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  1. The role of DNA base excision repair in brain homeostasis and disease

    DEFF Research Database (Denmark)

    Akbari, Mansour; Morevati, Marya; Croteau, Deborah;

    2015-01-01

    Chemical modification and spontaneous loss of nucleotide bases from DNA are estimated to occur at the rate of thousands per human cell per day. DNA base excision repair (BER) is a critical mechanism for repairing such lesions in nuclear and mitochondrial DNA. Defective expression or function...... of proteins required for BER or proteins that regulate BER have been consistently associated with neurological dysfunction and disease in humans. Recent studies suggest that DNA lesions in the nuclear and mitochondrial compartments and the cellular response to those lesions have a profound effect on cellular...... energy homeostasis, mitochondrial function and cellular bioenergetics, with especially strong influence on neurological function. Further studies in this area could lead to novel approaches to prevent and treat human neurodegenerative disease....

  2. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  3. Editor's Highlight: Base Excision Repair Variants and Pesticide Exposure Increase Parkinson's Disease Risk.

    Science.gov (United States)

    Sanders, Laurie H; Paul, Kimberly C; Howlett, Evan H; Lawal, Hakeem; Boppana, Sridhar; Bronstein, Jeff M; Ritz, Beate; Greenamyre, J Timothy

    2017-07-01

    Exposure to certain pesticides induces oxidative stress and increases Parkinson's disease (PD) risk. Mitochondrial DNA (mtDNA) damage is found in dopaminergic neurons in idiopathic PD and following pesticide exposure in experimental models thereof. Base excision repair (BER) is the major pathway responsible for repairing oxidative DNA damage in cells. Whether single nucleotide polymorphisms (SNPs) in BER genes alone or in combination with pesticide exposure influence PD risk is unknown. We investigated the contributions of functional SNPs in 2 BER genes (APEX1 and OGG1) and mitochondrial dysfunction- or oxidative stress-related pesticide exposure, including paraquat, to PD risk. We also studied the effect of paraquat on levels of mtDNA damage and mitochondrial bioenergetics. 619 PD patients and 854 population-based controls were analyzed for the 2 SNPs, APEX1 rs1130409 and OGG1 rs1052133. Ambient pesticide exposures were assessed with a geographic information system. Individually, or in combination, the BER SNPs did not influence PD risk. Mitochondrial-inhibiting (OR = 1.79, 95% CI [1.32, 2.42]), oxidative stress-inducing pesticides (OR = 1.61, 95% CI [1.22, 2.11]), and paraquat (OR = 1.54, 95% CI [1.23, 1.93]) were associated with PD. Statistical interactions were detected, including for a genetic risk score based on rs1130409 and rs1052133 and oxidative stress inducing pesticides, where highly exposed carriers of both risk genotypes were at the highest risk of PD (OR = 2.21, 95% CI [1.25, 3.86]); similar interactions were estimated for mitochondrial-inhibiting pesticides and paraquat alone. Additionally, paraquat exposure was found to impair mitochondrial respiration and increase mtDNA damage in in vivo and in vitro systems. Our findings provide insight into possible mechanisms involved in increased PD risk due to pesticide exposure in the context of BER genotype variants. © The Author 2017. Published by Oxford University Press on behalf of the

  4. Alzheimer’s Disease-Associated Neurotoxic Peptide Amyloid-Β Impairs Base Excision Repair in Human Neuroblastoma Cells

    Directory of Open Access Journals (Sweden)

    Anne Forestier

    2012-11-01

    Full Text Available Alzheimer’s disease (AD is the leading cause of dementia in developed countries. It is characterized by two major pathological hallmarks, one of which is the extracellular aggregation of the neurotoxic peptide amyloid-β (Aβ, which is known to generate oxidative stress. In this study, we showed that the presence of Aβ in a neuroblastoma cell line led to an increase in both nuclear and mitochondrial DNA damage. Unexpectedly, a concomitant decrease in basal level of base excision repair, a major route for repairing oxidative DNA damage, was observed at the levels of both gene expression and protein activity. Moreover, the addition of copper sulfate or hydrogen peroxide, used to mimic the oxidative stress observed in AD-affected brains, potentiates Aβ-mediated perturbation of DNA damage/repair systems in the “Aβ cell line”. Taken together, these findings indicate that Aβ could act as double-edged sword by both increasing oxidative nuclear/mitochondrial damage and preventing its repair. The synergistic effects of increased ROS production, accumulated DNA damage and impaired DNA repair could participate in, and partly explain, the massive loss of neurons observed in Alzheimer’s disease since both oxidative stress and DNA damage can trigger apoptosis.

  5. Mitochondrial base excision repair in mouse synaptosomes during normal aging and in a model of Alzheimer's disease.

    Science.gov (United States)

    Gredilla, Ricardo; Weissman, Lior; Yang, Jenq-Lin; Bohr, Vilhelm A; Stevnsner, Tinna

    2012-04-01

    Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of presymptomatic and symptomatic AD mice harboring mutated amyolid precursor protein (APP), Tau, and presinilin-1 (PS1) (3xTgAD). Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed.

  6. Base excision repair in sugarcane

    Directory of Open Access Journals (Sweden)

    Agnez-Lima Lucymara F.

    2001-01-01

    Full Text Available DNA damage can be induced by a large number of physical and chemical agents from the environment as well as compounds produced by cellular metabolism. This type of damage can interfere with cellular processes such as replication and transcription, resulting in cell death and/or mutations. The low frequency of mutagenesis in cells is due to the presence of enzymatic pathways which repair damaged DNA. Several DNA repair genes (mainly from bacteria, yeasts and mammals have been cloned and their products characterized. The high conservation, especially in eukaryotes, of the majority of genes related to DNA repair argues for their importance in the maintenance of life on earth. In plants, our understanding of DNA repair pathways is still very poor, the first plant repair genes having only been cloned in 1997 and the mechanisms of their products have not yet been characterized. The objective of our data mining work was to identify genes related to the base excision repair (BER pathway, which are present in the database of the Sugarcane Expressed Sequence Tag (SUCEST Project. This search was performed by tblastn program. We identified sugarcane clusters homologous to the majority of BER proteins used in the analysis and a high degree of conservation was observed. The best results were obtained with BER proteins from Arabidopsis thaliana. For some sugarcane BER genes, the presence of more than one form of mRNA is possible, as shown by the occurrence of more than one homologous EST cluster.

  7. DNA base excision repair nanosystem engineering: model development.

    Science.gov (United States)

    Sokhansanj, B A

    2005-01-01

    DNA base damage results from a combination of endogenous sources, (normal metabolism, increased metabolism due to obesity, stress from diseases such as arthritis and diabetes, and ischemia) and the environment (ingested toxins, ionizing radiation, etc.). If unrepaired DNA base damage can lead to diminished cell function, and potentially diseases and eventually mutations that lead to cancer. Sophisticated DNA repair mechanisms have evolved in all living cells to preserve the integrity of inherited genetic information and transcriptional control. Understanding a system like DNA repair is greatly enhanced by using engineering methods, in particular modeling interactions and using predictive simulation to analyze the impact of perturbations. We describe the use of such a "nanosystem engineering" approach to analyze the DNA base excision repair pathway in human cells, and use simulation to predict the impact of varying enzyme concentration on DNA repair capacity.

  8. Repair for acquired aortic valve disease.

    Science.gov (United States)

    Antunes, M J

    1996-10-01

    The favorable results of mitral valvuloplasty when compared with valve replacement have renewed the interest of many surgeons in aortic valve repair. However, these efforts have, for the most part, been unsuccessful. Also, the results of aortic valve replacement are usually better than those of mitral valve replacement. Yet, some patients appear to derive benefit from a conservative aortic valve procedure. The best examples are mild or moderate aortic valve disease associated with mitral valve or coronary artery disease, which constitute the primary indication for operation, where "prophylactic" aortic valve replacement does not appear justifiable. Other possible indications for aortic valvuloplasty includes patient's lack of compliance or contraindication to anticoagulation in young patients. Senile aortic stenosis, in very old patients with a small annulus, preserved leaflet morphology and nonsignificant commissural fusion should be considered for repair. However, since the procedure is not easily reproducible and the results not uniformly predictable, it cannot be recommended for generalized use. Nonetheless, experienced surgeons should be encouraged to continue these efforts.

  9. Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice.

    Science.gov (United States)

    Goula, Agathi-Vassiliki; Berquist, Brian R; Wilson, David M; Wheeler, Vanessa C; Trottier, Yvon; Merienne, Karine

    2009-12-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by expansion of an unstable CAG repeat in the coding sequence of the Huntingtin (HTT) gene. Instability affects both germline and somatic cells. Somatic instability increases with age and is tissue-specific. In particular, the CAG repeat sequence in the striatum, the brain region that preferentially degenerates in HD, is highly unstable, whereas it is rather stable in the disease-spared cerebellum. The mechanisms underlying the age-dependence and tissue-specificity of somatic CAG instability remain obscure. Recent studies have suggested that DNA oxidation and OGG1, a glycosylase involved in the repair of 8-oxoguanine lesions, contribute to this process. We show that in HD mice oxidative DNA damage abnormally accumulates at CAG repeats in a length-dependent, but age- and tissue-independent manner, indicating that oxidative DNA damage alone is not sufficient to trigger somatic instability. Protein levels and activities of major base excision repair (BER) enzymes were compared between striatum and cerebellum of HD mice. Strikingly, 5'-flap endonuclease activity was much lower in the striatum than in the cerebellum of HD mice. Accordingly, Flap Endonuclease-1 (FEN1), the main enzyme responsible for 5'-flap endonuclease activity, and the BER cofactor HMGB1, both of which participate in long-patch BER (LP-BER), were also significantly lower in the striatum compared to the cerebellum. Finally, chromatin immunoprecipitation experiments revealed that POLbeta was specifically enriched at CAG expansions in the striatum, but not in the cerebellum of HD mice. These in vivo data fit a model in which POLbeta strand displacement activity during LP-BER promotes the formation of stable 5'-flap structures at CAG repeats representing pre-expanded intermediate structures, which are not efficiently removed when FEN1 activity is constitutively low. We propose that the stoichiometry of BER enzymes is one critical

  10. Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Agathi-Vassiliki Goula

    2009-12-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder caused by expansion of an unstable CAG repeat in the coding sequence of the Huntingtin (HTT gene. Instability affects both germline and somatic cells. Somatic instability increases with age and is tissue-specific. In particular, the CAG repeat sequence in the striatum, the brain region that preferentially degenerates in HD, is highly unstable, whereas it is rather stable in the disease-spared cerebellum. The mechanisms underlying the age-dependence and tissue-specificity of somatic CAG instability remain obscure. Recent studies have suggested that DNA oxidation and OGG1, a glycosylase involved in the repair of 8-oxoguanine lesions, contribute to this process. We show that in HD mice oxidative DNA damage abnormally accumulates at CAG repeats in a length-dependent, but age- and tissue-independent manner, indicating that oxidative DNA damage alone is not sufficient to trigger somatic instability. Protein levels and activities of major base excision repair (BER enzymes were compared between striatum and cerebellum of HD mice. Strikingly, 5'-flap endonuclease activity was much lower in the striatum than in the cerebellum of HD mice. Accordingly, Flap Endonuclease-1 (FEN1, the main enzyme responsible for 5'-flap endonuclease activity, and the BER cofactor HMGB1, both of which participate in long-patch BER (LP-BER, were also significantly lower in the striatum compared to the cerebellum. Finally, chromatin immunoprecipitation experiments revealed that POLbeta was specifically enriched at CAG expansions in the striatum, but not in the cerebellum of HD mice. These in vivo data fit a model in which POLbeta strand displacement activity during LP-BER promotes the formation of stable 5'-flap structures at CAG repeats representing pre-expanded intermediate structures, which are not efficiently removed when FEN1 activity is constitutively low. We propose that the stoichiometry of BER enzymes

  11. Targeting base excision repair as a sensitization strategy in radiotherapy.

    NARCIS (Netherlands)

    Vens, C.; Begg, A.C.

