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Sample records for distinct repair strategies

  1. Complex networks repair strategies: Dynamic models

    NASA Astrophysics Data System (ADS)

    Fu, Chaoqi; Wang, Ying; Gao, Yangjun; Wang, Xiaoyang

    2017-09-01

    Network repair strategies are tactical methods that restore the efficiency of damaged networks; however, unreasonable repair strategies not only waste resources, they are also ineffective for network recovery. Most extant research on network repair focuses on static networks, but results and findings on static networks cannot be applied to evolutionary dynamic networks because, in dynamic models, complex network repair has completely different characteristics. For instance, repaired nodes face more severe challenges, and require strategic repair methods in order to have a significant effect. In this study, we propose the Shell Repair Strategy (SRS) to minimize the risk of secondary node failures due to the cascading effect. Our proposed method includes the identification of a set of vital nodes that have a significant impact on network repair and defense. Our identification of these vital nodes reduces the number of switching nodes that face the risk of secondary failures during the dynamic repair process. This is positively correlated with the size of the average degree < k > and enhances network invulnerability.

  2. 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)

  3. 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)

  4. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

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

  5. Myelin Repair Strategies: A Cellular View

    PubMed Central

    Gallo, Vittorio; Armstrong, Regina

    2009-01-01

    Purpose of review The development of successful myelin repair strategies depends on the detailed knowledge of the cellular and molecular processes underlying demyelination and remyelination in the CNS of animal models and in patients with multiple sclerosis (MS). Based on the complexity of the demyelination and remyelination processes, it should be expected that effective therapeutic approaches will require a combination of strategies for immunomodulation, neuroprotection, and myelin replacement. This brief review highlights recent cellular and molecular findings and indicates that future therapeutic strategies to enhance remyelination may also require combinatorial treatment to accomplish. Recent findings The relapsing-remitting course of some forms of MS has typically fueled hope for effective repair of MS lesions if demyelinating activity could be attenuated. Recent findings support the potential of endogenous neural stem cells and progenitor cells to generate remyelinating oligodendrocytes. Importantly, interactions with viable axons and supportive astrocytic responses are required for endogenous immature cells to fulfill their potential remyelinating capacity. Summary The research described here will help in identifying the major obstacles to effective remyelination and potential therapeutic targets to guide development of comprehensive approaches for testing in animal models and eventual treatment of patients with MS. PMID:18451710

  6. 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…

  7. 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…

  8. Cellular strategies for enhancement of fracture repair.

    PubMed

    Patterson, Thomas E; Kumagai, Ken; Griffith, Linda; Muschler, George F

    2008-02-01

    Tissue engineering seeks to translate scientific knowledge into tangible products to advance the repair, replacement, or regeneration of organs and tissues. Current tissue engineering strategies have progressed recently from a historical approach that is based primarily on biomaterials to a cell and tissue-based approach that includes understanding of cell-sourcing and bioactive stimuli. New options include methods for harvest and transplantation of tissue-forming cells, bioactive matrix materials that act as tissue scaffolds, and delivery of bioactive molecules within scaffolds. These strategies are already benefiting patients, and they place increasing demands on orthopaedic surgeons to have a solid foundation in the contemporary concepts and principles of cell-based tissue engineering. Essentially all orthopaedic tissue engineering strategies can be distilled to a strategy or combination of strategies that seek to increase the number or relative performance of bone-forming cells. The global term connective tissue progenitors has been used to define the heterogeneous populations of stem and progenitor cells that are found in native tissue and that are capable of differentiating into one or more connective tissue phenotypes. These stem or progenitor populations are found in various tissue sources, with varying degrees of ability to differentiate along connective tissue lineages. Available cell-based strategies include targeting local cells with use of scaffolds or bioactive factors, or transplantation of autogenous connective tissue progenitor cells derived from bone marrow or other tissues, with or without processing to change their concentration or prevalence. The future may include means of homing circulating connective tissue progenitor cells with use of intrinsic chemokine systems, or modifying the biological performance of connective tissue progenitor cells by means of genetic modifications.

  9. 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

  10. Single-stranded oligonucleotide-mediated gene repair in mammalian cells has a mechanism distinct from homologous recombination repair.

    PubMed

    Wang, Zai; Zhou, Zhong-Jun; Liu, De-Pei; Huang, Jian-Dong

    2006-11-24

    Single-stranded DNA oligonucleotide (SSO)-mediated gene repair has great potentials for gene therapy and functional genomic studies. However, its underlying mechanism remains unclear. Previous studies from other groups have suggested that DNA damage response via the ATM/ATR pathway may be involved in this process. In this study, we measured the effect of two ATM/ATR inhibitors caffeine and pentoxifylline on the correction efficiency in SSO-mediated gene repair. We also checked their effect on double-stranded break (DSB)-induced homologous recombination repair (HRR) as a control, which is well known to be dependent on the ATM/ATR pathway. We found these inhibitors could completely inhibit DSB-induced HRR, but could only partially inhibit SSO-mediated process, indicating SSO-mediated gene repair is not dependent on the ATM/ATR pathway. Furthermore, we found that thymidine treatment promotes SSO-mediated gene repair, but inhibits DSB-induced HRR. Collectively, our results demonstrate that SSO-mediated and DSB-induced gene repairs have distinct mechanisms.

  11. 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

  12. 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.

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

    PubMed

    Davis, Luther; Maizels, Nancy

    2014-03-11

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

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

    PubMed Central

    Davis, Luther; Maizels, Nancy

    2014-01-01

    DNA nicks are the most common form of DNA damage, and if unrepaired can give rise to genomic instability. In human cells, nicks are efficiently repaired via the single-strand break repair pathway, but relatively little is known about the fate of nicks not processed by that pathway. Here we show that homology-directed repair (HDR) at nicks occurs via a mechanism distinct from HDR at double-strand breaks (DSBs). HDR at nicks, but not DSBs, is associated with transcription and is eightfold more efficient at a nick on the transcribed strand than at a nick on the nontranscribed strand. HDR at nicks can proceed by a pathway dependent upon canonical HDR factors RAD51 and BRCA2; or by an efficient alternative pathway that uses either ssDNA or nicked dsDNA donors and that is strongly inhibited by RAD51 and BRCA2. Nicks generated by either I-AniI or the CRISPR/Cas9D10A nickase are repaired by the alternative HDR pathway with little accompanying mutagenic end-joining, so this pathway may be usefully applied to genome engineering. These results suggest that alternative HDR at nicks may be stimulated in physiological contexts in which canonical RAD51/BRCA2-dependent HDR is compromised or down-regulated, which occurs frequently in tumors. PMID:24556991

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

    PubMed Central

    Scolding, N

    1999-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  17. 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…

  18. Distinct Roles of FANCO/RAD51C Protein in DNA Damage Signaling and Repair

    PubMed Central

    Somyajit, Kumar; Subramanya, Shreelakshmi; Nagaraju, Ganesh

    2012-01-01

    RAD51C, a RAD51 paralog, has been implicated in homologous recombination (HR), and germ line mutations in RAD51C are known to cause Fanconi anemia (FA)-like disorder and breast and ovarian cancers. The role of RAD51C in the FA pathway of DNA interstrand cross-link (ICL) repair and as a tumor suppressor is obscure. Here, we report that RAD51C deficiency leads to ICL sensitivity, chromatid-type errors, and G2/M accumulation, which are hallmarks of the FA phenotype. We find that RAD51C is dispensable for ICL unhooking and FANCD2 monoubiquitination but is essential for HR, confirming the downstream role of RAD51C in ICL repair. Furthermore, we demonstrate that RAD51C plays a vital role in the HR-mediated repair of DNA lesions associated with replication. Finally, we show that RAD51C participates in ICL and double strand break-induced DNA damage signaling and controls intra-S-phase checkpoint through CHK2 activation. Our analyses with pathological mutants of RAD51C that were identified in FA and breast and ovarian cancers reveal that RAD51C regulates HR and DNA damage signaling distinctly. Together, these results unravel the critical role of RAD51C in the FA pathway of ICL repair and as a tumor suppressor. PMID:22167183

  19. 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

  20. 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

  1. 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…

  2. MEN1 and FANCD2 mediate distinct mechanisms of DNA crosslink repair

    PubMed Central

    Marek, Lorri R.; Kottemann, Molly C.; Glazer, Peter M.; Bale, Allen E.

    2008-01-01

    Cells mutant for multiple endocrine neoplasia type I (MEN1) or any of the Fanconi anemia (FA) genes are hypersensitive to the killing effects of crosslinking agents, but the precise roles of these genes in the response to interstrand crosslinks (ICLs) are unknown. To determine if MEN1 and the FA genes function cooperatively in the same repair process or in distinct repair processes, we exploited Drosophila genetics to compare the mutation frequency and spectra of MEN1 and FANCD2 mutants and to perform genetic interaction studies. We created a novel in vivo reporter system in Drosophila based on the supF gene and showed that MEN1 mutant flies were extremely prone to single base deletions within a homopolymeric tract. FANCD2 mutants, on the other hand, had a mutation frequency and spectrum similar to wild type using this assay. In contrast to the supF results, both MEN1 and FANCD2 mutants were hypermutable using a different assay based on the lats tumor suppressor gene. The lats assay showed that FANCD2 mutants had a high frequency of large deletions, which the supF assay was not able to detect, while large deletions were rare in MEN1 mutants. Genetic interaction studies showed that neither overexpression nor loss of MEN1 modified the ICL sensitivity of FANCD2 mutants. The strikingly different mutation spectra of MEN1 and FANCD2 mutants together with lack of evidence for genetic interaction between these genes indicate MEN1 plays an essential role in ICL repair distinct from the Fanconi anemia genes. PMID:18258493

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

    PubMed Central

    Ge, Jianqiao; Han, Shihui

    2008-01-01

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

  4. Distinct neurocognitive strategies for comprehensions of human and artificial intelligence.

    PubMed

    Ge, Jianqiao; Han, Shihui

    2008-07-30

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

  5. 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

  6. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions.

    PubMed

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

    2013-06-06

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

  7. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions

    PubMed Central

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

    2013-01-01

    SUMMARY The DNA damage response (DDR) protein 53BP1 protects DNA ends from excessive resection in G1, and thereby favors repair by non-homologous end joining (NHEJ) as opposed to homologous recombination (HR). During S phase, BRCA1 antagonizes 53BP1 to promote HR. The pro-NHEJ and anti-recombinase functions of 53BP1 are mediated in part by RIF1, the only known factor that requires 53BP1 phosphorylation for its recruitment to double strand breaks (DSBs). Here we show that a 53BP1 phospho-mutant 53BP18A, comprising alanine substitutions of the 8 most N-terminal S/TQ phosphorylation sites, mimics 53BP1 deficiency by restoring genome stability in BRCA1 deficient cells yet behaves like wild-type 53BP1 with respect to immunoglobulin class switch recombination (CSR). 53BP18A recruits RIF1 but fails to recruit the DDR protein PTIP to DSBs, and disruption of PTIP phenocopies 53BP18A. We conclude that 53BP1 promotes productive CSR and suppresses mutagenic DNA repair through distinct phospho-dependent interactions with RIF1 and PTIP. PMID:23727112

  8. 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

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

    PubMed

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

    2008-06-01

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

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

    PubMed

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

    2012-11-01

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

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

    PubMed

    Bunge, Mary Bartlett

    2008-01-01

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

  12. 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

  13. Different activation signals induce distinct mast cell degranulation strategies

    PubMed Central

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Keen, Deb

    2005-01-01

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

  15. 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

  16. 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. © The Author(s) 2014.

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

    SciTech Connect

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

    2016-11-22

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

  18. 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

  19. 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

  20. 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.

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

    SciTech Connect

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

    2016-05-06

    Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. In this paper, 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. Finally, this method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.

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

    DOE PAGES

    Jacobs, T. M.; Williams, B.; Williams, T.; ...

    2016-05-06

    Natural recombination combines pieces of preexisting proteins to create new tertiary structures and functions. In this paper, 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. Finally, thismore » method provides a new strategy to rapidly create large numbers of diverse and designable protein scaffolds.« less

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

    PubMed Central

    Jacobs, TM; Williams, B; Williams, T; Xu, X; Eletsky, A; Federizon, JF; Szyperski, T; Kuhlman, B

    2016-01-01

    Natural recombination combines pieces of pre-existing 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 to over 100 °C. High resolution structures of the designed proteins CA01 and DA05R1 were solved by X-ray crystallography (2.2 Å resolution) and NMR 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

  4. Is heart rate variability affected by distinct motor imagery strategies?

    PubMed

    Peixoto Pinto, Talita; Mello Russo Ramos, Maitê; Lemos, Thiago; Domingues Vargas, Claudia; Imbiriba, Luis Aureliano

    2017-08-01

    Although some studies have reported significant changes in autonomic responses according to the perspective-taking during motor imagery [first person perspective (1P) and third person perspective (3P)], investigations on how the strategies adopted to mentally simulate a given movement affect the heart rate variability (HRV) seem so far unexplored. Twenty healthy subjects mentally simulated the movement of middle-finger extension in 1P and 3P, while electrocardiogram was recorded. After each task, the level of easiness was self-reported. Motor imagery ability was also assessed through the revised version of Movement Imagery Questionnaire (MIQ-R) and a mental chronometry index. The traditional measures of HRV in the time- and frequency-domain were compared between 1P and 3P tasks by using Student's t-test for dependent samples. The MIQ-R results showed that subjects had the same facility to imagine movements in 1P or 3P. The mental chronometry index revealed a similar temporal course only between 1P and execution, while the 3P strategy had a shorter duration. Additionally, the subjective report was similar between the experimental tasks. Regarding the HRV measures, the low frequency component, in log-transformed unit, was significantly higher (p=0.017) in 1P than 3P, suggesting a higher activity of the sympathetic system during 1P. This log-transformed HRV parameter seems to be more sensitive than normalized values for the assessment of the motor imagery ability, together with questionnaires, scales and mental chronometry. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    ERIC Educational Resources Information Center

    Foster, Don; And Others

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

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

    ERIC Educational Resources Information Center

    Foster, Don; And Others

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

  7. The relative efficiency of homology-directed repair has distinct effects on proper anaphase chromosome separation

    PubMed Central

    Laulier, Corentin; Cheng, Anita; Stark, Jeremy M.

    2011-01-01

    Homology-directed repair (HDR) is essential to limit mutagenesis, chromosomal instability (CIN) and tumorigenesis. We have characterized the consequences of HDR deficiency on anaphase, using markers for incomplete chromosome separation: DAPI-bridges and Ultra-fine bridges (UFBs). We show that multiple HDR factors (Rad51, Brca2 and Brca1) are critical for complete chromosome separation during anaphase, while another chromosome break repair pathway, non-homologous end joining, does not affect chromosome segregation. We then examined the consequences of mild versus severe HDR disruption, using two different dominant-negative alleles of the strand exchange factor, Rad51. We show that mild HDR disruption is viable, but causes incomplete chromosome separation, as detected by DAPI-bridges and UFBs, while severe HDR disruption additionally results in multipolar anaphases and loss of clonogenic survival. We suggest that mild HDR disruption favors the proliferation of cells that are prone to CIN due to defective chromosome separation during anaphase, whereas, severe HDR deficiency leads to multipolar divisions that are prohibitive for cell proliferation. PMID:21459848

  8. 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

  9. Mechanical Restoration and Failure Analyses of a Hydrogel and Scaffold Composite Strategy for Annulus Fibrosus Repair

    PubMed Central

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

    2015-01-01

    Unrepaired defects in the annulus fibrosus of intervertebral discs are associated with degeneration and persistent back pain. A clinical need exists for a disc repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disc height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disc biomechanics with low herniation risk, suggesting further evaluation for disc repair may be warranted. PMID:26577987

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

    PubMed Central

    Spriggs, Chelsey C.

    2017-01-01

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

  11. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse.

    PubMed

    Buard, Jérôme; Barthès, Pauline; Grey, Corinne; de Massy, Bernard

    2009-09-02

    Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11(-/-) mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination.

  12. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse

    PubMed Central

    Buard, Jérôme; Barthès, Pauline; Grey, Corinne; de Massy, Bernard

    2009-01-01

    Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11−/− mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination. PMID:19644444

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

    PubMed

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

    2005-07-15

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

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

    PubMed

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

    2016-01-01

    Unrepaired defects in the annulus fibrosus of intervertebral disks are associated with degeneration and persistent back pain. A clinical need exists for a disk repair strategy that can seal annular defects, be easily delivered during surgical procedures, and restore biomechanics with low risk of herniation. Multiple annulus repair strategies were developed using poly(trimethylene carbonate) scaffolds optimized for cell delivery, polyurethane membranes designed to prevent herniation, and fibrin-genipin adhesive tuned to annulus fibrosus shear properties. This three-part study evaluated repair strategies for biomechanical restoration, herniation risk and failure mode in torsion, bending and compression at physiological and hyper-physiological loads using a bovine injury model. Fibrin-genipin hydrogel restored some torsional stiffness, bending ROM and disk height loss, with negligible herniation risk and failure was observed histologically at the fibrin-genipin mid-substance following rigorous loading. Scaffold-based repairs partially restored biomechanics, but had high herniation risk even when stabilized with sutured membranes and failure was observed histologically at the interface between scaffold and fibrin-genipin adhesive. Fibrin-genipin was the simplest annulus fibrosus repair solution evaluated that involved an easily deliverable adhesive that filled irregularly-shaped annular defects and partially restored disk biomechanics with low herniation risk, suggesting further evaluation for disk repair may be warranted. Lower back pain is the leading cause of global disability and commonly caused by defects and failure of intervertebral disk tissues resulting in herniation and compression of adjacent nerves. Annulus fibrosus repair materials and techniques have not been successful due to the challenging mechanical and chemical microenvironment and the needs to restore biomechanical behaviors and promote healing with negligible herniation risk while being delivered

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

    DOE PAGES

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

    2016-10-27

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

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

    PubMed

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

    2016-11-22

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

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

    SciTech Connect

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

    2016-10-27

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

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

    PubMed

    Spriggs, Chelsey C; Laimins, Laimonis A

    2017-02-14

    The life cycle of human papillomavirus (HPV) is dependent on the differentiation state of its host cell. HPV genomes are maintained as low-copy episomes in basal epithelial cells and amplified to thousands of copies per cell in differentiated layers. Replication of high-risk HPVs requires the activation of the ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR) DNA repair pathways. The Fanconi anemia (FA) pathway is a part of the DNA damage response and mediates cross talk between the ATM and ATR pathways. Our studies show that HPV activates the FA pathway, leading to the accumulation of a key regulatory protein, FANCD2, in large nuclear foci. These HPV-dependent foci colocalize with a distinct population of DNA repair proteins, including ATM components γH2AX and BRCA1, but infrequently with p-SMC1, which is required for viral genome amplification in differentiated cells. Furthermore, FANCD2 is found at viral replication foci, where it is preferentially recruited to viral genomes compared to cellular chromosomes and is required for maintenance of HPV episomes in undifferentiated cells. These findings identify FANCD2 as an important regulator of HPV replication and provide insight into the role of the DNA damage response in the differentiation-dependent life cycle of HPV.IMPORTANCE High-risk human papillomaviruses (HPVs) are the etiological agents of cervical cancer and are linked to the development of many other anogenital and oropharyngeal cancers. Identification of host cellular pathways involved in regulating the viral life cycle may be helpful in identifying treatments for HPV lesions. Mutations in genes of the Fanconi anemia (FA) DNA repair pathway lead to genomic instability in patients and a predisposition to HPV-associated malignancies. Our studies demonstrate that FA pathway component FANCD2 is recruited to HPV DNA, associates with members of the ATM DNA repair pathway, and is essential for the maintenance of viral episomes in basal

  19. 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...

