta, Michelle S.

    2013-01-01

    Background Context Degeneration and injuries of the intervertebral disc result in large alterations in biomechanical behaviors. Repair strategies using biomaterials can be optimized based on biomechanical and biological requirements. Purpose To review current literature on 1) effects of degeneration, simulated degeneration, and injury on biomechanics of the intervertebral disc with special attention paid to needle puncture injuries which are a pathway for diagnostics and regenerative therapies; and 2) promising biomaterials for disc repair with a focus on how those biomaterials may promote biomechanical repair. Study Design/Setting A narrative review to evaluate the role of biomechanics on disc degeneration and regenerative therapies with a focus on what biomechanical properties need to be repaired and how to evaluate and accomplish such repairs using biomaterials. Model systems for screening of such repair strategies are also briefly described. Methods Papers were selected from two main Pubmed searches using keywords: intervertebral AND biomechanics (1823 articles) and intervertebral AND biomaterials (361 articles). Additional keywords (injury, needle puncture, nucleus pressurization, biomaterials, hydrogel, sealant, tissue engineering) were used to narrow articles to the topics most relevant to this review. Results Degeneration and acute disc injuries have the capacity to influence nucleus pulposus pressurization and annulus fibrosus integrity, which are necessary for effective disc function, and therefore, require repair. Needle injection injuries are of particular clinical relevance with potential to influence disc biomechanics, cellularity, and metabolism, yet these effects are localized or small, and more research is required to evaluate and reduce potential clinical morbidity using such techniques. NP replacement strategies, such as hydrogels, are required to restore NP pressurization or lost volume. AF repair strategies, including crosslinked hydrogels

  18. Editorial Commentary: Arthroscopic Rotator Cuff Repair--Infection Rate After Rotator Cuff Repair With Arthroscopic, Open, and Mini-open Techniques.

    PubMed

    Brand, Jefferson C

    2016-03-01

    In "Risk Factors for Infection After Rotator Cuff Repair," B. G. Vopat et al. report a lower rate of postoperative infection with an arthroscopic rotator cuff repair than with an open or mini-open approach. Although there were only 14 infections (infection rate of 0.77%), the reason for the preponderance of male patients, 13 of the 14 infections, needs further research to determine effective preventive strategies.

  19. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 40 Protection of Environment 11 2012-07-01 2012-07-01 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...

  20. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... 40 Protection of Environment 11 2012-07-01 2012-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule....

  1. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Leak repair. 63.1024 Section 63.1024... Standards for Equipment Leaks-Control Level 2 Standards § 63.1024 Leak repair. (a) Leak repair schedule....

  2. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... 40 Protection of Environment 11 2014-07-01 2014-07-01 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. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

    The Gordon Research Conference (GRC) on Mammalian DNA Repair was held at Harbortown Resort, Ventura Beach, CA. Emphasis was placed on current unpublished research and discussion of the future target areas in this field.

  4. Wnt Signaling During Fracture Repair

    PubMed Central

    Secreto, Frank J.; Hoeppner, Luke H.; Westendorf, Jennifer J.

    2010-01-01

    Bone is one of the few tissues in the body with the capacity to regenerate and repair itself. In most cases, fractures are completely repaired in a relatively short period of time; however, in a small percentage of cases, healing never occurs and non-union is the result. Fracture repair and bone regeneration require the localized re-activation of signaling cascades that are crucial for skeletal development. The Wnt/β-catenin signaling pathway is one such developmental pathway whose role in bone formation and regeneration has been recently appreciated. During the last decade, much has learned about how Wnt pathways regulate bone mass. Small molecules and biologics aimed at this pathway are now being tested as potential new anabolic agents. Here we review recent data demonstrating that Wnt pathways are active during fracture repair and that increasing the activities of Wnt pathway components accelerates bone regeneration. PMID:19631031

  5. Nucleotide excision repair in humans.

    PubMed

    Spivak, Graciela

    2015-12-01

    The demonstration of DNA damage excision and repair replication by Setlow, Howard-Flanders, Hanawalt and their colleagues in the early 1960s, constituted the discovery of the ubiquitous pathway of nucleotide excision repair (NER). The serial steps in NER are similar in organisms from unicellular bacteria to complex mammals and plants, and 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. The transcription-coupled repair (TCR) subpathway of NER, discovered nearly two decades later, is dedicated to the removal of lesions from the template DNA strands of actively transcribed genes. In this review I will outline the essential factors and complexes involved in NER in humans, and will comment on additional factors and metabolic processes that affect the efficiency of this important process. PMID:26388429

  6. Nuclear compartmentalization of DNA repair.

    PubMed

    Kalousi, Alkmini; Soutoglou, Evi

    2016-04-01

    The continuous threats on genome integrity by endogenous and exogenous sources have rendered cells competent to overcome these challenges by activating DNA repair pathways. A complex network of proteins and their modifications participate in orchestrated signaling cascades, which are induced in response to DNA damage and may determine the choice of repair pathway. In this review, we summarize recent findings in the field of DNA Double Strand Break repair with regard to the positioning of the break in the highly compartmentalized nucleus. We aim to highlight the importance of chromatin state along with the nuclear position of the DNA lesions on the choice of DNA repair pathway and maintenance of genome integrity. PMID:27266837

  7. Rotator cuff repair - series (image)

    MedlinePlus

    ... shoulder and arm bones. The tendons can be torn from overuse or injury. ... Surgery to repair a torn rotator cuff is usually very successful at relieving pain in the shoulder. The procedure is less predictable at returning strength ...

  8. Precision Instrument and Equipment Repairers.

    ERIC Educational Resources Information Center

    Wyatt, Ian

    2001-01-01

    Explains the job of precision instrument and equipment repairers, who work on cameras, medical equipment, musical instruments, watches and clocks, and industrial measuring devices. Discusses duties, working conditions, employment and earnings, job outlook, and skills and training. (JOW)

  9. How the brain repairs stuttering.

    PubMed

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

    2009-10-01

    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 developmental plasticity. Here we explore what distinguishes this type of recovery from less optimal repair modes, i.e. therapy-induced assisted recovery and attempted compensation in subjects who are still affected. We show that persistent stuttering is associated with mobilization of brain regions contralateral to the structural anomalies for compensation attempt. In contrast, the only neural landmark of optimal repair is activation of the left BA 47/12 in the orbitofrontal cortex, adjacent to a region where a white matter anomaly is observed in persistent stutterers, but normalized in recovered subjects. These findings show that late repair of neurodevelopmental stuttering follows the principles of contralateral and perianomalous reorganization.

  10. On structural health monitoring of aircraft adhesively bonded repairs

    NASA Astrophysics Data System (ADS)

    Pavlopoulou, Sofia

    The recent interest in life extension of ageing aircraft and the need to address the repair challenges in the new age composite ones, led to the investigation of new repair methodologies such as adhesively bonded repair patches. The present thesis focuses on structural health monitoring aspects of the repairs, evaluating their performance with guided ultrasonic waves aiming to develop a monitoring strategy which would eliminate unscheduled maintenance and unnecessary inspection costs. To address the complex nature of the wave propagation phenomena, a finite element based model identified the existing challenges by exploring the interaction of the excitation waves with different levels of damage. The damage sensitivity of the first anti-symmetric mode was numerically investigated. An external bonded patch and a scarf repair, were further tested in static and dynamic loadings, and their performance was monitored with Lamb waves, excited by surface-bonded piezoelectric transducers.. The response was processed by means of advanced pattern recognition and data dimension reduction techniques such as novelty detection and principal component analysis. An optimisation of these tools enabled an accurate damage detection under complex conditions. The phenomena of mode isolation and precise arrival time determination under a noisy environment and the problem of inadequate training data were investigated and solved through appropriate transducer arrangements and advanced signal processing respectively. The applicability of the established techniques was demonstrated on an aluminium repaired helicopter tail stabilizer. Each case study utilised alternative non-destructive techniques for validation such as 3D digital image correlation, X-ray radiography and thermography. Finally a feature selection strategy was developed through the analysis of the instantaneous properties of guided waves for damage detection purposes..

  11. Assessment of the canine model of rotator cuff injury and repair

    PubMed Central

    Derwin, Kathleen A; Baker, Andrew R; Codsi, Michael J; Iannotti, Joseph P

    2007-01-01

    Animal shoulder models are used to systematically investigate the factors influencing rotator cuff injury and repair. Each model has advantages and disadvantages that must be considered in the context of the specific research questions being asked. Herein we evaluate the utility of the canine model for studies of acute, full-thickness rotator cuff tendon injury and repair. We found that time zero failure load is dependent on the suture type and configuration used for repair. Acute, full-width tendon repairs fail anatomically within the first days after surgery in the canine model, regardless of suture type, suture configuration or post-operative protocol. Robust scar tissue forms in the gap between the failed tendon end and the humerus, which can be visually, mechanically and histologically misconstrued as tendon if an objective test of repair connectivity is not performed. We conclude that a full-width injury and repair model in the canine will provide a rigorous test of whether a new repair strategy or post-operative protocol (such as casting or temporary muscle paralysis) can maintain repair integrity in a high load environment. Alternatively, a partial-width tendon injury model allows loads to be shared between the tendon repair and the remaining intact portion of the infraspinatus tendon and prohibits complete tendon retraction. Thus a partial-width injury in the canine may model the mechanical environment of many single tendon tears in the human injury condition and warrants further investigation. PMID:17560802

  12. DNA Repair Profiling Reveals Nonrandom Outcomes at Cas9-Mediated Breaks.

    PubMed

    van Overbeek, Megan; Capurso, Daniel; Carter, Matthew M; Thompson, Matthew S; Frias, Elizabeth; Russ, Carsten; Reece-Hoyes, John S; Nye, Christopher; Gradia, Scott; Vidal, Bastien; Zheng, Jiashun; Hoffman, Gregory R; Fuller, Christopher K; May, Andrew P

    2016-08-18

    The repair outcomes at site-specific DNA double-strand breaks (DSBs) generated by the RNA-guided DNA endonuclease Cas9 determine how gene function is altered. Despite the widespread adoption of CRISPR-Cas9 technology to induce DSBs for genome engineering, the resulting repair products have not been examined in depth. Here, the DNA repair profiles of 223 sites in the human genome demonstrate that the pattern of DNA repair following Cas9 cutting at each site is nonrandom and consistent across experimental replicates, cell lines, and reagent delivery methods. Furthermore, the repair outcomes are determined by the protospacer sequence rather than genomic context, indicating that DNA repair profiling in cell lines can be used to anticipate repair outcomes in primary cells. Chemical inhibition of DNA-PK enabled dissection of the DNA repair profiles into contributions from c-NHEJ and MMEJ. Finally, this work elucidates a strategy for using "error-prone" DNA-repair machinery to generate precise edits. PMID:27499295

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

    ERIC Educational Resources Information Center

    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…

  14. DNA double strand break repair pathway choice: a chromatin based decision?

    PubMed

    Clouaire, T; Legube, G

    2015-01-01

    DNA double-strand breaks (DSBs) are highly toxic lesions that can be rapidly repaired by 2 main pathways, namely Homologous Recombination (HR) and Non Homologous End Joining (NHEJ). The choice between these pathways is a critical, yet not completely understood, aspect of DSB repair. We recently found that distinct DSBs induced across the genome are not repaired by the same pathway. Indeed, DSBs induced in active genes, naturally enriched in the trimethyl form of histone H3 lysine 36 (H3K36me3), are channeled to repair by HR, in a manner depending on SETD2, the major H3K36 trimethyltransferase. Here, we propose that these findings may be generalized to other types of histone modifications and repair machineries thus defining a "DSB repair choice histone code". This "decision making" function of preexisting chromatin structure in DSB repair could connect the repair pathway used to the type and function of the damaged region, not only contributing to genome stability but also to its diversity. PMID:25675367

  15. Repair Integrity and Clinical Outcomes Following Arthroscopic Rotator Cuff Repair

    PubMed Central

    Williams, Ariel A.; Mark, P.; DiVenere, Jessica Megan; Klinge, Stephen Austin; Arciero, Robert A.; Mazzocca, Augustus D.

    2016-01-01

    Objectives: To prospectively evaluate the effect of early versus delayed motion on repair integrity on 6-month postoperative magnetic resonance imaging (MRI) scans following rotator cuff repair, and to correlate repair integrity with clinical and functional outcomes. We hypothesized that repair integrity would differ between the early and delayed groups and that patients with repair failures would have worse clinical and functional outcomes. Methods: This was a prospective, randomized, single blinded clinical trial comparing an early motion (post-op day 2-3) to a delayed motion (post-op day 28) rehabilitation protocol following arthroscopic repair of isolated supraspinatus tears. All patients underwent MRI at 6 months post-operatively as part of the study protocol. A blinded board-certified and fellowship-trained orthopaedic surgeon (not part of the surgical team) reviewed operative photos and video to confirm the presence of a full thickness supraspinatus tear and to ensure an adequate and consistent repair. The same surgeon along with a blinded sports medicine fellowship-trained musculoskeletal radiologist independently reviewed all MRIs to determine whether the repair was intact at 6 months. Outcome measures were collected by independent evaluators who were also blinded to group assignment. These included the Western Ontario Rotator Cuff (WORC) index, Single Assessment Numeric Evaluation (SANE) ratings, pain scores, sling use, and physical exam data. Enrolled patients were followed at 6 weeks, 6 months, and 1 year. Results: From October 2008 to April 2012, 73 patients met all inclusion criteria and were willing to participate. 36 patients were randomized to delayed motion and 37 were randomized to early motion. The final study group at 6 months consisted of 58 study participants. Postoperative MRIs were obtained on all of these patients at 6 months regardless of whether or not they were progressing as expected. These MRIs demonstrated an overall failure rate of

  16. Shining Light on Nanotechnology to Help Repair and Regeneration

    PubMed Central

    Gupta, Asheesh; Avci, Pinar; Sadasivam, Magesh; Chandran, Rakkiyappan; Parizotto, Nivaldo; Vecchio, Daniela; Antunes-Melo, Wanessa C; Dai, Tianhong; Chiang, Long Y.; Hamblin, Michael R.

    2012-01-01

    Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. PMID:22951919

  17. Distinct evolutionary strategies in the GGPPS family from plants

    PubMed Central

    Coman, Diana; Altenhoff, Adrian; Zoller, Stefan; Gruissem, Wilhelm; Vranová, Eva

    2014-01-01

    Multiple geranylgeranyl diphosphate synthases (GGPPS) for biosynthesis of geranylgeranyl diphosphate (GGPP) exist in plants. GGPP is produced in the isoprenoid pathway and is a central precursor for various primary and specialized plant metabolites. Therefore, its biosynthesis is an essential regulatory point in the isoprenoid pathway. We selected 119 GGPPSs from 48 species representing all major plant lineages, based on stringent homology criteria. After the diversification of land plants, the number of GGPPS paralogs per species increases. Already in the moss Physcomitrella patens, GGPPS appears to be encoded by multiple paralogous genes. In gymnosperms, neofunctionalization of GGPPS may have enabled optimized biosynthesis of primary and specialized metabolites. Notably, lineage-specific expansion of GGPPS occurred in land plants. As a representative species we focused here on Arabidopsis thaliana, which retained the highest number of GGPPS paralogs (twelve) among the 48 species we considered in this study. Our results show that the A. thaliana GGPPS gene family is an example of evolution involving neo- and subfunctionalization as well as pseudogenization. We propose subfunctionalization as one of the main mechanisms allowing the maintenance of multiple GGPPS paralogs in A. thaliana genome. Accordingly, the changes in the expression patterns of the GGPPS paralogs occurring after gene duplication led to developmental and/or condition specific functional evolution. PMID:24904625

  18. miRNA control of tissue repair and regeneration.

    PubMed

    Sen, Chandan K; Ghatak, Subhadip

    2015-10-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics.

  19. Prognostic value of DNA repair based stratification of hepatocellular carcinoma

    PubMed Central

    Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

    2016-01-01

    Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

  20. Macrophage-Mediated Injury and Repair After Ischemic Kidney Injury

    PubMed Central

    Huen, Sarah C.; Cantley, Lloyd G.

