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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

    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

  8. 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

  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. 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

  16. 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

  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

    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

  11. 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

  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. 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…

  1. 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…

  2. 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...

  3. 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.

  4. 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.

  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. 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

  1. 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

  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. 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;…

  19. 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;…

  20. 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;…

  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 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

  8. 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

  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. 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 ...

  12. 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…

  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. 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…

  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. 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 ...

  3. 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 ...

  4. 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. ...

  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. 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

  12. 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

  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. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  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. 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 ...

  2. 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).

  3. 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. ...

  4. 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)

  5. 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- ...

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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 - ...

  10. 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 ...

  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. 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.

  15. 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

  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. 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…

  12. 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 ...

  13. 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.

  14. 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

  15. 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

  16. 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…

  17. 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,…

  18. Repairing cracked glass

    NASA Technical Reports Server (NTRS)

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

    1979-01-01

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

  19. Automotive Body Repair Competencies.

    ERIC Educational Resources Information Center

    D'Armond, Jack; And Others

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

  20. Patent urachus repair

    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/ ...

  1. 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 ...

  2. Aircraft Propeller Hub Repair

    SciTech Connect

    Muth, Thomas R.; Peter, William H.

    2015-02-13

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

  3. 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 ...

  4. 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)

  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. 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…

  19. 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

  20. 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

  1. [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

  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 ...