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

    EPA Science Inventory

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

  1. 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. 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…

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

    SciTech Connect

    Not Available

    1983-07-01

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

  4. Nanomedicine boosts neurogenesis: new strategies for brain repair.

    PubMed

    Santos, Tiago; Maia, João; Agasse, Fabienne; Xapelli, Sara; Ferreira, Lino; Bernardino, Liliana

    2012-09-01

    The subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ) comprise two main germinal niches in the adult mammalian brain. Within these regions there are self-renewing and multipotent neural stem cells (NSCs) which can ultimately give rise to new neurons, astrocytes and oligodendrocytes. Understanding how to efficiently trigger NSCs differentiation is crucial to devise new cellular therapies aimed to repair the damaged brain. A large amount of data ranging from epigenetic alterations, chromatin remodelling and signalling pathways involved in NSCs differentiation are now within reach. Furthermore, a vast array of proteins and molecules have been described to modulate NSCs fate and tested in innovative therapeutic applications, however with little success so far. Nowadays, the main focus is on how to manipulate these factors to our full advantage. Unfortunately, concerns related to solubility, stability, concentration or spatial and temporal positioning can hinder their desirable effects. Biomaterials emerge as the ideal support to overcome these limitations and consequently boost NSCs differentiation towards desired phenotypes. However, the balance between biomaterials and differentiating factors must be well established, since the bioaccumulation and concomitant toxicity can be an undesired side-effect. Currently, innovative materials and formulations including more degradable carriers allow a controlled and efficient release of bioactive factors with minimal side-effects. Recently, micro- and nanoparticles have been successfully used to deliver molecules able to induce neurogenesis. This review presents recent research that highlights the role of both extracellular environmental factors as well as molecular remodelling mechanisms in the control of NSCs differentiation processes. Appropriate biomaterials that may trigger an efficient delivery of therapeutic molecules will be also discussed. Therefore, the interface between NSCs biology and tissue

  5. Strategies for Therapeutic Repair: The “R3” Regenerative Medicine Paradigm

    PubMed Central

    Nelson, Timothy J.; Behfar, Atta; Terzic, Andre

    2008-01-01

    Abstract Beyond the palliative reach of today, medical therapies of tomorrow aim to treat the root cause of chronic degenerative diseases. Therapeutic repair encompasses the converging triad of rejuvenation, regeneration or replacement strategies that rely on self‐healing processes, stem cell regeneration, and/or organ transplantation. Natural healing or rejuvenation exemplify inherent, baseline repair secured by tissue self‐renewal and de novo cell biogenesis, particularly effective in organs with a high endogenous reparative capacity. Transplant medicine exploits the replacement strategy as a valuable option to recycle used parts and restore failing organ function by means of exogenous substitutes—it is, however, limited by donor shortage. Stem cell‐based regeneration offers the next frontier of medical therapy through delivery of essentially unlimited pools of autologous or allogeneic, naive or modified, progenitor cells to achieve structural and functional repair. Translation into clinical applications requires the establishment of a regenerative medicine community of practice capable to bridge discovery with personalized treatment solutions. Indeed, this multidisciplinary specialized workforce will be capable to integrate the new science of embryology, immunology, and stem cell biology into bioinformatics and network medicine platforms, ensuring implementation of therapeutic repair strategies into individualized disease management algorithms. PMID:19756244

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

    ERIC Educational Resources Information Center

    Anderson, Karen

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Anderson, Karen

    2016-01-01

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

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

    PubMed

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

    2010-03-01

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

  9. 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

  10. 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

  11. 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

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

    PubMed

    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.

  13. Strategies to Improve Regeneration of the Soft Palate Muscles After Cleft Palate Repair

    PubMed Central

    Carvajal Monroy, Paola L.; Grefte, Sander; Kuijpers-Jagtman, Anne Marie; Wagener, Frank A.D.T.G.

    2012-01-01

    Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. These patients are unable to separate the nasal from the oral cavity leading to air loss during speech. Although surgical repair ameliorates soft palate function by joining the clefted muscles of the soft palate, optimal function is often not achieved. The regeneration of muscles in the soft palate after surgery is hampered because of (1) their low intrinsic regenerative capacity, (2) the muscle properties related to clefting, and (3) the development of fibrosis. Adjuvant strategies based on tissue engineering may improve the outcome after surgery by approaching these specific issues. Therefore, this review will discuss myogenesis in the noncleft and cleft palate, the characteristics of soft palate muscles, and the process of muscle regeneration. Finally, novel therapeutic strategies based on tissue engineering to improve soft palate function after surgical repair are presented. PMID:22697475

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

    PubMed Central

    Agarwal, Rachit; García, Andrés J.

    2015-01-01

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

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

    PubMed

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

    2012-12-01

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

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

    PubMed

    Agarwal, Rachit; García, Andrés J

    2015-11-01

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

  17. 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…

  18. 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…

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

    ERIC Educational Resources Information Center

    Liu, Jia

    2013-01-01

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

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

    PubMed

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

    2011-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. 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

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

    PubMed Central

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

    2014-01-01

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

  5. Resampling versus repair in evolution strategies applied to a constrained linear problem.

    PubMed

    Arnold, Dirk V

    2013-01-01

    We study the behaviour of multi-recombination evolution strategies for the problem of maximising a linear function with a single linear constraint. Two variants of the algorithm are considered: a strategy that resamples infeasible candidate solutions and one that applies a simple repair mechanism. Integral expressions that describe the strategies' one-generation behaviour are derived and used in a simple zeroth order model for the steady state attained when operating with constant step size. Applied to the analysis of cumulative step size adaptation, the approach provides an intuitive explanation for the qualitative difference in the algorithm variants' behaviour. The findings have implications for the design of constraint handling techniques to be used in connection with cumulative step size adaptation.

  6. Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial.

    PubMed

    Powell, Janet T; Sweeting, Michael J; Thompson, Matthew M; Ashleigh, Ray; Bell, Rachel; Gomes, Manuel; Greenhalgh, Roger M; Grieve, Richard; Heatley, Francine; Hinchliffe, Robert J; Thompson, Simon G; Ulug, Pinar

    2014-01-13

    To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. Randomised controlled trial. 30 vascular centres (29 UK, 1 Canadian), 2009-13. 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420; $1939) (95% confidence interval -£625 to £2997). A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. Current Controlled Trials ISRCTN48334791.

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

    PubMed

    2015-08-14

    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. 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). 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. ISRCTN 48334791. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  8. 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

  9. Evolutionarily distinct strategies for the acquisition of inorganic carbon from seawater in marine diatoms.

    PubMed

    Tsuji, Yoshinori; Mahardika, Anggara; Matsuda, Yusuke

    2017-06-01

    The acquisition of dissolved inorganic carbon (DIC) in CO2-limited seawater is a central issue to understand in marine primary production. We previously demonstrated the occurrence of direct HCO3- uptake by solute carrier (SLC) 4 transporters in a diatom, a major marine primary producer. Homologs of SLC are found in both centric and pennate marine diatoms, suggesting that SLC transporters are generally conserved. Here, the generality of SLC-mediated DIC uptake in diatoms was examined using an SLC inhibitor, diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), and an inhibitor of external carbonic anhydrase, acetazolamide. DIDS suppressed high-DIC-affinity photosynthesis in the pennate diatom Phaeodactylum tricornutum and the centric diatom Chaetoceros muelleri, but there was no effect on either the pennate Cylindrotheca fusiformis or the centric Thalassiosira pseudonana. Interestingly, the DIC affinity of DIDS-insensitive strains was sensitive to treatment with up to 100 μM acetazolamide, displaying a 2-4-fold increase in K0.5[DIC]. In contrast, acetazolamide did not affect the DIDS-sensitive group. These results indicate the occurrence of two distinct strategies for DIC uptake-one primarily facilitated by SLC and the other being passive CO2 entry facilitated by external carbonic anhydrase. The phylogenetic independence of these strategies suggests that environmental demands drove the evolution of distinct DIC uptake mechanisms in diatoms. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

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

    PubMed

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

    2015-09-01

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

  11. Strategies to develop endogenous stem cell-recruiting bioactive materials for tissue repair and regeneration.

    PubMed

    Pacelli, Settimio; Basu, Sayantani; Whitlow, Jonathan; Chakravarti, Aparna; Acosta, Francisca; Varshney, Arushi; Modaresi, Saman; Berkland, Cory; Paul, Arghya

    2017-07-19

    A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2011-01-01

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

  13. Landslide databases to compare regional repair and mitigation strategies of transportation infrastructure

    NASA Astrophysics Data System (ADS)

    Wohlers, Annika; Damm, Bodo

    2017-04-01

    Regional data of the Central German Uplands are extracted from the German landslide database in order to understand the complex interactions between landslide risks and public risk awareness considering transportation infrastructure. Most information within the database is gathered by means of archive studies from inventories of emergency agencies, state, press and web archives, company and department records as well as scientific and (geo)technical literature. The information includes land use practices, repair and mitigation measures with resultant costs of the German road network as well as railroad and waterway networks. It therefore contains valuable information of historical and current landslide impacts, elements at risk and provides an overview of spatiotemporal changes in social exposure and vulnerability to landslide hazards over the last 120 years. On a regional scale the recorded infrastructure damages, and consequential repair or mitigation measures were categorized and classified, according to relevant landslide types, processes and types of infrastructure. In a further step, the data of recent landslides are compared with historical and modern repair and mitigation measures and are correlated with socioeconomic concepts. As a result, it is possible to identify some complex interactions between landslide hazard, risk perception, and damage impact, including time lags and intensity thresholds. The data reveal distinct concepts of repairing respectively mitigating landslides on different types of transportation infrastructure, which are not exclusively linked to higher construction efforts (e.g. embankments on railroads and channels), but changing levels of economic losses and risk perception as well. In addition, a shift from low cost prevention measures such as the removal of loose rock and vegetation, rock blasting, and catch barriers towards expensive mitigation measures such as catch fences, soil anchoring and rock nailing over time can be noticed

  14. Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair

    PubMed Central

    Campalans, Anna; Kortulewski, Thierry; Amouroux, Rachel; Menoni, Hervé; Vermeulen, Wim; Radicella, J. Pablo

    2013-01-01

    Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected. PMID:23355608

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

    PubMed

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

    2016-12-19

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2010-01-01

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

  18. Convergent evolution of sexual dimorphism in skull shape using distinct developmental strategies.

    PubMed

    Sanger, Thomas J; Sherratt, Emma; McGlothlin, Joel W; Brodie, Edmund D; Losos, Jonathan B; Abzhanov, Arhat

    2013-08-01

    Studies integrating evolutionary and developmental analyses of morphological variation are of growing interest to biologists as they promise to shed fresh light on the mechanisms of morphological diversification. Sexually dimorphic traits tend to be incredibly divergent across taxa. Such diversification must arise through evolutionary modifications to sex differences during development. Nevertheless, few studies of dimorphism have attempted to synthesize evolutionary and developmental perspectives. Using geometric morphometric analysis of head shape for 50 Anolis species, we show that two clades have converged on extreme levels of sexual dimorphism through similar, male-specific changes in facial morphology. In both clades, males have evolved highly elongate faces whereas females retain faces of more moderate proportion. This convergence is accomplished using distinct developmental mechanisms; one clade evolved extreme dimorphism through the exaggeration of a widely shared, potentially ancestral, developmental strategy whereas the other clade evolved a novel developmental strategy not observed elsewhere in the genus. Together, our analyses indicate that both shared and derived features of development contribute to macroevolutionary patterns of morphological diversity among Anolis lizards. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  19. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Leininger, Elizabeth C; Kelley, Darcy B

    2013-04-07

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

  2. 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

  3. Distinct evolutionary strategies of human leucocyte antigen loci in pathogen-rich environments

    PubMed Central

    Sanchez-Mazas, Alicia; Lemaître, Jean-François; Currat, Mathias

    2012-01-01

    Human leucocyte antigen (HLA) loci have a complex evolution where both stochastic (e.g. genetic drift) and deterministic (natural selection) forces are involved. Owing to their extraordinary level of polymorphism, HLA genes are useful markers for reconstructing human settlement history. However, HLA variation often deviates significantly from neutral expectations towards an excess of genetic diversity. Because HLA molecules play a crucial role in immunity, this observation is generally explained by pathogen-driven-balancing selection (PDBS). In this study, we investigate the PDBS model by analysing HLA allelic diversity on a large database of 535 populations in relation to pathogen richness. Our results confirm that geographical distances are excellent predictors of HLA genetic differentiation worldwide. We also find a significant positive correlation between genetic diversity and pathogen richness at two HLA class I loci (HLA-A and -B), as predicted by PDBS, and a significant negative correlation at one HLA class II locus (HLA-DQB1). Although these effects are weak, as shown by a loss of significance when populations submitted to rapid genetic drift are removed from the analysis, the inverse relationship between genetic diversity and pathogen richness at different loci indicates that HLA genes have adopted distinct evolutionary strategies to provide immune protection in pathogen-rich environments. PMID:22312050

  4. A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines

    PubMed Central

    Aurich, Maike K.; Fleming, Ronan M. T.; Thiele, Ines

    2017-01-01

    The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models’ capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates. Interestingly, models based on metabolomic profiles of melanoma cells were distinguished from other models through their low oxygen uptake rates, which were associated with a glycolytic phenotype. A subset of the melanoma cell models required reductive carboxylation. The analysis of protein and RNA expression levels from the Human Protein Atlas showed that IDH2, which was an essential gene in the melanoma models, but not IDH1 protein, was detected in normal skin cell types and melanoma. Moreover, the von Hippel-Lindau tumor suppressor (VHL) protein, whose loss is associated with non-hypoxic HIF-stabilization, reductive carboxylation, and promotion of glycolysis, was uniformly absent in melanoma. Thus, the experimental data supported the predicted role of IDH2 and the absence of VHL protein supported the glycolytic and low oxygen phenotype predicted for melanoma. Taken together, our approach of integrating extracellular metabolomic data with metabolic modeling and the combination of different network interrogation methods allowed insights into the metabolism of cells. PMID:28806730

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

    PubMed

    Madry, Henning; Cucchiarini, Magali

    2014-10-01

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

  6. Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair

    PubMed Central

    Venkatesan, N.; Barré, L.; Benani, A.; Netter, P.; Magdalou, J.; Fournel-Gigleux, S.; Ouzzine, M.

    2004-01-01

    Osteoarthritis is a degenerative joint disease characterized by a progressive loss of articular cartilage components, mainly proteoglycans (PGs), leading to destruction of the tissue. We investigate a therapeutic strategy based on stimulation of PG synthesis by gene transfer of the glycosaminoglycan (GAG)-synthesizing enzyme, β1,3-glucuronosyltransferase-I (GlcAT-I) to promote cartilage repair. We previously reported that IL-1β down-regulated the expression and activity of GlcAT-I in primary rat chondrocytes. Here, by using antisense oligonucleotides, we demonstrate that GlcAT-I inhibition impaired PG synthesis and deposition in articular cartilage explants, emphasizing the crucial role of this enzyme in PG anabolism. Thus, primary chondrocytes and cartilage explants were engineered by lipid-mediated gene delivery to efficiently overexpress a human GlcAT-I cDNA. Interestingly, GlcAT-I overexpression significantly enhanced GAG synthesis and deposition as evidenced by 35S-sulfate incorporation, histology, estimation of GAG content, and fluorophore-assisted carbohydrate electrophoresis analysis. Metabolic labeling and Western blot analyses further suggested that GlcAT-I expression led to an increase in the abundance rather than in the length of GAG chains. Importantly, GlcAT-I delivery was able to overcome IL-1β-induced PG depletion and maintain the anabolic activity of chondrocytes. Moreover, GlcAT-I also restored PG synthesis to a normal level in cartilage explants previously depleted from endogenous PGs by IL-1β-treatment. In concert, our investigations strongly indicated that GlcAT-I was able to control and reverse articular cartilage defects in terms of PG anabolism and GAG content associated with IL-1β. This study provides a basis for a gene therapy approach to promote cartilage repair in degenerative joint diseases. PMID:15601778

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

    PubMed

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

    2014-07-01

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

  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. Strategies for the evaluation of DNA damage and repair mechanisms in cancer.

    PubMed

    Figueroa-González, Gabriela; Pérez-Plasencia, Carlos

    2017-06-01

    DNA lesions and the repair mechanisms that maintain the integrity of genomic DNA are important in preventing carcinogenesis and its progression. Notably, mutations in DNA repair mechanisms are associated with cancer predisposition syndromes. Additionally, these mechanisms maintain the genomic integrity of cancer cells. The majority of therapies established to treat cancer are genotoxic agents that induce DNA damage, promoting cancer cells to undergo apoptotic death. Effective methods currently exist to evaluate the diverse effects of genotoxic agents and the underlying molecular mechanisms that repair DNA lesions. The current study provides an overview of a number of methods that are available for the detection, analysis and quantification of underlying DNA repair mechanisms.

  10. Variation in Perfusion Strategies for Neonatal and Infant Aortic Arch Repair: Contemporary Practice in the STS Congenital Heart Surgery Database.

    PubMed

    Meyer, David B; Jacobs, Jeffrey P; Hill, Kevin; Wallace, Amelia S; Bateson, Brian; Jacobs, Marshall L

    2016-09-01

    Regional cerebral perfusion (RCP) is used as an adjunct or alternative to deep hypothermic circulatory arrest (DHCA) for neonates and infants undergoing aortic arch repair. Clinical studies have not demonstrated clear superiority of either strategy, and multicenter data regarding current use of these strategies are lacking. We sought to describe the variability in contemporary practice patterns for use of these techniques. The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2013) was queried to identify neonates and infants whose index operation involved aortic arch repair with cardiopulmonary bypass. Perfusion strategy was classified as isolated DHCA, RCP (with less than or equal to ten minutes of DHCA), or mixed (RCP with more than ten minutes of DHCA). Data were analyzed for the entire cohort and stratified by operation subgroups. Overall, 4,523 patients (105 centers) were identified; median age seven days (interquartile range: 5.0-13.0). The most prevalent perfusion strategy was RCP (43%). Deep hypothermic circulatory arrest and mixed perfusion accounted for 32% and 16% of cases, respectively. In all, 59% of operations involved some period of RCP. Regional cerebral perfusion was the most prevalent perfusion strategy for each operation subgroup. Neither age nor weight was associated with perfusion strategy, but reoperations were less likely to use RCP (31% vs 45%, P < .001). The combined duration of RCP and DHCA in the RCP group was longer than the DHCA time in the DHCA group (45 vs 36 minutes, P < .001). There is considerable variability in practice regarding perfusion strategies for arch repair in neonates and infants. In contemporary practice, RCP is the most prevalent perfusion strategy for these procedures. Use of DHCA is also common. Further investigation is warranted to ascertain possible relative merits of the various perfusion techniques. © The Author(s) 2016.

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    PubMed Central

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

    2016-01-01

    One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent 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 fully 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

  13. Right ventricular outflow tract strategies for repair of tetralogy of Fallot: effect of monocusp valve reconstruction.

