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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. Anti-Inflammatory Strategies in Cartilage Repair

    PubMed Central

    Zhang, Ying; Pizzute, Tyler

    2014-01-01

    Cartilage defects are normally concomitant with posttraumatic inflammation and pose a major challenge in cartilage repair. Due to the avascular nature of cartilage and its inability to surmount an inflammatory response, the cartilage is easily attacked by proinflammatory factors and oxidative stress; if left untreated, osteoarthritis may develop. Suppression of inflammation has always been a crux for cartilage repair. Pharmacological drugs have been successfully applied in cartilage repair; however, they cannot optimally work alone. This review article will summarize current pharmacological drugs and their application in cartilage repair. The development of extracellular matrix-based scaffolds and preconditioned tissue-specific stem cells will be emphasized because both of these tissue engineering components could contribute to an enhanced ability not only for cartilage regeneration but also for anti-inflammation. These strategies could be combined to boost cartilage repair under inflammatory conditions. PMID:24846478

  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. Visualization of Eukaryotic DNA Mismatch Repair Reveals Distinct Recognition and Repair Intermediates

    PubMed Central

    Hombauer, Hans; Campbell, Christopher S.; Smith, Catherine E.; Desai, Arshad; Kolodner, Richard D.

    2011-01-01

    Summary DNA Mismatch Repair (MMR) increases replication fidelity by eliminating mispaired bases resulting from replication errors. In Saccharomyces cerevisiae mispairs are primarily detected by the Msh2-Msh6 complex and corrected following subsequent recruitment of the Mlh1-Pms1 complex. Here, we visualized functional fluorescent versions of Msh2-Msh6 and Mlh1-Pms1 in living cells. Msh2-Msh6 formed foci in S-phase that colocalized with replication factories; this localized pool accounted for 10–15% of MMR in wild-type cells but was essential for MMR in the absence of the exonuclease Exo1. Mlh1-Pms1 also formed foci that, while requiring Msh2-Msh6 for their formation, rarely colocalized with Msh2-Msh6. Mlh1-Pms1 foci increased when the number of mispaired bases was increased; in contrast, Msh2-Msh6 foci were unaffected. These results suggest that (I) mispair recognition can occur via either a replication factory-targeted or a second distinct pool of Msh2-Msh6, and (II) superstoichiometric Mlh1-Pms1 assembly triggered by mispair-bound Msh2-Msh6 defines sites of active MMR. PMID:22118461

  5. 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

  6. Cellular Repair Strategies in Parkinson's Disease

    PubMed Central

    Winner, Beate; Vogt-Weisenhorn, Daniela M.; Lie, Chichung D.; Winkler, Jürgen

    2009-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 0.7% of the elderly population (defined as over 65 years of age). PD is clinically characterized by resting tremor, muscular rigidity, hypokinesia and postural instability. These motor symptoms result largely from the deficiency or dysfunction of dopaminergic neurons in the substantia nigra. Histopathological analysis reveals depletion of dopaminergic neurons as well as eosinophilic intracytoplasmic inclusions (Lewy bodies) in surviving neurons of the substantia nigra and other brain regions. The molecular pathogenesis is linked to protein misfolding by compromised alpha-synuclein and/or related proteins (synucleinopathy). Therefore, successful therapy of motor symptoms aims for the restoration of dopaminergic neurotransmission. Pharmacological drug treatment is usually effective only at an early stage of the disease but cannot halt progressive neuronal degeneration. With recent developments in stem cell technology, cell repair or replacement approaches came into focus. Here, we review new therapeutic strategies resulting from the innate propensity of the adult brain to generate new neurons, either by pharmacological stimulation of endogenous adult stem cell population or exogenous cell transplantation modalities. PMID:21180641

  7. Alternative applications for distinct RNA sequencing strategies

    PubMed Central

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

    2015-01-01

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

  8. Alternative applications for distinct RNA sequencing strategies.

    PubMed

    Han, Leng; Vickers, Kasey C; Samuels, David C; Guo, Yan

    2015-07-01

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

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

    PubMed Central

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

    2013-01-01

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

  10. Muscle injuries and strategies for improving their repair.

    PubMed

    Laumonier, Thomas; Menetrey, Jacques

    2016-12-01

    Satellite cells are tissue resident muscle stem cells required for postnatal skeletal muscle growth and repair through replacement of damaged myofibers. Muscle regeneration is coordinated through different mechanisms, which imply cell-cell and cell-matrix interactions as well as extracellular secreted factors. Cellular dynamics during muscle regeneration are highly complex. Immune, fibrotic, vascular and myogenic cells appear with distinct temporal and spatial kinetics after muscle injury. Three main phases have been identified in the process of muscle regeneration; a destruction phase with the initial inflammatory response, a regeneration phase with activation and proliferation of satellite cells and a remodeling phase with maturation of the regenerated myofibers. Whereas relatively minor muscle injuries, such as strains, heal spontaneously, severe muscle injuries form fibrotic tissue that impairs muscle function and lead to muscle contracture and chronic pain. Current therapeutic approaches have limited effectiveness and optimal strategies for such lesions are not known yet. Various strategies, including growth factors injections, transplantation of muscle stem cells in combination or not with biological scaffolds, anti-fibrotic therapies and mechanical stimulation, may become therapeutic alternatives to improve functional muscle recovery. PMID:27447481

  11. Strategies for CNS repair following TBI.

    PubMed

    Aertker, Benjamin M; Bedi, Supinder; Cox, Charles S

    2016-01-01

    Traumatic brain injury (TBI) imparts a significant health burden in the United States, leaving many patients with chronic deficits. Improvement in clinical outcome following TBI has been hindered by a lack of treatments that have proven successful during phase III trials. Research remains active into a variety of non-pharmacologic, small molecule, endocrine and cell based therapies. Of particular focus in this review are the recent therapeutic avenues that have undergone clinical investigation and the mechanisms by which cell therapies may mediate recovery in severe TBI. Preclinical data show cell therapies to provide benefit when administered systemically or with transplantation to the site of injury. Increasingly, studies have shown that these cells are able to attenuate the inflammatory response to injury and stimulate production of neurotrophic factors. In animal models, beneficial effects on blood-brain barrier permeability, neuroprotection and neural repair through enhanced axonal remodeling have been observed. Clinical investigation with cell therapies for TBI remains ongoing. PMID:25637707

  12. Strategies of Repair in EFL Learners' Oral Discourse

    ERIC Educational Resources Information Center

    Rabab'ah, Ghaleb

    2013-01-01

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

  13. 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. PMID:26014967

  14. 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

  15. 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

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

    PubMed

    Finell, Eerika; Liebkind, Karmela

    2010-06-01

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

  17. 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…

  18. Distinct Properties of Hexameric but Functionally Conserved Mycobacterium tuberculosis Transcription-Repair Coupling Factor

    PubMed Central

    Prabha, Swayam; Rao, Desirazu N.; Nagaraja, Valakunja

    2011-01-01

    Transcription coupled nucleotide excision repair (TC-NER) is involved in correcting UV-induced damage and other road-blocks encountered in the transcribed strand. Mutation frequency decline (Mfd) is a transcription repair coupling factor, involved in repair of template strand during transcription. Mfd from M. tuberculosis (MtbMfd) is 1234 amino-acids long harboring characteristic modules for different activities. Mtbmfd complemented Escherichia coli mfd (Ecomfd) deficient strain, enhanced survival of UV irradiated cells and increased the road-block repression in vivo. The protein exhibited ATPase activity, which was stimulated ∼1.5-fold in the presence of DNA. While the C-terminal domain (CTD) comprising amino acids 630 to 1234 showed ∼2-fold elevated ATPase activity than MtbMfd, the N-terminal domain (NTD) containing the first 433 amino acid residues was able to bind ATP but deficient in hydrolysis. Overexpression of NTD of MtbMfd led to growth defect and hypersensitivity to UV light. Deletion of 184 amino acids from the C-terminal end of MtbMfd (MfdΔC) increased the ATPase activity by ∼10-fold and correspondingly exhibited efficient translocation along DNA as compared to the MtbMfd and CTD. Surprisingly, MtbMfd was found to be distributed in monomer and hexamer forms both in vivo and in vitro and the monomer showed increased susceptibility to proteases compared to the hexamer. MfdΔC, on the other hand, was predominantly monomeric in solution implicating the extreme C-terminal region in oligomerization of the protein. Thus, although the MtbMfd resembles EcoMfd in many of its reaction characteristics, some of its hitherto unknown distinct properties hint at its species specific role in mycobacteria during transcription-coupled repair. PMID:21559463

  19. Distinct invasion strategies operating within a natural annual plant system.

    PubMed

    Lai, Hao Ran; Mayfield, Margaret M; Gay-des-Combes, Justine M; Spiegelberger, Thomas; Dwyer, John M

    2015-04-01

    Alien plant species are known to have a wide range of impacts on recipient communities, from resident species' exclusions to coexistence with resident species. It remains unclear; however, if this variety of impacts is due to different invader strategies, features of recipient communities or both. To test this, we examined multiple plant invasions of a single ecosystem in southwestern Australia. We used extensive community data to calculate pairwise segregation between target alien species and many co-occurring species. We related segregation to species' positions along community trait hierarchies and identified at least two distinct invasion strategies: 'exploiters' which occupy high positions along key trait hierarchies and reduce local native species diversity (particularly in nutrient-enriched situations), and 'coexisters' who occupy intermediate trait positions and have no discernable impact on native diversity. We conclude that trait hierarchies, linked to measures of competition, can provide valuable insights about the processes driving different invasion outcomes. PMID:25728390

  20. 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

  1. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  4. [Current cell therapy strategies for repairing the central nervous system].

    PubMed

    Féron, F

    2007-09-01

    One of the chief contemporary goals of neurologists and neuroscientists is to find a way to overcome the debilitating effects of brain diseases, especially neurodegenerative diseases. Since very few molecules have been found to be efficient in curing the patients and even halting the progression of the symptoms, cell therapy is now seen as an attractive alternative. Two therapeutic strategies are currently under investigation: i) the "substitution" strategy, based on grafts of cells capable of differentiating in the appropriate cells and restoring lost functions and ii) the "neuroprotective" or "conservative" strategy aiming to increase the resistance of spared cells to the toxicity of their environment and to reinforce the body's own mechanisms of healing. Twenty years ago, foetal neuroblasts were the first cells to be transplanted in the brains of patients with Parkinson's or Huntington disease. A phase II clinical trial is presently conducted in France for the latter disorder. However, the numerous ethical and technical issues raised by the use of embryonic and foetal cells have directed the focus of clinicians and researchers towards substitute cell types. In this review, we summarise the main findings of the most recent basic studies and clinical trials based on: i) the grafting of surrogate adult cells such as bone marrow mesenchymal stem cells and olfactory ensheathing cells; ii) the potential therapeutic applications of neuropoiesis - the persistent neurogenesis in the brain - as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells and iii) immune-based therapy (autologous activated macrophages and T cell vaccination) as well as administration of immunomodulatory molecules. Unexpectedly, it has been found that undifferentiated adult stem cells can display immune-like functions when they home in on an inflamed brain area while immune cells and immunosuppressors can improve functional and

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

    PubMed

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

    2006-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  7. 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

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

    PubMed

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

    2011-10-31

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed Central

    Chen, Zhangguo; Eder, Maxwell D.; Elos, Mihret T.; Viboolsittiseri, Sawanee S.; Chen, Xiaomi

    2016-01-01

    Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G mismatches, a rate-limiting step of Ab gene diversification. However, precise mechanisms regulating AID deamination frequency remain incompletely understood. Moreover, it is not known whether different sequence contexts influence the preferential access of mismatch repair or uracil glycosylase (UNG) to AID-initiated U:G mismatches. In this study, we employed two knock-in models to directly compare the mutability of core Sμ and VDJ exon sequences and their ability to regulate AID deamination and subsequent repair process. We find that the switch (S) region is a much more efficient AID deamination target than the V region. Igh locus AID-initiated lesions are processed by error-free and error-prone repair. S region U:G mismatches are preferentially accessed by UNG, leading to more UNG-dependent deletions, enhanced by mismatch repair deficiency. V region mutation hotspots are largely determined by AID deamination. Recurrent and conserved S region motifs potentially function as spacers between AID deamination hotspots. We conclude that the pattern of mutation hotspots and DNA break generation is influenced by sequence-intrinsic properties, which regulate AID deamination and affect the preferential access of downstream repair. Our studies reveal an evolutionarily conserved role for substrate sequences in regulating Ab gene diversity and AID targeting specificity. PMID:26810227

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

    PubMed

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

    2016-03-01

    Activation-induced deaminase (AID) functions by deaminating cytosines and causing U:G mismatches, a rate-limiting step of Ab gene diversification. However, precise mechanisms regulating AID deamination frequency remain incompletely understood. Moreover, it is not known whether different sequence contexts influence the preferential access of mismatch repair or uracil glycosylase (UNG) to AID-initiated U:G mismatches. In this study, we employed two knock-in models to directly compare the mutability of core Sμ and VDJ exon sequences and their ability to regulate AID deamination and subsequent repair process. We find that the switch (S) region is a much more efficient AID deamination target than the V region. Igh locus AID-initiated lesions are processed by error-free and error-prone repair. S region U:G mismatches are preferentially accessed by UNG, leading to more UNG-dependent deletions, enhanced by mismatch repair deficiency. V region mutation hotspots are largely determined by AID deamination. Recurrent and conserved S region motifs potentially function as spacers between AID deamination hotspots. We conclude that the pattern of mutation hotspots and DNA break generation is influenced by sequence-intrinsic properties, which regulate AID deamination and affect the preferential access of downstream repair. Our studies reveal an evolutionarily conserved role for substrate sequences in regulating Ab gene diversity and AID targeting specificity. PMID:26810227

  12. Mre11 Nuclease Activity has Essential Roles in DNA Repair and Genomic Stability Distinct from ATM Activation

    PubMed Central

    Buis, Jeffrey; Wu, Yipin; Deng, Yibin; Leddon, Jennifer; Westfield, Gerwin; Eckersdorff, Mark; Sekiguchi, JoAnn M.; Chang, Sandy; Ferguson, David O.

    2008-01-01

    Summary The Mre11/Rad50/NBS1 complex (MRN) maintains genomic stability by bridging DNA ends and initiating DNA damage signaling through activation of the ATM kinase. Mre11 possesses DNA nuclease activities that are highly conserved in evolution, but play unknown roles in mammals. To define functions of Mre11 we engineered targeted mouse alleles which either abrogate nuclease activities or inactivate the entire MRN complex. Mre11 nuclease deficiency causes a striking array of phenotypes indistinguishable from absence of MRN, including early embryonic lethality and dramatic genomic instability. We identify a crucial role for the nuclease activities in homology directed double strand break repair, and a contributing role in activating the ATR kinase. However, nuclease activities are not required to activate ATM after DNA damage or telomere deprotection. Therefore, nucleolytic processing by Mre11 is an essential function of fundamental importance in DNA repair distinct from MRN control of ATM signaling. PMID:18854157

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

    PubMed

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

    2015-05-01

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

  14. 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

  15. 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

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

    PubMed

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

    2016-05-01

    Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. We describe a computational protocol, called SEWING, which is inspired by this process and builds new proteins from connected or disconnected pieces of existing structures. Helical proteins designed with SEWING contain structural features absent from other de novo designed proteins and, in some cases, remain folded at more than 100°C. High-resolution structures of the designed proteins CA01 and DA05R1 were solved by x-ray crystallography (2.2 angstrom resolution) and nuclear magnetic resonance, respectively, and there was excellent agreement with the design models. This method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds. PMID:27151863

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

    PubMed

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

    2013-01-01

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

  18. 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

  19. Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.

    PubMed

    Varga, Tamas; Mounier, Rémi; Horvath, Attila; Cuvellier, Sylvain; Dumont, Florent; Poliska, Szilard; Ardjoune, Hamida; Juban, Gaëtan; Nagy, Laszlo; Chazaud, Bénédicte

    2016-06-01

    Macrophage gene expression determines phagocyte responses and effector functions. Macrophage plasticity has been mainly addressed in in vitro models that do not account for the environmental complexity observed in vivo. In this study, we show that microarray gene expression profiling revealed a highly dynamic landscape of transcriptomic changes of Ly6C(pos)CX3CR1(lo) and Ly6C(neg)CX3CR1(hi) macrophage populations during skeletal muscle regeneration after a sterile damage. Systematic gene expression analysis revealed that the time elapsed, much more than Ly6C status, was correlated with the largest differential gene expression, indicating that the time course of inflammation was the predominant driving force of macrophage gene expression. Moreover, Ly6C(pos)/Ly6C(neg) subsets could not have been aligned to canonical M1/M2 profiles. Instead, a combination of analyses suggested the existence of four main features of muscle-derived macrophages specifying important steps of regeneration: 1) infiltrating Ly6C(pos) macrophages expressed acute-phase proteins and exhibited an inflammatory profile independent of IFN-γ, making them damage-associated macrophages; 2) metabolic changes of macrophages, characterized by a decreased glycolysis and an increased tricarboxylic acid cycle/oxidative pathway, preceded the switch to and sustained their anti-inflammatory profile; 3) Ly6C(neg) macrophages, originating from skewed Ly6C(pos) cells, actively proliferated; and 4) later on, restorative Ly6C(neg) macrophages were characterized by a novel profile, indicative of secretion of molecules involved in intercellular communications, notably matrix-related molecules. These results show the highly dynamic nature of the macrophage response at the molecular level after an acute tissue injury and subsequent repair, and associate a specific signature of macrophages to predictive specialized functions of macrophages at each step of tissue injury/repair. PMID:27183604

  20. 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...

  1. Repair Strategies Used by Verbal Students with Autism during Free Play

    ERIC Educational Resources Information Center

    Ohtake, Yoshihisa; Wehmeyer, Michael L.; Nakaya, Akitaka; Takahashi, Shoji; Yanagihara, Masafumi

    2011-01-01

    This study assessed the repair strategies used by verbal students with autism (N = 12) when faced with verbal requests for clarification, gestural requests, not attending and not responding, and wrong responses. Data were collected in request contexts contrived by the communication partner during free play. The results indicated that most of the…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    SciTech Connect

    Not Available

    1983-07-01

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

  4. Strategies for Self-Repairing Shape Memory Alloy Actuators

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

  5. Gene Delivery Strategies to Promote Spinal Cord Repair

    PubMed Central

    Walthers, Christopher M; Seidlits, Stephanie K

    2015-01-01

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

  6. 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

  7. 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

  8. 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

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

    PubMed

    Kalderon, Nurit

    2005-01-01

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

  10. 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…

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

    PubMed

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

    2016-05-01

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

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

    SciTech Connect

    German, P.

    1996-12-31

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

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

    PubMed

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

    2016-07-01

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

  14. Potential Market for New Meniscus Repair Strategies: Evaluation of the MOON Cohort

    PubMed Central

    Fetzer, Gary B.; Spindler, Kurt P.; Amendola, Annunziato; Andrish, Jack T.; Bergfeld, John A.; Dunn, Warren R.; Flanigan, David C.; Jones, Morgan; Kaeding, Christopher C.; Marx, Robert G.; Matava, Matthew J.; McCarty, Eric C.; Parker, Richard D.; Wolcott, Michelle; Vidal, Armando; Wolf, Brian R.; Wright, Rick W.

    2013-01-01

    Background An estimated 200,000 ACL reconstructions are performed each year in the United States. The presence of concomitant meniscus tears and subsequent treatment at the time of ACL reconstruction may determine long-term outcomes of these knees. The authors contend that a substantial number of these meniscal tears are treated in a fashion that reduces meniscal function and that new technologies are needed to treat meniscal tears in a fashion that preserves function. A large cohort of patients with meniscal tears is needed to demonstrate this need. The purpose of this study is to determine the incidence of meniscal tears, describe tear morphology, and selected treatment in the MOON prospective longitudinal cohort of ACL reconstruction. We also will demonstrate based on national statistics the large potential market that exists for future tissue engineering aimed at preserving meniscal function. Methods A multicenter cohort of 1014 patients undergoing ACL reconstruction between January 2002 and December 2003 were evaluated. All procedures were performed by nine fellowship trained sports medicine orthopaedic surgeons. Data on patient demographics, presence of a meniscus tear at time of ACL reconstruction, tear morphology, and meniscal treatment were collected prospectively. Meniscal tears were categorized into three potential tissue engineering treatment strategies: all-biologic repair, advanced repair, and scaffold replacement. Results 1014 ACL reconstructions were performed over the two year period. The median age at the time of surgery was 24 years. Thirty-six percent of the knees had medial meniscal tears and 44% of the knees had lateral meniscal tears. Longitudinal tears were the most common tear morphology. The most frequent treatment modality was partial meniscectomy (60%). Thirty percent of medial meniscal tears and 10% of lateral meniscal tears could be treated with all-biologic repair, 32% of medial meniscal tears and 28% of lateral meniscal tears could

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

    PubMed Central

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

    2015-01-01

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

  16. Components separation technique and laparoscopic approach: a review of two evolving strategies for ventral hernia repair.

    PubMed

    Gonzalez, Rodrigo; Rehnke, Robert D; Ramaswamy, Archana; Smith, C Daniel; Clarke, John M; Ramshaw, Bruce J

    2005-07-01

    When faced with large ventral hernias, surgeons frequently must choose between higher incidence of recurrence after primary repair and higher incidence of wound complications after repair with mesh. The aim of this study is to compare early outcomes between laparoscopic repair (LR) and components separation technique (CST), two evolving strategies for the management of large ventral hernias. We reviewed 42 consecutive patients who underwent CST and 45 consecutive patients who underwent LR of ventral hernia defects of at least 12 cm2. Demographics, hernia characteristics, and short-term outcomes were compared between groups. Patients in the LR group were younger (53 +/- 2 vs 68 +/- 2 years, P < 0.0001), had greater body mass index (34 +/- 2 vs 29 +/- 1 kg/m2, P = 0.02), and had larger hernia defects (318 +/- 49 vs 101 +/- 16 cm2, P < 0.0001) than patients in the CST group. The LR resulted in shorter length of hospital stay (4.9 +/- 0.9 vs 9.6 +/- 1.8 days, P < 0.0001), lower incidence of ileus (7% vs 48%, P < 0.0001), and lower incidence of wound complications (2% vs 33%, P < 0.001) than the CST. Both techniques resulted in similar operative times, transfusion requirements, and mortality. Recurrences occurred in 7 per cent of patients at mean follow-up of 16 months in the CST group and 0 per cent at mean follow-up of 9 months after LR. The LR may have a short-term advantage over the CST in terms of incidence of ileus, wound complications, and hospital stay. Because of their unique advantage over traditional hernia repairs, both techniques may play a significant role in the future treatment of large ventral hernias. Adequate training will be essential for the safe and effective implementation of these techniques within the surgical community. PMID:16089127

  17. Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis

    PubMed Central

    Sloane, Peter A.; Rowe, Steven M.