    2016-01-01

    Acute ischemic kidney injury is a common complication in hospitalized patients. Currently no treatment is available for augmenting kidney repair or preventing progressive kidney fibrosis. Animal models of acute kidney injury demonstrate that activation of the innate immune system plays a major role in the systemic response to ischemia/reperfusion injury. Macrophage depletion studies suggest that macrophages, key participants in the innate immune response, augment the initial injury after reperfusion, but also promote tubular repair and contribute to long-term kidney fibrosis after ischemic injury. The distinct functional outcomes seen following macrophage depletion at different time points after ischemia/reperfusion injury suggest heterogeneity in macrophage activation states. Identifying the pathways that regulate the transitions of macrophage activation is thus critical for understanding the mechanisms that govern both macrophage-mediated injury and repair in the post-ischemic kidney. This review examines our current understanding of the complex and intricately controlled pathways that determine monocyte recruitment, macrophage activation, and macrophage effector functions after renal ischemia/reperfusion injury. Careful delineation of repair and resolution pathways could provide therapeutic targets for the development of effective treatments to offer patients with acute kidney injury. PMID:24442822

  1. Mesothelial cells in tissue repair and fibrosis

    PubMed Central

    Mutsaers, Steven E.; Birnie, Kimberly; Lansley, Sally; Herrick, Sarah E.; Lim, Chuan-Bian; Prêle, Cecilia M.

    2015-01-01

    Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis. In addition to secreting proinflammatory mediators and contributing to both coagulation and fibrinolysis, mesothelial cells undergo mesothelial-to-mesenchymal transition, a process analogous to epithelial-to-mesenchymal transition, and become fibrogenic cells. Fibrogenic mesothelial cells have now been identified in tissues where they have not previously been thought to occur, such as within the parenchyma of the fibrotic lung. These findings show a direct role for mesothelial cells in fibrogenesis and open therapeutic strategies to prevent or reverse the fibrotic process. PMID:26106328

  2. Myeloid Cells in Cutaneous Wound Repair.

    PubMed

    Cash, Jenna L; Martin, Paul

    2016-06-01

    Cutaneous wound repair is a complex, dynamic process with the goal of rapidly sealing any breach in the skin's protective barrier. Myeloid cells compose a significant proportion of the inflammatory cells recruited to a wound site and play important roles in decontaminating the injured tissue of any invading microorganisms. Subsequently, myeloid cells are able to influence many aspects of the healing response, in part through their capacity to release a large array of signaling molecules that allow them to communicate with and regulate the behavior of other wound cells and in turn, be themselves exquisitely regulated by the wound microenvironment. Macrophages, for example, appear to play important, temporally changing roles in the initiation of scarring and subsequently in matrix remodeling to resolve fibrosis. In this way, myeloid cells seem to play both positive (e.g., pathogen killing and matrix remodeling) and negative (e.g., scarring) roles in wound repair. Further research is of course needed to elucidate the precise temporal and spatial myeloid cell phenotypes and behaviors and ultimately to design effective strategies to optimize the beneficial functions of these cells while minimizing their detrimental contributions to improve wound healing in the clinic. PMID:27337466

  3. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  4. China English: Its Distinctive Features

    ERIC Educational Resources Information Center

    Yang, Wei-dong; Dai, Wei-ping

    2011-01-01

    This paper attempts to expound that China English boasting its own distinctive features on the levels of phonology, words, sentences and discourse has been playing an irreplaceable role in intercultural activities, though still in its infancy and in the process of developing and perfecting itself, and it now makes every effort to move towards…

  5. Distinctive Characteristics of Educational Donors

    ERIC Educational Resources Information Center

    James, Russell N., III.

    2008-01-01

    Examining the charitable behavior of 56,663 US households, this paper evaluates the distinctive characteristics of educational donors as compared with donors to noneducational charitable organizations and with nondonors. In general, educational donors had significantly greater income, wealth, and education than other donors. Educational donors…

  6. Restoring stem cell mobilization to promote vascular repair in diabetes.

    PubMed

    Albiero, Mattia; Avogaro, Angelo; Fadini, Gian Paolo

    2013-04-01

    Diabetes triggers endothelial dysfunction, which is linked to increased risk of cardiovascular diseases. Stem and progenitor cells from the bone marrow are involved in the maintenance of vascular integrity. Diabetic patients show a dysfunction of these cells, which might represent a novel pathophysiological mechanism of vascular disease. Specifically, stem and progenitor cells fail to egress from the bone marrow (BM) due to BM pathological alterations and unresponsiveness to mobilizing stimuli. In this review, we describe impaired stem cell mobilization in diabetes as a mechanism of failed vascular repair and we provide evidence that pharmacological strategies can restore mobilization. We discuss recent advances in the knowledge of aberrant organization of the diabetic BM and its implications for impaired mobilization. Finally, we describe in detail the pharmacological exploitation of the G-CSF/DPP-4(CD26)/SDF-1α axis as a novel strategy to improve mobilization and attain vascular repair in diabetes.

  7. Essentials of skin laceration repair.

    PubMed

    Forsch, Randall T

    2008-10-15

    Skin laceration repair is an important skill in family medicine. Sutures, tissue adhesives, staples, and skin-closure tapes are options in the outpatient setting. Physicians should be familiar with various suturing techniques, including simple, running, and half-buried mattress (corner) sutures. Although suturing is the preferred method for laceration repair, tissue adhesives are similar in patient satisfaction, infection rates, and scarring risk in low skin-tension areas and may be more cost-effective. The tissue adhesive hair apposition technique also is effective in repairing scalp lacerations. The sting of local anesthesia injections can be lessened by using smaller gauge needles, administering the injection slowly, and warming or buffering the solution. Studies have shown that tap water is safe to use for irrigation, that white petrolatum ointment is as effective as antibiotic ointment in postprocedure care, and that wetting the wound as early as 12 hours after repair does not increase the risk of infection. Patient education and appropriate procedural coding are important after the repair. PMID:18953970

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

    PubMed

    Grogan, Dennis W

    2015-01-01

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

  9. Evidence for independent mismatch repair processing on opposite sides of a double-strand break in Saccharomyces cerevisiae.

    PubMed Central

    Weng, Y S; Nickoloff, J A

    1998-01-01

    Double-strand break (DSB) induced gene conversion in Saccharomyces cerevisiae during meiosis and MAT switching is mediated primarily by mismatch repair of heteroduplex DNA (hDNA). We used nontandem ura3 duplications containing palindromic frameshift insertion mutations near an HO nuclease recognition site to test whether mismatch repair also mediates DSB-induced mitotic gene conversion at a non-MAT locus. Palindromic insertions included in hDNA are expected to produce a stem-loop mismatch, escape repair, and segregate to produce a sectored (Ura+/-) colony. If conversion occurs by gap repair, the insertion should be removed on both strands, and converted colonies will not be sectored. For both a 14-bp palindrome, and a 37-bp near-palindrome, approximately 75% of recombinant colonies were sectored, indicating that most DSB-induced mitotic gene conversion involves mismatch repair of hDNA. We also investigated mismatch repair of well-repaired markers flanking an unrepaired palindrome. As seen in previous studies, these additional markers increased loop repair (likely reflecting corepair). Among sectored products, few had additional segregating markers, indicating that the lack of repair at one marker is not associated with inefficient repair at nearby markers. Clear evidence was obtained for low levels of short tract mismatch repair. As seen with full gene conversions, donor alleles in sectored products were not altered. Markers on the same side of the DSB as the palindrome were involved in hDNA less often among sectored products than nonsectored products, but markers on the opposite side of the DSB showed similar hDNA involvement among both product classes. These results can be explained in terms of corepair, and they suggest that mismatch repair on opposite sides of a DSB involves distinct repair tracts. PMID:9475721

  10. Considerations for patients undergoing endovascular abdominal aortic aneurysm repair.

    PubMed

    Ullery, Brant W; Lee, Jason T

    2014-09-01

    Endovascular aneurysm repair has taken over open surgery as the primary strategy for treatment of patients with abdominal and thoracic aneurysms. The minimally invasive nature of these techniques requires alterations in preoperative workup, intraoperative management, and familiarity with unique complications that can occur. Familiarity from the anesthetic standpoint of endovascular techniques, including treatment of patients with fenestrated, chimney, snorkel, and periscope grafts, is necessary for the contemporary cardiac anesthesiologist.

  11. Immunopharmacological intervention for successful neural stem cell therapy: New perspectives in CNS neurogenesis and repair.

    PubMed

    Dooley, Dearbhaile; Vidal, Pia; Hendrix, Sven

    2014-01-01

    The pharmacological support and stimulation of endogenous and transplanted neural stem cells (NSCs) is a major challenge in brain repair. Trauma to the central nervous system (CNS) results in a distinct inflammatory response caused by local and infiltrating immune cells. This makes NSC-supported regeneration difficult due to the presence of inhibitory immune factors which are upregulated around the lesion site. The continual and dual role of the neuroinflammatory response leaves it difficult to decipher upon a single modulatory strategy. Therefore, understanding the influence of cytokines upon regulation of NSC self-renewal, proliferation and differentiation is crucial when designing therapies for CNS repair. There is a plethora of partially conflicting data in vitro and in vivo on the role of cytokines in modulating the stem cell niche and the milieu around NSC transplants. This is mainly due to the pleiotropic role of many factors. In order for cell-based therapy to thrive, treatment must be phase-specific to the injury and also be personalized for each patient, i.e. taking age, sex, neuroimmune and endocrine status as well as other key parameters into consideration. In this review, we will summarize the most relevant information concerning interleukin (IL)-1, IL-4, IL-10, IL-15, IFN-γ, the neuropoietic cytokine family and TNF-α in order to extract promising therapeutic approaches for further research. We will focus on the consequences of neuroinflammation on endogenous brain stem cells and the transplantation environment, the effects of the above cytokines on NSCs, as well as immunopharmacological manipulation of the microenvironment for potential therapeutic use.

  12. Endovascular Repair of Abdominal Aortic Aneurysms

    PubMed Central

    Chaikof, Elliot L.; Lin, Peter H.; Brinkman, William T.; Dodson, Thomas F.; Weiss, Victor J.; Lumsden, Alan B.; Terramani, Thomas T.; Najibi, Sasan; Bush, Ruth L.; Salam, Atef A.; Smith, Robert B.

    2002-01-01

    Objective The impact of co-morbid conditions on early and late clinical outcomes after endovascular treatment of abdominal aortic aneurysm (AAA) was assessed in concurrent cohorts of patients stratified with respect to risk for intervention. Summary Background Data As a minimally invasive strategy for the treatment of AAA, endovascular repair has been embraced with enthusiasm for all prospective patients who are suitable anatomical candidates because of the promise of achieving a durable result with a reduced risk of perioperative morbidity and mortality. Methods From April 1994 to March 2001, endovascular AAA repair was performed in 236 patients using commercially available systems. A subset of patients considered at increased risk for intervention (n = 123) were categorized, as such, based on a preexisting history of ischemic coronary artery disease, with documentation of myocardial infarction (60%) or congestive heart failure (35%), or due to the presence of chronic obstructive disease (21%), liver disease, or malignancy. Results Perioperative mortality (30-day) was 6.5% in the increased-risk patients as compared to 1.8% among those classified as low risk (P = NS). There was no difference between groups in age (74 ± 9 years vs. 72 ± 6 years; mean ± SD), surgical time (235 ± 95 minutes vs. 219 ± 84 minutes), blood loss (457 ± 432 mL vs. 351 ± 273 mL), postoperative hospital stay (4.8 ± 3.4 days vs. 4.0 ± 3.9 days), or days in the ICU (1.3 ± 1.8 days vs. 0.5 ± 1.6 days). Patients at increased risk of intervention had larger aneurysms than low-risk patients (59 ± 13 mm vs. 51 ± 14 mm;P < .05). Stent grafts were successfully implanted in 116 (95%) increased-risk versus 107 (95%) low-risk patients (P = NS). Conversion rates to open operative repair were similar in increased-risk and low-risk groups at 3% and 5%, respectively. The initial endoleak rate was 22% versus 20%, based on the first CT performed (either at discharge or 1 month;P = NS). To date

  13. Practical aspects of coating repair

    SciTech Connect

    Munger, C.G.

    1980-02-01

    Detailed information is given concerning the types of coatings failures that are amenable to repair and materials and methods effective in making them. Coatings failure types are analyzed, and recommended surface preparation for several types of failure are described in detail. Consequences of improper surface preparation are emphasized. Precautions necessary for selection of materials and for application methods effective in applying coatings over old coatings are presented in detail. Characteristics and causes are given for pinpoint rusting, delamination, chalking, and undercutting by rust. Characteristics and causes of gas and liquid blisters are described and methods of repairing coating underneath them are detailed. Special attention is given to repairs on galvanizing and inorganic zinc-loaded coatings and the correct procedures of surface preparation and overcoating. Importance of time after start of failure to begin recoating is emphasized.

  14. Genes and Junk in Plant Mitochondria—Repair Mechanisms and Selection

    PubMed Central

    Christensen, Alan C.

    2014-01-01

    Plant mitochondrial genomes have very low mutation rates. In contrast, they also rearrange and expand frequently. This is easily understood if DNA repair in genes is accomplished by accurate mechanisms, whereas less accurate mechanisms including nonhomologous end joining or break-induced replication are used in nongenes. An important question is how different mechanisms of repair predominate in coding and noncoding DNA, although one possible mechanism is transcription-coupled repair (TCR). This work tests the predictions of TCR and finds no support for it. Examination of the mutation spectra and rates in genes and junk reveals what DNA repair mechanisms are available to plant mitochondria, and what selective forces act on the repair products. A model is proposed that mismatches and other DNA damages are repaired by converting them into double-strand breaks (DSBs). These can then be repaired by any of the DSB repair mechanisms, both accurate and inaccurate. Natural selection will eliminate coding regions repaired by inaccurate mechanisms, accounting for the low mutation rates in genes, whereas mutations, rearrangements, and expansions generated by inaccurate repair in noncoding regions will persist. Support for this model includes the structure of the mitochondrial mutS homolog in plants, which is fused to a double-strand endonuclease. The model proposes that plant mitochondria do not distinguish a damaged or mismatched DNA strand from the undamaged strand, they simply cut both strands and perform homology-based DSB repair. This plant-specific strategy for protecting future generations from mitochondrial DNA damage has the side effect of genome expansions and rearrangements. PMID:24904012

  15. Entrepreneurship research in Spain: developments and distinctiveness.

    PubMed

    Sánchez, José C; Gutiérrez, Andrea

    2011-08-01

    This article presents a review of research on entrepreneurship in Spain, paying particular attention to its beginnings, nature and main focus of interest. We have developed a database based on the review of 471 works produced between 1977 and 2009, including articles published in national and international journals and dissertations (read in Spain) that allowed us to extract the following results. There is a preference for qualitative methods, conceptual contributions and the entrepreneurial process as the privileged research theme. There is also a strong focus of interest on micro and small enterprises. These characteristics of Spanish research in areas of entrepreneurship can make a distinctive contribution to international research. However, the dissemination of knowledge and inadequate strategies for international publication limit the diffusion of Spanish research in entrepreneurship. Lastly, we discuss the implications for future research.

  16. The Challenge and the Promise of Bone Marrow Cells for Human Cartilage Repair

    PubMed Central

    2015-01-01

    The cartilage repair potential of bone marrow–derived stem cells has been well described. Harnessing this potential for human articular cartilage repair remains challenging. Accessing bone marrow repair cells through marrow stimulation techniques such as microfracture is readily achieved with generally good but inconsistent results. Animal and human studies show feasibility for ex vivo processing of bone marrow to isolate, concentrate, and culture mesenchymal stem cells. Nevertheless, it has been difficult to show consistent and clinically meaningful improvement using bone marrow cell preparations above what has been achieved with microfracture. Consequently, microfracture continues to be the simplest and most commonly used method to enhance repair of focal articular cartilage defects. Emerging preclinical work in the equine model suggests a role for enhancing marrow-stimulation techniques through the use of natural scaffolds such as autologous platelet enriched fibrin as well as optimization of joint biology through localized gene therapy to support cartilage repair. In contrast to joint replacement where inert materials of known mechanical properties are used, host biology determines the relative success, failure, and durability of cartilage repair. As such, development of personalized strategies to improve the quality and durability of bone marrow cell–based articular cartilage repair represent exciting new areas of inquiry. Continued advances in stem cell biology, scaffold technologies, and methods to delineate and enhance host biology, both systemically and within the joint, hold promise for harnessing the full power of bone marrow cells to facilitate cartilage repair and regeneration. PMID:27340515

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

    PubMed

    Whittaker, Stephen G

    2003-07-01

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

  18. RNA interference against transcription elongation factor SII does not support its role in transcription-coupled nucleotide excision repair.