    2010-01-01

    Cellular DNA repair determines survival after ionizing radiation. Human tumors commonly exhibit aberrant DNA repair since they drive mutagenesis and chromosomal instability. Recent reports have shown alterations in the base excision repair (BER) and single strand break repair (SSBR) pathways in huma

  12. X-ray repair cross complementing protein 1 in base excision repair

    DEFF Research Database (Denmark)

    Hanssen-Bauer, Audun; Solvang-Garten, Karin; Akbari, Mansour;

    2012-01-01

    X-ray Repair Cross Complementing protein 1 (XRCC1) acts as a scaffolding protein in the converging base excision repair (BER) and single strand break repair (SSBR) pathways. XRCC1 also interacts with itself and rapidly accumulates at sites of DNA damage. XRCC1 can thus mediate the assembly of large...

  13. Repair of dental resin-based composites.

    Science.gov (United States)

    Baur, Veronika; Ilie, Nicoleta

    2013-03-01

    The study analyzed the reparability and compatibility of light-curing resin-based composites (RBCs) of the categories "microhybrid," "nanohybrid," and "packable." Six RBCs with different matrix and filler formulation--purely methacrylate-based composites (MBCs), ormocer-based composites (OBCs), and silorane-based composites (SBCs)--were used for the specimens. Every material was combined with itself and with the other five RBCs, resulting in a total of 36 combination groups (n = 20). The specimens were polymerized, aged for 8 weeks in distilled water at 37 °C, and then repaired by means of a repair kit. Shear bond strength and fracture mode were measured after aging of the specimens, undergoing storage for 24 h in distilled water at 37 °C followed by thermocycling (5,000 cycles, 5-55 °C) and an additional 4-week storage in distilled water at 37 °C. Data were statistically analyzed using ANOVA with TUKEY HSD post hoc test (α = 0.05). On average, the OBC Admira reached the highest value as a substrate material (30.41 MPa), and the SBC Filtek Silorane reached the lowest value (8.14 MPa). Filtek Silorane was identified as the repair material with the highest bond strength value (28.70 MPa), while a packable composite reached the lowest bond strength value (15.55 MPa). The analysis of the break modes showed that adhesive breaks are typical when strength is at its lowest (6.27 MPa). A large number of cohesive fractures are conspicuous when identical materials are used for repair, except Filtek Silorane (2 % cohesive fractures). The study demonstrated that the effect of the different materials on bond strength varies strongly, depending on whether the material is used as filling or as repair material. It is generally advisable but not compulsory to combine identical RBCs.

  14. Mitochondrial base excision repair assays

    DEFF Research Database (Denmark)

    Maynard, Scott; de Souza-Pinto, Nadja C; Scheibye-Knudsen, Morten

    2010-01-01

    The main source of mitochondrial DNA (mtDNA) damage is reactive oxygen species (ROS) generated during normal cellular metabolism. The main mtDNA lesions generated by ROS are base modifications, such as the ubiquitous 8-oxoguanine (8-oxoG) lesion; however, base loss and strand breaks may also occur...

  15. Recombinational DNA repair and human disease

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Larry H.; Schild, David

    2002-11-30

    We review the genes and proteins related to the homologous recombinational repair (HRR) pathway that are implicated in cancer through either genetic disorders that predispose to cancer through chromosome instability or the occurrence of somatic mutations that contribute to carcinogenesis. Ataxia telangiectasia (AT), Nijmegen breakage syndrome (NBS), and an ataxia-like disorder (ATLD), are chromosome instability disorders that are defective in the ataxia telangiectasia mutated (ATM), NBS, and Mre11 genes, respectively. These genes are critical in maintaining cellular resistance to ionizing radiation (IR), which kills largely by the production of double-strand breaks (DSBs). Bloom syndrome involves a defect in the BLM helicase, which seems to play a role in restarting DNA replication forks that are blocked at lesions, thereby promoting chromosome stability. The Werner syndrome gene (WRN) helicase, another member of the RecQ family like BLM, has very recently been found to help mediate homologous recombination. Fanconi anemia (FA) is a genetically complex chromosomal instability disorder involving seven or more genes, one of which is BRCA2. FA may be at least partially caused by the aberrant production of reactive oxidative species. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in HRR; BRCA2 associates with Rad51 and appears to regulate its activity. We discuss in detail the phenotypes of the various mutant cell lines and the signaling pathways mediated by the ATM kinase. ATM's phosphorylation targets can be grouped into oxidative stress-mediated transcriptional changes, cell cycle checkpoints, and recombinational repair. We present the DNA damage response pathways by using the DSB as the prototype lesion, whose incorrect repair can initiate and augment karyotypic abnormalities.

  16. Insights on accelerated skeletal repair in Cushing's disease

    Directory of Open Access Journals (Sweden)

    So-Young Kim

    2015-06-01

    In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.

  17. Pregnancy after fontan repair of complex congenital heart disease.

    Science.gov (United States)

    Hoare, J V; Radford, D

    2001-11-01

    We describe four successful pregnancies in three women who had previously had a Fontan repair for congenital heart disease. Each pregnancy resulted in a live birth and there was no maternal mortality The infants were premature, being delivered at 26, 30 and 35 weeks, and weighing 1,020, 1,333 and 1,930 g respectively The fourth infant was born at 32 weeks and no birthweight is available. Maternal complications occurred and were those anticipated after a Fontan repair. Two mothers required treatment for supraventricular arrhythmias (atrial flutter and fibrillation). Ventricular failure was present in two mothers and required ongoing drug treatment. Raised systemic venous pressures caused peripheral oedema in two mothers and hepatomegaly and ascites in one mother. The physiology, potential complications, anaesthetic concerns and drug treatment in pregnancy after Fontan repair are discussed.

  18. Estimating the effect of human base excision repair protein variants on the repair of oxidative DNA base damage.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Wilson, David M

    2006-05-01

    Epidemiologic studies have revealed a complex association between human genetic variance and cancer risk. Quantitative biological modeling based on experimental data can play a critical role in interpreting the effect of genetic variation on biochemical pathways relevant to cancer development and progression. Defects in human DNA base excision repair (BER) proteins can reduce cellular tolerance to oxidative DNA base damage caused by endogenous and exogenous sources, such as exposure to toxins and ionizing radiation. If not repaired, DNA base damage leads to cell dysfunction and mutagenesis, consequently leading to cancer, disease, and aging. Population screens have identified numerous single-nucleotide polymorphism variants in many BER proteins and some have been purified and found to exhibit mild kinetic defects. Epidemiologic studies have led to conflicting conclusions on the association between single-nucleotide polymorphism variants in BER proteins and cancer risk. Using experimental data for cellular concentration and the kinetics of normal and variant BER proteins, we apply a previously developed and tested human BER pathway model to (i) estimate the effect of mild variants on BER of abasic sites and 8-oxoguanine, a prominent oxidative DNA base modification, (ii) identify ranges of variation associated with substantial BER capacity loss, and (iii) reveal nonintuitive consequences of multiple simultaneous variants. Our findings support previous work suggesting that mild BER variants have a minimal effect on pathway capacity whereas more severe defects and simultaneous variation in several BER proteins can lead to inefficient repair and potentially deleterious consequences of cellular damage.

  19. Endovascular repair of aortic disease: a venture capital perspective.

    Science.gov (United States)

    Buchanan, Lucas W; Stavropoulos, S William; Resnick, Joshua B; Solomon, Jeffrey

    2009-03-01

    Endovascular devices for the treatment of abdominal and thoracic aortic disease are poised to become the next $1 billion medical device market. A shift from open repair to endovascular repair, advances in technology, screening initiatives, and new indications are driving this growth. Although billion-dollar medical device markets are rare, this field is fraught with risk and uncertainty for startups and their venture capital investors. Technological hurdles, daunting clinical and regulatory timelines, market adoption issues, and entrenched competitors pose significant barriers to successful new venture creation. In fact, the number of aortic endografts that have failed to reach commercialization or have been pulled from the market exceeds the number of Food and Drug Administration-approved endografts in the United States. This article will shed some light on the venture capital mind-set and decision-making paradigm in the context of aortic disease.

  20. Base Sequence Context Effects on Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Yuqin Cai

    2010-01-01

    Full Text Available Nucleotide excision repair (NER plays a critical role in maintaining the integrity of the genome when damaged by bulky DNA lesions, since inefficient repair can cause mutations and human diseases notably cancer. The structural properties of DNA lesions that determine their relative susceptibilities to NER are therefore of great interest. As a model system, we have investigated the major mutagenic lesion derived from the environmental carcinogen benzo[a]pyrene (B[a]P, 10S (+-trans-anti-B[a]P-2-dG in six different sequence contexts that differ in how the lesion is positioned in relation to nearby guanine amino groups. We have obtained molecular structural data by NMR and MD simulations, bending properties from gel electrophoresis studies, and NER data obtained from human HeLa cell extracts for our six investigated sequence contexts. This model system suggests that disturbed Watson-Crick base pairing is a better recognition signal than a flexible bend, and that these can act in concert to provide an enhanced signal. Steric hinderance between the minor groove-aligned lesion and nearby guanine amino groups determines the exact nature of the disturbances. Both nearest neighbor and more distant neighbor sequence contexts have an impact. Regardless of the exact distortions, we hypothesize that they provide a local thermodynamic destabilization signal for repair.