    2013-01-01

    Purpose of review Recent progress in understanding the production, processing, and function of the cystic fibrosis gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), has revealed new therapeutic targets to repair the mutant protein. Classification of CFTR mutations and new treatment strategies to address each will be described here. Recent findings High-throughput screening and other drug discovery efforts have identified small molecules that restore activity to mutant CFTR. Compounds such as VX-770 that potentiate CFTR have demonstrated exciting results in recent clinical trials and demonstrate robust effects across several CFTR mutation classes in the laboratory. A number of novel F508del CFTR processing correctors restore protein to the cell surface and improve ion channel function in vitro and are augmented by coadministration of CFTR potentiators. Ongoing discovery efforts that target protein folding, CFTR trafficking, and cell stress have also indicated promising results. Aminoglycosides and the novel small molecule ataluren induce translational readthrough of nonsense mutations in CFTR and other genetic diseases in vitro and in vivo and have shown activity in proof of concept trials, and ataluren is now being studied in confirmatory trials. Summary An improved understanding of the molecular mechanisms underlying the basic genetic defect in cystic fibrosis have led to new treatment strategies to repair the mutant protein. PMID:20829696

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-08-12

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

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

    PubMed

    Leininger, Elizabeth C; Kelley, Darcy B

    2013-04-01

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

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

    PubMed Central

    Leininger, Elizabeth C.; Kelley, Darcy B.

    2013-01-01

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

  5. [The staged approach--an overview on a strategy to reduce spinal cord injury in thoracoabdominal aortic aneurysm repair].

    PubMed

    Kari, F A; Brenner, R M; Müller, C S; Griepp, R B; Bischoff, M S

    2013-10-01

    The spinal cord is particularly susceptible to ischaemic injury following repair of extensive descending thoracic and thoracoabdominal aortic aneurysms (TAAA). For the past decade, the Mount Sinai group in New York has intensively studied the anatomy of the extensive vascular network surrounding the spinal cord, as well as its dynamic morphology in response to decreased blood pressure and flow. Along with clinical data, experimental findings gave rise to the Collateral Network Concept, by which spinal cord injury in open TAAA repair can be significantly reduced. With the more recent widespread use of endovascular repair, strategies to prevent ischaemic spinal cord damage after extensive segmental artery sacrifice/occlusion are still evolving. The hypothesis that dividing extensive aneurysm repair into two steps may mitigate the impact of diminished blood flow to the collateral network has led to a recently conducted series of staged repair experiments. By exploiting the resources of the collateral network, spinal cord injury could be minimised in staged open, as well as in staged hybrid repair and seems equally adoptable for endovascular procedures. The contribution presented herein provides an overview of clinical and experimental studies on the staged approach. Furthermore, it briefly assesses the anatomic rationale for the collateral network concept. PMID:23460105

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

    PubMed Central

    Herrmann, Marietta; Verrier, Sophie; Alini, Mauro

    2015-01-01

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

  7. Structural and functional analysis of the Crb2–BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair

    PubMed Central

    Kilkenny, Mairi L.; Doré, Andrew S.; Roe, S. Mark; Nestoras, Konstantinos; Ho, Jenny C.Y.; Watts, Felicity Z.; Pearl, Laurence H.

    2008-01-01

    Schizosaccharomyces pombe Crb2 is a checkpoint mediator required for the cellular response to DNA damage. Like human 53BP1 and Saccharomyces cerevisiae Rad9 it contains Tudor2 and BRCT2 domains. Crb2-Tudor2 domain interacts with methylated H4K20 and is required for recruitment to DNA dsDNA breaks. The BRCT2 domain is required for dimerization, but its precise role in DNA damage repair and checkpoint signaling is unclear. The crystal structure of the Crb2–BRCT2 domain, alone and in complex with a phosphorylated H2A.1 peptide, reveals the structural basis for dimerization and direct interaction with γ-H2A.1 in ionizing radiation-induced foci (IRIF). Mutational analysis in vitro confirms the functional role of key residues and allows the generation of mutants in which dimerization and phosphopeptide binding are separately disrupted. Phenotypic analysis of these in vivo reveals distinct roles in the DNA damage response. Dimerization mutants are genotoxin sensitive and defective in checkpoint signaling, Chk1 phosphorylation, and Crb2 IRIF formation, while phosphopeptide-binding mutants are only slightly sensitive to IR, have extended checkpoint delays, phosphorylate Chk1, and form Crb2 IRIF. However, disrupting phosphopeptide binding slows formation of ssDNA-binding protein (Rpa1/Rad11) foci and reduces levels of Rad22(Rad52) recombination foci, indicating a DNA repair defect. PMID:18676809

  8. 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…

  9. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

    PubMed

    Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

    2016-08-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

  10. Distinct Roles of the Salmonella enterica Serovar Typhimurium CyaY and YggX Proteins in the Biosynthesis and Repair of Iron-Sulfur Clusters

    PubMed Central

    Velayudhan, Jyoti; Karlinsey, Joyce E.; Frawley, Elaine R.; Becker, Lynne A.; Nartea, Margaret

    2014-01-01

    Labile [4Fe-4S]2+ clusters found at the active sites of many dehydratases are susceptible to damage by univalent oxidants that convert the clusters to an inactive [3Fe-4S]1+ form. Bacteria repair damaged clusters in a process that does not require de novo protein synthesis or the Isc and Suf cluster assembly pathways. The current study investigates the participation of the bacterial frataxin ortholog CyaY and the YggX protein, which are proposed to play roles in iron trafficking and iron-sulfur cluster repair. Previous reports found that individual mutations in cyaY or yggX were not associated with phenotypic changes in Escherichia coli and Salmonella enterica serovar Typhimurium, suggesting that CyaY and YggX might have functionally redundant roles. However, we have found that individual mutations in cyaY or yggX confer enhanced susceptibility to hydrogen peroxide in Salmonella enterica serovar Typhimurium. In addition, inactivation of the stm3944 open reading frame, which is located immediately upstream of cyaY and which encodes a putative inner membrane protein, dramatically enhances the hydrogen peroxide sensitivity of a cyaY mutant. Overexpression of STM3944 reduces the elevated intracellular free iron levels observed in an S. Typhimurium fur mutant and also reduces the total cellular iron content under conditions of iron overload, suggesting that the stm3944-encoded protein may mediate iron efflux. Mutations in cyaY and yggX have different effects on the activities of the iron-sulfur cluster-containing aconitase, serine deaminase, and NADH dehydrogenase I enzymes of S. Typhimurium under basal conditions or following recovery from oxidative stress. In addition, cyaY and yggX mutations have additive effects on 6-phosphogluconate dehydratase-dependent growth during nitrosative stress, and a cyaY mutation reduces Salmonella virulence in mice. Collectively, these results indicate that CyaY and YggX play distinct supporting roles in iron-sulfur cluster biosynthesis

  11. 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. PMID:22176926

  12. 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...

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

    PubMed

    Purcell, Braden A; Kiani, Roozbeh

    2016-08-01

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

  14. Low-fidelity alternative DNA repair carcinogenesis theory may interpret many cancer features and anticancer strategies.

    PubMed

    Jiang, Chuo; Starr, Shane; Chen, Fuxue; Wu, Jiaxi

    2016-08-01

    We have proposed that the low-fidelity compensatory backup alternative DNA repair pathways drive multistep carcinogenesis. Here, we apply it to interpret the clinical features of cancer, such as mutator phenotype, tissue specificity, age specificity, diverse types of cancers originated from the same type of tissue, cancer susceptibility of patients with DNA repair-defective syndromes, development of cancer only for a selected number of individuals among those that share the same genetic defect, invasion and metastasis. Clinically, the theory predicts that to improve the efficacy of molecular targeted or synthetic lethal therapy, it may be crucial to inhibit the low-fidelity compensatory alternative DNA repair either directly or by blocking the signal transducers of the sustained microenvironmental stress. PMID:27166654

  15. 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…

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

    PubMed

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

    2016-09-01

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

  17. 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…

  18. 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;…

  19. 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;…

  20. 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;…

  1. Distinct Motor Strategies Underlying Split-Belt Adaptation in Human Walking and Running

    PubMed Central

    Ogawa, Tetsuya; Kawashima, Noritaka; Obata, Hiroki; Kanosue, Kazuyuki; Nakazawa, Kimitaka

    2015-01-01

    The aim of the present study was to elucidate the adaptive and de-adaptive nature of human running on a split-belt treadmill. The degree of adaptation and de-adaptation was compared with those in walking by calculating the antero-posterior component of the ground reaction force (GRF). Adaptation to walking and running on a split-belt resulted in a prominent asymmetry in the movement pattern upon return to the normal belt condition, while the two components of the GRF showed different behaviors depending on the gaits. The anterior braking component showed prominent adaptive and de-adaptive behaviors in both gaits. The posterior propulsive component, on the other hand, exhibited such behavior only in running, while that in walking showed only short-term aftereffect (lasting less than 10 seconds) accompanied by largely reactive responses. These results demonstrate a possible difference in motor strategies (that is, the use of reactive feedback and adaptive feedforward control) by the central nervous system (CNS) for split-belt locomotor adaptation between walking and running. The present results provide basic knowledge on neural control of human walking and running as well as possible strategies for gait training in athletic and rehabilitation scenes. PMID:25775426

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

    PubMed

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

    2011-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. 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

  6. Predictors of intimate partner violence revictimization: the relative impact of distinct PTSD symptoms, dissociation, and coping strategies.

    PubMed

    Iverson, Katherine M; Litwack, Scott D; Pineles, Suzanne L; Suvak, Michael K; Vaughn, Rachel A; Resick, Patricia A

    2013-02-01

    Psychological distress and coping strategies following intimate partner violence (IPV) victimization may impact survivors' risk for future IPV. The current study prospectively examined the impact of distinct posttraumatic stress disorder (PTSD) symptom clusters (reexperiencing, avoidance, numbing, and hyperarousal), dissociation, and coping strategies (engagement and disengagement coping) on IPV revictimization among recently abused women. Women (N = 69) who were seeking services for IPV and experienced their most recent episode of physical IPV between 2 weeks and 6 months prior to study enrollment completed measures of physical IPV, psychological distress, and coping strategies at baseline and at 6-month follow-up. The women averaged 36 years of age and 67% of the sample was African American. Separate Poisson regression analyses revealed that PTSD hyperarousal symptoms, dissociation, engagement coping, and disengagement coping each significantly predicted physical IPV revictimization at the 6-month follow-up (with effect sizes ranging from a 1.20-1.34 increase in the likelihood of Time 2 physical IPV with a 1 SD increase in the predictor). When these significant predictors were examined together in a single Poisson regression model, only engagement and disengagement coping were found to predict physical IPV revictimization such that disengagement coping was associated with higher revictimization risk (1.29 increase in the likelihood of Time 2 physical IPV with one SD increase in disengagement coping) and engagement coping was associated with lower revictimization risk (1.30 decrease in the likelihood of Time 2 physical IPV with one SD increase in engagement coping). The current findings suggest that coping strategies are important and potentially malleable predictors of physical IPV revictimization. PMID:23417878

  7. 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. PMID:26320569

  8. 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. PMID:26902420

  9. 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. PMID:26876753

  10. 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

  11. Combination strategies for repair, plasticity, and regeneration using regulation of gene expression during the chronic phase after spinal cord injury.

    PubMed

    Gerin, Christine G; Madueke, Ikenna C; Perkins, Tina; Hill, Seritta; Smith, Kristin; Haley, Benjamin; Allen, Shannon A; Garcia, Richard P; Paunesku, Tanjana; Woloschak, Gayle

    2011-12-01

    Although recovery after spinal cord injury (SCI) is rare in humans, recent literature indicates that some patients do recover sensorimotor function years after the trauma. This study seeks to elucidate the genetic underpinnings of SCI repair through the investigation of neurodegenerative and regenerative associated genes involved in the response to SCI during the chronic phase in adult rats. Intervention on the level of gene regulation focused on enhancing naturally attempting SCI regenerative genes has the potential to promote SCI repair. Our aim was to analyze gene expression characteristics of candidate genes involved in the neuro-degenerative and -regenerative processes following various animal models of SCI. We compiled data showing gene expression changes after SCI in adult rats and created a chronological time-line of candidate genes differentially expressed during the chronic phase of SCI. Compiled data showed that SCI induced a transient upregulation of endogenous neuro-regenerative genes not only within a few hours but also within a few days, weeks, and months after SCI. For example, gene controlling growth-associated protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and others, showed significant changes in mRNA accumulation in SCI animals, from 48 hours to 12 weeks after SCI. Similarly, inhibitory genes, such as RhoA, LINGO-1, and others, were upregulated as late as 4 to 14 days after injury. This indicates that gene specific regulation changes, corresponding to repair and regenerative attempts, are naturally orchestrated over time after injury. These delayed changes after SCI give ample time for therapeutic gene modulation through upregulation or silencing of specific genes responsible for the synthesis of the corresponding biogenic proteins. By following the examination of differential gene regulation during the chronic phase, we have determined times, successions, co

  12. 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. PMID:25722002

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

    PubMed

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

    2015-11-01

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

  14. 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. PMID:25210033

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

    PubMed Central

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

    2006-01-01

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

  16. 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

  17. 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

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2013-01-01

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

  20. 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.

  1. Meningocele repair

    MedlinePlus

    ... dysraphism repair; Meningomyelocele repair; Neural tube defect repair; Spina bifida repair ... a medical team with experience in children with spina bifida. Your baby will likely have an MRI (magnetic ...

  2. 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.

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

    PubMed

    von Schwerin, Alexander

    2015-09-01

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

  4. 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.

    PubMed

    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. PMID:18351884

  5. 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.

  6. DNA repair

    SciTech Connect

    Friedberg, E.C.; Hanawalt, P.C. )

    1988-01-01

    Topics covered in this book included: Eukaryote model systems for DNA repair study; Sensitive detection of DNA lesions and their repair; and Defined DNA sequence probes for analysis of mutagenesis and repair.

  7. Lack of correlation between outcomes of membrane repair assay and correction of dystrophic changes in experimental therapeutic strategy in dysferlinopathy.

    PubMed

    Lostal, William; Bartoli, Marc; Roudaut, Carinne; Bourg, Nathalie; Krahn, Martin; Pryadkina, Marina; Borel, Perrine; Suel, Laurence; Roche, Joseph A; Stockholm, Daniel; Bloch, Robert J; Levy, Nicolas; Bashir, Rumaisa; Richard, Isabelle

    2012-01-01

    Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea that the pathophysiology of dysferlin deficiencies is due to a deficit in membrane repair. Here, we show using two different approaches that fulfilling membrane repair as asseyed by laser wounding assay is not sufficient for alleviating the dysferlin deficient pathology. First, we generated a transgenic mouse overexpressing myoferlin to test the hypothesis that myoferlin, which is homologous to dysferlin, can compensate for the absence of dysferlin. The myoferlin overexpressors show no skeletal muscle abnormalities, and crossing them with a dysferlin-deficient model rescues the membrane fusion defect present in dysferlin-deficient mice in vitro. However, myoferlin overexpression does not correct muscle histology in vivo. Second, we report that AAV-mediated transfer of a minidysferlin, previously shown to correct the membrane repair deficit in vitro, also fails to improve muscle histology. Furthermore, neither myoferlin nor the minidysferlin prevented myofiber degeneration following eccentric exercise. Our data suggest that the pathogenicity of dysferlin deficiency is not solely related to impairment in sarcolemmal repair and highlight the care needed in selecting assays to assess potential therapies for dysferlinopathies. PMID:22666441

  8. Lack of Correlation between Outcomes of Membrane Repair Assay and Correction of Dystrophic Changes in Experimental Therapeutic Strategy in Dysferlinopathy

    PubMed Central

    Krahn, Martin; Pryadkina, Marina; Borel, Perrine; Suel, Laurence; Roche, Joseph A.; Stockholm, Daniel; Bloch, Robert J.; Levy, Nicolas; Bashir, Rumaisa; Richard, Isabelle

    2012-01-01

    Mutations in the dysferlin gene are the cause of Limb-girdle Muscular Dystrophy type 2B and Miyoshi Myopathy. The dysferlin protein has been implicated in sarcolemmal resealing, leading to the idea that the pathophysiology of dysferlin deficiencies is due to a deficit in membrane repair. Here, we show using two different approaches that fullfiling membrane repair as asseyed by laser wounding assay is not sufficient for alleviating the dysferlin deficient pathology. First, we generated a transgenic mouse overexpressing myoferlin to test the hypothesis that myoferlin, which is homologous to dysferlin, can compensate for the absence of dysferlin. The myoferlin overexpressors show no skeletal muscle abnormalities, and crossing them with a dysferlin-deficient model rescues the membrane fusion defect present in dysferlin-deficient mice in vitro. However, myoferlin overexpression does not correct muscle histology in vivo. Second, we report that AAV-mediated transfer of a minidysferlin, previously shown to correct the membrane repair deficit in vitro, also fails to improve muscle histology. Furthermore, neither myoferlin nor the minidysferlin prevented myofiber degeneration following eccentric exercise. Our data suggest that the pathogenicity of dysferlin deficiency is not solely related to impairment in sarcolemmal repair and highlight the care needed in selecting assays to assess potential therapies for dysferlinopathies. PMID:22666441

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

    PubMed Central

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

    2016-01-01

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

  10. Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat-to-target strategy.

    PubMed

    Siemons, Liseth; Ten Klooster, Peter M; Vonkeman, Harald E; Glas, Cees A W; Van de Laar, Mart a F J

    2014-04-01

    Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, important individual variations exist in the course towards remission. Growth mixture modeling (GMM) provides more insight into this heterogeneity by identifying subgroups of patients with similar response patterns. This study aimed to identify distinct trajectories of disease activity in early RA patients following a T2T strategy, during their first year. Methods: Data on various clinical and patient-reported measures were collected from the DREAM remission induction cohort. GMM was applied to examine the impact of T2T on subgroups characterized by different types of growth trajectories, as measured with the Disease Activity Score for 28 joints. Results: Three distinct trajectories of disease activity were found. The normative trajectory contained most patients (82.6%), showing a quickly decreasing disease activity, stabilizing at remission after 9 months. This group performed best on clinical and patient-reported measures over time and were more likely to be men. A smaller group (14.1%) also approached remission, but demonstrated a slower response to treatment. Finally, a minority (3.3%) showed no improvement after 1 year, despite an initial quick decrease in disease activity during the first months of treatment. Conclusion: Disease activity in early RA patients during the first year of a T2T strategy does not follow a linear pattern, nor is a single developmental trajectory applicable to all patients. Future studies should attempt to identify more specific risk factors for poor outcome to enable early identification of patients in need of alternative therapeutic approaches. PMID:24106173

  11. EUVL Mask Blank Repair

    SciTech Connect

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

    2002-05-22

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

  12. 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

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

    PubMed

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

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

  14. Lamellar body mimetic system: An up-to-down repairing strategy of the stratum corneum lipid structure.

    PubMed

    Moner, Verónica; Fernández, Estibalitz; Rodríguez, Gelen; Cócera, Mercedes; Barbosa-Barros, Lucyanna; de la Maza, Alfonso; López, Olga

    2016-08-20

    Epidermal lamellar bodies (LBs) are organelles that secrete their content, mainly lipids and enzymes, into the intercorneocyte space of the stratum corneum (SC) to form the lamellar structure of this tissue. Thus, LBs have a key role in permeability and the microbial cutaneous barrier. In this work, a complex lipid system that mimics the morphology, structure and composition of LBs has been designed. To evaluate the effect of this system on delipidized SC, in vitro experiments using porcine skin were performed. The microstructure of SC samples (native, delipidized and, delipidized after treatment) was evaluated by freeze substitution transmission electron microscopy (FSTEM) and grazing-incidence small-angle X-ray scattering (GISAXS). Delipidized SC samples showed no evidence of lipid lamellae after extraction with organic solvents. However, after treatment with the LB mimetic system, new lamellar structures between corneocytes were detected by FSTEM, and high intensity peaks and reflections were found in the GISAXS pattern. These results demonstrate a strong effect of the treatment in repairing part of the lipid lamellar structure of the SC. Accordingly, future research could extend the use of this system to repair skin barrier dysfunction. PMID:27311355

  15. Human DNA repair genes.

    PubMed

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

    2001-02-16

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

  16. Clubfoot repair

    MedlinePlus

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

  17. 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

  18. “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

  19. Gene Therapy for Cartilage Repair

    PubMed Central

    Madry, Henning; Orth, Patrick; Cucchiarini, Magali

    2011-01-01

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

  20. 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

  1. 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

  2. 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.

  3. Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia-a new therapeutic strategy?

    PubMed

    Rösler, Barbara; Herold, Susanne

    2016-12-01

    Influenza viruses (IVs) circulate seasonally and are a common cause of respiratory infections in pediatric and adult patients. Additionally, recurrent pandemics cause massive morbidity and mortality worldwide. Infection may result in rapid progressive viral pneumonia with fatal outcome. Since accurate treatment strategies are still missing, research refocuses attention to lung pathology and cellular crosstalk to develop new therapeutic options.Alveolar epithelial cells (AECs) play an important role in orchestrating the pulmonary antiviral host response. After IV infection they release a cascade of immune mediators, one of which is granulocyte and macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to promote differentiation, activation and mobilization of myeloid cells. In the lung, GM-CSF drives immune functions of alveolar macrophages and dendritic cells (DCs) and also improves epithelial repair processes through direct interaction with AECs. During IV infection, AEC-derived GM-CSF shows a lung-protective effect that is also present after local GM-CSF application. This mini-review provides an overview on GM-CSF-modulated immune responses to IV pneumonia and its therapeutic potential in severe IV pneumonia. PMID:27480877

  4. Gastroschisis repair

    MedlinePlus

    ... and surgery in general are: Allergic reactions to medicines Breathing problems Bleeding Infection Risks for gastroschisis repair are: Breathing problems if the baby's belly area (abdominal space) is smaller than normal. The baby may need ...

  5. 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: ...

  6. 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.

  7. Complexities of the DNA Base Excision Repair Pathway for Repair of Oxidative DNA Damage

    PubMed Central

    Mitra, Sankar; Boldogh, Istvan; Izumi, Tadahide; Hazra, Tapas K.