    PubMed

    Sasson, Lior; Houri, Sion; Raucher Sternfeld, Alona; Cohen, Ilan; Lenczner, Orit; Bove, Edward L; Kapusta, Livia; Tamir, Akiva

    2013-04-01

    The absence of a pulmonary valve (PV) after tetralogy of Fallot (TOF) repair has been shown to impact postoperative right ventricular (RV) function. The purposes of this study were to (i) compare early outcomes after PV-sparing vs transannular patching (TAP) with monocusp valve reconstruction or TAP alone and (b) assess the mid-term results after polytetrafluoroethylene (PTFE) membrane monocusp reconstruction. From 2003 to 2009, 163 patients underwent TOF repair. Sixty-nine patients (42.3%) underwent a PV-sparing procedure (Group A), 74 (45.4%) underwent PTFE membrane monocusp valve reconstruction (Group B) and 20 (12.3%) underwent TAP only (Group C). Early outcomes were evaluated by the right-to-left ventricular pressure ratio, RV outflow tract gradient, tricuspid and PV function, intensive care unit (ICU) parameters and need for reintervention. Group B patients were also evaluated at intermediate term for clinical and echocardiographic parameters, including tricuspid and monocusp valve function and mobility. The median age, weight and PV Z-value of Group B patients were significantly lower; 20.5 months, 9.3 kg and -4, respectively. Postoperatively, the right-to-left ventricular pressure ratio was <0.5 in all groups. Mechanical ventilation time, fluid drainage duration and total ICU stay showed no significant difference between Groups A and B, while Group C was significantly longer (P < 0.01). There were five (3%) early deaths: three from Group A and two from Group B. The incidences of moderate or severe pulmonary insufficiency (PI) on discharge were 8.2% in Group A, 9% in Group B and 50% in Group C (P < 0.001). Among Group B patients, 85% of the evaluated patients had less than moderate PI in the intermediate-term follow-up, QRS duration <140 ms in 83.3% and right-to-left ventricular diameter ratio of 0.6 ± 0.2. Two (2.6%) patients underwent reoperation for monocusp replacement. There were two (2.7%) mid-term deaths. The use of a PTFE membrane monocusp valve and

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

    PubMed

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

    2012-01-01

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

  15. Distinctive Hemodynamics in the Immediate Postoperative Period of Patients with a Longer Cardiac Intensive Care Stay Post-Tetralogy of Fallot Repair.

    PubMed

    Beg, Kisha A; Haq, Anwarul; Amanullah, Muneer; Laique, Sobia N; Sadqani, Saleem; Aslam, Nadeem; Rehmat, Amina Wali; Hasan, Babar S

    2015-01-01

    After complete surgical repair the majority of tetralogy of Fallot (ToF), patients stay ≤2 days in the Cardiac Intensive Care Unit (CICU) while some may stay longer. We undertook this study to investigate the factors associated with shorter vs. longer length of stay in the CICU to help manage resources effectively. Patients who underwent ToF repair at Aga Khan University, Pakistan, between July 2006 and December 2011 were studied in a case-control design. Clinical parameters were compared between short stay group (SSG) (≤2 days) and long stay group (LSG) (>2 days). Odds ratios were calculated, and regression was performed. Ninety-eight patients (LSG 65, SSG 33) were included. Patients with lower preoperative saturation were 2.67 times more likely to be in the LSG group (P = .02). At 4 hours postoperatively, patients with a higher inotropic score (odds ratio [OR] = 3.03, confidence interval [CI] = 1.19-7.7, P = .02), higher central venous pressure (OR = 3.04, CI = 1.27-7.32, P = .013), and significant tachycardia at 4 hours (OR = 3.5, CI = 1.19-10.3. P = .02) were at risk for having a prolonged CICU stay. On multivariate analysis, significant postoperative tachycardia at 4 hours (z-score ≥3) was highly specific (sensitivity = 38.5%, specificity = 84.9%) for predicting the chances of being in the LSG. Other predictors included preop O(2) saturation ≤82.5% (sensitivity = 61.1%, specificity = 63.0%) and CVP ≥10 mm Hg at 4 hours (sensitivity = 55.4%, specificity = 71.9%). Patients who end up staying longer in the CICU have features that are distinctive in the immediate postoperative period, and this can help clinicians in identifying patients who may need more support. © 2015 Wiley Periodicals, Inc.

  16. 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

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

    PubMed

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

    2012-04-01

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

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

    EPA Science Inventory

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

  19. 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...

  20. Elective laparoscopic repair after reduction might be useful strategy for incarcerated obturator hernia: a case report.

    PubMed

    Kohga, Atsushi; Kawabe, Akihiro; Cao, Yuchen; Yajima, Kiyoshige; Okumura, Takuya; Yamashita, Kimihiro; Isogaki, Jun; Suzuki, Kenji

    2017-09-01

    Obturator hernia is a rare clinical condition that causes intestinal obstruction. Recent reports have suggested that laparoscopic repair may be useful for incarcerated obturator hernia in select patients. The patient was a 64-year-old female who presented to our emergency department with a chief complaint of abdominal pain. Computed tomography (CT) imaging revealed an incarcerated obturator hernia on her right side, without apparent findings of irreversible ischaemic change or perforation. She had a previous history of cardiovascular surgery and was taking an anticoagulant medication. We performed a reduction of the incarcerated intestine. After heparin displacement, laparoscopic repair was electively performed. During laparoscopy, an occult obturator hernia was found on the left side. We repaired the bilateral obturator hernia using a mesh prosthesis. Elective laparoscopic repair after reduction might be a useful procedure for incarcerated obturator hernias in those patients without findings of irreversible ischaemic change or perforation.

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

    PubMed

    Somech, Anit; Drach-Zahavy, Anat

    2007-01-01

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

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

    PubMed

    Purcell, Braden A; Kiani, Roozbeh

    2016-08-02

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

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

    PubMed Central

    Purcell, Braden A.; Kiani, Roozbeh

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Franquet, John-Edward

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

  5. A new intercostal artery management strategy for thoracoabdominal aortic aneurysm repair.

    PubMed

    Mell, Matthew W; Wynn, Martha M; Reeder, Scott B; Tefera, Girma; Hoch, John R; Acher, Charles W

    2009-06-01

    The purpose of this study is to describe a new approach for addressing the intraoperative management of intercostal arteries during thoracoabdominal aortic aneurysm (TAAA) repair, using preoperative spinal MRA for detection of intercostal arteries supplying the anterior spinal artery. Patients undergoing TAAA repair from August 2005 to September 2007 were included. Spinal artery MRA was performed to identify the anterior spinal artery, the artery of Adamkiewicz, and its major intercostal source artery (SA-AAK). Intraoperative spinal cord protection was carried out using standard techniques. Important intercostal arteries were either preserved or reimplanted as a button patch after removing aortic clamps. Demographic and perioperative data were collected for review. Analysis was performed with Fisher's exact test or Student's t-test, where applicable, using SAS ver. 8.0 (Cary, NC). Spinal artery MRA was performed in 27 patients. The SA-AAK was identified in 85% of preoperative studies. Open or endovascular repair was performed in 74% and 26% of patients, respectively. The SA-AAK was preserved or reimplanted in 13 (65%) of patients who underwent open repair. A mean of 1.67 (range 1-3) intercostal arteries were reimplanted. All patients undergoing endovascular repair necessitated coverage of the SA-AAK. No patient developed immediate or delayed paraplegia. Longer mean operative times in the reimplanted cohort were not statistically significant (330 versus 245 min, P = 0.1). The SA-AAK identified by MRA can be preserved or safely reimplanted after TAAA repair. Further study is warranted to determine if selective intercostal reimplantation can reduce the risk of immediate or delayed paraplegia.

  6. 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…

  7. 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

  8. 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;…

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

    ERIC Educational Resources Information Center

    Pitts, Jim; And Others

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

  10. 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;…

  11. 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…

  12. 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;…

  13. 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;…

  14. 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;…

  15. 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;…

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

    PubMed

    Mielecki, Damian; Grzesiuk, Elżbieta

    2014-06-01

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

  17. Nitrogen use strategies of seedlings from neotropical tree species of distinct successional groups.

    PubMed

    Oliveira, Halley Caixeta; da Silva, Ligia Maria Inocêncio; de Freitas, Letícia Dias; Debiasi, Tatiane Viegas; Marchiori, Nidia Mara; Aidar, Marcos Pereira Marinho; Bianchini, Edmilson; Pimenta, José Antonio; Stolf-Moreira, Renata

    2017-05-01

    Few studies have analyzed the strategies of neotropical tree seedlings for absorbing, translocating and assimilating the nitrogen. Here, we compared the nitrogen use strategies of seedlings from six tree species that are native to the Brazilian Atlantic Forest and that belong to different successional groups: Trema micrantha, Heliocarpus popayanensis and Cecropia pachystachya (pioneers), Cariniana estrellensis, Eugenia brasiliensis and Guarea kunthiana (non-pioneers). The effects of cultivating seedlings with nitrate or ammonium on the growth, physiology and nitrogen metabolism were analyzed. Nitrate-grown pioneer species had much higher leaf nitrate reductase activity than non-pioneer ones, but non-pioneer seedlings were also able to use nitrate as a nitrogen source. In addition to this remarkable difference between the groups in the capacity for leaf nitrate assimilation, substantial variations in the nitrogen use strategies were observed within the successional classes. Differently from the other non-pioneers, the canopy species C. estrellensis seemed to assimilate nitrate mainly in the leaves. Morphophysiological analyses showed a gradient of ammonium toxicity response, with E. brasiliensis as the most tolerant species, and T. micrantha and H. popayanensis as the most sensitive ones. Guarea kunthiana showed a relatively low tolerance to ammonium and an unusual high translocation of this cation in the xylem sap. In contrast to the other pioneers, C. pachystachya had a high plasticity in the use of nitrogen sources. Overall, these results suggest that nitrogen use strategies of neotropical tree seedlings were not determined solely by their successional position. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Preserving the pulmonary valve during early repair of tetralogy of Fallot: Anatomic substrates and surgical strategies.

    PubMed

    Vida, Vladimiro L; Angelini, Annalisa; Guariento, Alvise; Frescura, Carla; Fedrigo, Marni; Padalino, Massimo; Sanders, Stephen P; Thiene, Gaetano; Stellin, Giovanni

    2015-05-01

    To describe the anatomy of the PV in tetralogy of Fallot (TOF) and to define the influence of PV anatomy on the development of surgical techniques for PV preservation during early repair. The PV was evaluated in 79 anatomic specimens of patients with TOF who had not undergone surgery for repair, and in 82 patients who underwent early TOF repair at our institution. New surgical techniques for PV preservation during early repair are described. The PV in TOF was predominantly bicuspid (n = 118 of 160; 73.7%), less frequently tricuspid (n = 28 of 160; 17.5%), and seldom unicuspid (n = 14 of 160; 8.8%). In 82 cases (51.3%), the PV cusps were normal; in 78 cases (48.7%), they were thickened and dysplastic. Preservation of the PV was possible in 46 of 82 (56%) consecutive patients during TOF repair in our more recent experience, either using balloon dilation alone (18 of 46; 39%) or in association with other PV plasty procedures (28 of 46; 61%). Most bicuspid and tricuspid valves were salvageable, but unicuspid valves were not suitable. After a median follow-up time of 2.8 years (range, 0.5-6.8 years), the degree of PV regurgitation continued to be zero or mild in 40 patients (86%), and moderate in 6 (14%). The majority of patients with TOF (>90%) have a bicuspid or tricuspid PV, which is the most favorable surgical anatomy for preserving the PV, independent of the degree of leaflet dysplasia. The recent introduction of more-complex PV plasty techniques, such as delamination plasty, allowed us to further extend the applicability of PV-preservation techniques. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status.

    PubMed

    Oliveira, Carla; Westra, Jantine L; Arango, Diego; Ollikainen, Miina; Domingo, Enric; Ferreira, Ana; Velho, Sérgia; Niessen, Renee; Lagerstedt, Kristina; Alhopuro, Pia; Laiho, Paivi; Veiga, Isabel; Teixeira, Manuel R; Ligtenberg, Marjolijn; Kleibeuker, Jan H; Sijmons, Rolf H; Plukker, John T; Imai, Kohzoh; Lage, Pedro; Hamelin, Richard; Albuquerque, Cristina; Schwartz, Simo; Lindblom, Annika; Peltomaki, Päivi; Yamamoto, Hiroyuki; Aaltonen, Lauri A; Seruca, Raquel; Hofstra, Robert M W

    2004-10-01

    In sporadic colorectal tumours the BRAFV600E is associated with microsatellite instability (MSI-H) and inversely associated to KRAS mutations. Tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients carrying germline mutations in hMSH2 or hMLH1 do not show BRAFV600E, however no consistent data exist regarding KRAS mutation frequency and spectrum in HNPCC tumours. We investigated KRAS in 158 HNPCC tumours from patients with germline hMLH1, hMSH2 or hMSH6 mutations, 166 MSI-H and 688 microsatellite stable (MSS) sporadic carcinomas. All tumours were characterized for MSI and 81 of 166 sporadic MSI-H colorectal cancer (CRCs) were analysed for hMLH1 promoter hypermethylation. KRAS mutations were observed in 40% of HNPCC tumours, and the mutation frequency varied upon the mismatch repair gene affected: 48% (29/61) in hMSH2, 32% (29/91) in hMLH1 and 83% (5/6) in hMSH6 (P = 0.01). KRAS mutation frequency was different between HNPCC, MSS and MSI-H CRCs (P = 0.002), and MSI-H with hMLH1 hypermethylation (P = 0.005). Furthermore, HNPCC CRCs had more G13D mutations than MSS (P < 0.0001), MSI-H (P = 0.02) or MSI-H tumours with hMLH1 hypermethylation (P = 0.03). HNPCC colorectal and sporadic MSI-H tumours without hMLH1 hypermethylation shared similar KRAS mutation frequency, in particular G13D. In conclusion, we show that depending on the genetic/epigenetic mechanism leading to MSI-H, the outcome in terms of oncogenic activation may be different, reinforcing the idea that HNPCC, sporadic MSI-H (depending on the hMLH1 status) and MSS CRCs, may target distinct kinases within the RAS/RAF/MAPK pathway.

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

    PubMed Central

    Ernebjerg, Morten

    2012-01-01

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

  1. Evolving the selfish herd: emergence of distinct aggregating strategies in an individual-based model.

    PubMed

    Wood, Andrew J; Ackland, Graeme J

    2007-07-07

    From zebra to starlings, herring and even tadpoles, many creatures move in an organized group. The emergent behaviour arises from simple underlying movement rules, but the evolutionary pressure which favours these rules has not been conclusively identified. Various explanations exist for the advantage to the individual of group formation: reduction of predation risk; increased foraging efficiency or reproductive success. Here, we adopt an individual-based model for group formation and subject it to simulated predation and foraging; the haploid individuals evolve via a genetic algorithm based on their relative success under such pressure. Our work suggests that flock or herd formation is likely to be driven by predator avoidance. Individual fitness in the model is strongly dependent on the presence of other phenotypes, such that two distinct types of evolved group can be produced by the same predation or foraging conditions, each stable against individual mutation. We draw analogies with multiple Nash equilibria theory of iterated games to explain and categorize these behaviours. Our model is sufficient to capture the complex behaviour of dynamic collective groups, yet is flexible enough to manifest evolutionary behaviour.

  2. Distinct polyadenylation landscapes of diverse human tissues revealed by a modified PA-seq strategy

    PubMed Central

    2013-01-01

    Background Polyadenylation is a key regulatory step in eukaryotic gene expression and one of the major contributors of transcriptome diversity. Aberrant polyadenylation often associates with expression defects and leads to human diseases. Results To better understand global polyadenylation regulation, we have developed a polyadenylation sequencing (PA-seq) approach. By profiling polyadenylation events in 13 human tissues, we found that alternative cleavage and polyadenylation (APA) is prevalent in both protein-coding and noncoding genes. In addition, APA usage, similar to gene expression profiling, exhibits tissue-specific signatures and is sufficient for determining tissue origin. A 3′ untranslated region shortening index (USI) was further developed for genes with tandem APA sites. Strikingly, the results showed that different tissues exhibit distinct patterns of shortening and/or lengthening of 3′ untranslated regions, suggesting the intimate involvement of APA in establishing tissue or cell identity. Conclusions This study provides a comprehensive resource to uncover regulated polyadenylation events in human tissues and to characterize the underlying regulatory mechanism. PMID:24025092

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. An alternative cardiopulmonary bypass strategy for intracaval baffle repair of scimitar syndrome.

    PubMed

    Federici, Duccio; Montesi, Gianfranco; Ghitti, Davide; Galletti, Lorenzo

    2017-06-01

    Intracaval buffle repair of scimitar syndrome is classically performed under deep hypothermic circulatory arrest or using low-flow modalities of cardiopulmonary bypass with peripheral cannulation. We propose an alternative perfusion approach to the procedure using total intrapericardial cannulation under full-flow normothermic cardiopulmonary bypass. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. New strategies for CNS injury and repair using stem cells, nanomedicine, neurotrophic factors and novel neuroprotective agents.

    PubMed

    Sharma, Hari Shanker; Sharma, Aruna

    2011-08-01

    The 8th Annual Conference of the Global College of Neuroprotection and Neuroregeneration (GCNN) was global in the true sense of the word as it was held beyond European boundaries for the first time in the beautiful ambience of the ancient and modern environment of the Hashemite Kingdom of Jordan on 27-30 April 2011. The meeting was organized together with the 4th International Association of Neurorestoratology (IANR; Beijing, China) and the 11th meeting of the American Society for Neural Therapy and Repair (ASNTR; FL, USA). The first joint meeting was extremely successful and attracted more than 600 delegates including top experts, research students and educators from industry, academia, research organizations, universities and medical representatives from across the globe. The focal theme of this meeting was 'Exploring new strategies for neuroregenerative therapy for CNS injury and repair'. The Jordanian Association of Orthopedic Surgeons chaired by Ziad Al Zoubi served as the local host. HRH Princess Basma Bint Talal of Jordan inaugurated the congress. The salient new discoveries and recommendations for future strategies discussed during the meeting are summarized in this article.

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

    PubMed

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

    2014-07-01

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

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

    PubMed

    Russo, Jacqueline; Madec, Luc

    2013-01-01

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2014-03-14

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

  12. 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

  13. Molecular distinction between physiological and pathological cardiac hypertrophy: experimental findings and therapeutic strategies.

    PubMed

    Bernardo, Bianca C; Weeks, Kate L; Pretorius, Lynette; McMullen, Julie R

    2010-10-01

    Cardiac hypertrophy can be defined as an increase in heart mass. Pathological cardiac hypertrophy (heart growth that occurs in settings of disease, e.g. hypertension) is a key risk factor for heart failure. Pathological hypertrophy is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. In contrast, physiological cardiac hypertrophy (heart growth that occurs in response to chronic exercise training, i.e. the 'athlete's heart') is reversible and is characterized by normal cardiac morphology (i.e. no fibrosis or apoptosis) and normal or enhanced cardiac function. Given that there are clear functional, structural, metabolic and molecular differences between pathological and physiological hypertrophy, a key question in cardiovascular medicine is whether mechanisms responsible for enhancing function of the athlete's heart can be exploited to benefit patients with pathological hypertrophy and heart failure. This review summarizes key experimental findings that have contributed to our understanding of pathological and physiological heart growth. In particular, we focus on signaling pathways that play a causal role in the development of pathological and physiological hypertrophy. We discuss molecular mechanisms associated with features of cardiac hypertrophy, including protein synthesis, sarcomeric organization, fibrosis, cell death and energy metabolism and provide a summary of profiling studies that have examined genes, microRNAs and proteins that are differentially expressed in models of pathological and physiological hypertrophy. How gender and sex hormones affect cardiac hypertrophy is also discussed. Finally, we explore how knowledge of molecular mechanisms underlying pathological and physiological hypertrophy may influence therapeutic strategies for the treatment of cardiovascular disease and heart failure. 2010 Elsevier Inc. All rights reserved.

  14. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Prado, Félix

    2014-05-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

  18. 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.

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

    Hartman, P S; Eisenstark, A

    1978-01-01

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

  1. 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. Published by Elsevier Ireland Ltd.

