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Sample records for distinct repair strategies

  1. Strategy, Distinctive Competence, and Organizational Performance.

    ERIC Educational Resources Information Center

    Snow, Charles C.; Hrebiniak, Lawrence G.

    1980-01-01

    Focuses on the perceptions of top managers in four industries (plastics, semiconductors, automotives, and air transportation) who examined relationships among strategy, distinctive competence, and organizational performance. (Author/IRT)

  2. 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

  3. 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…

  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. 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.

  6. Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair.

    PubMed

    Davis, Luther; Maizels, Nancy

    2014-03-11

    DNA nicks are the most common form of DNA damage, and if unrepaired can give rise to genomic instability. In human cells, nicks are efficiently repaired via the single-strand break repair pathway, but relatively little is known about the fate of nicks not processed by that pathway. Here we show that homology-directed repair (HDR) at nicks occurs via a mechanism distinct from HDR at double-strand breaks (DSBs). HDR at nicks, but not DSBs, is associated with transcription and is eightfold more efficient at a nick on the transcribed strand than at a nick on the nontranscribed strand. HDR at nicks can proceed by a pathway dependent upon canonical HDR factors RAD51 and BRCA2; or by an efficient alternative pathway that uses either ssDNA or nicked dsDNA donors and that is strongly inhibited by RAD51 and BRCA2. Nicks generated by either I-AniI or the CRISPR/Cas9(D10A) nickase are repaired by the alternative HDR pathway with little accompanying mutagenic end-joining, so this pathway may be usefully applied to genome engineering. These results suggest that alternative HDR at nicks may be stimulated in physiological contexts in which canonical RAD51/BRCA2-dependent HDR is compromised or down-regulated, which occurs frequently in tumors.

  7. Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling

    PubMed Central

    Abreu-Blanco, Maria Teresa; Verboon, Jeffrey M.

    2011-01-01

    When single cells or tissues are injured, the wound must be repaired quickly in order to prevent cell death, loss of tissue integrity, and invasion by microorganisms. We describe Drosophila as a genetically tractable model to dissect the mechanisms of single-cell wound repair. By analyzing the expression and the effects of perturbations of actin, myosin, microtubules, E-cadherin, and the plasma membrane, we define three distinct phases in the repair process—expansion, contraction, and closure—and identify specific components required during each phase. Specifically, plasma membrane mobilization and assembly of a contractile actomyosin ring are required for this process. In addition, E-cadherin accumulates at the wound edge, and wound expansion is excessive in E-cadherin mutants, suggesting a role for E-cadherin in anchoring the actomyosin ring to the plasma membrane. Our results show that single-cell wound repair requires specific spatial and temporal cytoskeleton responses with distinct components and mechanisms required at different stages of the process. PMID:21518790

  8. Therapeutic strategies in multiple sclerosis. II. Long-term repair.

    PubMed Central

    Scolding, N

    1999-01-01

    Spontaneous myelin repair in multiple sclerosis (MS) provides a striking example of the brain's inherent capacity for sustained and stable regenerative tissue repair--but also clearly emphasizes the limitations of this capacity; remyelination ultimately fails widely in many patients, and disability and handicap accumulate. The observation of endogenous partial myelin repair has raised the possibility that therapeutic interventions designed to supplement or promote remyelination might have a useful and significant impact both in the short term, in restoring conduction, and in the long term, in safeguarding axons. Therapeutic remyelination interventions must involve manipulations to either the molecular or the cellular environment within lesions; both depend crucially on a detailed understanding of the biology of the repair process and of those glia implicated in spontaneous repair, or capable of contributing to exogenous repair. Here we explore the biology of myelin repair in MS, examining the glia responsible for successful remyelination, oligodendrocytes and Schwann cells, their 'target' cells, neurons and the roles of astrocytes. Options for therapeutic remyelinating strategies are reviewed, including glial cell transplantation and treatment with growth factors or other soluble molecules. Clinical aspects of remyelination therapies are considered--which patients, which lesions, which stage of the disease, and how to monitor an intervention--and the remaining obstacles and hazards to these approaches are discussed. PMID:10603622

  9. Hydrogels in Spinal Cord Injury Repair Strategies

    PubMed Central

    2011-01-01

    Nowadays there are at present no efficient therapies for spinal cord injury (SCI), and new approaches have to be proposed. Recently, a new regenerative medicine strategy has been suggested using smart biomaterials able to carry and deliver cells and/or drugs in the damaged spinal cord. Among the wide field of emerging materials, research has been focused on hydrogels, three-dimensional polymeric networks able to swell and absorb a large amount of water. The present paper intends to give an overview of a wide range of natural, synthetic, and composite hydrogels with particular efforts for the ones studied in the last five years. Here, different hydrogel applications are underlined, together with their different nature, in order to have a clearer view of what is happening in one of the most sparkling fields of regenerative medicine. PMID:22816020

  10. 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…

  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. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions.

    PubMed

    Callen, Elsa; Di Virgilio, Michela; Kruhlak, Michael J; Nieto-Soler, Maria; Wong, Nancy; Chen, Hua-Tang; Faryabi, Robert B; Polato, Federica; Santos, Margarida; Starnes, Linda M; Wesemann, Duane R; Lee, Ji-Eun; Tubbs, Anthony; Sleckman, Barry P; Daniel, Jeremy A; Ge, Kai; Alt, Frederick W; Fernandez-Capetillo, Oscar; Nussenzweig, Michel C; Nussenzweig, André

    2013-06-06

    The DNA damage response (DDR) protein 53BP1 protects DNA ends from excessive resection in G1, and thereby favors repair by nonhomologous end-joining (NHEJ) as opposed to homologous recombination (HR). During S phase, BRCA1 antagonizes 53BP1 to promote HR. The pro-NHEJ and antirecombinase functions of 53BP1 are mediated in part by RIF1, the only known factor that requires 53BP1 phosphorylation for its recruitment to double-strand breaks (DSBs). Here, we show that a 53BP1 phosphomutant, 53BP18A, comprising alanine substitutions of the eight most N-terminal S/TQ phosphorylation sites, mimics 53BP1 deficiency by restoring genome stability in BRCA1-deficient cells yet behaves like wild-type 53BP1 with respect to immunoglobulin class switch recombination (CSR). 53BP18A recruits RIF1 but fails to recruit the DDR protein PTIP to DSBs, and disruption of PTIP phenocopies 53BP18A. We conclude that 53BP1 promotes productive CSR and suppresses mutagenic DNA repair through distinct phosphodependent interactions with RIF1 and PTIP.

  13. Combined Orbital Fractures: Surgical Strategy of Sequential Repair

    PubMed Central

    Hur, Su Won; Kim, Sung Eun; Chung, Kyu Jin; Lee, Jun Ho; Kim, Tae Gon

    2015-01-01

    Background Reconstruction of combined orbital floor and medial wall fractures with a comminuted inferomedial strut (IMS) is challenging and requires careful practice. We present our surgical strategy and postoperative outcomes. Methods We divided 74 patients who underwent the reconstruction of the orbital floor and medial wall concomitantly into a comminuted IMS group (41 patients) and non-comminuted IMS group (33 patients). In the comminuted IMS group, we first reconstructed the floor stably and then the medial wall by using separate implant pieces. In the non-comminuted IMS group, we reconstructed the floor and the medial wall with a single large implant. Results In the follow-up of 6 to 65 months, most patients with diplopia improved in the first-week except one, who eventually improved at 1 year. All patients with an EOM limitation improved during the first month of follow-up. Enophthalmos (displacement, 2 mm) was observed in two patients. The orbit volume measured on the CT scans was statistically significantly restored in both groups. No complications related to the surgery were observed. Conclusions We recommend the reconstruction of orbit walls in the comminuted IMS group by using the following surgical strategy: usage of multiple pieces of rigid implants instead of one large implant, sequential repair first of the floor and then of the medial wall, and a focus on the reconstruction of key areas. Our strategy of step-by-step reconstruction has the benefits of easy repair, less surgical trauma, and minimal stress to the surgeon. PMID:26217562

  14. 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

  15. Caenorhabditis elegans POLQ-1 and HEL-308 function in two distinct DNA interstrand cross-link repair pathways.

    PubMed

    Muzzini, Diego M; Plevani, Paolo; Boulton, Simon J; Cassata, Giuseppe; Marini, Federica

    2008-06-01

    DNA interstrand cross-links (ICLs) are highly cytotoxic DNA lesions hindering DNA replication and transcription. Whereas in bacteria and yeast the molecular mechanisms involved in ICL repair are genetically well dissected, the scenario in multicellular organisms remains unclear. Here, we report that the two new mus308 genes, polq-1 and hel-308 are involved in ICL repair in Caenorhabditis elegans. After treatment with ICL agents, a decrease in survival and an increase in checkpoint-induced cell-cycle arrest and apoptosis of germ cells is observed in mutants of both genes. Although sensitive to ICL agents and to a minor extent to IR, cytological and epistatic analyses suggest that polq-1 and hel-308 are involved in different DNA repair pathways. While hel-308 functions in a Fanconi anemia-dependent pathway, polq-1 has a role in a novel distinct and brc-1 (CeBRCA1)-dependent ICL repair process in metazoans.

  16. Factors that impact rehabilitation strategies after rotator cuff repair.

    PubMed

    Mulligan, Edward P; Devanna, Raymond R; Huang, Mu; Middleton, Emily F; Khazzam, Michael

    2012-11-01

    Multiple factors influence rehabilitation strategies after rotator cuff repair. These variables may also impact the overall success of the surgical intervention. Physicians and rehabilitation specialists should be aware of prognostic indicators that can provide therapeutic guidance and offer insights into eventual clinical outcomes. The success of surgical and rehabilitative interventions is often evaluated in terms of patient-reported outcome measures, return to activity, and pain. Although these factors are somewhat interdependent, each of them independently influences the final result. This article presents a comprehensive overview of the recent literature in this area to provide insight as to the short- and long-term outcomes that patients should expect based on their unique presentations. This article examines both intrinsic and extrinsic patient factors to help therapists develop customized rehabilitation programs that optimize surgical outcomes.

  17. 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.

  18. 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

  19. Different activation signals induce distinct mast cell degranulation strategies

    PubMed Central

    Sibilano, Riccardo; Marichal, Thomas; Reber, Laurent L.; Cenac, Nicolas; McNeil, Benjamin D.; Dong, Xinzhong; Hernandez, Joseph D.; Sagi-Eisenberg, Ronit; Hammel, Ilan; Roers, Axel; Valitutti, Salvatore; Tsai, Mindy

    2016-01-01

    Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P–dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation. PMID:27643442

  20. 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…

  1. Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq

    SciTech Connect

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; Gaffrey, Matthew J.; Hu, Dehong; Szymanski, Craig J.; Xie, Yumei; Melby, Eric S.; Dohnalkova, Alice; Taylor, Ronald C.; Grate, Eva K.; Cooley, Scott K.; McDermott, Jason E.; Heredia-Langner, Alejandro; Orr, Galya

    2016-11-22

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with upregulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly downregulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong upregulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis and organelle activities. In contrast, strategies unique to carboxylated QDs showed upregulation of DNA repair and RNA activities, and decreased regulation of cell division, coupled in some cases with upregulation of stress responses and ATP related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified, proactive defenses or repairs of the NP insults.

  2. Mass Spectrometry-Based Quantitative Strategies for Assessing the Biological Consequences and Repair of DNA Adducts.

    PubMed

    You, Changjun; Wang, Yinsheng

    2016-02-16

    The genetic integrity of living organisms is constantly threatened by environmental and endogenous sources of DNA damaging agents that can induce a plethora of chemically modified DNA lesions. Unrepaired DNA lesions may elicit cytotoxic and mutagenic effects and contribute to the development of human diseases including cancer and neurodegeneration. Understanding the deleterious outcomes of DNA damage necessitates the investigation about the effects of DNA adducts on the efficiency and fidelity of DNA replication and transcription. Conventional methods for measuring lesion-induced replicative or transcriptional alterations often require time-consuming colony screening and DNA sequencing procedures. Recently, a series of mass spectrometry (MS)-based strategies have been developed in our laboratory as an efficient platform for qualitative and quantitative analyses of the changes in genetic information induced by DNA adducts during DNA replication and transcription. During the past few years, we have successfully used these MS-based methods for assessing the replicative or transcriptional blocking and miscoding properties of more than 30 distinct DNA adducts. When combined with genetic manipulation, these methods have also been successfully employed for revealing the roles of various DNA repair proteins or translesion synthesis DNA polymerases (Pols) in modulating the adverse effects of DNA lesions on transcription or replication in mammalian and bacterial cells. For instance, we found that Escherichia coli Pol IV and its mammalian ortholog (i.e., Pol κ) are required for error-free bypass of N(2)-(1-carboxyethyl)-2'-deoxyguanosine (N(2)-CEdG) in cells. We also found that the N(2)-CEdG lesions strongly inhibit DNA transcription and they are repaired by transcription-coupled nucleotide excision repair in mammalian cells. In this Account, we focus on the development of MS-based approaches for determining the effects of DNA adducts on DNA replication and transcription

  3. 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.

  4. 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

  5. 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…

  6. 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

  7. FANCD2 Binds Human Papillomavirus Genomes and Associates with a Distinct Set of DNA Repair Proteins to Regulate Viral Replication

    PubMed Central

    Spriggs, Chelsey C.

    2017-01-01

    ABSTRACT The life cycle of human papillomavirus (HPV) is dependent on the differentiation state of its host cell. HPV genomes are maintained as low-copy episomes in basal epithelial cells and amplified to thousands of copies per cell in differentiated layers. Replication of high-risk HPVs requires the activation of the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) DNA repair pathways. The Fanconi anemia (FA) pathway is a part of the DNA damage response and mediates cross talk between the ATM and ATR pathways. Our studies show that HPV activates the FA pathway, leading to the accumulation of a key regulatory protein, FANCD2, in large nuclear foci. These HPV-dependent foci colocalize with a distinct population of DNA repair proteins, including ATM components γH2AX and BRCA1, but infrequently with p-SMC1, which is required for viral genome amplification in differentiated cells. Furthermore, FANCD2 is found at viral replication foci, where it is preferentially recruited to viral genomes compared to cellular chromosomes and is required for maintenance of HPV episomes in undifferentiated cells. These findings identify FANCD2 as an important regulator of HPV replication and provide insight into the role of the DNA damage response in the differentiation-dependent life cycle of HPV. PMID:28196964

  8. Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair.

    PubMed

    Chai, Bob; Huang, Jian; Cairns, Bradley R; Laurent, Brehon C

    2005-07-15

    The failure of cells to repair damaged DNA can result in genomic instability and cancer. To efficiently repair chromosomal DNA lesions, the repair machinery must gain access to the damaged DNA in the context of chromatin. Here we report that both the RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes play key roles in double-strand break (DSB) repair, specifically by homologous recombination (HR). RSC and Swi/Snf are each recruited to an in vivo DSB site but with distinct kinetics. We show that Swi/Snf is required earlier, at or preceding the strand invasion step of HR, while RSC is required following synapsis for completion of the recombinational repair event.

  9. Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies As Revealed by Single-Cell RNA-Seq.

    PubMed

    Mitchell, Hugh D; Markillie, Lye Meng; Chrisler, William B; Gaffrey, Matthew J; Hu, Dehong; Szymanski, Craig J; Xie, Yumei; Melby, Eric S; Dohnalkova, Alice; Taylor, Ronald C; Grate, Eva K; Cooley, Scott K; McDermott, Jason E; Heredia-Langner, Alejandro; Orr, Galya

    2016-11-22

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells "overloaded" while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. Here, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.

  10. Cells respond to distinct nanoparticle properties with multiple strategies as revealed by single-cell RNA-Seq

    DOE PAGES

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; ...

    2016-10-27

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. In this paper, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantummore » dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Finally, together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.« less

  11. Cells respond to distinct nanoparticle properties with multiple strategies as revealed by single-cell RNA-Seq

    SciTech Connect

    Mitchell, Hugh D.; Markillie, Lye Meng; Chrisler, William B.; Gaffrey, Matthew J.; Hu, Dehong; Szymanski, Craig J.; Xie, Yumei; Melby, Eric S.; Dohnalkova, Alice; Taylor, Ronald C.; Grate, Eva K.; Cooley, Scott K.; McDermott, Jason E.; Heredia-Langner, Alejandro; Orr, Galya

    2016-10-27

    The impact of distinct nanoparticle (NP) properties on cellular response and ultimately human health is unclear. This gap is partially due to experimental difficulties in achieving uniform NP loads in the studied cells, creating heterogeneous populations with some cells “overloaded” while other cells are loaded with few or no NPs. Yet gene expression studies have been conducted in the population as a whole, identifying generic responses, while missing unique responses due to signal averaging across many cells, each carrying different loads. In this paper, we applied single-cell RNA-Seq to alveolar epithelial cells carrying defined loads of aminated or carboxylated quantum dots (QDs), showing higher or lower toxicity, respectively. Interestingly, cells carrying lower loads responded with multiple strategies, mostly with up-regulated processes, which were nonetheless coherent and unique to each QD type. In contrast, cells carrying higher loads responded more uniformly, with mostly down-regulated processes that were shared across QD types. Strategies unique to aminated QDs showed strong up-regulation of stress responses, coupled in some cases with regulation of cell cycle, protein synthesis, and organelle activities. In contrast, strategies unique to carboxylated QDs showed up-regulation of DNA repair and RNA activities and decreased regulation of cell division, coupled in some cases with up-regulation of stress responses and ATP-related functions. Finally, together, our studies suggest scenarios where higher NP loads lock cells into uniform responses, mostly shutdown of cellular processes, whereas lower loads allow for unique responses to each NP type that are more diversified proactive defenses or repairs of the NP insults.

  12. 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...

  13. 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…

  14. Enhancing digital driver models: identification of distinct postural strategies used by drivers.

    PubMed

    Kyung, Gyouhyung; Nussbaum, Maury A; Babski-Reeves, Kari L

    2010-03-01

    Driver workspace design and evaluation is, in part, based on assumed driving postures of users and determines several ergonomic aspects of a vehicle, such as reach, visibility and postural comfort. Accurately predicting and specifying standard driving postures, hence, are necessary to improve the ergonomic quality of the driver workspace. In this study, a statistical clustering approach was employed to reduce driving posture simulation/prediction errors, assuming that drivers use several distinct postural strategies when interacting with automobiles. 2-D driving postures, described by 16 joint angles, were obtained from 38 participants with diverse demographics (age, gender) and anthropometrics (stature, body mass) and in two vehicle classes (sedans and SUVs). Based on the proximity of joint angle sets, cluster analysis yielded three predominant postural strategies in each vehicle class (i.e. 'lower limb flexed', 'upper limb flexed' and 'extended'). Mean angular differences between clusters ranged from 3.8 to 52.4 degrees for the majority of joints, supporting the practical relevance of the distinct clusters. The existence of such postural strategies should be considered when utilising digital human models (DHMs) to enhance and evaluate driver workspace design ergonomically and proactively. STATEMENT OF RELEVANCE: This study identified drivers' distinct postural strategies, based on actual drivers' behaviours. Such strategies can facilitate accurate positioning of DHMs and hence help design ergonomic driver workspaces.

  15. 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

  16. 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

  17. 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

  18. Strategies to improve regeneration of the soft palate muscles after cleft palate repair.

    PubMed

    Carvajal Monroy, Paola L; Grefte, Sander; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A D T G; Von den Hoff, Johannes W

    2012-12-01

    Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. These patients are unable to separate the nasal from the oral cavity leading to air loss during speech. Although surgical repair ameliorates soft palate function by joining the clefted muscles of the soft palate, optimal function is often not achieved. The regeneration of muscles in the soft palate after surgery is hampered because of (1) their low intrinsic regenerative capacity, (2) the muscle properties related to clefting, and (3) the development of fibrosis. Adjuvant strategies based on tissue engineering may improve the outcome after surgery by approaching these specific issues. Therefore, this review will discuss myogenesis in the noncleft and cleft palate, the characteristics of soft palate muscles, and the process of muscle regeneration. Finally, novel therapeutic strategies based on tissue engineering to improve soft palate function after surgical repair are presented.

  19. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

    PubMed Central

    Agarwal, Rachit; García, Andrés J.

    2015-01-01

    Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

  20. Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair.

    PubMed

    Agarwal, Rachit; García, Andrés J

    2015-11-01

    Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair.

  1. 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…

  2. 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.

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

    PubMed Central

    Garash, Reham; Bajpai, Anamika; Marcinkiewicz, Brandon M

    2016-01-01

    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

  4. Distinct Functions of Human Cohesin-SA1 and Cohesin-SA2 in Double-Strand Break Repair

    PubMed Central

    Kong, Xiangduo; Ball, Alexander R.; Pham, Hoang Xuan; Zeng, Weihua; Chen, Hsiao-Yuan; Schmiesing, John A.; Kim, Jong-Soo; Berns, Michael

    2014-01-01

    Cohesin is an essential multiprotein complex that mediates sister chromatid cohesion critical for proper segregation of chromosomes during cell division. Cohesin is also involved in DNA double-strand break (DSB) repair. In mammalian cells, cohesin is involved in both DSB repair and the damage checkpoint response, although the relationship between these two functions is unclear. Two cohesins differing by one subunit (SA1 or SA2) are present in somatic cells, but their functional specificities with regard to DNA repair remain enigmatic. We found that cohesin-SA2 is the main complex corecruited with the cohesin-loading factor NIPBL to DNA damage sites in an S/G2-phase-specific manner. Replacing the diverged C-terminal region of SA1 with the corresponding region of SA2 confers this activity on SA1. Depletion of SA2 but not SA1 decreased sister chromatid homologous recombination repair and affected repair pathway choice, indicating that DNA repair activity is specifically associated with cohesin recruited to damage sites. In contrast, both cohesin complexes function in the intra-S checkpoint, indicating that cell cycle-specific damage site accumulation is not a prerequisite for cohesin's intra-S checkpoint function. Our findings reveal the unique ways in which cohesin-SA1 and cohesin-SA2 participate in the DNA damage response, coordinately protecting genome integrity in human cells. PMID:24324008

  5. The Treatment Efficacy of Bone Tissue Engineering Strategy for Repairing Segmental Bone Defects Under Osteoporotic Conditions.

    PubMed

    Wang, Zhen Xing; Chen, Cheng; Zhou, Quan; Wang, Xian Song; Zhou, Guangdong; Liu, Wei; Zhang, Zhi-Yong; Cao, Yilin; Zhang, Wen Jie

    2015-09-01

    The potential of increasing bone mass and preventing fractures in osteoporosis using stem cell therapy is currently an area of intense focus. However, there are very little data available regarding the postfracture bony defect healing efficacy under osteoporotic conditions. This study aims to investigate whether critical-sized segmental bone defects in a rabbit model of osteoporosis could be repaired using an allogenic stem cell-based tissue engineering (TE) approach and to investigate the potential influence of osteoporosis on the treatment efficacy. Rabbit fetal bone marrow mesenchymal stem cells (BMSCs) were harvested and expanded in vitro. Decalcified bone matrix (DBM) scaffolds were then seeded with allogenic fetal BMSCs and cultivated in osteogenic media to engineer BMSC/DBM constructs. Critical-sized radial defects were created in ovariectomized (OVX) rabbits and the defects were repaired either by insertion of BMSC/DBM constructs or by DBM scaffolds alone. Also, nonovariectomized age-matched (non-OVX) rabbits were served as control. At 3 months post-treatment under the osteoporotic condition (OVX rabbits), the BMSC/DBM constructs inserted within the defect generated significantly more bone tissue when compared to the DBM scaffold as demonstrated by the X-ray, microcomputed tomography, and histological analyses. In addition, when compared to a normal nonosteoporotic condition (age-matched non-OVX rabbits), the defect treatment efficacy was adversely affected by the osteoporotic condition with significantly less bone regeneration. This study demonstrated the potential of allogenic fetal BMSC-based TE strategy for repairing bone defects in an osteoporotic condition. However, the treatment efficacy could be considerably compromised in the OVX animals. Therefore, a more sophisticated strategy that addresses the complicated pathogenic conditions associated with osteoporosis is needed.

  6. Shape "break-and-repair" strategy and its application to automated medical image segmentation.

    PubMed

    Pu, Jiantao; Paik, David S; Meng, Xin; Roos, Justus E; Rubin, Geoffrey D

    2011-01-01

    In three-dimensional medical imaging, segmentation of specific anatomy structure is often a preprocessing step for computer-aided detection/diagnosis (CAD) purposes, and its performance has a significant impact on diagnosis of diseases as well as objective quantitative assessment of therapeutic efficacy. However, the existence of various diseases, image noise or artifacts, and individual anatomical variety generally impose a challenge for accurate segmentation of specific structures. To address these problems, a shape analysis strategy termed "break-and-repair" is presented in this study to facilitate automated medical image segmentation. Similar to surface approximation using a limited number of control points, the basic idea is to remove problematic regions and then estimate a smooth and complete surface shape by representing the remaining regions with high fidelity as an implicit function. The innovation of this shape analysis strategy is the capability of solving challenging medical image segmentation problems in a unified framework, regardless of the variability of anatomical structures in question. In our implementation, principal curvature analysis is used to identify and remove the problematic regions and radial basis function (RBF) based implicit surface fitting is used to achieve a closed (or complete) surface boundary. The feasibility and performance of this strategy are demonstrated by applying it to automated segmentation of two completely different anatomical structures depicted on CT examinations, namely human lungs and pulmonary nodules. Our quantitative experiments on a large number of clinical CT examinations collected from different sources demonstrate the accuracy, robustness, and generality of the shape "break-and-repair" strategy in medical image segmentation.

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

    PubMed Central

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

    2016-01-01

    Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress. PMID:27991914

  8. Special issues in brain plasticity, repair and rehabilitation: 20 years of a publishing strategy.

    PubMed

    Sabel, B A; Matzke, S; Prilloff, S

    2010-01-01

    The journal Restorative Neurology and Neuroscience (RNN) is focused on the emerging field of brain plasticity, repair and rehabilitation, including original and review papers both in basic research (in vitro studies, animal experiments) and in the clinical domain, including brain imaging studies. The publication of special issues on vital topics, summarizing the work of leading experts in the field of restoration and plasticity has become a major strategy of RNN and has attracted worldwide attention. Special issues are typically organized by specialized guest-editors familiar with the respective science field. Special issues cover a particular sub-discipline and often contain laboratory review papers. The first special issue appeared in 1990, and until today RNN has published a total of 25 special issues on a variety of basic science and clinical matters. In this way, RNN promotes the dissemination of information in the field of neuroplasticity, repair and rehabilitation, providing the reader with up-to-date information prepared by leading experts in the field.

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    Leininger, Elizabeth C; Kelley, Darcy B

    2013-04-07

    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.

  13. 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.

  14. Mismatch repair protein immunohistochemistry: a useful population screening strategy for Lynch syndrome.

    PubMed

    Musulén, Eva; Sanz, Carolina; Muñoz-Mármol, Ana María; Ariza, Aurelio

    2014-07-01

    Lynch syndrome (LS), the most frequent form of hereditary colorectal cancer, shows a highly penetrant, autosomal dominant pattern of inheritance. Distinction of LS colorectal carcinoma instances from the much more common sporadic colorectal carcinoma cases is of paramount importance. Revised Bethesda Guidelines were developed to diagnose LS by evaluating a combination of clinical and pathologic data. The aim of the present study was to evaluate the usefulness of the pathology items included in the Revised Bethesda Guidelines. We have prospectively studied a series of 1624 consecutive colorectal carcinomas with an algorithm including immunohistochemical analysis of mismatch repair proteins and molecular study of microsatellite instability and BRAF c.1799 T > A (p.V600E) gene mutations. Patients with tumors showing LS features were referred for germline mutation analysis. By applying our algorithmic approach, we were able to identify LS features in 89 colorectal cancer patients, of whom only 27 met Revised Bethesda Guidelines pathology criteria. Of the 89 patients, 47 were then studied at the Genetic Counseling Unit, and LS was confirmed in 18, of whom 7 had not been identified by the Revised Bethesda Guidelines. Our study shows that the Revised Bethesda Guidelines failed to detect 70% of patients at risk of LS. Our algorithmic approach is a realistic and effective tool for LS identification. We strongly recommend the implementation of universal population screening for LS among all patients with newly diagnosed colorectal carcinoma.

  15. 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…

  16. Regulation of base excision repair in eukaryotes by dynamic localization strategies.

    PubMed

    Swartzlander, Daniel B; Bauer, Nicholas C; Corbett, Anita H; Doetsch, Paul W

    2012-01-01

    This chapter discusses base excision repair (BER) and the known mechanisms defined thus far regulating BER in eukaryotes. Unlike the situation with nucleotide excision repair and double-strand break repair, little is known about how BER is regulated to allow for efficient and accurate repair of many types of DNA base damage in both nuclear and mitochondrial genomes. Regulation of BER has been proposed to occur at multiple, different levels including transcription, posttranslational modification, protein-protein interactions, and protein localization; however, none of these regulatory mechanisms characterized thus far affect a large spectrum of BER proteins. This chapter discusses a recently discovered mode of BER regulation defined in budding yeast cells that involves mobilization of DNA repair proteins to DNA-containing organelles in response to genotoxic stress.

  17. 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.

  18. 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...