    2016-01-01

    Oxidative damage represents the most significant insult to organisms because of continuous production of the reactive oxygen species (ROS) in vivo. Oxidative damage in DNA, a critical target of ROS, is repaired primarily via the base excision repair (BER) pathway which appears to be the simplest among the three excision repair pathways. However, it is now evident that although BER can be carried with four or five enzymes in vitro, a large number of proteins, including some required for nucleotide excision repair (NER), are needed for in vivo repair of oxidative damage. Furthermore, BER in transcribed vs. nontranscribed DNA regions requires distinct sets of proteins, as in the case of NER. We propose an additional complexity in repair of replicating vs. nonreplicating DNA. Unlike DNA bulky adducts, the oxidized base lesions could be incorporated in the nascent DNA strand, repair of which may share components of the mismatch repair process. Distinct enzyme specificities are thus warranted for repair of lesions in the parental vs. nascent DNA strand. Repair synthesis may be carried out by DNA polymerase β or replicative polymerases δ and ε. Thus, multiple subpathways are needed for repairing oxidative DNA damage, and the pathway decision may require coordination of the successive steps in repair. Such coordination includes transfer of the product of a DNA glycosylase to AP-endonuclease, the next enzyme in the pathway. Interactions among proteins in the pathway may also reflect such coordination, characterization of which should help elucidate these subpathways and their in vivo regulation. PMID:11746753

  8. Proteoglycans and cartilage repair.

    PubMed

    Ouzzine, Mohamed; Venkatesan, Narayanan; Fournel-Gigleux, Sylvie

    2012-01-01

    Repair of damaged articular cartilage in osteoarthritis (OA) is a clinical challenge. Because cartilage is an avascular and aneural tissue, normal mechanisms of tissue repair through recruitment of cells to the site of tissue destruction are not feasible. Proteoglycan (PG) depletion induced by the proinflammatory cytokine interleukin-1β, a principal mediator in OA, is a major factor in the onset and progression of joint destruction. Current symptomatic treatments of OA by anti-inflammatory drugs do not alter the progression of the disease. Various therapeutic strategies have been developed to antagonize the effect of proinflammatory cytokines. However, relatively few studies were conducted to stimulate anabolic activity, in an attempt to enhance cartilage repair. To this aim, a nonviral gene transfer strategy of glycosyltransferases responsible for PG synthesis has been developed and tested for its capacity to promote cartilage PG synthesis and deposition. Transfection of chondrocytes or cartilage explants by the expression vector for the glycosyltransferase β-1,3-glucuronosyltransferase-I (GlcAT-I) enhanced PG synthesis and deposition in the ECM by promoting the synthesis of chondroitin sulfate GAG chains of the cartilage matrix. This indicates that therapy mediated through GT gene delivery may constitute a new strategy for the treatment of OA. PMID:22252645

  9. 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

  10. 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

    2014-03-01

    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. PMID:24602816

  11. 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…

  12. 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…

  13. 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…

  14. Hydrocele repair

    MedlinePlus

    ... small surgical cut in the fold of the groin, and then drains the fluid. The sac (hydrocele) holding the fluid may be removed. The surgeon strengthens the muscle wall with stitches. This is called a hernia repair. Sometimes the surgeon uses a laparoscope to do ...

  15. Bladder exstrophy repair

    MedlinePlus

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... in boys and is often linked to other birth defects. Surgery is necessary to: Allow the child to ...

  16. 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.

  17. Meniscal Repair

    PubMed Central

    Yoon, Kyoung Ho

    2014-01-01

    The meniscus has several important roles, such as transmission of the load, absorption of the shock in the knee joint, acting as a secondary anteroposterior stabilizer of the knee joint, and contributing to proprioception of the knee joint. Degenerative changes of the knee joint develop in the long-term follow-up even after partial meniscectomy. Thus, there has been growing interest in meniscal repair. In addition, with increased understanding of the important roles of the meniscal root and advancement of diagnostic methods, efforts have been made to ensure preservation of the meniscal roots. In this review article, we will discuss operative techniques and clinical outcomes of arthroscopic repair of the meniscus and the meniscal root and postoperative rehabilitation and complications as well. PMID:24944971

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

    ERIC Educational Resources Information Center

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

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

  19. Persistent hyperactivity and distinctive strategy features in the Morris water maze in 3xTg-AD mice at advanced stages of disease.

    PubMed

    Baeta-Corral, Raquel; Giménez-Llort, Lydia

    2015-04-01

    Search strategies in the Morris water maze provide useful insights on cognitive function that may reveal genotype differences not reflected by escape latency or distance. Its analysis is pointed out as a complementary tool to better define the phenotype and the effect of treatments in animal models in which both cognitive impairment and behavioral symptoms reproduce the clinical complexity of the Alzheimer's disease patient. Here, we studied the performance of 13-month-old male 3xTg-AD mice in 3 different paradigms (cue learning, place task, and probe trial) and as compared with age-matched nontransgenic mice. The quantitative analysis (escape latency, distance, and speed) showed that in all tasks, the cognitive performance of 3xTg-AD mice was interfered with by a persistent hyperactive pattern. Their worse cognitive function was revealed by the qualitative features of nonsearch behaviors (floating and circling) and search strategies (single and /mixed, goal directed and nongoal directed). The search pattern was based on mixed and nongoal-directed strategies, in contrast to the single and goal-directed strategies used by controls. In the place task, poor cognitive flexibility of 3xTg-AD mice was also shown in persistence of search in the cue-trained position and the need to correct the strategy to find the new location. Trials involving a naïve situation (first trial of the cue task) or the difficulty of a new task (first trial of the place task and the probe trial) were the most suitable to show the deficits. This qualitative analysis may also be useful in the assessment of preventive or therapeutical treatments. PMID:25730122

  20. Current Biomechanical Concepts for Rotator Cuff Repair

    PubMed Central

    2013-01-01

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

  1. Cartilage defect repair in horses: Current strategies and recent developments in regenerative medicine of the equine joint with emphasis on the surgical approach.

    PubMed

    Cokelaere, Stefan; Malda, Jos; van Weeren, René

    2016-08-01

    Chondral and osteochondral lesions due to injury or other pathology are highly prevalent conditions in horses (and humans) and commonly result in the development of osteoarthritis and progression of joint deterioration. Regenerative medicine of articular cartilage is an emerging clinical treatment option for patients with articular cartilage injury or disease. Functional articular cartilage restoration, however, remains a major challenge, but the field is progressing rapidly and there is an increasing body of supportive clinical and scientific evidence. This review gives an overview of the established and emerging surgical techniques employed for cartilage repair in horses. Through a growing insight in surgical cartilage repair possibilities, surgeons might be more stimulated to explore novel techniques in a clinical setting. PMID:27387728

  2. Aortic aneurysm repair - endovascular

    MedlinePlus

    ... Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... leaking or bleeding. You may have an abdominal aortic aneurysm that is not causing any symptoms or problems. ...

  3. 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 ...

  4. 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 ...

  5. Aortic aneurysm repair - endovascular

    MedlinePlus

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... leaking or bleeding. You may have an abdominal aortic aneurysm that is not causing any symptoms or problems. ...

  6. Preferential DNA repair in expressed genes.

    PubMed Central

    Hanawalt, P C

    1987-01-01

    Potentially deleterious alterations to DNA occur nonrandomly within the mammalian genome. These alterations include the adducts produced by many chemical carcinogens, but not the UV-induced cyclobutane pyrimidine dimer, which may be an exception. Recent studies in our laboratory have shown that the excision repair of pyrimidine dimers and certain other lesions is nonrandom in the mammalian genome, exhibiting a distinct preference for actively transcribed DNA sequences. An important consequence of this fact is that mutagenesis and carcinogenesis may be determined in part by the activities of the relevant genes. Repair may also be processive, and a model is proposed in which excision repair is coupled to transcription at the nuclear matrix. Similar but freely diffusing repair complexes may account for the lower overall repair efficiencies in the silent domains of the genome. Risk assessment in relation to chemical carcinogenesis requires assays that determine effective levels of DNA damage for producing malignancy. The existence of nonrandom repair in the genome casts into doubt the reliability of overall indicators of DNA binding and lesion repair for such determinations. Furthermore, some apparent differences between the intragenomic repair heterogeneity in rodent cells and that in human cells mandate a reevaluation of rodent test systems for human risk assessment. Tissue-specific and cell-specific differences in the coordinate regulation of gene expression and DNA repair may account for corresponding differences in the carcinogenic response. Images FIGURE 1. FIGURE 1. PMID:3447906

  7. 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

  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. 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)

  10. Oxidative DNA Damage and Nucleotide Excision Repair

    PubMed Central

    Melis, Joost P.M.; Luijten, Mirjam

    2013-01-01

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

  11. 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. PMID:26962873

  12. DNA double-strand break repair inhibitors as cancer therapeutics.

    PubMed

    Srivastava, Mrinal; Raghavan, Sathees C

    2015-01-22

    Among DNA damages, double-strand breaks (DSBs) are one of the most harmful lesions to a cell. Failure in DSB repair could lead to genomic instability and cancer. Homologous recombination (HR) and nonhomologous end joining (NHEJ) are major DSB repair pathways in higher eukaryotes. It is known that expression of DSB repair genes is altered in various cancers. Activation of DSB repair genes is one of the reasons for chemo- and radioresistance. Therefore, targeting DSB repair is an attractive strategy to eliminate cancer. Besides, therapeutic agents introduce breaks in the genome as an intermediate. Therefore, blocking the residual repair using inhibitors can potentiate the efficacy of cancer treatment. In this review, we discuss the importance of targeting DSB repair pathways for the treatment of cancer. Recent advances in the development of DSB repair inhibitors and their clinical relevance are also addressed. PMID:25579208

  13. 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.

  14. 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.

  15. Animal models of cartilage repair

    PubMed Central

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

    2014-01-01

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

  16. DNA Mismatch Repair

    PubMed Central

    MARINUS, M. G.

    2014-01-01

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

  17. 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.

  18. Eye muscle repair - discharge

    MedlinePlus

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

  19. Umbilical hernia repair

    MedlinePlus

    Umbilical hernia repair is surgery to repair an umbilical hernia . An umbilical hernia is a sac (pouch) formed from the ... the hole or weak spot caused by the umbilical hernia. Your surgeon may also lay a piece ...

  20. Femoral hernia repair

    MedlinePlus

    ... pushed back in. The weakened area is sewn closed or strengthened. This repair can be done with ... end of the repair, the cuts are stitched closed. In laparascopic surgery: The surgeon makes three to ...

  1. 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 ...

  2. Aortic aneurysm repair - endovascular- discharge

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000236.htm Aortic aneurysm repair - endovascular - discharge To use the sharing features ... enable JavaScript. AAA repair - endovascular - discharge; Repair - aortic aneurysm - endovascular - discharge; EVAR - discharge; Endovascular aneurysm repair - discharge ...

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

    PubMed

    Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

    2015-06-01

    Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. PMID:25867977

  4. Regulatory Challenges for Cartilage Repair Technologies.

    PubMed

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible. PMID:26069647

  5. Laparoscopic mesh repair of parahiatal hernia: a case report.

    PubMed

    Lew, Pei Shi; Wong, Andrew Siang Yih

    2013-08-01

    We report a case of a primary parahiatal hernia that was repaired laparoscopically with a composite mesh. A 51-year-old woman presented with vomiting and epigastric pain. CT scan showed a giant paraesophageal hernia with intrathoracic gastric volvulus. Intraoperatively, a diaphragmatic muscular defect was found lateral to an attenuated left crus of the diaphragm, distinct from the normal esophageal hiatus. The defect ring was fibrotic, making a tension-free primary repair difficult. A laparoscopic mesh repair was performed with a composite mesh, which was covered with the hernia sac to prevent potential erosion into the esophagus or stomach. Recovery was uneventful and the patient was discharged on the 5 days postoperatively. She remained asymptomatic at subsequent follow-up. Laparoscopic repair of parahiatal hernia can be safely performed. In circumstances where a large or fibrotic defect prevents a tension-free primary repair, the use of a composite mesh can provide effective repair of the hernia. PMID:23879418

  6. 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

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

    PubMed

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

    2016-02-01

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

  8. DNA INTERSTRAND CROSSLINK REPAIR IN MAMMALIAN CELLS: STEP BY STEP

    PubMed Central

    Muniandy, Parameswary; Liu, Jia; Majumdar, Alokes; Liu, Su-ting; Seidman, Michael M.

    2009-01-01

    Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair scheme involving incisions on one strand on either side of the ICL (unhooking) producing a gapped intermediate with the incised oligonucleotide attached to the intact strand. The gap is filled by recombinational repair or lesion bypass synthesis. The remaining monoadduct is then removed by Nucleotide Excision Repair (NER). Despite considerable effort, our understanding of each step in mammalian cells is still quite limited. In part this reflects the variety of crosslinking compounds, each with distinct structural features, used by different investigators. Also, multiple repair pathways are involved, variably operative during the cell cycle. G1 phase repair requires functions from NER, although the mechanism of recognition has not been determined. Repair can be initiated by encounters with the transcriptional apparatus, or a replication fork. In the case of the latter, the reconstruction of a replication fork, stalled or broken by collision with an ICL, adds to the complexity of the repair process. The enzymology of unhooking, the identity of the lesion bypass polymerases required to fill the first repair gap, and the functions involved in the second repair cycle are all subjects of active inquiry. Here we will review current understanding of each step in ICL repair in mammalian cells. PMID:20039786

  9. Arthroscopic rotator cuff repair.

    PubMed

    Burkhart, Stephen S; Lo, Ian K Y

    2006-06-01

    Arthroscopic rotator cuff repair is being performed by an increasing number of orthopaedic surgeons. The principles, techniques, and instrumentation have evolved to the extent that all patterns and sizes of rotator cuff tear, including massive tears, can now be repaired arthroscopically. Achieving a biomechanically stable construct is critical to biologic healing. The ideal repair construct must optimize suture-to-bone fixation, suture-to-tendon fixation, abrasion resistance of suture, suture strength, knot security, loop security, and restoration of the anatomic rotator cuff footprint (the surface area of bone to which the cuff tendons attach). By achieving optimized repair constructs, experienced arthroscopic surgeons are reporting results equal to those of open rotator cuff repair. As surgeons' arthroscopic skill levels increase through attendance at surgical skills courses and greater experience gained in the operating room, there will be an increasing trend toward arthroscopic repair of most rotator cuff pathology. PMID:16757673

  10. 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

  11. 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

  12. Techniques for aortic arch endovascular repair.

    PubMed

    kHONGKU, 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. PMID:26940011

  13. Telocytes in cardiac regeneration and repair.

    PubMed

    Bei, Yihua; Zhou, Qiulian; Sun, Qi; Xiao, Junjie

    2016-07-01

    Telocytes (TCs) are a novel type of stromal cells reported by Popescu's group in 2010. The unique feature that distinguishes TCs from other "classical" stromal cells is their extremely long and thin telopodes (Tps). As evidenced by electron microscopy, TCs are widely distributed in almost all tissues and organs. TCs contribute to form a three-dimensional interstitial network and play as active regulators in intercellular communication via homocellular/heterocellular junctions or shed vesicles. Interestingly, increasing evidence suggests the potential role of TCs in regenerative medicine. Although the heart retains some limited endogenous regenerative capacity, cardiac regenerative and repair response is however insufficient to make up the loss of cardiomyocytes upon injury. Developing novel strategies to increase cardiomyocyte renewal and repair is of great importance for the treatment of cardiac diseases. In this review, we focus on the role of TCs in cardiac regeneration and repair. We particularly describe the intercellular communication between TCs and cardiomyocytes, stem/progenitor cells, endothelial cells, and fibroblasts. Also, we discuss the current knowledge about TCs in cardiac repair after myocardial injury, as well as their potential roles in cardiac development and aging. TC-based therapy or TC-derived exosome delivery might be used as novel therapeutic strategies to promote cardiac regeneration and repair. PMID:26826525

  14. The interplay between DNA repair and autophagy in cancer therapy.

    PubMed

    Zhang, Dan; Tang, Bo; Xie, Xia; Xiao, Yu-Feng; Yang, Shi-Ming; Zhang, Jian-Wei

    2015-01-01

    DNA is the prime target of anticancer treatments. DNA damage triggers a series of signaling cascades promoting cellular survival, including DNA repair, cell cycle arrest, and autophagy. The elevated basal and/or stressful levels of both DNA repair and autophagy observed in tumor cells, in contrast to normal cells, have been identified as the most important drug-responsive programs that impact the outcome of anticancer therapy. The exact relationship between DNA repair and autophagy in cancer cells remains unclear. On one hand, autophagy has been shown to regulate some of the DNA repair proteins after DNA damage by maintaining the balance between their synthesis, stabilization, and degradation. One the other hand, some evidence has demonstrated that some DNA repair molecular have a crucial role in the initiation of autophagy. In this review, we mainly discuss the interplay between DNA repair and autophagy in anticancer therapy and expect to enlighten some effective strategies for cancer treatment. PMID:25985143

  15. 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…

  16. Biomimetic Strategies for Bone Repair and Regeneration

    PubMed Central

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

    2012-01-01

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

  17. Through-focus EUV multilayer defect repair with nanomachining

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  18. Heterochromatin formation via recruitment of DNA repair proteins

    PubMed Central

    Kirkland, Jacob G.; Peterson, Misty R.; Still, Christopher D.; Brueggeman, Leo; Dhillon, Namrita; Kamakaka, Rohinton T.

    2015-01-01

    Heterochromatin formation and nuclear organization are important in gene regulation and genome fidelity. Proteins involved in gene silencing localize to sites of damage and some DNA repair proteins localize to heterochromatin, but the biological importance of these correlations remains unclear. In this study, we examined the role of double-strand-break repair proteins in gene silencing and nuclear organization. We find that the ATM kinase Tel1 and the proteins Mre11 and Esc2 can silence a reporter gene dependent on the Sir, as well as on other repair proteins. Furthermore, these proteins aid in the localization of silenced domains to specific compartments in the nucleus. We identify two distinct mechanisms for repair protein–mediated silencing—via direct and indirect interactions with Sir proteins, as well as by tethering loci to the nuclear periphery. This study reveals previously unknown interactions between repair proteins and silencing proteins and suggests insights into the mechanism underlying genome integrity. PMID:25631822

  19. 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.

  20. 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.

  1. Planning Maintenance and Repairs.

    ERIC Educational Resources Information Center

    Fitzemeyer, Ted

    2001-01-01

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

  2. Laparoscopic Ventral Hernia Repair

    MedlinePlus

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

  3. Easily repairable networks

    NASA Astrophysics Data System (ADS)

    Fink, Thomas

    2015-03-01

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

  4. 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. ...

  5. Tracheoesophageal fistula repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100103.htm Tracheoesophageal fistula repair - series To use the sharing features on ... Editorial team. Related MedlinePlus Health Topics Esophagus Disorders Fistulas Tracheal Disorders A.D.A.M., Inc. is ...

  6. Bone fracture repair - slideshow

    MedlinePlus

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

  7. Pectus excavatum repair

    MedlinePlus

    ... surgery to repair this condition -- open surgery and closed (minimally invasive) surgery. Either surgery is done while ... At the end of surgery, the incision is closed. The metal struts are removed in 6 to ...

  8. Anterior vaginal wall repair

    MedlinePlus

    ... Cystocele Anterior vaginal wall repair (surgical treatment of urinary incontinence) - series References Lentz GM. Anatomic defects of the ... 72. Read More Anterior Inflatable artificial sphincter Stress urinary incontinence Urinary catheters Urinary incontinence - injectable implant Urinary incontinence - ...

  9. Imperforate anus repair - slideshow

    MedlinePlus

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

  10. 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 ...

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

    PubMed

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

    2015-01-01

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

  12. 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

  13. Glaucoma and optic nerve repair.

    PubMed

    Diekmann, Heike; Fischer, Dietmar

    2013-08-01

    Glaucoma is a leading cause of irreversible blindness worldwide and causes progressive visual impairment attributable to the dysfunction and death of retinal ganglion cells (RGCs). Progression of visual field damage is slow and typically painless. Thus, glaucoma is often diagnosed after a substantial percentage of RGCs has been damaged. To date, clinical interventions are mainly restricted to the reduction of intraocular pressure (IOP), one of the major risk factors for this disease. However, the lowering of IOP is often insufficient to halt or reverse the progress of visual loss, underlining the need for the development of alternative treatment strategies. Several lines of evidence suggest that axonal damage of RGCs occurs primary at the optic nerve head, where axons appear to be most vulnerable. Axonal injury leads to the functional loss of RGCs and subsequently induces the death of the neurons. However, the detailed molecular mechanism(s) underlying IOP-induced optic nerve injury remain poorly understood. Moreover, whether glaucoma pathophysiology is primarily axonal, glial, or vascular remains unclear. Therefore, protective strategies to prevent further axonal and subsequent soma degeneration are of great importance to limit the progression of sight loss. In addition, strategies that stimulate injured RGCs to regenerate and reconnect axons with their central targets are necessary for functional restoration. The present review provides an overview of the context of glaucoma pathogenesis and surveys recent findings regarding potential strategies for axonal regeneration of RGCs and optic nerve repair, focusing on the role of cytokines and their downstream signaling pathways. PMID:23512141

  14. Robotic inguinal hernia repair.

    PubMed

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

    2015-09-01

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

  15. Repairing Foam Insulation

    NASA Technical Reports Server (NTRS)

    Corbin, J.; Buras, D.

    1986-01-01

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

  16. Repair of UV damage in Halobacterium salinarum.

    PubMed

    McCready, S; Marcello, L

    2003-06-01

    Halobacterium is one of the few known Archaea that tolerates high levels of sunlight in its natural environment. Photoreactivation is probably its most important strategy for surviving UV irradiation and we have shown that both of the major UV photoproducts, cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts, can be very efficiently repaired by photoreactivation in this organism. There are two putative photolyase gene homologues in the published genome sequence of Halobacterium sp. NRC-1. We have made a mutant deleted in one of these, phr2, and confirmed that this gene codes for a CPD photolyase. (6-4) photoproducts are still photoreactivated in the mutant so we are currently establishing whether the other homologue, phr1, codes for a (6-4) photolyase. We have also demonstrated an excision repair capacity that operates in the absence of visible light but the nature of this pathway is not yet known. There is probably a bacteria-type excision-repair mechanism, since homologues of uvrA, uvrB, uvrC and uvrD have been identified in the Halobacterium genome. However, there are also homologues of eukaryotic nucleotide-excision-repair genes ( Saccharomyces cerevisiae RAD3, RAD25 and RAD2 ) so there may be multiple repair mechanisms for UV damage in Halobacterium. PMID:12773185

  17. 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

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

    PubMed

    Carmichael, S Thomas

    2016-06-01

    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

  19. 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

  20. 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.

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

    PubMed Central

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

    2010-01-01

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

  2. 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

  3. Radiological assessment of steam generator repair and replacement

    SciTech Connect

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

    1983-12-01

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

  4. Arthroscopic hip labral repair.

    PubMed

    Philippon, Marc J; Faucet, Scott C; Briggs, Karen K

    2013-05-01

    Labral tears in the hip may cause painful clicking or locking of the hip, reduced range of motion, and disruption to sports and daily activities. The acetabular labrum aids stabilization of the hip joint, particularly during hip motion. The fibrocartilaginous structure extends the acetabular rim and provides a suction seal around the femoroacetabular interface. Treatment options for labral tears include debridement, repair, and reconstruction. Repair of the labrum has been shown to have better results than debridement. Labral refixation is achieved with sutures anchored into the acetabular rim. The acetabular rim is trimmed either to correct pincer impingement or to provide a bleeding bed to improve healing. Labral repair has shown excellent short-term to midterm outcomes and allows patients to return to activities and sports. Arthroscopic rim trimming and labral refixation comprise an effective treatment for labral tears with an underlying diagnosis of femoroacetabular impingement and are supported by the peer-reviewed literature. PMID:23875153

  5. 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.

  6. 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.