    PubMed

    Mackinnon-Roy, Christine; Stubbert, Lawton J; McKay, Bruce C

    2011-01-10

    RNA polymerase II is unable to bypass bulky DNA lesions induced by agents like ultraviolet light (UV light) and cisplatin that are located in the template strand of active genes. Arrested polymerases form a stable ternary complex at the site of DNA damage that is thought to pose an impediment to the repair of these lesions. Transcription-coupled nucleotide excision repair (TC-NER) preferentially repairs these DNA lesions through an incompletely defined mechanism. Based on elegant in vitro experiments, it was hypothesized that the transcription elongation factor IIS (TFIIS) may be required to couple transcription to repair by catalyzing the reverse translocation of the arrested polymerase, allowing access of repair proteins to the site of DNA damage. However the role of TFIIS in this repair process has not been tested in vivo. Here, silencing TFIIS using an RNA interference strategy did not affect the ability of cells to recover nascent RNA synthesis following UV exposure or the ability of cells to repair a UV-damaged reporter gene while a similar strategy to decrease the expression Cockayne syndrome group B protein (CSB) resulted in the expected repair defect. Furthermore, RNA interference against TFIIS did not increase the sensitivity of cells to UV light or cisplatin while decreased expression of CSB did. Taken together, these results indicate that TFIIS is not limiting for the repair of transcription-blocking DNA lesions and thus the present work does not support a role for TFIIS in TC-NER.

  19. Influence of XRCC1 Genetic Polymorphisms on Ionizing Radiation-Induced DNA Damage and Repair

    PubMed Central

    Sterpone, Silvia; Cozzi, Renata

    2010-01-01

    It is well known that ionizing radiation (IR) can damage DNA through a direct action, producing single- and double-strand breaks on DNA double helix, as well as an indirect effect by generating oxygen reactive species in the cells. Mammals have evolved several and distinct DNA repair pathways in order to maintain genomic stability and avoid tumour cell transformation. This review reports important data showing a huge interindividual variability on sensitivity to IR and in susceptibility to developing cancer; this variability is principally represented by genetic polymorphisms, that is, DNA repair gene polymorphisms. In particular we have focussed on single nucleotide polymorphisms (SNPs) of XRCC1, a gene that encodes for a scaffold protein involved basically in Base Excision Repair (BER). In this paper we have reported and presented recent studies that show an influence of XRCC1 variants on DNA repair capacity and susceptibility to breast cancer. PMID:20798883

  20. Proximal Rectus Femoris Avulsion Repair.

    PubMed

    Dean, Chase S; Arbeloa-Gutierrez, Lucas; Chahla, Jorge; Pascual-Garrido, Cecilia

    2016-06-01

    Proximal rectus femoris tendon avulsions are rare and occur mostly in male athletes. Currently, the standard of care for complete tendinous avulsions of the direct arm of the rectus femoris is nonoperative treatment. However, surgical repair may be considered in high-level athletes who have a high demand for repetitive hip flexion performed in an explosive manner or in patients in whom nonoperative treatment has failed. The purpose of this technical note is to describe the method for surgical repair of the proximal direct arm of the rectus femoris to its origin at the anterior inferior iliac spine using suture anchors. PMID:27656376

  1. Mountain Plains Learning Experience Guide: Automotive Repair. Course: Engine Repair.

    ERIC Educational Resources Information Center

    Schramm, C.; Osland, Walt

    One of twelve individualized courses included in an automotive repair curriculum, this course covers theory and construction, inspection diagnoses, and service and overhaul of automotive engines. The course is comprised of five units: (1) Fundamentals of Four-Cycle Engines, (2) Engine Construction, (3) Valve Train, (4) Lubricating Systems, and (5)…

  2. A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin.

    PubMed

    Janssen, Aniek; Breuer, Gregory A; Brinkman, Eva K; van der Meulen, Annelot I; Borden, Sean V; van Steensel, Bas; Bindra, Ranjit S; LaRocque, Jeannine R; Karpen, Gary H

    2016-07-15

    Repair of DNA double-strand breaks (DSBs) must be properly orchestrated in diverse chromatin regions to maintain genome stability. The choice between two main DSB repair pathways, nonhomologous end-joining (NHEJ) and homologous recombination (HR), is regulated by the cell cycle as well as chromatin context.Pericentromeric heterochromatin forms a distinct nuclear domain that is enriched for repetitive DNA sequences that pose significant challenges for genome stability. Heterochromatic DSBs display specialized temporal and spatial dynamics that differ from euchromatic DSBs. Although HR is thought to be the main pathway used to repair heterochromatic DSBs, direct tests of this hypothesis are lacking. Here, we developed an in vivo single DSB system for both heterochromatic and euchromatic loci in Drosophila melanogaster Live imaging of single DSBs in larval imaginal discs recapitulates the spatio-temporal dynamics observed for irradiation (IR)-induced breaks in cell culture. Importantly, live imaging and sequence analysis of repair products reveal that DSBs in euchromatin and heterochromatin are repaired with similar kinetics, employ both NHEJ and HR, and can use homologous chromosomes as an HR template. This direct analysis reveals important insights into heterochromatin DSB repair in animal tissues and provides a foundation for further explorations of repair mechanisms in different chromatin domains. PMID:27474442

  3. Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae.

    PubMed Central

    Milne, G T; Jin, S; Shannon, K B; Weaver, D T

    1996-01-01

    DNA double-strand break (DSB) repair in mammalian cells is dependent on the Ku DNA binding protein complex. However, the mechanism of Ku-mediated repair is not understood. We discovered a Saccharomyces cerevisiae gene (KU80) that is structurally similar to the 80-kDa mammalian Ku subunit. Ku8O associates with the product of the HDF1 gene, forming the major DNA end-binding complex of yeast cells. DNA end binding was absent in ku80delta, hdf1delta, or ku80delta hdf1delta strains. Antisera specific for epitope tags on Ku80 and Hdf1 were used in supershift and immunodepletion experiments to show that both proteins are directly involved in DNA end binding. In vivo, the efficiency of two DNA end-joining processes were reduced >10-fold in ku8Odelta, hdfldelta, or ku80delta hdf1delta strains: repair of linear plasmid DNA and repair of an HO endonuclease-induced chromosomal DSB. These DNA-joining defects correlated with DNA damage sensitivity, because ku80delta and hdf1delta strains were also sensitive to methylmethane sulfonate (MMS). Ku-dependent repair is distinct from homologous recombination, because deletion of KU80 and HDF1 increased the MMS sensitivity of rad52delta. Interestingly, rad5Odelta, also shown here to be defective in end joining, was epistatic with Ku mutations for MMS repair and end joining. Therefore, Ku and Rad50 participate in an end-joining pathway that is distinct from homologous recombinational repair. Yeast DNA end joining is functionally analogous to DSB repair and V(D)J recombination in mammalian cells. PMID:8754818

  4. Final report [DNA Repair and Mutagenesis - 1999

    SciTech Connect

    Walker, Graham C.

    2001-05-30

    The meeting, titled ''DNA Repair and Mutagenesis: Mechanism, Control, and Biological Consequences'', was designed to bring together the various sub-disciplines that collectively comprise the field of DNA Repair and Mutagenesis. The keynote address was titled ''Mutability Doth Play Her Cruel Sports to Many Men's Decay: Variations on the Theme of Translesion Synthesis.'' Sessions were held on the following themes: Excision repair of DNA damage; Transcription and DNA excision repair; UmuC/DinB/Rev1/Rad30 superfamily of DNA polymerases; Cellular responses to DNA damage, checkpoints, and damage tolerance; Repair of mismatched bases, mutation; Genome-instability, and hypermutation; Repair of strand breaks; Replicational fidelity, and Late-breaking developments; Repair and mutation in challenging environments; and Defects in DNA repair: consequences for human disease and aging.

  5. 24 CFR 206.47 - Property standards; repair work.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... be repaired in order to ensure that the repaired property will serve as adequate security for the insured mortgage. (b) Assurance that repairs are made. The mortgage may be closed before the repair...

  6. [A Nobel Prize for DNA repair].

    PubMed

    Jordan, Bertrand

    2016-01-01

    This year's Nobel Prize for chemistry recognizes the seminal contributions of three researchers who discovered the existence and the basic mechanisms of DNA repair: base excision repair, mismatch repair, and nucleotide excision repair. They have since been joined by many scientists elucidating diverse aspects of these complex mechanisms that now constitute a thriving research field with many applications, notably for understanding oncogenesis and devising more effective therapies. PMID:26850617

  7. [A Nobel Prize for DNA repair].

    PubMed

    Jordan, Bertrand

    2016-01-01

    This year's Nobel Prize for chemistry recognizes the seminal contributions of three researchers who discovered the existence and the basic mechanisms of DNA repair: base excision repair, mismatch repair, and nucleotide excision repair. They have since been joined by many scientists elucidating diverse aspects of these complex mechanisms that now constitute a thriving research field with many applications, notably for understanding oncogenesis and devising more effective therapies.

  8. Outcome of quadriceps tendon repair.

    PubMed

    Puranik, Gururaj S; Faraj, Adnan

    2006-04-01

    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.

  9. How the Brain Repairs Stuttering

    ERIC Educational Resources Information Center

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

    2009-01-01

    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…

  10. Microwave Oven Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    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…

  11. Computer Equipment Repair Curriculum Guide.

    ERIC Educational Resources Information Center

    Reneau, Fred; And Others

    This guide is intended for use in a course to train students to repair computer equipment and perform related administrative and customer service tasks. Addressed in the individual units are the following topics (with selected subtopics in brackets): performing administrative functions (preparing service bills, maintaining accounts and labor…

  12. Minilaparoscopy For Inguinal Hernia Repair

    PubMed Central

    Malcher, Flavio; Cavazzola, Leandro Totti; Araujo, Guilherme D. E.; Silva, José Antônio Da Cunha E.; Rao, Prashanth; Iglesias, Antonio Carlos

    2016-01-01

    Background and Objectives: Inguinal hernia repair is among the most common procedures performed worldwide and the laparoscopic totally extraperitoneal (TEP) approach is a recognized and effective surgical technique. Although technically advantageous because of the option of no mesh fixation and no need for creation of a peritoneal flap resulting, in less postoperative pain and faster recovery, TEP has not achieved the popularity it deserves, mainly because of its complexity and steep learning curve. Minilaparoscopy was first described in the 1990s and has recently gained significantly from better instrumentation that may increase TEP's effectiveness and acceptance. We performed a prospective study, to analyze the outcomes of minilaparoscopy in pain and operative time when compared to the conventional laparoscopic technique in hernia repair. Methods: Fifty-eight laparoscopic inguinal hernia repairs were performed: 36 by traditional laparoscopic technique and 22 by minilaparoscopic instruments (mini). A study protocol was applied prospectively for data collection. Variables analyzed were early postoperative pain (at hour 6 after procedure), pain at discharge, use of on-demand analgesics, and operative time. Results: The mini group presented reduced early postoperative pain and operative time. The present study also suggests less postoperative pain at discharge with mini procedures, although this difference was not statistically significant. No difference between the groups regarding on-demand use of analgesics was found. Conclusions: This study corroborates findings in previously published papers that have shown the feasibility of minilaparoscopy in laparoscopic TEP hernia repair and its benefits regarding postoperative pain, operative time, and aesthetic outcomes. PMID:27777499

  13. [Cell therapy in cartilage repair: cellular and molecular bases].

    PubMed

    Corvol, Marie-Thérèse; Tahiri, Khadija; Montembault, Alexandra; Daumard, Alain; Savouret, Jean-François; Rannou, François

    2008-01-01

    The destruction of articular cartilage represents the outcome of most inflammatory and degenerative rheumatic diseases and leads to severe disability. Articular cartilage being unable to repair spontaneously, alterations of the joint surface often results in end-stage osteoarthritis, requiring surgical intervention and total joint replacement. This makes damaged tissues repair a major challenge in our aging society. Cartilage harbors only one cell type, the chondrocyte, which synthesizes and secretes specific matrix proteins such as type II collagen and high molecular weight proteoglycans. Matrix proteins are responsible for the conservation of the chondrocyte phenotype and the maintenance of the mechanical functions of cartilage. Development of therapeutic strategies for cartilage repair should thus comprise not only the replacement of lost cartilage cells but also that of extracellular matrix with cartilage-like properties. Different protocols are under investigation. The most commonly employed materials include transplantation of autologous osteochondral tissue. More recently, cell-based therapies using autologous mature chondrocytes or pre-chondrogenic stem cells have drawn particular attention. Tissue-engineering procedures represent the actual trend in cartilage repair. This approach combines biodegradable polymeric three-dimensional matrixes and isolated prechondrogenic stem cells. The cells are seeded within the biocompatible matrix and then implanted into the joint. Numerous non-degradable and degradable polymers, which efficiently "mimic" the natural surroundings of cartilage cells, are currently under investigation.

  14. Regulation of targeted gene repair by intrinsic cellular processes.

    PubMed

    Engstrom, Julia U; Suzuki, Takayuki; Kmiec, Eric B

    2009-02-01

    Targeted gene alteration (TGA) is a strategy for correcting single base mutations in the DNA of human cells that cause inherited disorders. TGA aims to reverse a phenotype by repairing the mutant base within the chromosome itself, avoiding the introduction of exogenous genes. The process of how to accurately repair a genetic mutation is elucidated through the use of single-stranded DNA oligonucleotides (ODNs) that can enter the cell and migrate to the nucleus. These specifically designed ODNs hybridize to the target sequence and act as a beacon for nucleotide exchange. The key to this reaction is the frequency with which the base is corrected; this will determine whether the approach becomes clinically relevant or not. Over the course of the last five years, workers have been uncovering the role played by the cells in regulating the gene repair process. In this essay, we discuss how the impact of the cell on TGA has evolved through the years and illustrate ways that inherent cellular pathways could be used to enhance TGA activity. We also describe the cost to cell metabolism and survival when certain processes are altered to achieve a higher frequency of repair.

  15. The rad18 gene of Schizosaccharomyces pombe defines a new subgroup of the SMC superfamily involved in DNA repair

    SciTech Connect

    Lehmann, A.R.; Walicka, M.; Griffiths, D.J.F.; Carr, A.M.

    1995-12-01

    This report describes the cloning and sequencing of the rad18 gene of Schizosaccharomyces pombe and its essential role in cell proliferation. It also describes the isolation and sequencing of its homolog from Saccharomyces cerevisiae, designated RHC18. Genetic radiation effects were explored and results indicate the gene product`s importance in a DNA repair pathway that is distinct from classical nucleotide excision repair. 57 refs., 20 figs., 1 tab.

  16. Standardized Curriculum for Shoe and Boot Repair.

    ERIC Educational Resources Information Center

    Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

    This curriculum guide for shoe and boot repair was developed by the state of Mississippi to standardize vocational education course titles and core contents. The objectives contained in this document are common to all shoe and boot repair programs in the state. The guide contains objectives for shoe and boot repair I and II courses. Units in…

  17. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Bridge repairs. 115.40 Section 115.40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.40 Bridge repairs. Repairs to a bridge which...

  18. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Bridge repairs. 115.40 Section 115.40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.40 Bridge repairs. Repairs to a bridge which...

  19. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Bridge repairs. 115.40 Section 115.40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.40 Bridge repairs. Repairs to a bridge which...

  20. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Bridge repairs. 115.40 Section 115.40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.40 Bridge repairs. Repairs to a bridge which...

  1. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Bridge repairs. 115.40 Section 115.40 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES BRIDGE LOCATIONS AND CLEARANCES; ADMINISTRATIVE PROCEDURES § 115.40 Bridge repairs. Repairs to a bridge which...