  19. Strategies for coping with work-family conflict: the distinctive relationships of gender role ideology.

    PubMed

    Somech, Anit; Drach-Zahavy, Anat

    2007-01-01

    Study 1, with 266 employed parents, identified 8 coping strategies: super at home, good enough at home, delegation at home, priorities at home, super at work, good enough at work, delegation at work, and priorities at work. Study 2, with 679 employed parents, demonstrated a moderating effect of sex and gender role ideology in the relationship between coping strategy and work-family conflict. Specifically, the relationships between coping strategies (i.e., good enough at home, good enough at work, and delegation at work) and work interference with family were moderated by sex and gender role ideology. Regarding family interference with work, the relationships between coping strategies (i.e., good enough at home and good enough at work, delegation at home and delegation at work, and priorities at home) and family interference with work were moderated by sex and gender role ideology.

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

    PubMed Central

    Purcell, Braden A.; Kiani, Roozbeh

    2016-01-01

    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

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

    PubMed

    Purcell, Braden A; Kiani, Roozbeh

    2016-08-02

    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.

  2. 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

  3. 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…

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

    ERIC Educational Resources Information Center

    Dincer, Baris; Erbas, Dilek

    2010-01-01

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

  5. Ada response - a strategy for repair of alkylated DNA in bacteria.

    PubMed

    Mielecki, Damian; Grzesiuk, Elżbieta

    2014-06-01

    Alkylating agents are widespread in the environment and also occur endogenously. They can be cytotoxic or mutagenic to the cells introducing alkylated bases to DNA or RNA. All organisms have evolved multiple DNA repair mechanisms to counteract the effects of DNA alkylation: the most cytotoxic lesion, N(3)-methyladenine (3meA), is excised by AlkA glycosylase initiating base excision repair (BER); toxic N(1)-methyladenine (1meA) and N(3)-methylcytosine (3meC), induced in DNA and RNA, are removed by AlkB dioxygenase; and mutagenic and cytotoxic O(6)-methylguanine (O(6) meG) is repaired by Ada methyltransferase. In Escherichia coli, Ada response involves the expression of four genes, ada, alkA, alkB, and aidB, encoding respective proteins Ada, AlkA, AlkB, and AidB. The Ada response is conserved among many bacterial species; however, it can be organized differently, with diverse substrate specificity of the particular proteins. Here, an overview of the organization of the Ada regulon and function of individual proteins is presented. We put special effort into the characterization of AlkB dioxygenases, their substrate specificity, and function in the repair of alkylation lesions in DNA/RNA.

  6. 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;…

  7. 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;…

  8. 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;…

  9. Distinct Growth Strategies of Soil Bacteria as Revealed by Large-Scale Colony Tracking

    PubMed Central

    Ernebjerg, Morten

    2012-01-01

    Our understanding of microbial ecology has been significantly furthered in recent years by advances in sequencing techniques, but comprehensive surveys of the phenotypic characteristics of environmental bacteria remain rare. Such phenotypic data are crucial for understanding the microbial strategies for growth and the diversity of microbial ecosystems. Here, we describe a high-throughput measurement of the growth of thousands of bacterial colonies using an array of flat-bed scanners coupled with automated image analysis. We used this system to investigate the growth properties of members of a microbial community from untreated soil. The system provides high-quality measurements of the number of CFU, colony growth rates, and appearance times, allowing us to directly study the distribution of these properties in mixed environmental samples. We find that soil bacteria display a wide range of growth strategies which can be grouped into several clusters that cannot be reduced to any of the classical dichotomous divisions of soil bacteria, e.g., into copiotophs and oligotrophs. We also find that, at early times, cells are most likely to form colonies when other, nearby colonies are present but not too dense. This maximization of culturability at intermediate plating densities suggests that the previously observed tendency for high density to lead to fewer colonies is partly offset by the induction of colony formation caused by interactions between microbes. These results suggest new types of growth classification of soil bacteria and potential effects of species interactions on colony growth. PMID:22194284

  10. 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.

  11. 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.

  12. Treatment strategy for treating atrial-esophageal fistula: esophageal stenting or surgical repair?

    PubMed Central

    Zhou, Bing; Cen, Xue-Jiang; Qian, Lin-Yan; Pang, Jie; Zou, Hai; Ding, Ya-Hui

    2016-01-01

    Abstract Introduction: Atrial-esophageal fistula (AEF) is a rare severe disease, which may be associated with radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) or intraoperative radiofrequency ablation of atrial fibrillation (IRAAF). Clinical Findings: We reported a case of a 67-year-old man with AEF following RFCA of AF, who treated with esophageal stenting and surgical repair. Outcomes: He was attacked by out-of-control sepsis and infectious shock after surgery and died. Literature review: We analyzed 57 relevant articles about AEF from 2003 to 2015 by searching PubMed database. According literatures, the most common symptoms were fever, rigor, sepsis, and neurologic symptoms. Chest computer tomography (CT) and contrast enhanced CT may be the reliable noninvasive diagnosis methods because of high sensitive for AEF. Conclusion: Make a definition diagnosis in time with early primary surgical repair may save their lives. Conservative treatment or esophageal stenting alone may not be a better choice for AEF patients. PMID:27787367

  13. Linking immune patterns and life history shows two distinct defense strategies in land snails (gastropoda, pulmonata).

    PubMed

    Russo, Jacqueline; Madec, Luc

    2013-01-01

    Life history integration of the defense response was investigated at intra- and interspecific levels in land snails of the family Helicidae. Two hypotheses were tested: (i) fitness consequences of defense responses are closely related to life history traits such as size at maturity and life span; (ii) different pathways of the immune response based on "nonspecific" versus "specific" responses may reflect different defense options. Relevant immune responses to a challenge with E. coli were measured using the following variables: blood cell density, cellular or plasma antibacterial activity via reactive oxygen species (ROS) level, and bacterial growth inhibition. The results revealed that the largest snails did not exhibit the strongest immune response. Instead, body mass influenced the type of response in determining the appropriate strategy. Snails with a higher body mass at maturity had more robust plasma immune responses than snails with a lower mass, which had greater cell-mediated immune responses with a higher hemocyte density. In addition, ROS appeared also to be a stress mediator as attested by differences between sites and generations for the same species.

  14. 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.

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

    PubMed

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

    2014-07-01

    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

  16. 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.

  17. 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

  18. Reappraisal and Distraction Emotion Regulation Strategies Are Associated with Distinct Patterns of Visual Attention and Differing Levels of Cognitive Demand

    PubMed Central

    Strauss, Gregory P.; Ossenfort, Kathryn L.; Whearty, Kayla M.

    2016-01-01

    Multiple emotion regulation strategies have been identified and found to differ in their effectiveness at decreasing negative emotions. One reason for this might be that individual strategies are associated with differing levels of cognitive demand and require distinct patterns of visual attention to achieve their effects. In the current study, we tested this hypothesis in a sample of psychiatrically healthy participants (n = 25) who attempted to down-regulate negative emotion to photographs from the International Affective Picture System using cognitive reappraisal or distraction. Eye movements, pupil dilation, and subjective reports of negative emotionality were obtained for reappraisal, distraction, unpleasant passive viewing, and neutral passive viewing conditions. Behavioral results indicated that reappraisal and distraction successfully decreased self-reported negative affect relative to unpleasant passive viewing. Successful down regulation of negative affect was associated with different patterns of visual attention across regulation strategies. During reappraisal, there was an initial increase in dwell time to arousing scene regions and a subsequent shift away from these regions during later portions of the trial, whereas distraction was associated with reduced total dwell time to arousing interest areas throughout the entire stimulus presentation. Pupil dilation was greater for reappraisal than distraction or unpleasant passive viewing, suggesting that reappraisal may recruit more effortful cognitive control processes. Furthermore, greater decreases in self-reported negative emotion were associated with a lower proportion of dwell time within arousing areas of interest. These findings suggest that different emotion regulation strategies necessitate different patterns of visual attention to be effective and that individual differences in visual attention predict the extent to which individuals can successfully decrease negative emotion using reappraisal

  19. 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.

  20. Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination: homologous recombination tolerates replicative stress by Mrc1-regulated replication and repair activities operating at S and G2 in distinct subnuclear compartments.

    PubMed

    Prado, Félix

    2014-05-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability.

  1. Synergistic killing of Escherichia coli by near-UV radiation and hydrogen peroxide: distinction between recA-repairable and recA-nonrepairable damage.

    PubMed Central

    Hartman, P S; Eisenstark, A

    1978-01-01

    Wild-type cells and six DNA repair-deficient mutants (lexA, recA, recB, recA, recB, polA1, and uvrA) of Escherichia coli K-12 were treated with near-ultraviolet radiation plus hydrogen peroxide (H2O2). At low H2O2 concentrations (6 X 10(-6) to 6 X 10(-4) M), synergistic killing occurred in all strains except those containing a mutation in recA. This RecA-repairable damage was absent from stationary-phase cells but increased in logarithmic cells as a function of growth rate. At higher H2O2 concentrations (above 6 X 10(-4) M) plus near-ultraviolet radiation, all strains, including those with a mutation in recA, were synergistically killed; thus, at high H2O2 concentrations, the damage was not RecA repairable. PMID:342508

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

    PubMed

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

    2016-05-01

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

  3. Informing future cartilage repair strategies: a comparative study of three different human cell types for cartilage tissue engineering.

    PubMed

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin B

    2013-06-01

    A major clinical need exists for cartilage repair and regeneration. Despite many different strategies having been pursued, the identification of an optimised cell type and of pre-treatment conditions remains a challenge. This study compares the cartilage-like tissue generated by human bone marrow stromal cells (HBMSCs) and human neonatal and adult chondrocytes cultured on three-dimensional (3D) scaffolds under various conditions in vitro and in vivo with the aim of informing future cartilage repair strategies based upon tissue-engineering approaches. After 3 weeks in vitro culture, all three cell types showed cartilage-like tissue formation on 3D poly (lactide-co-glycolide) acid scaffolds only when cultured in chondrogenic medium. After 6 weeks of chondro-induction, neonatal chondrocyte constructs revealed the most cartilage-like tissue formation with a prominent superficial zone-like layer, a middle zone-like structure and the thinnest fibrous capsule. HBMSC constructs had the thickest fibrous capsule formation. Under basal culture conditions, neonatal articular chondrocytes failed to form any tissue, whereas HBMSCs and adult chondrocytes showed thick fibrous capsule formation at 6 weeks. After in vivo implantation, all groups generated more compact tissues compared with in vitro constructs. Pre-culturing in chondrogenic media for 1 week before implantation reduced fibrous tissue formation in all cell constructs at week 3. After 6 weeks, only the adult chondrocyte group pre-cultured in chondrogenic media was able to maintain a more chondrogenic/less fibrocartilaginous phenotype. Thus, pre-culture under chondrogenic conditions is required to maintain a long-term chondrogenic phenotype, with adult chondrocytes being a more promising cell source than HBMSCs for articular cartilage tissue engineering.

  4. Efficacy of Schwann cell transplantation for spinal cord repair is improved with combinatorial strategies.

    PubMed

    Bunge, Mary Bartlett

    2016-07-01

    When cells (including Schwann cells; SCs) of the peripheral nervous system (PNS) could be purified and expanded in number in tissue culture, Richard Bunge in 1975 envisioned that the SCs could be introduced to repair the central nervous system (CNS), as SCs enable axons to regenerate after PNS injury. Importantly, autologous human SCs could be transplanted into injured human spinal cord. Availability of the new culture systems to study interactions between sensory neurons, SCs and fibroblasts increased our knowledge of SC biology in the 1970s and '80s. Joining the Miami Project to Cure Paralysis in 1989 brought the opportunity to use this knowledge to initiate spinal cord repair studies. Development of a rat complete spinal cord transection/SC bridge model allowed the demonstration that axons regenerate into the SC bridge. Together with study of contused rat spinal cord, it was concluded that implanted SCs reduce cavitation, protect tissue around the lesion, support axon regeneration and form myelin. SC transplantation efficacy was improved when combined with neurotrophins, elevation of cyclic AMP levels, olfactory ensheathing cells, a steroid or chondroitinase. Increased efficacy meant higher numbers of axons, particularly from the brainstem, and more SC-myelinated axons in the implants and improvement in hindlimb movements. Human SCs support axon regeneration as do rat SCs. Astrocytes at the SC bridge-host spinal cord interfaces play a key role in determining whether axons enter the SC milieu. The SC work described here contributed to gaining approval from the FDA for an initial autologous human SC clinical trial (at the Miami Project) that has been completed and found to be safe.

  5. Social Stress Engages Neurochemically-Distinct Afferents to the Rat Locus Coeruleus Depending on Coping Strategy123

    PubMed Central

    Reyes, Beverly A. S.; Zitnik, Gerard; Foster, Celia; Van Bockstaele, Elisabeth J.

    2015-01-01

    Abstract Stress increases vulnerability to psychiatric disorders, partly by affecting brain monoamine systems, such as the locus coeruleus (LC)-norepinephrine system. During stress, LC activity is coregulated by corticotropin-releasing factor (CRF) and endogenous opioids. This study identified neural circuitry that regulates LC activity of intruder rats during the resident–intruder model of social stress. LC afferents were retrogradely labeled with Fluorogold (FG) and rats were subjected to one or five daily exposures to an aggressive resident. Sections through the nucleus paragigantocellularis (PGi) and central amygdalar nucleus (CNA), major sources of enkephalin (ENK) and CRF LC afferents, respectively, were immunocytochemically processed to detect c-fos, FG, and CRF or ENK. In response to a single exposure, intruder rats assumed defeat with a relatively short latency (SL). LC neurons, PGI-ENK LC afferents, and CNA-CRF LC afferents were activated in these rats as indicated by increased c-fos expression. With repeated stress, rats exhibited either a SL or long latency (LL) to defeat and these strategies were associated with distinct patterns of neuronal activation. In SL rats, LC neurons were activated, as were CNA-CRF LC afferents but not PGI-ENK LC afferents. LL rats had an opposite pattern, maintaining activation of PGi-ENK LC afferents but not CNA-CRF LC afferents or LC neurons. Together, these results indicate that the establishment of different coping strategies to social stress is associated with changes in the circuitry that regulates activity of the brain norepinephrine system. This may underlie differential vulnerability to the consequences of social stress that characterize these different coping strategies. PMID:26634226

  6. 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.

  7. 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.

  8. Meningocele repair

    MedlinePlus

    ... Myelodysplasia repair; Spinal dysraphism repair; Meningomyelocele repair; Neural tube defect repair; Spina bifida repair ... If your child has hydrocephalus, a shunt (plastic tube) will be put in the child's brain to ...

  9. Distinct roles of Ape1 protein, an enzyme involved in DNA repair, in high or low linear energy transfer ionizing radiation-induced cell killing.

    PubMed

    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

    2014-10-31

    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.

  10. Repair, Replace or Throw Away: Linking Sustainment Strategies to Data Requirements

    DTIC Science & Technology

    2015-02-01

    All information required for Options 1 and 2 • “Form, fit and function” ( FFF ) data (including perfor- mance specifications) for the internal parts of...government would require FFF data for each LRU as well as FFF data concerning the interface between each LRU and the rest of the vehicle. Under...the vehicle in the request for proposal (RFP) and require delivery of FFF data (ICDs) for each LRU. • Usefulness of this strategy also will depend on

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

    PubMed

    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

    2014-02-18

    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.

  12. Evidence that the Nijmegen breakage syndrome protein, an early sensor of double-strand DNA breaks (DSB), is involved in HIV-1 post-integration repair by recruiting the ataxia telangiectasia-mutated kinase in a process similar to, but distinct from, cellular DSB repair.

    PubMed

    Smith, Johanna A; Wang, Feng-Xiang; Zhang, Hui; Wu, Kou-Juey; Williams, Kevin Jon; Daniel, René

    2008-01-22

    Retroviral transduction involves integrase-dependent linkage of viral and host DNA that leaves an intermediate that requires post-integration repair (PIR). We and others proposed that PIR hijacks the host cell double-strand DNA break (DSB) repair pathways. Nevertheless, the geometry of retroviral DNA integration differs considerably from that of DSB repair and so the precise role of host-cell mechanisms in PIR remains unclear. In the current study, we found that the Nijmegen breakage syndrome 1 protein (NBS1), an early sensor of DSBs, associates with HIV-1 DNA, recruits the ataxia telangiectasia-mutated (ATM) kinase, promotes stable retroviral transduction, mediates efficient integration of viral DNA and blocks integrase-dependent apoptosis that can arise from unrepaired viral-host DNA linkages. Moreover, we demonstrate that the ATM kinase, recruited by NBS1, is itself required for efficient retroviral transduction. Surprisingly, recruitment of the ATR kinase, which in the context of DSB requires both NBS1 and ATM, proceeds independently of these two proteins. A model is proposed emphasizing similarities and differences between PIR and DSB repair. Differences between the pathways may eventually allow strategies to block PIR while still allowing DSB repair.

  13. Strategies to Minimize Adhesions to Intraperitoneally Placed Mesh in Laparoscopic Ventral Hernia Repair

    PubMed Central

    Saliba, Lucia; Chandratnam, Edward; Turingan, Isidro; Hawthorne, Wayne

    2012-01-01

    Introduction: Adhesions to mesh/tacks in laparoscopic ventral hernia repair are often cited as reasons not to adopt its evidence-based superiority over conventional open methods. This pilot study assessed the occurrence of adhesions to full-sized Polypropylene and Gore-tex DualMesh Plus meshes and the possibility for adhesion prevention using fibrin sealant. Methods: Two 10-cm to 15-cm pieces of mesh were placed and fixed laparoscopically in pigs (25kg to 55kg). Group I: 2 animals with Polypropylene mesh on one side and DualMesh on other side. Group II: 2 animals with DualMesh on each side with fibrin sealant applied to the periphery of mesh and staples to one side. Group III: 1 animal with 2 pieces of Polypropylene mesh with fibrin sealant applied to the entire mesh. All animals underwent laparoscopy 3 months later to assess the extent of adhesions, and full-thickness specimens were removed for histological evaluation. Results: More Polypropylene mesh was involved in adhesions than DualMesh. However, with the DualMesh involved in adhesions, more of the surface area was involved in forming adhesions than with Polypropylene mesh. None of the implanted DualMesh had visceral adhesions, while 2 out of 3 Polypropylene meshes had adhesions to both the liver and spleen but none to the bowel. Implanted Polypropylene mesh with fibrin sealant had no adhesions. DualMesh had shrunk more significantly than Polypropylene mesh. Histological evaluation showed absence of acute inflammatory response, significantly more chronic inflammatory response to DualMesh compared to Polypropylene and complete mesothelialization with both meshes. There was extensive collagen deposition between Polypropylene mesh fibers, while fibrosis occurred on both sides of DualMesh with synovial metaplasia over its peritoneal surface akin to encapsulation. Conclusions: DualMesh caused fewer omental and visceral adhesions than Polypropylene mesh did. Fibrin sealant eliminated adhesions to DualMesh and

  14. 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

  15. 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.

  16. 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.

  17. Strategies for psbA gene expression in cyanobacteria, green algae and higher plants: from transcription to PSII repair.

    PubMed

    Mulo, Paula; Sakurai, Isamu; Aro, Eva-Mari

    2012-01-01

    The Photosystem (PS) II of cyanobacteria, green algae and higher plants is prone to light-induced inactivation, the D1 protein being the primary target of such damage. As a consequence, the D1 protein, encoded by the psbA gene, is degraded and re-synthesized in a multistep process called PSII repair cycle. In cyanobacteria, a small gene family codes for the various, functionally distinct D1 isoforms. In these organisms, the regulation of the psbA gene expression occurs mainly at the level of transcription, but the expression is fine-tuned by regulation of translation elongation. In plants and green algae, the D1 protein is encoded by a single psbA gene located in the chloroplast genome. In chloroplasts of Chlamydomonas reinhardtii the psbA gene expression is strongly regulated by mRNA processing, and particularly at the level of translation initiation. In chloroplasts of higher plants, translation elongation is the prevalent mechanism for regulation of the psbA gene expression. The pre-existing pool of psbA transcripts forms translation initiation complexes in plant chloroplasts even in darkness, while the D1 synthesis can be completed only in the light. Replacement of damaged D1 protein requires also the assistance by a number of auxiliary proteins, which are encoded by the nuclear genome in green algae and higher plants. Nevertheless, many of these chaperones are conserved between prokaryotes and eukaryotes. Here, we describe the specific features and fundamental differences of the psbA gene expression and the regeneration of the PSII reaction center protein D1 in cyanobacteria, green algae and higher plants. This article is part of a Special Issue entitled Photosystem II.

  18. 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.

  19. 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.

  20. Defining the acute kidney injury and repair transcriptome.

    PubMed

    Kumar, Sanjeev; Liu, Jing; McMahon, Andrew P

    2014-07-01

    The mammalian kidney has an intrinsic ability to repair after significant injury. However, this process is inefficient: patients are at high risk for the loss of kidney function in later life. No therapy exists to treat established acute kidney injury (AKI) per se: strategies to promote endogenous repair processes and retard associated fibrosis are a high priority. Whole-organ gene expression profiling has been used to identify repair responses initiated with AKI, and factors that may promote the transition from AKI to chronic kidney disease. Transcriptional profiling has shown molecular markers and potential regulatory pathways of renal repair. Activation of a few key developmental pathways has been reported during repair. Whether these are comparable networks with similar target genes with those in earlier nephrogenesis remains unclear. Altered microRNA profiles, persistent tubular injury responses, and distinct late inflammatory responses highlight continuing kidney pathology. Additional insights into injury and repair processes will be gained by study of the repair transcriptome and cell-specific translatome using high-resolution technologies such as RNA sequencing and translational profiling tailored to specific cellular compartments within the kidney. An enhanced understanding holds promise for both the identification of novel therapeutic targets and biomarker-based evaluation of the damage-repair process.

  1. 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.

  2. Distinct Molecular Strategies for Hox-Mediated Limb Suppression in Drosophila: From Cooperativity to Dispensability/Antagonism in TALE Partnership

    PubMed Central

    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. PMID:23505377

  3. Differences in potential for amino acid change after mutation reveals distinct strategies for kappa and lambda light-chain variation.

    PubMed

    Hershberg, Uri; Shlomchik, Mark J

    2006-10-24

    B cells generate varied yet functional clones under high rates of mutation of their V genes. It has been proposed that as a result of the opposing demands of diversification and preservation of integrity, the V genes of heavy and light chains have evolved to overexpress codons prone to amino acid change in their complementarity determining regions (CDR) compared with the framework (FW) regions. We have analyzed the germ-line V genes of heavy and light chains (both kappa and lambda), comparing codons of CDR and FW of the germ-line V regions both to each other and to control regions. We found that in both germ-line heavy chains and lambda chains, CDR codons are prone to replacement mutations, whereas in the FW, the opposite is true. Furthermore, the difference between CDR and FW in heavy chains and lambda chains is based on codons that are prone to nonconservative changes of amino acid. In contrast, in germ-line kappa chains, the codons in both CDR and FW are more prone to replacement mutations. We also demonstrated that negative selection during immune responses is more sensitive to nonconservative amino acid substitutions than overall amino acid change, demonstrating the applicability of our analysis to real-time process of selection in the immune system. The differences in germ-line kappa and lambda light chains' potential reaction to mutation suggests that via these two differently evolved light-chain types, the B cell repertoire encompasses two different strategies to balance diversity and stability in an immune response.

  4. 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

  5. Titers of lentiviral vectors encoding shRNAs and miRNAs are reduced by different mechanisms that require distinct repair strategies.

    PubMed

    Liu, Ying Poi; Vink, Monique A; Westerink, Jan-Tinus; Ramirez de Arellano, Eva; Konstantinova, Pavlina; Ter Brake, Olivier; Berkhout, Ben

    2010-07-01

    RNAi-based gene therapy is a powerful approach to treat viral infections because of its high efficiency and sequence specificity. The HIV-1-based lentiviral vector system is suitable for the delivery of RNAi inducers to HIV-1 susceptible cells due to its ability to transduce nondividing cells, including hematopoietic stem cells, and its ability for stable transgene delivery into the host cell genome. However, the presence of anti-HIV short hairpin RNA (shRNA) and microRNA (miRNA) cassettes can negatively affect the lentiviral vector titers. We show that shRNAs, which target the vector genomic RNA, strongly reduced lentiviral vector titers but inhibition of the RNAi pathway via saturation could rescue vector production. The presence of miRNAs in the vector RNA genome (sense orientation) results in a minor titer reduction due to Drosha processing. A major cause for titer reduction of miRNA vectors is due to incompatibility of the cytomegalovirus promoter with the lentiviral vector system. Replacement of this promoter with an inducible promoter resulted in an almost complete restoration of the vector titer. We also showed that antisense poly(A) signal sequences can have a dramatic effect on the vector titer. These results show that not all sequences are compatible with the lentiviral vector system and that care should be taken in the design of lentiviral vectors encoding RNAi inducers.

  6. Titers of lentiviral vectors encoding shRNAs and miRNAs are reduced by different mechanisms that require distinct repair strategies

    PubMed Central

    Liu, Ying Poi; Vink, Monique A.; Westerink, Jan-Tinus; Ramirez de Arellano, Eva; Konstantinova, Pavlina; Ter Brake, Olivier; Berkhout, Ben

    2010-01-01

    RNAi-based gene therapy is a powerful approach to treat viral infections because of its high efficiency and sequence specificity. The HIV-1-based lentiviral vector system is suitable for the delivery of RNAi inducers to HIV-1 susceptible cells due to its ability to transduce nondividing cells, including hematopoietic stem cells, and its ability for stable transgene delivery into the host cell genome. However, the presence of anti-HIV short hairpin RNA (shRNA) and microRNA (miRNA) cassettes can negatively affect the lentiviral vector titers. We show that shRNAs, which target the vector genomic RNA, strongly reduced lentiviral vector titers but inhibition of the RNAi pathway via saturation could rescue vector production. The presence of miRNAs in the vector RNA genome (sense orientation) results in a minor titer reduction due to Drosha processing. A major cause for titer reduction of miRNA vectors is due to incompatibility of the cytomegalovirus promoter with the lentiviral vector system. Replacement of this promoter with an inducible promoter resulted in an almost complete restoration of the vector titer. We also showed that antisense poly(A) signal sequences can have a dramatic effect on the vector titer. These results show that not all sequences are compatible with the lentiviral vector system and that care should be taken in the design of lentiviral vectors encoding RNAi inducers. PMID:20498457

  7. 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

  8. “Same Day” Ex-vivo Regional Gene Therapy: A Novel Strategy to Enhance Bone Repair

    PubMed Central

    Virk, Mandeep S; Sugiyama, Osamu; Park, Sang H; Gambhir, Sanjiv S; Adams, Douglas J; Drissi, Hicham; Lieberman, Jay R

    2011-01-01

    Ex-vivo regional gene therapy with bone marrow cells (BMCs) overexpressing bone morphogenetic protein-2 (BMP-2) has demonstrated efficacy in healing critical sized bone defects in preclinical studies. The purpose of this preclinical study was to compare the osteoinductive potential of a novel “same day” ex-vivo regional gene therapy versus a traditional two-step approach, which involves culture expansion of the donor cells before implantation. In the “same day” strategy buffy coat cells were harvested from the rat bone marrow, transduced with a lentiviral vector-expressing BMP-2 for 1 hour and implanted into a rat femoral defect in the same sitting. There was no significant difference (P = 0.22) with respect to the radiographic healing rates between the femoral defects treated with the “same day” strategy (13/13; 100%) versus the traditional two-step approach (11/14; 78%). However, the femoral defects treated with the “same day” strategy induced earlier radiographic bone healing (P = 0.004) and higher bone volume (BV) [micro-computed tomography (micro-CT); P < 0.001]. The “same day” strategy represents a significant advance in the field of ex-vivo regional gene therapy because it offers a solution to limitations associated with the culture expansion process required in the traditional ex vivo approach. This strategy should be cost-effective when adapted for human use. PMID:21343916

  9. 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

  10. 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

  11. 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.

  12. Laparoscopic repair of inguinal hernia in adults

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. The procedures include intraperitoneal onlay mesh (IPOM) repair, transabdominal preperitoneal (TAPP) repair and total extraperitoneal (TEP) repair. These procedures have totally different anatomic point of view, process and technical key points from open operations. The technical details of these operations are discussed in this article, also the strategies of treatment for some special conditions. PMID:27867954

  13. Eardrum repair

    MedlinePlus

    ... Ossicular fixation - surgery Images Eardrum repair - series References Adams ME, El-Kashlan HK. Tympanoplasty and ossiculoplasty. In: ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  14. Hydrocele repair

    MedlinePlus

    ... is excellent. However, another hydrocele may form over time, or if there was also a hernia present. Alternative Names Hydrocelectomy Images Hydrocele repair - series References Aiken JJ, Oldham KT. Inguinal hernias. In: ...

  15. 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.

  16. Tissue repair

    PubMed Central

    2010-01-01

    As living beings that encounter every kind of traumatic event from paper cut to myocardial infarction, we must possess ways to heal damaged tissues. While some animals are able to regrow complete body parts following injury (such as the earthworm who grows a new head following bisection), humans are sadly incapable of such feats. Our means of recovery following tissue damage consists largely of repair rather than pure regeneration. Thousands of times in our lives, a meticulously scripted but unseen wound healing drama plays, with cells serving as actors, extracellular matrix as the setting and growth factors as the means of communication. This article briefly reviews the cells involved in tissue repair, their signaling and proliferation mechanisms and the function of the extracellular matrix, then presents the actors and script for the three acts of the tissue repair drama. PMID:21220961

  17. UVB-induced DNA and photosystem II damage in two intertidal green macroalgae: distinct survival strategies in UV-screening and non-screening Chlorophyta.