  1. Envisioning the molecular choreography of DNA base excision repair.

    Science.gov (United States)

    Parikh, S S; Mol, C D; Hosfield, D J; Tainer, J A

    1999-02-01

    Recent breakthroughs integrate individual DNA repair enzyme structures, biochemistry and biology to outline the structural cell biology of the DNA base excision repair pathways that are essential to genome integrity. Thus, we are starting to envision how the actions, movements, steps, partners and timing of DNA repair enzymes, which together define their molecular choreography, are elegantly controlled by both the nature of the DNA damage and the structural chemistry of the participating enzymes and the DNA double helix.

  2. DNA-repair in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Bucholtz, Nina; Demuth, Ilja

    2013-10-01

    While the pathogenesis of the sporadic form of Alzheimer disease (late onset Alzheimer disease, LOAD) is not fully understood, it seems to be clear that a combination of genetic and environmental factors are involved and influence the course of the disease. Among these factors, elevated levels of oxidative stress have been recognized and individual differences in the capacity to deal with DNA damage caused by its effects have been the subject of numerous studies. This review summarizes the research on DNA repair proteins and genes in the context of LOAD pathogenesis and its possible prodromal stage, mild cognitive impairment (MCI). The current status of the research in this field is discussed with respect to methodological issues which might have compromised the outcome of some studies and future directions of investigation on this subject are depicted.

  3. DREMECELS: A Curated Database for Base Excision and Mismatch Repair Mechanisms Associated Human Malignancies.

    Directory of Open Access Journals (Sweden)

    Ankita Shukla

    Full Text Available DNA repair mechanisms act as a warrior combating various damaging processes that ensue critical malignancies. DREMECELS was designed considering the malignancies with frequent alterations in DNA repair pathways, that is, colorectal and endometrial cancers, associated with Lynch syndrome (also known as HNPCC. Since lynch syndrome carries high risk (~40-60% for both cancers, therefore we decided to cover all three diseases in this portal. Although a large population is presently affected by these malignancies, many resources are available for various cancer types but no database archives information on the genes specifically for only these cancers and disorders. The database contains 156 genes and two repair mechanisms, base excision repair (BER and mismatch repair (MMR. Other parameters include some of the regulatory processes that have roles in these disease progressions due to incompetent repair mechanisms, specifically BER and MMR. However, our unique database mainly provides qualitative and quantitative information on these cancer types along with methylation, drug sensitivity, miRNAs, copy number variation (CNV and somatic mutations data. This database would serve the scientific community by providing integrated information on these disease types, thus sustaining diagnostic and therapeutic processes. This repository would serve as an excellent accompaniment for researchers and biomedical professionals and facilitate in understanding such critical diseases. DREMECELS is publicly available at http://www.bioinfoindia.org/dremecels.

  4. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

    Injuries to human native cartilage tissue are particularly troublesome because cartilage has little ability to heal or regenerate itself. The reconstruction, repair, and regeneration of cartilage tissue continue to be one of the greatest clinical challenges, especially in orthopaedic and plastic sur

  5. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

    Injuries to human native cartilage tissue are particularly troublesome because cartilage has little ability to heal or regenerate itself. The reconstruction, repair, and regeneration of cartilage tissue continue to be one of the greatest clinical challenges, especially in orthopaedic and plastic

  6. 循证护理在先天性心脏病修补术围手术期的应用%The Application of Evidence-Based Nursing in Perioperative Period of Repair Surgery of Congenital Heart Disease

    Institute of Scientific and Technical Information of China (English)

    廖平; 金素; 詹会智; 罗良琴; 阳亚男

    2015-01-01

    Objective To explore the application effect of evidence-based nursing in perioperative period of repair surgery of con-genital heart disease. Methods 130 children with congenital heart disease receiving repair surgery during the period from June, 2010 to Jan., 2014 were randomly divided into 2 groups:observation group and control group, 65 cases in each;evidence-based nursing was per-formed to cases in observation group while routine nursing to cases in control group;the effect of surgery, the time length of hospitaliza-tion and the occurrence of complication in the 2 groups were comparatively studied. Results The cure rate in observation group was much higher than that in control group;the time of hospitalization in observation group was shorter than that in control group;the case number of cardiac function grade Level I in observation group was bigger than that in control group (P<0.05);the total occurrence of complications in observation group was 24.62%, much lower than that in control group (69.23%);the occurrence of pulmonary hyperten-sion, arrhythmia, thrombosis and other complications in observation group was much lower than that in control group (P<0.05). Conclu-sions The application of evidence-based nursing in perioperative period of repair surgery of congenital heart disease can effectively de-crease the occurrence of complications and raise the success rate of the surgery.%目的:分析循证护理在先天性心脏病修补术围手术期的应用效果。方法对2010年6月~2014年1月我院行心脏修补术的130例先天性心脏病患儿随机分为对照组和观察组各65例。对照组采用常规护理,观察组则根据循证医学模式进行循证护理。比较两组间手术效果、住院时间差异及并发症发生率差异。结果观察组患者治愈率显著高于对照组,住院时间显著短于对照组,心功能等级为Ⅰ级的病例数亦显著高于对照组(P<0.05)。观察组总并发症发生率为24

  7. Modulation of DNA base excision repair during neuronal differentiation

    DEFF Research Database (Denmark)

    Sykora, Peter; Yang, Jenq-Lin; Ferrarelli, Leslie K

    2013-01-01

    Neurons are terminally differentiated cells with a high rate of metabolism and multiple biological properties distinct from their undifferentiated precursors. Previous studies showed that nucleotide excision DNA repair is downregulated in postmitotic muscle cells and neurons. Here, we characterize...... DNA damage susceptibility and base excision DNA repair (BER) capacity in undifferentiated and differentiated human neural cells. The results show that undifferentiated human SH-SY5Y neuroblastoma cells are less sensitive to oxidative damage than their differentiated counterparts, in part because...

  8. Polymorphism of the DNA Base Excision Repair Genes in Keratoconus

    Directory of Open Access Journals (Sweden)

    Katarzyna A. Wojcik

    2014-10-01

    Full Text Available Keratoconus (KC is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER. Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.–1370T>A polymorphism of the DNA polymerase γ (POLG gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1 were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1 nor the c.2285T>C polymorphism of the poly(ADP-ribose polymerase-1 (PARP-1 was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease.

  9. Laser repairing surface crack of Ni-based superalloy components

    Institute of Scientific and Technical Information of China (English)

    王忠柯; 叶和清; 许德胜; 黄索逸

    2001-01-01

    Surface crack of components of the cast nickel-base superalloy was repaired with twin laser beams under proper technological conditions. One laser beam was used to melt the substrate material of crack, and the other to fill in powder material to the crack region. The experimental results show that the surface crack with the width of 0.1~0.3mm could be repaired under the laser power of 3kW and the scanning speed of 6~8mm/s. The repaired deepness of crack region is below 6.5mm. The microstructure of repaired region is the cellular crystal, columnar crystal dendrite crystal from the transition region to the top filled layer. The phases in repaired region mainly consisted of supersaturated α-Co with plenty of Ni, some Cr and Al, Cr23C6, Co2B, Co-Ni-Mo, Ni4B3, TiSi and VSi. The hardness of filled layer in repaired region ranged from HV0.2450 to HV0.2500, and the hardness decreases gradually from the filled layer to joined zone.

  10. Stem cell-based biological tooth repair and regeneration.

    Science.gov (United States)

    Volponi, Ana Angelova; Pang, Yvonne; Sharpe, Paul T

    2010-12-01

    Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.

  11. Base excision repair of 8-oxoG in dinucleosomes

    NARCIS (Netherlands)

    H. Menoni (Hervé); M.S. Shukla (Manu Shubhdarshan); V. Gerson (Véronique); S. Dimitrov (Stefan); D. Angelov (Dimitar)

    2012-01-01

    textabstractIn this work we have studied the effect of chromatin structure on the base excision repair (BER) efficiency of 8-oxoG. As a model system we have used precisely positioned dinucleosomes assembled with linker histone H1. A single 8-oxoG was inserted either in the linker or the core particl

  12. Echocardiographic Follow-up of Robotic Mitral Valve Repair for Mitral Regurgitation due to Degenerative Disease

    Directory of Open Access Journals (Sweden)

    Yao Wang

    2016-01-01

    Conclusion: Robotic MV repair for MR due to degenerative disease is associated with a low rate of recurrent MR, and a significant improvement in MR grade, LAD, and LVEDD, but a significant decrease in LVEF at echocardiographic follow-up.

  13. On-bead fluorescent DNA nanoprobes to analyze base excision repair activities

    Energy Technology Data Exchange (ETDEWEB)

    Gines, Guillaume; Saint-Pierre, Christine; Gasparutto, Didier, E-mail: didier.gasparutto@cea.fr

    2014-02-17

    Graphical abstract: -- Highlights: •On magnetic beads fluorescent enzymatic assays. •Simple, easy, non-radioactive and electrophoresis-free functional assay. •Lesion-containing hairpin DNA probes are selective for repair enzymes. •The biosensing platform allows the measurement of DNA repair activities from purified enzymes or within cell free extracts. -- Abstract: DNA integrity is constantly threatened by endogenous and exogenous agents that can modify its physical and chemical structure. Changes in DNA sequence can cause mutations sparked by some genetic diseases or cancers. Organisms have developed efficient defense mechanisms able to specifically repair each kind of lesion (alkylation, oxidation, single or double strand break, mismatch, etc). Here we report the adjustment of an original assay to detect enzymes’ activity of base excision repair (BER), that supports a set of lesions including abasic sites, alkylation, oxidation or deamination products of bases. The biosensor is characterized by a set of fluorescent hairpin-shaped nucleic acid probes supported on magnetic beads, each containing a selective lesion targeting a specific BER enzyme. We have studied the DNA glycosylase alkyl-adenine glycosylase (AAG) and the human AP-endonuclease (APE1) by incorporating within the DNA probe a hypoxanthine lesion or an abasic site analog (tetrahydrofuran), respectively. Enzymatic repair activity induces the formation of a nick in the damaged strand, leading to probe's break, that is detected in the supernatant by fluorescence. The functional assay allows the measurement of DNA repair activities from purified enzymes or in cell-free extracts in a fast, specific, quantitative and sensitive way, using only 1 pmol of probe for a test. We recorded a detection limit of 1 μg mL{sup −1} and 50 μg mL{sup −1} of HeLa nuclear extracts for APE1 and AAG enzymes, respectively. Finally, the on-bead assay should be useful to screen inhibitors of DNA repair

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

    Science.gov (United States)

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

    2008-07-01

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

  15. Biomolecular Simulation of Base Excision Repair and Protein Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Straatsma, TP; McCammon, J A; Miller, John H; Smith, Paul E; Vorpagel, Erich R; Wong, Chung F; Zacharias, Martin W

    2006-03-03

    The goal of the Biomolecular Simulation of Base Excision Repair and Protein Signaling project is to enhance our understanding of the mechanism of human polymerase-β, one of the key enzymes in base excision repair (BER) and the cell-signaling enzymes cyclic-AMP-dependent protein kinase. This work used molecular modeling and simulation studies to specifically focus on the • dynamics of DNA and damaged DNA • dynamics and energetics of base flipping in DNA • mechanism and fidelity of nucleotide insertion by BER enzyme human polymerase-β • mechanism and inhibitor design for cyclic-AMP-dependent protein kinase. Molecular dynamics simulations and electronic structure calculations have been performed using the computer resources at the Molecular Science Computing Facility at the Environmental Molecular Sciences Laboratory.