  2. Standardized Curriculum for Small Engine Repair.

    ERIC Educational Resources Information Center

    Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

    This curriculum guide for small engine repair was developed by the state of Mississippi to standardize vocational education course titles and core contents. The objectives contained in this document are common to all small engine repair programs in the state. The guide contains objectives for small engine repair I and II courses. Units in course I…

  3. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY PROCEDURE FOR ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR...

  4. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY PROCEDURE FOR ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR...

  5. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY PROCEDURE FOR ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR...

  6. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY PROCEDURE FOR ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR...

  7. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION A-NATIONAL SHIPPING AUTHORITY PROCEDURE FOR ACCOMPLISHMENT OF VESSEL REPAIRS UNDER NATIONAL SHIPPING AUTHORITY MASTER LUMP SUM REPAIR...

  8. Fix-It Careers: Jobs in Repair

    ERIC Educational Resources Information Center

    Torpey, Elka Maria

    2010-01-01

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

  9. 40 CFR 65.105 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... leak. (3) Maximum instrument reading measured by Method 21 of appendix A of 40 CFR part 60 at the time... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Leak repair. 65.105 Section 65.105... FEDERAL AIR RULE Equipment Leaks § 65.105 Leak repair. (a) Leak repair schedule. The owner or...

  10. Welding/brazing for Space Station repair

    NASA Astrophysics Data System (ADS)

    Dickinson, David W.; Babel, H. W.; Conaway, H. R.; Hooper, W. H.

    Viewgraphs on welding/brazing for space station repair are presented. Topics covered include: fabrication and repair candidates; debris penetration of module panel; welded repair patch; mechanical assembly of utility fluid line; space station utility systems; Soviet aerospace fabrication - an overview; and processes under consideration.

  11. Auto Body Repair and Repainting: Instructional Units.

    ERIC Educational Resources Information Center

    Manuel, Edward F.; Penner, Wayman R.

    The guide contains 11 sections, each consisting of one or more units of instruction designed to provide students with entry-level skills in auto body repair. The sections deal with: introductory and related information; body and frame construction; tools; welding; basic metal repair; hardware, glass, and trim; major metal repair; refinishing;…

  12. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Repairs. 127.405 Section 127.405... Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that— (a) Equipment repairs are made so that— (1) The equipment continues to meet the applicable requirements in...

  13. 30 CFR 57.14104 - Tire repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 57.14104 Section 57.14104 Mineral... Devices and Maintenance Requirements § 57.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and...

  14. 30 CFR 56.14104 - Tire repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Tire repairs. 56.14104 Section 56.14104 Mineral... Devices and Maintenance Requirements § 56.14104 Tire repairs. (a) Before a tire is removed from a vehicle for tire repair, the valve core shall be partially removed to allow for gradual deflation and...

  15. 26 CFR 1.162-4 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Repairs. 1.162-4 Section 1.162-4 Internal... TAXES (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.162-4 Repairs. The cost of incidental repairs which neither materially add to the value of the property nor appreciably prolong its...

  16. Bringing mask repair to the next level

    NASA Astrophysics Data System (ADS)

    Edinger, K.; Wolff, K.; Steigerwald, H.; Auth, N.; Spies, P.; Oster, J.; Schneider, H.; Budach, M.; Hofmann, T.; Waiblinger, M.

    2014-10-01

    Mask repair is an essential step in the mask manufacturing process as the extension of 193nm technology and the insertion of EUV are drivers for mask complexity and cost. The ability to repair all types of defects on all mask blank materials is crucial for the economic success of a mask shop operation. In the future mask repair is facing several challenges. The mask minimum features sizes are shrinking and require a higher resolution repair tool. At the same time mask blanks with different new mask materials are introduced to optimize optical performance and long term durability. For EUV masks new classes of defects like multilayer and phase defects are entering the stage. In order to achieve a high yield, mask repair has to cover etch and deposition capabilities and must not damage the mask. These challenges require sophisticated technologies to bring mask repair to the next level. For high end masks ion-beam based and e-based repair technologies are the obvious choice when it comes to the repair of small features. Both technologies have their pro and cons. The scope of this paper is to review and compare the performance of ion-beam based mask repair to e-beam based mask repair. We will analyze the limits of both technologies theoretically and experimentally and show mask repair related performance data. Based on this data, we will give an outlook to future mask repair tools.

  17. Standardized Curriculum for Automotive Body Repair.

    ERIC Educational Resources Information Center

    Mississippi State Dept. of Education, Jackson. Office of Vocational, Technical and Adult Education.

    Standardized curricula are provided for two courses for the secondary vocational education program in Mississippi: automotive body repair I and II. The nine units in automotive body repair I are as follows: introduction; related information; basic tool usage and safety; body and frame construction; basic sheet metal repair; preparing for…

  18. Regeneration gaps: observations on stem cells and cardiac repair.

    PubMed

    Murry, Charles E; Reinecke, Hans; Pabon, Lil M

    2006-05-01

    Substantial evidence indicates that cell transplantation can improve function of the infarcted heart. A surprisingly wide range of non-myogenic cell types improves ventricular function, suggesting that benefit may result in part from mechanisms that are distinct from true myocardial regeneration. While clinical trials explore cells derived from skeletal muscle and bone marrow, basic researchers are investigating sources of new cardiomyocytes, such as resident myocardial progenitors and embryonic stem cells. In this commentary, we briefly review the evolution of cell-based cardiac repair, discuss the current state of clinical research, and offer some thoughts on how newcomers can critically evaluate this emerging field.

  19. A strategy planner for NASA robotics applications

    NASA Technical Reports Server (NTRS)

    Brodd, S. S.

    1985-01-01

    Automatic strategy or task planning is an important element of robotics systems. A strategy planner under development at Goddard Space Flight Center automatically produces robot plans for assembly, disassembly, or repair of NASA spacecraft from computer aided design descriptions of the individual parts of the spacecraft.

  20. Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase*

    PubMed Central

    Wang, Lan; Lee, Seung-Joo; Verdine, Gregory L.

    2015-01-01

    The highly mutagenic A:oxoG (8-oxoguanine) base pair in DNA most frequently arises by aberrant replication of the primary oxidative lesion C:oxoG. This lesion is particularly insidious because neither of its constituent nucleobases faithfully transmit genetic information from the original C:G base pair. Repair of A:oxoG is initiated by adenine DNA glycosylase, which catalyzes hydrolytic cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY in bacteria and MUTYH in humans, scrupulously avoid processing of C:oxoG because cleavage of the C residue in C:oxoG would actually promote mutagenic conversion to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY, using a synthetic crystallography approach to capture the enzyme in the process of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only fleetingly. We find that MutY uses two distinct strategies to avoid presentation of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves as a decoy for C, and secondly, repulsive forces with a key active site residue prevent stable insertion of C into the nucleobase recognition pocket within the enzyme active site. PMID:25995449

  1. Preconditioning allows engraftment of mouse and human embryonic lung cells, enabling lung repair in mice.

    PubMed

    Rosen, Chava; Shezen, Elias; Aronovich, Anna; Klionsky, Yael Zlotnikov; Yaakov, Yasmin; Assayag, Miri; Biton, Inbal Eti; Tal, Orna; Shakhar, Guy; Ben-Hur, Herzel; Shneider, David; Vaknin, Zvi; Sadan, Oscar; Evron, Shmuel; Freud, Enrique; Shoseyov, David; Wilschanski, Michael; Berkman, Neville; Fibbe, Willem E; Hagin, David; Hillel-Karniel, Carmit; Krentsis, Irit Milman; Bachar-Lustig, Esther; Reisner, Yair

    2015-08-01

    Repair of injured lungs represents a longstanding therapeutic challenge. We show that human and mouse embryonic lung tissue from the canalicular stage of development (20-22 weeks of gestation for humans, and embryonic day 15-16 (E15-E16) for mouse) are enriched with progenitors residing in distinct niches. On the basis of the marked analogy to progenitor niches in bone marrow (BM), we attempted strategies similar to BM transplantation, employing sublethal radiation to vacate lung progenitor niches and to reduce stem cell competition. Intravenous infusion of a single cell suspension of canalicular lung tissue from GFP-marked mice or human fetal donors into naphthalene-injured and irradiated syngeneic or SCID mice, respectively, induced marked long-term lung chimerism. Donor type structures or 'patches' contained epithelial, mesenchymal and endothelial cells. Transplantation of differentially labeled E16 mouse lung cells indicated that these patches were probably of clonal origin from the donor. Recipients of the single cell suspension transplant exhibited marked improvement in lung compliance and tissue damping reflecting the energy dissipation in the lung tissues. Our study provides proof of concept for lung reconstitution by canalicular-stage human lung cells after preconditioning of the pulmonary niche.

  2. Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase.

    PubMed

    Wang, Lan; Lee, Seung-Joo; Verdine, Gregory L

    2015-07-10

    The highly mutagenic A:oxoG (8-oxoguanine) base pair in DNA most frequently arises by aberrant replication of the primary oxidative lesion C:oxoG. This lesion is particularly insidious because neither of its constituent nucleobases faithfully transmit genetic information from the original C:G base pair. Repair of A:oxoG is initiated by adenine DNA glycosylase, which catalyzes hydrolytic cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY in bacteria and MUTYH in humans, scrupulously avoid processing of C:oxoG because cleavage of the C residue in C:oxoG would actually promote mutagenic conversion to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY, using a synthetic crystallography approach to capture the enzyme in the process of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only fleetingly. We find that MutY uses two distinct strategies to avoid presentation of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves as a decoy for C, and secondly, repulsive forces with a key active site residue prevent stable insertion of C into the nucleobase recognition pocket within the enzyme active site. PMID:25995449

  3. Repair of major system elements on Skylab

    NASA Technical Reports Server (NTRS)

    Pace, R. E., Jr.

    1975-01-01

    In-flight maintenance, as conceived and pre-planned for the Skylab Mission, was limited to simple scheduled and unscheduled replacement tasks and minor contingency repairs. Failures during the mission dictated complicated and sophisticated repairs to major systems so that the mission could continue. These repairs include the release of a large structure that failed to deploy, the assembly and deployment of large mechanical devices, the installation and checkout of precision electronic equipment, troubleshooting and repair of precision electromechanical equipment and tapping into and recharging a cooling system. The Skylab experience proves conclusively that crewmen can, with adequate training, make major system repairs in space using standard or special tools.

  4. Endovascular Repair of Thoracic Aortic Aneurysms

    PubMed Central

    Findeiss, Laura K.; Cody, Michael E.

    2011-01-01

    Degenerative aneurysms of the thoracic aorta are increasing in prevalence; open repair of descending thoracic aortic aneurysms is associated with high rates of morbidity and mortality. Repair of isolated descending thoracic aortic aneurysms using stent grafts was introduced in 1995, and in an anatomically suitable subgroup of patients with thoracic aortic aneurysm, repair with endovascular stent graft provides favorable outcomes, with decreased perioperative morbidity and mortality relative to open repair. The cornerstones of successful thoracic endovascular aneurysm repair are appropriate patient selection, thorough preprocedural planning, and cautious procedural execution, the elements of which are discussed here. PMID:22379281

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... 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.”...

  6. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... 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.”...

  7. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... 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.”...

  8. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... 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.”...

  9. Distinct structural alterations in PCNA block DNA mismatch repair†

    PubMed Central

    Dieckman, Lynne M.; Boehm, Elizabeth M.; Hingorani, Manju M.; Washington, M. Todd

    2013-01-01

    During DNA replication, mismatches and small loops in the DNA resulting from insertions or deletions are repaired by the mismatch repair (MMR) machinery. Proliferating cell nuclear antigen (PCNA) plays an important role in both mismatch-recognition and resynthesis stages of MMR. Previously, two mutant forms of PCNA were identified that cause defects in MMR with little, if any, other defects. The C22Y mutant PCNA protein completely blocks MutSα-dependent MMR, and the C81R mutant PCNA protein partially blocks both MutSα-dependent and MutSβ-dependent MMR. In order to understand the structural and mechanistic basis by which these two amino acid substitutions in PCNA proteins block MMR, we solved the X-ray crystal structures of both mutant proteins and carried out further biochemical studies. We found that these amino acid substitutions lead to subtle, distinct structural changes in PCNA. The C22Y substitution alters the positions of the α-helices lining the central hole of the PCNA ring, whereas the C81R substitution creates a distortion in an extended loop near the PCNA subunit interface. We conclude that the structural integrity of the α-helices lining the central hole and this loop are both necessary to form productive complexes with MutS α and mismatch-containing DNA. PMID:23869605

  10. Shuttle orbiter TPS flight repair kit development

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The design and application of a TPS repair kit is presented. The repair kit is designed for on orbit use by a crew member working in the manned maneuvering unit (MMU). The kit includes the necessary equipment and materials to accomplish the repair tasks which include the following: HRSI emittance coating repair, damaged tile repair, missing tile repair, and multiple tile repair. Two types of repair materials required to do the small area repair and the large area repair are described. The materials area cure in place, silicone base ablator for small damaged areas and precured ablator tile for repair of larger damaged areas is examined. The cure in place ablator is also used as an adhesive to bond the precured tiles in place. An applicator for the cure in place ablator, designed to contain a two-part silicon compound, mix the two components at correct ratio, and dispense the materials at rates compatible with mission timelines established for the EVA is described.

  11. Ultrasound determination of rotator cuff tear repairability

    PubMed Central

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

    2015-01-01

    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 < 0.0001) and a specificity of 67% (p < 0.0001). The strongest predictors of rotator cuff repairability were tear size (p < 0.001) and age (p = 0.004). Sonographic assessments of tear size ≥4 cm2 or anteroposterior tear length ≥25 mm indicated an irreparable 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

  12. Repair of parastomal hernias using polypropylene mesh.

    PubMed

    Byers, J M; Steinberg, J B; Postier, R G

    1992-10-01

    Parastomal hernias are a common complication of ostomy construction. We have developed a method of repair that uses two strips of polypropylene prosthetic mesh through a midline incision. The medical records of 19 patients who underwent parastomal hernia repair were retrospectively reviewed. All nine patients operated on for this condition by the senior author (R.G.P.) (group 1) underwent repairs with this technique. All ten patients operated on by other surgeons in our center (group 2) underwent repairs in which the stoma was moved, the fascia was directly repaired through a parastomal incision, or the fascia was repaired via a midline incision. No patients in group 1 had recurrences while five patients in group 2 had recurrences. Neither group developed strictures or stomal prolapse. Our method of repair is technically easy and has excellent results. It is especially suitable in very large hernias in which incisional hernia is likely in the original stoma site if the stoma is moved. PMID:1417494

  13. Dementia: Continuum or Distinct Entity?

    PubMed Central

    Walters, Glenn D.

    2009-01-01

    The latent structure of dementia was examined in a group of 10,775 older adults with indicators derived from a neuropsychological test battery. Subjecting these data to taxometric analysis using mean above minus below a cut (MAMBAC), maximum covariance (MAXCOV), and latent mode factor analysis (L-Mode) produced results more consistent with dementia as a dimensional (lying along a continuum) than categorical (representing a distinct entity) construct. A second study conducted on a group of 2375 21-to-64-year olds produced similar results. These findings denote that dementia, as measured by deficits in episodic memory, attention/concentration, executive function, and language, differs quantitatively rather than qualitatively from the cognitive status of non-demented adults. The implications of these results for classification, assessment, etiology, and prevention are discussed. PMID:20677881

  14. Methods of repairing a substrate

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

    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.

  15. Primary unilateral cleft lip repair

    PubMed Central

    Adenwalla, H. S.; Narayanan, P. V.

    2009-01-01

    The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web. PMID:19884683

  16. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target

    PubMed Central

    Paz, Jeanne T.; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D.; Wang, Gordon; Lemmens, Robin; Tran, Kevin V.; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A.; O’Rourke, Nancy; Smith, Stephen J.; Huguenard, John R.; Bliss, Tonya M.