    PubMed

    Pescheck, Frauke; Lohbeck, Kai T; Roleda, Michael Y; Bilger, Wolfgang

    2014-03-05

    Ultraviolet-B-induced (UVB, 280-315 nm) accumulation of cyclobutane pyrimidine dimers (CPDs) and deactivation of photosystem II (PS II) was quantified in two intertidal green macroalgae, Ulva clathrata and Rhizoclonium riparium. The species were chosen due to their shared habitats but contrasting UVB screening potentials. In the non-screening U. clathrata CPDs accumulated and PS II activity declined as a linear function of applied UVB irradiance. In R. riparium UVB-induced damage was significantly lower than in U. clathrata, demonstrating an efficient UVB protection of DNA and PS II by screening. Based on the UVB irradiance reaching the chloroplasts, both species showed an identical intrinsic sensitivity of PS II towards UVB, but DNA lesions accumulated slower in U. clathrata. While repair of CPDs was similar in both species, U. clathrata was capable of restoring its PS II function decidedly faster than R. riparium. In R. riparium efficient screening may represent an adaptation to its high light habitat, whereas in U. clathrata high repair rates of PS II appear to be important to survive natural UVB exposure. The role of shading of the nucleus by the large chloroplasts in U. clathrata is discussed.

  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. 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…

  20. 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…

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

    DOEpatents

    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. Biologic scaffold for CNS repair.

    PubMed

    Meng, Fanwei; Modo, Michel; Badylak, Stephen F

    2014-05-01

    Injury to the CNS typically results in significant morbidity and endogenous repair mechanisms are limited in their ability to restore fully functional CNS tissue. Biologic scaffolds composed of individual purified components have been shown to facilitate functional tissue reconstruction following CNS injury. Extracellular matrix scaffolds derived from mammalian tissues retain a number of bioactive molecules and their ability for CNS repair has recently been recognized. In addition, novel biomaterials for dural mater repairs are of clinical interest as the dura provides barrier function and maintains homeostasis to CNS. The present article describes the application of regenerative medicine principles to the CNS tissues and dural mater repair. While many approaches have been exploring the use of cells and/or therapeutic molecules, the strategies described herein focus upon the use of extracellular matrix scaffolds derived from mammalian tissues that are free of cells and exogenous factors.

  3. An alternative eukaryotic DNA excision repair pathway.

    PubMed Central

    Freyer, G A; Davey, S; Ferrer, J V; Martin, A M; Beach, D; Doetsch, P W

    1995-01-01

    DNA lesions induced by UV light, cyclobutane pyrimidine dimers, and (6-4)pyrimidine pyrimidones are known to be repaired by the process of nucleotide excision repair (NER). However, in the fission yeast Schizosaccharomyces pombe, studies have demonstrated that at least two mechanisms for excising UV photo-products exist; NER and a second, previously unidentified process. Recently we reported that S. pombe contains a DNA endonuclease, SPDE, which recognizes and cleaves at a position immediately adjacent to cyclobutane pyrimidine dimers and (6-4)pyrimidine pyrimidones. Here we report that the UV-sensitive S. pombe rad12-502 mutant lacks SPDE activity. In addition, extracts prepared from the rad12-502 mutant are deficient in DNA excision repair, as demonstrated in an in vitro excision repair assay. DNA repair activity was restored to wild-type levels in extracts prepared from rad12-502 cells by the addition of partially purified SPDE to in vitro repair reaction mixtures. When the rad12-502 mutant was crossed with the NER rad13-A mutant, the resulting double mutant was much more sensitive to UV radiation than either single mutant, demonstrating that the rad12 gene product functions in a DNA repair pathway distinct from NER. These data directly link SPDE to this alternative excision repair process. We propose that the SPDE-dependent DNA repair pathway is the second DNA excision repair process present in S. pombe. PMID:7623848

  4. Nuclear Dynamics of Heterochromatin Repair.

    PubMed

    Amaral, Nuno; Ryu, Taehyun; Li, Xiao; Chiolo, Irene

    2017-02-01

    Repairing double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. Recent studies in Drosophila cells revealed that faithful homologous recombination (HR) repair of heterochromatic DSBs relies on the relocalization of DSBs to the nuclear periphery before Rad51 recruitment. We summarize here the exciting progress in understanding this pathway, including conserved responses in mammalian cells and surprising similarities with mechanisms in yeast that deal with DSBs in distinct sites that are difficult to repair, including other repeated sequences. We will also point out some of the most important open questions in the field and emerging evidence suggesting that deregulating these pathways might have dramatic consequences for human health.

  5. Inflammation and repair processes in chronic obstructive pulmonary disease.

    PubMed

    Rennard, S I

    1999-11-01

    COPD is characterized by chronic inflammation and injury of both the airways and the parenchymal structures of the lung. These processes are associated with ongoing repair. Whether repair leads to restoration of normal tissue architecture or to altered tissue structure with loss of function depends on complex interrelationships of a variety of interacting mediators. The possibility that repair processes can be modulated by exogenous agents raises the possibility that therapeutic strategies aimed at repair can be effective. Such strategies offer tremendous promise both for slowing the relentlessly progressive natural history which most often characterizes COPD and, possibly, for restoring lung function. Rennard SI. Inflammation and repair processes in chronic obstructive pulmonary disease.

  6. 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 ...

  7. Eye muscle repair - discharge

    MedlinePlus

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

  8. INTERNAL REPAIR OF PIPELINES

    SciTech Connect

    Robin Gordon; Bill Bruce; Nancy Porter; Mike Sullivan; Chris Neary

    2003-05-01

    The two broad categories of deposited weld metal repair and fiber-reinforced composite repair technologies were reviewed for potential application for internal repair of gas transmission pipelines. Both are used to some extent for other applications and could be further developed for internal, local, structural repair of gas transmission pipelines. Preliminary test programs were developed for both deposited weld metal repairs and for fiber-reinforced composite repair. To date, all of the experimental work pertaining to the evaluation of potential repair methods has focused on fiber-reinforced composite repairs. Hydrostatic testing was also conducted on four pipeline sections with simulated corrosion damage: two with composite liners and two without.

  9. 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

  10. A look deep inside the a hillslope reveals a structured heterogeneity of isotopic reservoirs and distinct water use strategies for adjacent trees

    NASA Astrophysics Data System (ADS)

    Oshun, J.; Rempe, D. M.; Link, P.; Simonin, K. A.; Dietrich, W.; Dawson, T. E.; Fung, I.

    2012-12-01

    Whereas recent studies have begun to note the importance of weathered rock as a source of moisture for vegetation and, through transpiration, as a moderator of local and regional climate, no study has looked deeply into a hillslope in three-dimensions to explore dynamics in the hydrologic cycle and tree water use. Here, we use natural abundance stable isotope techniques to reveal distinct isotopic reservoirs within the hillslope, as well as quantify the movement of water from weathered rock and soil into vegetation. Our study site, at the Angelo Coast Range Reserve in Northern California, is a 4000 m2 unchanneled catchment that drains into Elder Creek, in the South Fork of the Eel River basin. Although average annual rainfall is 1900mm, 90% falls between October and May, forcing vegetation to find deep sources of moisture to survive the dry summer. An old-growth mixed conifer forest with trees as tall as 65 m grows on a 38° slope, with soils 10-60 cm thick underlain by vertically dipping, weathered turbidite sequences of the Coastal Franciscan Belt. A perched seasonally drains to unweathered bedrock. The water table fluctuates between 3 and 5 m below the surface near Elder Creek, and between 18 and 24 m below the surface at the hillslope divide. The site contains over 850 sensors monitoring the climatic variables and the movement of water through the subsurface, vegetation and into the atmosphere. Daily rainwater sampling during storm events from 2007-2012 shows a Local Meteoric Water Line, setting the context for our comparison of isotopic reservoirs. From Summer 2011 to Fall 2012, bi-weekly to tri-weekly samples were collected of tree xylem of over 30 individuals of Pseudotsuga menziesii, quercus agrifolia, arbutus menziesii, Umbellularia californica, Notholithocarpus densiflorus, acer macrophyllum, as well as from soil and rock to a depth of 1-1.3 m, and from the water table at 12 wells across the hillslope. Analysis reveals a structured heterogeneity of

  11. Mismatch repair.

    PubMed

    Fishel, Richard

    2015-10-30

    Highly conserved MutS homologs (MSH) and MutL homologs (MLH/PMS) are the fundamental components of mismatch repair (MMR). After decades of debate, it appears clear that the MSH proteins initiate MMR by recognizing a mismatch and forming multiple extremely stable ATP-bound sliding clamps that diffuse without hydrolysis along the adjacent DNA. The function(s) of MLH/PMS proteins is less clear, although they too bind ATP and are targeted to MMR by MSH sliding clamps. Structural analysis combined with recent real-time single molecule and cellular imaging technologies are providing new and detailed insight into the thermal-driven motions that animate the complete MMR mechanism.

  12. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

    PubMed Central

    Fellows, Christopher R.; Matta, Csaba; Zakany, Roza; Khan, Ilyas M.; Mobasheri, Ali

    2016-01-01

    Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. PMID:28066501

  13. 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)

  14. Integrated structural repair of a producing FPSO

    SciTech Connect

    Johnson, P.R.; Smith, T.A.

    1997-07-01

    The state of the art in FPSO design is advancing rapidly. The long-term reliability of FPSO systems has improved as maintenance issues, have received greater emphasis in both new-builds and conversions. Despite this new emphasis, problems will still arise and repairs will still be required. Ultimately, the ability of any FPSO to stay on location and on production will depend on the scope of repairs which can be economically performed in-situ. In 1994 and 1995, Marathon Petroleum Indonesia Limited (MPIL) performed an in-situ repair on the FPSO Kakap Natuna. The scope and complexity of this work suggests there are few, if any, limits on in-situ structural repairs which can be successfully performed on a producing FPSO. The use of an integrated execution strategy for the repairs greatly reduced their cost.

  15. 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.

  16. 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.

  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. 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

  19. 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

  20. 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.

  1. Inguinal hernia repair

    MedlinePlus

    ... This repair can be done with open or laparoscopic surgery. You and your surgeon can discuss which type ... the repair, the cuts are stitched closed. In laparoscopic surgery: The surgeon makes three to five small cuts ...

  2. 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 ...

  3. Collision Repair Campaign

    EPA Pesticide Factsheets

    The Collision Repair Campaign targets meaningful risk reduction in the Collision Repair source category to reduce air toxic emissions in their communities. The Campaign also helps shops to work towards early compliance with the Auto Body Rule.

  4. Enhancing CNS repair in neurological disease: challenges arising from neurodegeneration and rewiring of the network.

    PubMed

    Xu, Xiaohua; Warrington, Arthur E; Bieber, Allan J; Rodriguez, Moses

    2011-07-01

    Repair of the central nervous system (CNS) constitutes an integral part of treating neurological disease and plays a crucial role in restoring CNS architecture and function. Distinct strategies have been developed to reconstruct the damaged neural tissue, with many tested preclinically in animal models. We review cell replacement-based repair strategies. By taking spinal cord injury, cerebral ischaemia and degenerative CNS disorders as examples for CNS repair, we discuss progress and potential problems in utilizing embryonic stem cells and adult neural/non-neural stem cells to repair cell loss in the CNS. Nevertheless, CNS repair is not simply a matter of cell transplantation. The major challenge is to induce regenerating neural cells to integrate into the neural network and compensate for damaged neural function. The neural cells confront an environment very different from that of the developmental stage in which these cells differentiate to form interwoven networks. During the repair process, one of the challenges is neurodegeneration, which can develop from interrupted innervations to/from the targets, chronic inflammation, ischaemia, aging or idiopathic neural toxicity. Neurodegeneration, which occurs on the basis of a characteristic vascular and neural web, usually presents as a chronically progressive process with unknown aetiology. Currently, there is no effective treatment to stop or slow down neurodegeneration. Pathological changes from patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis indicate a broken homeostasis in the CNS. We discuss how the blood-brain barrier and neural networks are formed to maintain CNS homeostasis and their contribution to neurodegeneration in diseased conditions. Another challenge is that some inhibitors produced by CNS injury do not facilitate the regenerating neural cells to incorporate into a pre-existing network. We review glial responses to CNS injury. Of note, the reactive astrocytes

  5. 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.

  6. 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.

  7. Comparison of Shoulder Management Strategies after Stage I of Fingertip Skin Defect Repair with a Random-Pattern Abdominal Skin Flap

    PubMed Central

    Zhao, Feng; He, Wei; Zhang, Guoping; Liu, Shaojun; Yu, Kunlun; Bai, Jiangbo; Zhang, Hongjuan; Tian, Dehu

    2015-01-01

    Background In the absence of scientific evidence regarding the effectiveness of shoulder management strategies after stage I of fingertip reconstruction, the purpose of this study was to compare the clinical outcomes of various rehabilitation procedures. Material/Methods Patients who underwent fingertip reconstruction with a random-pattern abdominal skin flap between March 2007 and February 2013 were enrolled in the study (n=95). Thirty performed only active exercise (group A), 29 performed only passive exercise (group B), and 32 received a combination of active exercise and pulsed electromagnetic field (PEMF) (group C). The mean age at the time of treatment was 30.2 years in group A, 29.6 years in group B, and 31.8 years in group C. Results At the final follow-up, there were significant differences between group A and B in terms of Constant score (P=.001), VAS (P=.047), forward flexion of the shoulder (P=0.049), and muscle strength with forward flexion and external rotation (P=0.049 and P=0.042, respectively). A higher Constant score was observed in group C compared to group A, and although there were no differences in the other evaluations between groups A and C, a trend toward better function of the shoulder was demonstrated in group C. Conclusions The most important findings in our study are that a combination of active exercise and PEME produces superior patient-reported outcomes regarding relief of shoulder signs and symptoms. Given the limitations of this study, better-designed studies with large sample sizes and long-term follow-up are required. PMID:26449682

  8. Choreography of oxidative damage repair in mammalian genomes.

    PubMed

    Mitra, Sankar; Izumi, Tadahide; Boldogh, Istvan; Bhakat, Kishor K; Hill, Jeff W; Hazra, Tapas K

    2002-07-01

    The lesions induced by reactive oxygen species in both nuclear and mitochondrial genomes include altered bases, abasic (AP) sites, and single-strand breaks, all repaired primarily via the base excision repair (BER) pathway. Although the basic BER process (consisting of five sequential steps) could be reconstituted in vitro with only four enzymes, it is now evident that repair of oxidative damage, at least in mammalian cell nuclei, is more complex, and involves a number of additional proteins, including transcription- and replication-associated factors. These proteins may be required in sequential repair steps in concert with other cellular changes, starting with nuclear targeting of the early repair enzymes in response to oxidative stress, facilitation of lesion recognition, and access by chromatin unfolding via histone acetylation, and formation of metastable complexes of repair enzymes and other accessory proteins. Distinct, specific subclasses of protein complexes may be formed for repair of oxidative lesions in the nucleus in transcribed vs. nontranscribed sequences in chromatin, in quiescent vs. cycling cells, and in nascent vs. parental DNA strands in replicating cells. Characterizing the proteins for each repair subpathway, their signaling-dependent modifications and interactions in the nuclear as well as mitochondrial repair complexes, will be a major focus of future research in oxidative damage repair.

  9. Repair of furocoumarin adducts in mammalian cells

    SciTech Connect

    Zolan, M.E.; Smith, C.A.; Hanawalt, P.C.

    1984-12-01

    DNA repair was studied in cultured mammalian cells treated with the furocoumarins 8-methoxypsoralen (8-MOP), aminomethyl trioxsalen, or angelicin and irradiated with near UV light. The amount of DNA cross-linked by 8-MOP in normal human cells decreased by about one-half in 24 hours after treatment; no decrease was observed in xeroderma pigmentosum cells, group A. At present, it is not known to what extent this decrease represents complete repair events at the sites of cross-links. Furocoumarin adducts elicited excision repair in normal human and monkey cells but not in xeroderma pigmentosum group A cells. This excision repair resembled in several aspects that elicited by pyrimidine dimers, formed in DNA by irradiation with 254-nm UV light; however, it appeared that for at least 8-MOP and aminomethyl trioxsalen, removal of adducts was not as efficient as was the removal of pyrimidine dimers. A comparison was also made of repair in the 172-base-pair repetitive alpha-DNA component of monkey cells to repair in the bulk of the genome. Although repair elicited by pyrimidine dimers in alpha-DNA was the same as in the bulk DNA, that following treatment of cells with either aminomethyl trioxsalen or angelicin and near UV was markedly deficient in alpha-DNA. This deficiency reflected the removal of fewer adducts from alpha-DNA after the same initial adduct frequencies. These results could mean that each furocoumarin may produce several structurally distinct adducts to DNA in cells and that the capacity of cellular repair systems to remove these various adducts may vary greatly.

  10. 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

  11. Retinal detachment repair

    MedlinePlus

    Scleral buckling; Vitrectomy; Pneumatic retinopexy; Laser retinopexy; Rhegmatogenous retinal detachment repair ... it meets the hole in the retina. Scleral buckling can be done using numbing medicine while you ...

  12. 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

  13. 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

  14. Techniques for aortic arch endovascular repair.

    PubMed

    Hongku, Kiattisak; Dias, Nuno; Sonesson, Bjorn; Resch, Timothy

    2016-06-01

    This article reviews endovascular strategies for aortic arch repair. Open repair remains the gold standard particularly for good risk patients. Endovascular treatment potentially offers a less invasive repair. Principles, technical considerations, devices and outcomes of each technique are discussed and summarized. Hybrid repair combines less invasive revascularization options, instead of arch replacement while extending stent-graft into the arch. Outcomes vary with regard to extent of repair and aortic arch pathologies treated. Results of arch chimney and other parallel graft techniques perhaps make it a less preferable choice for elective cases. However, they are very appealing options for urgent or bailout situations. Fenestrated stent-grafting is subjected to many technical challenges in aortic arch due to difficulties in stent-graft orientation and fenestration positioning. In situ fenestration techniques emerge to avoid these problems, but durability of stent-grafts after fenestration and ischemic consequences of temporary carotid arteries coverage raises some concern total arch repair using this technique. Arch branched graft is a new technology. Early outcomes did not meet the expectation; however the results have been improving after its learning curve period. Refining stent-graft technologies and implantation techniques positively impact outcomes of endovascular approaches.

  15. Repairs of composite structures

    NASA Astrophysics Data System (ADS)

    Roh, Hee Seok

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

  16. Roles of chromatin remodellers in DNA double strand break repair.

    PubMed

    Jeggo, Penny A; Downs, Jessica A

    2014-11-15

    Now that we have a good understanding of the DNA double strand break (DSB) repair mechanisms and DSB-induced damage signalling, attention is focusing on the changes to the chromatin environment needed for efficient DSB repair. Mutations in chromatin remodelling complexes have been identified in cancers, making it important to evaluate how they impact upon genomic stability. Our current understanding of the DSB repair pathways suggests that each one has distinct requirements for chromatin remodelling. Moreover, restricting the extent of chromatin modifications could be a significant factor regulating the decision of pathway usage. In this review, we evaluate the distinct DSB repair pathways for their potential need for chromatin remodelling and review the roles of ATP-driven chromatin remodellers in the pathways.

  17. 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…

  18. Chain Saw Repair.

    ERIC Educational Resources Information Center

    Taylor, Mark; Helbling, Wayne

    This curriculum is designed to supplement the Comprehensive Small Engine Repair guide by covering in detail all aspects of chain saw repair. The publication contains materials for both teacher and student and is written in terms of student performance using measurable objectives. The course includes six units. Each unit contains some or all of the…

  19. Ribonucleotides in DNA: Origins, repair and consequences

    PubMed Central

    Williams, Jessica S.; Kunkel, Thomas A.

    2014-01-01

    While primordial life is thought to have been RNA-based (Cech, Cold Spring Harbor Perspect. Biol. 4 (2012) a006742), all living organisms store genetic information in DNA, which is chemically more stable. Distinctions between the RNA and DNA worlds and our views of “DNA” synthesis continue to evolve as new details emerge on the incorporation, repair and biological effects of ribonucleotides in DNA genomes of organisms from bacteria through humans. PMID:24794402

  20. Mesenchymal Stem Cells and Articular Cartilage Repair: Clinical Studies and Future Direction

    PubMed Central

    Punwar, Shahid; Khan, Wasim S

    2011-01-01

    Cartilage is frequently injured but shows little capacity for repair. Current treatment options include the use of procedures that stimulate repair through the stimulation of subchondral bone marrow and result in the formation of fibrocartilage. There is considerable interest in the use of cell-based treatment strategies and there are limited studies describing the use of mesenchymal stem cells for cartilage repair with promising early results. This paper reviews the current treatment strategies for articular cartilage, describes use of mesenchymal stem cells for articular cartilage repair along with the results of clinical studies, and describes the future direction that these strategies are likely to take. PMID:21886696

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Dynamic intermittent strain can rapidly impair ventral hernia repair.

    PubMed

    Kallinowski, Friedrich; Baumann, Elena; Harder, Felix; Siassi, Michael; Mahn, Axel; Vollmer, Matthias; Morlock, Michael M

    2015-11-26

    Ventral hernia repair fails frequently despite advanced mesh inserting surgery. A model for dynamic intermittent straining (DIS) of ventral hernia repairs was developed. The influence of phospholipids, position, overlap, fixation and tissue quality of various meshes on the durability of hernia repair was studied. DIS comprises the repetition of submaximal impacts delivered via a hydraulically driven plastic containment. Pig tissues simulate a ventral hernia with a standardized 5cm defect. Commercially available meshes strengthened with tacks, glue and sutures were used to bridge this defect in an underlay (IPOM) or sublay (retromuscular) position starting with a 5cm overlap in all directions. We tested 35 different ways of ventral hernia repair with up to 425 submaximal intermittent dynamic impacts until mesh dislocation occurred 10 times or a maximum of 4000 impacts each were withstood. The likelihood of a failing repair was related to the mesh, the lubricants, the position, the overlap, the fixation and the tissue quality. Most meshes dislocated easily and required fixation. One of the meshes tested was stable without fixation with a 5cm overlap and failed after reducing the overlap. Phospholipids exerted a strong influence on the biomaterial tested. The sublay position was about 10% more durable in comparison to the IPOM position. DIS revealed distinct degrees of stability with primarily stable, intermediate and primarily unstable repairs. Based on the DIS results available, the currently used ventral hernia repair options can be classified. In the future, DIS investigations can improve the durability of hernia repair.

  6. Brain aneurysm repair - discharge

    MedlinePlus

    ... gov/pubmed/22556195 . Szeder V, Tateshima S, Duckwiler GR. Intracranial aneurysms and subarachnoid hemorrhage. In: Daroff RB, Jankovic J, ... chap 67. Read More Aneurysm in the brain Brain aneurysm repair Brain surgery Recovering after stroke Seizures Smoking - ...

  7. Pectus excavatum repair

    MedlinePlus

    Gottlieb LJ, Reid RR, Lee JC. Pediatric chest and trunk defects. In: Neligan PC, ed. Plastic Surgery . 3rd ed. Philadelphia, PA: Elsevier; 2013:chap 41. Lumpkins KM, Colombani P, Abdullah F. Repair ...

  8. Diaphragmatic hernia repair - slideshow

    MedlinePlus

    ... presentations/100014.htm Diaphragmatic hernia repair - series—Normal anatomy To use the sharing ... Overview The chest cavity includes the heart and lungs. The abdominal cavity includes the liver, the stomach, ...

  9. 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)

  10. Hypospadias repair - discharge

    MedlinePlus

    ... Campbell-Walsh Urology . 10th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap 130. Read More Hypospadias Hypospadias repair Kidney removal Review Date 1/21/2015 Updated by: Scott Miller, MD, Urologist in private practice in Atlanta, ...

  11. Meningocele repair - slideshow

    MedlinePlus

    ... ency/presentations/100128.htm Meningocele repair - series—Normal anatomy To use the sharing features on this page, ... Sinai Medical Center, Los Angeles and Department of Anatomy, University of California, San Francisco, CA. Review provided ...

  12. 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 ...

  13. Bone fracture repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100077.htm Bone fracture repair - series—Indications To use the sharing features ... Go to slide 4 out of 4 Overview Fractures of the bones are classified in a number ...

  14. Femur fracture repair - discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000166.htm Femur fracture repair - discharge To use the sharing features on this page, please enable JavaScript. You had a fracture (break) in the femur in your leg. It ...

  15. Pectus excavatum repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100035.htm Pectus excavatum repair - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Pectus excavatum is a deformity of the front of the ...

  16. 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. ...

  17. Ventral hernia repair

    MedlinePlus

    ... Philadelphia. PA: Elsevier Saunders; 2014:539-545. Nagle AP, Soper NJ. Laparoscopic ventral hernia repair. In: Khatri ... Support Get email updates Subscribe to RSS Follow us Disclaimers Copyright Privacy Accessibility Quality Guidelines Viewers & Players ...

  18. 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 ...

  19. Imperforate anus repair - slideshow

    MedlinePlus

    ... presentations/100030.htm Imperforate anus repair - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  20. Rotator cuff repair - slideshow

    MedlinePlus

    ... presentations/100229.htm Rotator cuff repair - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  1. Carpal tunnel repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100078.htm Carpal tunnel repair - series—Normal anatomy To use the sharing ... in the wrist and the wrist bones (carpal tunnel). Review Date 5/9/2015 Updated by: C. ...

  2. Proximal Hamstring Repair Strength

    PubMed Central

    Harvey, Margaret Ann; Singh, Hardeep; Obopilwe, Elifho; Charette, Ryan; Miller, Suzanne

    2015-01-01

    Background: Proximal hamstring repair for complete ruptures has become a common treatment. There is no consensus in the literature about postoperative rehabilitation protocols following proximal hamstring repair. Some protocols describe bracing to prevent hip flexion or knee extension while others describe no immobilization. There are currently no biomechanical studies evaluating proximal hamstring repairs; nor are there any studies evaluating the effect of different hip flexion angles on these repairs. Hypothesis: As hip flexion increases from 0° to 90°, there will be a greater gap with cyclical loading. Study Design: Controlled laboratory study. Methods: Proximal hamstring insertions were detached from the ischial tuberosity in 24 cadavers and were repaired with 3 single-loaded suture anchors in the hamstring footprint with a Krakow suture technique. Cyclic loading from 10 to 125 N at 1 Hz was then performed for 0°, 45°, and 90° of hip flexion for 1500 cycles. Gap formation, stiffness, yield load, ultimate load, and energy to ultimate load were compared between groups using paired t tests. Results: Cyclic loading demonstrated the least amount of gap formation (P < .05) at 0° of hip flexion (2.39 mm) and most at 90° of hip flexion (4.19 mm). There was no significant difference in ultimate load between hip flexion angles (326, 309, and 338 N at 0°, 45°, and 90°, respectively). The most common mode of failure occurred with knot/suture failure (n = 17). Conclusion: Increasing hip flexion from 0° to 90° increases the displacement across proximal hamstring repairs. Postoperative bracing that limits hip flexion should be considered. Clinical Relevance: Repetitive motion involving hip flexion after a proximal hamstring repair may cause compromise of the repair. PMID:26665049

  3. Transcriptomic Approaches to Neural Repair

    PubMed Central

    Antunes-Martins, Ana; Chandran, Vijayendran; Costigan, Michael; Lerch, Jessica K.; Willis, Dianna E.; Tuszynski, Mark H.

    2015-01-01

    Understanding why adult CNS neurons fail to regenerate their axons following injury remains a central challenge of neuroscience research. A more complete appreciation of the biological mechanisms shaping the injured nervous system is a crucial prerequisite for the development of robust therapies to promote neural repair. Historically, the identification of regeneration associated signaling pathways has been impeded by the limitations of available genetic and molecular tools. As we progress into an era in which the high-throughput interrogation of gene expression is commonplace and our knowledge base of interactome data is rapidly expanding, we can now begin to assemble a more comprehensive view of the complex biology governing axon regeneration. Here, we highlight current and ongoing work featuring transcriptomic approaches toward the discovery of novel molecular mechanisms that can be manipulated to promote neural repair. SIGNIFICANCE STATEMENT Transcriptional profiling is a powerful technique with broad applications in the field of neuroscience. Recent advances such as single-cell transcriptomics, CNS cell type-specific and developmental stage-specific expression libraries are rapidly enhancing the power of transcriptomics for neuroscience applications. However, extracting biologically meaningful information from large transcriptomic datasets remains a formidable challenge. This mini-symposium will highlight current work using transcriptomic approaches to identify regulatory networks in the injured nervous system. We will discuss analytical strategies for transcriptomics data, the significance of noncoding RNA networks, and the utility of multiomic data integration. Though the studies featured here specifically focus on neural repair, the approaches highlighted in this mini-symposium will be of broad interest and utility to neuroscientists working in diverse areas of the field. PMID:26468186

  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. Cockayne syndrome: defective repair of transcription?