  16. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  17. Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk

    National Research Council Canada - National Science Library

    Kathryn Hughes Barry; Stella Koutros; Sonja I. Berndt; Gabriella Andreotti; Jane A. Hoppin; Dale P. Sandler; Laurie A. Burdette; Meredith Yeager; Laura E. Beane Freeman; Jay H. Lubin; Xiaomei Ma; Tongzhang Zheng; Michael C. R. Alavanja

    2011-01-01

    .... OBJECTIVES: Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs...

  18. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    Science.gov (United States)

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  19. Repairable-conditionally repairable damage model based on dual Poisson processes.

    Science.gov (United States)

    Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

    2003-09-01

    The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

  20. 2-Hydrazinobenzothiazole-based etheno-adduct repair protocol (HERP): a method for quantitative determination of direct repair of etheno-bases.

    Science.gov (United States)

    Shivange, Gururaj; Kodipelli, Naveena; Anindya, Roy

    2015-04-01

    Etheno-DNA adducts are mutagenic and lead to genomic instability. Enzymes belonging to Fe(II)/2-oxoglutarate-dependent dioxygenase family repair etheno-DNA adducts by directly removing alkyl chain as glyoxal. Presently there is no simple method to assess repair reaction of etheno-adducts. We have developed a rapid and sensitive assay for studying etheno-DNA adduct repair by Fe(II)/2-oxoglutarate-dependent dioxygenases. Using AlkB as model Fe(II)/2-oxoglutarate-dependent dioxygenases, we performed in vitro repair of etheno-adducts containing DNA and detected glyoxal by reacting with 2-hydrazinobenzothiazole which forms complex yellow color compound with distinct absorption spectrum with a peak absorption at 365 nm. We refer this method as 2-hydrazinobenzothiazole-based etheno-adduct repair protocol or HERP. Our novel approach for determining repair of etheno-adducts containing DNA overcomes several drawbacks of currently available radioisotope-based assay.

  1. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.D.; Barashnev, Yu.I.; Vasil' eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N. (AN SSSR, Moscow. Inst. Obshchej Genetiki)

    A study was made of blood cell sensitivity of children with some hereditary diseases, to ..gamma..-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes.

  2. DNA repair pathways underlie a common genetic mechanism modulating onset in polyglutamine diseases

    Science.gov (United States)

    Bettencourt, Conceição; Hensman‐Moss, Davina; Flower, Michael; Wiethoff, Sarah; Brice, Alexis; Goizet, Cyril; Stevanin, Giovanni; Koutsis, Georgios; Karadima, Georgia; Panas, Marios; Yescas‐Gómez, Petra; García‐Velázquez, Lizbeth Esmeralda; Alonso‐Vilatela, María Elisa; Lima, Manuela; Raposo, Mafalda; Traynor, Bryan; Sweeney, Mary; Wood, Nicholas; Giunti, Paola; Durr, Alexandra; Holmans, Peter; Houlden, Henry; Tabrizi, Sarah J.

    2016-01-01

    Objective The polyglutamine diseases, including Huntington's disease (HD) and multiple spinocerebellar ataxias (SCAs), are among the commonest hereditary neurodegenerative diseases. They are caused by expanded CAG tracts, encoding glutamine, in different genes. Longer CAG repeat tracts are associated with earlier ages at onset, but this does not account for all of the difference, and the existence of additional genetic modifying factors has been suggested in these diseases. A recent genome‐wide association study (GWAS) in HD found association between age at onset and genetic variants in DNA repair pathways, and we therefore tested whether the modifying effects of variants in DNA repair genes have wider effects in the polyglutamine diseases. Methods We assembled an independent cohort of 1,462 subjects with HD and polyglutamine SCAs, and genotyped single‐nucleotide polymorphisms (SNPs) selected from the most significant hits in the HD study. Results In the analysis of DNA repair genes as a group, we found the most significant association with age at onset when grouping all polyglutamine diseases (HD+SCAs; p = 1.43 × 10–5). In individual SNP analysis, we found significant associations for rs3512 in FAN1 with HD+SCAs (p = 1.52 × 10–5) and all SCAs (p = 2.22 × 10–4) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 × 10–5), all in the same direction as in the HD GWAS. Interpretation We show that DNA repair genes significantly modify age at onset in HD and SCAs, suggesting a common pathogenic mechanism, which could operate through the observed somatic expansion of repeats that can be modulated by genetic manipulation of DNA repair in disease models. This offers novel therapeutic opportunities in multiple diseases. Ann Neurol 2016;79:983–990 PMID:27044000

  3. A Corpus-based Study on Self-repairs in Chinese EFL Learners' Spoken English

    Institute of Scientific and Technical Information of China (English)

    张付花

    2009-01-01

    Self-repair mentioned in this paper actually refers to self-initiated same-turn self-repair, which comprises a particular set of repair strategies in which trouble source and repairing segments occur in the same turn and the repair is beth initiated and performed by the speaker of trouble source. This study aims to study the self-repair behaviour of Chinese EFL learners based on the Spoken English Corpus of Chinese Learners as the observing corpus and the reference corpus SBNC. This study is mainly concerned with use frequency, distributions and structures of the self-repair on the basis of a clear classification of the self-repalr, aiming to find out whether there are significant differences in these three aspects of the self-repair between the Chinese EFL learners and the native speakers. Some implications and applications of the findings are also available for English teaching and learning in China.

  4. Defects in Base Excision Repair Sensitize Cells to Manganese in S. cerevisiae

    Directory of Open Access Journals (Sweden)

    Adrienne P. Stephenson

    2013-01-01

    Full Text Available Manganese (Mn is essential for normal physiologic functioning; therefore, deficiencies and excess intake of manganese can result in disease. In humans, prolonged exposure to manganese causes neurotoxicity characterized by Parkinson-like symptoms. Mn2+ has been shown to mediate DNA damage possibly through the generation of reactive oxygen species. In a recent publication, we showed that Mn induced oxidative DNA damage and caused lesions in thymines. This study further investigates the mechanisms by which cells process Mn2+-mediated DNA damage using the yeast S. cerevisiae. The strains most sensitive to Mn2+ were those defective in base excision repair, glutathione synthesis, and superoxide dismutase mutants. Mn2+ caused a dose-dependent increase in the accumulation of mutations using the CAN1 and lys2-10A mutator assays. The spectrum of CAN1 mutants indicates that exposure to Mn results in accumulation of base substitutions and frameshift mutations. The sensitivity of cells to Mn2+ as well as its mutagenic effect was reduced by N-acetylcysteine, glutathione, and Mg2+. These data suggest that Mn2+ causes oxidative DNA damage that requires base excision repair for processing and that Mn interferes with polymerase fidelity. The status of base excision repair may provide a biomarker for the sensitivity of individuals to manganese.

  5. Altered DNA repair, oxidative stress and antioxidant status in coronary artery disease

    Indian Academy of Sciences (India)

    A Supriya Simon; V Chithra; Anoop Vijayan; Roy D Dinesh; T Vijayakumar

    2013-06-01

    Coronary artery disease (CAD) is a multifactorial disease caused by the interplay of environmental risk factors with multiple predisposing genes. The present study was undertaken to evaluate the role of DNA repair efficiency and oxidative stress and antioxidant status in CAD patients. Malonaldehyde (MDA), which is an indicator of oxidative stress, and mean break per cell (b/c) values, which is an indicator of decreased DNA repair efficiency, were found to be significantly increased in patients compared to normal controls ( < 0.05) whereas ascorbic acid and GSH were found to be lower among patients than the control group. It has been found that elevated oxidative stress decreased antioxidant level and decreased DNA repair efficiency can contribute to the development of CAD. This study also showed that high MDA, low ascorbic acid and GSH were significantly associated with high b/c value.

  6. In vitro measurement of DNA base excision repair in isolated mitochondria.

    Science.gov (United States)

    Page, Melissa M; Stuart, Jeffrey A

    2009-01-01

    Mitochondrial DNA (mtDNA) is in relatively close proximity to reactive oxygen species (ROS) arising from spontaneous superoxide formation during respiration. As a result, it sustains oxidative damage that may include base modifications, base loss, and strand breaks. mtDNA replication past sites of oxidative damage can result in the introduction of mutations. mtDNA mutations are associated with various human diseases and can manifest as loss of bioenergetic function. DNA repair processes exist in mitochondria from apparently all metazoans. A fully functional DNA base excision repair (BER) pathway is present in mitochondria of vertebrates. This pathway is catalyzed by a number of DNA glycosylases, an AP endonuclease, polymerase gamma, and a DNA ligase. This chapter outlines the step-by-step protocols for isolating mitochondrial fractions, from a number of different model organisms, of sufficient purity to allow mtDNA repair activities to be measured. It details in vitro assays for the measurement of BER enzyme activities in lysates prepared from isolated mitochondria.

  7. Advances of stem cell based-therapeutic approaches for tendon repair

    Directory of Open Access Journals (Sweden)

    Lidi Liu

    2017-04-01

    The translational potential of this article: This paper reviews recent progress on stem cell-based therapeutic approaches for tendon repair, which highlights its translational potential and challenges.