  7. Normalizing Transantiago: on the challenges (and limits) of repairing infrastructures.

    PubMed

    Ureta, Sebastián

    2014-06-01

    This article looks to propose a new way to understand the repair of failing large sociotechnical systems. Leaving aside romantic valuations, repair always involves a certain degree of normalization. Derived from conceptualizations by Foucault, repair as normalization is understood as a particular form of power that, first, recognizes a certain normal state to which the failing system should evolve and, second, develops different strategies to reach it, usually involving the deployment of particular disciplinary devices. The ultimate aim of such practices is usually not only the improvement of the system but centrally the maintenance of a certain kind of power. In order to show the empirical usability of such conceptualization, the article analyzes the case of Transantiago, a thoroughgoing reform of the public transport system of Santiago, Chile. The start of Transantiago in February 2007 was marred by multiple failures, becoming one of the biggest public controversies in the country in recent decades. Given this, several different strategies were developed to repair such failures, understanding them explicitly as normalization. The article analyzes two particular strategies: attempts to change the negative 'public perception' about Transantiago through the use of quantitative indicators and the introduction of an unexpected type of infrastructure to increase the overall speed of the system. Finally, the conclusion analyzes how the conception of repair as normalization can help us better understand the complexities involved in dealing with failing large sociotechnical systems such as Transantiago, pointing to the need to sometimes move beyond repair. PMID:25051587

  8. Bone fracture repair - series (image)

    MedlinePlus

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

  9. 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.

  10. A distinctive neurologic syndrome after induced profound hypothermia.

    PubMed

    Wical, B S; Tomasi, L G

    1990-01-01

    Four patients suffered a distinctive neurologic syndrome after undergoing profound hypothermia and complete circulatory arrest for congenital heart lesion repair. Symptom onset was delayed 24-120 hours postoperatively. The syndrome consists of choreoathetosis and oral-facial dyskinesias, hypotonia, affective changes, and pseudobulbar signs (CHAP). Precise anatomic localization is uncertain. Magnetic resonance imaging of 2 patients did not reveal basal ganglia lesions. Pathogenesis is obscure. PMID:2360962

  11. 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…

  12. 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,…

  13. Repairing cracked glass

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  14. 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,…

  15. Patent urachus repair

    MedlinePlus

    ... Drugs & Supplements Videos & Tools About MedlinePlus Show Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Patent urachus repair URL of this page: //medlineplus.gov/ ...

  16. Patent urachus repair - slideshow

    MedlinePlus

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

  17. Repairing damaged platforms

    SciTech Connect

    Moore, R.E.; Kwok, P.H.; Wang, S.S.

    1995-10-01

    This paper introduces a unique method for strengthening of platforms and replacing damaged members. Extending the life of existing infrastructure is approved means of decreasing cash expenditures for new platforms and facilities. Platforms can be affected by corrosion, overloading and fatigue. The renovation and repair of existing offshore installations is an important part of offshore engineering. The basis behind this paper is an April, 1993 incident in the Arabian Gulf. A vessel broke loose from its moorings in a severe storm and collided with a wellhead platform. The collision severely damaged the platform buckling seven major support members and cracking joints throughout the structure. In view of the significant damage, there was an urgent need to repair the structure to avoid any further damage from potentially sever winter storm conditions. Various means of repair and their associated costs were evaluated: traditional dry hyperbaric welding, adjacent platforms, grouted clamped connections, and mechanical pipe connectors. The repair was completed using an innovative combination of clamps and wet welding to attach external braces to the structure.

  18. Proteoglycans and brain repair.

    PubMed

    Properzi, Francesca; Fawcett, James W

    2004-02-01

    Proteoglycans are complex molecules composed of long, unbranched sugar chains attached to a protein core. In the mammalian central nervous system, they are a major component of the extracellular matrix and of the cellular surface. After a central nervous system injury, their expression in the lesion area changes strongly and contributes to the inhibition of axon regrowth and brain repair. PMID:14739401

  19. Targeting Nuclear Envelope Repair.

    PubMed

    2016-06-01

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

  20. Auto Repair Gets Technical.

    ERIC Educational Resources Information Center

    Steiger, Jim; Shoemaker, Byrl

    1989-01-01

    Rapid advances in automotive technology and the growth of the automotive service industry have created opportunities in car repair, parts supply, and body work. Certification is the best way for vocational educators to ensure that their programs prepare students for work in the automotive industry. (JOW)

  1. Aircraft Propeller Hub Repair

    SciTech Connect

    Muth, Thomas R.; Peter, William H.

    2015-02-13

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

  2. Achilles tendon repair

    MedlinePlus

    ... ency/article/007643.htm Achilles tendon repair To use the sharing features on this page, please enable JavaScript. Your Achilles tendon joins your calf muscle to your heel. You can tear your Achilles tendon if you land hard on your heel during sports, from a ...

  3. 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…

  4. Femoral hernia repair

    MedlinePlus

    ... bulges out of a weak spot in the groin. Usually this tissue is part of the intestine. ... Your surgeon makes a cut (incision) in your groin area. The hernia is ... wall. This repairs the weakness in the wall. At the end ...

  5. 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

  6. Repair of high performance multilayer coatings

    SciTech Connect

    Gaines, D.P. . Dept. of Physics and Astronomy); Ceglio, N.M. ); Vernon, S.P. ); Krumrey, M.; Mueller, P. . VUV Radiometric Lab.)

    1991-07-01

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

  7. Repair of high-performance multilayer coatings

    NASA Astrophysics Data System (ADS)

    Gaines, David P.; Ceglio, Natale M.; Vernon, Stephen P.; Krumrey, Michael K.; Mueller, Peter

    1992-01-01

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

  8. 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.

  9. Touch communicates distinct emotions.

    PubMed

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. PMID:16938094

  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. Cleft lip repair - series (image)

    MedlinePlus

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

  12. Automotive Engine Maintenance and Repair.

    ERIC Educational Resources Information Center

    Marine Corps Inst., Washington, DC.

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

  13. Distinct facilitated diffusion mechanisms by E. coli Type II restriction endonucleases.

    PubMed

    Pollak, Adam J; Chin, Aaron T; Reich, Norbert O

    2014-11-18

    The passive search by proteins for particular DNA sequences involving nonspecific DNA is essential for gene regulation, DNA repair, phage defense, and diverse epigenetic processes. Distinct mechanisms contribute to these searches, and it remains unresolved as to which mechanism or blend of mechanisms best suits a particular protein and, more importantly, its biological role. To address this, we compare the translocation properties of two well-studied bacterial restriction endonucleases (ENases), EcoRI and EcoRV. These dimeric, magnesium-dependent enzymes hydrolyze related sites (EcoRI ENase, 5'-GAATTC-3'; EcoRV ENase, 5'-GATATC-3'), leaving overhangs and blunt DNA segments, respectively. Here, we demonstrate that the extensive sliding by EcoRI ENase, involving sliding up to ∼600 bp prior to dissociating from the DNA, contrasts with a larger reliance on hopping mechanism(s) by EcoRV ENase. The mechanism displayed by EcoRI ENase results in a highly thorough search of DNA, whereas the EcoRV ENase mechanism results in an extended, yet less rigorous, interrogation of DNA sequence space. We describe how these mechanistic distinctions are complemented by other aspects of these endonucleases, such as the 10-fold higher in vivo concentrations of EcoRI ENase compared to that of EcoRV ENase. Further, we hypothesize that the highly diverse enzyme arsenal that bacteria employ against foreign DNA involves seemingly similar enzymes that rely on distinct but complementary search mechanisms. Our comparative approach reveals how different proteins utilize distinct site-locating strategies. PMID:25350874

  14. Base Excision Repair and Cancer

    PubMed Central

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

    2012-01-01

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

  15. Disease of distinction.

    PubMed

    Schwartz, Stephan A

    2006-01-01

    Gout is one of the rare diseases that defines its sufferers by class and culture. It is also one of the first chronic diseases to be clinically described. The Egyptians had identified gout as a distinct disorder by 2640 bce. This paper traces the history of gout from its earliest recorded period down to modern times, with a particular emphasis on the cultural, political, geopolitical, and social aspects. Included is a discussion of its role in the American Revolution. Today, gout is a well-understood clinically managed arthritic disease that excites little comment. This is an entirely modern perspective. For most of human history, gout was a disease of distinction that dominated much of medicine, playing the same role in Rome's third century bce aristocracy it would later play in the aristocracies of 17th and 18th century France and England, when each of these countries dominated the world. Because it was considered a disease of lifestyle until modern times, when genetics began to be understood, gout was associated with rich, high status Caucasian men and their excessive consumption of drink and rich foods. It was virtually unknown in Asia, until Western dietary practices became widespread there. From earliest history, gout has been linked with high IQ and sexual promiscuity, which made it grist for artists and writers, and their social commentary up to the time of Dickens; this is discussed, with examples. Because of its association with the rich, gout also developed a powerful moralistic aspect, particularly during the Christian era when the concept of sin was a cultural fundamental. The loose living and indulgence of the rich and the gout it produced made the disease a parable of Christian ethics. The Italian poet Francesco Petrarch (1304-1374) was one of the first to establish this nuance, and it influenced how gout was seen for centuries. Part of what gave gout its special character was that while it tortured, it rarely killed. Indeed, when death was a

  16. Distinct intervertebral disc cell populations adopt similar phenotypes in three-dimensional culture.

    PubMed

    Chou, Alice I; Reza, Anna T; Nicoll, Steven B

    2008-12-01

    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

  17. 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

  18. Targeting base excision repair for chemosensitization.

    PubMed

    Adhikari, Sanjay; Choudhury, Sujata; Mitra, Partha S; Dubash, Jerita J; Sajankila, Shyama P; Roy, Rabindra

    2008-05-01

    In both bacteria and eukaryotes the alkylated, oxidized, and deaminated bases and depurinated lesions are primarily repaired via an endogenous preventive pathway, i.e. base excision repair (BER). Radiation therapy and chemotherapy are two important modes of cancer treatment. Many of those therapeutic agents used in the clinic have the ability to induce the DNA damage; however, they may also be highly cytotoxic, causing peripheral toxicity and secondary cancer as adverse side effects. In addition, the damage produced by the therapeutic agents can often be repaired by the BER proteins, which in effect confers therapeutic resistance. Efficient inhibition of a particular BER protein(s) may increase the efficacy of current chemotherapeutic regimes, which minimizes resistance and ultimately decreases the possibility of the aforementioned negative side effects. Therefore, pharmacological inhibition of DNA damage repair pathways may be explored as a useful strategy to enhance chemosensitivity. Various agents have shown excellent results in preclinical studies in combination chemotherapy. Early phase clinical trials are now being carried out using DNA repair inhibitors targeting enzymes such as PARP, DNA-PK or MGMT. In the case of BER proteins, elimination of N-Methylpurine DNA glycosylase (MPG) or inhibition of AP-endonuclease (APE) increased sensitivity of cancer cells to alkylating chemotherapeutics. MPG(-/-) embryonic stem cells and cells having MPG knock-down by siRNA are hypersensitive to alkylating agents, whereas inhibition of APE by small molecule inhibitors sensitized cancer cells to alkylating chemotherapeutics. Thus, MPG and other BER proteins could be potential targets for chemosensitization. PMID:18473720

  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. [Tissue engineered skin and regenerative wound repair].

    PubMed

    Han, Chun-mao; Wang, Xin-gang

    2013-04-01

    Various skin defects resulting from mechanical injury, burns, chronic ulcers, and resection of tumor etc. are very common in clinic. The traditional treatment measure, such as grafting of autologous split-thickness skin remains the gold standard. However, its limitations are obvious, such as shortage of donor sites, creation of new injury, and scar formation. To realize regenerative or scarless repair of tissue defects has always been the dream of human being. The advent of tissue engineered skin (TES) provides an ideal access to tissue regeneration. After decades of development, several kinds of TES products have been developed and used in clinic, with promising effects. However, a large number of basic scientific problems regarding TES, as well as difficulties in translation of basic research to bedside should be taken into serious consideration. This article presents a comprehensive overview of strategies of construction of TES, the role of TES in regenerative wound repair, and its opportunities and challenges. PMID:23985197

  1. Cardiac progenitor cells for heart repair

    PubMed Central

    Le, TYL; Chong, JJH

    2016-01-01

    Stem cell therapy is being investigated as an innovative and promising strategy to restore cardiac function in patients with heart failure. Several stem cell populations, including adult (multipotent) stem cells from developed organs and tissues, have been tested for cardiac repair with encouraging clinical and pre-clinical results. The heart has been traditionally considered a post-mitotic organ, however, this view has recently changed with the identification of stem/progenitor cells residing within the adult heart. Given their cardiac developmental origins, these endogenous cardiac progenitor cells (CPCs) may represent better candidates for cardiac cell therapy compared with stem cells from other organs such as the bone marrow and adipose tissue. This brief review will outline current research into CPC populations and their cardiac repair/regenerative potential. PMID:27551540

  2. Prokaryotic nucleotide excision repair.

    PubMed

    Kisker, Caroline; Kuper, Jochen; Van Houten, Bennett

    2013-03-01

    Nucleotide excision repair (NER) has allowed bacteria to flourish in many different niches around the globe that inflict harsh environmental damage to their genetic material. NER is remarkable because of its diverse substrate repertoire, which differs greatly in chemical composition and structure. Recent advances in structural biology and single-molecule studies have given great insight into the structure and function of NER components. This ensemble of proteins orchestrates faithful removal of toxic DNA lesions through a multistep process. The damaged nucleotide is recognized by dynamic probing of the DNA structure that is then verified and marked for dual incisions followed by excision of the damage and surrounding nucleotides. The opposite DNA strand serves as a template for repair, which is completed after resynthesis and ligation. PMID:23457260

  3. 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

  4. 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

  5. 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

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

    PubMed

    Meas, Rithy; Smerdon, Michael J

    2016-01-01

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

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

    PubMed

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

    2016-08-01

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

  8. 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

  9. Testicular torsion repair - slideshow

    MedlinePlus

    ... Go to slide 4 out of 4 Normal anatomy Overview The testicles are suspended in the scrotal ... M. is among the first to achieve this important distinction for online health information and services. Learn ...

  10. Pectus excavatum repair - slideshow

    MedlinePlus

    ... Go to slide 4 out of 4 Normal anatomy Overview Pectus excavatum is a deformity of the ... M. is among the first to achieve this important distinction for online health information and services. Learn ...

  11. Gastroschisis repair - slideshow

    MedlinePlus

    ... Go to slide 4 out of 4 Normal anatomy Overview In the womb, fetal intestines develop outside ... M. is among the first to achieve this important distinction for online health information and services. Learn ...

  12. Carpal tunnel repair - slideshow

    MedlinePlus

    ... Go to slide 4 out of 4 Normal anatomy Overview The tendons and nerve to the hand ( ... M. is among the first to achieve this important distinction for online health information and services. Learn ...

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

    ERIC Educational Resources Information Center

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

    2006-01-01

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

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

    PubMed

    Emanuel, Patrick; Scheinfeld, Noah

    2007-01-01

    Few other organs have the environmental exposure-neoplasia relationship that has been observed between epithelial cutaneous malignancy and UVB exposure. A significant DNA type of defective linking of DNA nucleotides involves pyrimidine dimers. Important insight into the molecular processes that affect the response of cells to UVB have been provided by the study of rare inherited diseases characterized by DNA repair defects. Nucleotide excision repair is the best characterized of these and its importance is illustrated by the disease, xeroderma pigmentosum. This heterogenous disorder clinically characterized by malignant tumor development and molecularly by distinct alterations in the nucleotide excision repair apparatus. More recently, other DNA mechanisms have been shown to have some role in skin cancer, such as DNA-mismatch repair and double-stranded DNA breaks. Herein, we discuss the DNA-repair adjuvants a aqueous extract of Urcaria tomentosa (AC-11, Optigenex, Inc.), and T4 endonuclease V that is prepared in a liposome lotion (Dimericine, Applied Genetics Inc. Dermatics). The positive effects on the integrity DNA of other substances (from nature, heat shock proteins and cytokines) including IL-12, Polypodium leucotomos, and ubiquitin are also reviewed. Understanding DNA repair mechanisms is far from complete; further understanding will provide insight into the pathogenesis of cancer and pave the way for efficacious therapeutic agents. PMID:18328204

  15. Open aortic surgery after thoracic endovascular aortic repair.

    PubMed

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

    2016-08-01

    In the last decade, thoracic endovascular aortic aneurysm repair (TEVAR) has emerged as an appealing alternative to the traditional open aortic aneurysm repair. This is largely due to generally improved early outcomes associated with TEVAR, including lower perioperative mortality and morbidity. However, it is relatively common for patients who undergo TEVAR to need a secondary intervention. In select circumstances, these secondary interventions are performed as an open procedure. Although it is difficult to assess the rate of open repairs after TEVAR, the rates in large series of TEVAR cases (>300) have ranged from 0.4 to 7.9 %. Major complications of TEVAR that typically necessitates open distal aortic repair (i.e., repair of the descending thoracic or thoracoabdominal aorta) include endoleak (especially type I), aortic fistula, endograft infection, device collapse or migration, and continued expansion of the aneurysm sac. Conversion to open repair of the distal aorta may be either elective (as for many endoleaks) or emergent (as for rupture, retrograde complicated dissection, malperfusion, and endograft infection). In addition, in select patients (e.g., those with a chronic aortic dissection), unrepaired sections of the aorta may progressively dilate, resulting in the need for multiple distal aortic repairs. Open repairs after TEVAR can be broadly classified as full extraction, partial extraction, or full salvage of the stent-graft. Although full and partial stent-graft extraction imply failure of TEVAR, such failure is generally absent in cases where the stent-graft can be fully salvaged. We review the literature regarding open repair after TEVAR and highlight operative strategies. PMID:27314956

  16. The back and forth of axonal injury and repair after stroke

    PubMed Central

    Hinman, Jason D.

    2015-01-01

    Purpose of review The axon plays a central role in both the injury and repair phases after stroke. This review highlights emerging principles in the study of axonal injury in stroke and the role of the axon in neural repair after stroke. Recent findings Ischemic stroke produces a rapid and significant loss of axons in the acute phase. This early loss of axons results from a primary ischemic injury that triggers a wave of calcium signaling, activating proteolytic mechanisms and downstream signaling cascades. A second progressive phase of axonal injury occurs during the subacute period and damages axons that survive the initial ischemic insult but go on to experience a delayed axonal degeneration driven in part by changes in axoglial contact and axonal energy metabolism. Recovery from stroke is dependent on axonal sprouting and reconnection that occurs during a third degenerative/regenerative phase. Despite this central role played by the axon, comparatively little is understood about the molecular pathways that contribute to early and subacute axonal degeneration after stroke. Recent advances in axonal neurobiology and signaling suggest new targets that hold promise as potential molecular therapeutics including axonal calcium signaling, axoglial energy metabolism and cell adhesion as well as retrograde axonal mitogen-activated protein kinase pathways. These novel pathways must be modeled appropriately as the type and severity of axonal injury vary by stroke subtype. Summary Stroke-induced injury to axons occurs in three distinct phases each with a unique molecular underpinning. A wealth of new data about the molecular organization and molecular signaling within axons is available but not yet robustly applied to the study of axonal injury after stroke. Identifying the spatiotemporal patterning of molecular pathways within the axon that contribute to injury and repair may offer new therapeutic strategies for the treatment of stroke. PMID:25364952

  17. Intraoral repair of cosmetic restorations.

    PubMed

    Denehy, G; Bouschlicher, M; Vargas, M

    1998-10-01

    The longevity of porcelain and composite resin restorations can often be prolonged by using sound principles, up-to-date materials, and judicious attention to repair when fracture problems arise. Careful case selection and correct usage of surface treatment agents, followed by the use of a quality bonding system and restorative materials, can result in a repair that exhibits excellent retention and natural color blending. This article outlines procedures and materials to repair both resin composite and porcelain intraorally. PMID:9891653

  18. Leishmania major and Trypanosoma cruzi present distinct DNA damage responses.

    PubMed

    Garcia, Juliana B F; Rocha, João P Vieira da; Costa-Silva, Héllida M; Alves, Ceres L; Machado, Carlos R; Cruz, Angela K

    2016-05-01

    Leishmania major and Trypanosoma cruzi are medically relevant parasites and interesting model organisms, as they present unique biological processes. Despite increasing data regarding the mechanisms of gene expression regulation, there is little information on how the DNA damage response (DDR) occurs in trypanosomatids. We found that L. major presented a higher radiosensitivity than T. cruzi. L. major showed G1 arrest and displayed high mortality in response to ionizing radiation as a result of the inefficient repair of double-strand breaks (DSBs). Conversely, T. cruzi exhibited arrest in the S/G2 cell cycle phase, was able to efficiently repair DSBs and did not display high rates of cell death after exposure to gamma irradiation. L. major showed higher resistance to alkylating DNA damage, and only L. major was able to promote DNA repair and growth recovery in the presence of MMS. ASF1c overexpression did not interfere with the efficiency of DNA repair in either of the parasites but did accentuate the DNA damage checkpoint response, thereby delaying cell fate after damage. The observed differences in the DNA damage responses of T. cruzi and L. major may originate from the distinct preferred routes of genetic plasticity of the two parasites, i.e., DNA recombination versus amplification. PMID:27188657

  19. 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

  20. 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.

  1. Skeletal myoblasts for cardiac repair

    PubMed Central

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

    2011-01-01

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

  2. 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

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

    PubMed Central

    Zuliani-Alvarez, Lorena; Midwood, Kim S.

    2015-01-01

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

  4. 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

  5. Language Learning Strategies and Communication Strategies: A Synthesis

    ERIC Educational Resources Information Center

    Husain, Kausar

    2006-01-01

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

  6. Surgical repair of myelomeningocele.

    PubMed

    Lanigan, M W

    1993-12-01

    The birth of an infant with myelomeningocele provides a devastating experience for parents, a management dilemma for medical personnel, and an economic liability of immense proportions associated with the multiple disciplinary management program throughout the patient's life. Although undue delay in the onset of therapy is to be avoided, time can be taken for through assessment and appropriate discussion with the family without compromising the outcome. Once decisions are made to proceed with repair, early cover of the myelomeningocele defect is necessary to prevent progressive loss of neural tissue through exposure, desiccation, and sepsis. Many techniques of repair have been advocated. In principle, the ideal should be applicable to all sizes of defect, should be able to be executed in the neonatal age group with minimal morbidity, and should provide long-term, stable soft tissue cover without significant secondary scarring. A technique adhering to these principles is described and supported by results in a personal series of 84 patients during a 12-year period. PMID:8297082

  7. Pectoralis Major Tendon Repair

    PubMed Central

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

    2016-01-01

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

  8. 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.

  9. 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

  10. Potentials of endogenous neural stem cells in cortical repair

    PubMed Central

    Saha, Bhaskar; Jaber, Mohamed; Gaillard, Afsaneh

    2012-01-01

    In the last few decades great thrust has been put in the area of regenerative neurobiology research to combat brain injuries and neurodegenerative diseases. The recent discovery of neurogenic niches in the adult brain has led researchers to study how to mobilize these cells to orchestrate an endogenous repair mechanism. The brain can minimize injury-induced damage by means of an immediate glial response and by initiating repair mechanisms that involve the generation and mobilization of new neurons to the site of injury where they can integrate into the existing circuit. This review highlights the current status of research in this field. Here, we discuss the changes that take place in the neurogenic milieu following injury. We will focus, in particular, on the cellular and molecular controls that lead to increased proliferation in the Sub ventricular Zone (SVZ) as well as neurogenesis. We will also concentrate on how these cellular and molecular mechanisms influence the migration of new cells to the affected area and their differentiation into neuronal/glial lineage that initiate the repair mechanism. Next, we will discuss some of the different factors that limit/retard the repair process and highlight future lines of research that can help to overcome these limitations. A clear understanding of the underlying molecular mechanisms and physiological changes following brain damage and the subsequent endogenous repair should help us develop better strategies to repair damaged brains. PMID:22509153

  11. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

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

  12. 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.