    PubMed Central

    van Gool, A J; van der Horst, G T; Citterio, E; Hoeijmakers, J H

    1997-01-01

    In the past years, it has become increasingly evident that basal metabolic processes within the cell are intimately linked and influenced by one another. One such link that recently has attracted much attention is the close interplay between nucleotide excision DNA repair and transcription. This is illustrated both by the preferential repair of the transcribed strand of active genes (a phenomenon known as transcription-coupled repair, TCR) as well as by the distinct dual involvement of proteins in both processes. The mechanism of TCR in eukaryotes is still largely unknown. It was first discovered in mammals by the pioneering studies of Hanawalt and colleagues, and subsequently identified in yeast and Escherichia coli. In the latter case, one protein, the transcription repair-coupling factor, was found to accomplish this function in vitro, and a plausible model for its activity was proposed. While the E. coli model still functions as a paradigm for TCR in eukaryotes, recent observations prompt us to believe that the situation in eukaryotes is much more complex, involving dual functionality of multiple proteins. PMID:9250659

  7. 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.

  8. 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.

  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. Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.

    PubMed

    Brown, Jessica S; O'Carrigan, Brent; Jackson, Stephen P; Yap, Timothy A

    2017-01-01

    Germline aberrations in critical DNA-repair and DNA damage-response (DDR) genes cause cancer predisposition, whereas various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2-mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell-cycle checkpoint activation, trigger apoptosis, and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.

  11. DNA repair in normal human and xeroderma pigmentosum group A fibroblasts following treatment with various methanesulfonates and the demonstration of a long-patch repair component

    SciTech Connect

    Snyder, R.D.; Regan, J.D.

    1982-01-01

    Excision repair of DNA in normal and xeroderma pigmentosum complementation group A fibroblasts were examined following treatment with methyl-, ethyl-, and isopropyl methanesulfonate. Studies utilizing repair synthesis methods and inhibition with arabinofuranosyl cytosine revealed two distinct phases of repair; one commencing and terminating within the first 3-5 h after the treatment, and a second much longer phase extending from 9-35 h post-treatment. Both phases of repair have a long-patch component, which establishes for the first time the existence of this mode of repair in response to alkane sulfonate damage. While xeroderma cells display somewhat fewer alkaline labile sites in their DNA following alkylation treatment than do their normal counterparts, researchers are unable to demonstrate a deficiency of these cells in either of the two phases of repair.

  12. 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

  13. Incisional hernia repair.

    PubMed

    Millikan, Keith W

    2003-10-01

    Incisional ventral hernias are a common problem encountered by surgeons, with over 100,000 repairs being performed annually in the United States. Although many predisposing factors for incisional ventral hernia are patient-related, some factors such as type of primary closure and materials used may reduce the overall incidence of incisional ventral hernia. With the advent of prosthetic meshes being used for incisional ventral hernia repair, the recurrence rate has dropped to approximately 10%. More recently, with the development of prosthetic mesh that is now safe to place intraperitoneally, the recurrence rate has dropped to under 5%. The current controversies that exist for incisional ventral hernia repair are which approach to use (open versus laparoscopic) and what type of fixation (partial- versus full-thickness abdominal muscular/fascial wall) is necessary to stabilize the position of the mesh while tissue ingrowth occurs. During the next decade the answers to these controversies should be available in the surgical literature.

  14. Enhanced cartilage repair in 'healer' mice-New leads in the search for better clinical options for cartilage repair.

    PubMed

    Fitzgerald, Jamie

    2017-02-01

    Adult articular cartilage has a poor capacity to undergo intrinsic repair. Current strategies for the repair of large cartilage defects are generally unsatisfactory because the restored cartilage does not have the same resistance to biomechanical loading as authentic articular cartilage and degrades over time. Recently, an exciting new research direction, focused on intrinsic cartilage regeneration rather than fibrous repair by external means, has emerged. This review explores the new findings in this rapidly moving field as they relate to the clinical goal of restoration of structurally robust, stable and non-fibrous articular cartilage following injury.

  15. Rescheduling with iterative repair

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  16. 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.

  17. 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.

  18. 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.

  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. Getting Ready To Repair.

    ERIC Educational Resources Information Center

    Stryker, Rick

    2002-01-01

    Successful camp repairs require careful planning. Prioritize projects by program needs first, then by cost. Determine the cause of deterioration and address it. Build goodwill with suppliers by knowing what you want and giving them ample time to prepare estimates. Include labor costs, even for staff labor. A cost-estimate table for a sample…

  1. Single cell wound repair

    PubMed Central

    Abreu-Blanco, Maria Teresa; Verboon, Jeffrey M

    2011-01-01

    Cell wounding is a common event in the life of many cell types, and the capacity of the cell to repair day-to-day wear-and-tear injuries, as well as traumatic ones, is fundamental for maintaining tissue integrity. Cell wounding is most frequent in tissues exposed to high levels of stress. Survival of such plasma membrane disruptions requires rapid resealing to prevent the loss of cytosolic components, to block Ca2+ influx and to avoid cell death. In addition to patching the torn membrane, plasma membrane and cortical cytoskeleton remodeling are required to restore cell function. Although a general understanding of the cell wound repair process is in place, the underlying mechanisms of each step of this response are not yet known. We have developed a model to study single cell wound repair using the early Drosophila embryo. Our system combines genetics and live imaging tools, allowing us to dissect in vivo the dynamics of the single cell wound response. We have shown that cell wound repair in Drosophila requires the coordinated activities of plasma membrane and cytoskeleton components. Furthermore, we identified an unexpected role for E-cadherin as a link between the contractile actomyosin ring and the newly formed plasma membrane plug. PMID:21922041

  2. 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.

  3. Hydrocele repair - slideshow

    MedlinePlus

    ... anatomy URL of this page: //medlineplus.gov/ency/presentations/100163.htm Hydrocele repair - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 4 Go to slide 2 ...

  4. Eardrum repair - slideshow

    MedlinePlus

    ... anatomy URL of this page: //medlineplus.gov/ency/presentations/100015.htm Eardrum repair - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 4 Go to slide 2 ...

  5. 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,…

  6. Hiatal hernia repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100028.htm Hiatal hernia repair - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Hiatal Hernia A.D.A.M., Inc. is accredited by ...

  7. 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…

  8. Intestinal obstruction repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100116.htm Intestinal obstruction repair - series—Normal anatomy To use the sharing ... M. Editorial team. Related MedlinePlus Health Topics Adhesions Intestinal Obstruction A.D.A.M., Inc. is accredited by ...

  9. Remote repair grinding of cracks underwater

    SciTech Connect

    Thomessen, T.; Lien, T.K.; Johnsen, K.

    1994-12-31

    This paper presents a new approach for remote repair grinding of cracks underwater. The approach uses Controlled Material Removal Rate (CMRR) grinding strategy which is based on a force controlled manipulator for handling the grinding machine. The CMRR-strategy requires an empirical model of the grinding process. Different grinding wheels were tested in underwater grinding, and experiments were carried out to derived an empirical model of the grinding process for a cylindrical grinding wheel. Finally, the CMRR-strategy was applied to grind a groove according to given specifications. The force control system was used to measure the groove geometry after grinding. The results were promising and demonstrate clearly that the CMRR-strategy is very useful in underwater grinding due to its high flexibility.

  10. 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…

  11. Laparoscopic repair of femoral hernia

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

    Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed effects. Femoral hernia could be repaired through the laparoscopic procedures for inguinal hernia. These procedures have clear anatomic view in the operation and preoperatively undiagnosed femoral hernia could be confirmed and treated. Lower recurrence ratio was reported in laparoscopic procedures compared with open procedures for repair of femoral hernia. The technical details of laparoscopic repair of femoral hernia, especially the differences to laparoscopic repair of inguinal hernia are discussed in this article. PMID:27826574

  12. Distinct Intervertebral Disc Cell Populations Adopt Similar Phenotypes in Three-Dimensional Culture

    PubMed Central

    Chou, Alice I.; Reza, Anna T.

    2008-01-01

    Tissue engineering strategies have the potential to improve upon current techniques for intervertebral disc repair. However, determining a suitable biomaterial scaffold for disc regeneration is difficult due to the complex fibrocartilaginous structure of the tissue. In this study, cells isolated from three distinct regions of the intervertebral disc, the outer and inner annulus fibrosus and nucleus pulposus, were expanded and seeded on resorbable polyester fiber meshes and encapsulated in calcium crosslinked alginate hydrogels, both chosen to approximate the native tissue architecture. Three-dimensional (3D) constructs were cultured for 14 days in vitro and evaluated histologically and quantitatively for gene expression and production of types I and II collagen and proteoglycans. During monolayer expansion, the cell populations maintained their distinct phenotypic morphology and gene expression profiles. However, after 14 days in 3D culture, there were no significant differences in morphology, gene expression, or protein production between all three cell populations grown in either alginate or polyester fiber meshes. The results of this study indicate that the culture environment may have a greater impact on cellular behavior than the intrinsic origin of the cells, and suggest that only a single-cell type may be required for intervertebral disc regenerative therapies. PMID:18636941

  13. Phase-independent multilayer defect repair for EUV photomasks

    NASA Astrophysics Data System (ADS)

    Zhao, Shuo; Qi, Zhengqing John

    2016-10-01

    EUV mask repair techniques have primarily focused on absorber biasing to recover the imaging contrast loss originating from multilayer blank defects, while exploratory efforts have investigated local multilayer modification for compensating any through-focus Bossung asymmetry. The work here evaluates these repair techniques and attempts to expand upon them through finite-difference time-domain (FDTD) simulations. In particular, the possibility of local material deposition as an added repair technique is considered, and the interactions between various compensation strategies and illumination modes are explored. A multilayer defect repair methodology that is non-disruptive to the multilayer stack is introduced for the recovery of both the amplitude loss and phase error originating from native blank defects. The effectiveness of the compensation technique is shown to be independent of the defect type, providing a repair solution that is impartial to the phase offset induced by the multilayer defect. Significant lithographic process window improvements are reported, as compared to conventional absorber-based repair, attributed primarily to the restoration of symmetric printing behavior through defocus. This provides an alternative, viable approach to HVM multilayer defect repair.

  14. Minimally Invasive Spigelian Hernia Repair

    PubMed Central

    Baucom, Catherine; Nguyen, Quan D.; Hidalgo, Marco

    2009-01-01

    Introduction: Spigelian hernia is an uncommon ventral hernia characterized by a defect in the linea semilunaris. Repair of spigelian hernia has traditionally been accomplished via an open transverse incision and primary repair. The purpose of this article is to present 2 case reports of incarcerated spigelian hernia that were successfully repaired laparoscopically using Gortex mesh and to present a review of the literature regarding laparoscopic repair of spigelian hernias. Methods: Retrospective chart review and Medline literature search. Results: Two patients underwent laparoscopic mesh repair of incarcerated spigelian hernias. Both were started on a regular diet on postoperative day 1 and discharged on postoperative days 2 and 3. One patient developed a seroma that resolved without intervention. There was complete resolution of preoperative symptoms at the 12-month follow-up. Conclusion: Minimally invasive repair of spigelian hernias is an alternative to the traditional open surgical technique. Further studies are needed to directly compare the open and the laparoscopic repair. PMID:19660230

  15. 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

  16. 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

  17. 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.

  18. Macrophage Phenotype in Liver Injury and Repair.

    PubMed

    Sun, Y-Y; Li, X-F; Meng, X-M; Huang, C; Zhang, L; Li, J

    2017-03-01

    Macrophages hold a critical position in the pathogenesis of liver injury and repair, in which their infiltrations is regarded as a main feature for both acute and chronic liver diseases. It is noted that, based on the distinct phenotypes and origins, hepatic macrophages are capable of clearing pathogens, promoting/or inhibiting liver inflammation, while regulating liver fibrosis and fibrolysis through interplaying with hepatocytes and hepatic stellate cells (HSC) via releasing different types of pro- or anti-inflammatory cytokines and growth factors. Macrophages are typically categorized into M1 or M2 phenotypes by adapting to local microenvironment during the progression of liver injury. In most occasions, M1 macrophages play a pro-inflammatory role in liver injury, while M2 macrophages exert an anti-inflammatory or pro-fibrotic role during liver repair and fibrosis. In this review, we focused on the up-to-date information about the phenotypic and functional plasticity of the macrophages and discussed the detailed mechanisms through which the phenotypes and functions of macrophages are regulated in different stages of liver injury and repair. Moreover, their roles in determining the fate of liver diseases were also summarized. Finally, the macrophage-targeted therapies against liver diseases were also be evaluated.

  19. 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…

  20. Rapid Runway Repair Study.

    DTIC Science & Technology

    This report describes a series of tests to evaluate a system for rapidly repairing airfield pavement using polymer concrete (synthetic polymer plus...aggregate), thermally cured by microwave power. The technique, developed by the Syracuse University Research Corporation (SURC) for highway...maintenance, uses a truck-mounted 50-kilowatt microwave generator to irradiate areas patched with polymer concrete . Test results indicate that the polymer

  1. 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

  2. The RecQ DNA helicases in DNA Repair

    PubMed Central

    Bernstein, Kara A.; Gangloff, Serge; Rothstein, Rodney

    2014-01-01

    The RecQ helicases are conserved from bacteria to humans and play a critical role in genome stability. In humans, loss of RecQ gene function is associated with cancer predisposition and/or premature aging. Recent data have shown that the RecQ helicases function during two distinct steps during DNA repair; DNA end resection and resolution of double Holliday junctions (dHJs). RecQ functions in these different processing steps has important implications for its role in repair of double-strand breaks (DSBs) that occur during DNA replication, meiosis and at specific genomic loci such as telomeres. PMID:21047263

  3. Chromatin organization and dynamics in double-strand break repair.

    PubMed

    Seeber, Andrew; Gasser, Susan M

    2016-10-31

    Chromatin is organized and segmented into a landscape of domains that serve multiple purposes. In contrast to transcription, which is controlled by defined sequences at distinct sites, DNA damage can occur anywhere. Repair accordingly must occur everywhere, yet it is inevitably affected by its chromatin environment. In this review, we summarize recent work investigating how changes in chromatin organization facilitate and/or guide DNA double-strand break repair. In addition, we examine new live cell studies on the dynamics of chromatin and the mechanisms that regulate its movement.

  4. Cardiopoietic programming of embryonic stem cells for tumor-free heart repair.

    PubMed

    Behfar, Atta; Perez-Terzic, Carmen; Faustino, Randolph S; Arrell, D Kent; Hodgson, Denice M; Yamada, Satsuki; Puceat, Michel; Niederländer, Nicolas; Alekseev, Alexey E; Zingman, Leonid V; Terzic, Andre

    2007-02-19

    Embryonic stem cells have the distinct potential for tissue regeneration, including cardiac repair. Their propensity for multilineage differentiation carries, however, the liability of neoplastic growth, impeding therapeutic application. Here, the tumorigenic threat associated with embryonic stem cell transplantation was suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-alpha, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF-alpha to promote cardiac differentiation was recapitulated in embryoid bodies in vitro. The procardiogenic action required an intact endoderm and was mediated by secreted cardio-inductive signals. Resolved TNF-alpha-induced endoderm-derived factors, combined in a cocktail, secured guided differentiation of embryonic stem cells in monolayers produce cardiac progenitors termed cardiopoietic cells. Characterized by a down-regulation of oncogenic markers, up-regulation, and nuclear translocation of cardiac transcription factors, this predetermined population yielded functional cardiomyocyte progeny. Recruited cardiopoietic cells delivered in infarcted hearts generated cardiomyocytes that proliferated into scar tissue, integrating with host myocardium for tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone stem cell pluripotency, offering a tumor-resistant approach for regeneration.

  5. Flexural Fatigue Response of Repaired S2-Glass/Vinyl Ester Composites

    DTIC Science & Technology

    2009-08-01

    vacuum-assisted resin transfer molding ( VARTM ) (2), performance evaluations have assumed increasing importance due to the lack of historical databases on...composites produced affordably, including VARTM and those that possess thick sections. There is a need to standardize repair strategies for affordably...produced composites. This report presents preliminary work on VARTM -produced laminates subjected to idealized damage and repaired through different

  6. The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

    PubMed Central

    Sun, Dong

    2016-01-01

    Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent development in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury. PMID:26981070

  7. DNA excision repair at telomeres.

    PubMed

    Jia, Pingping; Her, Chengtao; Chai, Weihang

    2015-12-01

    DNA damage is caused by either endogenous cellular metabolic processes such as hydrolysis, oxidation, alkylation, and DNA base mismatches, or exogenous sources including ultraviolet (UV) light, ionizing radiation, and chemical agents. Damaged DNA that is not properly repaired can lead to genomic instability, driving tumorigenesis. To protect genomic stability, mammalian cells have evolved highly conserved DNA repair mechanisms to remove and repair DNA lesions. Telomeres are composed of long tandem TTAGGG repeats located at the ends of chromosomes. Maintenance of functional telomeres is critical for preventing genome instability. The telomeric sequence possesses unique features that predispose telomeres to a variety of DNA damage induced by environmental genotoxins. This review briefly describes the relevance of excision repair pathways in telomere maintenance, with the focus on base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). By summarizing current knowledge on excision repair of telomere damage and outlining many unanswered questions, it is our hope to stimulate further interest in a better understanding of excision repair processes at telomeres and in how these processes contribute to telomere maintenance.

  8. 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.

  9. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  10. Profiling base excision repair glycosylases with synthesized transition state analogs.

    PubMed

    Chu, Aurea M; Fettinger, James C; David, Sheila S

    2011-09-01

    Two base excision repair glycosylase (BER) transition state (TS) mimics, (3R,4R)-1-benzyl (hydroxymethyl) pyrrolidin-3-ol (1NBn) and (3R,4R)-(hydroxymethyl) pyrrolidin-3-ol (1N), were synthesized using an improved method. Several BER glycosylases that repair oxidized DNA bases, bacterial formamidopyrimdine glycosylase (Fpg), human OG glycosylase (hOGG1) and human Nei-like glycosylase 1 (hNEIL1) exhibit exceptionally high affinity (K(d)∼pM) with DNA duplexes containing the 1NBn and 1N nucleotide. Notably, comparison of the K(d) values of both TS mimics relative to an abasic analog (THF) in duplex contexts paired opposite C or A suggest that these DNA repair enzymes use distinctly different mechanisms for damaged base recognition and catalysis despite having overlapping substrate specificities.

  11. 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

  12. Bioactive Glass for Large Bone Repair.

    PubMed

    Jia, Weitao; Lau, Grace Y; Huang, Wenhai; Zhang, Changqing; Tomsia, Antoni P; Fu, Qiang

    2015-12-30

    There has been an ongoing quest for new biomedical materials for the repair and regeneration of large segmental bone defects caused by disease or trauma. Autologous bone graft (ABG) remains the gold standard for bone repair despite their limited supply and donor-site morbidity. The current tissue engineering approach with synthetically derived bone grafts requires a bioactive ceramic or polymeric scaffold loaded with growth factors for osteoinduction and angiogenesis, and bone marrow stromal cells (BMSCs) for osteogenic properties. Unfortunately, this approach has serious drawbacks: the low mechanical strength of scaffolds, the high cost of growth factors, and a lack of optimal strategies for growth-factor delivery. Here, it is shown that, for the first time, a synthetic material alone can repair large bone defects as efficiently as the gold standard ABG. Through the use of strong and resorbable bioactive glass scaffolds, complete bone healing, and defect bridging can be achieved in a rabbit femur segmental defect model without growth factors or BMSCs. New bone and blood vessel formation, in both inner and peripheral scaffolds, demonstrates the excellent osteoinductive and osteogenic properties of these scaffolds similar as ABG.

  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. Mononuclear cells and vascular repair in HHT.

    PubMed

    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.

  16. 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

  17. W. M. Keck Observatory primary mirror segment repair project: overview and status

    NASA Astrophysics Data System (ADS)

    Meeks, Robert L.; Doyle, Steve; Higginson, Jamie; Hudek, John S.; Irace, William; McBride, Dennis; Pollard, Mike; Tai, Kuochou; Von Boeckmann, Tod; Wold, Leslie; Wold, Truman

    2016-07-01

    The W. M. Keck Observatory Segment Repair Project is repairing stress-induced fractures near the support points in the primary mirror segments. The cracks are believed to result from deficiencies in the original design and implementation of the adhesive joints connecting the Invar support components to the ZERODUR mirror. Stresses caused by temperature cycling over 20 years of service drove cracks that developed at the glass-metal interfaces. Over the last few years the extent and cause of the cracks have been studied, and new supports have been designed. Repair of the damaged glass required development of specialized tools and procedures for: (1) transport of the segments; (2) pre-repair metrology to establish the initial condition; (3) removal of support hardware assemblies; (4) removal of the original supports; (5) grinding and re-surfacing the damaged glass areas; (6) etching to remove sub-surface damage; (7) bonding new supports; (8) re-installation of support assemblies; and (9) post-repair metrology. Repair of the first segment demonstrated the new tools and processes. On-sky measurements before and after repair verified compliance with the requirements. This paper summarizes the repair process, on-sky results, and transportation system, and also provides an update on the project status and schedule for repairing all 84 mirror segments. Strategies for maintaining quality and ensuring that repairs are done consistently are also presented.

  18. 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.

  19. 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,…

  20. 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.

  1. Development of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Meyer, Peggy L.

    Since the beginning of man's awareness of his language capabilities and language structure, he has assumed that speech is composed of discrete entities. The linguist attempts to establish a model of the workings of these distinctive sounds in a language. Utilizing an historical basis for discussion, this general survey of the distinctive feature…

  2. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... emissions of purged material resulting from immediate repair would be greater than the fugitive emissions likely to result from delay of repair, and (ii) When repair procedures are effected, the purged...

  3. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... purged material resulting from immediate repair would be greater than the fugitive emissions likely to result from delay of repair, and (ii) When repair procedures are effected, the purged material...

  4. 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.

  5. 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

  6. Cartilage repair with autogenic perichondrium cell and polylactic acid grafts.

    PubMed

    Dounchis, J S; Bae, W C; Chen, A C; Sah, R L; Coutts, R D; Amiel, D

    2000-08-01

    The repair of articular cartilage injuries remains a challenge, with many of the current therapeutic strategies based on the grafting or recruitment of chondrogenic tissues or cells. This 1-year study compared the repair of a 3.7-mm diameter by 3-mm deep osteochondral defect in the medial femoral condyle of 24 New Zealand White rabbits; the defect was obtained using an autogenic perichondrium cell polylactic acid composite graft with a contralateral control in which the osteochondral defect remained empty. To elucidate the effect of host immune responses on the repair process after perichondrium cell transplantation, the results of the autogenic perichondrium cell polylactic acid graft group were compared with those obtained in the authors' previous 1-year study of allogenic perichondrium cell polylactic acid composite grafts implanted in a similar model. One year after surgery, the repair site underwent gross inspection and histologic, histomorphometric, biochemical, and biomechanical analyses. The autogenic perichondrium cell polylactic acid graft group (92%) and the control group in which the osteochondral defect remained empty (88%) resulted in a high percentage of grossly acceptable repairs. The autogenic grafts appeared to augment the intrinsic healing capacity of the animals (as compared with the animals in the No Implant Group). The autogenic perichondrium cell polylactic and grafts improved the histologic appearance and percentage of Type II collagen of the cartilaginous repair tissue. Compared with allogenic grafts, the autogenic grafts had better reconstitution of the subchondral bone. However, the results of this experimental model suggest a suboptimal concentration of glycosaminoglycans in the neocartilage matrix, a depressed surface of the repair tissue, a histologic appearance that was not equivalent to that of normal articular cartilage, and reduced biomechanical properties for the repair tissue. The future application of growth factors to this

  7. 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

  8. 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…

  9. 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…

  10. 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.

  11. Small Crater Expedient Repair Test.

    DTIC Science & Technology

    1980-08-01

    Crater 4, the timed polymer-concrete repair, failed due to material quality. An estimated 20 of the 464 bags of SilikalO lacked the benzoyl ... peroxide catalyst required for polymerization. As a result of this omission, several areas of the repair failed to harden, causing the unpolymerized mateiial

  12. 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.

  13. Tissue-specific accelerated aging in nucleotide excision repair deficiency

    PubMed Central

    Niedernhofer, Laura J.

    2008-01-01

    Nucleotide excision repair (NER) is a multi-step DNA repair mechanism that removes helix-distorting modified nucleotides from the genome. NER is divided into two subpathways depending on the location of DNA damage in the genome and how it is first detected. Global genome NER identifies and repairs DNA lesions throughout the genome. This subpathway of NER primarily protects against the accumulation of mutations in the genome. Transcription-coupled (TC) NER rapidly repairs lesions in the transcribed strand of DNA that block transcription by RNA polymerase II. TC-NER prevents cell death in response to stalled transcription. Defects in NER cause three distinct human diseases: xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Each of these syndromes is characterized by premature onset of pathologies that overlap with those associated with old age in humans. This reveals the contribution of DNA damage to multiple age-related diseases. Tissues affected include the skin, eye, bone marrow, nervous system and endocrine axis. This review emphasizes accelerated aging associated with xeroderma pigmentosum and discusses the cause of these pathologies, either mutation accumulation or cell death as a consequence of failure to repair DNA damage. PMID:18538374

  14. Rethinking transcription coupled DNA repair.

    PubMed

    Kamarthapu, Venu; Nudler, Evgeny

    2015-04-01

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

  15. Laparoscopic repair of recurrent hernias.

    PubMed

    Felix, E L; Michas, C A; McKnight, R L

    1995-02-01

    The purpose of this study was to evaluate the results of a laparoscopic approach to recurrent inguinal hernia repair which dissected the entire inguinal floor and repaired all potential areas of recurrence without producing tension. Both a transabdominal preperitoneal and a totally extraperitoneal laparoscopic approach were utilized. Ninety recurrent hernias were repaired in 81 patients. The patients had 26 indirect, 36 direct, and 26 pantaloon recurrent hernias of which eight had a femoral component. In all but one patient the primary operations were open anterior repairs. The median follow-up was 14 months, ranging from 1 to 28 months. Patients returned to normal activities in an average of 1 week. The only recurrence observed was in the one patient whose primary repair was laparoscopic. When the entire inguinal floor of the recurrent hernia was redissected and buttressed with mesh, early recurrence was eliminated and recovery was shortened.

  16. 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.

  17. 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.

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

    PubMed

    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

    2009-06-04

    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.

  20. How to repair an episiotomy.

    PubMed

    Steen, Mary; Cummins, Bernie

    2016-02-17

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

  1. Nucleotide excision repair and photolyase repair of UV photoproducts in nucleosomes: assessing the existence of nucleosome and non-nucleosome rDNA chromatin in vivo.

    PubMed

    Tremblay, Maxime; Toussaint, Martin; D'Amours, Annie; Conconi, Antonio

    2009-02-01

    The genome is organized into nuclear domains, which create microenvironments that favor distinct chromatin structures and functions (e.g., highly repetitive sequences, centromeres, telomeres, noncoding sequences, inactive genes, RNA polymerase II and III transcribed genes, and the nucleolus). Correlations have been drawn between gene silencing and proximity to a heterochromatic compartment. At the other end of the scale are ribosomal genes, which are transcribed at a very high rate by RNA polymerase I (~60% of total transcription), have a loose chromatin structure, and are clustered in the nucleolus. The rDNA sequences have 2 distinct structures: active rRNA genes, which have no nucleosomes; and inactive rRNA genes, which have nucleosomes. Like DNA transcription and replication, DNA repair is modulated by the structure of chromatin, and the kinetics of DNA repair vary among the nuclear domains. Although research on DNA repair in all chromosomal contexts is important to understand the mechanisms of genome maintenance, this review focuses on nucleotide excision repair and photolyase repair of UV photoproducts in the first-order packing of DNA in chromatin: the nucleosome. In addition, it summarizes the studies that have demonstrated the existence of the 2 rDNA chromatins, and the way this feature of the rDNA locus allows for direct comparison of DNA repair in 2 very different structures: nucleosome and non-nucleosome DNA.

  2. Bone repair and stem cells.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

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

  3. Repair Types, Procedures - Part 2

    DTIC Science & Technology

    2010-05-01

    acceptable only if at least one undamaged flange remains in the existing internal structure. Sandwich repairs using extrusions or formed parts are better...easily be affected by bridging the damage with two L-angle extrusions fastened together through undamaged portions of the existing rod to form a ‘splint...Cell Repairs Rubber fuel bladders with damage less than 3 inches/7.6 cm can be repaired in a manner similar to patching tire inner-tubes using Buna-N

  4. 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

  5. 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.

  6. Repair of bilateral cleft lip and its variants

    PubMed Central

    Mulliken, John B.

    2009-01-01

    The surgeon who lifts a scalpel to repair a bilateral cleft lip and nasal deformity is accountable for: 1) precise craftsmanship based on three-dimensional features and four-dimensional changes; 2) periodic assessment throughout the child's growth; and 3) technical modifications during primary closure based on knowledge gained from long-term follow-up evaluation. These children should not have to endure the stares prompted by nasolabial stigmata that result from outdated concepts and technical misadventures. The principles for repair of bilateral complete cleft lip have evolved to such a level that the child's appearance should be equivalent to, or surpass, that of a unilateral complete cleft lip. These same principles also apply to the repair of the variants of bilateral cleft lip, although strategies and execution differ slightly. PMID:19884685

  7. 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

  8. Enhanced cartilage repair in ‘healer’ mice—New leads in the search for better clinical options for cartilage repair

    PubMed Central

    Fitzgerald, Jamie

    2016-01-01

    Adult articular cartilage has a poor capacity to undergo intrinsic repair. Current strategies for the repair of large cartilage defects are generally unsatisfactory because the restored cartilage does not have the same resistance to biomechanical loading as authentic articular cartilage and degrades over time. Recently, an exciting new research direction, focused on intrinsic cartilage regeneration rather than fibrous repair by external means, has emerged. This review explores the new findings in this rapidly moving field as they relate to the clinical goal of restoration of structurally robust, stable and non-fibrous articular cartilage following injury. PMID:27130635

  9. 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.