  2. 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

  3. The impact of surgical strategy on survival after repair of type A aortic dissection.

    PubMed

    Lawton, Jennifer S; Liu, Jingxia; Kulshrestha, Kevin; Moon, Marc R; Damiano, Ralph J; Maniar, Hersh; Pasque, Michael K

    2015-08-01

    A diverse group of operative strategies are utilized for treatment of acute Stanford type A aortic dissection. We hypothesized that a surgical strategy to prevent cross-clamp injury or false lumen pressurization would be associated with reduced morbidity, mortality, persistent false lumen patency, and improved survival. This study was designed to determine the differences in outcomes between operative techniques. Outcomes and postoperative imaging were compared in patients who underwent surgery for acute type A aortic dissection. Two groups were compared, based on operative strategy. The surgical strategy for group 1 consisted of no aortic cross-clamp use, use of deep hypothermic circulatory arrest, and use of only antegrade perfusion after aortic replacement. The surgical strategy for group 2 consisted of any other combination that lacked 1 of these 3 technical steps. Between January 1, 1996, and December 31, 2012, a total of 196 patients underwent surgery for acute type A aortic dissection. Operative mortality and postoperative morbidity were not statistically different between groups. Mean follow-up time was 3.95 (range: 0-15.4) years. Persistence of a false lumen was not statistically different between groups (P = .78). Overall survival was significantly better in group 1, versus group 2 (P = .0020). Multivariate Cox regression identified preoperative renal failure, chronic lung disease, greater number of packed red blood cells transfused, and being in group 2 as risk factors for poor long-term survival. The operative strategy of group 1 (no cross-clamp, use of DHCA and antegrade perfusion) was associated with a highly significant improvement in survival, despite a lack of statistical difference in the incidence of persistent false aortic lumen between groups. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. 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.

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

    DTIC Science & Technology

    2015-02-01

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

  7. Meningocele repair

    MedlinePlus

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

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

    PubMed

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

    2014-02-18

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

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

    PubMed

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

    2014-10-31

    High linear energy transfer (LET) radiation from space heavy charged particles or a heavier ion radiotherapy machine kills more cells than low LET radiation, mainly because high LET radiation-induced DNA damage is more difficult to repair. Relative biological effectiveness (RBE) is the ratio of the effects generated by high LET radiation to low LET radiation. Previously, our group and others demonstrated that the cell-killing RBE is involved in the interference of high LET radiation with non-homologous end joining but not homologous recombination repair. This effect is attributable, in part, to the small DNA fragments (≤40 bp) directly produced by high LET radiation, the size of which prevents Ku protein from efficiently binding to the two ends of one fragment at the same time, thereby reducing non-homologous end joining efficiency. Here we demonstrate that Ape1, an enzyme required for processing apurinic/apyrimidinic (known as abasic) sites, is also involved in the generation of small DNA fragments during the repair of high LET radiation-induced base damage, which contributes to the higher RBE of high LET radiation-induced cell killing. This discovery opens a new direction to develop approaches for either protecting astronauts from exposure to space radiation or benefiting cancer patients by sensitizing tumor cells to high LET radiotherapy. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. 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

  11. 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

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

    PubMed

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

    2008-01-22

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

  13. 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.

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

    PubMed

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

    2012-01-01

    The Photosystem (PS) II of cyanobacteria, green algae and higher plants is prone to light-induced inactivation, the D1 protein being the primary target of such damage. As a consequence, the D1 protein, encoded by the psbA gene, is degraded and re-synthesized in a multistep process called PSII repair cycle. In cyanobacteria, a small gene family codes for the various, functionally distinct D1 isoforms. In these organisms, the regulation of the psbA gene expression occurs mainly at the level of transcription, but the expression is fine-tuned by regulation of translation elongation. In plants and green algae, the D1 protein is encoded by a single psbA gene located in the chloroplast genome. In chloroplasts of Chlamydomonas reinhardtii the psbA gene expression is strongly regulated by mRNA processing, and particularly at the level of translation initiation. In chloroplasts of higher plants, translation elongation is the prevalent mechanism for regulation of the psbA gene expression. The pre-existing pool of psbA transcripts forms translation initiation complexes in plant chloroplasts even in darkness, while the D1 synthesis can be completed only in the light. Replacement of damaged D1 protein requires also the assistance by a number of auxiliary proteins, which are encoded by the nuclear genome in green algae and higher plants. Nevertheless, many of these chaperones are conserved between prokaryotes and eukaryotes. Here, we describe the specific features and fundamental differences of the psbA gene expression and the regeneration of the PSII reaction center protein D1 in cyanobacteria, green algae and higher plants. This article is part of a Special Issue entitled Photosystem II. © 2011 Elsevier B.V. All rights reserved.

  15. 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.

  16. 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.

  17. 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.

  18. Neural Architecture of Selective Stopping Strategies: Distinct Brain Activity Patterns Are Associated with Attentional Capture But Not with Outright Stopping.

    PubMed

    Sebastian, Alexandra; Rössler, Kora; Wibral, Michael; Mobascher, Arian; Lieb, Klaus; Jung, Patrick; Tüscher, Oliver

    2017-10-04

    In stimulus-selective stop-signal tasks, the salient stop signal needs attentional processing before genuine response inhibition is completed. Differential prefrontal involvement in attentional capture and response inhibition has been linked to the right inferior frontal junction (IFJ) and ventrolateral prefrontal cortex (VLPFC), respectively. Recently, it has been suggested that stimulus-selective stopping may be accomplished by the following different strategies: individuals may selectively inhibit their response only upon detecting a stop signal (independent discriminate then stop strategy) or unselectively whenever detecting a stop or attentional capture signal (stop then discriminate strategy). Alternatively, the discrimination process of the critical signal (stop vs attentional capture signal) may interact with the go process (dependent discriminate then stop strategy). Those different strategies might differentially involve attention- and stopping-related processes that might be implemented by divergent neural networks. This should lead to divergent activation patterns and, if disregarded, interfere with analyses in neuroimaging studies. To clarify this crucial issue, we studied 87 human participants of both sexes during a stimulus-selective stop-signal task and performed strategy-dependent functional magnetic resonance imaging analyses. We found that, regardless of the strategy applied, outright stopping displayed indistinguishable brain activation patterns. However, during attentional capture different strategies resulted in divergent neural activation patterns with variable activation of right IFJ and bilateral VLPFC. In conclusion, the neural network involved in outright stopping is ubiquitous and independent of strategy, while different strategies impact on attention-related processes and underlying neural network usage. Strategic differences should therefore be taken into account particularly when studying attention-related processes in stimulus

  19. Neuroprotective Strategies Can Prevent Permanent Paraplegia in the Majority of Patients Who Develop Spinal Cord Ischaemia After Endovascular Repair of Thoracoabdominal Aortic Aneurysms.

    PubMed

    Rossi, S H; Patel, A; Saha, P; Gwozdz, A; Salter, R; Gkoutzios, P; Carrell, T; Abisi, S; Modarai, B

    2015-11-01

    Spinal cord ischaemia (SCI) following endovascular thoracoabdominal aortic aneurysm (TAAA) repair is a devastating and unpredictable complication. This study describes a single unit's experience of SCI in patients who have had endovascular TAAA repair. A prospectively maintained database of patients having endovascular TAAA repair using branched and fenestrated stent grafts between 2008 and 2014 at a single high volume centre was reviewed. Patients who developed neurological symptoms and signs related to SCI were identified and factors associated with onset and recovery of neurology were analysed. Sixty-nine patients (median age 73 years, 52 male; Crawford classification type I [n = 4], type II [n = 11], type III [n = 33], type IV [n = 14], type V [n = 7]) underwent endovascular TAAA repair. Twelve patients developed neurological symptoms/signs related to SCI but this was successfully reversed in eight patients, leaving four (5.8%) with permanent paraplegia. The median length of aorta covered was not significantly different in the 12 patients who developed SCI compared with the cohort that did not. Eleven of the patients who developed SCI had an intraoperative mean arterial pressure (MAP) below 80 mmHg. Cutaneous atheroemboli were noted in half of the patients in the SCI group compared with 11% of the non-SCI group (p < .05). Strategies used to reverse SCI included raising MAP, cerebrospinal fluid drainage, angioplasty of stenosed internal iliac arteries, and restoring perfusion to the aneurysm sac. This series highlights some of the risk factors associated with the development of SCI after endovascular repair of TAAAs. It also illustrates the importance of a dedicated institutional protocol aimed at ensuring the early diagnosis of SCI and prompt intervention to reverse permanent paraplegia in the majority of cases. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  20. 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.

  1. Defining the acute kidney injury and repair transcriptome.

    PubMed

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

    2014-07-01

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

  2. Network repair based on community structure

    NASA Astrophysics Data System (ADS)

    Wang, Tianyu; Zhang, Jun; Sun, Xiaoqian; Wandelt, Sebastian

    2017-06-01

    Real-world complex systems are often fragile under disruptions. Accordingly, research on network repair has been studied intensively. Recently proposed efficient strategies for network disruption, based on collective influence, call for more research on efficient network repair strategies. Existing strategies are often designed to repair networks with local information only. However, the absence of global information impedes the creation of efficient repairs. Motivated by this limitation, we propose a concept of community-level repair, which leverages the community structure of the network during the repair process. Moreover, we devise a general framework of network repair, with in total six instances. Evaluations on real-world and random networks show the effectiveness and efficiency of the community-level repair approaches, compared to local and random repairs. Our study contributes to a better understanding of repair processes, and reveals that exploitation of the community structure improves the repair process on a disrupted network significantly.

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

    PubMed Central

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

    2013-01-01

    The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution. Sequence divergence of paralogous proteins accounts for functional specialization, promoting axial morphological diversification in bilaterian animals. Yet functionally specialized paralogous Hox proteins also continue performing ancient common functions. In this study, we investigate how highly divergent Hox proteins perform an identical function. This was achieved by comparing in Drosophila the mode of limb suppression by the central (Ultrabithorax and AbdominalA) and posterior class (AbdominalB) Hox proteins. Results highlight that Hox-mediated limb suppression relies on distinct modes of DNA binding and a distinct use of TALE cofactors. Control of common functions by divergent Hox proteins, at least in the case studied, relies on evolving novel molecular properties. Thus, changes in protein sequences not only provide the driving force for functional specialization of Hox paralogue proteins, but also provide means to perform common ancient functions in distinct ways. PMID:23505377

  4. 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

  5. Exploiting Synthetic Lethal Relationships: Chemical Inhibition of Recombinational Repair as a Strategy to Selectively Target Tumor Cells

    DTIC Science & Technology

    2011-03-01

    14. ABSTRACT Homologous recombination is a key cellular pathway to repair or tolerate complex DNA damage such as DNA double-stranded breaks...interstrand DNA crosslinks, or single-stranded DNA gaps. In addition, homologous recombination is required for the recovery of stalled or broken...interstrand crosslinkers) agents as principal modalities in anti-tumor therapy. The importance of the homologous recombination pathway for breast cancer

  6. Issues in the repair of x-ray masks

    NASA Astrophysics Data System (ADS)

    Stewart, Diane K.; Doherty, John A.

    1991-03-01

    Although full implementation of x-ray lithography as a production technology remains a few years in the future, there are now many world wide efforts to accelerate this introduction. Unlike other more common lithographic techniques, such as image projection, x-rya lithography requires the fabrication of a mask with a thick absorber to efficiently block the X-rays. This important distinction from the reticles used in wafer steppers requires a completely new approach to many of the techniques of mask making, including inspection and repairs. Focused ion beam systems have been suggested as a possible repair strategy, and a number of groups have utilized the inherent advantages of FIB methods to repair X-ray masks in the laboratory. Although FIB systems have achieve substantial acceptance in the photomask making community for repair of chrome masks and reticles, a simple reapplication of these systems to repair of X-ray masks will not produce the quality levels required in X- ray lithography. The purpose of this paper will be to review the primary technical problems in the repair of X-ray masks and to discuss the implications of these requirements on the design of an FIB system. The current state-of-the-art in X-ray mask repair will be reviewed and some unique results will be presented.

  7. 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.

  8. New diagnostic criteria and operative strategy for cesarean scar syndrome: Endoscopic repair for secondary infertility caused by cesarean scar defect.

    PubMed

    Tanimura, Satoshi; Funamoto, Hiroshi; Hosono, Takashi; Shitano, Yasushi; Nakashima, Masao; Ametani, Yuka; Nakano, Takashi

    2015-09-01

    The aim of the present study was to assess the efficacy of endoscopic repair for secondary infertility caused by post-cesarean scar defect (PCSD). Our investigation focused on the validity of new diagnostic criteria and selection methods. The subjects were 22 women with secondary infertility due to PCSD with retention of bloody fluid in the uterine cavity. Women with a residual myometrial thickness of ≥ 2.5 mm and an anteflexed or straight uterus underwent hysteroscopic surgery, while all others underwent laparoscopic repair. Hysteroscopic surgery involved resection and coagulation of scarred areas, whereas laparoscopic surgery involved removal of scarred areas combined with hysteroscopy, followed by resuturing. Fourteen of the 22 women (63.6%) who were followed up for ≥ 1 year after surgery achieved pregnancy. Pregnancies occurred in all four women (100%) who underwent hysteroscopic surgery and in 10 of the 18 women (55.6%) who underwent laparoscopic surgery. Three out of four women who underwent hysteroscopic surgery had term deliveries. Among the women who underwent laparoscopic surgery, five had term deliveries. No cases of uterine rupture were experienced, and the delivery method was cesarean section in all cases. We propose that infertility associated with PCSD, cesarean scar syndrome, is caused by the retention of bloody fluid in the uterine cavity and scarring. Endoscopic treatment, such as hysteroscopy or laparoscopy, was effective for cesarean scar syndrome. © 2015 Japan Society of Obstetrics and Gynecology.

  9. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. 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

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

    PubMed

    Hershberg, Uri; Shlomchik, Mark J

    2006-10-24

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

  12. Evolving strategies for preserving the pulmonary valve during early repair of tetralogy of Fallot: mid-term results.

    PubMed

    Vida, Vladimiro L; Guariento, Alvise; Castaldi, Biagio; Sambugaro, Matteo; Padalino, Massimo A; Milanesi, Ornella; Stellin, Giovanni

    2014-02-01

    The aim of the study was to evaluate our results with pulmonary valve (PV) preservation in selected patients with tetralogy of Fallot (TOF). From January 2007, 69 patients who underwent early transatrial TOF repair were enrolled in the study. The patients were divided into 2 groups: PV preservation by PV annulus balloon dilation (group 1) and PV cusp reconstruction after annular incision (group 2). Thirty-four patients underwent a successful PV annular preservation (49%). Median age at surgery was 113 days (range, 36-521 days) (group-1 vs group-2, P = not significant). Median preoperative PV Z score was -3.15 (range, -0.95 to -5.62) (group-1 vs group-2, P = .03). Median intensive care unit and hospital stays were 3 and 10 days, respectively (group 1 vs group 2, P = not significant). Median follow-up time was 580 days (range, 189-1940 days) (group 1 vs group 2, P = .08). Two patients were reoperated for residual right ventricular outflow tract (RVOT) obstruction (1 in group 1 and 1 in group 2). The remaining patients are alive and well. Median peak RVOT gradient was 25 mm Hg (range, 8-60 mm Hg) (group 1 vs group 2, P = not significant). The degree of PV regurgitation in group 1 was none/mild in 24 patients (80%) and moderate in 6 (20%) and was none/mild in 8 patients (25%), moderate in 11 (34.4%), and severe in 13 (28.6%) in group 2 (P = .001). Median right ventricular fractional area change was 55% (range, 42%-70%) in group 1 and 50% (range, 40%-63%) in group 2 (P = .003). The integrity and function of the PV can be preserved in selected patients during early repair of TOF by concomitant balloon dilation, leading to a better mid-term right ventricular function. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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

    PubMed

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

    2010-07-01

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

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

    PubMed Central

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

    2010-01-01

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

  15. Tendon repair

    MedlinePlus

    ... the area to see if there are any injuries to nerves and blood vessels. When the repair is complete, the wound is closed. If the tendon damage is too severe, the repair and reconstruction ... to repair part of the injury. Another surgery will be done at a later ...

  16. 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

  17. 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

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

    PubMed

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

    2016-04-01

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

  19. 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

  20. Combination of multifaceted strategies to maximize the therapeutic benefits of neural stem cell transplantation for spinal cord repair.

    PubMed

    Hwang, Dong H; Kim, Hyuk M; Kang, Young M; Joo, In S; Cho, Chong-Su; Yoon, Byung-Woo; Kim, Seung U; Kim, Byung G

    2011-01-01

    Neural stem cells (NSCs) possess therapeutic potentials to reverse complex pathological processes following spinal cord injury (SCI), but many obstacles remain that could not be fully overcome by NSC transplantation alone. Combining complementary strategies might be required to advance NSC-based treatments to the clinical stage. The present study was undertaken to examine whether combination of NSCs, polymer scaffolds, neurotrophin-3 (NT3), and chondroitinase, which cleaves chondroitin sulfate proteoglycans at the interface between spinal cord and implanted scaffold, could provide additive therapeutic benefits. In a rat hemisection model, poly(ɛ-caprolactone) (PCL) was used as a bridging scaffold and as a vehicle for NSC delivery. The PCL scaffolds seeded with F3 NSCs or NT3 overexpressing F3 cells (F3.NT3) were implanted into hemisected cavities. F3.NT3 showed better survival and migration, and more frequently differentiated into neurons and oligodendrocytes than F3 cells. Animals with PCL scaffold containing F3.NT3 cells showed the best locomotor recovery, and motor evoked potentials (MEPs) following transcranial magnetic stimulation were recorded only in PCL-F3.NT3 group in contralateral, but not ipsilateral, hindlimbs. Implantation of PCL scaffold with F3.NT3 cells increased NT3 levels, promoted neuroplasticity, and enhanced remyelination of contralateral white matter. Combining chondroitinase treatment after PCL-F3.NT3 implantation further enhanced cell migration and promoted axonal remodeling, and this was accompanied by augmented locomotor recovery and restoration of MEPs in ipsilateral hindlimbs. We demonstrate that combining multifaceted strategies can maximize the therapeutic benefits of NSC transplantation for SCI. Our results may have important clinical implications for the design of future NSC-based strategies.

  1. Clubfoot repair

    MedlinePlus

    ... Clubfoot release; Talipes equinovarus - repair; Tibialis anterior tendon transfer ... complete blood count and check electrolytes or clotting factors) Always tell your child's provider: What drugs your ...

  2. Base Excision Repair

    PubMed Central

    Krokan, Hans E.; Bjørås, Magnar

    2013-01-01

    Base excision repair (BER) corrects DNA damage from oxidation, deamination and alkylation. Such base lesions cause little distortion to the DNA helix structure. BER is initiated by a DNA glycosylase that recognizes and removes the damaged base, leaving an abasic site that is further processed by short-patch repair or long-patch repair that largely uses different proteins to complete BER. At least 11 distinct mammalian DNA glycosylases are known, each recognizing a few related lesions, frequently with some overlap in specificities. Impressively, the damaged bases are rapidly identified in a vast excess of normal bases, without a supply of energy. BER protects against cancer, aging, and neurodegeneration and takes place both in nuclei and mitochondria. More recently, an important role of uracil-DNA glycosylase UNG2 in adaptive immunity was revealed. Furthermore, other DNA glycosylases may have important roles in epigenetics, thus expanding the repertoire of BER proteins. PMID:23545420

  3. 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.

  4. 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.