  13. Optimal Distinctiveness Signals Membership Trust.

    PubMed

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

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

  14. Laparoscopic paracolostomy hernia mesh repair.

    PubMed

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

    2007-12-01

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

  15. 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…

  16. Cobbler's Technique for Iridodialysis Repair

    PubMed Central

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

    2016-01-01

    We describe a novel “Cobbler's technique” for iridodialysis repair in the right eye of a patient aged 18 years, with a traumatic iridodialysis secondary to open globe injury with an iron rod. Our technique is simple with easy surgical maneuvers, that is, effective for repairing iridodialysis. The “Cobbler's technique” allows a maximally functional and cosmetic result for iridodialysis. PMID:26957855

  17. 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.

  18. 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…

  19. Membrane Repair: Mechanisms and Pathophysiology.

    PubMed

    Cooper, Sandra T; McNeil, Paul L

    2015-10-01

    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

  20. 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. PMID:25596348

  1. Engineering skeletal muscle repair.

    PubMed

    Juhas, Mark; Bursac, Nenad

    2013-10-01

    Healthy skeletal muscle has a remarkable capacity for regeneration. Even at a mature age, muscle tissue can undergo a robust rebuilding process that involves the formation of new muscle cells and extracellular matrix and the re-establishment of vascular and neural networks. Understanding and reverse-engineering components of this process is essential for our ability to restore loss of muscle mass and function in cases where the natural ability of muscle for self-repair is exhausted or impaired. In this article, we will describe current approaches to restore the function of diseased or injured muscle through combined use of myogenic stem cells, biomaterials, and functional tissue-engineered muscle. Furthermore, we will discuss possibilities for expanding the future use of human cell sources toward the development of cell-based clinical therapies and in vitro models of human muscle disease. PMID:23711735

  2. 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.

  3. Wound repair in Pocillopora.

    PubMed

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

    2016-09-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals. PMID:27397755

  4. 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.

  5. Future perspectives in nerve repair and regeneration.

    PubMed

    Tos, Pierluigi; Ronchi, Giulia; Geuna, Stefano; Battiston, Bruno

    2013-01-01

    After peripheral nerve injuries, the process of nerve regeneration and target reinnervation is very complex and depends on many different events occurring not only at the lesion site but also proximally and distally to it. In spite of the recent scientific and technological advancements, the need to find out new strategies to improve clinical nerve repair and regeneration remains. To reach this goal, the therapeutic strategy should thus exert its effects at different levels in order to simultaneously potentiate axonal regeneration, increase neuronal survival, modulate central reorganization, and inhibit or reduce target organ atrophy. It is expected that this multilevel approach might lead to significant improvement in the functional outcome and thus the quality of life of the patients suffering from peripheral nerve injury. PMID:24093612

  6. Defect repair performance using the nanomachining repair technique

    NASA Astrophysics Data System (ADS)

    Morikawa, Yasutaka; Kokubo, Haruo; Nishiguchi, Masaharu; Hayashi, Naoya; White, Roy; Bozak, Ron; Terrill, Lee

    2003-08-01

    Nanomachining is a new technique for repairing photomask defects. The advantages of this technique are no substrate damage, precise edge placement position and Z height accuracy when compared with current Laser zapper or FIB GAE repair techniques. This technique can be applied to any type of opaque defects at any type of film materials and quartz bump defects on Alternating Aperture Phase Sifting Masks (AAPSM). Furthermore, these characteristics enable complex pattern repairs of most advanced photomasks for 193nm lithography and enables iterative repair to achieve improved printing performance when analyzed with an AIMS 193nm tool. Dai Nippon Printing Co., Ltd. (DNP) has been producing AAPSMs in mass production for quite some time. The standard type of AAPSMs manufactured has been etched quartz, single trench with an undercut structure. On this structure, there is a potential for quartz defects underneath the chrome overhang based on the combination of dry and wet etching to create the undercut. For this study, we fabricated this kind of designed quartz defects and repaired them using the nanomachining system. These types of defects are particularly difficult to repair perfectly because they exist underneath the chrome overhang. We will show some options to achieve better printing results through the repair of these kinds of defects. In this report, we confirmed basic performance of this technique such as edge placement accuracy, Z height accuracy and AIMS printability. Additionally, we also tried to repair some complex defects such as quartz defects of AAPSM, quartz defects of CPL mask and oversized Serifs for application options. We will show these nanomachining repairs with evaluation results of printing performance simulated by the AIMS 193nm tool.

  7. Microvascular Repair: Post-Angiogenesis Vascular Dynamics

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Inta, Dragos; Gass, Peter

    2015-07-01

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

  9. CD22ΔE12 as a molecular target for corrective repair using a RNA trans-splicing strategy: Anti-leukemic activity of a rationally designed RNA trans-splicing molecule

    PubMed Central

    Uckun, Fatih M.; Qazi, Sanjive; Ma, Hong; Reaman, Gregory H.; Mitchell, Lloyd G.

    2015-01-01

    Our recent studies have demonstrated that the CD22 exon 12 deletion (CD22ΔE12) is a characteristic genetic defect of therapy-refractory clones in pediatric B-precursor acute lymphoblastic leukemia (BPL) and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory pediatric BPL. The purpose of the present study was to further evaluate the biologic significance of the CD22ΔE12 molecular lesion and determine if it could serve as a molecular target for corrective repair using RNA trans-splicing therapy. We show that both pediatric and adult B-lineage lymphoid malignancies are characterized by a very high incidence of the CD22ΔE12 genetic defect. We provide experimental evidence that the correction of the CD22ΔE12 genetic defect in human CD22ΔE12+ BPL cells using a rationally designed CD22 RNA trans-splicing molecule (RTM) caused a pronounced reduction of their clonogenicity. The RTM-mediated correction replaced the downstream mutation-rich segment of Intron 12 and remaining segments of the mutant CD22 pre-mRNA with wildtype CD22 Exons 10-14, thereby preventing the generation of the cis-spliced aberrant CD22ΔE12 product. The anti-leukemic activity of this RTM against BPL xenograft clones derived from CD22ΔE12+ leukemia patients provides the preclinical proof-of-concept that correcting the CD22ΔE12 defect with rationally designed CD22 RTMs may provide the foundation for therapeutic innovations that are needed for successful treatment of high-risk and relapsed BPL patients. PMID:25567759

  10. Endoscopic Endonasal Repair of Spontaneous and Traumatic Cerebrospinal Fluid Rhinorrhea: A Review and Local Experience.

    PubMed

    Gonen, Lior; Monteiro, Eric; Klironomos, George; Alghonaim, Yazeed; Vescan, Allan; Zadeh, Gelareh; Gentili, Fred

    2015-07-01

    This article presents an overview of endoscopic endonasal repair of cerebrospinal fluid (CSF) rhinorrhea. In recent years, endoscopic repair has become the standard of care for managing this condition, because it gradually replaces the traditional open transcranial approach. Discussion includes the etiologic classification of CSF rhinorrhea, management paradigm for each category, diagnosis algorithm, comprehensive description of the surgical technique, and an updated review of the literature regarding the safety and efficacy of this procedure. In addition, the authors present their experience, including 2 surgical videos demonstrating endoscopic repair of CSF rhinorrhea in 2 distinct clinical scenarios. PMID:26141354

  11. The differences between ICL repair during and outside of S phase.

    PubMed

    Williams, Hannah L; Gottesman, Max E; Gautier, Jean

    2013-08-01

    DNA interstrand crosslinks (ICLs) are complex lesions that block essential DNA transactions including DNA replication, recombination, and RNA transcription. Naturally occurring ICLs are rare, yet these lesions are the major cause of toxicity following treatment with several classes of crosslinking cancer chemotherapeutic drugs. ICLs are repaired during and outside of S phase by pathways with overlapping as well as distinct features. Here, we discuss some recent insights into the mechanisms of replication-dependent and replication-independent repair of ICLs with special emphasis on the differences between these repair pathways. PMID:23830640

  12. 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 . PMID:26884039

  13. rAAV-mediated overexpression of sox9, TGF-β and IGF-I in minipig bone marrow aspirates to enhance the chondrogenic processes for cartilage repair.

    PubMed

    Frisch, J; Rey-Rico, A; Venkatesan, J K; Schmitt, G; Madry, H; Cucchiarini, M

    2016-03-01

    Administration of therapeutic gene sequences coding for chondrogenic and chondroreparative factors in bone marrow aspirates using the clinically adapted recombinant adeno-associated virus (rAAV) vector may provide convenient, single-step approaches to improve cartilage repair. Here, we tested the ability of distinct rAAV constructs coding for the potent SOX9, transforming growth factor beta (TGF-β) and insulin-like growth factor I (IGF-I) candidate factors to modify marrow aspirates from minipigs to offer a preclinical large animal model system adapted for a translational evaluation of cartilage repair upon transplantation in sites of injury. Our results demonstrate that high, prolonged rAAV gene transfer efficiencies were achieved in the aspirates (up to 100% for at least 21 days) allowing to produce elevated amounts of the transcription factor SOX9 that led to increased levels of matrix synthesis and chondrogenic differentiation and of the growth factors TGF-β and IGF-I that both increased cell proliferation, matrix synthesis and chondrogenic differentiation (although to a lower level than SOX9) compared with control (lacZ) condition. Remarkably, application of the candidate SOX9 vector also led to reduced levels of hypertrophic differentiation in the aspirates, possibly by modulating the β-catenin, Indian hedgehog and PTHrP pathways. The present findings show the benefits of modifying minipig marrow concentrates via rAAV gene transfer as a future means to develop practical strategies to promote cartilage repair in a large animal model. PMID:26583804

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

    PubMed Central

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

    2009-01-01

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

  15. Organ repair and regeneration: an overview.

    PubMed

    Baddour, Joëlle A; Sousounis, Konstantinos; Tsonis, Panagiotis A

    2012-03-01

    A number of organs have the intrinsic ability to regenerate, a distinctive feature that varies among organisms. Organ regeneration is a process not fully yet understood. However, when its underlying mechanisms are unraveled, it holds tremendous therapeutic potential for humans. In this review, we chose to summarize the repair and regenerative potential of the following organs and organ systems: thymus, adrenal gland, thyroid gland, intestine, lungs, heart, liver, blood vessels, germ cells, nervous system, eye tissues, hair cells, kidney and bladder, skin, hair follicles, pancreas, bone, and cartilage. For each organ, a review of the following is presented: (a) factors, pathways, and cells that are involved in the organ's intrinsic regenerative ability, (b) contribution of exogenous cells - such as progenitor cells, embryonic stem cells, induced pluripotent stem cells, and bone marrow-, adipose- and umbilical cord blood-derived stem cells - in repairing and regenerating organs in the absence of an innate intrinsic regenerative capability, (c) and the progress made in engineering bio-artificial scaffolds, tissues, and organs. Organ regeneration is a promising therapy that can alleviate humans from diseases that have not been yet cured. It is also superior to already existing treatments that utilize exogenous sources to substitute for the organ's lost structure and/or function(s). PMID:22457174

  16. A spacecraft computer repairable via command.

    NASA Technical Reports Server (NTRS)

    Fimmel, R. O.; Baker, T. E.

    1971-01-01

    The MULTIPAC is a central data system developed for deep-space probes with the distinctive feature that it may be repaired during flight via command and telemetry links by reprogramming around the failed unit. The computer organization uses pools of identical modules which the program organizes into one or more computers called processors. The interaction of these modules is dynamically controlled by the program rather than hardware. In the event of a failure, new programs are entered which reorganize the central data system with a somewhat reduced total processing capability aboard the spacecraft. Emphasis is placed on the evolution of the system architecture and the final overall system design rather than the specific logic design.

  17. Retinoschisis transposition following a retinal detachment repair

    PubMed Central

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

    2015-01-01

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

  18. DNA repair in Mycoplasma gallisepticum

    PubMed Central

    2013-01-01

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

  19. Scalp repair using tissue expanders.

    PubMed

    Mangubat, E Antonio

    2013-08-01

    Repair of scalp defects is often challenging, because without careful planning, excision of the defect may leave unsatisfactory cosmesis. Contemporary techniques in hair restoration surgery allow creation of natural and undetectable results, but these techniques are often unsuitable for repairing large scarred areas of hair loss. However, by using older techniques of scalp reduction and tissue expansion, excision of many large scarring defects can be accomplished. Combining older methods with modern hair restoration surgery permits the satisfactory treatment of many previously untreatable conditions. This article focuses on tissue expansion as an adjunct to repairing large scalp defects. PMID:24017990

  20. 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.

  1. Exercise as Gene Therapy: BDNF and DNA Damage Repair.

    PubMed

    Schmidt, Robin H; Nickerson, John M; Boatright, Jeffrey H

    2016-01-01

    DNA damage is a common feature of neurodegenerative illnesses, and the ability to repair DNA strand breaks and lesions is crucial for neuronal survival, reported by Jeppesen et al (Prog Neurobiol. 2011;94:166-200) and Shiwaku et al (Curr Mol Med. 2015;15:119-128). Interventions aimed at repairing these lesions, therefore, could be useful for preventing or delaying the progression of disease. One potential strategy for promoting DNA damage repair (DDR) is exercise. Although the role of exercise in DDR is not understood, there is increasing evidence that simple physical activity may impact clinical outcomes for neurodegeneration. Here, we discuss what is currently known about the molecular mechanisms of brain-derived neurotrophic factor and how these mechanisms might influence the DDR process. PMID:27488073

  2. Video-atlas of open thoracoabdominal aortic aneurysm repair

    PubMed Central

    Melissano, Germano; Civilini, Efrem; Bertoglio, Luca; Rinaldi, Enrico; Marone, Enrico Maria; Tshomba, Yamume

    2012-01-01

    Open surgical repair of thoracoabdominal aortic aneurysms has evolved significantly over the last decades thanks to technical improvements, especially in the area of organ protection. However, despite adjunctive strategies, morbidity and mortality rates are still not negligible. Repair of the thoracoabdominal aorta represents a formidable challenge for surgeons, anesthesiologists and patients alike. While operative repair is generally carried out in specialized institutions, knowledge of the state-of-the-art diagnostic, anesthesiologic, surgical and endovascular aspects will certainly be of great value to all physicians involved in the care of these patients at any level. This “How to” video will explain all of these diagnostic, anesthesiologic and surgical aspects in our daily practice. PMID:23977526

  3. A new approach to elucidating repair reactions of resveratrol.

    PubMed

    Kerzig, Christoph; Henkel, Selgar; Goez, Martin

    2015-06-01

    The repair by co-antioxidants of the phenoxy radical of resveratrol, the famous health-preserving ingredient of red wine, is a key step of radical scavenging cascades in nature. To generate that radical, we employed 355 nm photoionization as a direct and selective access that reduces the chemical complexity and is equally applicable in organized phases; to monitor it, we used its hitherto unreported absorption in the red where no other species in our systems interfere. With this novel approach, we measured rate constants and H/D kinetic isotope effects for the repairs by ascorbate, trolox (a vitamin E analogue) and 4-aminophenol, and identified the mechanisms as one-step hydrogen abstractions. Cysteine and glutathione are unreactive. In micellar solution (SDS), the repair by ascorbate is much slower and involves only the hydrophilic phenoxy moieties protruding from the micelles. The new experimental strategy also led to a reevaluation of extinction coefficients, rate constants and mechanisms. PMID:25948021

  4. Distinct evolutionary strategies in the GGPPS family from plants

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints

    PubMed Central

    Rolauffs, Bernd; Williams, James M.; Grodzinsky, Alan J.; Kuettner, Klaus E.; Cole, Ada A.

    2008-01-01

    A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view. The resulting horizontal chondrocyte arrangements were tested for randomness, homogeneity or a significant grouping via point pattern analysis and were correlated with the joint type in which they occurred. The present study demonstrated that human superficial chondrocytes occurred in four distinct patterns of strings, clusters, pairs or single chondrocytes. Those patterns represented a significant grouping (p<0.0001) with horizontal alignment. Each articular joint surface was dominated by only one of these four patterns (p<0.001). Specific patterns correlated with specific diarthrodial joint types (p<0.001). Further studies need to establish whether these organizational patterns are a consequence of their surrounding environment or whether they are linked to a functional purpose. PMID:18325787

  7. Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints.

    PubMed

    Rolauffs, Bernd; Williams, James M; Grodzinsky, Alan J; Kuettner, Klaus E; Cole, Ada A

    2008-05-01

    A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view. The resulting horizontal chondrocyte arrangements were tested for randomness, homogeneity or a significant grouping via point pattern analysis and were correlated with the joint type in which they occurred. The present study demonstrated that human superficial chondrocytes occurred in four distinct patterns of strings, clusters, pairs or single chondrocytes. Those patterns represented a significant grouping (p < 0.0001) with horizontal alignment. Each articular joint surface was dominated by only one of these four patterns (p < 0.001). Specific patterns correlated with specific diarthrodial joint types (p < 0.001). Further studies need to establish whether these organizational patterns are a consequence of their surrounding environment or whether they are linked to a functional purpose. PMID:18325787

  8. On structural health monitoring of aircraft adhesively bonded repairs

    NASA Astrophysics Data System (ADS)

    Pavlopoulou, Sofia

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

  9. Repair of webbed fingers - slideshow

    MedlinePlus

    ... gov/ency/presentations/100096.htm Repair of webbed fingers - series—Normal anatomy To use the sharing features ... Health Solutions, Ebix, Inc. Related MedlinePlus Health Topics Finger Injuries and Disorders A.D.A.M., Inc. ...

  10. Cleft lip and palate repair

    MedlinePlus

    Orofacial cleft; Craniofacial birth defect repair; Cheiloplasty; Cleft rhinoplasty; Palatoplasty; Tip rhinoplasty ... A cleft lip is a birth defect: A cleft lip may be just a small notch in the lip. It may also be a complete split in the ...

  11. Rotator cuff repair - series (image)

    MedlinePlus

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

  12. Nucleotide excision repair in humans.

    PubMed

    Spivak, Graciela

    2015-12-01

    The demonstration of DNA damage excision and repair replication by Setlow, Howard-Flanders, Hanawalt and their colleagues in the early 1960s, constituted the discovery of the ubiquitous pathway of nucleotide excision repair (NER). The serial steps in NER are similar in organisms from unicellular bacteria to complex mammals and plants, and involve recognition of lesions, adducts or structures that disrupt the DNA double helix, removal of a short oligonucleotide containing the offending lesion, synthesis of a repair patch copying the opposite undamaged strand, and ligation, to restore the DNA to its original form. The transcription-coupled repair (TCR) subpathway of NER, discovered nearly two decades later, is dedicated to the removal of lesions from the template DNA strands of actively transcribed genes. In this review I will outline the essential factors and complexes involved in NER in humans, and will comment on additional factors and metabolic processes that affect the efficiency of this important process. PMID:26388429

  13. 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)

  14. Anterior Repair with Processed Dermis

    MedlinePlus Videos and Cool Tools

    Anterior Repair with Axis® Tutoplast® Processed Dermis and Digitex® - Performed by Dr. Manish Patel Click Here to view the BroadcastMed, Inc. Privacy Policy and Legal Notice © 2016 BroadcastMed, Inc. ...

  15. 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.

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

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

    PubMed

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

    2016-08-18

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

  2. Coracoclavicular ligament reconstruction: biomechanical comparison of tendon graft repairs to a synthetic double bundle augmentation.

    PubMed

    Wellmann, Mathias; Kempka, Jan P; Schanz, Steffen; Zantop, Thore; Waizy, Hazibullah; Raschke, Michael J; Petersen, Wolf

    2009-05-01

    For currently presented anatomical coracoclavicular ligament repairs issues such as autologous tendon graft versus synthetic suture augmentation and the optimum fixation strategies for both types of reconstruction are not solved. The purpose of the study was to compare the biomechanical properties of different tendon graft repairs to the characteristics of a synthetic polyester augmentation. Four anatomical coracoclavicular ligament repairs were biomechanically tested: 5 mm coracoclavicular tendon loop with suture fixation, tendon loop with flip button fixation, tendon loop with interference screw fixation versus a double 1.0-mm polyester repair with flip button fixation. The biomechanical testing included cyclic superio-inferior loading and a subsequent load to failure protocol. The ultimate failure loads were significantly higher for the double polyester/flip button repair (927 N) compared to all tendon repair techniques (maximum 640 N). In contrast the stiffness level was higher for the tendon repairs compared to the polyester/flip button repair (68.7 N/mm) but strongly dependent on the fixation technique (interference screw 97.2 N/mm, flip button 84.9 N/mm, side to side suture 60.9 N/mm). A synthetic coracoclavicular augmentation using a polyester suture provides adequate structural properties compared to a tendon repair. Therefore the decision for a tendon graft should be made by the necessity of a biologic substrate rather than by the assumption of a biomechanical advantage. PMID:19225755

  3. Repair and Regenerative Therapies of the Annulus Fibrosus of the Intervertebral Disc.

    PubMed

    Li, Xiaolong; Dou, Qingyu; Kong, Qingquan

    2016-02-01

    Degeneration of the intervertebral disc is implicated as the main cause of low back pain. Current treatment strategies for degenerative disc disease, such as conservative treatments and surgeries, only relieve the symptoms of low back pain without treating the causes of underlying degeneration. Surgical treatments cannot reverse the degeneration of the intervertebral disc degeneration, and may even accelerate the degeneration. The development of tissue engineering and regenerative therapeutic strategies have brought new hope for repair and regeneration of the degenerated intervertebral disc. These strategies have been developed mainly targeting to the repair and regeneration of the nucleus pulposus of the degenerated but intervertebral disc. Although many studies that focused on the nucleus pulposus repair have achieved successes in laboratory settings but disc repair without giving much regard to annulus fibrosus could not recover the normal mechanical environment, which might make the disc degenerative change continuously exacerbate. Lately, the strategy to simultaneously repair the damaged annulus fibrosus and nucleus pulposus has attracted more attention, which could be considered to slow the disc degenerative rate and obtain better repair effect. An extensive literature search up to March 2015 for annulus fibrosus repair and regeneration in vitro or in vivo studies and clinical trials with the key words of "annulus fibrosus, repair, regeneration, tissue engineering, intervertebral disc and scaffold" were performed through PubMed, China National Knowledge Infrastructure and China Biology Medicine. The goal of this paper was to review the current research progress of annulus fibrosus repair and regeneration, and also suggest directions for future research. PMID:26876403

  4. Mitral valve repair versus replacement

    PubMed Central

    Keshavamurthy, Suresh; Gillinov, A. Marc

    2015-01-01

    Degenerative, ischemic, rheumatic and infectious (endocarditis) processes are responsible for mitral valve disease in adults. Mitral valve repair has been widely regarded as the optimal surgical procedure to treat mitral valve dysfunction of all etiologies. The supporting evidence for repair over replacement is strongest in degenerative mitral regurgitation. The aim of the present review is to summarize the data in each category of mitral insufficiency and to provide recommendations based upon this data. PMID:26309824

  5. Initiation of DNA Interstrand Cross-link Repair in Mammalian Cells

    PubMed Central

    Hlavin, Erica M.; Smeaton, Michael B.; Miller, Paul S.