  10. State of the art in focused ion-beam mask repair systems

    NASA Astrophysics Data System (ADS)

    Stewart, Diane K.; Doherty, John A.; Doyle, Andrew F.; Morgan, John C.

    1995-07-01

    Focused ion beam (FIB) systems are commonly used to repair lithographic masks with features below one micron. We will summarize the development of focused ion beam mask repair systems starting from the original tools developed for photomasks approximately 10 years ago. The present state of the art in FIB mask repair systems is incorporated in two types of tools-one for repair of proximity print X-ray masks, and the other for repair of photomasks and some phase shift masks. Similarities of the two styles of systems include the gallium ion optics, the lithographic stage for accurate positioning, a thermal enclosure to minimize system drift, deflection and scanning electronics, and an interface to inspection data. The differences include the process chemistries, repair strategies, and imaging techniques. Examples of a variety of repaired defects on both X-ray and phase shift masks will be shown. Advanced masks such as those for EUV (Extreme Ultraviolet), DUV (Deep Ultraviolet), and SCALPEL (Scattering with Angular Limitation in Projection Electron Lithography) will have to be repaired should those technologies mature, and presumably with FIB tools. Preliminary research and development of advanced mask repair problems will be described and possible approaches will be suggested.

  11. 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.

  12. 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... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must...

  13. 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... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must...

  14. 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... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must...

  15. 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... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must...

  16. 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... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must...

  17. Aortic aneurysm repair - endovascular- discharge

    MedlinePlus

    ... MRI scan Aortic aneurysm repair - endovascular Aortic angiography Hardening of ... Center-Shreveport, Shreveport, LA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla ...

  18. 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.

  19. 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.

  20. Nucleotide excision repair in humans

    PubMed Central

    Spivak, Graciela

    2015-01-01

    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

  1. 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)

  2. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways.

    PubMed Central

    Boulton, S J; Jackson, S P

    1996-01-01

    Ku, a heterodimer of polypeptides of approximately 70 kDa and 80 kDa (Ku70 and Ku80, respectively), binds avidly to DNA double-strand breaks (DSBs). Mammalian cells defective in Ku are hypersensitive to ionizing radiation due to a deficiency in DSB repair. Here, we show that the simple inactivation of the Saccharomyces cerevisiae Ku70 homologue (Yku70p), does not lead to increased radiosensitivity. However, yku70 mutations enhance the radiosensitivity of rad52 strains, which are deficient in homologous recombination. Through establishing a rapid and reproducible in vivo plasmid rejoining assay, we show that Yku70p plays a crucial role in the repair of DSBs bearing cohesive termini. Whereas this damage is repaired accurately in YKU70 backgrounds, in yku70 mutant strains terminal deletions of up to several hundred bp occur before ligation ensues. Interestingly, this error-prone DNA repair pathway utilizes short homologies between the two recombining molecules and is thus highly reminiscent of a predominant form of DSB repair that operates in vertebrates. These data therefore provide evidence for two distinct and evolutionarily conserved illegitimate recombination pathways. One of these is accurate and Yku70p-dependent, whereas the other is error-prone and Yku70-independent. Furthermore, our studies suggest that Yku70 promotes genomic stability both by promoting accurate DNA repair and by serving as a barrier to error-prone repair processes. Images PMID:8890183

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

    PubMed

    Rupp, W Dean

    2013-12-13

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

  4. Structural aspects of DNA repair: the role of restricted diffusion.

    PubMed

    Minsky, Abraham

    2003-10-01

    DNA repair and protection processes impose arduous demands upon cellular systems. The high-fidelity recombinational repair pathway entails a rapid genome-wide search for sequence homology. The efficiency of this transaction is intriguing in light of the uniquely adverse diffusion traits of the involved species. DNA protection in cells exposed to continuous stress or prolonged starvation is equally enigmatic, because the ability of such cells to deploy energy-dependent enzymatic repair processes is hampered as a result of progressive perturbation of the intracellular energy balance. DNA repair in radio-resistant bacteria, which involves accurate chromosome reconstruction from multiple fragments, is similarly associated with apparently insurmountable logistical obstacles. The studies reviewed here imply that the mechanisms deployed to overcome these intrinsic hurdles have a basic common denominator. In all these cases, condensed and ordered chromatin assemblies are formed, within which molecular diffusion is restricted and confined. Restricted diffusion thus appears as a general strategy that is exploited by nature to facilitate homologous search, to promote energy-independent DNA protection through physical DNA sequestration and attenuated accessibility to damaging agents, and to enable error-free repair of multiple double-strand DNA breaks.

  5. 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

  6. Shining light on nanotechnology to help repair and regeneration.

    PubMed

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

    2013-01-01

    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.

  7. 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…

  8. Rehabilitation after Rotator Cuff Repair

    PubMed Central

    Nikolaidou, Ourania; Migkou, Stefania; Karampalis, Christos

    2017-01-01

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

  9. Shotcrete for Expedient Structural Repair

    DTIC Science & Technology

    1991-12-01

    AD-A260 788 ESL-TR-90-14 SHOTCRETE FOR EXPEDIENT STRUCTURAL REPAIR 4t ’Pit at MARK ANDERSON APPLIED RESEARCH ASSOCIATES, INC. P.O. BOX 40128...SUBTITrrLE S. FUNDING NUMBERS Shotcrete for Expedient Structural Repair 4. AUTHOR(S) F08635-88-C-0067 Anderson, Mark 7. PERFORMING ORGANIZATION NAME(S) AND...AVAILABILITY STATEMENT 12b. DISTRIBUTION CODE Approved for public release. Distribution unlimited. 13. ABSTRACT (Maximum 200 words) Shotcrete , or

  10. Durability of Expedient Repair Materials

    DTIC Science & Technology

    1993-03-01

    by the Flofida Department of Transportation. I&. SUWIUET" TERMS 󈧓. NUMBER OF 1A1ES Expedient Repair Materials 21PAGE Shotcrete Air Force Base...produced by CTS Cemem Company. A dry process shotcrete standard, MicrosilR, and a State of Florida corrosion - resistant concrete system, referred to as...34 durability of the rapid repair materials tested by conventional methods for determining durability. E. CONCLUSIONS The blended Rapid-SetR shotcrete system

  11. Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways

    PubMed Central

    Crippa, Stefania; Nemir, Mohamed; Ounzain, Samir; Ibberson, Mark; Berthonneche, Corinne; Sarre, Alexandre; Boisset, Gaëlle; Maison, Damien; Harshman, Keith; Xenarios, Ioannis; Diviani, Dario; Schorderet, Daniel; Pedrazzini, Thierry

    2016-01-01

    Aims The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary-conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish. Methods and results Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart. Conclusions This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart. PMID:26857418

  12. Role of mismatch repair in the Escherichia coli UVM response.

    PubMed

    Murphy, H S; Palejwala, V A; Rahman, M S; Dunman, P M; Wang, G; Humayun, M Z

    1996-12-01

    Mutagenesis at 3,N4-ethenocytosine (epsilonC), a nonpairing mutagenic lesion, is significantly enhanced in Escherichia coli cells pretreated with UV, alkylating agents, or H2O2. This effect, termed UVM (for UV modulation of mutagenesis), is distinct from known DNA damage-inducible responses, such as the SOS response, the adaptive response to alkylating agents, or the oxyR-mediated response to oxidative agents. Here, we have addressed the hypothesis that UVM results from transient depletion of a mismatch repair activity that normally acts to reduce mutagenesis. To test whether the loss of mismatch repair activities results in the predicted constitutive UVM phenotype, E. coli cells defective for methyl-directed mismatch repair, for very-short-patch repair, or for the N-glycosylase activities MutY and MutM were treated with the UVM-inducing agent 1-methyl-3-nitro-1-nitrosoguanidine, with subsequent transfection of M13 viral single-stranded DNA bearing a site-specific epsilonC lesion. Survival of the M13 DNA was measured as transfection efficiency, and mutation fixation at the lesion was characterized by multiplex sequencing technology. The results showed normal UVM induction patterns in all the repair-defective strains tested. In addition, normal UVM induction was observed in cells overexpressing MutH, MutL, or MutS. All strains displayed UVM reactivation, the term used to describe the increased survival of epsilonC-containing DNA in UVM-induced cells. Taken together, these results indicate that the UVM response is independent of known mismatch repair systems in E. coli and may thus represent a previously unrecognized misrepair or misreplication pathway.

  13. Arthroscopic revision of Bankart repair.

    PubMed

    Neri, Brian R; Tuckman, David V; Bravman, Jonathan T; Yim, Duke; Sahajpal, Deenesh T; Rokito, Andrew S

    2007-01-01

    The success of revision surgery for failed Bankart repair is not well known. This purpose of this study was to report the success rates achieved using arthroscopic techniques to revise failed Bankart repairs. Twelve arthroscopic revision Bankart repairs were performed on patients with recurrent unidirectional shoulder instability after open or arthroscopic Bankart repair. Follow-up was available on 11 of the 12 patients at a mean of 34.4 months (range, 25-56 months). The surgical findings, possible modes of failure, shoulder scores (Rowe score, University of California Los Angeles [UCLA], Simple Shoulder Test), and clinical outcome were evaluated. Various modes of failure were recognized during revision arthroscopic Bankart repairs. Good-to-excellent results were obtained in 8 patients (73%) undergoing revision stabilization according to Rowe and UCLA scoring. A subluxation or dislocation event occurred in 3 (27%) of the 11 patients at a mean of 8.7 months (range, 6-12 months) postoperatively. Arthroscopic revision Bankart repairs are technically challenging procedures but can be used to achieve stable, pain-free, functional shoulders with return to prior sport. Owing to limited follow-up and the small number of patients in this study, we were unable to conclude any pattern of failure or selection criteria for this procedure.

  14. Parastomal hernia repair. An update.

    PubMed

    Wara, P

    2011-04-01

    Repair of parastomal hernia remains controversial. Open suture repair of the fascial defect or stoma resiting are both associated with high morbidity and unacceptably high recurrence rates and are no longer recommended for routine use. Mesh repair appears to provide the best results. Following the first anectodal reports there are accumulating evidence that laparoscopic mesh repair is feasible and has a promising potential in the management of parastomal hernia. Two laparoscopic techniques have emerged, the use of a mesh with a slit and a central keyhole and a mesh without a slit, the latter often termed as a modified Sugarbaker. Published series, however, are observational and often with a short length of follow-up. Most series suffer from small sample size and controlled trials are lacking. The limited data, therefore, make it difficult to draw conclusions. At present none of the methods of open or laparoscopic mesh repair has proved superior. In spite of this laparoscopic repair has gained increasing acceptance. A polypropylene based mesh with an anti-adhesive layer covering the visceral side seems to be applicable using the keyhole technique with a slit as well as the modified Sugarbaker technique. A PTFE mesh should preferably be used with the modified Sugarbaker technique. If a PTFE mesh is used with the keyhole technique parastomal hernia is likely to recur.

  15. Treatment of Infected Aneurysms of the Abdominal Aorta and Iliac Artery with Endovascular Aneurysm Repair and Percutaneous Drainage.

    PubMed

    Chino, Shuji; Kato, Noriyuki; Noda, Yoshihiro; Oue, Kensuke; Tanaka, Satofumi; Hashimoto, Takashi; Higashigawa, Takatoshi; Miyake, Yoichiro; Okabe, Manabu

    2016-10-01

    Infected aneurysm remains one of the most challenging diseases for vascular surgeons. We describe the successful treatment of 2 cases of infected aneurysms with endovascular aneurysm repair and percutaneous computed tomography-guided drainage. This strategy may be an effective alternative to open surgical repair in selected patients.

  16. miRNA Control of Tissue Repair and Regeneration

    PubMed Central

    Sen, Chandan K.; Ghatak, Subhadip

    2016-01-01

    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. PMID:26056933

  17. Results of arthroscopic meniscal repair

    PubMed Central

    Orlowski, María Belén; Arroquy, Damián; Chahla, Jorge; Guiñazú, Jorge; Bisso, Martín Carboni; Vilaseca, Tomás

    2017-01-01

    Objectives: Currently the arthroscopic treatment of meniscal pathology has become one of the most common procedures in orthopedic practice and although in most cases meniscectomy is done, meniscal sutures are the treatment of choice when a reparable lesion is diagnosed, especially in young patients. It has been reported that the meniscal repair leads to a lower incidence of developing degenerative changes in the long-term when compared with meniscectomy and nonsurgical treatment of meniscal injuries. The aim of this study was to determine the success rate of meniscal repair achieved in our sports medicine practice. Methods: Between 2006 and 2015, 62 meniscal tears in 58 patients with a mean age of 31 years (range 15-58) were repaired. Mean follow-up was 52 months (range 6-120 months). In 16 patients (28%) was associated with arthroscopic ACL reconstruction. The repair techniques used included outside-in sutures, inside-out sutures, all-inside sutures and a combination of techniques. Failure of the repair was defined by the requirement for repeat knee arthroscopy and partial or subtotal meniscectomy. The indication of arthroscopic revision was based on the presence of mechanical symptoms, after the suture. Results: Failure of meniscus repair occurred in four patients (failure rate: 6.45%), one case was associated with ACL reconstruction (failure rate: 6.25%) and 3 had undergone isolated meniscal suture (failure rate: 8%). The average time for the reoperation was 15 months (4-24). We had no intraoperative complications. Conclusion: The reported failure rate of meniscal repair in stable knees varies between 12% and 43%, with reports that demonstrate a clinical success rate of 100%. In this study, we obtained a success rate of 93.5%. These results are slightly higher than those in the literature, which can be attributed to careful selection of patients and the fact that clinical success tends to be better than the assessed arthroscopically. In summary, we consider the

  18. TRIM proteins in therapeutic membrane repair of muscular dystrophy.

    PubMed

    Alloush, Jenna; Weisleder, Noah

    2013-07-01

    Muscular dystrophy represents a major unmet medical need; only palliative treatments exist for this group of debilitating diseases. Because multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity, a therapeutic approach that can target this loss of membrane function could be applicable to a number of these distinct diseases.One promising therapeutic approach involves the process the cell uses to repair injuries to the plasma membrane. Recent discoveries of genes associated with the membrane repair process provide an opportunity to promote this process as a way to treat muscular dystrophy. One such gene is mitsugumin 53 (MG53), a member of the tripartite motif (TRIM) family of proteins (TRIM72), which is an essential component of the membrane repair pathway in muscle. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the disease in mouse models of muscular dystrophy. There is great potential for the use of recombinant human MG53 in treating muscular dystrophy and other diseases in which compromised membrane integrity contributes to the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.

  19. Biomechanical Study of Two Peripheral Suture Methods on Repaired Tendons

    PubMed Central

    Qiu, Zhenling

    2015-01-01

    Flexor digitorum tendon injuries are challenging conditions to manage to ensure optimal patient outcomes. While several surgical approaches with high success rates have been developed, there remains no gold standard for suture technique for the repair of flexor tendon injuries. In this study, we compared two distinct peripheral suture methods on the strength of repaired tendons. Pig flexor digitorum profundus tendons were used in biomechanical studies and the biomechanical influence on tendon repair of continuous running peripheral suture (CRPS) and continuous locking peripheral suture (CLPS), were compared, using stitch length ranging from 1mm to 5mm. In CRPS, the 1mm stitch length group displayed the highest maximum load and breaking power, which was 1.57 fold higher than the 2mm stitch length group. Pairwise comparison revealed that the 1 and 2mm groups were statistically different from the 3, 4, and 5mm stitch length groups while comparison among the latter groups was not statistically significant. For CLPS, the 1mm group exhibited consistently the highest maximum load strength and breaking power, which was twice the strength displayed by the 2mm group. Pairwise comparisons between groups showed statistical significance. For future repairs of flexor tendon injuries, 1mm stitch length is highly recommended for simple peripheral suture.

  20. Human embryonic stem cells and cardiac repair.

    PubMed

    Zhu, Wei-Zhong; Hauch, Kip D; Xu, Chunhui; Laflamme, Michael A

    2009-01-01

    The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges.

  1. 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…

  2. 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…

  3. Distinctiveness Maps for Image Matching

    NASA Technical Reports Server (NTRS)

    Manduchi, Roberto; Tomasi, Carlo

    2000-01-01

    Stereo correspondence is hard because different image features can look alike. We propose a measure for the ambiguity of image points that allows matching distinctive points first and breaks down the matching task into smaller and separate subproblems. Experiments with an algorithm based on this measure demonstrate the ensuing efficiency and low likelihood of incorrect matches.

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

    PubMed

    de Semir, David; Aran, Josep M

    2006-08-01

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

  5. Algorithms for treating redundancy in repairable and non-repairable systems

    SciTech Connect

    Campbell, J.E.; Longsine, D.E.; Atkins, J.

    1993-10-01

    This report presents equations and computational algorithms for analyzing reliability of several forms of redundancy in repairable and non-repairable systems. For repairable systems, active, standby, and R of N redundancy with and without repair are treated. For non-repairable systems, active, standby, and R of N redundancy are addressed. These equations can be used to calculate mean time between failures, mean time to repair, and reliability for complex systems involving redundancy.

  6. 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.

  7. The design of repairable advanced composite structures

    NASA Technical Reports Server (NTRS)

    Hart-Smith, L. J.

    1985-01-01

    This paper addresses the repair of advanced composite structures by mechanical fasteners or by adhesive bonding. It is shown that many of today's composite designs are unreasonably difficult to repair. Conversely, the knowledge to design repairable structures is already available, if only it is applied during the initial design stage. Bolted or riveted repairs require only the avoidance of extremely orthotropic composite fiber patterns; those near the quasi-isotropic layup are the most suitable. Mildly orthotropic fiber patterns are appropriate for structures in which there is a dominant load direction. Thick composite structures are shown to require bolted or riveted repairs while thin structures favor adhesively bonded permanent repairs, although provisions can be easily made for temporary mechanical repairs. The reasons why integrally stiffened cocured composite designs are usually impractical to repair are explained and alternative repairable design concepts are presented.

  8. 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

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a) Purpose. Bacterial DNA damage or repair tests measure DNA damage which is expressed as differential...

  9. 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

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a) Purpose. Bacterial DNA damage or repair tests measure DNA damage which is expressed as differential...

  10. 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

    ... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.” (a) Purpose. Bacterial DNA damage or repair tests measure DNA damage which is expressed as differential...

  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. 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.

  13. 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.

  14. Bonded composite repair of composite structures

    NASA Astrophysics Data System (ADS)

    Mahler, Mary A.

    Repair and maintenance cost drives a large percentage of the lifetime cost of aircraft structures. Understanding repair issues can lead to a structure that significantly lowers the lifetime cost. Advanced composite materials, while offering the potential to increase aircraft capabilities with minimum weight, are more susceptible to repairable damage than conventional aircraft materials. Improved inspection and repair methods are required to ensure structural integrity and aircraft readiness in the existing operational environment. Many of today's innovative composite designs may result in aircraft structures that are unreasonably difficult to repair. As a first step, technical issues associated with bonded composite repair of composite structures were investigated. An extensive literature review identified many areas where real world composite repairs are being used successfully. An electronic database was developed summarizing the publications found during the literature review. The database includes publication, experimental test results and analytical results of advanced composite bonded repairs. The current analysis of repair does not account for the variations that exist in repair. To facilitate the analysis, a finite element interface was developed to provide analysts with a tool that would create complete finite element models of repaired structures efficiently and in a 3-dimensional view. The finite element models created by the developed interface were successfully correlated to test data for accuracy of the results. Parametric studies were performed using the interface to evaluate effects of repair variables. Thermal impact of repair on the repair panel is one area lacking attention in the repair literature. To understand the impact of heat and thermal gradients of the repair, an analytical investigation was performed to evaluate. the parameters affected by heat. For a solid laminate, the temperature at the adhesive bondline was investigated. The primary

  15. Percutaneous Rescue for Critical Mitral Stenosis Late After Mitral Valve Repair.

    PubMed

    Salenger, Rawn; Diao, Xavier; Dawood, Murtaza Y; Herr, Daniel L; Sample, George A; Pichard, Augusto; Gammie, James S

    2016-11-01

    We report a case of catastrophic hemodynamic compromise secondary to pannus ingrowth and severe mitral stenosis occurring years after repair of a nonrheumatic mitral valve. The initial repair included closure of a posterior leaflet cleft and implantation of an annuloplasty ring. We describe a hybrid treatment strategy for this severely compromised patient, which included initial placement of a right ventricular assist device followed by percutaneous balloon mitral valvuloplasty and, eventually, a definitive mitral valve reoperation. This case report reinforces the importance of routine clinical and echocardiographic follow-up for patients after mitral valve repair, and it includes the description of a novel therapeutic approach.

  16. Genes and junk in plant mitochondria-repair mechanisms and selection.

    PubMed

    Christensen, Alan C

    2014-06-05

    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.

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

    PubMed

    Chu, Constance R

    2015-04-01

    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.

  18. The RecQ DNA helicases in DNA repair.

    PubMed

    Bernstein, Kara A; Gangloff, Serge; Rothstein, Rodney

    2010-01-01

    The RecQ helicases are conserved from bacteria to humans and play a critical role in genome stability. In humans, loss of RecQ gene function is associated with cancer predisposition and/or premature aging. Recent experiments have shown that the RecQ helicases function during distinct steps during DNA repair; DNA end resection, displacement-loop (D-loop) processing, branch migration, and resolution of double Holliday junctions (dHJs). RecQ function in these different processing steps has important implications for its role in repair of double-strand breaks (DSBs) that occur during DNA replication and meiosis, as well as at specific genomic loci such as telomeres.

  19. 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.

  20. Unique methods for on-orbit structural repair, maintenance, and assembly

    NASA Technical Reports Server (NTRS)

    Anderson, Ray; Fuson, Phil

    1994-01-01

    This paper reviews the MDA independent research and development (IRAD) efforts since 1986 in the development of two distinctly different approaches to on-orbit tube repair: (1) one-piece mechanical tube fittings that are forced, under pressure, onto the tube outer surface to effect the repair; and (2) electron beam weldings as demonstrated with the Paton-developed universal hand tool (UHT) space welding system for the repair of fluid lines and tubular components. Other areas of potential on-orbit repair using the UHT include damage to the flat or curved surfaces of habitation modules and truss assemblies. This paper will also address MDA evaluation of the Paton UHT system for on-orbit coating, cleaning, brazing, and cutting of metals. MDA development of an on-orbit compatible nondestructive evaluation (NDE) system for the inspection of tube welds is an important part of this complete space welding capability and will be discussed in a separate paper.

  1. 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

  2. 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.

  3. Grima: A Distinct Emotion Concept?

    PubMed

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as 'grima' with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of 'grima' was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as 'grima', whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers.

  4. Grima: A Distinct Emotion Concept?

    PubMed Central

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M.; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as ‘grima’ with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of ‘grima’ was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as ‘grima’, whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers. PMID:28217102

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

    PubMed Central

    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.

    2016-01-01

    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

  6. Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival.

    PubMed

    Kumar, Azad; Purohit, Shruti; Sharma, Nilesh Kumar

    2016-12-01

    Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma.

  7. Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy

    PubMed Central

    Vila, Maria C; Rayavarapu, Sree; Hogarth, Marshall W; Van der Meulen, Jack H; Horn, Adam; Defour, Aurelia; Takeda, Shin'ichi; Brown, Kristy J; Hathout, Yetrib; Nagaraju, Kanneboyina; Jaiswal, Jyoti K

    2017-01-01

    Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic age for dysferlin-deficient mice. Restoring partial dystrophin expression by exon skipping improves mitochondrial function and offers potential to improve myofiber repair. These findings identify that mitochondrial deficit in muscular dystrophy compromises the repair of injured myofibers and show that this repair mechanism is distinct from and complimentary to the dysferlin-mediated repair of injured myofibers. PMID:27834955

  8. Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival

    PubMed Central

    Kumar, Azad; Purohit, Shruti; Sharma, Nilesh Kumar

    2016-01-01

    Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma. PMID:28053956

  9. BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

    PubMed Central

    Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

    2013-01-01

    BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

  10. 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)…

  11. Effect of polyamine depletion on DNA damage and repair following UV irradiation of HeLa cells.

    PubMed

    Snyder, R D; Sunkara, P S

    1990-09-01

    Treatment of HeLa cells with the polyamine biosynthesis inhibitors, methylglyoxal bis(guanylhydrazone) (MGBG), difluoromethylornithine (DFMO) or a combination of the two, resulted in reduction in cellular polyamine levels. Analysis of UV light-induced DNA damage and repair in these polyamine depleted cells revealed distinct differences in the repair process relative to that seen in cells possessing a normal polyamine complement. Initial yield of thymine dimers and rate of removal of these lesions from cellular DNA appeared normal in polyamine-depleted cells. However, depleted cells exhibited retarded sealing of DNA strand breaks resulting from cellular repair processes, reduced repair synthesis and an increased sensitivity to UV killing. Incision at damaged sites was not affected since ara-C repair-dependent breaks accumulated in a normal fashion. Molecular analysis of inhibited repair sites by exonuclease III and T4 DNA ligase probes suggest that the strand interruptions consist of gaps rather than ligatable nicks, consistent with an interpretation of the repair defect being at the gap-filling stage rather than the ligation step. Observed patterns of differential polyamine depletion by DFMO and MGBG, and partial reversal of repair inhibition by polyamine supplementation, suggests that polyamine depletion per se, rather than some secondary effect of inhibitor treatment, is responsible for the inhibition of repair.

  12. The culture of olfactory ensheathing cells (OECs)—a distinct glial cell type

    PubMed Central

    Higginson, Jennifer R.; Barnett, Susan C.

    2011-01-01

    Olfactory ensheathing cells (OECs) have become a popular candidate for the transplant-mediated repair of the damaged CNS. In this review a description is made of the origins of these cells and a historical development of their purification and maintenance in culture. In addition, we illustrate the cellular and molecular characteristics of OECs and emphasise that although they share many properties with Schwann cells, they possess several inherent differences which may allow them to be more beneficial for CNS repair. In summary, OECs are distinct glial cells and the detailed understanding of their biological and molecular properties is essential in ensuring their clinical efficacy after cell transplantation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair. PMID:20816825

  13. 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.

  14. Outreach Materials for the Collision Repair Campaign

    EPA Pesticide Factsheets

    The Collision Repair Campaign offers outreach materials to help collision repair shops reduce toxic air exposure. Materials include a DVD, poster, training video, and materials in Spanish (materiales del outreach en español).

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

    PubMed

    Sesia, Sergio B; Haecker, Frank-Martin; Mayr, Johannes

    2009-01-01

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

  16. Possible Muscle Repair in the Human Cardiovascular System.

    PubMed

    Sommese, Linda; Zullo, Alberto; Schiano, Concetta; Mancini, Francesco P; Napoli, Claudio

    2017-04-01

    The regenerative potential of tissues and organs could promote survival, extended lifespan and healthy life in multicellular organisms. Niches of adult stemness are widely distributed and lead to the anatomical and functional regeneration of the damaged organ. Conversely, muscular regeneration in mammals, and humans in particular, is very limited and not a single piece of muscle can fully regrow after a severe injury. Therefore, muscle repair after myocardial infarction is still a chimera. Recently, it has been recognized that epigenetics could play a role in tissue regrowth since it guarantees the maintenance of cellular identity in differentiated cells and, therefore, the stability of organs and tissues. The removal of these locks can shift a specific cell identity back to the stem-like one. Given the gradual loss of tissue renewal potential in the course of evolution, in the last few years many different attempts to retrieve such potential by means of cell therapy approaches have been performed in experimental models. Here we review pathways and mechanisms involved in the in vivo repair of cardiovascular muscle tissues in humans. Moreover, we address the ongoing research on mammalian cardiac muscle repair based on adult stem cell transplantation and pro-regenerative factor delivery. This latter issue, involving genetic manipulations of adult cells, paves the way for developing possible therapeutic strategies in the field of cardiovascular muscle repair.

  17. 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…

  18. 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…

  19. Anodization As A Repair Technique

    NASA Technical Reports Server (NTRS)

    Groff, Roy E.; Maloney, Robert D.; Reeser, Robert W.

    1988-01-01

    Thin, hard oxide layer added to aluminum part. Surfaces on aluminum part worn out of tolerance by no more than 0.004 in. often repaired by anodizing to build up aluminum oxide layers. Oxide layers very hard and grounded to desired final dimensions.

  20. 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…

  1. 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…

  2. Welding/brazing for Space Station repair

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

    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.

  3. 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…

  4. 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…

  5. 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...

  6. 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...

  7. 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…

  8. 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.