  8. Exercise Performance in Children and Young Adults After Complete and Incomplete Repair of Congenital Heart Disease.

    Science.gov (United States)

    Rosenblum, Omer; Katz, Uriel; Reuveny, Ronen; Williams, Craig A; Dubnov-Raz, Gal

    2015-12-01

    Few previous studies have addressed exercise capacity in patients with corrected congenital heart disease (CHD) and significant anatomical residua. The aim of this study was to determine the aerobic fitness and peak cardiac function of patients with corrected CHD with complete or incomplete repairs, as determined by resting echocardiography. Children, adolescents and young adults (heart defect had decreased aerobic fitness, with evidence of impaired peak cardiac function and lower pulmonary perfusion. Patients that had undergone a complete repair had decreased aerobic fitness attributed only to deconditioning. These newly identified differences explain why in previous studies, the lowest fitness was seen in patients with the most hemodynamically significant heart malformations.

  9. Oxidative DNA damage background estimated by a system model of base excision repair.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Wilson, David M

    2004-08-01

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level, based on measuring 8-oxoguanine lesions as a biomarker, have led to estimates that vary over three to four orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our findings show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  10. Oxidative DNA damage background estimated by a system model of base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Sokhansanj, B A; Wilson, III, D M

    2004-05-13

    Human DNA can be damaged by natural metabolism through free radical production. It has been suggested that the equilibrium between innate damage and cellular DNA repair results in an oxidative DNA damage background that potentially contributes to disease and aging. Efforts to quantitatively characterize the human oxidative DNA damage background level based on measuring 8-oxoguanine lesions as a biomarker have led to estimates varying over 3-4 orders of magnitude, depending on the method of measurement. We applied a previously developed and validated quantitative pathway model of human DNA base excision repair, integrating experimentally determined endogenous damage rates and model parameters from multiple sources. Our estimates of at most 100 8-oxoguanine lesions per cell are consistent with the low end of data from biochemical and cell biology experiments, a result robust to model limitations and parameter variation. Our results show the power of quantitative system modeling to interpret composite experimental data and make biologically and physiologically relevant predictions for complex human DNA repair pathway mechanisms and capacity.

  11. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    Science.gov (United States)

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  12. Gap junction remodeling in skin repair following wounding and disease.

    Science.gov (United States)

    Churko, Jared M; Laird, Dale W

    2013-05-01

    In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change cellular phenotypes and lead to diseases of the skin. We also consider the therapeutic value of targeting connexins in wound healing.

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

    Directory of Open Access Journals (Sweden)

    Emanuel Santos

    Full Text Available 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.

  14. Repair or replacement of defective restorations by dentists in The Dental Practice-Based Research Network

    DEFF Research Database (Denmark)

    Gordan, Valeria V; Riley, Joseph L; Geraldeli, Saulo

    2012-01-01

    The authors aimed to determine whether dentists in practices belonging to The Dental Practice-Based Research Network (DPBRN) were more likely to repair or to replace a restoration that they diagnosed as defective; to quantify dentists' specific reasons for repairing or replacing restorations......; and to test the hypothesis that certain dentist-, patient- and restoration-related variables are associated with the decision between repairing and replacing restorations....

  15. Optimization and translation of MSC-based hyaluronic acid hydrogels for cartilage repair

    Science.gov (United States)

    Erickson, Isaac E.

    2011-12-01

    Traumatic injury and disease disrupt the ability of cartilage to carry joint stresses and, without an innate regenerative response, often lead to degenerative changes towards the premature development of osteoarthritis. Surgical interventions have yet to restore long-term mechanical function. Towards this end, tissue engineering has been explored for the de novo formation of engineered cartilage as a biologic approach to cartilage repair. Research utilizing autologous chondrocytes has been promising, but clinical limitations in their yield have motivated research into the potential of mesenchymal stem cells (MSCs) as an alternative cell source. MSCs are multipotent cells that can differentiate towards a chondrocyte phenotype in a number of biomaterials, but no combination has successfully recapitulated the native mechanical function of healthy articular cartilage. The broad objective of this thesis was to establish an MSC-based tissue engineering approach worthy of clinical translation. Hydrogels are a common class of biomaterial used for cartilage tissue engineering and our initial work demonstrated the potential of a photo-polymerizable hyaluronic acid (HA) hydrogel to promote MSC chondrogenesis and improved construct maturation by optimizing macromer and MSC seeding density. The beneficial effects of dynamic compressive loading, high MSC density, and continuous mixing (orbital shaker) resulted in equilibrium modulus values over 1 MPa, well in range of native tissue. While compressive properties are crucial, clinical translation also demands that constructs stably integrate within a defect. We utilized a push-out testing modality to assess the in vitro integration of HA constructs within artificial cartilage defects. We established the necessity for in vitro pre-maturation of constructs before repair to achieve greater integration strength and compressive properties in situ. Combining high MSC density and gentle mixing resulted in integration strength over 500 k

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

    Science.gov (United States)

    Rennard, Stephen I; Wachenfeldt, Karin von

    2011-08-01

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

  17. The Reinforcement Effect of Nano-Zirconia on the Transverse Strength of Repaired Acrylic Denture Base

    Directory of Open Access Journals (Sweden)

    Mohammed Gad

    2016-01-01

    Full Text Available Objective. The aim of this study was to evaluate the effect of incorporation of glass fiber, zirconia, and nano-zirconia on the transverse strength of repaired denture base. Materials and Methods. Eighty specimens of heat polymerized acrylic resin were prepared and randomly divided into eight groups (n=10: one intact group (control and seven repaired groups. One group was repaired with autopolymerized resin while the other six groups were repaired using autopolymerized resin reinforced with 2 wt% or 5 wt% glass fiber, zirconia, or nano-zirconia particles. A three-point bending test was used to measure the transverse strength. The results were analyzed using SPSS and repeated measure ANOVA and post hoc least significance (LSD test (P≤0.05. Results. Among repaired groups it was found that autopolymerized resin reinforced with 2 or 5 wt% nano-zirconia showed the highest transverse strength (P≤0.05. Repairs with autopolymerized acrylic resin reinforced with 5 wt% zirconia showed the lowest transverse strength value. There was no significant difference between the groups repaired with repair resin without reinforcement, 2 wt% zirconia, and glass fiber reinforced resin. Conclusion. Reinforcing of repair material with nano-zirconia may significantly improve the transverse strength of some fractured denture base polymers.

  18. The Reinforcement Effect of Nano-Zirconia on the Transverse Strength of Repaired Acrylic Denture Base.

    Science.gov (United States)

    Gad, Mohammed; ArRejaie, Aws S; Abdel-Halim, Mohamed Saber; Rahoma, Ahmed

    2016-01-01

    Objective. The aim of this study was to evaluate the effect of incorporation of glass fiber, zirconia, and nano-zirconia on the transverse strength of repaired denture base. Materials and Methods. Eighty specimens of heat polymerized acrylic resin were prepared and randomly divided into eight groups (n = 10): one intact group (control) and seven repaired groups. One group was repaired with autopolymerized resin while the other six groups were repaired using autopolymerized resin reinforced with 2 wt% or 5 wt% glass fiber, zirconia, or nano-zirconia particles. A three-point bending test was used to measure the transverse strength. The results were analyzed using SPSS and repeated measure ANOVA and post hoc least significance (LSD) test (P ≤ 0.05). Results. Among repaired groups it was found that autopolymerized resin reinforced with 2 or 5 wt% nano-zirconia showed the highest transverse strength (P ≤ 0.05). Repairs with autopolymerized acrylic resin reinforced with 5 wt% zirconia showed the lowest transverse strength value. There was no significant difference between the groups repaired with repair resin without reinforcement, 2 wt% zirconia, and glass fiber reinforced resin. Conclusion. Reinforcing of repair material with nano-zirconia may significantly improve the transverse strength of some fractured denture base polymers.

  19. Potential of cardiac stem/progenitor cells and induced pluripotent stem cells for cardiac repair in ischaemic heart disease.

    Science.gov (United States)

    Wang, Wei Eric; Chen, Xiongwen; Houser, Steven R; Zeng, Chunyu

    2013-10-01

    Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also have the capacity to differentiate into necessary cells to rebuild injured cardiac tissue. Both types of stem cells have brought promise for cardiac repair. The present review summarizes recent advances in cardiac cell therapy based on these two cell sources and discusses the advantages and limitations of each candidate. We conclude that, although both types of stem cells can be considered for autologous transplantation with promising outcomes in animal models, CS/PCs have advanced more in their clinical application because iPSCs and their derivatives possess inherent obstacles for clinical use. Further studies are needed to move cell therapy forward for the treatment of heart disease.

  20. Mammalian Base Excision Repair: Functional Partnership between PARP-1 and APE1 in AP-Site Repair.

    Directory of Open Access Journals (Sweden)

    Rajendra Prasad

    Full Text Available The apurinic/apyrimidinic- (AP- site in genomic DNA arises through spontaneous base loss and base removal by DNA glycosylases and is considered an abundant DNA lesion in mammalian cells. The base excision repair (BER pathway repairs the AP-site lesion by excising and replacing the site with a normal nucleotide via template directed gap-filling DNA synthesis. The BER pathway is mediated by a specialized group of proteins, some of which can be found in multiprotein complexes in cultured mouse fibroblasts. Using a DNA polymerase (pol β immunoaffinity-capture technique to isolate such a complex, we identified five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1, however, was not present. Nevertheless, the complex was capable of BER activity, since repair was initiated by PARP-1's AP lyase strand incision activity. Addition of purified APE1 increased the BER activity of the pol β complex. Surprisingly, the pol β complex stimulated the strand incision activity of APE1. Our results suggested that PARP-1 was responsible for this effect, whereas other proteins in the complex had no effect on APE1 strand incision activity. Studies of purified PARP-1 and APE1 revealed that PARP-1 was able to stimulate APE1 strand incision activity. These results illustrate roles of PARP-1 in BER including a functional partnership with APE1.

  1. Cell-based and biomaterial approaches to connective tissue repair

    Science.gov (United States)

    Stalling, Simone Suzette

    vitro as well as in a subcutaneous mouse model. Stable MA-MC hydrogels, of varying weight percentages, demonstrated tunable swelling and mechanical properties in the absence of cytotoxic degradation products. In vivo, 6wt% MA-MC hydrogels maintained their shape and mechanical integrity while eliciting a minimal inflammatory response; highly desirable properties for soft tissue reconstruction. These cellulose-based photopolymerizable hydrogels can be further optimized for drug delivery and tissue engineering applications to enhance wound repair.