    2010-01-01

    Interstrand cross-links (ICLs) are among the most cytotoxic DNA lesions to cells because they prevent the two DNA strands from separating, thereby precluding replication and transcription. Even though chemotherapeutic cross-linking agents are well established in clinical use, and numerous repair proteins have been implicated in the initial events of mammalian ICL repair, the precise mechanistic details of these events remain to be elucidated. This review will summarize our current understanding of how ICL repair is initiated with an emphasis on the context (replicating, transcribed or quiescent DNA) in which the ICL is recognized, and how the chemical and physical properties of ICLs influence repair. Although most studies have focused on replication-dependent repair because of the relation to highly replicative tumor cells, replication-independent ICL repair is likely to be important in the circumvention of cross-link cytotoxicity in non-dividing, terminally differentiated cells that may be challenged with exogenous or endogenous sources of ICLs. Consequently, the ICL repair pathway that should be considered ‘dominant’ appears to depend on the cell type and the DNA context in which the ICL is encountered. The ability to define and inhibit distinct pathways of ICL repair in different cell cycle phases may help in developing methods that increase cytotoxicity to cancer cells while reducing side-effects in non-dividing normal cells. This may also lead to a better understanding of pathways that protect against malignancy and aging. PMID:20658650

  6. Brain capacity for repair of oxidatively damaged DNA and preservation of neuronal function.

    PubMed

    Englander, Ella W

    2008-01-01

    Accumulation of oxidative DNA damage in the human brain has been implicated in etiologies of post-traumatic and age-associated declines in neuronal function. In neurons, because of high metabolic rates and prolonged life span, exposure to free radicals is intense and risk for accumulation of damaged DNA is amplified. While data indicate that the brain is equipped to repair nuclear and mitochondrial DNA, it is unclear whether repair is executed by distinct subsets of the DNA-repair machinery. Likewise, there are no firm assessments of brain capacity for accurate DNA repair under normal and more so compromised conditions. Consequently, the scope of DNA repair in the brain and the impact of resolution of oxidative lesions on neuronal survival and function remain largely unknown. This review considers evidences for brain levels and activities of the base excision repair (BER) pathway in the context of newly available, comprehensive in situ hybridization analyses of genes encoding repair enzymes. These analyses suggest that not all subsets of BER are equally represented in the brain. Because BER is the major repair process for oxidatively damaged DNA, to what extent parsimonious BER may contribute to development of neuronal dysfunction and brain injury under compromised conditions, is discussed. PMID:18374390

  7. 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

  8. Large steam turbine repair: A survey

    SciTech Connect

    Findlan, S.J.; Lube, B. )

    1991-07-01

    This report covers a survey taken to document the current state-of-the-art in repairs to large steam turbines. One objective was to provide information to assist utilities in making repair or replacement decisions. The survey revealed that a large number of repairs have been successfully repaired involving both mechanical and welding repair techniques. Repair techniques have been improving in recent years and are being used more frequently. No guidelines or codes exist for the repair of steam turbine components so each repair is primarily controlled by agreement between the utility, contractor and insurer. Types of repairs are reviewed in this report and in addition, the capabilities of various contractors who are currently active in providing repair service. 40 refs., 10 figs., 4 tabs.

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. From pluripotency to distinct cardiomyocyte subtypes.

    PubMed

    David, Robert; Franz, Wolfgang-Michael

    2012-06-01

    Differentiated adult cardiomyocytes (CMs) lack significant regenerative potential, which is one reason why degenerative heart diseases are the leading cause of death in the western world. For future cardiac repair, stem cell-based therapeutic strategies may become alternatives to donor heart transplantation. The principle of reprogramming adult terminally differentiated cells (iPSC) had a major impact on stem cell biology. One can now generate autologous pluripotent cells that highly resemble embryonic stem cells (ESC) and that are ethically inoffensive as opposed to human ESC. Yet, due to genetic and epigenetic aberrations arising during the full reprogramming process, it is questionable whether iPSC will enter the clinic in the near future. Therefore, the recent achievement of directly reprogramming fibroblasts into cardiomyocytes via a milder approach, thereby avoiding an initial pluripotent state, may become of great importance. In addition, various clinical scenarios will depend on the availability of specific cardiac cellular subtypes, for which a first step was achieved via our own programming approach to achieve cardiovascular cell subtypes. In this review, we discuss recent progress in the cardiovascular stem cell field addressing the above mentioned aspects. PMID:22689787

  12. Human Embryonic Stem Cells and Cardiac Repair

    PubMed Central

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

    2008-01-01

    The muscle lost after a myocardial infarction is replaced with non-contractile 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. hESC-derived cardiomyocytes (hESC-CMs) 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 to 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-CMs and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges. PMID:18657407

  13. Myeloid Cells in Cutaneous Wound Repair.

    PubMed

    Cash, Jenna L; Martin, Paul

    2016-06-01

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

  14. Mesothelial cells in tissue repair and fibrosis

    PubMed Central

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

    2015-01-01

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

  15. Distinctive Characteristics of Educational Donors

    ERIC Educational Resources Information Center

    James, Russell N., III.

    2008-01-01

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

  16. 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…

  17. 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.

  18. 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…

  19. Integrated transducer for color distinction

    NASA Astrophysics Data System (ADS)

    Kato, Hisao; Kojima, Masahiko; Yoshida, Akira

    1983-06-01

    A method for fabricating the improved version of an integrated transducer for color distinction is proposed. It consists of three SnO2(n)-Si(n) photodiodes on a Si wafer and a trichromatic filter prepared by arranging filters of the three primary colors (Eastman Kodak gelatin filters; Nos. 47B, 58, and 25) on an infrared glass filter (Hoya Glass; B-460). Its photoelectric characteristics and dependence of error of color distinction on the dimension of the transducer are reported. The photodiodes employed in this conversion assembly are produced by the simple spray method and are most suitable for detecting the low illumination. Since this transducer adapts the trichromatic color resolution method, highly accurate color distinction is possible. With this type of transducer, three photodiodes sensitive to the primary colors, red, green, and blue, respectively, are arranged on a plane. An error in color distinction can occur due to the differences in the strength of the light incident upon the respective photodiodes. This problem is reduced by making the transducer more compact. Finally, 11 kinds of colors are discerned in this experiment as an application of the transducer.

  20. Distinctive Qualities of Expert Teachers

    ERIC Educational Resources Information Center

    Tsui, Amy B. M.

    2009-01-01

    This paper attempts to identify the distinctive qualities of successful veteran teachers, referred to as "expert teachers", which separates them not only from novice teachers but more importantly from experienced non-expert teachers. Based on earlier case studies, this paper maintains that the critical differences between expert and non-expert…

  1. 49 CFR 1242.42 - Administration, repair and maintenance, machinery repair, equipment damaged, dismantling retired...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  2. Luminescent Dual Sensors Reveal Extracellular pH-Gradients and Hypoxia on Chronic Wounds That Disrupt Epidermal Repair

    PubMed Central

    Schreml, Stephan; Meier, Robert J.; Kirschbaum, Michael; Kong, Su Chii; Gehmert, Sebastian; Felthaus, Oliver; Küchler, Sarah; Sharpe, Justin R.; Wöltje, Kerstin; Weiß, Katharina T.; Albert, Markus; Seidl, Uwe; Schröder, Josef; Morsczeck, Christian; Prantl, Lukas; Duschl, Claus; Pedersen, Stine F.; Gosau, Martin; Berneburg, Mark; Wolfbeis, Otto S.; Landthaler, Michael; Babilas, Philipp

    2014-01-01

    Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields. PMID:24883122

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Repair of the Ankle Syndesmosis

    PubMed Central

    Backus, Jonathan D.; Clanton, Thomas O.; Whitlow, Scott R.; Williams, Brady T.; Liechti, Daniel; Dornan, Grant J.; Saroki, Adriana; Turnbull, Travis Lee; LaPrade, Robert F.

    2016-01-01

    Objectives: Significant debate exists regarding the optimal repair techniques for unstable syndesmosis injuries. Techniques range from one to multiple screw fixation, suture-button fixation devices, or a combination of the two. The purpose of the current investigation was to biomechanically compare three common syndesmotic repair techniques using a simulated weight-bearing protocol with internal and external rotation of the foot. Methods: Twenty-four, lower leg specimens with mean age 54.25 years (range, 38 to 68 years) were utilized for testing. Following the creation of a complete syndesmotic injury (AITFL, ITFL, PITFL, interosseous membrane) specimens were repaired using one of three randomly assigned repair techniques: (1) one 3.5 mm syndesmotic screw, (2) one suture-button construct, and (3) two divergent suture-button constructs. For testing, specimens were oriented in neutral plantar/dorsiflexion and neutral internal/external rotation with the respect to the vertical tibia. Repairs were then cycled for 500 cycles between 7.5 Nm of internal/external rotation torque under a constant 750 N axial compressive load. At 0, 10, 100, and 500 cycles, torsional cyclic loading was interrupted to assess torsional stiffness and resistance to rotation within a physiologic range of motion. While axially loaded to 750 N, the foot was externally rotated to 15° and then rotated to 10° of internal rotation. Torsional cyclic loading was then resumed. Torque (Nm) and rotational position (degrees) were recorded continuously throughout testing. Three-dimensional data was also collected throughout testing to characterize the relative spatial relationships of the tibiofibular articulation. Results: Biomechanically, there were no significant differences between techniques when repairs were compared to the intact syndesmosis. Three-dimensional analysis revealed significant differences between all repair techniques for sagittal fibular translation with external rotation of the foot

  6. 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. PMID:21774901

  7. Essentials of skin laceration repair.

    PubMed

    Forsch, Randall T

    2008-10-15

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

  8. DNA repair in mammalian embryos.

    PubMed

    Jaroudi, Souraya; SenGupta, Sioban

    2007-01-01

    Mammalian cells have developed complex mechanisms to identify DNA damage and activate the required response to maintain genome integrity. Those mechanisms include DNA damage detection, DNA repair, cell cycle arrest and apoptosis which operate together to protect the conceptus from DNA damage originating either in parental gametes or in the embryo's somatic cells. DNA repair in the newly fertilized preimplantation embryo is believed to rely entirely on the oocyte's machinery (mRNAs and proteins deposited and stored prior to ovulation). DNA repair genes have been shown to be expressed in the early stages of mammalian development. The survival of the embryo necessitates that the oocyte be sufficiently equipped with maternal stored products and that embryonic gene expression commences at the correct time. A Medline based literature search was performed using the keywords 'DNA repair' and 'embryo development' or 'gametogenesis' (publication dates between 1995 and 2006). Mammalian studies which investigated gene expression were selected. Further articles were acquired from the citations in the articles obtained from the preliminary Medline search. This paper reviews mammalian DNA repair from gametogenesis to preimplantation embryos to late gestational stages. PMID:17141556

  9. Imaging of cartilage repair procedures

    PubMed Central

    Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

    2014-01-01

    The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts. PMID:25114387

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

    PubMed

    Ullery, Brant W; Lee, Jason T

    2014-09-01

    Endovascular aneurysm repair has taken over open surgery as the primary strategy for treatment of patients with abdominal and thoracic aneurysms. The minimally invasive nature of these techniques requires alterations in preoperative workup, intraoperative management, and familiarity with unique complications that can occur. Familiarity from the anesthetic standpoint of endovascular techniques, including treatment of patients with fenestrated, chimney, snorkel, and periscope grafts, is necessary for the contemporary cardiac anesthesiologist. PMID:25113729

  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. PMID:23954656

  12. Repairing Solar Max: The Solar Maximum Repair Mission

    NASA Technical Reports Server (NTRS)

    Mcmahan, T.; Neal, V.

    1984-01-01

    Technology and procedures designed for replacing a faulty attitude control module and scientific instruments on the only orbiting solar observatory are described. The rationale for the repair mission is given and the operations of the flight support system within the cargo bay of the space shuttle are discussed. The use of the manned maneuvering unit in capturing the satellite and of the remote manipulator arm in berthing it are discussed, as well as the space tools to be used for repair operations. The space crew and their responsibilities are identified.

  13. STUDY ON LIFECYCLE PERFORMANCE OF REPAIR PAINTING FOR DETERIORATED METALLIZED STEEL

    NASA Astrophysics Data System (ADS)

    Itoh, Yoshito; Hosoi, Akihiro; Kitane, Yasuo; Sugiura, Yuki; Kurita, Koji

    Recently, various metallic coating systems have been adopted for steel bridges. In order to examine the performance of repaired painting on steel plates with four types of deteriorated metallic coating systems, acid rain combined cyclic corrosion tests were performed. The four types of metallic coating systems were zinc hot dip galvanized coating, zinc-aluminum alloy coating, zinc-aluminum pseudoalloy coating and aluminum coating. The effect of remaining thickness of metallic coating on the performance of repair paint was discussed. Finally, the lifecycle cost analysis was performed for various repair strategies for the four types of metallic coating systems.

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

    PubMed Central

    Christensen, Alan C.

    2014-01-01

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

  15. Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    2015-01-01

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

  17. 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

  18. Nanoscale dimensional focused ion beam repair of quartz defects on 90-nm node alternating aperture phase shift masks

    NASA Astrophysics Data System (ADS)

    Robinson, Tod E.; Graupera, Anthony; Morrison, Troy B.; Ramstein, Marcus

    2004-08-01

    The effort to produce perfect dimension repairs of quartz bump defects on Alternating-Aperture Phase Shift Masks (AAPSM) has been brought to a new level with process developments to meet 90 nm technology node specifications. Decreasing photomask line and space dimensions pushes performance requirements for a mask repair system in terms of fine control in difficult to access structures on the mask surface. New repair strategies using a recently improved focused ion beam mask repair system for different defect types are discussed, along with their relative effectiveness. These strategies are then applied to the repair of full height extension and bridging defects in a line and space array. The role of quartz topography and its optical effects, Cr edge bias, and the combination of both strategies in a quartz bump repair are discussed. Additionally, effective process controls in repair are also discussed, along with analysis of metrology data received from a stylus nano-profilometer (SNP) system, and their relationship to potential imaging on the wafer by examination of AIMS data at a high numerical aperture. Several possible mask repair process flows are also reviewed in light of this work.

  19. Nucleotide excision repair proteins and interstrand crosslink repair

    PubMed Central

    Wood, Richard D.

    2010-01-01

    Although various schemes for interstrand crosslink (ICL) repair incorporate recombination, replication, and double-strand break intermediate steps, action of the NER system or some variation of it is a common feature of most models. In the bacterium Escherichia coli, the NER enzyme UvrABC can incise on either side of an ICL to unhook the crosslink, and repair can proceed via a subsequent recombination step. The relevance of NER to ICL repair in mammalian cells has been challenged. Of all NER mutants, it is clear that ERCC1 and XPF-defective cells show the most pronounced sensitivities to ICL-inducing agents, and defects in ICL repair. However, there is good evidence that cells defective in NER proteins including XPA and XPG are also more sensitive than normal to ICL-inducing agents. These results are summarized here, together with evidence for defective crosslink removal in NER-defective cells. Studies of incision at sites of ICL by cell extracts and purified proteins have been done, but these studies are not all consistent with one another and further research is required. PMID:20658645

  20. 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)…

  1. 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.

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

    PubMed

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

    2016-07-15

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

  3. Fanconi Anemia Proteins, DNA Interstrand Crosslink Repair Pathways, and Cancer Therapy

    PubMed Central

    Andreassen, Paul R.; Ren, Keqin

    2016-01-01

    DNA interstrand crosslinkers, a chemically diverse group of compounds which also induce alkylation of bases and DNA intrastrand crosslinks, are extensively utilized for cancer therapy. Understanding the cellular response to DNA damage induced by these agents is critical for more effective utilization of these compounds and for the identification of novel therapeutic targets. Importantly, the repair of DNA interstrand crosslinks (ICLs) involves many distinct DNA repair pathways, including nucleotide excision repair, translesion synthesis (TLS), and homologous recombination (HR). Additionally, proteins implicated in the pathophysiology of the multigenic disease Fanconi anemia (FA) have a role in the repair of ICLs that is not well understood. Cells from FA patients are hypersensitive to agents that induce ICLs, therefore FA proteins are potentially novel therapeutic targets. Here we will review current research directed at identifying FA genes and understanding the function of FA proteins in DNA damage responses. We will also examine interactions of FA proteins with other repair proteins and pathways, including signaling networks, which are potentially involved in ICL repair. Potential approaches to the modulation of FA protein function to enhance therapeutic outcome will be discussed. Also, mutation of many genes that encode proteins involved in ICL repair, including FA genes, increases susceptibility to cancer. A better understanding of these pathways is therefore critical for the design of individualized therapies tailored to the genetic profile of a particular malignancy. For this purpose, we will also review evidence for the association of mutation of FA genes with cancer in non-FA patients. PMID:19200054

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

    PubMed Central

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

    1996-01-01

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

  5. Abdominal aortic aneurysm repair - open - discharge

    MedlinePlus

    AAA - open - discharge; Repair - aortic aneurysm - open - discharge ... You had open aortic aneurysm surgery to repair an aneurysm (a widened part) in your aorta, the large artery that carries blood to your ...

  6. 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.

  7. Small Engine Repair Course Outline.

    ERIC Educational Resources Information Center

    DeClouet, Fred

    Small engines as referred to here are engines used on lawn mowers, chain saws, power plants, outboards, and cycles. It does not include engines used on automobiles. The course outlined is intended to show how small two-cycle and four-cycle gas engines are constructed, how they operate, what goes wrong, and how to service and repair them. It is…

  8. URIC ACID AND TISSUE REPAIR

    PubMed Central

    NERY, Rodrigo Araldi; KAHLOW, Barbara Stadler; SKARE, Thelma L; TABUSHI, Fernando Issamu; CASTRO, Adham do Amaral e

    2015-01-01

    Uric acid, a metabolic product of purines, may exert a role in tissue healing. In this review we will explore its role as an alarm initiating the inflammatory process that is necessary for tissue repair, as a scavenger of oxygen free radicals, as a mobilizer of progenitor endothelial cells and as supporter of adaptive immune system. PMID:26734804

  9. 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…

  10. 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.

  11. Laparoscopic repair of paraesophageal hernia.

    PubMed Central

    Willekes, C L; Edoga, J K; Frezza, E E

    1997-01-01

    OBJECTIVE: The purpose of this report is to describe the authors' technique for the laparoscopic repair of paraesophageal hernias and the outcome in their series of patients. METHODS: Thirty patients underwent elective laparoscopic repair of paraesophageal hernias. All were pure type II paraesophageal hernias as defined by upper gastrointestinal contrast studies. All operations were performed by a single surgeon (JKE) assisted by five different chief surgical residents. The authors have used various prototypes of a laparoscopic utility belt to reduce the physician requirement to the surgeon and a first assistant. The operative setup and specific techniques of the repair are described and illustrated. A concomitant anti-reflux procedure was performed in the last 23 patients. RESULTS: Satisfactory repair using video-laparoscopic techniques was achieved in all cases. There were no deaths. Complications occurred in 8 of 30 patients. Postoperative gastroesophageal reflux developed in three of the first seven patients in whom fundoplication was not performed. Three consecutive patients had left lower lobe atelectasis believed to be related to endotracheal tube displacement during the passage of the bougie. One patient had postoperative dysphagia. There was one case of major deep venous thrombosis with pulmonary embolism. Twenty-eight of 30 patients were discharged home by postoperative day 3. Twenty-four of 30 patients had returned to normal activity by the time of their first postoperative office visit 1 week after surgery. Images Figure 9. Figure 10. PMID:8998118

  12. 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…

  13. 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…

  14. [A Nobel Prize for DNA repair].

    PubMed

    Jordan, Bertrand

    2016-01-01

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

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

    SciTech Connect

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

    1995-12-01

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

  16. DNA repair mechanisms and their clinical impact in glioblastoma.

    PubMed

    Erasimus, Hélène; Gobin, Matthieu; Niclou, Simone; Van Dyck, Eric

    2016-01-01

    Despite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide, glioblastoma remains one of the most lethal cancers, due in great part to the action of DNA repair mechanisms that drive resistance and tumor relapse. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. In this review, we introduce the various cellular systems and animal models that are used in studies of DNA repair in glioblastoma. We summarize recent progress in our knowledge of the pathways and factors involved in the removal of DNA lesions induced by ionizing radiation and temozolomide. We introduce the therapeutic strategies relying on DNA repair inhibitors that are currently being tested in vitro or in clinical trials, and present the challenges raised by drug delivery across the blood brain barrier as well as new opportunities in this field. Finally, we review the genetic and epigenetic alterations that help shape the DNA repair makeup of glioblastoma cells, and discuss their potential therapeutic impact and implications for personalized therapy. PMID:27543314

  17. 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…

  18. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired...) Repair requires replacing the existing seal design with a new system that the owner or operator has... repaired within 15 calendar days after discovery of the leak as specified in paragraphs (f)(4)(i) and...

  19. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  20. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  1. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  2. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  3. 33 CFR 115.40 - Bridge repairs.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  4. Bringing mask repair to the next level

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  5. 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.

  6. 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…

  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. Cartilage repair: 2013 Asian update.