  9. Cleft palate repair and variations

    PubMed Central

    Agrawal, Karoon

    2009-01-01

    Cleft palate affects almost every function of the face except vision. Today a child born with cleft palate with or without cleft lip should not be considered as unfortunate, because surgical repair of cleft palate has reached a highly satisfactory level. However for an average cleft surgeon palatoplasty remains an enigma. The surgery differs from centre to centre and surgeon to surgeon. However there is general agreement that palatoplasty (soft palate at least) should be performed between 6-12 months of age. Basically there are three groups of palatoplasty techniques. One is for hard palate repair, second for soft palate repair and the third based on the surgical schedule. Hard palate repair techniques are Veau-Wardill-Kilner V-Y, von Langenbeck, two-flap, Aleveolar extension palatoplasty, vomer flap, raw area free palatoplasty etc. The soft palate techniques are intravelar veloplasty, double opposing Z-plasty, radical muscle dissection, primary pharyngeal flap etc. And the protocol based techniques are Schweckendiek's, Malek's, whole in one, modified schedule with palatoplasty before lip repair etc. One should also know the effect of each technique on maxillofacial growth and speech. The ideal technique of palatoplasty is the one which gives perfect speech without affecting the maxillofacial growth and hearing. The techniques are still evolving because we are yet to design an ideal one. It is always good to know all the techniques and variations so that one can choose whichever gives the best result in one's hands. A large number of techniques are available in literature, and also every surgeon incorporates his own modification to make it a variation. However there are some basic techniques, which are described in details which are used in various centres. Some of the important variations are also described. PMID:19884664

  10. Distinct responses to reduplicated chromosomes require distinct Mad2 responses.

    PubMed

    Stormo, Benjamin M; Fox, Donald T

    2016-05-09

    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.

  11. Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width.

    PubMed

    von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Meyenburg, Martina; Qin, Qianqian; Parekh, Sapun; Hellmann, Nadja; Husmann, Matthias

    2017-02-14

    Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca(2+) influx, lysosomal exocytosis, and membrane repair. And yet, replacing tryptophan (W318) with serine in Vibrio cholerae cytolysin enhanced toxicity. The data reveal divergent strategies evolved by two related small β-pore-forming toxins to manipulate target cells: phobalysin leads to fulminant perturbation of ion concentrations, closely followed by Ca(2+) influx-dependent membrane repair. In contrast, V. cholerae cytolysin causes insidious perturbations and escapes control by the cellular wounded membrane repair-like response.IMPORTANCE Previous studies demonstrated that large transmembrane pores, such as those formed by perforin or bacterial toxins of the cholesterol-dependent cytolysin family, trigger rapid, Ca(2+) influx-dependent repair mechanisms. In contrast, recovery from attack by the small β-pore-forming Staphylococcus aureus alpha-toxin or aerolysin is slow in comparison and does not depend on extracellular Ca(2+) To further elucidate the scope of Ca(2+) influx-dependent repair and understand its limitations, we compared the cellular responses to phobalysin and V. cholerae cytolysin, two related small β-pore-forming toxins which create membrane pores of slightly different sizes. The data indicate that the channel width of a small β-pore-forming toxin is a critical determinant of both primary

  12. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover.

    PubMed

    Street, John; Bao, Min; deGuzman, Leo; Bunting, Stuart; Peale, Franklin V; Ferrara, Napoleone; Steinmetz, Hope; Hoeffel, John; Cleland, Jeffrey L; Daugherty, Ann; van Bruggen, Nicholas; Redmond, H Paul; Carano, Richard A D; Filvaroff, Ellen H

    2002-07-23

    Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.

  13. 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.

  14. 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

  15. Antivesicant Strategies Based on DNA Repair and Apoptosis

    DTIC Science & Technology

    2005-10-01

    blood agents, hydrogen cyanide and cyanogen chloride; and respiratory agents, phosgene and diphosgene. Here we discuss sulfur mustard (SM), which...associated events such as oxidative stress, protease stimulation, lipid peroxidation etc., and (e) DNA damage-induced apoptosis via increase in PARP, p53 and...HEK (Rosenthal et al., 1998), and the p53 inhibitor curcumin inhibits SM-induced apoptosis in HEK (Ray et al., 2001). As will be explained later, we

  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. Repair of a Bacterial Small β-Barrel Toxin Pore Depends on Channel Width

    PubMed Central

    von Hoven, Gisela; Rivas, Amable J.; Neukirch, Claudia; Meyenburg, Martina; Qin, Qianqian; Parekh, Sapun

    2017-01-01

    ABSTRACT Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca2+-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae. In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca2+ influx, lysosomal exocytosis, and membrane repair. And yet, replacing tryptophan (W318) with serine in Vibrio cholerae cytolysin enhanced toxicity. The data reveal divergent strategies evolved by two related small β-pore-forming toxins to manipulate target cells: phobalysin leads to fulminant perturbation of ion concentrations, closely followed by Ca2+ influx-dependent membrane repair. In contrast, V. cholerae cytolysin causes insidious perturbations and escapes control by the cellular wounded membrane repair-like response. PMID:28196960

  18. Planned hernia repair and late abdominal wall reconstruction.

    PubMed

    Leppäniemi, Ari; Tukiainen, Erkki

    2012-03-01

    Planned ventral hernia is a management strategy in which the abdominal fascial layer has been left unclosed and the viscera are covered only with original or grafted skin. Leaving the fascia open can be deliberate or unavoidable and most commonly results from staged repair of the abdominal wall due to trauma, peritonitis, pancreatitis, abdominal vascular emergencies, or abdominal compartment syndrome. The abdominal wall defects can be categorized as type I or II defects depending on whether there is intact, stable skin coverage. In defects with intact skin coverage, the most commonly used methods are the components separation technique and a prosthetic repair, sometimes used in combination. The advantages of the components separation technique is the ability to close the linea alba at the midline, creating a better functional result than a repair with inert mesh. Although the reherniation risk seems higher after components separation, the risk of infection is considerably lower. With a type II defect, with absent or unstable skin coverage, fascial repair alone is inadequate. Of the more complex reconstruction techniques, the use of a free tensor fasciae latae (TFL) flap utilizing a saphenous vein arteriovenous loop is the most promising. The advantages of the TFL flap include constant anatomy of the pedicle, a strong fascial layer, large-caliber vessels matching the size of the AV loop, and the ability to use large flaps (up to 20 × 35 cm). Whatever technique is used, the repair of complex abdominal wall defects requires close collaboration with plastic and abdominal surgeons, which is best managed in specialized centers.

  19. 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.

  20. 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

  1. 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

    2016-08-25

    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.

  2. 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.

  3. 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.

  4. Rationale and emerging approaches for targeting lung repair and regeneration in the treatment of chronic obstructive pulmonary disease.

    PubMed

    Rennard, Stephen I; Wachenfeldt, Karin von

    2011-08-01

    Lung repair and regeneration are appropriate therapeutic targets for the treatment of chronic obstructive pulmonary disease (COPD). Abnormal repair results if fibrosis of the airways is a major contributor to fixed airflow limitation in airway disease. Inadequate repair in the face of tissue injury can contribute to the development of emphysema. With respect to the latter, acute exposure to cigarette smoke can impair repair responses of several cell types in the lung. Fibroblasts cultured from the lungs of patients with emphysema have persistent defects in repair that include modulation of extracellular matrix as well as production of growth factors that modulate other lung parenchymal cells. Some of the deficient repair functions appear to result from insensitivity to TGF-β and overproduction of prostaglandin E. Pharmacologic interventions targeting these pathways have the potential to at least partially reverse the abnormal repair. Alternate strategies that could modulate lung repair and regeneration could target resident or circulating stem/progenitor cells or potentially involve transplantation of new stem cells. Therapy directed at lung repair has the potential to restore lost lung function. In contrast to therapy designed to slow the progression of COPD, it may be much easier and less expensive to demonstrate efficacy for a therapy that restores lung function.

  5. 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

  6. 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

  7. Automatic OPC repair flow: optimized implementation of the repair recipe

    NASA Astrophysics Data System (ADS)

    Bahnas, Mohamed; Al-Imam, Mohamed; Word, James

    2007-10-01

    Virtual manufacturing that is enabled by rapid, accurate, full-chip simulation is a main pillar in achieving successful mask tape-out in the cutting-edge low-k1 lithography. It facilitates detecting printing failures before a costly and time-consuming mask tape-out and wafer print occur. The OPC verification step role is critical at the early production phases of a new process development, since various layout patterns will be suspected that they might to fail or cause performance degradation, and in turn need to be accurately flagged to be fed back to the OPC Engineer for further learning and enhancing in the OPC recipe. At the advanced phases of the process development, there is much less probability of detecting failures but still the OPC Verification step act as the last-line-of-defense for the whole RET implemented work. In recent publication the optimum approach of responding to these detected failures was addressed, and a solution was proposed to repair these defects in an automated methodology and fully integrated and compatible with the main RET/OPC flow. In this paper the authors will present further work and optimizations of this Repair flow. An automated analysis methodology for root causes of the defects and classification of them to cover all possible causes will be discussed. This automated analysis approach will include all the learning experience of the previously highlighted causes and include any new discoveries. Next, according to the automated pre-classification of the defects, application of the appropriate approach of OPC repair (i.e. OPC knob) on each classified defect location can be easily selected, instead of applying all approaches on all locations. This will help in cutting down the runtime of the OPC repair processing and reduce the needed number of iterations to reach the status of zero defects. An output report for existing causes of defects and how the tool handled them will be generated. The report will with help further learning

  8. Lower nucleotide excision repair capacity in newborns compared to their mothers: a pilot study.

    PubMed

    Vande Loock, Kim; Decordier, Ilse; Plas, Gina; Ciardelli, Roberta; Haumont, Dominique; Kirsch-Volders, Micheline

    2014-01-01

    Recognition of the potential vulnerability of children and newborns and protection of their health is essential, especially regarding to genotoxic compounds. Benzo(a)pyrene B(a)P a commonly found carcinogen, and its metabolite BPDE, are known to cross the placenta. To investigate how well newborns are able to cope with BPDE-induced DNA damage, a recent developed nucleotide excision repair cell phenotype assay was applied in a pilot study of 25 newborn daughters and their mothers, using the Alkaline Comet Assay and taking demographic data into account. Newborns seemed to be less able to repair BPDE-induced DNA damage since lower repair capacity levels were calculated compared to their mothers although statistical significance was not reached. Assessment of repair capacity in combination with genotypes will provide important information to support preventive strategies in neonatal care and to define science based exposure limits for pregnant women and children.

  9. 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.

  10. Electrical stimulation enhances cell migration and integrative repair in the meniscus

    NASA Astrophysics Data System (ADS)

    Yuan, Xiaoning; Arkonac, Derya E.; Chao, Pen-Hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Electrical signals have been applied towards the repair of articular tissues in the laboratory and clinical settings for over seventy years. We focus on healing of the meniscus, a tissue essential to knee function with limited innate repair potential, which has been largely unexplored in the context of electrical stimulation. Here we demonstrate for the first time that electrical stimulation enhances meniscus cell migration and integrative tissue repair. We optimize pulsatile direct current electrical stimulation parameters on cells at the micro-scale, and apply these to healing of full-thickness defects in explants at the macro-scale. We report increased expression of the adenosine A2b receptor in meniscus cells after stimulation at the micro- and macro-scale, and propose a role for A2bR in meniscus electrotransduction. Taken together, these findings advance our understanding of the effects of electrical signals and their mechanisms of action, and contribute to developing electrotherapeutic strategies for meniscus repair.

  11. DNA repair capacity of zebrafish.

    PubMed

    Sussman, Raquel

    2007-08-14

    Damage to the genome is unavoidable in living creatures, because of sunlight exposure as well as environmental chemicals present in food and drinking water. There is a need to monitor and purify the drinking water; therefore, several methods of detection have been developed. A very promising model system for this purpose is the zebrafish (Danio rerio), which is endowed with special qualities for detecting external as well as internal abnormalities. Grossman and Wei's assay [Grossman L, Wei Q (1995) Clin Chem 12:1854-1863], which measures the expression level of a nonreplicating recombinant plasmid DNA containing a UV-damaged luciferase reporter gene, shows that zebrafish can repair chromosomal lesions to a much greater extent than the human population. This vertebrate model is still very promising after possible down-regulation of the DNA repair enzymes.

  12. 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.

  13. The Cinderella of Communication Strategies: Reception Strategies in Interactive Listening.

    ERIC Educational Resources Information Center

    Vandergrift, Laurens

    1997-01-01

    Investigated the types of reception strategies and the frequency of their use by students of French as a second language at different levels of language proficiency, measured by an oral proficiency interview. A number of distinct strategies were identified: kinesics, global reprises, hypothesis testing in English and uptaking. Results are…

  14. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2015-10-01

    regeneration using our approach with an acellular nerve allograft to be equivalent to standard autograft repair in rodent models. An ongoing large animal ...be clinically acceptable for use in the animal studies in Aim 2. The anatomy of HAM is shown pictorially in Figure 7. In vivo, the epithelial...product. Given that the large animal studies with large caliber nerves in Aim 3 will use AxoGuard we feel that the single layer SIS material is totally

  15. Large Extremity Peripheral Nerve Repair

    DTIC Science & Technology

    2015-10-01

    approach with an acellular nerve allograft to be equivalent to standard autograft repair in rodent models. An ongoing large animal validation study...the animal studies in Aim 2. The anatomy of HAM is shown pictorially in Figure 7. In vivo, the epithelial layer is in contact with the amniotic...AxoGuard and Oasis SIS products are manufactured by Cook Medical. AxoGuard is simply a multi-layered SIS product. Given that the large animal studies with

  16. 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

  17. Magnesium Repair by Cold Spray

    DTIC Science & Technology

    2008-05-01

    were conducted using microstructural analysis, hardness, bond strength, and corrosion testing. 15. SUBJECT TERMS Cold spray, magnesium, aluminum ... corrosion pitting are the primary causes for removing the components from service. In addition, any repair must be confined to nonstructural areas of...unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT The U.S. Army has experienced significant corrosion problems with magnesium alloys that are used to

  18. Structural Health Monitoring of Repairs

    DTIC Science & Technology

    2010-05-01

    monitoring, the monitoring system consists of several design elements with defined interfaces. The raw monitoring signals are generated by a sensor with...is directly connected or integrated in the structure or repair. In Figure 2.3-1, the design element 1 is showing a surface mounted sensor. The...aircraft bus system. The monitoring data from the bus system are transferred to the next design element (element 4), where an onboard processing

  19. Targeted exome sequencing reveals distinct pathogenic variants in Iranians with colorectal cancer

    PubMed Central

    Ashktorab, Hassan; Mokarram, Pooneh; Azimi, Hamed; Olumi, Hasti; Varma, Sudhir; Nickerson, Michael L.; Brim, Hassan

    2017-01-01

    PURPOSE Next Generation Sequencing (NGS) is currently used to establish mutational profiles in many multigene diseases such as colorectal cancer (CRC), which is on the rise in many parts of the developing World including, Iran. Little is known about its genetic hallmarks in these populations. AIM To identify variants in 15 CRC-associated genes in patients of Iranian descent. RESULTS There were 51 validated variants distributed on 12 genes: 22% MSH3 (n = 11/51), 10% MSH6 (n = 5/51), 8% AMER1 (n = 4/51), 20% APC (n = 10/51), 2% BRAF (n = 1/51), 2% KRAS (n = 1/51), 12% PIK3CA (n = 6/51), 8% TGFβR2A (n = 4/51), 2% SMAD4 (n = 1/51), 4% SOX9 (n = 2/51), 6% TCF7L2 (n = 3/51), and 6% TP53 (n = 3/51). Most known and distinct variants were in mismatch repair genes (MMR, 32%) and APC (20%). Among oncogenes, PIK3CA was the top target (12%). MATERIALS AND METHODS CRC specimens from 63 Shirazi patients were used to establish the variant' profile on an Ion Torrent platform by targeted exome sequencing. To rule-out technical artifacts, the variants were validated in 13 of these samples using an Illumina NGS platform. Validated variants were annotated and compared to variants from publically available databases. An in-silico functional analysis was performed. MSI status of the analyzed samples was established. CONCLUSION These results illustrate for the first time CRC mutational profile in Iranian patients. MSH3, MSH6, APC and PIK3CA genes seem to play a bigger role in the path to cancer in this population. These findings will potentially lead to informed genetic diagnosis protocol and targeted therapeutic strategies. PMID:28002797

  20. Recombinational Repair of DNA Damage in Escherichia coli and Bacteriophage λ

    PubMed Central

    Kuzminov, Andrei

    1999-01-01

    Although homologous recombination and DNA repair phenomena in bacteria were initially extensively studied without regard to any relationship between the two, it is now appreciated that DNA repair and homologous recombination are related through DNA replication. In Escherichia coli, two-strand DNA damage, generated mostly during replication on a template DNA containing one-strand damage, is repaired by recombination with a homologous intact duplex, usually the sister chromosome. The two major types of two-strand DNA lesions are channeled into two distinct pathways of recombinational repair: daughter-strand gaps are closed by the RecF pathway, while disintegrated replication forks are reestablished by the RecBCD pathway. The phage λ recombination system is simpler in that its major reaction is to link two double-stranded DNA ends by using overlapping homologous sequences. The remarkable progress in understanding the mechanisms of recombinational repair in E. coli over the last decade is due to the in vitro characterization of the activities of individual recombination proteins. Putting our knowledge about recombinational repair in the broader context of DNA replication will guide future experimentation. PMID:10585965

  1. Effect of overuse-induced tendinopathy on tendon healing in a rat supraspinatus repair model.

    PubMed

    Tucker, Jennica J; Riggin, Corinne N; Connizzo, Brianne K; Mauck, Robert L; Steinberg, David R; Kuntz, Andrew F; Soslowsky, Louis J; Bernstein, Joseph

    2016-01-01

    Supraspinatus tears often result in the setting of chronic tendinopathy. However, the typical repair model utilizes an acute injury. In recognition of that distinction, our laboratory developed an overuse animal model; however it is unclear whether induced overuse is necessary in the repair model. We studied the repair properties of overuse-induced tendons compared to normal tendons. We hypothesized that histological and mechanical properties would not be altered between the overuse-induced and normal tendons 1 and 4 weeks after repair. Thirty-one adult male Sprague-Dawley rats were subjected to either overuse or cage activity for 4 weeks prior to bilateral supraspinatus tendon repair surgery. Rats were sacrificed at 1 and 4 weeks post-surgery and evaluated for histology and mechanics. Results at 1 week showed no clear histologic changes, but increased inflammatory protein expression in overuse tendons. At 4 weeks, percent relaxation was slightly increased in the overuse group. No other alterations in mechanics or histology were observed. Our results suggest that the effects of the surgical injury overshadow the changes evoked by overuse. Because clinically relevant mechanical parameters were not altered in the overuse group, we conclude that when examining tendons 4 weeks after repair in the classic rat supraspinatus model, inducing overuse prior to surgery is likely to be unnecessary.

  2. 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

  3. 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

  4. Exploiting the homologous recombination DNA repair network for targeted cancer therapy.

    PubMed

    Peng, Guang; Lin, Shiaw-Yih

    2011-02-10

    Genomic instability is a characteristic of cancer cells. In order to maintain genomic integrity, cells have evolved a complex DNA repair system to detect, signal and repair a diversity of DNA lesions. Homologous recombination (HR)-mediated DNA repair represents an error-free repair mechanism to maintain genomic integrity and ensure high-fidelity transmission of genetic information. Deficiencies in HR repair are of tremendous importance in the etiology of human cancers and at the same time offer great opportunities for designing targeted therapeutic strategies. The increase in the number of proteins identified as being involved in HR repair has dramatically shifted our concept of the proteins involved in this process: traditionally viewed as existing in a linear and simple pathway, today they are viewed as existing in a dynamic and interconnected network. Moreover, exploration of the targets within this network that can be modulated by small molecule drugs has led to the discovery of many effective kinase inhibitors, such as ATM, ATR, DNA-PK, CHK1, and CHK2 inhibitors. In preclinical studies, these inhibitors have been shown to sensitize cancer cells to chemotherapy and radiation therapy. The most exciting discovery in the field of HR repair is the identification of the synthetic lethality relationship between poly (ADP-ribose) polymerase (PARP) inhibitors and HR deficiency. The promises of clinical applications of PARP inhibitors and the concept of synthetic lethality also bring challenges into focus. Future research directions in the area of HR repair include determining how to identify the patients most likely to benefit from PARP inhibitors and developing strategies to overcome resistance to PARP inhibitors.

  5. 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.

  6. Laparoscopic Repair of Incidentally Found Spigelian Hernia

    PubMed Central

    Nickloes, Todd; Mancini, Greg; Solla, Julio A.

    2011-01-01

    Background and Objectives: A Spigelian hernia is a rare type of hernia that occurs through a defect in the anterior abdominal wall adjacent to the linea semilunaris. Estimation of its incidence has been reported as 0.12% of all abdominal wall hernias. Traditionally, the method of repair has been an open approach. Herein, we discuss a series of laparoscopic repairs. Methods: Case series and review of the literature. Cases: Three patients are presented. All were evaluated and taken to surgery initially for a different disease process, and all were incidentally found to have a spigelian hernia. These patients underwent laparoscopic repair of their hernias; 2 were repaired intraperitoneally and one was repaired totally extraperitoneally. Two patients initially underwent a mesh repair, while the third had an attempted primary repair. Conclusions: There is evidence that supports the use of laparoscopy for both diagnosis and repair of spigelian hernias. There are also reports of successful repairs both primarily and with mesh. In our experience with the preceding 3 patients, we found that laparoscopic repair of incidentally discovered spigelian hernias is a viable option, and we also found that implantation of mesh, when possible, resulted in satisfactory results and no recurrence. PMID:21902949

  7. The Interaction between Polynucleotide Kinase Phosphatase and the DNA Repair Protein XRCC1 Is Critical for Repair of DNA Alkylation Damage and Stable Association at DNA Damage Sites*

    PubMed Central

    Della-Maria, Julie; Hegde, Muralidhar L.; McNeill, Daniel R.; Matsumoto, Yoshihiro; Tsai, Miaw-Sheue; Ellenberger, Tom; Wilson, David M.; Mitra, Sankar; Tomkinson, Alan E.

    2012-01-01

    XRCC1 plays a key role in the repair of DNA base damage and single-strand breaks. Although it has no known enzymatic activity, XRCC1 interacts with multiple DNA repair proteins and is a subunit of distinct DNA repair protein complexes. Here we used the yeast two-hybrid genetic assay to identify mutant versions of XRCC1 that are selectively defective in interacting with a single protein partner. One XRCC1 mutant, A482T, that was defective in binding to polynucleotide kinase phosphatase (PNKP) not only retained the ability to interact with partner proteins that bind to different regions of XRCC1 but also with aprataxin and aprataxin-like factor whose binding sites overlap with that of PNKP. Disruption of the interaction between PNKP and XRCC1 did not impact their initial recruitment to localized DNA damage sites but dramatically reduced their retention there. Furthermore, the interaction between PNKP and the DNA ligase IIIα-XRCC1 complex significantly increased the efficiency of reconstituted repair reactions and was required for complementation of the DNA damage sensitivity to DNA alkylation agents of xrcc1 mutant cells. Together our results reveal novel roles for the interaction between PNKP and XRCC1 in the retention of XRCC1 at DNA damage sites and in DNA alkylation damage repair. PMID:22992732

  8. 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.

  9. Universal Principles in the Repair of Communication Problems.

    PubMed

    Dingemanse, Mark; Roberts, Seán G; Baranova, Julija; Blythe, Joe; Drew, Paul; Floyd, Simeon; Gisladottir, Rosa S; Kendrick, Kobin H; Levinson, Stephen C; Manrique, Elizabeth; Rossi, Giovanni; Enfield, N J

    2015-01-01

    There would be little adaptive value in a complex communication system like human language if there were no ways to detect and correct problems. A systematic comparison of conversation in a broad sample of the world's languages reveals a universal system for the real-time resolution of frequent breakdowns in communication. In a sample of 12 languages of 8 language families of varied typological profiles we find a system of 'other-initiated repair', where the recipient of an unclear message can signal trouble and the sender can repair the original message. We find that this system is frequently used (on average about once per 1.4 minutes in any language), and that it has detailed common properties, contrary to assumptions of radical cultural variation. Unrelated languages share the same three functionally distinct types of repair initiator for signalling problems and use them in the same kinds of contexts. People prefer to choose the type that is the most specific possible, a principle that minimizes cost both for the sender being asked to fix the problem and for the dyad as a social unit. Disruption to the conversation is kept to a minimum, with the two-utterance repair sequence being on average no longer that the single utterance which is being fixed. The findings, controlled for historical relationships, situation types and other dependencies, reveal the fundamentally cooperative nature of human communication and offer support for the pragmatic universals hypothesis: while languages may vary in the organization of grammar and meaning, key systems of language use may be largely similar across cultural groups. They also provide a fresh perspective on controversies about the core properties of language, by revealing a common infrastructure for social interaction which may be the universal bedrock upon which linguistic diversity rests.

  10. Yeast cells can access distinct quiescent states.

    PubMed

    Klosinska, Maja M; Crutchfield, Christopher A; Bradley, Patrick H; Rabinowitz, Joshua D; Broach, James R

    2011-02-15

    We conducted a phenotypic, transcriptional, metabolic, and genetic analysis of quiescence in yeast induced by starvation of prototrophic cells for one of three essential nutrients (glucose, nitrogen, or phosphate) and compared those results with those obtained with cells growing slowly due to nutrient limitation. These studies address two related questions: (1) Is quiescence a state distinct from any attained during mitotic growth, and (2) does the nature of quiescence differ depending on the means by which it is induced? We found that either limitation or starvation for any of the three nutrients elicits all of the physiological properties associated with quiescence, such as enhanced cell wall integrity and resistance to heat shock and oxidative stress. Moreover, the starvations result in a common transcriptional program, which is in large part a direct extrapolation of the changes that occur during slow growth. In contrast, the metabolic changes that occur upon starvation and the genetic requirements for surviving starvation differ significantly depending on the nutrient for which the cell is starved. The genes needed by cells to survive starvation do not overlap the genes that are induced upon starvation. We conclude that cells do not access a unique and discrete G(0) state, but rather are programmed, when nutrients are scarce, to prepare for a range of possible future stressors. Moreover, these survival strategies are not unique to quiescence, but are engaged by the cell in proportion to nutrient scarcity.

  11. 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.

  12. 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.

  13. 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.

  14. Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults.

    PubMed

    LeDoux, S P; Druzhyna, N M; Hollensworth, S B; Harrison, J F; Wilson, G L

    2007-04-14

    Cells of the CNS are constantly exposed to agents which damage DNA. Although much attention has been paid to the effects of this damage on nuclear DNA, the nucleus is not the only organelle containing DNA. Within each cell, there are hundreds to thousands of mitochondria. Within each mitochondrion are multiple copies of the mitochondrial genome. These genomes are extremely vulnerable to insult and mutations in mitochondrial DNA (mtDNA) have been linked to several neurodegenerative diseases, as well as the normal process of aging. The principal mechanism utilized by cells to avoid DNA mutations is DNA repair. Multiple pathways of DNA repair have been elucidated for nuclear DNA. However, it appears that only base excision repair is functioning in mitochondria. This repair pathway is responsible for the removal of most endogenous damage including alkylation damage, depurination reactions and oxidative damage. Within the rat CNS, there are cell-specific differences mtDNA repair. Astrocytes exhibit efficient repair, whereas, other glial cell types and neuronal cells exhibit a reduced ability to remove lesions from mtDNA. Additionally, a correlation was observed between those cells with reduced mtDNA repair and an increase in the induction of apoptosis. To demonstrate a causative relationship, a strategy of targeting DNA repair proteins to mitochondria to enhance mtDNA repair capacity was employed. Enhancement of mtDNA repair in oligodendrocytes provided protection from reactive oxygen species- and cytokine-induced apoptosis. These experiments provide a novel strategy for protecting sensitive CNS cells from genotoxic insults and thus provide new treatment options for neurodegenerative diseases.

  15. Diver assisted pipeline repair manual. Volume 3

    SciTech Connect

    Not Available

    1992-12-01

    This manual is comprised of vendor supplied parts lists and information on various aspects of underwater pipeline repair. Topics include mechanical repair components, welded repair components, inspection vehicles-tools, pipeline handling systems, cleaning and coatings removal tools, bolt-stud tensioning tools, friction welding, NDT tools, handling tools, pipe anchoring components, pigging and plugging equipment, corrosion preventative coatings, trenching-burial equipment. Also listed are diving contractors, support vessel operators and a bibliography of technical publications.

  16. Spall Repair of Wet Concrete Surfaces

    DTIC Science & Technology

    1990-01-01

    ILE COPY REPAIR, EVALUATION, MAINTENANCE, AND REHABILITATION RESEARCH PROGRAM TECHNICAL REPORT REMR-CS-25 SPALL REPAIR OF WET CONCRETE SURFACES by J...of the number designating technical reports of research published under the Repair, Evaluation. Maintenance. and Rehabilitation (REMR) Research ...Program identify the problem area under which the report was prepared Problem Area Problem Area CS Concrete and Steel Structures EM Electrical and

  17. 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.

  18. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development.

    PubMed

    Orii, Kenji E; Lee, Youngsoo; Kondo, Naomi; McKinnon, Peter J

    2006-06-27

    The repair of DNA double-strand breaks (DSBs) occurs via nonhomologous end-joining (NHEJ) or homologous recombination (HR). These mechanistically distinct pathways are critical for maintenance of genomic integrity and organismal survival. Although inactivation of either pathway leads to embryonic lethality, here we show selective requirements for each DNA DSB repair pathway at different stages of mammalian nervous system development. DNA damage-induced apoptosis resulting from inactivation of HR (Xrcc2 deficiency) only occurred in proliferating neural precursor cells, whereas disruption of NHEJ (DNA ligase IV deficiency) mainly affected differentiating cells at later developmental stages. Therefore, these data suggest that NHEJ is dispensable for a substantial portion of early development because DSB repair during this period utilizes HR. Moreover, DNA damage-induced apoptosis required the ataxia telangiectasia mutated (Atm) kinase after disruption of NHEJ, but not HR, during neurogenesis. However, embryonic lethality arising from disruption of either repair pathway was rescued by loss of p53 and resulted in specific tumor types reflective of the particular DSB repair pathway inactivated. Thus, these data reveal distinct tissue- and cell-type requirements for each DNA DSB repair pathway during neural development and provide insights for understanding the contributions of DNA DSB responses to disease.