    2016-01-01

    Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem’s potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. PMID:26685158

  17. Brain repair and reprogramming: the route to clinical translation.

    PubMed

    Grealish, S; Drouin-Ouellet, J; Parmar, M

    2016-09-01

    The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell-replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being successfully translated from preclinical findings to clinical trials. These trials demonstrate that cell-replacement therapy is a viable option for patients with Parkinson's disease, but more importantly also show how the limited availability of foetal cells calls for development of novel cell sources and methods for generating new neurons for brain repair. We focus on new stem cell sources that are on the threshold of clinical application for brain repair and discuss emerging cellular reprogramming technologies. Reviewing the current status of direct neural conversion, both in vitro and in vivo, where somatic cells are directly reprogrammed into functional neurons without passing through a stem cell intermediate, we conclude that both methods result in the successful replacement of new neurons that mature and integrate into the host brain. Thus, this new field shows great promise for future brain repair, although much work is still needed in preclinical animal models before it can be seriously considered for clinical applications. PMID:27539906

  18. DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

    PubMed Central

    Peacock, Matthew; Brem, Reto; Macpherson, Peter; Karran, Peter

    2014-01-01

    Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage. PMID:25414333

  19. Which mesh for hernia repair?

    PubMed Central

    Brown, CN; Finch, JG

    2010-01-01

    INTRODUCTION The concept of using a mesh to repair hernias was introduced over 50 years ago. Mesh repair is now standard in most countries and widely accepted as superior to primary suture repair. As a result, there has been a rapid growth in the variety of meshes available and choosing the appropriate one can be difficult. This article outlines the general properties of meshes and factors to be considered when selecting one. MATERIALS AND METHODS We performed a search of the medical literature from 1950 to 1 May 2009, as indexed by Medline, using the PubMed search engine (). To capture all potentially relevant articles with the highest degree of sensitivity, the search terms were intentionally broad. We used the following terms: ‘mesh, pore size, strength, recurrence, complications, lightweight, properties’. We also hand-searched the bibliographies of relevant articles and product literature to identify additional pertinent reports. RESULTS AND CONCLUSIONS The most important properties of meshes were found to be the type of filament, tensile strength and porosity. These determine the weight of the mesh and its biocompatibility. The tensile strength required is much less than originally presumed and light-weight meshes are thought to be superior due to their increased flexibility and reduction in discomfort. Large pores are also associated with a reduced risk of infection and shrinkage. For meshes placed in the peritoneal cavity, consideration should also be given to the risk of adhesion formation. A variety of composite meshes have been promoted to address this, but none appears superior to the others. Finally, biomaterials such as acellular dermis have a place for use in infected fields but have yet to prove their worth in routine hernia repair. PMID:20501011

  20. Cell therapy for bone repair.

    PubMed

    Rosset, P; Deschaseaux, F; Layrolle, P

    2014-02-01

    When natural bone repair mechanisms fail, autologous bone grafting is the current standard of care. The osteogenic cells and bone matrix in the graft provide the osteo-inductive and osteo-conductive properties required for successful bone repair. Bone marrow (BM) mesenchymal stem cells (MSCs) can differentiate into osteogenic cells. MSC-based cell therapy holds promise for promoting bone repair. The amount of MSCs available from iliac-crest aspirates is too small to be clinically useful, and either concentration or culture must therefore be used to expand the MSC population. MSCs can be administered alone via percutaneous injection or implanted during open surgery with a biomaterial, usually biphasic hydroxyapatite/β-calcium-triphosphate granules. Encouraging preliminary results have been obtained in patients with delayed healing of long bone fractures or avascular necrosis of the femoral head. Bone tissue engineering involves in vitro MSC culturing on biomaterials to obtain colonisation of the biomaterial and differentiation of the cells. The biomaterial-cell construct is then implanted into the zone to be treated. Few published data are available on bone tissue engineering. Much work remains to be done before determining whether this method is suitable for the routine filling of bone tissue defects. Increasing cell survival and promoting implant vascularisation are major challenges. Improved expertise with culturing techniques, together with the incorporation of regulatory requirements, will open the way to high-quality clinical trials investigating the usefulness of cell therapy as a method for achieving bone repair. Cell therapy avoids the drawbacks of autologous bone grafting, preserving the bone stock and diminishing treatment invasiveness.

  1. Endovascular repair of traumatic thoracic aortic injuries: a critical appraisal.

    PubMed

    Lin, Peter H; Huynh, Tam T; Kougias, Panagiotis; Wall, Mathew J; Coselli, Joseph S; Mattox, Kenneth L

    2008-08-01

    Blunt trauma to the thoracic aorta is life-threatening, with instant fatality in at least 75% of victims. If left untreated, nearly half of those who survive the initial injury will die within the first 24 hours. Surgical repair has been the standard treatment of blunt aortic injury, but immediate operative intervention is frequently difficult due to concomitant injuries. Although endovascular treatment of traumatic aortic disruption is less invasive than conventional repair via thoracotomy, this strategy remains controversial in young patients due to anatomical considerations and device limitations. This article reviews the likely advantages of endovascular interventions for blunt thoracic aortic injuries. Potential limitations and clinical outcomes of this minimally invasive technique are also discussed.

  2. TAT-mediated delivery of a DNA repair enzyme to skin cells rapidly initiates repair of UV-induced DNA damage

    PubMed Central

    Johnson, Jodi L.; Lowell, Brian C.; Ryabinina, Olga P.; Lloyd, R. Stephen; McCullough, Amanda K.

    2011-01-01

    Ultraviolet (UV) light causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Although human cells possess a mechanism (Nucleotide Excision Repair, NER) to repair UV-induced DNA damage, mutagenesis still occurs when DNA is replicated prior to repair of these photoproducts. While human cells have all the enzymes necessary to complete an alternate repair pathway, Base Excision Repair (BER), they lack a DNA glycosylase that can initiate BER of dipyrimidine photoproducts. Certain prokaryotes and viruses produce pyrimidine dimer-specific DNA glycosylases (pdgs) that initiate BER of cyclobutane pyrimidine dimers (CPDs), the predominant UV-induced lesions. Such a pdg was identified in the Chlorella virus PBCV-1 and termed Cv-pdg. The Cv-pdg protein was engineered to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (TAT). Here, we demonstrate that the Cv-pdg-NLS-TAT protein was delivered to repair-proficient keratinocytes and fibroblasts, and to a human skin model, where it rapidly initiated removal of CPDs. These data suggest a potential strategy for prevention of human skin cancer. PMID:20927123

  3. Distinct responses to reduplicated chromosomes require distinct Mad2 responses

    PubMed Central

    Stormo, Benjamin M; Fox, Donald T

    2016-01-01

    Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2’s control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention. DOI: http://dx.doi.org/10.7554/eLife.15204.001 PMID:27159240

  4. Calcium signaling in membrane repair

    PubMed Central

    Cheng, Xiping; Zhang, Xiaoli; Yu, Lu; Xu, Haoxing

    2015-01-01

    Resealing allows cells to mend damaged membranes rapidly when plasma membrane (PM) disruptions occur. Models of PM repair mechanisms include the “lipid-patch”, “endocytic removal”, and “macro-vesicle shedding” models, all of which postulate a dependence on local increases in intracellular Ca2+ at injury sites. Multiple calcium sensors, including synaptotagmin (Syt) VII, dysferlin, and apoptosis-linked gene-2 (ALG-2), are involved in PM resealing, suggesting that Ca2+ may regulate multiple steps of the repair process. Although earlier studies focused exclusively on external Ca2+, recent studies suggest that Ca2+ release from intracellular stores may also be important for PM resealing. Hence, depending on injury size and the type of injury, multiple sources of Ca2+ may be recruited to trigger and orchestrate repair processes. In this review, we discuss the mechanisms by which the resealing process is promoted by vesicular Ca2+ channels and Ca2+ sensors that accumulate at damage sites. PMID:26519113

  5. Probing the substrate specificity of the bacterial Pnkp/Hen1 RNA repair system using synthetic RNAs.

    PubMed

    Zhang, Can; Chan, Chio Mui; Wang, Pei; Huang, Raven H

    2012-02-01

    Ribotoxins cleave essential RNAs involved in protein synthesis as a strategy for cell killing. RNA repair systems exist in nature to counteract the lethal actions of ribotoxins, as first demonstrated by the RNA repair system from bacteriophage T4 25 yr ago. Recently, we found that two bacterial proteins, named Pnkp and Hen1, form a stable complex and are able to repair ribotoxin-cleaved tRNAs in vitro. However, unlike the well-studied T4 RNA repair system, the natural RNA substrates of the bacterial Pnkp/Hen1 RNA repair system are unknown. Here we present comprehensive RNA repair assays with the recombinant Pnkp/Hen1 proteins from Anabaena variabilis using a total of 33 different RNAs as substrates that might mimic various damaged forms of RNAs present in living cells. We found that unlike the RNA repair system from bacteriophage T4, the bacterial Pnkp/Hen1 RNA repair system exhibits broad substrate specificity. Based on the experimental data presented here, a model of preferred RNA substrates of the Pnkp/Hen1 repair system is proposed.

  6. Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene

    PubMed Central

    Hollywood, Jennifer A.; Lee, Ciaran M.; Scallan, Martina F.; Harrison, Patrick T.

    2016-01-01

    To maximise the efficiency of template-dependent gene editing, most studies describe programmable and/or RNA-guided endonucleases that make a double-stranded break at, or close to, the target sequence to be modified. The rationale for this design strategy is that most gene repair tracts will be very short. Here, we describe a CRISPR Cas9/gRNA selection-free strategy which uses deep sequencing to characterise repair tracts from a donor plasmid containing seven nucleotide differences across a 216 bp target region in the human CFTR gene. We found that 90% of the template-dependent repair tracts were >100 bp in length with equal numbers of uni-directional and bi-directional repair tracts. The occurrence of long repair tracts suggests that a single gRNA could be used with variants of the same template to create or correct specific mutations within a 200 bp range, the size of ~80% of human exons. The selection-free strategy used here also allowed detection of non-homologous end joining events in many of the homology-directed repair tracts. This indicates a need to modify the donor, possibly by silent changes in the PAM sequence, to prevent creation of a second double-stranded break in an allele that has already been correctly edited by homology-directed repair. PMID:27557525

  7. Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene.

    PubMed

    Hollywood, Jennifer A; Lee, Ciaran M; Scallan, Martina F; Harrison, Patrick T

    2016-01-01

    To maximise the efficiency of template-dependent gene editing, most studies describe programmable and/or RNA-guided endonucleases that make a double-stranded break at, or close to, the target sequence to be modified. The rationale for this design strategy is that most gene repair tracts will be very short. Here, we describe a CRISPR Cas9/gRNA selection-free strategy which uses deep sequencing to characterise repair tracts from a donor plasmid containing seven nucleotide differences across a 216 bp target region in the human CFTR gene. We found that 90% of the template-dependent repair tracts were >100 bp in length with equal numbers of uni-directional and bi-directional repair tracts. The occurrence of long repair tracts suggests that a single gRNA could be used with variants of the same template to create or correct specific mutations within a 200 bp range, the size of ~80% of human exons. The selection-free strategy used here also allowed detection of non-homologous end joining events in many of the homology-directed repair tracts. This indicates a need to modify the donor, possibly by silent changes in the PAM sequence, to prevent creation of a second double-stranded break in an allele that has already been correctly edited by homology-directed repair. PMID:27557525

  8. Immune modulation by MANF promotes tissue repair and regenerative success in the retina.

    PubMed

    Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro; Konjikusic, Mia; Riley, Rebeccah; Chew, Shereen; Qi, Yanyan; Jasper, Heinrich; Lamba, Deepak A

    2016-07-01

    Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies. PMID:27365452

  9. Fine-mapping of DNA damage and repair in specific genomic segments.

    PubMed Central

    Govan, H L; Valles-Ayoub, Y; Braun, J

    1990-01-01

    The susceptibility of various genomic regions to DNA damage and repair is heterogeneous. While this can be related to factors such as primary sequence, physical conformation, and functional status, the exact mechanisms involved remain unclear. To more precisely define the key features of a genomic region targeted for these processes, a useful tool would be a method for fine-mapping gene-specific DNA damage and repair in vivo. Here, a polymerase chain reaction-based assay is described for measuring DNA damage and repair in small (less than 500 bp) genomic segments of three transcriptionally active but functionally distinct loci (rearranged immunoglobulin heavy chain variable region [Ig VDJ], low-density lipoprotein receptor gene, and N-ras proto-oncogene) in human tonsillar B lymphocytes. Analysis of ultraviolet (254 nm)-induced DNA damage revealed single-hit kinetics and a similar level of sensitivity (D50% approximately 6000 joule/m2) in all three regions, indicating that a single photoproduct was sufficient to fully block PCR amplification. A similar time period per unit length was required for repair of this DNA damage (average t1/2 per fragment length = 23.5 seconds per bp). DNA damage and repair was also detectable with the base adducting agent, 4-nitroquinoline-1-oxide. However, in this case IgVDJ differed from segments within the other two loci by its relative inaccessibility to alkylation. This assay thus permits high-resolution mapping of DNA damage and repair activity. Images PMID:2115669

  10. International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

    PubMed Central

    Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

    2011-01-01

    Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

  11. Bond strength of repaired amalgam restorations.

    PubMed

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi

    2015-01-01

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

  12. Bond strength of repaired amalgam restorations.

    PubMed

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi

    2015-01-01

    This in vitro study investigated the interfacial flexural strength (FS) of amalgam repairs and the optimal combination of repair materials and mechanical retention required for a consistent and durable repair bond. Amalgam bricks were created, each with 1 end roughened to expose a fresh surface before repair. Four groups followed separate repair protocols: group 1, bonding agent with amalgam; group 2, bonding agent with composite resin; group 3, mechanical retention (slot) with amalgam; and group 4, slot with bonding agent and amalgam. Repaired specimens were stored in artificial saliva for 1, 10, 30, 120, or 360 days before being loaded to failure in a 3-point bending test. Statistical analysis showed significant changes in median FS over time in groups 2 and 4. The effect of the repair method on the FS values after each storage period was significant for most groups except the 30-day storage groups. Amalgam-amalgam repair with adequate condensation yielded the most consistent and durable bond. An amalgam bonding agent could be beneficial when firm condensation on the repair surface cannot be achieved or when tooth structure is involved. Composite resin can be a viable option for amalgam repair in an esthetically demanding region, but proper mechanical modification of the amalgam surface and selection of the proper bonding system are essential. PMID:26325656

  13. Mutational analysis of ERCC3, which is involved in DNA repair and transcription initiation: identification of domains essential for the DNA repair function.

    PubMed

    Ma, L; Westbroek, A; Jochemsen, A G; Weeda, G; Bosch, A; Bootsma, D; Hoeijmakers, J H; van der Eb, A J

    1994-06-01

    The human ERCC3 gene, which corrects specifically the nucleotide excision repair defect in human xeroderma pigmentosum group B and cross-complements the repair deficiency in rodent UV-sensitive mutants of group 3, encodes a presumed DNA helicase that is identical to the p89 subunit of the general transcription factor TFIIH/BTF2. To examine the significance of the postulated functional domains in ERCC3, we have introduced mutations in the ERCC3 cDNA by means of site-specific mutagenesis and have determined the repair capacity of each mutant to complement the UV-sensitive phenotype of rodent group 3 cells. A conservative substitution of arginine for the invariant lysine residue in the ATPase motif (helicase domain I), six deletion mutations in the other helicase domains, and a deletion in the potential helix-turn-helix DNA-binding motif fail to complement the ERCC3 excision repair defect of rodent group 3 mutants, which implies that the helicase domains as well as the potential DNA-binding motif are required for the repair function of ERCC3. Analysis of carboxy-terminal deletions suggests that the carboxy-terminal exon may comprise a distinct determinant for the DNA repair function. In addition, we show that a functional epitope-tagged version of ERCC3 accumulates in the nucleus. Deletion of the putative nuclear location signal impairs neither the nuclear location nor the repair function, indicating that other sequences may (also) be involved in translocation of ERCC3 to the nucleus. PMID:8196650

  14. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.