  2. Graphene-Based Bionic Composites with Multifunctional and Repairing Properties.

    Science.gov (United States)

    Valentini, L; Bittolo Bon, S; Signetti, S; Pugno, N M

    2016-03-01

    In this work, a novel bionic composite inspired by the concept of yeast fermentation has been proposed. It was observed that the addition of graphene nanoplatelets during the fermentation of extract of Saccharomyces cerevisiae fungi allows coupling of the graphene sheets to the yeast cell wall. This process resulted in the formation of a composite film with improved mechanical and electrical properties along with the capability of converting the light stimulus in the electrical signal. The mechanical properties of the prepared composites, namely, the fracture strength and Young's modulus, were studied via numerical simulations and are related to the properties of the constituent phases via rules of mixture. Finally, it was observed that graphene nanoplatelets, added to the nutrient broth, were able to reassemble onto the stressed cell surface and repair the surface cracking, partially restoring the pristine electrical and mechanical properties. The method reported here may find potential application in the development of self-healable bioelectronic devices and microorganism-based strain and chemical biosensors.

  3. DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease

    Energy Technology Data Exchange (ETDEWEB)

    Dupuy, Aurélie [Laboratory of Genetic Instability and Oncogenesis UMR8200CNRS, Institut Gustave Roussy and University Paris-Sud, Villejuif (France); Sarasin, Alain, E-mail: alain.sarasin@gustaveroussy.fr [Laboratory of Genetic Instability and Oncogenesis UMR8200CNRS, Institut Gustave Roussy and University Paris-Sud, Villejuif (France); Service de Génétique, Institut Gustave Roussy (France)

    2015-06-15

    Graphical abstract: - Highlights: • Full correction of mutation in the XPC gene by engineered nucleases. • Meganucleases and TALENs are inhibited by 5-MeC for inducing double strand breaks. • Gene therapy of XP cells is possible using homologous recombination for DSB repair. - Abstract: Xeroderma pigmentosum (XP) is a genetic disease characterized by hypersensitivity to ultra-violet and a very high risk of skin cancer induction on exposed body sites. This syndrome is caused by germinal mutations on nucleotide excision repair genes. No cure is available for these patients except a complete protection from all types of UV radiations. We reviewed the various techniques to complement or to correct the genetic defect in XP cells. We, particularly, developed the correction of XP-C skin cells using the fidelity of the homologous recombination pathway during repair of double-strand break (DSB) in the presence of XPC wild type sequences. We used engineered nucleases (meganuclease or TALE nuclease) to induce a DSB located at 90 bp of the mutation to be corrected. Expression of specific TALE nuclease in the presence of a repair matrix containing a long stretch of homologous wild type XPC sequences allowed us a successful gene correction of the original TG deletion found in numerous North African XP patients. Some engineered nucleases are sensitive to epigenetic modifications, such as cytosine methylation. In case of methylated sequences to be corrected, modified nucleases or demethylation of the whole genome should be envisaged. Overall, we showed that specifically-designed TALE-nuclease allowed us to correct a 2 bp deletion in the XPC gene leading to patient's cells proficient for DNA repair and showing normal UV-sensitivity. The corrected gene is still in the same position in the human genome and under the regulation of its physiological promoter. This result is a first step toward gene therapy in XP patients.

  4. Nucleotide sequence, DNA damage location and protein stoichiometry influence base excision repair outcome at CAG/CTG repeats

    Science.gov (United States)

    Goula, Agathi-Vasiliki; Pearson, Christopher E.; Della Maria, Julie; Trottier, Yvon; Tomkinson, Alan E.; Wilson, David M.; Merienne, Karine

    2012-01-01

    Expansion of CAG/CTG repeats is the underlying cause of >fourteen genetic disorders, including Huntington’s disease (HD) and myotonic dystrophy. The mutational process is ongoing, with increases in repeat size enhancing the toxicity of the expansion in specific tissues. In many repeat diseases the repeats exhibit high instability in the striatum, whereas instability is minimal in the cerebellum. We provide molecular insights as to how base excision repair (BER) protein stoichiometry may contribute to the tissue-selective instability of CAG/CTG repeats by using specific repair assays. Oligonucleotide substrates with an abasic site were mixed with either reconstituted BER protein stoichiometries mimicking the levels present in HD mouse striatum or cerebellum, or with protein extracts prepared from HD mouse striatum or cerebellum. In both cases, repair efficiency at CAG/CTG repeats and at control DNA sequences was markedly reduced under the striatal conditions, likely due to the lower level of APE1, FEN1 and LIG1. Damage located towards the 5’ end of the repeat tract was poorly repaired accumulating incompletely processed intermediates as compared to an AP lesion in the centre or at the 3’ end of the repeats or within a control sequences. Moreover, repair of lesions at the 5’ end of CAG or CTG repeats involved multinucleotide synthesis, particularly under the cerebellar stoichiometry, suggesting that long-patch BER processes lesions at sequences susceptible to hairpin formation. Our results show that BER stoichiometry, nucleotide sequence and DNA damage position modulate repair outcome, and suggest that a suboptimal LP-BER activity promotes CAG/CTG repeat instability. PMID:22497302

  5. Hydrogels for osteochondral repair based on photocrosslinkable carbamate dendrimers.

    Science.gov (United States)

    Degoricija, Lovorka; Bansal, Prashant N; Söntjens, Serge H M; Joshi, Neel S; Takahashi, Masaya; Snyder, Brian; Grinstaff, Mark W

    2008-10-01

    First generation, photocrosslinkable dendrimers consisting of natural metabolites (i.e., succinic acid, glycerol, and beta-alanine) and nonimmunogenic poly(ethylene glycol) (PEG) were synthesized divergently in high yields using ester and carbamate forming reactions. Aqueous solutions of these dendrimers were photocrosslinked with an eosin-based photoinitiator to afford hydrogels. The hydrogels displayed a range of mechanical properties based on their structure, generation size, and concentration in solution. All of the hydrogels showed minimal swelling characteristics. The dendrimer solutions were then photocrosslinked in situ in an ex vivo rabbit osteochondral defect (3 mm diameter and 10 mm depth), and the resulting hydrogels were subjected to physiologically relevant dynamic loads. Magnetic resonance imaging (MRI) showed the hydrogels to be fixated in the defect site after the repetitive loading regimen. The ([G1]-PGLBA-MA) 2-PEG hydrogel was chosen for the 6 month pilot in vivo rabbit study because this hydrogel scaffold could be prepared at low polymer weight (10 wt %) and possessed the largest compressive modulus of the 10% formulations, a low swelling ratio, and contained carbamate linkages, which are more hydrolytically stable than the ester linkages. The hydrogel-treated osteochondral defects showed good attachment in the defect site and histological analysis showed the presence of collagen II and glycosaminoglycans (GAGs) in the treated defects. By contrast, the contralateral unfilled defects showed poor healing and negligible GAG or collagen II production. Good mechanical properties, low swelling, good attachment to the defect site, and positive in vivo results illustrate the potential of these dendrimer-based hydrogels as scaffolds for osteochondral defect repair.

  6. High-Throughput Microplate-Based Assay to Monitor Plasma Membrane Wounding and Repair

    Directory of Open Access Journals (Sweden)

    Sarika Pathak-Sharma

    2017-07-01

    Full Text Available The plasma membrane of mammalian cells is susceptible to disruption by mechanical and biochemical damages that frequently occur within tissues. Therefore, efficient and rapid repair of the plasma membrane is essential for maintaining cellular homeostasis and survival. Excessive damage of the plasma membrane and defects in its repair are associated with pathological conditions such as infections, muscular dystrophy, heart failure, diabetes, and lung and neurodegenerative diseases. The molecular events that remodel the plasma membrane during its repair remain poorly understood. In the present work, we report the development of a quantitative high-throughput assay that monitors the efficiency of the plasma membrane repair in real time using a sensitive microplate reader. In this assay, the plasma membrane of living cells is perforated by the bacterial pore-forming toxin listeriolysin O and the integrity and recovery of the membrane are monitored at 37°C by measuring the fluorescence intensity of the membrane impermeant dye propidium iodide. We demonstrate that listeriolysin O causes dose-dependent plasma membrane wounding and activation of the cell repair machinery. This assay was successfully applied to cell types from different origins including epithelial and muscle cells. In conclusion, this high-throughput assay provides a novel opportunity for the discovery of membrane repair effectors and the development of new therapeutic compounds that could target membrane repair in various pathological processes, from degenerative to infectious diseases.

  7. Prospect of Induced Pluripotent Stem Cell Genetic Repair to Cure Genetic Diseases

    Directory of Open Access Journals (Sweden)

    Jeanne Adiwinata Pawitan

    2012-01-01

    Full Text Available In genetic diseases, where the cells are already damaged, the damaged cells can be replaced by new normal cells, which can be differentiated from iPSC. To avoid immune rejection, iPSC from the patient’s own cell can be developed. However, iPSC from the patients’s cell harbors the same genetic aberration. Therefore, before differentiating the iPSCs into required cells, genetic repair should be done. This review discusses the various technologies to repair the genetic aberration in patient-derived iPSC, or to prevent the genetic aberration to cause further damage in the iPSC-derived cells, such as Zn finger and TALE nuclease genetic editing, RNA interference technology, exon skipping, and gene transfer method. In addition, the challenges in using the iPSC and the strategies to manage the hurdles are addressed.

  8. Echocardiographic Follow-up of Robotic Mitral Valve Repair for Mitral Regurgitation due to Degenerative Disease

    Institute of Scientific and Technical Information of China (English)

    Yao Wang; Chang-Qing Gao; Yah-Song Shen; Gang Wang

    2016-01-01

    Background:Mitral valve (MV) repair can now be carried out through small incisions with the use of robotic assistance.Previous reports have demonstrated the excellent clinical result of robotic MV repair for degenerative mitral regurgitation (MR).However,there has been limited information regarding the echocardiographic follow-up of these patients.The present study was therefore to evaluate the echocardiographic follow-up outcomes after robotic MV repair in patients with MR due to degenerative disease of the MV.Methods:A retrospective analysis was undertaken using data from the echocardiographic database of our department.Between March 2007 and February 2015,84 patients with degenerative MR underwent robotic MV repair.The repair techniques included leaflet resection in 67 patients (79.8%),artificial chordae in 20 (23.8%),and ring annuloplasty in 79 (94.1%).Eighty-one (96.4%) of the 84 patients were eligible for echocardiographic follow-up assessment,and no patients were lost to follow-up.Results:At a median echocardiographic follow-up of 36.0 months (interquartile range 14.3-59.4 months),four patients (4.9%) developed recurrent mild MR,and no patients had more than mild MR.Mean MR grade,left atrial diameter (LAD),left ventricular end-diastolic diameter (LVEDD),and left ventricular ejection fraction (LVEF) were significantly decreased when compared with preoperative values.Mean MR grade decreased from 3.96 ± 0.13 to 0.17 ± 0.49 (Z =-8.456,P < 0.001),LAD from 43.8 ± 5.9 to 35.5 ± 3.8 mm (t =15.131,P < 0.001),LVEDD from 51.0 ± 5.0 to 43.3 ± 2.2 mm (t =14.481,P < 0.001),and LVEF from 67.3 ± 7.0% to 63.9 ± 5.1% (t =4.585,P < 0.001).Conclusion:Robotic MV repair for MR due to degenerative disease is associated with a low rate of recurrent MR,and a significant improvement in MR grade,LAD,and LVEDD,but a significant decrease in LVEF at echocardiographic follow-up.