  19. 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

  20. Plasma Membrane Repair in Health and Disease

    PubMed Central

    Demonbreun, Alexis R.; McNally, Elizabeth M.

    2016-01-01

    Since an intact membrane is required for normal cellular homeostasis, membrane repair is essential for cell survival. Human genetic studies, combined with the development of novel animal models and refinement of techniques to study cellular injury, have now uncovered series of repair proteins highly relevant for human health. Many of the deficient repair pathways manifest in skeletal muscle, where defective repair processes result in myopathies or other forms of muscle disease. Dysferlin is a membrane-associated protein implicated in sarcolemmal repair and also linked to other membrane functions including the maintenance of transverse tubules in muscle. MG53, annexins, and Eps15-homology domain (EHD)-containing proteins interact with dysferlin to form a membrane repair complex and similarly have roles in membrane trafficking in muscle. These molecular features of membrane repair are not unique to skeletal muscle, but rather skeletal muscle, due to its high demands, is more dependent on an efficient repair process. Phosphatidylserine and phosphatidylinositol 4, 5 bisphosphate, as well as Ca2+, are central regulators of membrane organization during repair. Given the importance of muscle health in disease and in aging, these pathways are targets to enhance muscle function and recovery from injury. PMID:26781830

  1. 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

  2. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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—...

  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. 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...

  5. 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...

  6. Oversized AAV transductifon is mediated via a DNA-PKcs-independent, Rad51C-dependent repair pathway.

    PubMed

    Hirsch, Matthew L; Li, Chengwen; Bellon, Isabella; Yin, Chaoying; Chavala, Sai; Pryadkina, Marina; Richard, Isabelle; Samulski, Richard Jude

    2013-12-01

    A drawback of gene therapy using adeno-associated virus (AAV) is the DNA packaging restriction of the viral capsid (<4.7 kb). Recent observations demonstrate oversized AAV genome transduction through an unknown mechanism. Herein, AAV production using an oversized reporter (6.2 kb) resulted in chloroform and DNase-resistant particles harboring distinct "fragment" AAV (fAAV) genomes (5.0, 2.4, and 1.6 kb). Fractionation experiments determined that only the larger "fragments" mediated transduction in vitro, and relatively efficient transduction was also demonstrated in the muscle, the eye, and the liver. In contrast with concatemerization-dependent large-gene delivery by split AAV, fAAV transduction is independent of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in vitro and in vivo while disproportionately reliant on the DNA strand-annealing protein Rad51C. Importantly, fAAV's unique dependence on DNA repair proteins, compared with intact AAV, strongly suggests that the majority of oversized AAV transduction is mediated by fragmented genomes. Although fAAV transduction is less efficient than intact AAV, it is enhanced fourfold in muscle and sevenfold in the retina compared with split AAV transduction. Furthermore, fAAV carrying codon-optimized therapeutic dysferlin cDNA in a 7.5 kb expression cassette restored dysferlin levels in a dystrophic model. Collectively, oversized AAV genome transduction requires unique DNA repair pathways and offers an alternative, more efficient strategy for large-gene therapy.

  7. Laparoscopic repair of parastomal hernia

    PubMed Central

    Yang, Xuefei; He, Kai; Hua, Rong; Shen, Qiwei

    2017-01-01

    Parastomal hernia is one of the most common long-term complications after abdominal ostomy. Surgical treatment for parastomal hernia is the only cure but a fairly difficult field because of the problems of infection, effects, complications and recurrence. Laparoscopic repair operations are good choices for Parastomal hernia because of their mini-invasive nature and confirmed effects. There are several major laparoscopic procedures for parastomal hernioplasty. The indications, technical details and complications of them will be introduced and discussed in this article. PMID:28251124

  8. RNF20-SNF2H Pathway of Chromatin Relaxation in DNA Double-Strand Break Repair.

    PubMed

    Kato, Akihiro; Komatsu, Kenshi

    2015-07-14

    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.

  9. Knee Articular Cartilage Repair and Restoration Techniques

    PubMed Central

    Richter, Dustin L.; Schenck, Robert C.; Wascher, Daniel C.; Treme, Gehron

    2015-01-01

    Context: Isolated chondral and osteochondral defects of the knee are a difficult clinical challenge, particularly in younger patients for whom alternatives such as partial or total knee arthroplasty are rarely advised. Numerous surgical techniques have been developed to address focal cartilage defects. Cartilage treatment strategies are characterized as palliation (eg, chondroplasty and debridement), repair (eg, drilling and microfracture [MF]), or restoration (eg, autologous chondrocyte implantation [ACI], osteochondral autograft [OAT], and osteochondral allograft [OCA]). Evidence Acquisition: PubMed was searched for treatment articles using the keywords knee, articular cartilage, and osteochondral defect, with a focus on articles published in the past 5 years. Study Design: Clinical review. Level of Evidence: Level 4. Results: In general, smaller lesions (<2 cm2) are best treated with MF or OAT. Furthermore, OAT shows trends toward greater longevity and durability as well as improved outcomes in high-demand patients. Intermediate-size lesions (2-4 cm2) have shown fairly equivalent treatment results using either OAT or ACI options. For larger lesions (>4 cm2), ACI or OCA have shown the best results, with OCA being an option for large osteochondritis dissecans lesions and posttraumatic defects. Conclusion: These techniques may improve patient outcomes, though no single technique can reproduce normal hyaline cartilage. PMID:26502188

  10. Targeting human oligodendrocyte progenitors for myelin repair.

    PubMed

    Dietz, Karen C; Polanco, Jessie J; Pol, Suyog U; Sim, Fraser J

    2016-09-01

    Oligodendrocyte development has been studied for several decades, and has served as a model system for both neurodevelopmental and stem/progenitor cell biology. Until recently, the vast majority of studies have been conducted in lower species, especially those focused on rodent development and remyelination. In humans, the process of myelination requires the generation of vastly more myelinating glia, occurring over a period of years rather than weeks. Furthermore, as evidenced by the presence of chronic demyelination in a variety of human neurologic diseases, it appears likely that the mechanisms that regulate development and become dysfunctional in disease may be, in key ways, divergent across species. Improvements in isolation techniques, applied to primary human neural and oligodendrocyte progenitors from both fetal and adult brain, as well as advancements in the derivation of defined progenitors from human pluripotent stem cells, have begun to reveal the extent of both species-conserved signaling pathways and potential key differences at cellular and molecular levels. In this article, we will review the commonalities and differences in myelin development between rodents and man, describing the approaches used to study human oligodendrocyte differentiation and myelination, as well as heterogeneity within targetable progenitor pools, and discuss the advances made in determining which conserved pathways may be both modeled in rodents and translate into viable therapeutic strategies to promote myelin repair.

  11. Ligament repair: a molecular and immunohistological characterization.

    PubMed

    Roseti, L; Buda, R; Cavallo, C; Desando, G; Facchini, A; Grigolo, B

    2008-01-01

    The anterior cruciate ligament (ACL) is the most commonly injured tissue of the human knee. Its poor ability to regenerate after injury represents a challenge to ligament tissue engineering. An understanding of the molecular composition of the structures used for its repair is essential for clinical assessments and for the implementation of tissue engineering strategies. The objective of this study was to evaluate, both at gene and protein levels, the expression of characteristic molecules in human ACL, patellar, semitendinosus and gracilis tendons and in the ligament reconstructed with patellar or semitendinosus and gracilis tendons. We demonstrated that primary ACL and tendon tissues all express collagen I, II, Sox-9, tenascin-C and aggrecan. Collagen X expression was detected at very low levels or undetectable. Cathepsin B, MMP-1 and MMP-13 were expressed at higher levels in the ACL reconstructed by the two tendons, showing that a remodeling process occurs during "ligamentization". Both our molecular and immunohistochemical evaluations did not reveal significative differences between the tendons and ligaments analyzed. However, ACL reconstructed with semitendinosus and gracilis tendon seems to present a higher expression of collagen type II when compared to that reconstructed with patellar tendon. This study could give a reasonable identification of genetic and protein markers specific to tendon/ligament tissues and be helpful in testing tissue engineering approaches for ACL reconstruction.

  12. Mood repair via attention refocusing or recall of positive autobiographical memories by adolescents with pediatric onset major depression

    PubMed Central

    Kovacs, Maria; Yaroslavsky, Ilya; Rottenberg, Jonathan; George, Charles J.; Baji, Ildikó; Benák, István; Dochnal, Roberta; Halas, Kitti; Kiss, Enikő; Vetró, Ágnes; Kapornai, Krisztina

    2014-01-01

    Background Impaired emotion regulation is increasingly recognized as a core feature of depressive disorders. Indeed, currently and previously depressed adults both report greater problems in attenuating sadness (mood repair) in daily life than healthy controls. In contrast, studies of various strategies to attenuate sad affect have mostly found that currently or previously depressed adults and controls were similarly successful at mood repair in the laboratory. But few studies have examined mood repair among depression-prone youths or the effects of trait characteristics on mood repair outcomes in the laboratory. Methods Adolescents, whose first episode of major depressive disorder (MDD) had onset at age 9, on average (probands), and were either in remission or depressed, and control peers, watched a sad film clip. Then, they were instructed to engage in re-focusing attention (distraction) or recalling happy memories. Using affect ratings provided by the youths, we tested two developmentally informed hypotheses about whether the subject groups would be similarly able to attenuate sadness via the two mood repair strategies. We also explored if self-reported habitual (trait) mood repair influenced laboratory performance. Results Contrary to expectations, attention re-focusing and recall of happy memories led to comparable mood benefits across subjects. Control adolescents reported significantly greater reductions in sadness than did depressed (Cohen’s d=.48) or remitted (Cohen’s d=.32) probands, regardless of mood repair strategy, while currently depressed probands remained the saddest after mood repair. Habitual mood repair styles moderated the effects of instructed (state) mood repair in the laboratory. Conclusions Whether depressed or in remission, adolescents with MDD histories are not as efficient at mood repair in the laboratory as controls. But proband-control group differences in mood repair outcomes were modest in scope, suggesting that the abilities

  13. Roles of PTEN with DNA Repair in Parkinson's Disease.

    PubMed

    Ogino, Mako; Ichimura, Mayuko; Nakano, Noriko; Minami, Akari; Kitagishi, Yasuko; Matsuda, Satoru

    2016-06-15

    Oxidative stress is considered to play key roles in aging and pathogenesis of many neurodegenerative diseases such as Parkinson's disease, which could bring DNA damage by cells. The DNA damage may lead to the cell apoptosis, which could contribute to the degeneration of neuronal tissues. Recent evidence suggests that PTEN (phosphatase and tensin homolog on chromosome 10) may be involved in the pathophysiology of the neurodegenerative disorders. Since PTEN expression appears to be one dominant determinant of the neuronal cell death, PTEN should be a potential molecular target of novel therapeutic strategies against Parkinson's disease. In addition, defects in DNA damage response and DNA repair are often associated with modulation of hormone signaling pathways. Especially, many observations imply a role for estrogen in a regulation of the DNA repair action. In the present review, we have attempted to summarize the function of DNA repair molecules at a viewpoint of the PTEN signaling pathway and the hormone related functional modulation of cells, providing a broad interpretation on the molecular mechanisms for treatment of Parkinson's disease. Particular attention will be paid to the mechanisms proposed to explain the health effects of food ingredients against Parkinson's disease related to reduce oxidative stress for an efficient therapeutic intervention.

  14. 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.

  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. Collective epithelial migration drives kidney repair after acute injury.

    PubMed

    Palmyre, Aurélien; Lee, Jeongeun; Ryklin, Gennadiy; Camarata, Troy; Selig, Martin K; Duchemin, Anne-Laure; Nowak, Paul; Arnaout, M Amin; Drummond, Iain A; Vasilyev, Aleksandr

    2014-01-01

    Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney's remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.

  17. Percutaneous Stent-Graft Repair of Anastomotic Pseudoaneurysms following Vascular Bypass Procedures: A Report of Two Cases

    PubMed Central

    Rundback, John; Haug, James; Herman, Kevin; Manno, Joseph; Cerda, Martin

    2013-01-01

    Anastomotic pseudoaneurysms are common entities following vascular bypass procedures and, if left untreated, serious complications such as thromboses, infection, and rupture can frequently occur. Therefore, attempts to employ various methods of repair have been utilized in treating anastomotic pseudoaneurysms to maximize operational success and future risk reduction. Herein, the authors report two cases of anastomotic pseudoaneurysms which were repaired percutaneously utilizing a combination of strategies such as careful preoperational image planning, multiple commercially available devices, and secondary embolization techniques. PMID:23365781

  18. Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infection.

    PubMed

    Heaton, Brook E; Barkan, Daniel; Bongiorno, Paola; Karakousis, Petros C; Glickman, Michael S

    2014-08-01

    Mycobacterium tuberculosis persistence within its human host requires mechanisms to resist the effector molecules of host immunity, which exert their bactericidal effects through damaging pathogen proteins, membranes, and DNA. Substantial evidence indicates that bacterial pathogens, including M. tuberculosis, require DNA repair systems to repair the DNA damage inflicted by the host during infection, but the role of double-strand DNA break (DSB) repair systems is unclear. Double-strand DNA breaks are the most cytotoxic form of DNA damage and must be repaired for chromosome replication to proceed. M. tuberculosis elaborates three genetically distinct DSB repair systems: homologous recombination (HR), nonhomologous end joining (NHEJ), and single-strand annealing (SSA). NHEJ, which repairs DSBs in quiescent cells, may be particularly relevant to M. tuberculosis latency. However, very little information is available about the phenotype of DSB repair-deficient M. tuberculosis in animal models of infection. Here we tested M. tuberculosis strains lacking NHEJ (a Δku ΔligD strain), HR (a ΔrecA strain), or both (a ΔrecA Δku strain) in C57BL/6J mice, C3HeB/FeJ mice, guinea pigs, and a mouse hollow-fiber model of infection. We found no difference in bacterial load, histopathology, or host mortality between wild-type and DSB repair mutant strains in any model of infection. These results suggest that the animal models tested do not inflict DSBs on the mycobacterial chromosome, that other repair pathways can compensate for the loss of NHEJ and HR, or that DSB repair is not required for M. tuberculosis pathogenesis.

  19. 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...

  20. 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.

  1. HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies

    PubMed Central

    Dok, Rüveyda; Nuyts, Sandra

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous disease that is the result of tobacco and/or alcohol abuse or infection with high-risk Human papillomaviruses. Despite the fact that HPV positive HNSCC cancers form a distinct clinical entity with better treatment outcome, all HNSCC are currently treated uniformly with the same treatment modality. At present, biologic basis of these different outcomes and their therapeutic influence are areas of intense investigation. In this review, we will summarize the molecular basis for this different outcome, novel treatment opportunities and possible biomarkers for HPV positive HNSCC. In particular, the focus will be on several molecular targeted strategies that can improve the chemoradiation response by influencing DNA repair mechanisms. PMID:27043631

  2. The segmentation of Thangka damaged regions based on the local distinction

    NASA Astrophysics Data System (ADS)

    Xuehui, Bi; Huaming, Liu; Xiuyou, Wang; Weilan, Wang; Yashuai, Yang

    2017-01-01

    Damaged regions must be segmented before digital repairing Thangka cultural relics. A new segmentation algorithm based on local distinction is proposed for segmenting damaged regions, taking into account some of the damaged area with a transition zone feature, as well as the difference between the damaged regions and their surrounding regions, combining local gray value, local complexity and local definition-complexity (LDC). Firstly, calculate the local complexity and normalized; secondly, calculate the local definition-complexity and normalized; thirdly, calculate the local distinction; finally, set the threshold to segment local distinction image, remove the over segmentation, and get the final segmentation result. The experimental results show that our algorithm is effective, and it can segment the damaged frescoes and natural image etc.

  3. 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

  4. The roles of vascular endothelial growth factor in bone repair and regeneration.

    PubMed

    Hu, Kai; Olsen, Bjorn R

    2016-10-01

    Vascular endothelial growth factor-A (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. Since bone is a highly vascularized organ and angiogenesis plays an important role in osteogenesis, VEGF also influences skeletal development and postnatal bone repair. Compromised bone repair and regeneration in many patients can be attributed to impaired blood supply; thus, modulation of VEGF levels in bones represents a potential strategy for treating compromised bone repair and improving bone regeneration. This review (i) summarizes the roles of VEGF at different stages of bone repair, including the phases of inflammation, endochondral ossification, intramembranous ossification during callus formation and bone remodeling; (ii) discusses different mechanisms underlying the effects of VEGF on osteoblast function, including paracrine, autocrine and intracrine signaling during bone repair; (iii) summarizes the role of VEGF in the bone regenerative procedure, distraction osteogenesis; and (iv) reviews evidence for the effects of VEGF in the context of repair and regeneration techniques involving the use of scaffolds, skeletal stem cells and growth factors.

  5. Misdirection and guidance of regenerating axons after experimental nerve injury and repair.

    PubMed

    de Ruiter, Godard C W; Spinner, Robert J; Verhaagen, Joost; Malessy, Martijn J A

    2014-02-01

    Misdirection of regenerating axons is one of the factors that can explain the limited results often found after nerve injury and repair. In the repair of mixed nerves innervating different distal targets (skin and muscle), misdirection may, for example, lead to motor axons projecting toward skin, and vice versa-that is, sensory axons projecting toward muscle. In the repair of motor nerves innervating different distal targets, misdirection may result in reinnervation of the wrong target muscle, which might function antagonistically. In sensory nerve repair, misdirection might give an increased perceptual territory. After median nerve repair, for example, this might lead to a dysfunctional hand. Different factors may be involved in the misdirection of regenerating axons, and there may be various mechanisms that can later correct for misdirection. In this review the authors discuss these different factors and mechanisms that act along the pathway of the regenerating axon. The authors review recently developed evaluation methods that can be used to investigate the accuracy of regeneration after nerve injury and repair (including the use of transgenic fluorescent mice, retrograde tracing techniques, and motion analysis). In addition, the authors discuss new strategies that can improve in vivo guidance of regenerating axons (including physical guidance with multichannel nerve tubes and biological guidance accomplished using gene therapy).

  6. Alterations of the subchondral bone in osteochondral repair--translational data and clinical evidence.

    PubMed

    Orth, P; Cucchiarini, M; Kohn, D; Madry, H

    2013-06-28

    Alterations of the subchondral bone are pathological features associated with spontaneous osteochondral repair following an acute injury and with articular cartilage repair procedures. The aim of this review is to discuss their incidence, extent and relevance, focusing on recent knowledge gained from both translational models and clinical studies of articular cartilage repair. Efforts to unravel the complexity of subchondral bone alterations have identified (1) the upward migration of the subchondral bone plate, (2) the formation of intralesional osteophytes, (3) the appearance of subchondral bone cysts, and (4) the impairment of the osseous microarchitecture as potential problems. Their incidence and extent varies among the different small and large animal models of cartilage repair, operative principles, and over time. When placed in the context of recent clinical investigations, these deteriorations of the subchondral bone likely are an additional, previously underestimated, factor that influences the long-term outcome of cartilage repair strategies. Understanding the role of the subchondral bone in both experimental and clinical articular cartilage repair thus holds great promise of being translated into further improved cell- or biomaterial-based techniques to preserve and restore the entire osteochondral unit.

  7. 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.

  8. Network-based characterization and prediction of human DNA repair genes and pathways

    PubMed Central

    Li, Yan-Hui; Zhang, Gai-Gai

    2017-01-01

    Network biology is a useful strategy to understand cell’s functional organization. In this study, for the first time, we successfully introduced network approaches to study properties of human DNA repair genes. Compared with non-DNA repair genes, we found distinguishing features for DNA repair genes: (i) they tend to have higher degrees; (ii) they tend to be located at global network center; (iii) they tend to interact directly with each other. Based on these features, we developed the first algorithm to predict new DNA repair genes. We tested several machine-learning models and found that support vector machine with kernel function of radial basis function (RBF) achieve the best performance, with precision = 0.74 and area under curve (AUC) = 0.96. In the end, we applied the algorithm to predict new DNA repair genes and got 32 new candidates. Literature supporting four of the predictions was found. We believe the network approaches introduced here might open a new avenue to understand DNA repair genes and pathways. The suggested algorithm and the predicted genes might be helpful for scientists in the field. PMID:28368026

  9. 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

  10. Mitral valve repair for ischemic mitral regurgitation: lessons from the Cardiothoracic Surgical Trials Network randomized study.

    PubMed

    Mihos, Christos G; 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.

  11. Inhibition of X-ray-induced DNA strand break repair in polyamine-depleted HeLa cells.

    PubMed

    Snyder, R D

    1989-05-01

    Treatment of HeLa cells with the polyamine biosynthesis inhibitors, alpha-difluoromethylornithine (DFMO) or methylglyoxal bis(guanylhydrazone) (MGBG), results in, depending on the conditions, partial or complete depletion of the cellular polyamines: putrescine, spermidine and spermine. In this compromised state cells exhibited a distinct deficiency in repair of X-ray-induced DNA strand breaks. The half-time for return of normal DNA sedimentation following 1.6 Gy was 9.5 min for untreated control cells and 22, 32 and 50 min for cells treated with MGBG, DFMO + MGBG and DFMO, respectively. Normal repair kinetics were restored to these cells upon a short incubation in media containing all three polyamines. The rapid early phase of repair following higher X-ray doses (16 Gy) was also delayed in polyamine-depleted cells but later repair occurring 1-4 h post-irradiation, representing chromatin reconstitution, was apparently normal.

  12. DNA repair and cytotoxic drugs: the potential role of RAD51 in clinical outcome of non-small-cell lung cancer patients.

    PubMed

    Nogueira, Augusto; Assis, Joana; Catarino, Raquel; Medeiros, Rui

    2013-04-01

    Many of the cytotoxic drugs used in the treatment of non-small-cell lung carcinoma patients can interfere with DNA activity and the definition of an individual DNA repair profile could be a key strategy to achieve better response to chemotherapeutic treatment. Although DNA repair mechanisms are important factors in the prevention of carcinogenesis, these molecular pathways are also involved in therapy response. RAD51 is a crucial element in DNA repair by homologous recombination and has been shown to interfere with the prognosis of patients treated with chemoradiotherapy. There is increasing evidence that genetic polymorphisms in repair enzymes can influence DNA repair capacity and, consequently, affect chemotherapy efficacy. We conducted this review to show the possible influence of the RAD51 genetic variants in damage repair capacity and treatment response in non-small-cell lung carcinoma patients.

  13. Regenerative endodontics: regeneration or repair?

    PubMed

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

    2014-04-01

    Recent advances in biotechnology and translational research have made it possible to provide treatment modalities that protect the vital pulp, allow manipulation of reactionary and reparative dentinogenesis, and, more recently, permit revascularization of an infected root canal space. These approaches are referred to as regenerative procedures. The method currently used to determine the origin of the tissue secreted during the repair/regeneration process is largely based on the identification of cellular markers (usually proteins) left by cells that were responsible for this tissue production. The presence of these proteins in conjunction with other indicators of cellular behavior (especially biomineralization) and analysis of the structure of the newly generated tissue allow conclusions to be made of how it was formed. Thus far, it has not been possible to truly establish the biological mechanism controlling tertiary dentinogenesis. This article considers current therapeutic techniques to treat the dentin-pulp complex and contextualize them in terms of reparative and regenerative processes. Although it may be considered a semantic argument rather than a biological one, the definitions of regeneration and repair are explored to clarify our position in this era of regenerative endodontics.

  14. Dynamics of DNA Mismatch Repair

    NASA Astrophysics Data System (ADS)

    Coats, Julie; Lin, Yuyen; Rasnik, Ivan

    2009-11-01

    DNA mismatch repair protects the genome from spontaneous mutations by recognizing errors, excising damage, and re-synthesizing DNA in a pathway that is highly conserved. Mismatch recognition is accomplished by the MutS family of proteins which are weak ATPases that bind specifically to damaged DNA, but the specific molecular mechanisms by which these proteins recognize damage and initiate excision are not known. Previous structural investigations have implied that protein-induced conformational changes are central to mismatch recognition. Because damage detection is a highly dynamic process in which conformational changes of the protein-DNA complexes occur on a time scale of a few seconds, it is difficult to obtain meaningful kinetic information with traditional ensemble techniques. In this work, we use single molecule fluorescence resonance energy transfer (smFRET) to study the conformational dynamics of fluorescently labeled DNA substrates in the presence of the mismatch repair protein MutS from E. coli and its human homolog MSH2/MSH6. Our studies allow us to obtain quantitative kinetic information about the rates of binding and dissociation and to determine the conformational states for each protein-DNA complex.

  15. 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

  16. Motivational Spiral Models (MSM): common and distinct motivations in context.

    PubMed

    Fisher, Laurel J

    2013-01-01

    Motivational Spiral Models (MSM) show links over time among self concepts, feelings, strategies, skills and participation in everyday activities. In theory, MSM have many common features, with distinct features in particular contexts. This project examined children's motivation to participate in literacy (MSM-L), social (MSM-S) and physical activities (MSM-P). The participants in Study 1 (N = 32) were 9 to 11 years old, and in Study 2 (N = 73) were 4 to 12 year old children. Locations were close to the Australian national average in socio-economic indicators, and initial screening showed these were representative samples. Analyses used variable-oriented correlational models as well as person-oriented clusters that suggest the standard and alternative motivational pathways. The results of Study 1 suggested bi-directional links between children's self concepts and participation in activities. Study 2 identified the common features as: openness and stability over time; and self concepts that motivate and justify participation in activities. Distinct features of MSM-L show the few negative feelings that may limit reading. In MSM-S, self concepts support the positive feelings, and in MSM-P, positive feelings support the task strategies. In conclusion, findings support MSM theory with common features based on self concepts and distinct features of developing motivations in particular contexts. MSM provide a sound base for future research in the contexts of everyday activities for children. In addition, there are practical applications of the findings to prevention, monitoring and intervention programmes.

  17. Municipal solid waste landfills harbor distinct microbiomes

    USGS Publications Warehouse

    Stamps, Blake W.; Lyles, Christopher N.; Suflita, Joseph M.; Masoner, Jason R.; Cozzarelli, Isabelle M.; Kolpin, Dana W.; Stevenson, Bradley S.

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its “built environments.” Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of “landfill microbiomes” and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity.

  18. Municipal Solid Waste Landfills Harbor Distinct Microbiomes

    PubMed Central

    Stamps, Blake W.; Lyles, Christopher N.; Suflita, Joseph M.; Masoner, Jason R.; Cozzarelli, Isabelle M.; Kolpin, Dana W.; Stevenson, Bradley S.

    2016-01-01

    Landfills are the final repository for most of the discarded material from human society and its “built environments.” Microorganisms subsequently degrade this discarded material in the landfill, releasing gases (largely CH4 and CO2) and a complex mixture of soluble chemical compounds in leachate. Characterization of “landfill microbiomes” and their comparison across several landfills should allow the identification of environmental or operational properties that influence the composition of these microbiomes and potentially their biodegradation capabilities. To this end, the composition of landfill microbiomes was characterized as part of an ongoing USGS national survey studying the chemical composition of leachates from 19 non-hazardous landfills across 16 states in the continental U.S. The landfills varied in parameters such as size, waste composition, management strategy, geography, and climate zone. The diversity and composition of bacterial and archaeal populations in leachate samples were characterized by 16S rRNA gene sequence analysis, and compared against a variety of physical and chemical parameters in an attempt to identify their impact on selection. Members of the Epsilonproteobacteria, Gammaproteobacteria, Clostridia, and candidate division OP3 were the most abundant. The distribution of the observed phylogenetic diversity could best be explained by a combination of variables and was correlated most strongly with the concentrations of chloride and barium, rate of evapotranspiration, age of waste, and the number of detected household chemicals. This study illustrates how leachate microbiomes are distinct from those of other natural or built environments, and sheds light on the major selective forces responsible for this microbial diversity. PMID:27148222

  19. Outcome of Staged Repair of Tetralogy of Fallot with Pulmonary Atresia and a Ductus-dependent Pulmonary Circulation: Should Primary Repair Be Considered?