    PubMed

    Dutta, Arijit; Yang, Chunying; Sengupta, Shiladitya; Mitra, Sankar; Hegde, Muralidhar L

    2015-05-01

    Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mispairing property, are continuously induced by endogenous reactive oxygen species and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydroxyuracil, produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of the five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1's role in replicating template strand repair. The key requirement for this event, which we named as the 'cow-catcher' mechanism of pre-replicative BER, is NEIL1's non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in reannealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U and Y-box-binding protein 1 as well as high mobility group box 1 protein, whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repairs cross-complementing protein 1 and poly (ADP-ribose) polymerase 1 and other accessory

  15. Cartilage regeneration and repair testing in a surrogate large animal model.

    PubMed

    Simon, Timothy M; Aberman, Harold M

    2010-02-01

    The aging human population is experiencing increasing numbers of symptoms related to its degenerative articular cartilage (AC), which has stimulated the investigation of methods to regenerate or repair AC. However, the seemingly inherent limited capacity for AC to regenerate persists to confound the various repair treatment strategies proposed or studied. Animal models for testing AC implant devices and reparative materials are an important and required part of the Food and Drug Administration approval process. Although final testing is ultimately performed in humans, animal testing allows for a wider range of parameters and combinations of test materials subjected to all the biological interactions of a living system. We review here considerations, evaluations, and experiences with selection and use of animal models and describe two untreated lesion models useful for testing AC repair strategies. These created lesion models, one deep (6 mm and through the subchondral plate) the other shallow (to the level of the subchondral bone plate) were placed in the middle one-third of the medial femoral condyle of the knee joints of goats. At 1-year neither the deep nor the shallow full-thickness chondral defects generated a repair that duplicated natural AC. Moreover, progressive deleterious changes occurred in the AC surrounding the defects. There are challenges in translation from animals to humans as anatomy and structures are different and immobilization to protect delicate repairs can be difficult. The tissues potentially generated by proposed cartilage repair strategies must be compared with the spontaneous changes that occur in similarly created untreated lesions. The prevention of the secondary changes in the surrounding cartilage and subchondral bone described in this article should be addressed with the introduction of treatments for repairs of the articulating surface.

  16. Interface tissue engineering: next phase in musculoskeletal tissue repair.

    PubMed

    Sahoo, Sambit; Teh, Thomas Kh; He, Pengfei; Toh, Siew Lok; Goh, James Ch

    2011-05-01

    Increasing incidence of musculoskeletal injuries coupled with limitations in the current treatment options have necessitated tissue engineering and regenerative medicine- based approaches. Moving forward from engineering isolated musculoskeletal tissues, research strategies are now being increasingly focused on repairing and regenerating the interfaces between dissimilar musculoskeletal tissues with the aim to achieve seamless integration of engineered musculoskeletal tissues. This article reviews the state-of-the-art in the tissue engineering of musculoskeletal tissue interfaces with a focus on Singapore's contribution in this emerging field. Various biomimetic scaffold and cellbased strategies, the use of growth factors, gene therapy and mechanical loading, as well as animal models for functional validation of the tissue engineering strategies are discussed.

  17. Genomic survey and expression analysis of DNA repair genes in the genus Leptospira.

    PubMed

    Martins-Pinheiro, Marinalva; Schons-Fonseca, Luciane; da Silva, Josefa B; Domingos, Renan H; Momo, Leonardo Hiroyuki Santos; Simões, Ana Carolina Quirino; Ho, Paulo Lee; da Costa, Renata M A

    2016-04-01

    Leptospirosis is an emerging zoonosis with important economic and public health consequences and is caused by pathogenic leptospires. The genus Leptospira belongs to the order Spirochaetales and comprises saprophytic (L. biflexa), pathogenic (L. interrogans) and host-dependent (L. borgpetersenii) members. Here, we present an in silico search for DNA repair pathways in Leptospira spp. The relevance of such DNA repair pathways was assessed through the identification of mRNA levels of some genes during infection in animal model and after exposition to spleen cells. The search was performed by comparison of available Leptospira spp. genomes in public databases with known DNA repair-related genes. Leptospires exhibit some distinct and unexpected characteristics, for instance the existence of a redundant mechanism for repairing a chemically diverse spectrum of alkylated nucleobases, a new mutS-like gene and a new shorter version of uvrD. Leptospira spp. shares some characteristics from Gram-positive, as the presence of PcrA, two RecQ paralogs and two SSB proteins; the latter is considered a feature shared by naturally competent bacteria. We did not find a significant reduction in the number of DNA repair-related genes in both pathogenic and host-dependent species. Pathogenic leptospires were enriched for genes dedicated to base excision repair and non-homologous end joining. Their evolutionary history reveals a remarkable importance of lateral gene transfer events for the evolution of the genus. Up-regulation of specific DNA repair genes, including components of SOS regulon, during infection in animal model validates the critical role of DNA repair mechanisms for the complex interplay between host/pathogen.

  18. Thermal protection system repair kit program

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The feasibility and conceptual design aspects of repair materials and procedures for in orbit repair of the space shuttle orbiter TPS tiles are investigated. Material studies to investigate cure in place materials are described including catalyst and cure studies, ablation tests and evaluations, and support mixing and applicator design. The feasibility of the repair procedures, the storage of the TPS, dispensing, and cure problems are addressed.

  19. Cellular repair/misrepair track model

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.

    1991-01-01

    A repair/misrepair cell kinetics model is superimposed onto the track structure model of Katz to provide for a repair mechanism. The model is tested on the repair-dependent data of Yang et al. and provides an adequate description of that data. The misrepair rate determines the maximum relative biological effectiveness (RBE), but similar results could arise from indirect X-ray lethality not include in the present model.

  20. Laparoscopic repair for vesicouterine fistulae

    PubMed Central

    Maioli, Rafael A.; Macedo, André R. S.; Garcia, André R. L.; de Almeida, Silvio H. M.; Rodrigues, Marco Aurélio Freitas

    2015-01-01

    ABSTRACT Objective: The purpose of this video is to present the laparoscopic repair of a VUF in a 42-year-old woman, with gross hematuria, in the immediate postoperative phase following a cesarean delivery. The obstetric team implemented conservative management, including Foley catheter insertion, for 2 weeks. She subsequently developed intermittent hematuria and cystitis. The urology team was consulted 15 days after cesarean delivery. Cystoscopy indicated an ulcerated lesion in the bladder dome of approximately 1.0cm in size. Hysterosalpingography and a pelvic computed tomography scan indicated a fistula. Materials and Methods: Laparoscopic repair was performed 30 days after the cesarean delivery. The patient was placed in the lithotomy position while also in an extreme Trendelenburg position. Pneumoperitoneum was established using a Veress needle in the midline infra-umbilical region, and a primary 11-mm port was inserted. Another 11-mm port was inserted exactly between the left superior iliac spine and the umbilicus. Two other 5-mm ports were established under laparoscopic guidance in the iliac fossa on both sides. The omental adhesions in the pelvis were carefully released and the peritoneum between the bladder and uterus was incised via cautery. Limited cystotomy was performed, and the specific sites of the fistula and the ureteral meatus were identified; thereafter, the posterior bladder wall was adequately mobilized away from the uterus. The uterine rent was then closed using single 3/0Vicryl sutures and two-layer watertight closure of the urinary bladder was achieved by using 3/0Vicryl sutures. An omental flap was mobilized and inserted between the uterus and the urinary bladder, and was fixed using two 3/0Vicryl sutures, followed by tube drain insertion. Results: The operative time was 140 min, whereas the blood loss was 100ml. The patient was discharged 3 days after surgery, and the catheter was removed 12 days after surgery. Discussion: Laparoscopy has

  1. Mutagenic DNA repair in enterobacteria.

    PubMed Central

    Sedgwick, S G; Ho, C; Woodgate, R

    1991-01-01

    Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD' fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD' antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium umu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention. Images PMID:1885540

  2. Current Trends in Laparoscopic Ventral Hernia Repair

    PubMed Central

    Patapis, Paul; Zavras, Nick; Tzanetis, Panagiotis; Machairas, Anastasios

    2015-01-01

    Background and Objectives: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. Database: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. Conclusions: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury. PMID:26273186

  3. Repair and rehabilitation with polymer concrete

    SciTech Connect

    Kukacka, L.E.

    1988-09-01

    As a result of their fast setting characteristics and excellent mechanical and physical properties, polymer concretes (PC) are finding ever increasing useage for the repair of deteriorated portland cement concrete structures. Applications include the repair of highway pavements and bridge decks, airport runways, hydrotechnical structures, tunnels, and industrial flooring. The most commonly used resins and monomer systems for these applications are epoxies, polyesters and methylmethacrylate. Furfuryl alcohol has been used experimentally, and shows promise for use in making emergency repairs under adverse moisture or extreme temperature conditions. In the paper, repair procedures will be discussed and several case histories given. 6 refs.

  4. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that—...

  5. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that—...

  6. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that—...

  7. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that—...

  8. Photomask repair using low-energetic electrons

    NASA Astrophysics Data System (ADS)

    Edinger, K.; Wolff, K.; Spies, P.; Luchs, T.; Schneider, H.; Auth, N.; Hermanns, Ch. F.; Waiblinger, M.

    2015-10-01

    Mask repair is an essential step in the mask manufacturing process as the extension of 193nm technology and the insertion of EUV are drivers for mask complexity and cost. The ability to repair all types of defects on all mask blank materials is crucial for the economic success of a mask shop operation. In the future mask repair is facing several challenges. The mask minimum features sizes are shrinking and require a higher resolution repair tool. At the same time mask blanks with different new mask materials are introduced to optimize optical performance and long term durability. For EUV masks new classes of defects like multilayer and phase defects are entering the stage. In order to achieve a high yield, mask repair has to cover etch and deposition capabilities and must not damage the mask. We will demonstrate in this paper that low energetic electron-beam (e-beam)-based mask repair is a commercially viable solution. Therefore we developed a new repair platform called MeRiT® neXT to address the technical challenges of this new technology. We will analyze the limits of the existing as well as lower energetic electron induced repair technologies theoretically and experimentally and show performance data on photomask reticles. Based on this data, we will give an outlook to future mask repair technology.

  9. Bladder and urethral repair - series (image)

    MedlinePlus

    ... urethral repair is usually performed to prevent urine leakage associated with stress incontinence. Stress incontinence is the involuntary leakage of urine when laughing, coughing, sneezing, or lifting, ...

  10. Scheduling and rescheduling with iterative repair

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    This paper describes the GERRY scheduling and rescheduling system being applied to coordinate Space Shuttle Ground Processing. The system uses constraint-based iterative repair, a technique that starts with a complete but possibly flawed schedule and iteratively improves it by using constraint knowledge within repair heuristics. In this paper we explore the tradeoff between the informedness and the computational cost of several repair heuristics. We show empirically that some knowledge can greatly improve the convergence speed of a repair-based system, but that too much knowledge, such as the knowledge embodied within the MIN-CONFLICTS lookahead heuristic, can overwhelm a system and result in degraded performance.

  11. Integrated Electrical Wire Insulation Repair System

    NASA Technical Reports Server (NTRS)

    Williams, Martha; Jolley, Scott; Gibson, Tracy; Parks, Steven

    2013-01-01

    An integrated system tool will allow a technician to easily and quickly repair damaged high-performance electrical wire insulation in the field. Low-melt polyimides have been developed that can be processed into thin films that work well in the repair of damaged polyimide or fluoropolymer insulated electrical wiring. Such thin films can be used in wire insulation repairs by affixing a film of this low-melt polyimide to the damaged wire, and heating the film to effect melting, flow, and cure of the film. The resulting repair is robust, lightweight, and small in volume. The heating of this repair film is accomplished with the use of a common electrical soldering tool that has been modified with a special head or tip that can accommodate the size of wire being repaired. This repair method can furthermore be simplified for the repair technician by providing replaceable or disposable soldering tool heads that have repair film already "loaded" and ready for use. The soldering tool heating device can also be equipped with a battery power supply that will allow its use in areas where plug-in current is not available

  12. National results after ventral hernia repair.

    PubMed

    Helgstrand, Frederik

    2016-07-01

    Ventral hernia repairs are among the most frequently performed surgical procedures. The variations of repair techniques are multiple and outcome has been unacceptable. Despite the high volume, it has been difficult to obtain sufficient data to provide evidence for best practice. In order to monitor national surgical quality and provide the warranted high volume data, the first national ventral hernia register (The Danish Ventral Hernia Database) was established in 2007 in Denmark. The present study series show that data from a well-established database supported by clinical examinations, patient files, questionnaires, and administrative data makes it possible to obtain nationwide high volume data and to achieve evidence for better outcome in a complex surgical condition as ventral hernia. Due to the high volume and included variables on surgical technique, it is now possible to make analyses adjusting for a variety of surgical techniques and different hernia specifications. We documented high 30-day complications and recurrence rates for both primary and secondary ventral hernias in a nationwide cohort. Furthermore, recurrence found by clinical examination was shown to exceed the number of patients undergoing reoperation for recurrence by a factor 4-5. The nationwide adjusted analyses proved that open mesh and laparoscopic repair for umbilical and epigastric hernias does not differ in 30-day outcome or in risk of recurrence. There is a minor risk reduction in early complications after open sutured repairs. However, the risk for a later recurrence repair is significantly higher after sutured repairs compared with mesh repairs. The study series showed that large hernia defects and open re-pairs were independent predictors for 30-day complications after an incisional hernia repair. Open procedures and large hernia defects were independent risk factors for a later recurrence re-pair. However, patients with large defects (> 15 cm) seemed to benefit from an open mesh

  13. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  14. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  15. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  16. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  17. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  18. 14 CFR 145.207 - Repair station manual.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Repair station manual. 145.207 Section 145...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Operating Rules § 145.207 Repair station manual. (a) A certificated repair station must prepare and follow a repair station manual acceptable to...

  19. 40 CFR 60.482-9 - Standards: Delay of repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 6 2010-07-01 2010-07-01 false Standards: Delay of repair. 60.482-9... Standards: Delay of repair. (a) Delay of repair of equipment for which leaks have been detected will be allowed if repair within 15 days is technically infeasible without a process unit shutdown. Repair of...

  20. 21 CFR 870.1350 - Catheter balloon repair kit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Catheter balloon repair kit. 870.1350 Section 870... repair kit. (a) Identification. A catheter balloon repair kit is a device used to repair or replace the... effect the repair or replacement. (b) Classification. Class III (premarket approval). (c) Date PMA...

  1. 14 CFR 145.207 - Repair station manual.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Repair station manual. 145.207 Section 145...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Operating Rules § 145.207 Repair station manual. (a) A certificated repair station must prepare and follow a repair station manual acceptable to...

  2. 24 CFR 206.47 - Property standards; repair work.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Property standards; repair work... Property standards; repair work. (a) Need for repairs. Properties must meet the applicable property... insured mortgage. (b) Assurance that repairs are made. The mortgage may be closed before the repair...

  3. 24 CFR 206.47 - Property standards; repair work.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Property standards; repair work... Property standards; repair work. (a) Need for repairs. Properties must meet the applicable property... insured mortgage. (b) Assurance that repairs are made. The mortgage may be closed before the repair...

  4. Stem cell-based therapies for bone repair.

    PubMed

    Milner, Peter I; Clegg, Peter D; Stewart, Matthew C

    2011-08-01

    This article provides an overview of the cellular and molecular events involved in bone repair and the current approaches to using stem cells as an adjunct to this process. The article emphasizes the key role of osteoprogenitor cells in the formation of bone and where the clinical applications of current research may lend themselves to large animal orthopaedics. The processes involved in osteogenic differentiation are presented and strategies for bone formation, including induction by osteogenic factors, bioscaffolds, and gene therapy, are reviewed. PMID:21872760

  5. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

    PubMed Central

    Siebert, Justin R.; Conta Steencken, Amanda; Osterhout, Donna J.