  5. Laparoscopic repair of inguinal hernia in adults

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

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

  6. The Specific Requirements of Neural Repair Trials for Stroke.

    PubMed

    Dobkin, Bruce H; Carmichael, S Thomas

    2016-06-01

    Novel molecular, cellular, and pharmacological therapies to stimulate repair of sensorimotor circuits after stroke are entering clinical trials. Compared with acute neuroprotection and thrombolysis studies, clinical trials for repair in subacute and chronic hemiplegic participants have a different time course for delivery of an intervention, different mechanisms of action within the milieu of the injury, distinct relationships to the amount of physical activity and skills practice of participants, and need to include more refined outcome measures. This review examines the biological interaction of targeted rehabilitation with neural repair strategies to optimize outcomes. We suggest practical guidelines for the incorporation of inexpensive skills training and exercise at home. In addition, we describe some novel outcome measurement tools, including wearable sensors, to obtain the more detailed outcomes that may identify at least some minimal level of success from cellular and regeneration interventions. Thus, proceeding in the shadow of acute stroke trial designs may unnecessarily limit the mechanisms of action of new repair strategies, reduce their impact on participants, and risk missing important behavioral outcomes. © The Author(s) 2015.

  7. Aneurysm Repair

    MedlinePlus

    ... repair of abdominal aortic aneurysms Cardiologists at the Texas Heart Institute were among the first to use ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  8. 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.

  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

    2014-03-05

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

  11. 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…

  12. Snowmobile Repair.

    ERIC Educational Resources Information Center

    Helbling, Wayne

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

  13. 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…

  14. Surgical revision after percutaneous mitral valve repair by edge-to-edge device: when the strategy fails in the highest risk surgical population.

    PubMed

    Alozie, Anthony; Westphal, Bernd; Kische, Stephan; Kaminski, Alexander; Paranskaya, Liliya; Bozdag-Turan, Ilkay; Ortak, Jasmin; Schubert, Jochen; Steinhoff, Gustav; Ince, Hüseyin

    2014-07-01

    Percutaneous edge-to-edge devices for non-surgical repair of mitral valve regurgitation are under clinical evaluation in high-risk patients deemed not suitable for conventional surgery. To address guidelines for initial therapy decision, we here report on 13 cases of surgery after failed percutaneous edge-to-edge mitral valve repair or attempted repair, and discuss methodology and prognostic factors for operative outcome in this high-risk situation. Thirteen patients referred to our cardiothoracic unit after failed percutaneous mitral valve repair or attempted repair using the edge-to-edge technique, were treated surgically for mitral valve failure between June 2010 and December 2012. Pathology of mitral valve before and after interventional mitral valve repair (especially prevalent mode of failure) was evaluated and classified for each individual patient by echocardiography and intraoperative direct visualization. Number of implanted edge-to-edge devices were identified. Preoperative risk scores were matched with intraoperative observations and histopathological findings of valve tissue. Postoperative morbidity and mortality were analysed with respect to mitral valve and patient-related data. Three of 10 patients were referred with severe mitral valve regurgitation/stenosis after initially successful percutaneous edge-to-edge therapy or attempted therapy. In 3 patients, ≥ 2 edge-to-edge devices were implanted leading to very tight edge-to-edge leaflet connection and fibrosis. All patients underwent successful surgical mitral valve replacement and concomitant complete cardiac surgery (CABG, aortic or tricuspid valve surgery, ASD closure and pulmonary vein isolation for atrial fibrillation). The likelihood of repair was reduced with respect to multiple edge-to-edge technology. One device could not be harvested surgically because of embolization. One patient died on the second postoperative day due to sepsis with multiple organ failure. The remaining 12 patients

  15. 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.

  16. DNA-Protein Crosslink Proteolysis Repair.

    PubMed

    Vaz, Bruno; Popovic, Marta; Ramadan, Kristijan

    2017-06-01

    Proteins that are covalently bound to DNA constitute a specific type of DNA lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles to the progression of DNA replication. If not repaired, DPCs cause stalling of DNA replication forks that consequently leads to DNA double-strand breaks, the most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of DPC repair was unclear until now. Recent work unveiled that DPC repair is orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis repair as a separate DNA repair pathway for genome stability and protection from accelerated aging and cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Laceration repair in children.

    PubMed

    Lawton, Benjamin; Hadj, Andrew

    2014-09-01

    Issues faced in the management of lacerations in children include control of pain and distress, wound cleaning and closure, referral decisions, awareness of potential associated injuries and strategies to prevent complications and optimise cosmetic outcome. The possibility of non-accidental injury may also require exploration. This update will attempt to offer a current, evidence-informed approach to management of the most commonly seen lacerations, and discuss when specialist referral is appropriate. Successful laceration repair in children is a procedure that blends the arts of anaesthesia, distraction and reassurance with the mechanics of tissue repair itself. Although each laceration and each child deserves an individualised approach, certain principles remain consistent and provide the backbone of a decision-making structure in this therapeutic area.

  18. Biologic scaffold for CNS repair.

    PubMed

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

    2014-05-01

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

  19. [Mechanisms of repair after renal injury].

    PubMed

    Menè, P; Polci, R; Festuccia, F

    2003-01-01

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

  20. An alternative eukaryotic DNA excision repair pathway.

    PubMed Central

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

    1995-01-01

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

  1. 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

  2. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Nuclear Dynamics of Heterochromatin Repair.

    PubMed

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

    2017-02-01

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

  4. The Use of Conversational Repairs by African American Preschoolers

    ERIC Educational Resources Information Center

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

    2008-01-01

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

  5. Dorsal variant blister aneurysm repair.

    PubMed

    Couldwell, William T; Chamoun, Roukoz

    2012-01-01

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

  6. Research on complex networks' repairing characteristics due to cascading failure

    NASA Astrophysics Data System (ADS)

    Chaoqi, Fu; Ying, Wang; Xiaoyang, Wang

    2017-09-01

    In reality, most of the topological structures of complex networks are not ideal. Considering the restrictions from all aspects, we cannot timely adjust and improve network defects. Once complex networks collapse under cascading failure, an appropriate repair strategy must be implemented. This repair process is divided into 3 kinds of situations. Based on different types of opening times, we presented 2 repair modes, and researched 4 kinds of repair strategies. Results showed that network efficiency recovered faster when the repair strategies were arranged in descending order by parameters under the immediate opening condition. However, the risk of secondary failure and additional expansion capacity were large. On the contrary, when repair strategies were in ascending order, the demand for additional capacity caused by secondary failure was greatly saved, but the recovery of network efficiency was relatively slow. Compared to immediate opening, delayed opening alleviated the contradiction between network efficiency and additional expansion capacity, particularly to reduce the risk of secondary failure. Therefore, different repair methods have different repair characteristics. This paper investigates the impact of cascading effects on the network repair process, and by presenting a detailed description of the status of each repaired node, helps us understand the advantages and disadvantages of different repair strategies.

  7. Repairing native defects on EUV mask blanks

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  8. 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. ...

  9. 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 ...

  10. Brain aneurysm repair

    MedlinePlus

    ... aneurysm repair; Dissecting aneurysm repair; Endovascular aneurysm repair - brain; Subarachnoid hemorrhage - aneurysm ... Your scalp, skull, and the coverings of the brain are opened. A metal clip is placed at ...

  11. National Trends in Rotator Cuff Repair

    PubMed Central

    Colvin, Alexis Chiang; Egorova, Natalia; Harrison, Alicia K.; Moskowitz, Alan; Flatow, Evan L.

    2012-01-01

    Background: Recent publications suggest that arthroscopic and open rotator cuff repairs have had comparable clinical results, although each technique has distinct advantages and disadvantages. National hospital and ambulatory surgery databases were reviewed to identify practice patterns for rotator cuff repair. Methods: The rates of medical visits for rotator cuff pathology, and the rates of open and arthroscopic rotator cuff repair, were examined for the years 1996 and 2006 in the United States. The national incidence of rotator cuff repairs and related data were obtained from inpatient (National Hospital Discharge Survey, NHDS) and ambulatory surgery (National Survey of Ambulatory Surgery, NSAS) databases. These databases were queried with use of International Classification of Diseases, Ninth Revision (ICD-9) procedure codes for arthroscopic (ICD-9 codes 83.63 and 80.21) and open (code 83.63 without code 80.21) rotator cuff repair. We also examined where the surgery was performed (inpatient versus ambulatory surgery center) and characteristics of the patients, including age, sex, and comorbidities. Results: The unadjusted volume of all rotator cuff repairs increased 141% in the decade from 1996 to 2006. The unadjusted number of arthroscopic procedures increased by 600% while open repairs increased by only 34% during this time interval. There was a significant shift from inpatient to outpatient surgery (p < 0.001). Conclusions: The increase in national rates of rotator cuff repair over the last decade has been dramatic, particularly for arthroscopic assisted repair. PMID:22298054

  12. Preferential DNA repair in expressed genes

    SciTech Connect

    Hanawalt, P.C.

    1987-12-01

    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 relations 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.

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

    PubMed

    Rennard, S I

    1999-11-01

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

  14. 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

  15. 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.

  16. Mismatch repair.

    PubMed

    Fishel, Richard

    2015-10-30

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

  17. Techniques in Endovascular Aneurysm Repair

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  19. Monofunctional platinum-DNA adducts are strong inhibitors of transcription and substrates for nucleotide excision repair in live mammalian cells.

    PubMed

    Zhu, Guangyu; Myint, MyatNoeZin; Ang, Wee Han; Song, Lina; Lippard, Stephen J

    2012-02-01

    To overcome drug resistance and reduce the side effects of cisplatin, a widely used antineoplastic agent, major efforts have been made to develop next generation platinum-based anticancer drugs. Because cisplatin-DNA adducts block RNA polymerase II unless removed by transcription-coupled excision repair, compounds that react similarly but elude repair are desirable. The monofunctional platinum agent pyriplatin displays antitumor activity in mice, a cytotoxicity profile in cell cultures distinct from that of cisplatin, and a unique in vitro transcription inhibition mechanism. In this study, we incorporated pyriplatin globally or site specifically into luciferase reporter vectors to examine its transcription inhibition profiles in live mammalian cells. Monofunctional pyriplatin reacted with plasmid DNA as efficiently as bifunctional cisplatin and inhibited transcription as strongly as cisplatin in various mammalian cells. Using repair-defective nucleotide excision repair (NER)-, mismatch repair-, and single-strand break repair-deficient cells, we show that NER is mainly responsible for removal of pyriplatin-DNA adducts. These findings reveal that the mechanism by which pyriplatin generates its antitumor activity is very similar to that of cisplatin, despite the chemically different nature of their DNA adducts, further supporting a role for monofunctional platinum anticancer agents in human cancer therapy. This information also provides support for the validity of the proposed mechanism of action of cisplatin and provides a rational basis for the design of more potent platinum anticancer drug candidates using a monofunctional DNA-damaging strategy. ©2011 AACR.

  20. 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)

  1. Patient-reported opioid analgesic requirements after elective inguinal hernia repair: A call for procedure-specific opioid-administration strategies.

    PubMed

    Mylonas, Konstantinos S; Reinhorn, Michael; Ott, Lauren R; Westfal, Maggie L; Masiakos, Peter T

    2017-08-01

    A better understanding of the analgesia needs of patients who undergo common operative procedures is necessary as we address the growing opioid public health crisis in the United States. The aim of this study was to evaluate patient experience with our opioid prescribing practice after elective inguinal hernia repairs. A prospective, observational study was conducted between October 1, 2015, and September 30, 2016, in a single-surgeon, high-volume, practice of inguinal hernia operation. Adult patients undergoing elective inguinal herniorrhaphy under local anesthesia with intravenous sedation were invited to participate. All patients were prescribed 10 opioid analgesic tablets postoperatively and were counseled to reserve opioids for pain not controlled by nonopioid analgesics. Their experience was captured by completing a questionnaire 2 to 3 weeks postoperatively during their postoperative visit. A total of 185 patients were surveyed. The majority of the participants were males (177, 95.7%) and ≥60 years old (96, 51.9%). Of the 185 patients, 159 (85.9%) reported using ≤4 opioid tablets; 110 patients (59.5%) reported that they used no opioid analgesics postoperatively. None of the patients was taking opioids within 7 days of their postoperative appointment. Of the 147 patients who were employed, 111 (75.5%) reported missing ≤3 work days, 57 of whom (51.4%) missed no work at all. Patients who were employed were more likely to take opioid analgesics postoperatively (P = .049). Patients who took no opioid analgesics experienced less maximum (P < .001) and persistent groin pain (P = .037). Pain interfered less with daily activities (P = .012) and leisure activities (P = .018) for patients who did not use opioids. The majority of our patients reported that they did not require any opioid analgesics, and nearly all of those who thought that they did need opioids used <5 tablets. Our data suggest that for elective inguinal hernia repair under a local

  2. Integrated structural repair of a producing FPSO

    SciTech Connect

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

    1997-07-01

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

  3. An end-joining repair mechanism in Escherichia coli

    PubMed Central

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

    2010-01-01

    Bridging broken DNA ends via nonhomologous end-joining (NHEJ) contributes to the evolution and stability of eukaryote genomes. Although some bacteria possess a simplified NHEJ mechanism, the human commensal Escherichia coli is thought to rely exclusively on homology-directed mechanisms to repair DNA double-strand breaks (DSBs). We show here that laboratory and pathogenic E. coli strains possess a distinct end-joining activity that repairs DSBs and generates genome rearrangements. This mechanism, named alternative end-joining (A-EJ), does not rely on the key NHEJ proteins Ku and Ligase-D which are absent in E. coli. Differently from classical NHEJ, A-EJ is characterized by extensive end-resection largely due to RecBCD, by overwhelming usage of microhomology and extremely rare DNA synthesis. We also show that A-EJ is dependent on the essential Ligase-A and independent on Ligase-B. Importantly, mutagenic repair requires a functional Ligase-A. Although generally mutagenic, accurate A-EJ also occurs and is frequent in some pathogenic bacteria. Furthermore, we show the acquisition of an antibiotic-resistance gene via A-EJ, refuting the notion that bacteria gain exogenous sequences only by recombination-dependent mechanisms. This finding demonstrates that E. coli can integrate unrelated, nonhomologous exogenous sequences by end-joining and it provides an alternative strategy for horizontal gene transfer in the bacterial genome. Thus, A-EJ contributes to bacterial genome evolution and adaptation to environmental challenges. Interestingly, the key features of A-EJ also appear in A-NHEJ, an alternative end-joining mechanism implicated in chromosomal translocations associated with human malignancies, and we propose that this mutagenic repair might have originated in bacteria. PMID:20133858

  4. 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.

  5. 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.

  6. The immune system and cardiac repair.

    PubMed

    Frangogiannis, Nikolaos G

    2008-08-01

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

  7. The immune system and cardiac repair

    PubMed Central

    Frangogiannis, Nikolaos G.

    2008-01-01

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

  8. Wnt Signaling and Injury Repair

    PubMed Central

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

    2012-01-01

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

  9. Mechanisms of DNA-protein crosslink repair.

    PubMed

    Stingele, Julian; Bellelli, Roberto; Boulton, Simon J

    2017-09-01

    Covalent DNA-protein crosslinks (DPCs, also known as protein adducts) of topoisomerases and other proteins with DNA are highly toxic DNA lesions. Of note, chemical agents that induce DPCs include widely used classes of chemotherapeutics. Their bulkiness blocks virtually every chromatin-based process and makes them intractable for repair by canonical repair pathways. Distinct DPC repair pathways employ unique points of attack and are crucial for the maintenance of genome stability. Tyrosyl-DNA phosphodiesterases (TDPs) directly hydrolyse the covalent linkage between protein and DNA. The MRE11-RAD50-NBS1 (MRN) nuclease complex targets the DNA component of DPCs, excising the fragment affected by the lesion, whereas proteases of the spartan (SPRTN)/weak suppressor of SMT3 protein 1 (Wss1) family target the protein component. Loss of these pathways renders cells sensitive to DPC-inducing chemotherapeutics, and DPC repair pathways are thus attractive targets for combination cancer therapy.

  10. Distinct Presentations of Hernia of Umbilical Cord

    PubMed Central

    Mirza, Bilal; Ali, Waqas

    2016-01-01

    Hernia of umbilical cord is a well-known entity which presents with herniation of small bowel into the proximal part of umbilical cord. It has very good prognosis after surgical repair. Occasionally, it can have distinct presentations and varied malformations at the umbilicus which have bearing on the course of treatment and final outcome. Herein, we describe various presentations and malformations associated with hernia of umbilical cord. Embryological extrapolation is attempted for the malformations at umbilicus. PMID:27896161

  11. Distinct Presentations of Hernia of Umbilical Cord.

    PubMed

    Mirza, Bilal; Ali, Waqas

    2016-01-01

    Hernia of umbilical cord is a well-known entity which presents with herniation of small bowel into the proximal part of umbilical cord. It has very good prognosis after surgical repair. Occasionally, it can have distinct presentations and varied malformations at the umbilicus which have bearing on the course of treatment and final outcome. Herein, we describe various presentations and malformations associated with hernia of umbilical cord. Embryological extrapolation is attempted for the malformations at umbilicus.

  12. 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.

  13. 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.

  14. Collision Repair Campaign

    EPA Pesticide Factsheets

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

  15. 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 ...

  16. Inguinal hernia repair

    MedlinePlus

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

  17. Pallet repair and salvage

    Treesearch

    Richard E. Frost; Hollis R. Large

    1975-01-01

    Efficient unit-load handling with permanent pallets requires a well-organized pallet repair program. To provide basic infomation on pallet damage that could be used in establishing repair standards, we inspected a total of 1700 damaged pallets at four repair facilities. All damage was recorded by type, severity, and location. This survey determined that missing...

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

    PubMed

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

    2011-07-01

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

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

    PubMed

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

    2012-10-01

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

  20. Dental materials for cleft palate repair.

    PubMed

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

    2016-04-01

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

  1. Feasibility of Transvesical Robotic VVF Repair in Porcine Model.

    PubMed

    Han, Jang Hee; Kim, Hong-Wook; Rha, Koon Ho; Kim, Jang Hwan

    2017-06-01

    Extraperitoneal transvesicoscopic vesicovaginal fistula (VVF) repair has received limited use because of its narrow working space, longer operation time, and technical difficulty. The present study describes the feasibility of robotic-assisted transvesicoscopic VVF repair in an animal model. Two Yorkshire swine underwent robotic-assisted laparoscopic (RAL) VVF repair. With the 4 trocars, an artificial VVF was made in the supratrigonal area and VVF repair was performed in 3 layers as in open VVF repair methods. The mean operation time was 108 minutes. The operation time was prolonged in 1 case due to weak fixation of bladder to anterior abdominal wall. Equipment interference did not occur. Tissue manipulation and suturing were easy. The results of this study suggest that extraperitoneal RAL procedures for VVF repair may be an effective minimally invasive modality with reduced morbidity. A shorter operation time and easy suturing technique were the distinct merits of the extraperitoneal RAL technique.

  2. 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

  3. Percutaneous mitral valve repair with the MitraClip system: perioperative and 1-year follow-up results using standard or multiple clipping strategy.