    PubMed Central

    Kim, Hyungtae; Chang, Yun Hee; Jung, Wonkil; Lee, Hyoung Doo; Park, Ji Ae; Huh, Up

    2011-01-01

    Background The tetralogy of Fallot (TOF) with pulmonary atresia (PA) and a ductus-dependent pulmonary circulation (no major aorto-pulmonary collateral arteries (MAPCAs)) has been treated with staged repair or primary repair depending on the preference of surgeons or institutions. We evaluated the 19-year outcome of staged repair for this anomaly to find out whether our surgical strategy should be changed. Materials and Methods Forty-four patients with TOF/PA with patent ductus arteriosus (PDA) who underwent staged repair from June 1991 to October 2010 were included in this retrospective study. The patients with MAPCAs were excluded. The average age at the first palliative shunt surgery was 40.8±67.5 days (range: 0~332 days). Thirty-one patients (31/44, 70%) were neonates. The average weight was 3.5±1.6 kg (range: 1.6~8.7 kg). A modified Blalock-Taussig (BT) shunt was performed in 38 patients, classic BT shunt in 4 patients, and central shunt in 2 patients. Six patients required concomitant procedures: pulmonary artery angioplasty was performed in 4 patients, pulmonary artery reconstruction in one patient, and re-implantation of the left pulmonary artery to the main pulmonary artery in one patient. Four patients required a second shunt operation before the definitive repair was performed. Thirty-three patients underwent definitive repair at 24.2±13.3 months (range: 7.3~68 months) after the first palliative operation. The average age at the time of definitive repair was 25.4±13.5 months (range: 7.6~68.6 months) and their average weight was 11.0±2.1 kg. For definitive repair, 3 types of right ventricular outflow procedures were used: extra-cardiac conduit was performed in 30 patients, trans-annular patch in 2 patients, and REV operation in 1 patient. One patient was lost to follow-up after hospital discharge. The mean follow-up duration for the rest of the patients was 72±37 months (range: 4~160 months). Results Ten patients (10/44, 22.7%) died before the

  20. Evaluation of Vibratory Rollers for Bomb Damage Repair.

    DTIC Science & Technology

    1980-08-01

    Repair Base Course Bomb Damage Repair Crushed Stone Vibratory Rollers\\ Soil Compaction Unsurfaced Repairs 0. ABSTRACT (Continue on reveres aide if...3 Test Areas ....... ............. ............ 3 Vibratory Rollers............................... 3 Soils ...Roller Evaluation Tests ................. 16 Soil Preparation and Placement ................ 16 Compaction .................................... 16

  1. 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)

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 40 CFR 60.482-9 - Standards: Delay of repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... purged material resulting from immediate repair are greater than the fugitive emissions likely to result from delay of repair, and (2) When repair procedures are effected, the purged material is collected...

  13. 40 CFR 61.242-10 - Standards: Delay of repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... repair for valves will be allowed if: (1) The owner or operator demonstrates that emissions of purged... delay of repair, and (2) When repair procedures are effected, the purged material is collected...

  14. 5. EXTERIOR VIEW OF THE NORTH REPAIR BAY OF THE ...

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

    5. EXTERIOR VIEW OF THE NORTH REPAIR BAY OF THE MOTOR REPAIR SHOP, BUILDING 104, LOOKING WEST. - Mill Valley Air Force Station, Motor Repair & Auto Hobby Shop, East Ridgecrest Boulevard, Mount Tamalpais, Mill Valley, Marin County, CA

  15. HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins

    PubMed Central

    Hrecka, Kasia; Hao, Caili; Shun, Ming-Chieh; Kaur, Sarabpreet; Swanson, Selene K.; Florens, Laurence; Washburn, Michael P.; Skowronski, Jacek

    2016-01-01

    HIV replication in nondividing host cells occurs in the presence of high concentrations of noncanonical dUTP, apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) cytidine deaminases, and SAMHD1 (a cell cycle-regulated dNTP triphosphohydrolase) dNTPase, which maintains low concentrations of canonical dNTPs in these cells. These conditions favor the introduction of marks of DNA damage into viral cDNA, and thereby prime it for processing by DNA repair enzymes. Accessory protein Vpr, found in all primate lentiviruses, and its HIV-2/simian immunodeficiency virus (SIV) SIVsm paralogue Vpx, hijack the CRL4DCAF1 E3 ubiquitin ligase to alleviate some of these conditions, but the extent of their interactions with DNA repair proteins has not been thoroughly characterized. Here, we identify HLTF, a postreplication DNA repair helicase, as a common target of HIV-1/SIVcpz Vpr proteins. We show that HIV-1 Vpr reprograms CRL4DCAF1 E3 to direct HLTF for proteasome-dependent degradation independent from previously reported Vpr interactions with base excision repair enzyme uracil DNA glycosylase (UNG2) and crossover junction endonuclease MUS81, which Vpr also directs for degradation via CRL4DCAF1 E3. Thus, separate functions of HIV-1 Vpr usurp CRL4DCAF1 E3 to remove key enzymes in three DNA repair pathways. In contrast, we find that HIV-2 Vpr is unable to efficiently program HLTF or UNG2 for degradation. Our findings reveal complex interactions between HIV-1 and the DNA repair machinery, suggesting that DNA repair plays important roles in the HIV-1 life cycle. The divergent interactions of HIV-1 and HIV-2 with DNA repair enzymes and SAMHD1 imply that these viruses use different strategies to guard their genomes and facilitate their replication in the host. PMID:27335459

  16. 40 CFR 65.105 - Leak repair.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... pump that meets the requirements of § 65.107(e)(2) will be installed; or (C) A system that routes.... First attempt at repair for pumps includes, but is not limited to, tightening the packing gland nuts and... destroyed or recovered in a control device complying with § 65.115. (4) Delay of repair for pumps is...

  17. Robot Service and Repair. Teacher's Guide.

    ERIC Educational Resources Information Center

    Pittsburg State Univ., KS. Kansas Vocational Curriculum Dissemination Center.

    This document is a teacher's guide for teaching a course on robot service and repair. The guide is organized in four units covering the following topics: introduction to robots, power supply, robot control systems, and service and repair. Each unit contains several lesson plans on the unit topic. Lesson plans consist of objectives, tools and…

  18. Robot Service and Repair. Student Guide.

    ERIC Educational Resources Information Center

    Pittsburg State Univ., KS. Kansas Vocational Curriculum Dissemination Center.

    This document is a student guide for a course on robot service and repair. It is organized in four units covering the following topics: introduction to robots, power supply, robot control systems, and service and repair. Each unit contains several lesson plans on the unit topic. Lesson plans consist of lesson objectives, lists of teaching aids and…

  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. Flavonoids and DNA Repair in Prostate Cancer

    DTIC Science & Technology

    2005-12-01

    hours of naringenin treatment. The tea flavonoid EGC and apigenin from parsley did not show any DNA repair-stimulatory activity. 15. SUBJECT TERMS No...flavonoids to continue the investigations on the stimulatory effect on DNA repair: -naringenin from citrus -apigenin from parsley -epicatechin

  1. 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.

  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. 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.

  4. 46 CFR 160.006-2 - Repairing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 6 2010-10-01 2010-10-01 false Repairing. 160.006-2 Section 160.006-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS.... No repairs, except in emergency, shall be made to an approved life preserver without advance...

  5. 30 CFR 56.6801 - Vehicle repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 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...

  6. 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...

  7. 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...

  8. 30 CFR 56.6801 - Vehicle repair.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 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...

  9. 30 CFR 57.6801 - Vehicle repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 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 57.6801 - Vehicle repair.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 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...

  11. 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...

  12. 30 CFR 57.6801 - Vehicle repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 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. 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...

  14. 30 CFR 56.6801 - Vehicle repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 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...

  15. Anatomy essentials for laparoscopic inguinal hernia repair

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

    Laparoscopic inguinal hernia repair is performed more and more nowadays. The anatomy of these procedures is totally different from traditional open procedures because they are performed from different direction and in different space. The important anatomy essentials for laparoscopic inguinal hernia repair will be discussed in this article. PMID:27826575

  16. Evaluation of Rapid-Setting Concretes for Airfield Spall Repair

    DTIC Science & Technology

    1991-04-01

    repair concretes for Rapid Runway Repair (RRR). The three were a methyl methacrylate binder (Silikal RI7AF), a magnesium phosphate mortar mix (Set-45...Performance Reauirements Definition of small repair 5. The Rapid Runway Repair Program of the US Air Force (USAF) includes the activities that must be performed...scenario for wartime spall repair includes the expectation that a runway will be damaged by tens to hundreds of spalls at one time. The repair activity

  17. Evidence for a dynamic role for mononuclear phagocytes during endometrial repair and remodelling

    PubMed Central

    Cousins, Fiona L.; Kirkwood, Phoebe M.; Saunders, Philippa T. K.; Gibson, Douglas A.

    2016-01-01

    In women, endometrial breakdown, which is experienced as menstruation, is characterised by high concentrations of inflammatory mediators and immune cells which account for ~40% of the stromal compartment during tissue shedding. These inflammatory cells are known to play a pivotal role in tissue breakdown but their contribution to the rapid scarless repair of endometrium remains poorly understood. In the current study we used a mouse model of menstruation to investigate dynamic changes in mononuclear phagocytes during endometrial repair and remodelling. Menstruation was simulated in MacGreen mice to allow visualisation of CSF1R+ mononuclear phagocytes. Immunohistochemistry revealed dynamic spatio-temporal changes in numbers and location of CSF1R-EGFP+ cells and Ly6G+ neutrophils. Flow cytometry confirmed a striking increase in numbers of GFP+ cells during repair (24 h): influxed cells were 66% F4/80+Gr-1+ and 30% F4/80−Gr-1+. Immunostaining identified distinct populations of putative ‘classical’ monocytes (GFP+F4/80−), monocyte-derived macrophages (GFP+F4/80+) and a stable population of putative tissue-resident macrophages (GFP-F4/80+) localised to areas of breakdown, repair and remodelling respectively. Collectively, these data provide the first compelling evidence to support a role for different populations of monocytes/macrophages in endometrial repair and provide the platform for future studies on the role of these cells in scarless healing. PMID:27827431

  18. The power of DNA double-strand break (DSB) repair testing to predict breast cancer susceptibility.

    PubMed

    Keimling, Marlen; Deniz, Miriam; Varga, Dominic; Stahl, Andreea; Schrezenmeier, Hubert; Kreienberg, Rolf; Hoffmann, Isabell; König, Jochem; Wiesmüller, Lisa

    2012-05-01

    Most presently known breast cancer susceptibility genes have been linked to DSB repair. To identify novel markers that may serve as indicators for breast cancer risk, we performed DSB repair analyses using a case-control design. Thus, we examined 35 women with defined familial history of breast and/or ovarian cancer (first case group), 175 patients with breast cancer (second case group), and 245 healthy women without previous cancer or family history of breast cancer (control group). We analyzed DSB repair in peripheral blood lymphocytes (PBLs) by a GFP-based test system using 3 pathway-specific substrates. We found increases of microhomology-mediated nonhomologous end joining (mmNHEJ) and nonconservative single-strand annealing (SSA) in women with familial risk vs. controls (P=0.0001-0.0022) and patients with breast cancer vs. controls (P=0.0004-0.0042). Young age (<50) at initial diagnosis of breast cancer, which could be indicative of genetic predisposition, was associated with elevated SSA using two different substrates, amounting to similar odds ratios (ORs=2.54-4.46, P=0.0059-0.0095) as for familial risk (ORs=2.61-4.05, P=0.0007-0.0045). These findings and supporting validation data underscore the great potential of detecting distinct DSB repair activities in PBLs as method to estimate breast cancer susceptibility beyond limitations of genotyping and to predict responsiveness to therapeutics targeting DSB repair-dysfunctional tumors.

  19. Rad5-dependent DNA repair functions of the Saccharomyces cerevisiae FANCM protein homolog Mph1.

    PubMed

    Daee, Danielle L; Ferrari, Elisa; Longerich, Simonne; Zheng, Xiao-feng; Xue, Xiaoyu; Branzei, Dana; Sung, Patrick; Myung, Kyungjae

    2012-08-03

    Interstrand cross-links (ICLs) covalently link complementary DNA strands, block DNA replication, and transcription and must be removed to allow cell survival. Several pathways, including the Fanconi anemia (FA) pathway, can faithfully repair ICLs and maintain genomic integrity; however, the precise mechanisms of most ICL repair processes remain enigmatic. In this study we genetically characterized a conserved yeast ICL repair pathway composed of the yeast homologs (Mph1, Chl1, Mhf1, Mhf2) of four FA proteins (FANCM, FANCJ, MHF1, MHF2). This pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2. In addition, consistent with the FANCM role in stabilizing ICL-stalled replication forks, we present evidence that Mph1 prevents ICL-stalled replication forks from collapsing into double-strand breaks. This unique repair function of Mph1 is specific for ICL damage and does not extend to other types of damage. These studies reveal the functional conservation of the FA pathway and validate the yeast model for future studies to further elucidate the mechanism of the FA pathway.

  20. Modulation of Saccharomyces Cerevisiae DNA Double-Strand Break Repair by Srs2 and Rad51

    PubMed Central

    Milne, G. T.; Ho, T.; Weaver, D. T.

    1995-01-01

    RAD52 function is required for virtually all DNA double-strand break repair and recombination events in Saccharomyces cerevisiae. To gain greater insight into the mechanism of RAD52-mediated repair, we screened for genes that suppress partially active alleles of RAD52 when mutant or overexpressed. Described here is the isolation of a phenotypic null allele of SRS2 that suppressed multiple alleles of RAD52 (rad52B, rad52D, rad52-1 and KlRAD52) and RAD51 (KlRAD51) but failed to suppress either a rad52δ or a rad51δ. These results indicate that SRS2 antagonizes RAD51 and RAD52 function in recombinational repair. The mechanism of suppression of RAD52 alleles by srs2 is distinct from that which has been previously described for RAD51 overexpression, as both conditions were shown to act additively with respect to the rad52B allele. Furthermore, overexpression of either RAD52 or RAD51 enhanced the recombination-dependent sensitivity of an srs2δ RAD52 strain, suggesting that RAD52 and RAD51 positively influence recombinational repair mechanisms. Thus, RAD52-dependent recombinational repair is controlled both negatively and positively. PMID:7768432

  1. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    PubMed

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail.

  2. Studying nucleotide excision repair of mammalian DNA in a cell-free system

    SciTech Connect

    Wood, R.D.

    1994-12-31

    During nucleotide excision repair, a multiprotein system locates a lesion in DNA and catalyzes enzymatic cleavage of the altered strand. The damaged oligonucleotide and the incision proteins are then displaced, DNA synthesis proceeds to form a short patch using the nonmodified strand as a template, and repair is completed by a DNA ligase. Many gene products participate in these reactions, the best known of which correspond to the seven genetic complementation groups XP-A to XP-G of the disease xeroderma pigmentosum (XP). Cells representing any of these XP groups appear to exhibit, to varying degrees, defects in the first steps of nucleotide excision repair. Individuals affected with XP are hypersensitive to sunlight; most have a predisposition to skin cancer, and some patients show severe neurological abnormalities. In addition to XP, other UV-sensitive mutants of mammalian cells are providing insight into nucleotide excision repair. Of particular interest are mutants isolated from the rodent cells, which have been assigned to 11 different complementation groups. Human genes that can correct the repair defects of rodent mutants in these complementation groups are denoted. ERCC (excision repair cross-complementing) genes are are referred to by number, ERCC1 to ERCC11. Some of these genes are proving to be equivalent to particular XP-complementing genes, while others are distinct. The process of nucleotide excision repair is evolutionarily conserved in eukaryotes, and functional homologues of many of the ERCC and XP genes have been identified in other organisms; studies in yeast are proving to be particularly informative.

  3. DNA Repair by Reversal of DNA Damage

    PubMed Central

    Yi, Chengqi; He, Chuan

    2013-01-01

    Endogenous and exogenous factors constantly challenge cellular DNA, generating cytotoxic and/or mutagenic DNA adducts. As a result, organisms have evolved different mechanisms to defend against the deleterious effects of DNA damage. Among these diverse repair pathways, direct DNA-repair systems provide cells with simple yet efficient solutions to reverse covalent DNA adducts. In this review, we focus on recent advances in the field of direct DNA repair, namely, photolyase-, alkyltransferase-, and dioxygenase-mediated repair processes. We present specific examples to describe new findings of known enzymes and appealing discoveries of new proteins. At the end of this article, we also briefly discuss the influence of direct DNA repair on other fields of biology and its implication on the discovery of new biology. PMID:23284047

  4. Repair Development for a Composite Cryotank

    NASA Technical Reports Server (NTRS)

    Cox, Sarah B.; Danley, Susan E.; Caraccio, Anne J.; Cheshire, Brian C.; Sampson, Jeffrey W.; Taylor, Brian J.

    2014-01-01

    The Composite Cryotank Technologies and Demonstration Project is working to advance the technologies for composite cryogenic propellant tanks at diameters suitable for future heavy lift vehicles and other in-space applications. The main goals of the project are to reduce weight and cost. One aspect of this project has focused on damage evaluation and repair development. Test panels have been impacted, repaired, and tested. Several repair methods were used to compare their effectiveness at restoring the integrity of the composite. Panels were evaluated by nondestructive evaluations at several points during the process to assess the damage and repair. The testing performed and the results and conclusions from the nondestructive evaluations and the destructive testing will be discussed. These results will lead to further development of inspection techniques and repair methods.

  5. Effect of acrylamide on hepatocellular DNA repair

    SciTech Connect

    Miller, M.J.; McQueen, C.A.

    1986-01-01

    Acrylamide has recently been reported to induce tumors in laboratory animals. The effect of acrylamide on unscheduled DNA synthesis using the hepatocyte primary culture (HPC)/DNA repair test was examined. Isolated hepatocytes were exposed to acrylamide and (3H)thymidine ( (3H)TdR) for 18 hr. Incorporation of (3H)TdR into DNA was determined by autoradiography. No DNA repair was observed at acrylamide concentrations up to 10(-2) M. These findings were confirmed using density gradients. Acrylamide concentrations exceeding 10(-2) M were cytotoxic to hepatocytes. Because both autoradiography and density gradients measure DNA repair as an endpoint, the ability of acrylamide to inhibit these repair processes was also determined. Acrylamide had no effect on the repair of UV-damaged DNA. These results show that acrylamide is not genotoxic in isolated hepatocytes.

  6. Laparoscopic herniorrhaphy. Transabdominal preperitoneal floor repair.

    PubMed

    Felix, E L; Michas, C A; McKnight, R L

    1994-02-01

    The purpose of this study was to evaluate the results of a laparoscopic transabdominal preperitoneal (TAPP) approach to inguinal hernia repair which dissected the entire inguinal floor and repaired the indirect, direct, and femoral areas in all patients without tension. In our series, 183 patients had 205 hernia repairs and were followed for more than 6 months. Of this group, 128 hernias were indirect, 55 direct, 22 pantaloon, 26 recurrent, and 22 bilateral. All 12 females and the first 11 males had a single-buttress repair with polypropylene mesh. The other 160 male patients had a double-buttress repair. With median follow-up of 12 months, ranging from 6 to 21 months, no recurrences were found. Patients returned to normal activity in an average of 1 week. Dissection and buttressing of the entire inguinal floor with mesh appeared to solve the problem of early recurrence first seen in laparoscopic herniorrhaphy.

  7. Mitral valve repair for ischemic mitral regurgitation.

    PubMed

    Mohebali, Jahan; Chen, Frederick Y

    2015-05-01

    Mitral valve repair for ischemic mitral valve regurgitation remains controversial. In moderate mitral regurgitation (MR), controversy exists whether revascularization alone will be adequate to restore native valve geometry or whether intervention on the valve (repair) should be performed concomitantly. When MR is severe, the need for valve intervention is not disputed. Rather, the controversy is whether repair versus replacement should be undertaken. In contrast to degenerative or myxomatous disease that directly affects leaflet integrity and morphology, ischemic FMR results from a distortion and dilation of native ventricular geometry that normally supports normal leaflet coaptation. To address this, the first and most crucial step in successful valve repair is placement of an undersized, complete remodeling annuloplasty ring to restore the annulus to its native geometry. The following article outlines the steps for repair of ischemic mitral regurgitation.

  8. DNA Triplet Repeat Expansion and Mismatch Repair

    PubMed Central

    Iyer, Ravi R.; Pluciennik, Anna; Napierala, Marek; Wells, Robert D.

    2016-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. PMID:25580529

  9. Systems Maintenance Automated Repair Tasks (SMART)

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  10. INTERNAL REPAIR OF PIPELINES REVIEW & EVALUATION OF INTERNAL PIPELINE REPAIR TRIALS REPORT

    SciTech Connect

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

    2004-09-01

    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. 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, indicating that this type of liner is generally ineffective at restoring the pressure containing capabilities of pipelines. Failure pressure for pipe repaired with carbon fiber-reinforced composite liner was greater than that of the un-repaired pipe section with damage, indicating that this type of liner is effective at restoring the pressure containing capability of pipe. Pipe repaired with weld deposition failed at pressures lower than that of un-repaired pipe in both the virgin and damaged conditions, indicating that this repair technology is less effective at restoring the pressure containing capability of pipe than a carbon fiber-reinforced liner repair. Physical testing indicates that carbon fiber-reinforced liner repair is the most promising technology evaluated to-date. Development of a comprehensive test plan for this process is recommended for use in the next phase of this project.

  11. Distinct enzyme combinations in AKAP signalling complexes permit functional diversity.

    PubMed

    Hoshi, Naoto; Langeberg, Lorene K; Scott, John D

    2005-11-01

    Specificity in cell signalling can be influenced by the targeting of different enzyme combinations to substrates. The A-kinase anchoring protein AKAP79/150 is a multivalent scaffolding protein that coordinates the subcellular localization of second-messenger-regulated enzymes, such as protein kinase A, protein kinase C and protein phosphatase 2B. We developed a new strategy that combines RNA interference of the endogenous protein with a protocol that selects cells that have been rescued with AKAP79/150 forms that are unable to anchor selected enzymes. Using this approach, we show that AKAP79/150 coordinates different enzyme combinations to modulate the activity of two distinct neuronal ion channels: AMPA-type glutamate receptors and M-type potassium channels. Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates.

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

    PubMed

    Slegtenhorst, Bendix R; Dor, Frank J M F; Elkhal, Abdala; Rodriguez, Hector; Yang, Xiaoyong; Edtinger, Karoline; Quante, Markus; Chong, Anita S; Tullius, Stefan G

    2014-06-15

    Donor organ scarcity remains a significant clinical challenge in transplantation. Older organs, increasingly utilized to meet the growing demand for donor organs, have been linked to inferior transplant outcomes. Susceptibility to organ injury, reduced repair capacity, and increased immunogenicity are interrelated and impacted by physiological and pathological aging processes. Insights into the underlying mechanisms are needed to develop age-specific interventional strategies with regards to organ preservation, immunosuppression, and allocation. In this overview, we summarize current knowledge of injury and repair mechanisms and the effects of aging relevant to transplantation.

  13. Long-term durability of open thoracic and thoracoabdominal aneurysm repair.

    PubMed

    Fischbein, Michael P; Miller, D Craig

    2009-06-01

    Results of open surgical repair of descending and thoracoabdominal aortic aneurysms have improved dramatically over the years. Nevertheless, while adjunctive protective strategies, such as spinal cord drainage and distal aortic perfusion, have improved outcomes, clinical challenges remain. In the current era, thoracic aortic surgeons must possess both open and endovascular stent-graft capabilities to offer these complex patients the most optimal and individualized treatment approach. Herein we summarize the contemporary outcomes of open surgical repair of patients with either descending thoracic or thoracoabdominal aortic aneurysms, focusing on the risk of complications and means for preventing their occurrence.

  14. INTERNAL REPAIR OF GAS PIPLINES SURVEY OF OPERATOR EXPERIENCE AND INDUSTRY NEEDS REPORT

    SciTech Connect

    Ian D. Harris

    2003-09-01

    A repair method that can be applied from the inside of a gas transmission pipeline (i.e., a trenchless repair) is an attractive alternative to conventional repair methods since the need to excavate the pipeline is precluded. This is particularly true for pipelines in environmentally sensitive and highly populated areas. The objectives of the project are to evaluate, develop, demonstrate, and validate internal repair methods for pipelines; develop a functional specification for an internal pipeline repair system; and prepare a recommended practice for internal repair of pipelines. The purpose of this survey is to better understand the needs and performance requirements of the natural gas transmission industry regarding internal repair. A total of fifty-six surveys were sent to pipeline operators. A total of twenty completed surveys were returned, representing a 36% response rate, which is considered very good given the fact that tailored surveys are known in the marketing industry to seldom attract more than a 10% response rate. The twenty survey responses produced the following principal conclusions: (1) Use of internal weld repair is most attractive for river crossings, under other bodies of water (e.g., lakes and swamps) in difficult soil conditions, under highways, under congested intersections, and under railway crossings. All these areas tend to be very difficult and very costly if, and where, conventional excavated repairs may be currently used. (2) Internal pipe repair offers a strong potential advantage to the high cost of horizontal direct drilling (HDD) when a new bore must be created to solve a leak or other problem in a water/river crossing. (3) The typical travel distances required 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.). In concept, these groups require pig-based systems; despooled umbilical systems could be considered for the first two groups

  15. Gene repair and transposon-mediated gene therapy.

    PubMed

    Richardson, Paul D; Augustin, Lance B; Kren, Betsy T; Steer, Clifford J

    2002-01-01

    The main strategy of gene therapy has traditionally been focused on gene augmentation. This approach typically involves the introduction of an expression system designed to express a specific protein in the transfected cell. Both the basic and clinical sciences have generated enough information to suggest that gene therapy would eventually alter the fundamental practice of modern medicine. However, despite progress in the field, widespread clinical applications and success have not been achieved. The myriad deficiencies associated with gene augmentation have resulted in the development of alternative approaches to treat inherited and acquired genetic disorders. One, derived primarily from the pioneering work of homologous recombination, is gene repair. Simply stated, the process involves targeting the mutation in situ for gene correction and a return to normal gene function. Site-specific genetic repair has many advantages over augmentation although it too is associated with significant limitations. This review outlines the advantages and disadvantages of gene correction. In particular, we discuss technologies based on chimeric RNA/DNA oligonucleotides, single-stranded and triplex-forming oligonucleotides, and small fragment homologous replacement. While each of these approaches is different, they all share a number of common characteristics, including the need for efficient delivery of nucleic acids to the nucleus. In addition, we review the potential application of a novel and exciting nonviral gene augmentation strategy--the Sleeping Beauty transposon system.

  16. Postreplication repair in Saccharomyces cerevisiae

    SciTech Connect

    Resnick, M.A.; Boyce, J.; Cox, B.

    1981-04-01

    Postreplication events in logarithmically growing excision-defective mutants of Saccharomyces cerevisiae were examined after low doses of ultraviolet light. Pulse-labeled deoxyribonucleic acid had interruptions, and when the cells were chased, the interruptions were no longer detected. Since the loss of interruptions was not associated with an exchange of pyrimidine dimers at a detection level of 10 to 20% of the induced dimers, it was concluded that postreplication repair in excision-defective mutants does not involve molecular recombination. Pyrimidine dimers were assayed by utilizing the ultraviolet-endonuclease activity in extracts of Micrococcus luteus and newly developed alkaline sucrose gradient techniques, which yielded chromosomal-size deoxyribonucleic acid after treatment of irradiated cells.

  17. Shuttle Repair Tools Automate Vehicle Maintenance

    NASA Technical Reports Server (NTRS)

    2013-01-01

    Successfully building, flying, and maintaining the space shuttles was an immensely complex job that required a high level of detailed, precise engineering. After each shuttle landed, it entered a maintenance, repair, and overhaul (MRO) phase. Each system was thoroughly checked and tested, and worn or damaged parts replaced, before the shuttle was rolled out for its next mission. During the MRO period, workers needed to record exactly what needed replacing and why, as well as follow precise guidelines and procedures in making their repairs. That meant traceability, and with it lots of paperwork. In 2007, the number of reports generated during electrical system repairs was getting out of hand-placing among the top three systems in terms of paperwork volume. Repair specialists at Kennedy Space Center were unhappy spending so much time at a desk and so little time actually working on the shuttle. "Engineers weren't spending their time doing technical work," says Joseph Schuh, an electrical engineer at Kennedy. "Instead, they were busy with repetitive, time-consuming processes that, while important in their own right, provided a low return on time invested." The strain of such inefficiency was bad enough that slow electrical repairs jeopardized rollout on several occasions. Knowing there had to be a way to streamline operations, Kennedy asked Martin Belson, a project manager with 30 years experience as an aerospace contractor, to co-lead a team in developing software that would reduce the effort required to document shuttle repairs. The result was System Maintenance Automated Repair Tasks (SMART) software. SMART is a tool for aggregating and applying information on every aspect of repairs, from procedures and instructions to a vehicle s troubleshooting history. Drawing on that data, SMART largely automates the processes of generating repair instructions and post-repair paperwork. In the case of the space shuttle, this meant that SMART had 30 years worth of operations

  18. Teenage Drinking, Symbolic Capital and Distinction

    ERIC Educational Resources Information Center

    Jarvinen, Margaretha; Gundelach, Peter

    2007-01-01

    This article analyses alcohol-related lifestyles among Danish teenagers. Building on Bourdieu's reasoning on symbolic capital and distinction, we analyse three interrelated themes. First, we show that alcohol-related variables (drinking patterns, drinking debut, experience of intoxication, etc.) can be used to identify some very distinctive life…

  19. 14 CFR 1252.411 - Age distinctions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Age distinctions. 1252.411 Section 1252.411 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION NONDISCRIMINATION ON THE BASIS OF AGE IN... Procedures § 1252.411 Age distinctions. There are no Federal statutes or regulations containing...

  20. Triton College: One Institution's Search for Distinctiveness.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.; Catanzaro, James L.

    1989-01-01

    Recounts Triton College's efforts to identify its distinctive elements. Reviews empirical evidence showing that Triton's school schedule, curricular offerings, and continuing education and support services are distinctive among local colleges. Discusses students' and staff members' perceptions of Triton. Considers the value of the research to the…