    2014-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. PMID:25309928

  6. Surgical Repair of an Asymptomatic Giant Right Coronary Artery Aneurysm

    PubMed Central

    Jahangeer, Saleem; Anjum, Nadeem; O'Donnell, Aonghus; Doddakula, Kishore

    2013-01-01

    Background Coronary artery aneurysm (CAA) is a rare finding, being mostly diagnosed on angiography or at autopsies. It is defined as being a dilation of the coronary artery that exceeds the diameter of the patient's largest coronary vessel by 1.5 to 2 times. Case Report We describe the operative correction of a giant right CAA measuring in excess of 10 cm. Conclusion Management of giant CAAs is not standardized and surgical strategy remains controversial. In our case, the patient has a successful surgical repair with no postoperative shunts on follow-up investigations. PMID:25360401

  7. RNF20-SNF2H Pathway of Chromatin Relaxation in DNA Double-Strand Break Repair

    PubMed Central

    Kato, Akihiro; Komatsu, Kenshi

    2015-01-01

    Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which has been used as a surrogate marker of DSBs. The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. This modification is required for DSB repair and regulated by a distinctive pathway from that of histone H2AX phosphorylation. Moreover, the connection between H2B ubiquitylation and the chromatin remodeling activity of SNF2H has been elucidated. In this review, we summarize the current knowledge of RNF20-mediated processes and the molecular link to H2AX-mediated processes during DSB repair. PMID:26184323

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

    PubMed

    Friedberg, Errol C

    2016-01-01

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

  9. Initiating Repair and Beyond: The Use of Two Repeat-Formatted Repair Initiations in Mandarin Conversation

    ERIC Educational Resources Information Center

    Wu, Ruey-Jiuan Regina

    2006-01-01

    As part of a growing effort to understand the organization of repair across languages, this study examines 2 repeat-formatted other-initiated repair practices in Mandarin conversation. Using the methodology of conversation analysis as a central framework, this study shows that the 2 Mandarin repair initiations under examination, like…

  10. 49 CFR 1242.42 - Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... repair, equipment damaged, dismantling retired property, fringe benefits, other casualties and insurance, lease rentals, joint facility rents, other rents, depreciation, joint facility, repairs billed to others... PASSENGER SERVICE FOR RAILROADS 1 Operating Expenses-Equipment § 1242.42 Administration, repair...

  11. Tissue engineering strategies for the regeneration of orthopedic interfaces.

    PubMed

    Lu, Helen H; Subramony, Siddarth D; Boushell, Margaret K; Zhang, Xinzhi

    2010-06-01

    A major focus in the field of orthopedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), necessitates a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone, or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality.

  12. Tissue Engineering Strategies for the Regeneration of Orthopaedic Interfaces

    PubMed Central

    Lu, Helen H.; Subramony, Siddarth D.; Boushell, Margaret K.; Zhang, Xinzhi

    2013-01-01

    A major focus in the field of orthopaedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), requires a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties that mimics that of the multi-tissue transition between bone and soft tissues. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone or cartilage-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality. PMID:20422291

  13. Consonantal and Syllabic Repairs of Arabic and Dutch Loanwords in Indonesian: A Phonological Account

    ERIC Educational Resources Information Center

    Batais, Saleh Saeed

    2013-01-01

    The dissertation study aims to contribute mainly to the field of loanword phonology in general and particularly to Indonesian and its phonology that are rarely studied to date. The study investigates what consonantal and syllabic repair strategies are employed by Indonesian in adapting Arabic and Dutch loanwords, whether these adaptation…

  14. Green tea and skin cancer: photoimmunology, angiogenesis and DNA repair.

    PubMed

    Katiyar, Suchitra; Elmets, Craig A; Katiyar, Santosh K

    2007-05-01

    Human skin is constantly exposed to numerous noxious physical, chemical and environmental agents. Some of these agents directly or indirectly adversely affect the skin. Cutaneous overexposure to environmental solar ultraviolet (UV) radiation (290-400 nm) has a variety of adverse effects on human health, including the development of melanoma and nonmelanoma skin cancers. Therefore, there is a need to develop measures or strategies, and nutritional components are increasingly being explored for this purpose. The polyphenols present in green tea (Camellia sinensis) have been shown to have numerous health benefits, including protection from UV carcinogenesis. (-)-Epigallocatechin-3-gallate (EGCG) is the major and most photoprotective polyphenolic component of green tea. In this review article, we have discussed the most recent investigations and mechanistic studies that define and support the photoprotective efficacy of green tea polyphenols (GTPs) against UV carcinogenesis. The oral administration of GTPs in drinking water or the topical application of EGCG prevents UVB-induced skin tumor development in mice, and this prevention is mediated through: (a) the induction of immunoregulatory cytokine interleukin (IL) 12; (b) IL-12-dependent DNA repair following nucleotide excision repair mechanism; (c) the inhibition of UV-induced immunosuppression through IL-12-dependent DNA repair; (d) the inhibition of angiogenic factors; and (e) the stimulation of cytotoxic T cells in a tumor microenvironment. New mechanistic information strongly supports and explains the chemopreventive activity of GTPs against photocarcinogenesis.

  15. Bone tissue engineering and repair by gene therapy.

    PubMed

    Betz, Volker M; Betz, Oliver B; Harris, Mitchel B; Vrahas, Mark S; Evans, Christopher H

    2008-01-01

    Many clinical conditions require the stimulation of bone growth. The use of recombinant bone morphogenetic proteins does not provide a satisfying solution to these conditions due to delivery problems and high cost. Gene therapy has emerged as a very promising approach for bone repair that overcomes limitations of protein-based therapy. Several preclinical studies have shown that gene transfer technology has the ability to deliver osteogenic molecules to precise anatomical locations at therapeutic levels for sustained periods of time. Both in-vivo and ex-vivo transduction of cells can induce bone formation at ectopic and orthotopic sites. Genetic engineering of adult stem cells from various sources with osteogenic genes has led to enhanced fracture repair, spinal fusion and rapid healing of bone defects in animal models. This review describes current viral and non-viral gene therapy strategies for bone tissue engineering and repair including recent work from the author's laboratory. In addition, the article discusses the potential of gene-enhanced tissue engineering to enter widespread clinical use.

  16. Component-Level Electronic-Assembly Repair (CLEAR) Operational Concept

    NASA Technical Reports Server (NTRS)

    Oeftering, Richard C.; Bradish, Martin A.; Juergens, Jeffrey R.; Lewis, Michael J.; Vrnak, Daniel R.

    2011-01-01

    This Component-Level Electronic-Assembly Repair (CLEAR) Operational Concept document was developed as a first step in developing the Component-Level Electronic-Assembly Repair (CLEAR) System Architecture (NASA/TM-2011-216956). The CLEAR operational concept defines how the system will be used by the Constellation Program and what needs it meets. The document creates scenarios for major elements of the CLEAR architecture. These scenarios are generic enough to apply to near-Earth, Moon, and Mars missions. The CLEAR operational concept involves basic assumptions about the overall program architecture and interactions with the CLEAR system architecture. The assumptions include spacecraft and operational constraints for near-Earth orbit, Moon, and Mars missions. This document addresses an incremental development strategy where capabilities evolve over time, but it is structured to prevent obsolescence. The approach minimizes flight hardware by exploiting Internet-like telecommunications that enables CLEAR capabilities to remain on Earth and to be uplinked as needed. To minimize crew time and operational cost, CLEAR exploits offline development and validation to support online teleoperations. Operational concept scenarios are developed for diagnostics, repair, and functional test operations. Many of the supporting functions defined in these operational scenarios are further defined as technologies in NASA/TM-2011-216956.

  17. Targeting Microtubules for Wound Repair

    PubMed Central

    Charafeddine, Rabab A.; Nosanchuk, Joshua D.; Sharp, David J.

    2016-01-01

    Significance: Fast and seamless healing is essential for both deep and chronic wounds to restore the skin and protect the body from harmful pathogens. Thus, finding new targets that can both expedite and enhance the repair process without altering the upstream signaling milieu and causing serious side effects can improve the way we treat wounds. Since cell migration is key during the different stages of wound healing, it presents an ideal process and intracellular structural machineries to target. Recent Advances and Critical Issues: The microtubule (MT) cytoskeleton is rising as an important structural and functional regulator of wound healing. MTs have been reported to play different roles in the migration of the various cell types involved in wound healing. Specific microtubule regulatory proteins (MRPs) can be targeted to alter a section or subtype of the MT cytoskeleton and boost or hinder cell motility. However, inhibiting intracellular components can be challenging in vivo, especially using unstable molecules, such as small interfering RNA. Nanoparticles can be used to protect these unstable molecules and topically deliver them to the wound. Utilizing this approach, we recently showed that fidgetin-like 2, an uncharacterized MRP, can be targeted to enhance cell migration and wound healing. Future Directions: To harness the full potential of the current MRP therapeutic targets, studies should test them with different delivery platforms, dosages, and skin models. Screening for new MT effectors that boost cell migration in vivo would also help find new targets for skin repair. PMID:27785378

  18. Repair of overheating linear accelerator

    SciTech Connect

    Barkley, Walter; Baldwin, William; Bennett, Gloria; Bitteker, Leo; Borden, Michael; Casados, Jeff; Fitzgerald, Daniel; Gorman, Fred; Johnson, Kenneth; Kurennoy, Sergey; Martinez, Alberto; O’Hara, James; Perez, Edward; Roller, Brandon; Rybarcyk, Lawrence; Stark, Peter; Stockton, Jerry

    2004-01-01

    Los Alamos Neutron Science Center (LANSCE) is a proton accelerator that produces high energy particle beams for experiments. These beams include neutrons and protons for diverse uses including radiography, isotope production, small feature study, lattice vibrations and material science. The Drift Tube Linear Accelerator (DTL) is the first portion of a half mile long linear section of accelerator that raises the beam energy from 750 keV to 100 MeV. In its 31st year of operation (2003), the DTL experienced serious issues. The first problem was the inability to maintain resonant frequency at full power. The second problem was increased occurrences of over-temperature failure of cooling hoses. These shortcomings led to an investigation during the 2003 yearly preventative maintenance shutdown that showed evidence of excessive heating: discolored interior tank walls and coper oxide deposition in the cooling circuits. Since overheating was suspected to be caused by compromised heat transfer, improving that was the focus of the repair effort. Investigations revealed copper oxide flow inhibition and iron oxide scale build up. Acid cleaning was implemented with careful attention to protection of the base metal, selection of components to clean and minimization of exposure times. The effort has been very successful in bringing the accelerator through a complete eight month run cycle allowing an incredible array of scientific experiments to be completed this year (2003-2004). This paper will describe the systems, investigation analysis, repair, return to production and conclusion.

  19. DNA Damage and Repair in Eukaryotic Cells

    PubMed Central

    Painter, R. B.

    1974-01-01

    Damage in DNA after irradiation can be classified into five kinds: base damage, single-strand breaks, double-strand breaks, DNA–DNA cross-linking, and DNA-protein cross-linking. Of these, repair of base damage is the best understood. In eukaryotes, at least three repair systems are known that can deal with base damage: photoreactivation, excision repair, and post-replication repair. Photoreactivation is specific for UV-induced damage and occurs widely throughout the biosphere, although it seems to be absent from placental mammals. Excision repair is present in prokaryotes and in animals but does not seem to be present in plants. Post-replication repair is poorly understood. Recent reports indicate that growing points in mammalian DNA simply skip past UV-induced lesions, leaving gaps in newly made DNA that are subsequently filled in by de novo synthesis. Evidence that this concept is oversimplified or incorrect is presented.—Single-strand breaks are induced by ionizing radiation but most cells can rapidly repair most or all of them, even after supralethal doses. The chemistry of the fragments formed when breaks are induced by ionizing radiation is complex and poorly understood. Therefore, the intermediate steps in the repair of single-strand breaks are unknown. Double-strand breaks and the two kinds of cross-linking have been studied very little and almost nothing is known about their mechanisms for repair.—The role of mammalian DNA repair in mutations is not known. Although there is evidence that defective repair can lead to cancer and/or premature aging in humans, the relationship between the molecular defects and the diseased state remains obscure. PMID:4442699

  20. Molded Parallel Endografts for Branch Vessel Preservation during Endovascular Aneurysm Repair in Challenging Anatomy.

    PubMed

    Minion, David

    2012-06-01

    Parallel endografts (also known as snorkels or chimneys) are a proposed strategy for increasing the applicability of endovascular repair to aneurysms involving branch vessels. One major disadvantage of this strategy is the imperfect nature of seal inherent to having multiple side-by-side endografts. In this article, the use of odd-shaped parallel endografts to facilitate apposition and improve seal is proposed and a technique to mold a round stent graft into an "eye" shape using balloons is described.

  1. Ultraviolet-sensitive syndrome cells are defective in transcription-coupled repair of cyclobutane pyrimidine dimers.

    PubMed

    Spivak, Graciela; Itoh, Toshiki; Matsunaga, Tsukasa; Nikaido, Osamu; Hanawalt, Philip; Yamaizumi, Masaru

    2002-08-01

    Patients with ultraviolet-sensitive syndrome (UV(S)S) are sensitive to sunlight, but present neither developmental nor neurological deficiencies. Complementation studies with hereditary DNA repair syndromes show that UV(S)S is distinct from all known xeroderma pigmentosum (XP) and Cockayne syndrome (CS) groups. UV(S)S cells exhibit some characteristics typical of CS, including normal global genomic (GGR) repair of UV-photoproducts, poor clonal survival and defective recovery of RNA synthesis after UV exposure. Those observations have led us to suggest that UV(S)S cells, like those from CS, are defective in transcription-coupled repair (TCR) of cyclobutane pyrimidine dimers (CPD). We have now examined the repair of CPD in the transcribed and non-transcribed strands of the active dihydrofolate reductase (DHFR) and p53 genes, and of the silent alpha-fetoprotein (AFP) and mid-size neurofilament (NF-M) genes in normal human cells and in cells belonging to UV(S)S and CS complementation group B. Our results provide compelling evidence that the UV(S)S gene is essential for TCR of CPD and probably other bulky DNA lesions. As a possible distinction between UV(S)S and CS patients, we postulate that the UV(S)S gene may not be required for TCR of oxidative lesions. We have also found that repair of CPD in either DNA strand of the genomic fragments examined, occurs at a slower rate in TCR-deficient cells than in the non-transcribed strands in normal cells; we suggest that in the absence of TCR, global repair complexes have hindered access to lesions in genomic regions that extend beyond individual transcription units. PMID:12509286

  2. Effect of repair surface design, repair material, and processing method on the transverse strength of repaired acrylic denture resin.

    PubMed

    Ward, J E; Moon, P C; Levine, R A; Behrendt, C L

    1992-06-01

    The transverse strengths of blocks of denture base acrylic resin repaired with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer were measured with a three-point bending test. Three repair joints were studied: butt, round, and 45-degree bevel. Three processing methods were used: bench cure, hydroflask with hot water for 10 minutes, and hydroflask with hot water for 30 minutes. The strengths of repairs made with round and 45-degree bevel joint designs were similar and significantly greater than those with a butt joint design. The strengths of repairs processed in a hydroflask for 10 minutes and 30 minutes were similar and significantly greater than those cured on the bench top. There was no difference in the strength of repairs made with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer.