  9. Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de, E-mail: nadja@iq.usp.br

    2015-06-15

    Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin.

  10. Fault self-repair strategy based on evolvable hardware and reparation balance technology

    Institute of Scientific and Technical Information of China (English)

    Zhang Junbin; Cai Jinyan; Meng Yafeng; Meng Tianzhen

    2014-01-01

    In the face of harsh natural environment applications such as earth-orbiting and deep space satellites, underwater sea vehicles, strong electromagnetic interference and temperature stress, the circuits faults appear easily. Circuit faults will inevitably lead to serious losses of availability or impeded mission success without self-repair over the mission duration. Traditional fault-repair methods based on redundant fault-tolerant technique are straightforward to implement, yet their area, power and weight cost can be excessive. Moreover they utilize all plug-in or component level circuits to realize redundant backup, such that their applicability is limited. Hence, a novel self-repair technology based on evolvable hardware (EHW) and reparation balance technology (RBT) is proposed. Its cost is low, and fault self-repair of various circuits and devices can be realized through dynamic configuration. Making full use of the fault signals, correcting circuit can be found through EHW technique to realize the balance and compensation of the fault out-put-signals. In this paper, the self-repair model was analyzed which based on EHW and RBT tech-nique, the specific self-repair strategy was studied, the corresponding self-repair circuit fault system was designed, and the typical faults were simulated and analyzed which combined with the actual electronic devices. Simulation results demonstrated that the proposed fault self-repair strategy was feasible. Compared to traditional techniques, fault self-repair based on EHW consumes fewer hardware resources, and the scope of fault self-repair was expanded significantly.

  11. A novel electron-beam-based photomask repair tool

    Science.gov (United States)

    Edinger, Klaus; Becht, Hans; Becker, Rainer; Bert, Volker; Boegli, Volker A.; Budach, Michael; G÷hde, Susanne; Guyot, Jochen; Hofmann, Thorsten; Hoinkis, Ottmar; Kaya, Alexander; Koops, Hans W.; Spies, Petra; Weyrauch, Bernd; Bihr, Johannes

    2003-12-01

    High-resolution electron-beam assisted deposition and etching is an enabling technology for current and future generation photo mask repair. NaWoTec in collaboration with LEO Electron Microscopy has developed a mask repair beta tool capable of processing a wide variety of mask types, such as quartz binary masks, phase shift masks, EUV masks, and e-beam projection stencil masks. Specifications currently meet the 65 nm device node requirements, and tool performance is extendible to 45 nm and below. The tool combines LEO's ultra-high resolution Supra SEM platform with NaWoTec's e-beam deposition and etching technology, gas supply and pattern generation hardware, and repair software. It is expected to ship to the first customer in October this year. In this paper, we present the tool platform, its work flow oriented repair software, and associated deposition and etch processes. Unique features are automatic drift compensation, critical edge detection, and arbitrary pattern copy with automatic placement. Repair of clear and opaque programmed defects on Cr, TaN, and MoSi quartz masks, as well as on SiC and Si stencil masks is demonstrated. We show our development roadmap towards a production tool, which will be available by the end of this year.

  12. Inspection-Repair based Availability Optimization of Distribution Systems using Teaching Learning based Optimization

    Science.gov (United States)

    Tiwary, Aditya; Arya, L. D.; Arya, Rajesh; Choube, S. C.

    2016-09-01

    This paper describes a technique for optimizing inspection and repair based availability of distribution systems. Optimum duration between two inspections has been obtained for each feeder section with respect to cost function and subject to satisfaction of availability at each load point. Teaching learning based optimization has been used for availability optimization. The developed algorithm has been implemented on radial and meshed distribution systems. The result obtained has been compared with those obtained with differential evolution.

  13. Evidence-based outcomes following inferior alveolar and lingual nerve injury and repair: a systematic review.

    Science.gov (United States)

    Kushnerev, E; Yates, J M

    2015-10-01

    The inferior alveolar nerve (IAN) and lingual (LN) are susceptible to iatrogenic surgical damage. Systematically review recent clinical evidence regarding IAN/LN repair methods and to develop updated guidelines for managing injury. Recent publications on IAN/LN microsurgical repair from Medline, Embase and Cochrane Library databases were screened by title/abstract. Main texts were appraised for exclusion criteria: no treatment performed or results provided, poor/lacking procedural description, cohort deficit shows no improvement 90 days post-diagnosis. Nerve transection diagnosed intra-operatively should be repaired in situ; minor nerve injury repair can be delayed. No consensus exists regarding optimal methods and timing for IAN/LN repair. We suggest a schematic guideline for treating IAN/LN injury, based on the most current evidence. We acknowledge that additional RCTs are required to provide definitive confirmation of optimal treatment approaches.

  14. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sara Sepe

    2016-05-01

    Full Text Available The underlying relation between Parkinson’s disease (PD etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  15. Potential of bacteria-based repair solution as healing agent for porous network concrete

    NARCIS (Netherlands)

    Wiktor, V.A.C.; Sangadji, S.; Jonkers, H.M.; Schlangen, H.E.J.G.

    2013-01-01

    Bacterially induced calcium carbonate precipitation has received considerable attention for its potential application in enforcing or repairing construction material. The mechanism of bacterially mediated calcite precipitation in those studies is primarily based on the enzymatic hydrolysis of urea.

  16. Potential of bacteria-based repair solution as healing agent for porous network concrete

    NARCIS (Netherlands)

    Wiktor, V.A.C.; Sangadji, S.; Jonkers, H.M.; Schlangen, H.E.J.G.

    2013-01-01

    Bacterially induced calcium carbonate precipitation has received considerable attention for its potential application in enforcing or repairing construction material. The mechanism of bacterially mediated calcite precipitation in those studies is primarily based on the enzymatic hydrolysis of urea.

  17. Risk Based Optimal Inspection and Repair Planning for Ship Structures Subjected to Corrosion Deterioration

    Institute of Scientific and Technical Information of China (English)

    李典庆; 张圣坤; 唐文勇

    2004-01-01

    A framework of risk based inspection and repair planning was presented to optimize for the ship structures subjected to corrosion deterioration. The planning problem was formulated as an optimization problem where the expected lifetime costs were minimized with a constraint on the minimum acceptable reliability index. The safety margins were established for the inspection events, the repair events and the failure events for ship structures. Moreover, the formulae were derived to calculate failure probabilities and repair probabilities. Based on them, a component subjected to corrosion is investigated for illustration of the process of selecting the optimal inspection and repair strategy. Furthermore, some sensitivity studies were provided. The results show that the optimal inspection instants should take place before the reliability index reaches the minimum acceptable reliability index. The optimal target failure probability is 10-3. In addition, a balance can be achieved between the risk cost and total expected inspection and repair costs by means of the risk-based optimal inspection and repair method, which is very effective in selecting the optimal inspection and repair strategy.

  18. MRI-based Assessment of Endovascular Abdominal Aortic Aneurysm Repair

    NARCIS (Netherlands)

    Laan, M.J. van der

    2007-01-01

    Imaging techniques play a key role in the Endovascular Abdominal Aortic Aneurysm Repair (EVAR) follow-up. The most important parameters monitored after EVAR are the aneurysm size and the presence of endoleaks. Currently, computed tomographic angiography (CTA) is the most commonly used imaging modali

  19. DNA damage and gene therapy of xeroderma pigmentosum, a human DNA repair-deficient disease.

    Science.gov (United States)

    Dupuy, Aurélie; Sarasin, Alain

    2015-06-01

    Xeroderma pigmentosum (XP) is a genetic disease characterized by hypersensitivity to ultra-violet and a very high risk of skin cancer induction on exposed body sites. This syndrome is caused by germinal mutations on nucleotide excision repair genes. No cure is available for these patients except a complete protection from all types of UV radiations. We reviewed the various techniques to complement or to correct the genetic defect in XP cells. We, particularly, developed the correction of XP-C skin cells using the fidelity of the homologous recombination pathway during repair of double-strand break (DSB) in the presence of XPC wild type sequences. We used engineered nucleases (meganuclease or TALE nuclease) to induce a DSB located at 90 bp of the mutation to be corrected. Expression of specific TALE nuclease in the presence of a repair matrix containing a long stretch of homologous wild type XPC sequences allowed us a successful gene correction of the original TG deletion found in numerous North African XP patients. Some engineered nucleases are sensitive to epigenetic modifications, such as cytosine methylation. In case of methylated sequences to be corrected, modified nucleases or demethylation of the whole genome should be envisaged. Overall, we showed that specifically-designed TALE-nuclease allowed us to correct a 2 bp deletion in the XPC gene leading to patient's cells proficient for DNA repair and showing normal UV-sensitivity. The corrected gene is still in the same position in the human genome and under the regulation of its physiological promoter. This result is a first step toward gene therapy in XP patients.

  20. A Collective Review on Mesh-Based Repair of Umbilical and Epigastric Hernias.

    Science.gov (United States)

    Ponten, Jeroen E H; Thomassen, Irene; Nienhuijs, Simon W

    2014-10-01

    In accordance with the tension-free principles for other hernias, umbilical and epigastric hernia repair should probably be mesh-based. The number of randomized studies is increasing, most of them showing significantly less recurrences with the use of a mesh. Different devices are available and are applicable by several approaches. The objective of this review was to evaluate recent literature for the different types of mesh for umbilical and epigastric hernia repair and recurrences after mesh repair. A multi-database search was conducted to reveal relevant studies since 2001 reporting mesh-based repair of primary umbilical/epigastric hernia and their outcomes in adult patients. A total of 20 studies were included, 15 of them solely involved umbilical hernias, whereas the remaining studies included epigastric hernias as well. A median of 124 patients (range, 17-384) was investigated per study. Three quarters of the included studies had a follow-up of at least 2 years. Six studies described the results of laparoscopic approach, of which one reported a recurrence rate of 2.7 %; in the remaining studies, no recurrences occurred. Two comparative studies reported a lower incidence of complications and postoperative pain after laparoscopic repair compared to open repair. Seventeen studies reported results of open techniques, of which seven studies showed no recurrence. Other studies reported recurrence rates up to 3.1 %. A wide range of complication rates were reported (0-33 %). This collective review showed acceptable recurrence rates for mesh-based umbilical and epigastric hernia repair. A wide range of devices was investigated. A tendency toward more complications after laparoscopic repair was found compared to open repair.