    PubMed

    Paranskaya, Liliya; D'Ancona, Giuseppe; Bozdag-Turan, Ilkay; Akin, Ibrahim; Kische, Stephan; Turan, Gökmen R; Divchev, Dimitar; Rehders, Tim; Westphal, Bernd; Schubert, Jochen; Nienaber, Christoph A; Ince, Hüseyin

    2013-06-01

    The purpose of this study was to compare outcomes using standard clipping (SC) (one to two clips) or multiple clipping (MC) (more than two clips). MitraClip implantation using MC has been proposed to treat severe mitral regurgitation (MR) in high-risk patients. A tailored strategy was used implanting as many clips as required to eliminate MR. A total of 85 consecutive patients [78 ± 6 years, 48 men (56.5%) ] with MR (grade 3+ or 4+) were included. EuroSCORE was 24 ± 12 (2.5-56.3) and STS-score 12 ± 7 (1.2-31.2). SC was used in 61 (71.8%) and MC in 24 (28.2%) patients. Patients in MC group had larger mitral valve (MV) annuli (P = 0.025), MV orifice areas (MVOA) (P = 0.01), and MR degree (P = 0.005). Successful clip placement was achieved in 82 patients (96.5%). At discharge, no patient had grade 4+ MR. MR 3+ presented in 4 patients (7.0%) in the SC group and in 1 (4.5%) in the MC group (P = 0.72). There were 3 (3.5%) in-hospital deaths. Follow up (211 ± 173 days, range 4-652) echocardiography confirmed similar MVOA (P = 0.83) and MV gradients (P = 0.54) in the both groups. At linear regression there was no independent correlation between clips number and postoperative MVOA/gradient. One-year survival was 71.1% without difference between groups (P = 0.74). Although the hemodynamic and anatomical basis of MR may differ, every procedure should aim at eliminating MR. In some patients this goal can be achieved using MC with minimized risk of MV stenosis if preoperative anatomy/mechanism of MV regurgitation are adequately assessed. Copyright © 2012 Wiley Periodicals, Inc.

  4. 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.

  5. 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

  6. Choreography of oxidative damage repair in mammalian genomes.

    PubMed

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

    2002-07-01

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

  7. The use of conversational repairs by African American preschoolers.

    PubMed

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

    2008-10-01

    This study aimed to describe the types and frequency of conversational repairs used by African American (AA) children in relationship to their geographic locations and levels of performance on commonly used speech-language measures. The strategies used to initiate repairs and respond to repair requests were identified in audiovisual records of spontaneous speech sampled from 120 Head Start students in Michigan (n = 69) and Louisiana (n = 51) at 3 years of age. The 30-40-min samples were elicited with common stimuli and activities while the children interacted with an adult examiner. All participants initiated repairs and responded to examiner requests for conversational repairs. Some repair strategies were observed more often than others. The frequency, but not the types, of some of the strategies used varied significantly with participant location and level of speech-language performance. AA children used the same types of conversational repair strategies that have been observed among young speakers of Standard English varieties. Use of conversational repairs should be included among the pragmatic behaviors expected for 3-year-old AA children.

  8. Repair of furocoumarin adducts in mammalian cells

    SciTech Connect

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

    1984-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Retinal detachment repair

    MedlinePlus

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

  11. Attitudes, practice, and experience of German dentists regarding repair restorations.

    PubMed

    Kanzow, Philipp; Hoffmann, Robin; Tschammler, Claudia; Kruppa, Jochen; Rödig, Tina; Wiegand, Annette

    2017-05-01

    The aim of the present study was to perform a representative survey among German dentists about attitudes, practice, and experience regarding single-tooth repair restorations. An anonymous questionnaire was designed and mailed to all registered dentists in Lower Saxony (n = 6600). Twenty-eight percent were returned (n = 1852), and n = 1805 could be analyzed. Statistical analyses were done by Wilcoxon signed-rank tests, Kruskal-Wallis tests, and ordered logistic regressions (p < 0.05). Only 2.2 % of the dentists declared to never perform repair restorations. Composite restorations were repaired significantly more often than all other materials. Frequency of performing repair restorations was partially associated to dentist-related factors. The decision for repairing a restoration was dependent on several tooth- and restoration-associated variables. The main indications for repair were the partial loss of restoration or adjacent tooth structure as well as chipping and endodontic access cavities of crowns. Repair restorations were mostly done with composite using various different preconditioning techniques. Overall patients' acceptance was reported to be high. Most of the dentists considered repair restorations as permanent restoration with a moderate to high longevity. Estimated success of repair restorations depended significantly on the dentists' experiences (frequency and techniques of repair restorations). Repair restorations were often performed and were well accepted by dentists and patients, but indications for repair restorations as well as applied materials and techniques varied distinctly. Repairs of single-tooth restorations are well accepted and frequently performed, but indications, techniques, and materials require further research.

  12. Variation in Base Excision Repair Capacity

    PubMed Central

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

    2010-01-01

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

  13. Repair of Electronics for Long Duration Spaceflight

    NASA Technical Reports Server (NTRS)

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

    2007-01-01

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

  14. 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

  15. Techniques for aortic arch endovascular repair.

    PubMed

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

    2016-06-01

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

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

    PubMed

    Jeggo, Penny A; Downs, Jessica A

    2014-11-15

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

  17. Snowmobile Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Hennessy, Stephen S.; Conrad, Rex

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

  18. Imperforate anus repair

    MedlinePlus

    ... repair URL of this page: //medlineplus.gov/ency/article/002926.htm Imperforate anus repair To use the sharing features on this page, ... done. Why the Procedure is Performed ... blood clots, infection Risks of this procedure include: Damage to the urethra (tube that carries urine out ...

  19. Chain Saw Repair.

    ERIC Educational Resources Information Center

    Taylor, Mark; Helbling, Wayne

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

  20. Ribonucleotides in DNA: Origins, repair and consequences

    PubMed Central

    Williams, Jessica S.; Kunkel, Thomas A.

    2014-01-01

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

  1. Does Renal Repair Recapitulate Kidney Development?

    PubMed

    Little, Melissa Helen; Kairath, Pamela

    2017-01-01

    Over a decade ago, it was proposed that the regulation of tubular repair in the kidney might involve the recapitulation of developmental pathways. Although the kidney cannot generate new nephrons after birth, suggesting a low level of regenerative competence, the tubular epithelial cells of the nephrons can proliferate to repair the damage after AKI. However, the debate continues over whether this repair involves a persistent progenitor population or any mature epithelial cell remaining after injury. Recent reports have highlighted the expression of Sox9, a transcription factor critical for normal kidney development, during postnatal epithelial repair in the kidney. Indeed, the proliferative response of the epithelium involves expression of several pathways previously described as being involved in kidney development. In some instances, these pathways are also apparently involved in the maladaptive responses observed after repeated injury. Whether development and repair in the kidney are the same processes or we are misinterpreting the similar expression of genes under different circumstances remains unknown. Here, we review the evidence for this link, concluding that such parallels in expression may more correctly represent the use of the same pathways in a distinct context, likely triggered by similar stressors. Copyright © 2016 by the American Society of Nephrology.

  2. Regulatory players of DNA damage repair mechanisms: Role in Cancer Chemoresistance.

    PubMed

    Sakthivel, Kunnathur Murugesan; Hariharan, Sreedharan

    2017-09-01

    DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence. In this review, we summarize how the various signaling pathways in cancer cells regulates DNA repair and induce chemoresistance. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Biological consequences of formation and repair of complex DNA damage.

    PubMed

    Magnander, Karin; Elmroth, Kecke

    2012-12-31

    Endogenous processes or genotoxic agents can induce many types of single DNA damage (single-strand breaks, oxidized bases and abasic sites). In addition, ionizing radiation induces complex lesions such as double-strand breaks and clustered damage. To preserve the genomic stability and prevent carcinogenesis, distinct repair pathways have evolved. Despite this, complex DNA damage can cause severe problems and is believed to contribute to the biological consequences observed in cells exposed to genotoxic stress. In this review, the current knowledge of formation and repair of complex DNA damage is summarized and the risks and biological consequences associated with their repair are discussed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2008-04-01

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

  5. Rapid road repair vehicle

    SciTech Connect

    Mara, L.M.

    1999-09-07

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

  6. 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.

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

    PubMed Central

    Punwar, Shahid; Khan, Wasim S

    2011-01-01

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

  8. Designing Hydrogel Adhesives for Corneal Wound Repair

    PubMed Central

    Grinstaff, Mark W.

    2013-01-01

    Today, corneal wounds are repaired using nylon sutures. Yet there are a number of complications associated with suturing the cornea, and thus there is interest in an adhesive to replace or supplement sutures in the repair of corneal wounds. We are designing and evaluating corneal adhesives prepared from dendrimers – single molecular weight, highly branched polymers. We have explored two strategies to form these ocular adhesives. The first involves a photocrosslinking reaction and the second uses a peptide ligation reactions to couple the individual dendrimers together to from the adhesive. These adhesives were successfully used to repair corneal perforations, close the flap produced in a LASIK procedure, and secure a corneal transplant. PMID:17889330

  9. Learning to improve iterative repair scheduling

    NASA Technical Reports Server (NTRS)

    Zweben, Monte; Davis, Eugene

    1992-01-01

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

  10. 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.

  11. Hiatal hernia repair - slideshow

    MedlinePlus

    ... presentations/100028.htm Hiatal hernia repair - series—Normal anatomy To use the sharing features on ... Overview The esophagus runs through the diaphragm to the stomach. It functions to carry food from the mouth ...

  12. Ventral hernia repair

    MedlinePlus

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

  13. Hypospadias repair - discharge

    MedlinePlus

    ... JC, Brock JW. Repair of proximal hypospadias. In: Smith JA, Howards SS, Preminger GM, Dmochowski RR, eds. Hinman's ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

  14. Eye muscle repair - slideshow

    MedlinePlus

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

  15. Patent urachus repair

    MedlinePlus

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

  16. 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 ...

  17. Repairing ceramic insulating tiles

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  18. Diaphragmatic hernia repair - slideshow

    MedlinePlus

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

  19. Timpani Repair and Maintenance.

    ERIC Educational Resources Information Center

    Combs, F. Michael

    1980-01-01

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

  20. Femoral hernia repair

    MedlinePlus

    ... medicine to relax you . Your surgeon makes a cut (incision) in your groin area. The hernia is ... wall. At the end of the repair, the cuts are stitched closed. In laparascopic surgery: The surgeon ...

  1. Pectus excavatum repair

    MedlinePlus

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

  2. Bone fracture repair - slideshow

    MedlinePlus

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

  3. Femur fracture repair - discharge

    MedlinePlus

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

  4. Tracheoesophageal fistula repair - slideshow

    MedlinePlus

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

  5. Pectus excavatum repair - slideshow

    MedlinePlus

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

  6. Achilles tendon repair

    MedlinePlus

    Achilles tendon rupture-surgery; Percutaneous Achilles tendon rupture repair ... To fix your torn Achilles tendon, the surgeon will: Make a cut down the back of your heel Make several small cuts rather than one large cut ...

  7. Retinal detachment repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100132.htm Retinal detachment repair - series—Normal anatomy To use the ... to slide 6 out of 6 Overview The retina is the internal layer of the eye that ...

  8. Transconjunctival epiblepharon repair.

    PubMed

    Wladis, Edward J

    2014-01-01

    To document the use of a transconjunctival approach to lower eyelid epiblepharon repair. Retrospective chart review of all patients who underwent transconjunctival lower eyelid epiblepharon repair. Nine patients underwent repair via this approach. All patients experienced the resolution of their keratitis and cilia-cornea touch by a 3-month postoperative interval, and no patient developed a postoperative complication. Furthermore, no patient developed cutaneous scarring. Conventional approaches to lower eyelid epiblepharon repair have necessitated the creation of a skin and muscle flap, thus risking the development of scarring and a cosmetically unacceptable eyelid crease. This report documents the use of a transconjunctival approach for the management of this condition that avoids external incisions and provides excellent outcomes without scarring of the anterior lamella of the eyelid.

  9. Umbilical hernia repair - slideshow

    MedlinePlus

    ... page: //medlineplus.gov/ency/presentations/100105.htm Umbilical hernia repair - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Hernia A.D.A.M., Inc. is accredited by ...

  10. Cleft lip repair - slideshow

    MedlinePlus

    ... presentations/100010.htm Cleft lip repair - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  11. Carpal tunnel repair - slideshow

    MedlinePlus

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

  12. Rotator cuff repair - slideshow

    MedlinePlus

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

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

    PubMed

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

    2015-11-26

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

  14. Repair Process Performance Analysis

    DTIC Science & Technology

    1988-05-01

    CRITICAL HURDLE W/S UNIT REPAIR COST : xx xx x x.xx CURRENT POSITION...NAME u/s MAXO(N ALC SOR INS CRITICAL HURDLE RANK UNIT REPAIR COST axxKXXX xi ilixiX xx xii xiiii xx Xiii iXi.ii *ON...GAIE PLAN GET WELL DATE-JUNE 19I1 NSN XXXX-XX- XXX -XXXx 7OTAL REQUIREENT :RPC: :RPV: - -..... -- ,---,° . I::""C I I ..... .....RPC: C ----: R

  15. Proximal Hamstring Repair Strength

    PubMed Central

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

    2015-01-01

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

  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.

  17. Revision arthroscopic Bankart repair.

    PubMed

    Abouali, Jihad Alexander Karim; Hatzantoni, Katerina; Holtby, Richard; Veillette, Christian; Theodoropoulos, John

    2013-09-01

    Failed anterior shoulder stabilization procedures have traditionally been treated with open procedures. Recent advances in arthroscopic techniques have allowed for certain failed stabilization procedures to be treated by arthroscopic surgery. The aim of this systematic review was to determine the outcomes of revision arthroscopic Bankart repair. We searched Medline, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) for articles on revision arthroscopic Bankart repairs. Key words included shoulder dislocation, anterior shoulder instability, revision surgery, and arthroscopic Bankart repair. Two reviewers selected studies for inclusion, assessed methodologic quality, and extracted data. We included 16 studies comprising 349 patients. All studies were retrospective (1 Level II study and 15 Level IV studies). The mean incidence of recurrent instability after revision arthroscopic Bankart repair was 12.7%, and the mean follow-up period was 35.4 months. The most common cause for failure of the primary surgeries was a traumatic injury (62.1%), and 85.1% of patients returned to playing sports. The reasons for failure of revision cases included glenohumeral bone loss, hyperlaxity, and return to contact sports. With proper patient selection, the outcomes of revision arthroscopic Bankart repair appear similar to those of revision open Bankart repair. Prospective, randomized clinical trials are required to confirm these findings. Level IV, systematic review of Level II and Level IV studies. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  18. Distinct functions for ERKs?

    PubMed Central

    Lloyd, Alison C

    2006-01-01

    The Ras/Raf/MEK/ERK signaling pathway is one of the best understood signal routes in cells. Recent studies add complexity to this cascade by indicating that the two ERK kinases, ERK1 (p44ERK1) and ERK2 (p42ERK2), may have distinct functions. PMID:16879721

  19. 77 FR 30053 - Repair Stations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-21

    ...This action would amend the regulations for repair stations by revising the system of ratings, the repair station certification requirements, and the regulations on repair stations providing maintenance for air carriers. This action is necessary because many portions of the existing repair station regulations do not reflect current repair station aircraft maintenance and business practices, or advances in aircraft technology. These changes would modernize the regulations to keep pace with current industry standards and practices.

  20. 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

  1. 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. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

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

    PubMed Central

    2016-01-01

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

  3. 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

  4. Cockayne syndrome: defective repair of transcription?

    PubMed Central

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

    1997-01-01

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

  5. Equine Models of Articular Cartilage Repair

    PubMed Central

    McIlwraith, C. Wayne; Fortier, Lisa A.; Frisbie, David D.; Nixon, Alan J.

    2011-01-01

    Articular cartilage injuries of the knee and ankle are common, and a number of different methods have been developed in an attempt to improve their repair. Clinically, there are 2 distinct aims of cartilage repair: 1) restoration of joint function and 2) prevention or at least delay of the onset of osteoarthritis. These goals can potentially be achieved through replacement of damaged or lost articular cartilage with tissue capable of functioning under normal physiological environments for an extended period, but limitations of the final repair product have long been recognized and still exist today. Screening of potential procedures for human clinical use is done by preclinical studies using animal models. This article reviews equine chondral defect models that have been recently recognized to have specific advantages for translation into human articular cartilage regeneration. Defect models in the femoropatellar, femorotibial, and tibiotalar joints have been developed. The horse provides the closest approximation to humans in terms of articular cartilage and subchondral bone thickness, and it is possible to selectively leave the entire calcified cartilage layer or completely remove it. The defect on the equine medial femoral condyle emulates medial femoral condylar lesions in humans. Other advantages of the equine model include an ability to use an arthroscope to create lesions and perform second-look arthroscopies, the large lesion size allowing for more tissue for evaluation, and the ability to have controlled exercise and test the ability of the repair to cope with athletic exercise as well as institute rehabilitation regimens. PMID:26069590

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

    PubMed

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

    2015-09-18

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

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

    PubMed Central

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

    2015-01-01

    Aging in mammals is accompanied by a progressive atrophy of tissues and organs, and stochastic damage accumulation to the macromolecules DNA, RNA, proteins, and lipids. The sequence of the human genome represents our genetic blueprint, and accumulating evidence suggests that loss of genomic maintenance may causally contribute to aging. Distinct evidence for a role of imperfect DNA repair in aging is that several premature aging syndromes have underlying genetic DNA repair defects. Accumulation of DNA damage may be particularly prevalent in the central nervous system owing to the low DNA repair capacity in postmitotic brain tissue. It is generally believed that the cumulative effects of the deleterious changes that occur in aging, mostly after the reproductive phase, contribute to species-specific rates of aging. In addition to nuclear DNA damage contributions to aging, there is also abundant evidence for a causative link between mitochondrial DNA damage and the major phenotypes associated with aging. Understanding the mechanistic basis for the association of DNA damage and DNA repair with aging and age-related diseases, such as neurodegeneration, would give insight into contravening age-related diseases and promoting a healthy life span. PMID:26385091

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

    SciTech Connect

    Katzen, Barry T. MacLean, Alexandra A.

    2006-12-15

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

  9. 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Immunoengineering nerve repair

    PubMed Central

    Mokarram, Nassir; Dymanus, Kyle; Srinivasan, Akhil; Tipton, John; Chu, Jason; English, Arthur W.; Bellamkonda, Ravi V.

    2017-01-01

    Injuries to the peripheral nervous system are major sources of disability and often result in painful neuropathies or the impairment of muscle movement and/or normal sensations. For gaps smaller than 10 mm in rodents, nearly normal functional recovery can be achieved; for longer gaps, however, there are challenges that have remained insurmountable. The current clinical gold standard used to bridge long, nonhealing nerve gaps, the autologous nerve graft (autograft), has several drawbacks. Despite best efforts, engineering an alternative “nerve bridge” for peripheral nerve repair remains elusive; hence, there is a compelling need to design new approaches that match or exceed the performance of autografts across critically sized nerve gaps. Here an immunomodulatory approach to stimulating nerve repair in a nerve-guidance scaffold was used to explore the regenerative effect of reparative monocyte recruitment. Early modulation of the immune environment at the injury site via fractalkine delivery resulted in a dramatic increase in regeneration as evident from histological and electrophysiological analyses. This study suggests that biasing the infiltrating inflammatory/immune cellular milieu after injury toward a proregenerative population creates a permissive environment for repair. This approach is a shift from the current modes of clinical and laboratory methods for nerve repair, which potentially opens an alternative paradigm to stimulate endogenous peripheral nerve repair. PMID:28611218

  11. 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

  12. Targeting DNA Repair in Cancer: Beyond PARP Inhibitors.

    PubMed

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

    2017-01-01

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

  13. Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

    PubMed Central

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

    2017-01-01

    Germline aberrations in critical DNA repair and DNA-damage response (DDR) genes cause cancer predisposition, while various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2 mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell cycle checkpoint activation, trigger apoptosis and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations. PMID:28003236

  14. Incisional hernia repair.

    PubMed

    Millikan, Keith W

    2003-10-01

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

  15. DNA repair mechanisms in cancer development and therapy

    PubMed Central

    Torgovnick, Alessandro; Schumacher, Björn

    2015-01-01

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

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

    SciTech Connect

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

    1982-01-01

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

  17. 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.