    PubMed

    Hui, James H P; Goyal, Deepak; Nakamura, Norimasa; Ochi, Mitsuo

    2013-12-01

    Despite financial and regulatory hurdles, Asian scientists and clinicians have made important contributions in the area of cartilage repair. Because it is impossible to include observations on all the published articles in one review, our attempt is to highlight Asian progress in this area during recent years (2005 to the present), reviewing research development and clinical studies. In the former, our discussion of in vitro studies focuses on (1) potential sources of stem cells--such as mesenchymal stem cells (MSCs) from marrow, cord blood, synovium, and mobilized peripheral blood--which are capable of enhancing cartilage repair and (2) the use of growth factors and scaffolds with and without cells. Our discussion of animal studies attempts to summarize activities in evaluating surgical procedures and determining the route of cell administration, as well as studies on matrices and scaffolds. It ranges from the use of small animals such as rats and rabbits to larger animals like pigs and dogs. The local adherent technique, enhancement of microfracture with poly(l-lactic-co-glycolic acid) scaffold, adenovirus-mediated bone morphogenic protein (BMP) genes, and MSCs--whether they are magnetically labeled, suspended in hyaluronic acid, or immobilized with transforming growth factor-β (TGF-β)--have all been able to engineer a repair of the osteochondral defect. Although published Asian reports of clinical studies on cartilage repair are few, the findings of relevant trials are summarized in our discussion of these investigations. There has been a long history of use of laboratory-derived MSCs for cartilage repair. Recent progress has suggested the potential utility of cord blood and mobilized peripheral blood in this area, as well as more injectable bone marrow (BM)-derived stem cells. Finally, we make a few suggestions on the direction of research and development activities and the need for collaborative approaches by regulatory agencies. PMID:24286798

  9. Laparoscopic Repair of Ventral Hernias

    PubMed Central

    Heniford, B Todd; Park, Adrian; Ramshaw, Bruce J.; Voeller, Guy

    2003-01-01

    Objective: To evaluate the efficacy and safety of laparoscopic repair of ventral hernias. Summary Background Data: The recurrence rate after standard repair of ventral hernias may be as high as 12-52%, and the wide surgical dissection required often results in wound complications. Use of a laparoscopic approach may decrease rates of complications and recurrence after ventral hernia repair. Methods: Data on all patients who underwent laparoscopic ventral hernia repair (LVHR) performed by 4 surgeons using a standardized procedure between November 1993 and October 2002 were collected prospectively (85% of patients) or retrospectively. Results: LVHR was completed in 819 of the 850 patients (422 men; 428 women) in whom it was attempted. Thirty-four percent of completed LVHRs were for recurrent hernias. The patient mean body mass index was 32; the mean defect size was 118 cm2. Mesh, averaging 344 cm2, was used in all cases. Mean operating time was 120 min, mean estimated blood loss was 49 mL, and hospital stay averaged 2.3 days. There were 128 complications in 112 patients (13.2%). One patient died of a myocardial infarction. The most common complications were ileus (3%) and prolonged seroma (2.6%). During a mean follow-up time of 20.2 months (range, 1-94 months), the hernia recurrence rate was 4.7%. Recurrence was associated with large defects, obesity, previous open repairs, and perioperative complications. Conclusion: In this large series, LVHR had a low rate of conversion to open surgery, a short hospital stay, a moderate complication rate, and a low risk of recurrence. PMID:14501505

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

    PubMed Central

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

    2015-01-01

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

  11. 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. PMID:26168294

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

    PubMed

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

    2015-07-10

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

  13. Chronic type B aortic dissection: indications and strategies for treatment.

    PubMed

    Rohlffs, F; Tsilimparis, N; Diener, H; Larena-Avellaneda, A; Von Kodolitsch, Y; Wipper, S; Debus, E S; Kölbel, T

    2015-04-01

    Chronic type B aortic dissection is a distinctive condition that needs individual treatment strategies and different considerations than in therapy of acute or subacute type B aortic dissection. The most common indication for treatment of this complex disease is aneurysmal dilatation of the dissected aortic segment. While open repair of the enlarged dissected aorta remains the best option for good-risk patients and patients with connective tissue disorders in high-volume centers with respective expertise, endovascular management of chronic type B aortic dissection with postdissection aneurysms has significantly gained ground in the past years. But the concept of TEVAR with implantation of a tubular stent-graft into the thoracic aorta to seal the proximal entry tear and reroute the blood flow into the true lumen alone, is not associated with satisfactory results. This is mainly due to the sparse remodeling capacity of the aortic tissue compared to earlier stages of the disease as the aortic wall and the dissection membrane are thickened and more rigid. On the other hand, it is restricted by the most limiting factor for endovascular success in chronic type B aortic dissection: persistent false lumen perfusion. This problem also affects patients with residual dissection after surgical repair of a DeBakey type I aortic dissection or dissection after ascending aortic repair for other pathologies. Hence, it is evident that strategies to achieve endovascular false lumen occlusion are of increasing importance and novel techniques have been introduced to solve the problem of persisting false lumen flow. Thus, the evolution of a large variety of techniques to address the false lumen perfusion issue indicates that complicated chronic type B dissection involves a high diversity in clinical presentation and morphology. A large armamentarium of catheter skills as well as critical individualized treatment strategies are required to address the heterogenous morphological disease

  14. Nucleolin mediates nucleosome disruption critical for DNA double-strand break repair.

    PubMed

    Goldstein, Michael; Derheimer, Frederick A; Tait-Mulder, Jacqueline; Kastan, Michael B

    2013-10-15

    Recruitment of DNA repair factors and modulation of chromatin structure at sites of DNA double-strand breaks (DSBs) is a complex and highly orchestrated process. We developed a system that can induce DSBs rapidly at defined endogenous sites in mammalian genomes and enables direct assessment of repair and monitoring of protein recruitment, egress, and modification at DSBs. The tight regulation of the system also permits assessments of relative kinetics and dependencies of events associated with cellular responses to DNA breakage. Distinct advantages of this system over focus formation/disappearance assays for assessing DSB repair are demonstrated. Using ChIP, we found that nucleosomes are partially disassembled around DSBs during nonhomologous end-joining repair in G1-arrested mammalian cells, characterized by a transient loss of the H2A/H2B histone dimer. Nucleolin, a protein with histone chaperone activity, interacts with RAD50 via its arginine-glycine rich domain and is recruited to DSBs rapidly in an MRE11-NBS1-RAD50 complex-dependent manner. Down-regulation of nucleolin abrogates the nucleosome disruption, the recruitment of repair factors, and the repair of the DSB, demonstrating the functional importance of nucleosome disruption in DSB repair and identifying a chromatin-remodeling protein required for the process. Interestingly, the nucleosome disruption that occurs during DSB repair in cycling cells differs in that both H2A/H2B and H3/H4 histone dimers are removed. This complete nucleosome disruption is also dependent on nucleolin and is required for recruitment of replication protein A to DSBs, a marker of DSB processing that is a requisite for homologous recombination repair. PMID:24082117

  15. Endovascular Repair of Thoracic Aortic Aneurysms

    PubMed Central

    Findeiss, Laura K.; Cody, Michael E.

    2011-01-01

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

  16. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.”...

  17. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.”...

  18. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.”...

  19. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.”...

  20. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... recommendations as specified under 40 CFR part 792, subpart J the following specific information should be... repair proficient and repair deficient bacteria: âBacterial DNA damage or repair tests.â 798.5500 Section... inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA damage or repair tests.”...

  1. Ultrasound determination of rotator cuff tear repairability

    PubMed Central

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

    2015-01-01

    Background Rotator cuff repair aims to reattach the torn tendon to the greater tuberosity footprint with suture anchors. The present study aimed to assess the diagnostic accuracy of ultrasound in predicting rotator cuff tear repairability and to assess which sonographic and pre-operative features are strongest in predicting repairability. Methods The study was a retrospective analysis of measurements made prospectively in a cohort of 373 patients who had ultrasounds of their shoulder and underwent rotator cuff repair. Measurements of rotator cuff tear size and muscle atrophy were made pre-operatively by ultrasound to enable prediction of rotator cuff repairability. Tears were classified following ultrasound as repairable or irreparable, and were correlated with intra-operative repairability. Results Ultrasound assessment of rotator cuff tear repairability has a sensitivity of 86% (p < 0.0001) and a specificity of 67% (p < 0.0001). The strongest predictors of rotator cuff repairability were tear size (p < 0.001) and age (p = 0.004). Sonographic assessments of tear size ≥4 cm2 or anteroposterior tear length ≥25 mm indicated an irreparable rotator cuff tear. Conclusions Ultrasound assessment is accurate in predicting rotator cuff tear repairability. Tear size or anteroposterior tear length and age were the best predictors of repairability. PMID:27582996

  2. 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.

  3. Distinct responses to reduplicated chromosomes require distinct Mad2 responses

    PubMed Central

    Stormo, Benjamin M; Fox, Donald T

    2016-01-01

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

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

    PubMed

    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. PMID:27159240

  5. 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

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

    PubMed

    Hiu, Takeshi; Farzampour, Zoya; 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; Steinberg, Gary K

    2016-02-01

    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

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

    PubMed

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

    2016-09-01

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

  8. STRUCTURALLY DISTINCT UBIQUITIN- AND SUMO-MODIFIED PCNA: IMPLICATIONS FOR THEIR DISTINCT ROLES IN THE DNA DAMAGE RESPONSE

    PubMed Central

    Xu, Xiaojun; Weinacht, Christopher P.; Freudenthal, Bret D.; Yang, Kun; Zhuang, Zhihao; Washington, M. Todd; Tainer, John A.; Ivanov, Ivaylo

    2015-01-01

    SUMMARY Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO consistent with small angle X-ray scattering (SAXS) data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation. PMID:25773143

  9. Materials Science and Tissue Engineering: Repairing the Heart

    PubMed Central

    Radisic, Milica; Christman, Karen L.

    2013-01-01

    Heart failure following a myocardial infarction continues to be a leading killer in the western world. Currently there are no therapies that effectively prevent or reverse the cardiac damage and negative left ventricular remodeling process that follows a myocardial infarction. Since the heart has limited regenerative capacity, there has been significant effort to develop new therapies that could repair and regenerate the myocardium. While cell transplantation alone was initially studied, more recently tissue engineering strategies using biomaterial scaffolds have been explored. In this review, we cover the different approaches to engineer the myocardium. These include cardiac patches, which are in vitro engineered constructs of functional myocardium, as well as injectable scaffolds that can either encourage endogenous repair and regeneration, or act as vehicles to support delivery of cells and other therapeutics. PMID:23910415

  10. 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.

  11. 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

  12. Analysis of gene repair tracts from Cas9/gRNA double-stranded breaks in the human CFTR gene.

    PubMed

    Hollywood, Jennifer A; Lee, Ciaran M; Scallan, Martina F; Harrison, Patrick T

    2016-01-01

    To maximise the efficiency of template-dependent gene editing, most studies describe programmable and/or RNA-guided endonucleases that make a double-stranded break at, or close to, the target sequence to be modified. The rationale for this design strategy is that most gene repair tracts will be very short. Here, we describe a CRISPR Cas9/gRNA selection-free strategy which uses deep sequencing to characterise repair tracts from a donor plasmid containing seven nucleotide differences across a 216 bp target region in the human CFTR gene. We found that 90% of the template-dependent repair tracts were >100 bp in length with equal numbers of uni-directional and bi-directional repair tracts. The occurrence of long repair tracts suggests that a single gRNA could be used with variants of the same template to create or correct specific mutations within a 200 bp range, the size of ~80% of human exons. The selection-free strategy used here also allowed detection of non-homologous end joining events in many of the homology-directed repair tracts. This indicates a need to modify the donor, possibly by silent changes in the PAM sequence, to prevent creation of a second double-stranded break in an allele that has already been correctly edited by homology-directed repair. PMID:27557525

  13. Laparoscopic Repair of Paraesophageal Hernias

    PubMed Central

    Borao, Frank; Squillaro, Anthony; Mansson, Jonas; Barker, William; Baker, Thomas

    2014-01-01

    Background and Objectives: Laparoscopy has quickly become the standard surgical approach to repair paraesophageal hernias. Although many centers routinely perform this procedure, relatively high recurrence rates have led many surgeons to question this approach. We sought to evaluate outcomes in our cohort of patients with an emphasis on recurrence rates and symptom improvement and their correlation with true radiologic recurrence seen on contrast imaging. Methods: We retrospectively identified 126 consecutive patients who underwent laparoscopic repair of a large paraesophageal hernia between 2000 and 2010. Clinical outcomes were reviewed, and data were collected regarding operative details, perioperative and postoperative complications, symptoms, and follow-up imaging. Radiologic evidence of any size hiatal hernia was considered to indicate a recurrence. Results: There were 95 female and 31 male patients with a mean age (± standard deviation) of 71 ± 14 years. Laparoscopic repair was completed successfully in 120 of 126 patients, with 6 operations converted to open procedures. Crural reinforcement with mesh was performed in 79% of patients, and 11% underwent a Collis gastroplasty. Fundoplications were performed in 90% of patients: Nissen (112), Dor (1), and Toupet (1). Radiographic surveillance, obtained at a mean time interval of 23 months postoperatively, was available in 89 of 126 patients (71%). Radiographic evidence of a recurrence was present in 19 patients (21%). Reoperation was necessary in 6 patients (5%): 5 for symptomatic recurrence (4%) and 1 for dysphagia (1%). The median length of stay was 4 days. Conclusion: Laparoscopic paraesophageal hernia repair results in an excellent outcome with a short length of stay when performed at an experienced center. Radiologic recurrence is observed relatively frequently with routine surveillance; however, many of these recurrences are small, and few patients require correction of the recurrence. Furthermore, these

  14. 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. PMID:22190744

  15. Immune modulation by MANF promotes tissue repair and regenerative success in the retina.

    PubMed

    Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro; Konjikusic, Mia; Riley, Rebeccah; Chew, Shereen; Qi, Yanyan; Jasper, Heinrich; Lamba, Deepak A

    2016-07-01

    Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies. PMID:27365452

  16. 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

  17. 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

  18. Rectal trauma: management based on anatomic distinctions.

    PubMed

    McGrath, V; Fabian, T C; Croce, M A; Minard, G; Pritchard, F E

    1998-12-01

    Principles of rectal wound management, including routine diversion, injury repair, presacral drainage and distal washout, evolved from World War II and the Vietnam conflict and have been questioned in recent years. We believe significant confusion arises because of imprecise definition of injury location relative to retroperitoneal involvement. Our 5-year experience with penetrating rectal injuries at a Level I trauma center was analyzed. Injuries to the anterior and lateral surfaces of the upper two-thirds of the rectum were classified as intraperitoneal (IP, serosalized), and those of the posterior surface extraperitoneal (EP, no serosa); injuries to the lower one-third were EP. A total of 58 injuries were managed (92% gunshot wounds). Of these, 16 were IP, and 42 had some EP component. Ten patients underwent repair without diversion (6 IP, 4 EP); there were no leaks. Ten septic complications occurred in the remaining population: 2 necrotizing fasciitis, 5 abdominal abscess, and 3 presacral infections (PIs) (2 presacral abscesses and 1 wound tract infection). PI is the only complication that can be specifically associated with EP rectal injuries relative to management; as associated injury confounds interpretation of the other complications. The operative management in the 38 patients with diverted EP wounds with respect to presacral infection (PI) demonstrated the following: repair injury (n = 10), 0 PI versus no repair (n = 28), 3 PI (P = 0.55); washout (n = 33), 2 PI versus no washout (n = 5), 1 PI (P = 0.35); presacral drain (n = 30), 1 PI versus no drain (n = 8), 2 PI (P = 0.11). We conclude that most IP injuries can be managed with primary repair. EP wounds to the upper two-thirds of the rectum should usually be repaired. EP wounds to the lower one-third, which are explored and repaired, do not require drainage. EP wounds that are not explored should be managed with presacral drainage to minimize the incidence of presacral abscess. PMID:9843331

  19. The attentional blink provides episodic distinctiveness

    PubMed Central

    Wyble, Brad; Bowman, Howard; Nieuwenstein, Mark

    2009-01-01

    The attentional blink (Raymond et al 1992) refers to an apparent gap in perception that can be elicited when a second target follows a first at a temporal lag of several hundred milliseconds. . Theoretical and computational work have provided a variety of explanations for early sets of blink data, but more recent data have challenged these accounts by showing that the blink is attenuated when subjects encode entire strings of stimuli (Nieuwenstein & Potter, 2006, Olivers et al 2007, Kawahara et al 2007), are distracted (Olivers & Nieuwenhuis 2005) or are provided with irrelevant motion cues (Arend, Johnston, & Shapiro 2006) while viewing the RSVP stream. In this paper, we describe the Episodic Simultaneous Type Serial Token model (eSTST), a computational account of encoding visual stimuli into working memory which suggests that the attentional blink is a cognitive strategy rather than a resource limitation. This model is composed of neurobiologically plausible neural elements and simulates the attentional blink with a competitive attentional mechanism facilitates the formation of episodically distinct representations within working memory. In addition to the blink, the model addresses the phenomena of repetition blindness and whole report superiority, producing predictions which are supported by experimental work. PMID:19485692

  20. Bond strength of repaired amalgam restorations.

    PubMed

    Rey, Rosalia; Mondragon, Eduardo; Shen, Chiayi

    2015-01-01

    This in vitro study investigated the interfacial flexural strength (FS) of amalgam repairs and the optimal combination of repair materials and mechanical retention required for a consistent and durable repair bond. Amalgam bricks were created, each with 1 end roughened to expose a fresh surface before repair. Four groups followed separate repair protocols: group 1, bonding agent with amalgam; group 2, bonding agent with composite resin; group 3, mechanical retention (slot) with amalgam; and group 4, slot with bonding agent and amalgam. Repaired specimens were stored in artificial saliva for 1, 10, 30, 120, or 360 days before being loaded to failure in a 3-point bending test. Statistical analysis showed significant changes in median FS over time in groups 2 and 4. The effect of the repair method on the FS values after each storage period was significant for most groups except the 30-day storage groups. Amalgam-amalgam repair with adequate condensation yielded the most consistent and durable bond. An amalgam bonding agent could be beneficial when firm condensation on the repair surface cannot be achieved or when tooth structure is involved. Composite resin can be a viable option for amalgam repair in an esthetically demanding region, but proper mechanical modification of the amalgam surface and selection of the proper bonding system are essential. PMID:26325656

  1. Biologically distinct subsets of nevi.

    PubMed

    Rogers, Tova; Marino, Maria L; Raciti, Patricia; Jain, Manu; Busam, Klaus J; Marchetti, Michael A; Marghoob, Ashfaq A

    2016-08-01

    Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups. PMID:27119653

  2. Penoscrotal porokeratosis: A distinct entity

    PubMed Central

    Joshi, Rajiv; Jadhav, Yatin

    2015-01-01

    A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition. PMID:26500866

  3. Penoscrotal porokeratosis: A distinct entity.

    PubMed

    Joshi, Rajiv; Jadhav, Yatin

    2015-01-01

    A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition. PMID:26500866

  4. Spatially distinct and metabolically active membrane domain in mycobacteria.

    PubMed

    Hayashi, Jennifer M; Luo, Chu-Yuan; Mayfield, Jacob A; Hsu, Tsungda; Fukuda, Takeshi; Walfield, Andrew L; Giffen, Samantha R; Leszyk, John D; Baer, Christina E; Bennion, Owen T; Madduri, Ashoka; Shaffer, Scott A; Aldridge, Bree B; Sassetti, Christopher M; Sandler, Steven J; Kinoshita, Taroh; Moody, D Branch; Morita, Yasu S

    2016-05-10

    Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemporal regulation is a potential strategy for controlling mycobacterial infections. Our biochemical analysis previously revealed two functionally distinct membrane fractions in Mycobacterium smegmatis cell lysates: plasma membrane tightly associated with the cell wall (PM-CW) and a distinct fraction of pure membrane free of cell wall components (PMf). To provide further insight into the functions of these membrane fractions, we took the approach of comparative proteomics and identified more than 300 proteins specifically associated with the PMf, including essential enzymes involved in cell envelope synthesis such as a mannosyltransferase, Ppm1, and a galactosyltransferase, GlfT2. Furthermore, comparative lipidomics revealed the distinct lipid composition of the PMf, with specific association of key cell envelope biosynthetic precursors. Live-imaging fluorescence microscopy visualized the PMf as patches of membrane spatially distinct from the PM-CW and notably enriched in the pole of the growing cells. Taken together, our study provides the basis for assigning the PMf as a spatiotemporally distinct and metabolically active membrane domain involved in cell envelope biogenesis. PMID:27114527

  5. 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. PMID:26527082

  6. Outcome of pediatric hypospadias repair in adulthood

    PubMed Central

    Chertin, Boris; Prat, Dan; Shenfeld, Ofer Z

    2010-01-01

    Purpose To review the evolution of the technique of hypospadias repair. Methods A search of Pubmed, Medline and the Journal of Pediatric Urology was performed, and papers dealing with surgical techniques for hypospadias repair were critally reviewed. Special emphasis was given to papers on the effects in the long term of hypospadias repair on voiding and sexual dysfunction. Results The techniques for hypospadias repair have evolved over the years. The most popular technique now is tubularized incised plate urethroplasty. Long-term results with the use of the new techniques of the hypospadias repair in terms of voiding and sexual problems should be addressed. Conclusion There is a need for valid studies on the outcomes of hypospadias repair in adults that were performed in childhood in terms of cosmetic appearance, voiding and sexual performance. PMID:24198614

  7. Efficacy of Different Rotator Cuff Repair Techniques.

    PubMed

    Gurnani, Navin; van Deurzen, Derek Friedrich Petrus; Flipsen, Mark; Raven, Eric Ernest Joseph; van den Bekerom, Michel Pieter Jozef

    2015-05-01

    The purpose of this review article is to describe the currently used techniques for rotator cuff repair and after treatment. The literature was searched for the different surgical techniques and additional treatment including: [1] full arthroscopic and arthroscopic assisted rotator cuff repair, [2] acromioplasty as an additional treatment to rotator cuff repair, [3] the use of plasma rich platelets (PRP) after rotator cuff repair, [4] the single and double row fixation techniques, [5] long head of the biceps brachii tenotomy or tenodesis with rotator cuff repair, [6] scaffolds in rotator cuff surgery, and [7] early motion or immobilization after rotator cuff repair. The rationale, the results, and the scientific evidence were reported for the eligible procedures. PMID:26055023

  8. Laparoscopic repair for vesicouterine fistulae

    PubMed Central

    Maioli, Rafael A.; Macedo, André R. S.; Garcia, André R. L.; de Almeida, Silvio H. M.; Rodrigues, Marco Aurélio Freitas

    2015-01-01

    ABSTRACT Objective: The purpose of this video is to present the laparoscopic repair of a VUF in a 42-year-old woman, with gross hematuria, in the immediate postoperative phase following a cesarean delivery. The obstetric team implemented conservative management, including Foley catheter insertion, for 2 weeks. She subsequently developed intermittent hematuria and cystitis. The urology team was consulted 15 days after cesarean delivery. Cystoscopy indicated an ulcerated lesion in the bladder dome of approximately 1.0cm in size. Hysterosalpingography and a pelvic computed tomography scan indicated a fistula. Materials and Methods: Laparoscopic repair was performed 30 days after the cesarean delivery. The patient was placed in the lithotomy position while also in an extreme Trendelenburg position. Pneumoperitoneum was established using a Veress needle in the midline infra-umbilical region, and a primary 11-mm port was inserted. Another 11-mm port was inserted exactly between the left superior iliac spine and the umbilicus. Two other 5-mm ports were established under laparoscopic guidance in the iliac fossa on both sides. The omental adhesions in the pelvis were carefully released and the peritoneum between the bladder and uterus was incised via cautery. Limited cystotomy was performed, and the specific sites of the fistula and the ureteral meatus were identified; thereafter, the posterior bladder wall was adequately mobilized away from the uterus. The uterine rent was then closed using single 3/0Vicryl sutures and two-layer watertight closure of the urinary bladder was achieved by using 3/0Vicryl sutures. An omental flap was mobilized and inserted between the uterus and the urinary bladder, and was fixed using two 3/0Vicryl sutures, followed by tube drain insertion. Results: The operative time was 140 min, whereas the blood loss was 100ml. The patient was discharged 3 days after surgery, and the catheter was removed 12 days after surgery. Discussion: Laparoscopy has

  9. 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.

  10. Cellular repair/misrepair track model

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.

    1991-01-01

    A repair/misrepair cell kinetics model is superimposed onto the track structure model of Katz to provide for a repair mechanism. The model is tested on the repair-dependent data of Yang et al. and provides an adequate description of that data. The misrepair rate determines the maximum relative biological effectiveness (RBE), but similar results could arise from indirect X-ray lethality not include in the present model.

  11. Biophysical modeling of mismatch repair proteins

    NASA Astrophysics Data System (ADS)

    Salsbury, Freddie

    2009-03-01

    Mismatch repair proteins play a vital role in the bology of cancer due to their dual functions as repair proteins and as sensors of DNA damage. Computational modeling of mismatch repair proteins in conjunction with biological experimentation has demonstrated the role of long-range communication in the functions of these proteins. Furthermore, different conformations have been shown to be associated with different cellular functions, and these differences are being exploited in drug discovery. The latest results in this modeling will be presented.