  3. Endovascular Repair of Descending Thoracic Aortic Aneurysm

    PubMed Central

    2005-01-01

    repair (EVAR) using a stent graft, a procedure called endovascular stent-graft (ESG) placement, is a new alternative to the traditional surgical approach. It is less invasive, and initial results from several studies suggest that it may reduce mortality and morbidity associated with the repair of descending TAAs. The goal in endovascular repair is to exclude the aneurysm from the systemic circulation and prevent it from rupturing, which is life-threatening. The endovascular placement of a stent graft eliminates the systemic pressure acting on the weakened wall of the aneurysm that may lead to the rupture. However, ESG placement has some specific complications, including endovascular leak (endoleak), graft migration, stent fracture, and mechanical damage to the access artery and aortic wall. The Talent stent graft (manufactured by Medtronic Inc., Minneapolis, MN) is licensed in Canada for the treatment of patients with TAA (Class 4; licence 36552). The design of this device has evolved since its clinical introduction. The current version has a more flexible delivery catheter than did the original system. The prosthesis is composed of nitinol stents between thin layers of polyester graft material. Each stent is secured with oversewn sutures to prevent migration. Review Strategy Objectives To compare the effectiveness and cost-effectiveness of ESG placement in the treatment of TAAs with a conventional surgical approach To summarize the safety profile and effectiveness of ESG placement in the treatment of descending TAAs Measures of Effectiveness Primary Outcome Mortality rates (30-day and longer term) Secondary Outcomes Technical success rate of introducing a stent graft and exclusion of the aneurysm sac from systemic circulation Rate of reintervention (through surgical or endovascular approach) Measures of Safety Complications were categorized into 2 classes: Those specific to the ESG procedure, including rates of aneurysm rupture, endoleak, graft migration, stent fracture

  4. Mitral valve repair for ischemic mitral regurgitation: lessons from the Cardiothoracic Surgical Trials Network randomized study

    PubMed Central

    Santana, Orlando

    2016-01-01

    Approximately 30% to 50% of patients will develop ischemic mitral regurgitation (MR) after a myocardial infarction, which is a result of progressive left ventricular remodeling and dysfunction of the subvalvular apparatus, and portends a poor long-term prognosis. Surgical treatment is centered on mitral valve repair utilizing a restrictive annuloplasty, or valve replacement with preservation of the subvalvular apparatus. In the recent Cardiothoracic Surgical Trials Network (CSTN) study, patients with severe ischemic MR were randomized to mitral valve repair with a restrictive annuloplasty versus chordal-sparing valve replacement, and concomitant coronary artery bypass grafting, if indicated. At 2-year follow-up, mitral valve repair was associated with a significantly higher incidence of moderate or greater recurrent MR and heart failure, with no difference in the indices of left ventricular reverse remodeling, as compared with valve replacement. The current appraisal aims to provide insight into the CSTN trial results, and discusses the evidence supporting a pathophysiologic-guided repair strategy incorporating combined annuloplasty and subvalvular repair techniques to optimize the outcomes of mitral valve repair in ischemic MR. PMID:26904260

  5. Cisplatin DNA damage and repair maps of the human genome at single-nucleotide resolution

    PubMed Central

    Hu, Jinchuan; Lieb, Jason D.; Sancar, Aziz; Adar, Sheera

    2016-01-01

    Cisplatin is a major anticancer drug that kills cancer cells by damaging their DNA. Cancer cells cope with the drug by removal of the damages with nucleotide excision repair. We have developed methods to measure cisplatin adduct formation and its repair at single-nucleotide resolution. “Damage-seq” relies on the replication-blocking properties of the bulky base lesions to precisely map their location. “XR-seq” independently maps the removal of these damages by capturing and sequencing the excised oligomer released during repair. The damage and repair maps we generated reveal that damage distribution is essentially uniform and is dictated mostly by the underlying sequence. In contrast, cisplatin repair is heterogeneous in the genome and is affected by multiple factors including transcription and chromatin states. Thus, the overall effect of damages in the genome is primarily driven not by damage formation but by the repair efficiency. The combination of the Damage-seq and XR-seq methods has the potential for developing novel cancer therapeutic strategies. PMID:27688757

  6. Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

    DOE PAGES

    Hang, Bo

    2010-01-01

    DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking-related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N -nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O 6more » -alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen-associated genotoxic and carcinogenic effects.« less

  7. Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

    PubMed Central

    Hang, Bo

    2010-01-01

    DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking-related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N-nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O6-alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen-associated genotoxic and carcinogenic effects. PMID:21234336

  8. Hodgkin Lymphoma Risk: Role of Genetic Polymorphisms and Gene-Gene Interactions in DNA repair pathways

    PubMed Central

    Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa

    2011-01-01

    DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL. PMID:21374732

  9. Laser engineered net shaping (LENS) for the repair and modification of NWC metal components.

    SciTech Connect

    Atwood, Clinton J.; Smugeresky, John E. (Sandia National Labs, Livermore,CA); Gill, David Dennis

    2006-11-01

    Laser Engineered Net Shaping{trademark} (LENS{reg_sign}) is a layer additive manufacturing process that creates fully dense metal components using a laser, metal powder, and a computer solid model. This process has previously been utilized in research settings to create metal components and new material alloys. The ''Qualification of LENS for the Repair and Modification of Metal NWC Components'' project team has completed a Technology Investment project to investigate the use of LENS for repair of high rigor components. The team submitted components from four NWC sites for repair or modification using the LENS process. These components were then evaluated for their compatibility to high rigor weapons applications. The repairs included hole filling, replacement of weld lips, addition of step joints, and repair of surface flaws and gouges. The parts were evaluated for mechanical properties, corrosion resistance, weldability, and hydrogen compatibility. This document is a record of the LENS processing of each of these component types and includes process parameters, build strategies, and lessons learned. Through this project, the LENS process was shown to successfully repair or modify metal NWC components.

  10. Evidence of K+ channel function in epithelial cell migration, proliferation, and repair

    PubMed Central

    Girault, Alban

    2013-01-01

    Efficient repair of epithelial tissue, which is frequently exposed to insults, is necessary to maintain its functional integrity. It is therefore necessary to better understand the biological and molecular determinants of tissue regeneration and to develop new strategies to promote epithelial repair. Interestingly, a growing body of evidence indicates that many members of the large and widely expressed family of K+ channels are involved in regulation of cell migration and proliferation, key processes of epithelial repair. First, we briefly summarize the complex mechanisms, including cell migration, proliferation, and differentiation, engaged after epithelial injury. We then present evidence implicating K+ channels in the regulation of these key repair processes. We also describe the mechanisms whereby K+ channels may control epithelial repair processes. In particular, changes in membrane potential, K+ concentration, cell volume, intracellular Ca2+, and signaling pathways following modulation of K+ channel activity, as well as physical interaction of K+ channels with the cytoskeleton or integrins are presented. Finally, we discuss the challenges to efficient, specific, and safe targeting of K+ channels for therapeutic applications to improve epithelial repair in vivo. PMID:24196531

  11. International congress on DNA damage and repair: Book of abstracts

    SciTech Connect

    Not Available

    1987-01-01

    This document contains the abstracts of 105 papers presented at the Congress. Topics covered include the Escherichia coli nucleotide excision repair system, DNA repair in malignant transformations, defective DNA repair, and gene regulation. (TEM)

  12. AUTOMOTIVE REPAIR SHOP, DETAIL OF BUILDING CORNER (MAIN WING) SHOWING ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF BUILDING CORNER (MAIN WING) SHOWING WOOD EAVE AND STUCCO RAKEBOARD ON GABLE END, WITH SCALE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  13. AUTOMOTIVE REPAIR SHOP, INTERIOR VIEW TO SOUTHEAST, DOORWAYS TO SHOP ...

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

    AUTOMOTIVE REPAIR SHOP, INTERIOR VIEW TO SOUTHEAST, DOORWAYS TO SHOP OFFICE AND SOUTH WING, WITH SCALE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  14. AUTOMOTIVE REPAIR SHOP, DETAIL OF FABRICATING PRESS IN EAST END ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF FABRICATING PRESS IN EAST END OF MAIN WING, WITH SCALE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  15. AUTOMOTIVE REPAIR SHOP, INTERIOR VIEW TO SOUTHEAST, DOORWAYS TO SHOP ...

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

    AUTOMOTIVE REPAIR SHOP, INTERIOR VIEW TO SOUTHEAST, DOORWAYS TO SHOP OFFICE AND SOUTH WING. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  16. AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREWFEED ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREW-FEED COAL HOPPER ON RIGHT SIDE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  17. AUTOMOTIVE REPAIR SHOP, SLIDING DOOR LEADING TO BOILER ROOM ON ...

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

    AUTOMOTIVE REPAIR SHOP, SLIDING DOOR LEADING TO BOILER ROOM ON SOUTH SIDE OF SOUTH WING, WITH SCALE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  18. Lube rack of Automotive and Tractor Repair Shops with Warehousefield ...

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

    Lube rack of Automotive and Tractor Repair Shops with Warehouse-field Equipment Repair Shop Building's wall to the right, looking from the south - Kekaha Sugar Company, Automotive and Tractor Repair Shops, 8315 Kekaha Road, Kekaha, Kauai County, HI

  19. AUTOMOTIVE REPAIR SHOP, SLIDING DOOR LEADING TO BOILER ROOM ON ...

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

    AUTOMOTIVE REPAIR SHOP, SLIDING DOOR LEADING TO BOILER ROOM ON SOUTH SIDE OF SOUTH WING. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  20. AUTOMOTIVE REPAIR SHOP, DETAIL OF BUILDING CORNER (MAIN WING) SHOWING ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF BUILDING CORNER (MAIN WING) SHOWING WOOD EAVE AND STUCCO RAKEBOARD ON GABLE END. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  1. AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREWFEED ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREW-FEED COAL HOPPER ON RIGHT SIDE, WITH SCALE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  2. Railroad track repairs are complete at KSC

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Railroad track repairs have been completed at Kennedy Space Center. This section of track is located on KSC property, just north of the NASA Causeway in the KSC Industrial Area. The repairs were required following the minor derailment of two solid rocket booster segment cars on July 18.

  3. Repair of major system elements on Skylab

    NASA Technical Reports Server (NTRS)

    Pace, R. E., Jr.

    1974-01-01

    In-flight maintenance, as conceived and preplanned for the Skylab mission was limited to simple scheduled and unscheduled replacement tasks and minor contingency repairs. Tools and spares were provided accordingly. However, failures during the mission dictated complicated and sophisticated repairs to major systems so that the mission could continue. These repairs included the release of a large structure that failed to deploy, the assembly and deployment of large mechanical devices, the installation and checkout of precision electronic equipment, troubleshooting and repair of precision electromechanical equipment, and tapping into and recharging a cooling system. The repairs were conducted both inside the spacecraft and during extravehicular activities. Some of the repair tasks required team effort on the part of the crewmen including close procedural coordination between internal and extravehicular crewmen. The Skylab experience indicates that crewmen can, with adequate training, make major system repairs in space using standard or special tools. Design of future spacecraft systems should acknowledge this capability and provide for more extensive in-flight repair and maintenance.

  4. Appliance Repair. Post Secondary Curriculum Guide.

    ERIC Educational Resources Information Center

    Watkins, James F.; And Others

    This curriculum guide was designed for use in postsecondary appliance repair education programs in Georgia. Its purpose is to provide for development of entry level skills in appliance repair in the areas of knowledge, theoretical structure, tool usage, diagnostic ability, related supportive skills, and occupational survival skills. The first…

  5. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  6. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  7. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  8. Thermal protection system flight repair kit

    NASA Technical Reports Server (NTRS)

    1979-01-01

    A thermal protection system (TPS) flight repair kit required for use on a flight of the Space Transportation System is defined. A means of making TPS repairs in orbit by the crew via extravehicular activity is discussed. A cure in place ablator, a precured ablator (large area application), and packaging design (containers for mixing and dispensing) for the TPS are investigated.

  9. 30 CFR 57.6801 - Vehicle repair.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Vehicle repair. 57.6801 Section 57.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... and Underground § 57.6801 Vehicle repair. Vehicles containing explosive material and oxidizers...

  10. 30 CFR 56.6801 - Vehicle repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 56.6801 Section 56.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Vehicle repair. Vehicles containing explosive material and oxidizers shall not be taken into a...

  11. 30 CFR 56.6801 - Vehicle repair.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Vehicle repair. 56.6801 Section 56.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Vehicle repair. Vehicles containing explosive material and oxidizers shall not be taken into a...

  12. 30 CFR 57.6801 - Vehicle repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Vehicle repair. 57.6801 Section 57.6801 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... and Underground § 57.6801 Vehicle repair. Vehicles containing explosive material and oxidizers...

  13. Novel EUV Mask Blank Defect Repair Developments

    SciTech Connect

    Hau-Riege, S; Barty, A; Mirkarimi, P

    2003-03-31

    The development of defect-free reticle blanks is an important challenge facing the commercialization of extreme ultraviolet lithography (EUVL). The basis of EUVL reticles are mask blanks consisting of a substrate and a reflective Mo/Si multilayer. Defects on the substrate or defects introduced during multilayer deposition can result in critical phase and amplitude defects. Amplitude- or phase-defect repair techniques are being developed with the goal to repair many of these defects. In this report, we discuss progress in two areas of defect repair: (1) We discuss the effect of the residual reflectance variation over the repair zone after amplitude-defect repair on the process window. This allows the determination of the maximum tolerable residual damage induced by amplitude defect repair. (2) We further performed a quantitative assessment of the yield improvement due to defect repair. We found that amplitude- and phase-defect repair have the potential to significantly improve mask blank yield. Our calculations further show that yield can be maximized by increasing the number of Mo/Si bilayers.

  14. 33 CFR 127.1405 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Repairs. 127.1405 Section 127.1405 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... Waterfront Facilities Handling Liquefied Hazardous Gas Maintenance § 127.1405 Repairs. Each operator of...

  15. Self repairing composites for drone air vehicles

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn

    2015-04-01

    The objective of this effort was to demonstrate the feasibility of impact-initiated delivery of repair chemicals through hollow fiber architectures embedded within graphite fiber reinforced polymer matrix composites, representative of advanced drone aircraft component material systems. Self-repairing structures through coupon and elements were demonstrated, and evaluated.

  16. 40 CFR 280.33 - Repairs allowed.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STANDARDS AND CORRECTIVE ACTION REQUIREMENTS FOR OWNERS AND OPERATORS OF UNDERGROUND STORAGE TANKS (UST) General Operating Requirements § 280.33 Repairs allowed. Owners and operators of UST systems must ensure... operating properly. (f) UST system owners and operators must maintain records of each repair for...

  17. 40 CFR 280.33 - Repairs allowed.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STANDARDS AND CORRECTIVE ACTION REQUIREMENTS FOR OWNERS AND OPERATORS OF UNDERGROUND STORAGE TANKS (UST) General Operating Requirements § 280.33 Repairs allowed. Owners and operators of UST systems must ensure... operating properly. (f) UST system owners and operators must maintain records of each repair for...

  18. Self-repairing composites for airplane components

    NASA Astrophysics Data System (ADS)

    Dry, Carolyn

    2008-03-01

    Durability and damage tolerance criteria drives the design of most composite structures. Those criteria could be altered by developing structure that repairs itself from impact damage. This is a technology for increasing damage tolerance for impact damage. Repaired damage would enable continued function and prevent further degradation to catastrophic failure in the case of an aircraft application. Further, repaired damage would enable applications to be utilized without reduction in performance due to impacts. Self repairing structures are designed to incorporate hollow fibers, which will release a repairing agent when the structure is impacted, so that the repairing agent will fill delaminations, voids and cracks in les than one minute, thus healing matrix voids. The intent is to modify the durability and damage tolerance criteria by incorporation of self-healing technologies to reduce overall weight: The structure will actually remain lighter than current conventional design procedures allow. Research objective(s) were: Prove that damage can be repaired to within 80-90% of original flexural strength in less than one minute, in laminates that are processed at 300-350F typical for aircraft composites. These were successfully met. The main focus was on testing of elements in compression after impact and a larger component in shear at Natural Process Design, Inc. Based on these results the advantages purposes are assessed. The results show potential; with self repairing composites, compressive strength is maintained sufficiently so that less material can be used as per durability and damage tolerance, yielding a lighter structure.

  19. Human DNA repair and recombination genes

    SciTech Connect

    Thompson, L.H.; Weber, C.A.; Jones, N.J.

    1988-09-01

    Several genes involved in mammalian DNA repair pathways were identified by complementation analysis and chromosomal mapping based on hybrid cells. Eight complementation groups of rodent mutants defective in the repair of uv radiation damage are now identified. At least seven of these genes are probably essential for repair and at least six of them control the incision step. The many genes required for repair of DNA cross-linking damage show overlap with those involved in the repair of uv damage, but some of these genes appear to be unique for cross-link repair. Two genes residing on human chromosome 19 were cloned from genomic transformants using a cosmid vector, and near full-length cDNA clones of each gene were isolated and sequenced. Gene ERCC2 efficiently corrects the defect in CHO UV5, a nucleotide excision repair mutant. Gene XRCC1 normalizes repair of strand breaks and the excessive sister chromatid exchange in CHO mutant EM9. ERCC2 shows a remarkable /approximately/52% overall homology at both the amino acid and nucleotide levels with the yeast RAD3 gene. Evidence based on mutation induction frequencies suggests that ERCC2, like RAD3, might also be an essential gene for viability. 100 refs., 4 tabs.

  20. Repairers must relabel instruments, court rules.

    PubMed

    2002-08-01

    A federal appeals court decided that repair companies must be sure that endoscopic instruments they have worked on, especially those they have drastically altered, must be clearly identified as such. In some cases, that could mean that the original manufacturer's name must be removed, or the repairer's name added to the device's label. PMID:12232895