  18. 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.

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

    PubMed

    Fitzgerald, Jamie

    2017-02-01

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

  20. Joking Repair and the Organization of Repair in Conversation.

    ERIC Educational Resources Information Center

    Norrick, Neal R.

    This analysis looks at the humorous use of second-speaker repeats to initiate conversational repair. It is proposed that consideration of joking repeats forces reanalysis of the organization of conversational repair. The preference analysis theory is rejected in favor of a locally governed analysis of conversational repair in which participants…

  1. Building and Repairing the Heart: What Can We Learn from Embryonic Development?

    PubMed Central

    Freire, Ana G.; Resende, Tatiana P.; Pinto-do-Ó, Perpétua

    2014-01-01

    Mammalian heart formation is a complex morphogenetic event that depends on the correct temporal and spatial contribution of distinct cell sources. During cardiac formation, cellular specification, differentiation, and rearrangement are tightly regulated by an intricate signaling network. Over the last years, many aspects of this network have been uncovered not only due to advances in cardiac development comprehension but also due to the use of embryonic stem cells (ESCs) in vitro model system. Additionally, several of these pathways have been shown to be functional or reactivated in the setting of cardiac disease. Knowledge withdrawn from studying heart development, ESCs differentiation, and cardiac pathophysiology may be helpful to envisage new strategies for improved cardiac repair/regeneration. In this review, we provide a comparative synopsis of the major signaling pathways required for cardiac lineage commitment in the embryo and murine ESCs. The involvement and possible reactivation of these pathways following heart injury and their role in tissue recovery will also be discussed. PMID:24864252

  2. Imperforate anus repair - series (image)

    MedlinePlus

    ... for passage of stool. Complete absence of an anal opening requires emergency surgery for the newborn. Surgical ... for several months before attempting the more complex anal repair. The anal repair involves an abdominal incision, ...

  3. Abdominal aortic aneurysm repair - open

    MedlinePlus

    AAA - open; Repair - aortic aneurysm - open ... Open surgery to repair an AAA is sometimes done as an emergency procedure when there is bleeding inside your body from the aneurysm. You may have an ...

  4. About the Collision Repair Campaign

    EPA Pesticide Factsheets

    EPA developed the Collision Repair Campaign to focus on meaningful risk reduction in the Collision Repair source sector to complement ongoing community air toxics work and attain reductions at a faster rate.

  5. 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.

  6. Monolith Joint Repairs: Case Histories

    DTIC Science & Technology

    1989-08-01

    REPAIR, EVALUATION, MAINTENANCE, AND REHABILITATION RESEARCH PROGRAM TECHNICAL REPORT REMR-CS-22 MONOLITH JOINT REPAIRS: CASE HISTORVS.Z by James G ...Washington, DC 20314-1000 32307 S11. TITLE (Include Security Classification) Monolith Joint Repairs: Case Histories 12. PERSONAL AUTHOR(S) May. James G ...Research Work Unit 32307, "Tech- niques for Joint Repair and Rehabilitation," for which MAJ James G . May, CE, is the Principal Investigator. This work unit

  7. 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.

  8. 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…

  9. Intestinal obstruction repair - slideshow

    MedlinePlus

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

  10. 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…

  11. 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,…

  12. Krikalev during Elektron repair

    NASA Image and Video Library

    2005-05-05

    ISS011-E-05509 (5 May 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, uses a power tool as he makes repairs to the Elektron oxygen generator in the Zvezda Service Module of the International Space Station (ISS).

  13. Krikalev during Elektron repair

    NASA Image and Video Library

    2005-05-05

    ISS011-E-05513 (5 May 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, poses beside the disconnected Liquid Unit #5 (BZh-5) and the O2 end-filter (BD, secondary purification unit) from the BZh5 he removed while making repairs to the Elektron oxygen generator in the Zvezda Service Module of the international space station.

  14. Krikalev during Elektron repair

    NASA Image and Video Library

    2005-05-05

    ISS011-E-05504 (5 May 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, uses a video camera to document repairs to the Elektron oxygen generator in the Zvezda Service Module of the International Space Station (ISS).

  15. Krikalev during Elektron repair

    NASA Image and Video Library

    2005-05-05

    ISS011-E-05510 (5 May 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, uses a power tool as he makes repairs to the Elektron oxygen generator in the Zvezda Service Module of the International Space Station (ISS).

  16. 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.

  17. Eardrum repair - slideshow

    MedlinePlus

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

  18. 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,…

  19. 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)

  20. Getting Ready To Repair.

    ERIC Educational Resources Information Center

    Stryker, Rick

    2002-01-01

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

  1. 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,…

  2. 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

  3. Augmentation techniques for rotator cuff repair.

    PubMed

    Papalia, Rocco; Franceschi, Francesco; Zampogna, Biagio; D'Adamio, Stefano; Maffulli, Nicola; Denaro, Vincenzo

    2013-01-01

    There is a high rate of recurrence of tear and failed healing after rotator cuff repair. Several strategies have proposed to augment rotator cuff repairs to improve postoperative outcome and shoulder performance. We systematically review the literature on clinical outcome following rotator cuff augmentation. We performed a comprehensive search of Medline, CINAHL, Embase and the Cochrane Central Registry of Controlled Trials, from inception of the database to 20 June 2012, using various combinations of keywords. The reference lists of the previously selected articles were then examined by hand. Only studies focusing on clinical outcomes of human patients who had undergone augmented rotator cuff repair were selected. We then evaluated the methodological quality of each article using the Coleman methodology score (CMS), a 10 criteria scoring list assessing the methodological quality of the selected studies (CMS). Thirty-two articles were included in the present review. Two were retrospective studies, and 30 were prospective. Biologic, synthetic and cellular devices were used in 24, 7 and 1 studies, respectively. The mean modified Coleman methodology score was 64.0. Heterogeneity of the clinical outcome scores makes it difficult to compare different studies. None of the augmentation devices available is without problems, and each one presents intrinsic weaknesses. There is no dramatic increase in clinical and functional assessment after augmented procedures, especially if compared with control groups. More and better scientific evidence is necessary to use augmentation of rotator cuff repairs in routine clinical practice.

  4. Repairing Holes in Pressure Walls

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

  5. 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…

  6. 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…

  7. 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.

  8. Remote repair grinding of cracks underwater

    SciTech Connect

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

    1994-12-31

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

  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. (c) 2006 APA, all rights reserved

  10. 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.

  11. Laparoscopic repair of femoral hernia

    PubMed Central

    Yang, Xue-Fei

    2016-01-01

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

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

    PubMed Central

    Chou, Alice I.; Reza, Anna T.

    2008-01-01

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

  13. 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

  14. Phase-independent multilayer defect repair for EUV photomasks

    NASA Astrophysics Data System (ADS)

    Zhao, Shuo; Qi, Zhengqing John

    2016-10-01

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

  15. DNA repair: Dynamic defenders against cancer and aging

    SciTech Connect

    Fuss, Jill O.; Cooper, Priscilla K.

    2006-04-01

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

  16. Macrophage Phenotype in Liver Injury and Repair.

    PubMed

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

    2017-03-01

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

  17. Carbon nanotubes in neuroregeneration and repair.

    PubMed

    Fabbro, Alessandra; Prato, Maurizio; Ballerini, Laura

    2013-12-01

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

  18. 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

  19. Prokaryotic Nucleotide Excision Repair

    PubMed Central

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

    2013-01-01

    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

  20. 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.

  1. Rapid Runway Repair Study.

    DTIC Science & Technology

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

  2. Repair of Auricular Defects.

    PubMed

    Watson, Deborah; Hecht, Avram

    2017-08-01

    Repairing defects of the auricle requires an appreciation of the underlying 3-dimensional framework, the flexible properties of the cartilages, and the healing contractile tendencies of the surrounding soft tissue. In the analysis of auricular defects and planning of their reconstruction, it is helpful to divide the auricle into subunits for which different techniques may offer better functional and aesthetic outcomes. This article reviews many of the reconstructive options for defects of the various auricular subunits. Published by Elsevier Inc.

  3. 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…

  4. 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…

  5. Viral manipulation of DNA repair and cell cycle checkpoints

    PubMed Central

    Chaurushiya, Mira S.; Weitzman, Matthew D.

    2009-01-01

    Recognition and repair of DNA damage is critical for maintaining genomic integrity and suppressing tumorigenesis. In eukaryotic cells, the sensing and repair of DNA damage are exquisitely coordinated with cell cycle progression and checkpoints, in order to prevent the propagation of damaged DNA. The carefully maintained cellular response to DNA damage is challenged by viruses, which produce a large amount of exogenous DNA during infection. Viruses also express proteins that perturb cellular DNA repair and cell cycle pathways, promoting tumorigenesis in their quest for cellular domination. This review presents an overview of strategies employed by viruses to manipulate DNA damage responses and cell cycle checkpoints as they commandeer the cell to maximize their own viral replication. Studies of viruses have identified key cellular regulators and revealed insights into molecular mechanisms governing DNA repair, cell cycle checkpoints, and transformation. PMID:19473887

  6. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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

  8. Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis.

    PubMed

    Adar, Sheera; Hu, Jinchuan; Lieb, Jason D; Sancar, Aziz

    2016-04-12

    We recently developed a high-resolution genome-wide assay for mapping DNA excision repair named eXcision Repair-sequencing (XR-seq) and have now used XR-seq to determine which regions of the genome are subject to repair very soon after UV exposure and which regions are repaired later. Over a time course, we measured repair of the UV-induced damage of cyclobutane pyrimidine dimers (CPDs) (at 1, 4, 8, 16, 24, and 48 h) and (6-4)pyrimidine-pyrimidone photoproducts [(6-4)PPs] (at 5 and 20 min and 1, 2, and 4 h) in normal human skin fibroblasts. Each type of damage has distinct repair kinetics. The (6-4)PPs are detected as early as 5 min after UV treatment, with the bulk of repair completed by 4 h. Repair of CPDs, which we previously showed is intimately coupled to transcription, is slower and in certain regions persists even 2 d after UV irradiation. We compared our results to the Encyclopedia of DNA Elements data regarding histone modifications, chromatin state, and transcription. For both damage types, and for both transcription-coupled and general excision repair, the earliest repair occurred preferentially in active and open chromatin states. Conversely, repair in regions classified as "heterochromatic" and "repressed" was relatively low at early time points, with repair persisting into the late time points. Damage that remains during DNA replication increases the risk for mutagenesis. Indeed, late-repaired regions are associated with a higher level of cancer-linked mutations. In summary, we show that XR-seq is a powerful approach for studying relationships among chromatin state, DNA repair, genome stability, mutagenesis, and carcinogenesis.

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

    PubMed

    Seeber, Andrew; Gasser, Susan M

    2016-10-31

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

  10. 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

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

    PubMed

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

    2007-02-19

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

  12. A distinctly disorganised dwarf

    NASA Image and Video Library

    2016-03-28

    Despite being less famous than their elliptical and spiral galactic cousins, irregular dwarf galaxies, such as the one captured in this NASA/ESA Hubble Space Telescope image, are actually one of the most common types of galaxy in the Universe. Known as UGC 4459, this dwarf galaxy is located approximately 11 million light-years away in the constellation of Ursa Major (The Great Bear), a constellation that is also home to the Pinwheel Galaxy (M101), the Owl Nebula (M97), Messier 81, Messier 82 and several other galaxies all part of the M81 group. UGC 4459’s diffused and disorganised appearance is characteristic of an irregular dwarf galaxy. Lacking a distinctive structure or shape, irregular dwarf galaxies are often chaotic in appearance, with neither a nuclear bulge — a huge, tightly packed central group of stars — nor any trace of spiral arms — regions of stars extending from the centre of the galaxy. Astronomers suspect that some irregular dwarf galaxies were once spiral or elliptical galaxies, but were later deformed by the gravitational pull of nearby objects. Rich with young blue stars and older red stars, UGC 4459 has a stellar population of several billion. Though seemingly impressive, this is small when compared to the 200 to 400 billion stars in the Milky Way! Observations with Hubble have shown that because of their low masses, star formation is very low compared to larger galaxies. Only very little of their original gas has been turned into stars. Thus, these small galaxies are interesting to study to better understand primordial environments and the star formation process.

  13. Strategies for the etiological therapy of cystic fibrosis.

    PubMed

    Maiuri, Luigi; Raia, Valeria; Kroemer, Guido

    2017-11-01

    Etiological therapies aim at repairing the underlying cause of cystic fibrosis (CF), which is the functional defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein owing to mutations in the CFTR gene. Among these, the F508del CFTR mutation accounts for more than two thirds of CF cases worldwide. Two somehow antinomic schools of thought conceive CFTR repair in a different manner. According to one vision, drugs should directly target the mutated CFTR protein to increase its plasma membrane expression (correctors) or improve its ion transport function (potentiators). An alternative strategy consists in modulating the cellular environment and proteostasis networks in which the mutated CFTR protein is synthesized, traffics to its final destination, the plasma membrane, and is turned over. We will analyze distinctive advantages and drawbacks of these strategies in terms of their scientific and clinical dimensions, and we will propose a global strategy for CF research and development based on a reconciliatory approach. Moreover, we will discuss the utility of preclinical biomarkers that may guide the personalized, patient-specific implementation of CF therapies.

  14. Improved Acquisition for System Sustainment: Availability-Based Importance Framework for Maintenance, Repair, and Overhaul Acquisition

    DTIC Science & Technology

    2015-06-30

    SPONSORED REPORT SERIES Improved Acquisition for System Sustainment: Availability- Based Importance Framework for Maintenance, Repair, and Overhaul...Sustainment: Availability- Based Importance Framework for Maintenance, Repair, and Overhaul Acquisition Prime Offeror Institution University of Oklahoma...Availability- Based Importance Measures . An effective defense strategy requires aircraft, among other weapons systems, to be available and ready for use when

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

    DTIC Science & Technology

    2009-08-01

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

  16. Making Technological Timelines: Anticipatory Repair and Testing in High Performance Scientific Computing

    DOE PAGES

    Sims, Benjamin

    2017-05-23

    Think of some examples of repair in everyday life. Maybe you had a car accident and took your car to the body shop. Maybe the head came off your child’s doll and you had to glue it back on. Maybe the handle of your shovel cracked and you wrapped the cracked area with duct tape to hold it together. These are examples of what could be called reactive repair, where an unexpected accident initiates a sequence of action and decision-making that ends in repair. In these cases, most of the thinking and planning surrounding repair takes place after a breakdownmore » has been identified. This type of repair is often taken to be distinct from deliberate design, as it occurs within the context of technology that is already in operation, often has an improvisational character, and may be performed by end users or technicians rather than credentialed experts. But does repair always have to be reactive? And if not, what does this tell us about the distinction between design and repair, and their respective roles in shaping technological change? The short answer is that repair, like design, can play a dynamic and forward-looking role in shaping technological trajectories – not only stabilizing existing systems, but anticipating change and generating new technological futures.« less

  17. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

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

  18. DNA repair in cultured keratinocytes

    SciTech Connect

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

    1983-07-01

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

  19. DNA excision repair at telomeres.

    PubMed

    Jia, Pingping; Her, Chengtao; Chai, Weihang

    2015-12-01

    DNA damage is caused by either endogenous cellular metabolic processes such as hydrolysis, oxidation, alkylation, and DNA base mismatches, or exogenous sources including ultraviolet (UV) light, ionizing radiation, and chemical agents. Damaged DNA that is not properly repaired can lead to genomic instability, driving tumorigenesis. To protect genomic stability, mammalian cells have evolved highly conserved DNA repair mechanisms to remove and repair DNA lesions. Telomeres are composed of long tandem TTAGGG repeats located at the ends of chromosomes. Maintenance of functional telomeres is critical for preventing genome instability. The telomeric sequence possesses unique features that predispose telomeres to a variety of DNA damage induced by environmental genotoxins. This review briefly describes the relevance of excision repair pathways in telomere maintenance, with the focus on base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). By summarizing current knowledge on excision repair of telomere damage and outlining many unanswered questions, it is our hope to stimulate further interest in a better understanding of excision repair processes at telomeres and in how these processes contribute to telomere maintenance. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

    Sun, Dong

    2016-01-01

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

  1. Combinatorial Reliability and Repair

    DTIC Science & Technology

    1992-07-01

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

  2. Electric motor model repair specifications. Final report

    SciTech Connect

    1996-06-01

    These Model Repair Specifications list the minimum requirements for the repair and overhaul of polyphase AC squirrel cage motors. All power ranges, voltages, and speeds of squirrel cage motors are covered, although not all repair situations are covered. Requirements are given for electric motor repair procedures, quality control, documentation, and repair shop evaluation. The document includes references to relevant industry standards.

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

    PubMed

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

    2011-09-01

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

  4. Progress in Neuroprotective Strategies for Preventing Epilepsy

    PubMed Central

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

    2008-01-01

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

  5. Skeletal myoblasts for cardiac repair.

    PubMed

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

    2010-11-01

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

  6. Bioactive Glass for Large Bone Repair.

    PubMed

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

    2015-12-30

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

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

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

    PubMed Central

    Abbotts, Rachel; Thompson, Nicola; Madhusudan, Srinivasan

    2014-01-01

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

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

    PubMed

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

    2007-11-01

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

  10. Mononuclear cells and vascular repair in HHT.

    PubMed

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

    2015-01-01

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

  11. Cycling with BRCA2 from DNA repair to mitosis

    SciTech Connect

    Lee, Hyunsook

    2014-11-15

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

  12. 40 CFR 63.1024 - Leak repair.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2016-09-26

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

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

    SciTech Connect

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

    1993-10-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. Pipe inspection and repair system

    NASA Technical Reports Server (NTRS)

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

    2004-01-01

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

  18. Instructional Guide for Autobody Repair.

    ERIC Educational Resources Information Center

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

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

  19. Membrane Repair: Mechanisms and Pathophysiology

    PubMed Central

    Cooper, Sandra T.; McNeil, Paul L.

    2015-01-01

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

  20. Major Appliance Repair. Teacher Edition.

    ERIC Educational Resources Information Center

    Smreker, Eugene; Calvert, King

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

  1. Small Crater Expedient Repair Test.

    DTIC Science & Technology

    1980-08-01

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

  2. Cobbler's Technique for Iridodialysis Repair

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  4. Development of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Meyer, Peggy L.

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

  5. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

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

  6. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

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

  7. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

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

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

    PubMed

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

    2000-08-01

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

  9. Optimal Distinctiveness Signals Membership Trust.

    PubMed

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

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

  10. Laparoscopic repair of recurrent hernias.

    PubMed

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

    1995-02-01

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

  11. Rethinking transcription coupled DNA repair.

    PubMed

    Kamarthapu, Venu; Nudler, Evgeny

    2015-04-01

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

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

    PubMed Central

    Niedernhofer, Laura J.