  12. Mutagenic DNA repair in enterobacteria

    SciTech Connect

    Sedgwick, S.G. ); Chao Ho; Woodgate, R. )

    1991-09-01

    Sixteen species of enterobacteria have been screened for mutagenic DNA repair activity. In Escherichia coli, mutagenic DNA repair is encoded by the umuDC operon. Synthesis of UmuD and UmuC proteins is induced as part of the SOS response to DNA damage, and after induction, the UmuD protein undergoes an autocatalytic cleavage to produce the carboxy-terminal UmuD{prime} fragment needed for induced mutagenesis. The presence of a similar system in other species was examined by using a combined approach of inducible-mutagenesis assays, cross-reactivity to E. coli UmuD and UmuD{prime} antibodies to test for induction and cleavage of UmuD-like proteins, and hybridization with E. coli and Salmonella typhimurium u mu DNA probes to map umu-like genes. The results indicate a more widespread distribution of mutagenic DNA repair in other species than was previously thought. They also show that umu loci can be more complex in other species than in E. coli. Differences in UV-induced mutability of more than 200-fold were seen between different species of enteric bacteria and even between multiple natural isolates of E. coli, and yet some of the species which display a poorly mutable phenotype still have umu-like genes and proteins. It is suggested that umuDC genes can be curtailed in their mutagenic activities but that they may still participate in some other, unknown process which provides the continued stimulus for their retention.

  13. 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

  14. The design of bonded structure repairs

    NASA Astrophysics Data System (ADS)

    Armstrong, K. B.

    1983-01-01

    This paper illustrates the problems of the repair engineer in the field when no stress analysis or structural repair manual is available. In this extreme situation he can only seek to restore the original strength of the damaged part whether or not all of that strength is actually required. Two major design factors are considered, i.e. overlap shear joints and core to skin bond strength. Back-up by rivets or bolts is discussed and also sealing the repair with a fabric overlay to prevent or minimize water ingress. The paper concludes with a practical example of a repair using the data provided.

  15. Scheduling and rescheduling with iterative repair

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

    This paper describes the GERRY scheduling and rescheduling system being applied to coordinate Space Shuttle Ground Processing. The system uses constraint-based iterative repair, a technique that starts with a complete but possibly flawed schedule and iteratively improves it by using constraint knowledge within repair heuristics. In this paper we explore the tradeoff between the informedness and the computational cost of several repair heuristics. We show empirically that some knowledge can greatly improve the convergence speed of a repair-based system, but that too much knowledge, such as the knowledge embodied within the MIN-CONFLICTS lookahead heuristic, can overwhelm a system and result in degraded performance.

  16. 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

  17. 33 CFR 127.405 - Repairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Natural Gas Maintenance § 127.405 Repairs. The operator shall ensure that—...

  18. 33 CFR 127.1405 - Repairs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) WATERFRONT FACILITIES WATERFRONT FACILITIES HANDLING LIQUEFIED NATURAL GAS AND LIQUEFIED HAZARDOUS GAS Waterfront Facilities Handling Liquefied Hazardous Gas Maintenance § 127.1405 Repairs. Each operator of...

  19. Photomask repair using low-energetic electrons

    NASA Astrophysics Data System (ADS)

    Edinger, K.; Wolff, K.; Spies, P.; Luchs, T.; Schneider, H.; Auth, N.; Hermanns, Ch. F.; Waiblinger, M.

    2015-10-01

    Mask repair is an essential step in the mask manufacturing process as the extension of 193nm technology and the insertion of EUV are drivers for mask complexity and cost. The ability to repair all types of defects on all mask blank materials is crucial for the economic success of a mask shop operation. In the future mask repair is facing several challenges. The mask minimum features sizes are shrinking and require a higher resolution repair tool. At the same time mask blanks with different new mask materials are introduced to optimize optical performance and long term durability. For EUV masks new classes of defects like multilayer and phase defects are entering the stage. In order to achieve a high yield, mask repair has to cover etch and deposition capabilities and must not damage the mask. We will demonstrate in this paper that low energetic electron-beam (e-beam)-based mask repair is a commercially viable solution. Therefore we developed a new repair platform called MeRiT® neXT to address the technical challenges of this new technology. We will analyze the limits of the existing as well as lower energetic electron induced repair technologies theoretically and experimentally and show performance data on photomask reticles. Based on this data, we will give an outlook to future mask repair technology.

  20. National results after ventral hernia repair.

    PubMed

    Helgstrand, Frederik

    2016-07-01

    Ventral hernia repairs are among the most frequently performed surgical procedures. The variations of repair techniques are multiple and outcome has been unacceptable. Despite the high volume, it has been difficult to obtain sufficient data to provide evidence for best practice. In order to monitor national surgical quality and provide the warranted high volume data, the first national ventral hernia register (The Danish Ventral Hernia Database) was established in 2007 in Denmark. The present study series show that data from a well-established database supported by clinical examinations, patient files, questionnaires, and administrative data makes it possible to obtain nationwide high volume data and to achieve evidence for better outcome in a complex surgical condition as ventral hernia. Due to the high volume and included variables on surgical technique, it is now possible to make analyses adjusting for a variety of surgical techniques and different hernia specifications. We documented high 30-day complications and recurrence rates for both primary and secondary ventral hernias in a nationwide cohort. Furthermore, recurrence found by clinical examination was shown to exceed the number of patients undergoing reoperation for recurrence by a factor 4-5. The nationwide adjusted analyses proved that open mesh and laparoscopic repair for umbilical and epigastric hernias does not differ in 30-day outcome or in risk of recurrence. There is a minor risk reduction in early complications after open sutured repairs. However, the risk for a later recurrence repair is significantly higher after sutured repairs compared with mesh repairs. The study series showed that large hernia defects and open re-pairs were independent predictors for 30-day complications after an incisional hernia repair. Open procedures and large hernia defects were independent risk factors for a later recurrence re-pair. However, patients with large defects (> 15 cm) seemed to benefit from an open mesh

  1. Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair

    PubMed Central

    Siebert, Justin R.; Conta Steencken, Amanda; Osterhout, Donna J.

    2014-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration. PMID:25309928

  2. Oversized AAV Transductifon Is Mediated via a DNA-PKcs-independent, Rad51C-dependent Repair Pathway

    PubMed Central

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

    2013-01-01

    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. PMID:23939025

  3. Consonantal and Syllabic Repairs of Arabic and Dutch Loanwords in Indonesian: A Phonological Account

    ERIC Educational Resources Information Center

    Batais, Saleh Saeed

    2013-01-01

    The dissertation study aims to contribute mainly to the field of loanword phonology in general and particularly to Indonesian and its phonology that are rarely studied to date. The study investigates what consonantal and syllabic repair strategies are employed by Indonesian in adapting Arabic and Dutch loanwords, whether these adaptation…

  4. 24 CFR 206.47 - Property standards; repair work.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 2 2012-04-01 2012-04-01 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...

  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. 24 CFR 206.47 - Property standards; repair work.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 2 2014-04-01 2014-04-01 false Property standards; repair work... Property standards; repair work. (a) Need for repairs. Properties must meet the applicable property... insured mortgage. (b) Assurance that repairs are made. The mortgage may be closed before the repair...

  7. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  8. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  9. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  10. 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...

  11. 14 CFR 145.107 - Satellite repair stations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Satellite repair stations. 145.107 Section... Data § 145.107 Satellite repair stations. (a) A certificated repair station under the managerial control of another certificated repair station may operate as a satellite repair station with its...

  12. 14 CFR 145.207 - Repair station manual.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Repair station manual. 145.207 Section 145...) SCHOOLS AND OTHER CERTIFICATED AGENCIES REPAIR STATIONS Operating Rules § 145.207 Repair station manual. (a) A certificated repair station must prepare and follow a repair station manual acceptable to...

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

    PubMed

    Li, Jing; Xu, Xingzhi

    2016-07-01

    Deoxyribonucleic acid double-strand breaks (DSBs) are cytotoxic lesions that must be repaired either through homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways. DSB repair is critical for genome integrity, cellular homeostasis and also constitutes the biological foundation for radiotherapy and the majority of chemotherapy. The choice between HR and NHEJ is a complex yet not completely understood process that will entail more future efforts. Herein we review our current understandings about how the choice is made over an antagonizing balance between p53-binding protein 1 and breast cancer 1 in the context of cell cycle stages, downstream effects, and distinct chromosomal histone marks. These exciting areas of research will surely bring more mechanistic insights about DSB repair and be utilized in the clinical settings. PMID:27217474

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

    PubMed Central

    Kato, Akihiro; Komatsu, Kenshi

    2015-01-01

    Rapid progress in the study on the association of histone modifications with chromatin remodeling factors has broadened our understanding of chromatin dynamics in DNA transactions. In DNA double-strand break (DSB) repair, the well-known mark of histones is the phosphorylation of the H2A variant, H2AX, which has been used as a surrogate marker of DSBs. The ubiquitylation of histone H2B by RNF20 E3 ligase was recently found to be a DNA damage-induced histone modification. This modification is required for DSB repair and regulated by a distinctive pathway from that of histone H2AX phosphorylation. Moreover, the connection between H2B ubiquitylation and the chromatin remodeling activity of SNF2H has been elucidated. In this review, we summarize the current knowledge of RNF20-mediated processes and the molecular link to H2AX-mediated processes during DSB repair. PMID:26184323

  15. The C-terminal domain of Cernunnos/XLF is dispensable for DNA repair in vivo.

    PubMed

    Malivert, Laurent; Callebaut, Isabelle; Rivera-Munoz, Paola; Fischer, Alain; Mornon, Jean-Paul; Revy, Patrick; de Villartay, Jean-Pierre

    2009-03-01

    The core nonhomologous end-joining DNA repair pathway is composed of seven factors: Ku70, Ku80, DNA-PKcs, Artemis, XRCC4 (X4), DNA ligase IV (L4), and Cernunnos/XLF (Cernunnos). Although Cernunnos and X4 are structurally related and participate in the same complex together with L4, they have distinct functions during DNA repair. L4 relies on X4 but not on Cernunnos for its stability, and L4 is required for optimal interaction of Cernunnos with X4. We demonstrate here, using in vitro-generated Cernunnos mutants and a series of functional assays in vivo, that the C-terminal region of Cernunnos is dispensable for its activity during DNA repair. PMID:19103754

  16. Protein Engineering for Cardiovascular Therapeutics: Untapped Potential for Cardiac Repair

    PubMed Central

    Jay, Steven M.; Lee, Richard T.

    2013-01-01

    Numerous new and innovative approaches for repairing damaged myocardium are currently under investigation, with several encouraging results. In addition to the progression of stem cell-based approaches and gene therapy/silencing methods, evidence continues to emerge that protein therapeutics may be used to directly promote cardiac repair and even regeneration. However, proteins are often limited in their therapeutic potential by short local half-lives and insufficient bioavailability and/or bioactivity, and many academic laboratories studying cardiovascular diseases are more comfortable with molecular and cellular biology compared with protein biochemistry. Protein engineering has been employed broadly to overcome weaknesses traditionally associated with protein therapeutics and has the potential to specifically enhance the efficacy of molecules for cardiac repair. Yet protein engineering as a strategy has not yet been employed in the development of cardiovascular therapeutics to the degree that it has in other fields. In this review, we discuss the role of engineered proteins in cardiovascular therapies to date. Further, we address the promise of applying emerging protein engineering technologies to cardiovascular medicine and the barriers that must be overcome to enable the ultimate success of this approach. PMID:24030023

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

    PubMed

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

    2016-01-01

    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. PMID:27314344

  18. Biologic and pharmacologic augmentation of rotator cuff repairs.

    PubMed

    Edwards, Sara L; Lynch, T Sean; Saltzman, Matthew D; Terry, Michael A; Nuber, Gordon W

    2011-10-01

    As rotator cuff repair techniques have improved, failure of the tendon to heal to the proximal humerus is less likely to occur from weak tendon-to-bone fixation. More likely causes of failure include biologic factors such as intrinsic tendon degeneration, fatty atrophy, fatty infiltration of muscle, and lack of vascularity of the tendons. High failure rates have led to the investigation of biologic augmentation to potentially enhance the healing response. Histologic studies have shown that restoration of the rotator cuff footprint during repair can help reestablish the enthesis. In animal models, growth factors and their delivery scaffolds as well as tissue engineering have shown promise in decreasing scar tissue while maintaining biomechanical strength. Platelet-rich plasma may be a safe adjuvant to rotator cuff repair, but it has not been shown to improve healing or function. Many of these strategies need to be further defined to permit understanding of, and to optimize, the biologic environment; in addition, techniques need to be refined for clinical use. PMID:21980023

  19. 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.

  20. Starting System 2. Repair the Starter Rewind Spring. Student Manual. Small Engine Repair Series. First Edition.

    ERIC Educational Resources Information Center

    Hill, Pamela

    This student manual on repairing the starter rewind spring on a small gas engine is the third of three in an instructional package on the starting system in the Small Engine Repair Series for handicapped students. The stated purpose for the booklet is to help students learn what tools and equipment to use in repairing the starter rewind spring and…

  1. The Covert Repair Hypothesis: Prearticulatory Repair Processes in Normal and Stuttered Disfluencies.

    ERIC Educational Resources Information Center

    Postma, Albert; Kolk, Herman

    1993-01-01

    This paper discusses the speech monitoring process that underlies overt self-repairing of speech errors; the covert repair hypothesis, dealing particularly with explaining the variety of disfluency types from a restricted set of repair principles; quantitative and qualitative characteristics of disfluency in people who stutter; and the covert…

  2. Molded Parallel Endografts for Branch Vessel Preservation during Endovascular Aneurysm Repair in Challenging Anatomy.

    PubMed

    Minion, David

    2012-06-01

    Parallel endografts (also known as snorkels or chimneys) are a proposed strategy for increasing the applicability of endovascular repair to aneurysms involving branch vessels. One major disadvantage of this strategy is the imperfect nature of seal inherent to having multiple side-by-side endografts. In this article, the use of odd-shaped parallel endografts to facilitate apposition and improve seal is proposed and a technique to mold a round stent graft into an "eye" shape using balloons is described. PMID:23730134

  3. 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

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

    PubMed

    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

  5. Complete regression of a symptomatic, mycotic juxtarenal abdominal aortic aneurysm after treatment with fenestrated endovascular aneurysm repair.

    PubMed

    Durgin, Jonathan M; Arous, Edward J; Kumar, Shivani; Robinson, William P; Simons, Jessica P; Schanzer, Andres

    2016-09-01

    Mycotic abdominal aortic aneurysms are rare and present unique challenges when potential treatment options are considered. Although aortic resection with in situ grafting techniques or extra-anatomic reconstruction are the treatments of choice, endovascular aortic repair has emerged as a suitable alternative in critically ill patients. We report the successful endovascular repair of a symptomatic, mycotic juxtarenal aortic aneurysm using a physician-modified fenestrated endograft. In this patient, with >6 months of follow-up, the aneurysm has completely regressed, illustrating that in select patients with complex mycotic aneurysms, endovascular repair combined with appropriate medical management is a viable treatment strategy. PMID:26747681

  6. Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

    DOE PAGESBeta

    Hang, Bo

    2010-01-01

    DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking-related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N -nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O 6more » -alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen-associated genotoxic and carcinogenic effects.« less

  7. Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

    PubMed Central

    Hang, Bo

    2010-01-01

    DNA adducts play a central role in chemical carcinogenesis. The analysis of formation and repair of smoking-related DNA adducts remains particularly challenging as both smokers and nonsmokers exposed to smoke are repetitively under attack from complex mixtures of carcinogens such as polycyclic aromatic hydrocarbons and N-nitrosamines. The bulky DNA adducts, which usually have complex structure, are particularly important because of their biological relevance. Several known cellular DNA repair pathways have been known to operate in human cells on specific types of bulky DNA adducts, for example, nucleotide excision repair, base excision repair, and direct reversal involving O6-alkylguanine DNA alkyltransferase or AlkB homologs. Understanding the mechanisms of adduct formation and repair processes is critical for the assessment of cancer risk resulting from exposure to cigarette smoke, and ultimately for developing strategies of cancer prevention. This paper highlights the recent progress made in the areas concerning formation and repair of bulky DNA adducts in the context of tobacco carcinogen-associated genotoxic and carcinogenic effects. PMID:21234336

  8. Hodgkin Lymphoma Risk: Role of Genetic Polymorphisms and Gene-Gene Interactions in DNA repair pathways

    PubMed Central

    Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa

    2011-01-01

    DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL. PMID:21374732

  9. Laser engineered net shaping (LENS) for the repair and modification of NWC metal components.

    SciTech Connect

    Atwood, Clinton J.; Smugeresky, John E. (Sandia National Labs, Livermore,CA); Gill, David Dennis

    2006-11-01

    Laser Engineered Net Shaping{trademark} (LENS{reg_sign}) is a layer additive manufacturing process that creates fully dense metal components using a laser, metal powder, and a computer solid model. This process has previously been utilized in research settings to create metal components and new material alloys. The ''Qualification of LENS for the Repair and Modification of Metal NWC Components'' project team has completed a Technology Investment project to investigate the use of LENS for repair of high rigor components. The team submitted components from four NWC sites for repair or modification using the LENS process. These components were then evaluated for their compatibility to high rigor weapons applications. The repairs included hole filling, replacement of weld lips, addition of step joints, and repair of surface flaws and gouges. The parts were evaluated for mechanical properties, corrosion resistance, weldability, and hydrogen compatibility. This document is a record of the LENS processing of each of these component types and includes process parameters, build strategies, and lessons learned. Through this project, the LENS process was shown to successfully repair or modify metal NWC components.

  10. 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. PMID:27353702

  11. Evidence of K+ channel function in epithelial cell migration, proliferation, and repair

    PubMed Central

    Girault, Alban

    2013-01-01

    Efficient repair of epithelial tissue, which is frequently exposed to insults, is necessary to maintain its functional integrity. It is therefore necessary to better understand the biological and molecular determinants of tissue regeneration and to develop new strategies to promote epithelial repair. Interestingly, a growing body of evidence indicates that many members of the large and widely expressed family of K+ channels are involved in regulation of cell migration and proliferation, key processes of epithelial repair. First, we briefly summarize the complex mechanisms, including cell migration, proliferation, and differentiation, engaged after epithelial injury. We then present evidence implicating K+ channels in the regulation of these key repair processes. We also describe the mechanisms whereby K+ channels may control epithelial repair processes. In particular, changes in membrane potential, K+ concentration, cell volume, intracellular Ca2+, and signaling pathways following modulation of K+ channel activity, as well as physical interaction of K+ channels with the cytoskeleton or integrins are presented. Finally, we discuss the challenges to efficient, specific, and safe targeting of K+ channels for therapeutic applications to improve epithelial repair in vivo. PMID:24196531

  12. Municipal Solid Waste Landfills Harbor Distinct Microbiomes.

    PubMed

    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

  13. 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

  14. Learning our ABCs: Rad50 directs MRN repair functions via adenylate kinase activity from the conserved ATP binding cassette.

    PubMed

    Williams, R Scott; Tainer, John A

    2007-03-23

    In groundbreaking work, Bhaskara et al. (2007) demonstrate in a recent issue of Molecular Cell that the Mre11/Rad50/Nbs1 (MRN) complex harbors distinct, yet chemically related, ATPase and adenylate kinase catalytic activities that together orchestrate multiple requisite MRN functional and conformational states in dsDNA break repair sensing and signaling with general implications for ABC ATPases. PMID:17386254

  15. Open Repair of Aneurysms of the Thoracoabdominal Aorta.

    PubMed

    Kazen, Ulrika Palmer; Blohmé, Linus; Olsson, Christian; Hultgren, Rebecka

    2016-06-01

    Background Open surgical repair of aneurysms in the descending and thoracoabdominal aorta remains the dominating treatment of choice at many institutions worldwide. Patients treated with open repair most probably differ from endovascularly treated patients. With the present distribution of procedures performed for thoracoabdominal aortic aneurysms (TAAA), one cannot foresee any randomized controlled trial within the field. Several reports have, however, described similar midterm survival after open and endovascular repair. The objective of this report is to contribute the results from a contemporary series of open repair for TAAA at a dedicated aortic center. Methods All patients treated with open surgery for TAAA in the Stockholm County from 2007 to 2012 were included in the analysis. They were identified in the hospital administrative chart systems for operations and care. Results Twenty-eight patients were treated for TAAA, with a mean age of 61 (30-85) years, and 75% were male. Mean operative time was 573 (±190 minutes); left heart bypass was used in 75% of the operations and cardiopulmonary bypass in 25%. All patients had two to five visceral arteries reimplanted. During a 1-year follow-up period, one patient (3.6%) suffered permanent hemodialysis, one (3.6%) had a stroke, three (10.7%) had bowel ischemia, four (14.3%) had postoperative symptoms of spinal ischemia, and two of them (7.1%) had permanent paraplegia. No one died within 30 days, three patients (10.7%) died within 3 months, and 1-year mortality was 10.7%. Conclusion In an era of evolving endovascular alternatives to open surgery for TAAA, this contemporary series from an aortic center show excellent results that are comparable to most series of treated TAAA, both open and endovascular. It is highly probable that the case selection for the two treatment options should be made in centralized dedicated aortic centers with skills to handle all strategies of care. PMID:26402738

  16. Erosion of repaired exstrophy bladder by a large vesical calculus

    PubMed Central

    Hai, Abdul; Sinha, Arvind; Bisht, Mayank; Gola, Neelkamal

    2011-01-01

    Formation of stones in repaired exstrophy bladder is common; however, erosion of stone through the repaired bladder and anterior abdominal wall has never been reported. We report one such case of erosion after three years of repair. PMID:21897570

  17. 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...

  18. 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...

  19. 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)

  20. 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

  1. AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREWFEED ...

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

    AUTOMOTIVE REPAIR SHOP, DETAIL OF MILLS COAL BOILER WITH SCREW-FEED COAL HOPPER ON RIGHT SIDE. - Cedar City Automotive Repair Shop, Automotive Repair Shop, 820 North Main Street, Cedar City, Iron County, UT

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 40 CFR 63.1005 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... successful repair of the leak. (3) Maximum instrument reading measured by Method 21 of 40 CFR part 60... replacing the existing seal design with a new system that the owner or operator has determined will provide... delayed” and the reason for the delay if a leak is not repaired within 15 calendar days after discovery...

  12. 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…

  13. 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…

  14. 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.

  15. Repairing high-temperature glazed tiles

    NASA Technical Reports Server (NTRS)

    Ecord, G. M.; Schomburg, C.

    1981-01-01

    Tetraethyl orthosilicate (TEOS) mixture fills chips and cracks in glazed tile surface. Filler is made by mixing hydrolyzed TEOS, silicon tetraboride powder, and pulverized tile material. Repaired tiles survived testing by intense acoustic emissions, arc jets, and intense heat radiation. Repair is reliable and rapid, performed in 1-1 1/2 hours with tile in any or orientation.

  16. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  17. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  18. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... reading measured by Method 21 of 40 CFR part 60, appendix A at the time the leak is successfully repaired... detected. First attempt at repair for pumps includes, but is not limited to, tightening the packing gland... the bonnet bolts, and/or tightening the packing gland nuts, and/or injecting lubricant into...

  19. 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.

  20. 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...