    2008-01-01

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

  13. TPS Inspection and Repair

    NASA Technical Reports Server (NTRS)

    Parazynski, Scott

    2012-01-01

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

  14. Wound repair in Pocillopora.

    PubMed

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

    2016-09-01

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

  15. Coal bunker repairs

    SciTech Connect

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

    1992-01-01

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

  16. Wound repair in Pocillopora

    USGS Publications Warehouse

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

    2016-01-01

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

  17. TPS Inspection and Repair

    NASA Technical Reports Server (NTRS)

    Parazynski, Scott

    2012-01-01

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

  18. Increasing Intergroup Distinctiveness: The Benefits of Third Party Helping.

    PubMed

    van Leeuwen, Esther; Harinck, Fieke

    2016-10-01

    Discrimination is often used to increase public perceptions of group distinctiveness. The current research studied the effectiveness of third party helping as an alternative, more benign strategy to this end. Across four studies, we examined whether helping a third party can position the helping group as more distinct from, or more similar to, a comparison group, depending on the nature of the comparison group's relationship with the third party. Results from three studies showed that third party helping was as effective as discrimination of the comparison group, but third party helping elicited a more positive public image of the group compared with discrimination. Study 4 provided evidence for the spontaneous use of third party helping in response to distinctiveness threat. These findings extend insights from classic balance theories and research on strategic intergroup helping to the domain of intergroup differentiation, and highlight a benign strategy to achieve positive group distinctiveness. © 2016 by the Society for Personality and Social Psychology, Inc.

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

    PubMed

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

    2009-06-04

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

  20. How to repair an episiotomy.

    PubMed

    Steen, Mary; Cummins, Bernie

    2016-02-17

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

  1. Repairing pipes on the fly

    SciTech Connect

    1997-04-01

    When piping develops leaks, the natural instinct is to shut the process down, purge the lines and call in maintenance crews to make the repairs. There is, however, an alternative: on-the-fly repairs. Through the use of specialized tools, equipment and technicians, shut-off valves can be installed and leaks repaired without interrupting production. The split sleeve offers one of the simpler approaches to on-the-fly repairs. Two half cylinders with inside diameter slightly larger than the outside diameter slightly larger than the outside diameter of the pipe to be repaired are slipped over the latter some distance form the leak and loosely bolted together. The cylinder is then slid over the leaking area and the bolts tightened. Gaskets inside the half cylinders provide the needed seal between the pipe and the cylinder. Installing a shut-off valve in an operating pipeline requires much more specialized equipment and skills than does repairing a leak with a split sleeve. A device available from International Piping Services Co. allows a trained crew to isolate a section of pipe, drill out the isolated portion, install a blocking valve and then remove the isolation system--all while continuing to operate the pipeline at temperatures to 700 F and pressures to 700 psi. But Herb Porter, CEO of Ipsco, cautions that unlike the repairing leaks with a split sleeve, installing a blocking valve on-the-fly always demands the services of a highly trained crew.

  2. A spacecraft computer repairable via command.

    NASA Technical Reports Server (NTRS)

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

    1971-01-01

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

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

    PubMed

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

    2009-02-01

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

  4. DNA Repair Deficiency in Neurodegeneration

    PubMed Central

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

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby causing Huntington’s disease. Single-strand breaks are common DNA lesions and are associated with the neurodegenerative diseases, ataxia-oculomotor apraxia-1 and spinocerebellar ataxia with axonal neuropathy-1. DNA double-strand breaks are toxic lesions and two main pathways exist for their repair: homologous recombination and non-homologous end-joining. Ataxia telangiectasia and related disorders with defects in these pathways illustrate that such defects can lead to early childhood neurodegeneration. Aging is a risk factor for neurodegeneration and accumulation of oxidative mitochondrial DNA damage may be linked with the age-associated neurodegenerative disorders Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Mutation in the WRN protein leads to the premature aging disease Werner syndrome, a disorder that features neurodegeneration. In this article we review the evidence linking deficiencies in the DNA repair pathways with neurodegeneration. PMID:21550379

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  9. 40 CFR 798.5500 - Differential growth inhibition of repair proficient and repair deficient bacteria: “Bacterial DNA...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  10. Surveillance after endovascular aortic repair.

    PubMed

    Zaiem, Feras; Almasri, Jehad; Tello, Mouaffaa; Prokop, Larry J; Chaikof, Elliot L; Murad, Mohammad Hassan

    2017-06-26

    The objective of this systematic review and meta-analysis was to evaluate the optimal modality and frequency of surveillance after endovascular aortic repair (EVAR) in adult patients with abdominal aortic aneurysms. We searched for studies of post-EVAR surveillance in MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Scopus through May 10, 2016. The outcomes of interest were endoleaks, mortality, limb ischemia, renal complications, late rupture, and aneurysm-related mortality. Outcomes were pooled using a random-effects model and were reported as incidence rate and 95% confidence interval. Of 1099 candidate references, we included 6 meta-analyses and 52 observational studies. Complication rates were common after EVAR, particularly in the first year. Magnetic resonance imaging had a higher detection rate of endoleaks than computed tomography angiography. Doppler ultrasound had lower diagnostic accuracy, whereas contrast-enhanced ultrasound was likely to be as sensitive as computed tomography angiography. The highest endoleak detection rates were in surveillance approaches that used combined tests. There were no studies that compared different surveillance intervals to determine optimal intervals; however, most studies reported detection rates of patient-important outcomes at 1, 6, 12, 24, 36, 48, and 60 months. Data were insufficient to provide comparative inferences about the best strategy to reduce the risk of patient-important outcomes, such as mortality, limb ischemia, rupture, and renal complications. Several tests with reasonable diagnostic accuracy are available for surveillance after EVAR. The available evidence suggests a high complication rate, particularly in the first year, and provides a rationale for surveillance. Published by Elsevier Inc.

  11. Bone repair and stem cells.

    PubMed

    Ono, Noriaki; Kronenberg, Henry M

    2016-10-01

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

  12. Repair Types, Procedures - Part 2

    DTIC Science & Technology

    2010-05-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

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

    PubMed Central

    Madry, Henning

    2016-01-01

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

  15. Repair of bilateral cleft lip and its variants

    PubMed Central

    Mulliken, John B.

    2009-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Fitzgerald, Jamie

    2016-01-01

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

  18. On structural health monitoring of aircraft adhesively bonded repairs

    NASA Astrophysics Data System (ADS)

    Pavlopoulou, Sofia

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

  19. Advances in biology and mechanics of rotator cuff repair.

    PubMed

    Lorbach, Olaf; Baums, Mike H; Kostuj, Tanja; Pauly, Stephan; Scheibel, Markus; Carr, Andrew; Zargar, Nasim; Saccomanno, Maristella F; Milano, Giuseppe

    2015-02-01

    High initial fixation strength, mechanical stability and biological healing of the tendon-to-bone interface are the main goals after rotator cuff repair surgery. Advances in the understanding of rotator cuff biology and biomechanics as well as improvements in surgical techniques have led to the development of new strategies that may allow a tendon-to-bone interface healing process, rather than the formation of a fibrovascular scar tissue. Although single-row repair remains the most cost-effective technique to address a rotator cuff tear, some biological intervention has been recently introduced to improve tissue healing and clinical outcome of rotator cuff repair. Animal models are critical to ensure safety and efficacy of new treatment strategies; however, although rat shoulders as well as sheep and goats are considered the most appropriate models for studying rotator cuff pathology, no one of them can fully reproduce the human condition. Emerging therapies involve growth factors, stem cells and tissue engineering. Experimental application of growth factors and platelet-rich plasma demonstrated promising results, but has not yet been transferred into standardized clinical practice. Although preclinical animal studies showed promising results on the efficacy of enhanced biological approaches, application of these techniques in human rotator cuff repairs is still very limited. Randomized controlled clinical trials and post-marketing surveillance are needed to clearly prove the clinical efficacy and define proper indications for the use of combined biological approaches. The following review article outlines the state of the art of rotator cuff repair and the use of growth factors, scaffolds and stem cells therapy, providing future directions to improve tendon healing after rotator cuff repair. Expert opinion, Level V.

  20. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must be...

  1. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must be...

  2. 46 CFR Sec. 19 - Ship Repair Summaries.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must be...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Ship Repair Summaries. Sec. 19 Section 19 Shipping... Sec. 19 Ship Repair Summaries. (a) Ship Repair Summaries shall be prepared on Form MA-159 by the... jurisdiction and submitted to the District Ship Repair and Maintenance office involved. The summaries must be...

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

    NASA Astrophysics Data System (ADS)

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

    1995-07-01

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

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

    PubMed

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

    2016-08-18

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

  6. Verb class distinctions and AAC language-encoding limitations.

    PubMed

    Sutton, A E; Gallagher, T M

    1993-12-01

    This study explored the status of an English grammatical distinction in the language of individuals who have never been able to encode that distinction previously. English past tense marking was used as a context to examine regular and irregular verb class distinctions in the language of two adults with severe congenital physical impairments who rely on augmentative and alternative communication (AAC) systems to communicate. In the subjects' lexically based AAC systems, past tense was marked on regular verbs and irregular verbs using the same strategy. The subjects accessed their AAC displays using four-digit eye gaze number codes. They were shown a novel affixation strategy through manipulation of the four-digit codes that allowed them to mark past tense on regular verbs via an affixation process. Their semantic strategy for marking past tense on irregular verbs was not changed. The subjects' patterns of use of the two strategies on exemplars of each verb class revealed limited evidence of distinctive use of the two strategies based on verb class membership. Theoretical and clinical implications are discussed.

  7. Mammalian DNA Repair. Final Report

    SciTech Connect

    2003-01-24

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

  8. Precision Instrument and Equipment Repairers.

    ERIC Educational Resources Information Center

    Wyatt, Ian

    2001-01-01

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

  9. Mismatch repair in heteroduplex DNA.

    PubMed Central

    Wildenberg, J; Meselson, M

    1975-01-01

    DNA with base pair mismatches was prepared by annealing mixtures of genetically marked DNA from bacteriophage lambda. This heteroduplex DNA was used to transfect bacteria under conditions minimizing recombination. Genetic analysis of the progeny phages indicates that: (i) Mismatch repair occurs, usually giving rise to a DNA molecule with one chain with the genotype arising from repair and one parental chain. (ii) The frequency of repair of a given mismatch to wild type depends on the marker, ranging from 3 to 20%. (iii) Excision tracts may extend several hundred nucleotides but are usually shorter than about 2000 nucleotides. (iv) In Rec-mediated bacteriophage crosses, recombination of markers closer than about 10-3 nucleotide pairs frequently occurs by mismatch repair within heteroduplex DNA. (V) The average amount of heteroduplex DNA formed in a Rec-mediated recombination event is a few thousand nucleotide pairs. PMID:1094458

  10. Aortic aneurysm repair - endovascular- discharge

    MedlinePlus

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

  11. Anterior cruciate ligament repair - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100230.htm Anterior cruciate ligament repair - Series—Normal anatomy To use the sharing ... to slide 5 out of 5 Overview The anterior cruciate ligament (ACL) is a ligament in the center of ...

  12. Hypospadias repair: the seagull meatoplasty.

    PubMed

    Roberts, A H; Dickinson, J C

    1987-01-01

    An operation is described which has been used in six cases to produce a single stream of urine in patients who were spraying following hypospadias repair. It has also been used in four patients to advance the meatus terminally.

  13. Bladder and urethral repair - slideshow

    MedlinePlus

    ... 100002.htm Bladder and urethral repair - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

  14. Nucleotide excision repair in humans

    PubMed Central

    Spivak, Graciela

    2015-01-01

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

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

    PubMed

    Rupp, W Dean

    2013-12-13

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

  16. Aging impairs double-strand break repair by homologous recombination in Drosophila germ cells.

    PubMed

    Delabaere, Laetitia; Ertl, Henry A; Massey, Dashiell J; Hofley, Carolyn M; Sohail, Faraz; Bienenstock, Elisa J; Sebastian, Hans; Chiolo, Irene; LaRocque, Jeannine R

    2017-04-01

    Aging is characterized by genome instability, which contributes to cancer formation and cell lethality leading to organismal decline. The high levels of DNA double-strand breaks (DSBs) observed in old cells and premature aging syndromes are likely a primary source of genome instability, but the underlying cause of their formation is still unclear. DSBs might result from higher levels of damage or repair defects emerging with advancing age, but repair pathways in old organisms are still poorly understood. Here, we show that premeiotic germline cells of young and old flies have distinct differences in their ability to repair DSBs by the error-free pathway homologous recombination (HR). Repair of DSBs induced by either ionizing radiation (IR) or the endonuclease I-SceI is markedly defective in older flies. This correlates with a remarkable reduction in HR repair measured with the DR-white DSB repair reporter assay. Strikingly, most of this repair defect is already present at 8 days of age. Finally, HR defects correlate with increased expression of early HR components and increased recruitment of Rad51 to damage in older organisms. Thus, we propose that the defect in the HR pathway for germ cells in older flies occurs following Rad51 recruitment. These data reveal that DSB repair defects arise early in the aging process and suggest that HR deficiencies are a leading cause of genome instability in germ cells of older animals. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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

    PubMed Central

    Boulton, S J; Jackson, S P

    1996-01-01

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

  18. Rehabilitation after Rotator Cuff Repair

    PubMed Central

    Nikolaidou, Ourania; Migkou, Stefania; Karampalis, Christos

    2017-01-01

    Background: Rotator cuff tears are a very common condition that is often incapacitating. Whether non-surgical or surgical, successful management of rotator cuff disease is dependent on appropriate rehabilitation. If conservative management is insufficient, surgical repair is often indicated. Postsurgical outcomes for patients having had rotator cuff repair can be quite good. A successful outcome is much dependent on surgical technique as it is on rehabilitation. Numerous rehabilitation protocols for the management of rotator cuff disease are based primarily on clinical experience and expert opinion. This article describes the different rehabilitation protocols that aim to protect the repair in the immediate postoperative period, minimize postoperative stiffness and muscle atrophy. Methods: A review of currently available literature on rehabilitation after arthroscopic rotator cuff tear repair was performed to illustrate the available evidence behind various postoperative treatment modalities. Results: There were no statistically significant differences between a conservative and an accelerated rehabilitation protocol . Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. Conclusion: The currently available literature did not identify any significant differences in functional outcomes and relative risks of re-tears between delayed and early motion in patients undergoing arthroscopic rotator cuff repairs. A gentle rehabilitation protocol with limits in range of motion and exercise times after arthroscopic rotator cuff repair would be better for tendon healing without taking any substantial risks. A close communication between the surgeon, the patient and the physical therapy team is important and should continue throughout the whole recovery process. PMID:28400883

  19. Kaumalapau Harbor, Hawaii, Breakwater Repair

    DTIC Science & Technology

    2012-05-01

    state includes a global wave model, Hawaii wave model, and separate nearshore domains for Kauai , Oahu, Maui, and the Big Island (The Maui domain...ER D C/ CH L TR -1 2 -7 Monitoring Completed Navigation Projects Program Kaumalapau Harbor, Hawaii , Breakwater Repair C oa st al a n d...Monitoring Completed Navigation Projects Program ERDC/CHL TR-12-7 May 2012 Kaumalapau Harbor, Hawaii , Breakwater Repair Jessica H. Podoski and

  20. Rehabilitation after Rotator Cuff Repair.

    PubMed

    Nikolaidou, Ourania; Migkou, Stefania; Karampalis, Christos

    2017-01-01

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

  1. Shotcrete for Expedient Structural Repair

    DTIC Science & Technology

    1991-12-01

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

  2. Durability of Expedient Repair Materials

    DTIC Science & Technology

    1993-03-01

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

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

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

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

  4. Shining Light on Nanotechnology to Help Repair and Regeneration

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Minsky, Abraham

    2003-10-01

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

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

    PubMed

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

    2013-01-01

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

  7. Repair-Resistant DNA Lesions

    PubMed Central

    2017-01-01

    The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

  8. Parastomal hernia repair. An update.

    PubMed

    Wara, P

    2011-04-01

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

  9. Arthroscopic revision of Bankart repair.

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    1996-12-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. The impact of endovascular aneurysm repair on mortality for elective abdominal aortic aneurysm repair in England and the United States.

    PubMed

    Karthikesalingam, Alan; Holt, Peter J; Vidal-Diez, Alberto; Bahia, Sandeep S; Patterson, Benjamin O; Hinchliffe, Robert J; Thompson, Matthew M

    2016-08-01

    Procedural mortality is of paramount importance for patients undergoing elective abdominal aortic aneurysm (AAA) repair. Previous comparative studies have demonstrated international differences in the care of ruptured AAA. This study compared the use of endovascular aneurysm repair (EVAR) and in-hospital mortality for elective AAA repair in England and the United States. The English Hospital Episode Statistics and the U.S. Nationwide Inpatient Sample (NIS) were interrogated for elective AAA repair from 2005 to 2010. In-hospital mortality and the use of EVAR were analyzed separately for each health care system, after within-country risk adjustment for age, gender, year, and an accepted national comorbidity index. The study included 21,272 patients with AAA in England, of whom 86.61% were male, with median (interquartile range) age of 74 (69-79) years. There were 196,113 AAA patients in the United States, of whom 76.14% were male, with median (interquartile range) age of 73 (67-78) years. In-hospital mortality was greater in England (4.09% vs 1.96 %; P < .01) and EVAR less common (37.33% vs 64.36%; P < .01). These observations persisted in age- and gender-matched comparison. In both countries, lower mortality and greater use of EVAR were seen in centers performing greater numbers of AAA repairs per annum. In England, lower mortality and greater use of EVAR were seen in teaching hospitals with larger bed capacity. In-hospital survival and the uptake of EVAR are lower in England than in the United States. In both countries, mortality was lowest in high-caseload centers performing a greater proportion of cases with endovascular repair. These common factors suggest strategies for improving outcomes for patients requiring elective AAA repair. Copyright © 2016. Published by Elsevier Inc.

  13. miRNA Control of Tissue Repair and Regeneration

    PubMed Central

    Sen, Chandan K.; Ghatak, Subhadip

    2016-01-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics. PMID:26056933

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

    PubMed

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

    2016-10-01

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

  15. Results of arthroscopic meniscal repair

    PubMed Central

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

    2017-01-01

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

  16. Distinctive photosystem II photoinactivation and protein dynamics in marine diatoms.

    PubMed

    Wu, Hongyan; Cockshutt, Amanda M; McCarthy, Avery; Campbell, Douglas A

    2011-08-01

    Diatoms host chlorophyll a/c chloroplasts distinct from green chloroplasts. Diatoms now dominate the eukaryotic oceanic phytoplankton, in part through their exploitation of environments with variable light. We grew marine diatoms across a range of temperatures and then analyzed their PSII function and subunit turnover during an increase in light to mimic an upward mixing event. The small diatom Thalassiosira pseudonana initially responds to increased photoinactivation under blue or white light with rapid acceleration of the photosystem II (PSII) repair cycle. Increased red light provoked only modest PSII photoinactivation but triggered a rapid clearance of a subpool of PsbA. Furthermore, PsbD and PsbB content was greater than PsbA content, indicating a large pool of partly assembled PSII repair cycle intermediates lacking PsbA. The initial replacement rates for PsbD (D2) were, surprisingly, comparable to or higher than those for PsbA (D1), and even the supposedly stable PsbB (CP47) dropped rapidly upon the light shift, showing a novel aspect of rapid protein subunit turnover in the PSII repair cycle in small diatoms. Under sustained high light, T. pseudonana induces sustained nonphotochemical quenching, which correlates with stabilization of PSII function and the PsbA pool. The larger diatom Coscinodiscus radiatus showed generally similar responses but had a smaller allocation of PSII complexes relative to total protein content, with nearly equal stiochiometries of PsbA and PsbD subunits. Fast turnover of multiple PSII subunits, pools of PSII repair cycle intermediates, and photoprotective induction of nonphotochemical quenching are important interacting factors, particularly for small diatoms, to withstand and exploit high, fluctuating light.

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

    PubMed

    Alloush, Jenna; Weisleder, Noah

    2013-07-01

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

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

    PubMed Central

    Qiu, Zhenling

    2015-01-01

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

  19. Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.

    PubMed

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

    2014-01-01

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

  20. Human embryonic stem cells and cardiac repair.

    PubMed

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

    2009-01-01

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