  1. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease

    Directory of Open Access Journals (Sweden)

    Kenneth Maiese

    2015-01-01

    Full Text Available Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4 to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.

  2. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease

    Institute of Scientific and Technical Information of China (English)

    Kenneth Maiese

    2015-01-01

    Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in sig-niifcant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Dia-betes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel target-ing of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and au-tophagy. Pathways that involve insulin-like growth factor-1, ifbroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4) to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signal-ing is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.

  3. Successful Aortic Aneurysm Repair in a Woman with Severe von Willebrand (Type 3 Disease

    Directory of Open Access Journals (Sweden)

    Victoria Campbell

    2015-01-01

    Full Text Available von Willebrand disease type 3 (VWD3 is a rare but the most severe form of von Willebrand disease; it is due to almost complete lack of von Willebrand factor activity (VWF:RCo. It is inherited as autosomal recessive trait; whilst heterozygote carriers have mild, or no symptoms, patients with VWD3 show severe bleeding symptoms. In the laboratory, this is characterised by undetectable VWF:Ag, VWF:RCo, and reduced levels of factor VIII < 0.02 IU/dL. The bleeding is managed with von Willebrand/FVIII factor concentrate replacement therapy. In this rare but challenging case we report on the successful excision and repair of an ascending aortic aneurysm following adequate VWF/FVIII factor concentrate replacement using Haemate-P.

  4. The role of aging and DNA repair in chronic disease. Final progress report, December 1, 1985--September 29, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, L.

    1993-11-01

    We carried out a molecular epidemiological study of the DNA repair of photochemical damage as a risk factor in basal cell carcinoma (BCC). In that clinic-based control study of 88 cases and 135 cancer-free control it was found that DNA repair in the controls declined linearly at a rate of 0.61% per year over a 30-60 year age group. However, repair in younger BCC cases, significantly less than their age-matched controls, did not decline at the same rate so that the repair differences between the cases and the controls disappeared as the cases grew older. Besides this age effect, the odds are high (5:1) that an individual with low repair overexposed to sunlight will have basal cell carcinoma. That these odds increase to 10:1 for females compared to male subjects led to the observation that repair may be sensitive to hormonal control. Because of the ease of BCC diagnosis it is possible to demonstrate significantly that the level of DNA repair directly influences the multiplicity of tumors. Further, both those cases and controls with a family history of BCC invariably have reduced levels of DNA repair (p<0-05).

  5. Nonlinear Dynamical Behavior in Neuron Model Based on Small World Network with Attack and Repair Strategy

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue; YANG Qiu-Ying; ZHENG Tai-Yu; ZHANG Ying-Yue; ZHENG Li; ZHANG Gui-Qing; CHEN Tian-Lun

    2008-01-01

    In this paper, we investigate the effect due to the change of topology structure of network on the nonlinear dynamical behavior, by virtue of the OFC neuron evolution model with attack and repair strategy based on the small world. In particular, roles of various parameters relating to the dynamical behavior are carefully studied and analyzed. In addition, the avalanche and EEG-like wave activities with attack and repair strategy are also explored in detail in this work.

  6. Endoscopic repair of high-flow cranial base defects using a bilayer button.

    Science.gov (United States)

    Luginbuhl, Adam J; Campbell, Peter G; Evans, James; Rosen, Marc

    2010-05-01

    Repair of the skull base still begins with a direct repair of the dural defect. We present a new button closure for primary repair of the dura for high flow defects. Retrospective review. We reviewed our 20 cases of primary button grafts and compared the results to the previous 20 high-flow open-cistern cerebrospinal fluid (CSF) cases. Subjects were excluded if they had no violation of the arachnoid space or potential for low-flow CSF leak. The button is constructed so that the inlay portion is at least 25% larger than the dural defect, and the onlay portion is just large enough to cover the dural defect. The two grafts are sutured together using two 4-0 Neurolon sutures and placed with the inlay portion intradurally and the onlay portion extradurally. The button graft repair of open-cisternal defects had a drop in CSF leak complications to 10% (2/20), and these two leaks were repaired with the button technique as the salvage surgery. This is a significant improvement over the 45% leak rate in the prebutton graft group (P button graft group we used nasoseptal flaps on 16/20 repairs, and 1/2 repairs that leaked in the button group did not have a nasoseptal flap. Lumbar drains were used in approximately 38% in both groups (P = .83). The button graft can be used in conjunction with the nasal septal flap or as a stand-alone repair with good results reducing the postoperative leak rate to 10% for high-flow CSF repairs. Laryngoscope, 2010.

  7. Assessment of Pulmonary Artery Stiffness of Repaired Congenital Heart Disease Patients

    Science.gov (United States)

    Lee, Namheon; Banerjee, Rajit; Taylor, Michael; Hor, Kan

    2012-10-01

    Surgical correction or palliation of congenital heart disease (CHD) often requires augmenting the main pulmonary artery (MPA) with non-native material or placing a cylindrical graft. The degree to which this intervention affects PA compliance is largely unknown. In this study, the MPA stiffness characteristics were assessed by its compliance, distensibility, and pressure-strain modulus. Coregistered velocity encoded phase-contrast MRI and cardiac catheterization data were available for a cohort of repaired CHD patients (n=8) and controls (n=3). All patients were repaired with either an RV-PA conduit or a RV outflow tract patch. We measured the MPA area change by MRI and MPA pressure during the cath. The measurements were taken through or just distal to the conduit. The MPA compliance and distensibility for the patients were significantly lower than the controls: compliance (9.8±10.8 vs 28.3±7.7mm^2/mmHg, p<0.05), distensibility (2.2±1.5 vs 6.6±2.1%Area change/mmHg, p=0.05). The patients had a significantly higher pressure-strain modulus (152.3±116.4mmHg, p<0.05) than the controls (35.8±10.6mmHg). The abnormally elevated PA stiffness due to the rigidity of the conduit or patch material may cause a compliance mismatch resulting in high stress levels contributing to the observed progressive PA dilatation. This may be a factor in the progressive RV dilatation seen in this cohort of repaired CHD patients.

  8. Non-machined Surface Protection Process of Electrochemical Machining Based on Repaired Turbine Blade

    Directory of Open Access Journals (Sweden)

    LIU Wei-dong

    2016-11-01

    Full Text Available In order to improve the efficiency of turbine blade repairing, protection processes of non-machined surface in Electrochemical Machining (ECM based on blade repairing were studied. Mathematical model of electric field was developed to obtain current density distribution on anode surface, and to study the repairing principle and consequently analyze the defects forming mechanism by conventional electrolytic repair process. Sacrificial layer process was proposed to protect the non-machined surface in this work and an experimental system was developed to shape overlay welded TC4 blades. The results show that directly shaping process and insulated layer process produce stray dissolution and "stair" defects respectively,while sacrificial layer process achieves acceptable machining performance. With shaping time of 60s, the efficiency is improved; shaped blades have higher precision and surface roughness is Ra≤0.6μm, and with higher repeatability, the design requirements can be met.

  9. The new base excision repair pathway in mammals mediated by tyrosyl-DNA-phosphodiesterase 1

    Directory of Open Access Journals (Sweden)

    Lavrik O. I.

    2012-06-01

    Full Text Available Human tyrosyl-DNA phosphodiesterase 1 (Tdp1 hydrolyzes the phosphodiester bond at a DNA 3' end linked to a tyrosyl moiety and has been implicated in the repair of Topoisomerase I (TopI-DNA covalent complexes. Tdp1 can also hydrolyze other 3' end DNA alterations including 3' phosphoglycolate and 3' abasic (AP sites, and exhibits the 3' nucleosidase activity indicating that it may function as a general 3' end-processing DNA repair enzyme. Recently we have shown a new Tdp1 activity generating DNA strand break with the 3' phosphate termini from the AP site. AP sites are formed spontaneously and are inevitable intermediates during base excision repair of DNA base damages. AP sites are both mutagenic and cytotoxic, and key enzymes for their removal are AP endonucleases. However, AP endonuclease independent repair, initiated by DNA glycosylases performing beta, delta-elimination cleavage of the AP sites, has been described in mammalian cells. Here, we describe another AP endonuclease independent repair pathway for removal of AP sites that is initiated by tyrosyl phosphodiesterase Tdp1. We propose that repair is completed by the action of a polynucleotide kinase, a DNA polymerase and finally a DNA ligase to seal the gap.

  10. Airway epithelial repair, regeneration, and remodeling after injury in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Puchelle, Edith; Zahm, Jean-Marie; Tournier, Jean-Marie; Coraux, Christelle

    2006-11-01

    In chronic obstructive pulmonary disease (COPD), exacerbations are generally associated with several causes, including pollutants, viruses, bacteria that are responsible for an excess of inflammatory mediators, and proinflammatory cytokines released by activated epithelial and inflammatory cells. The normal response of the airway surface epithelium to injury includes a succession of cellular events, varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even complete denudation of the basement membrane. The epithelium then has to repair and regenerate to restore its functions, through several mechanisms, including basal cell spreading and migration, followed by proliferation and differentiation of epithelial cells. In COPD, the remodeling of the airway epithelium, such as squamous metaplasia and mucous hyperplasia that occur during injury, may considerably disturb the innate immune functions of the airway epithelium. In vitro and in vivo models of airway epithelial wound repair and regeneration allow the study of the spatiotemporal modulation of cellular and molecular interaction factors-namely, the proinflammatory cytokines, the matrix metalloproteinases and their inhibitors, and the intercellular adhesion molecules. These factors may be markedly altered during exacerbation periods of COPD and their dysregulation may induce remodeling of the airway mucosa and a leakiness of the airway surface epithelium. More knowledge of the mechanisms involved in airway epithelium regeneration may pave the way to cytoprotective and regenerative therapeutics, allowing the reconstitution of a functional, well-differentiated airway epithelium in COPD.

  11. Effect of an Extra Hydrophobic Resin Layer on Repair Shear Bond Strength of a Silorane-Based Composite Resin.

    Science.gov (United States)

    Mohammadi, Narmin; Bahari, Mahmoud; Kimyai, Soodabeh; Rahbani Nobar, Behnam

    2015-12-01

    Composite repair is a minimally invasive and conservative approach. This study aimed to evaluate the effect of an additional hydrophobic resin layer on the repair shear bond strength of a silorane-based composite repaired with silorane or methacrylate-based composite. Sixty bar-shaped composite blocks were fabricated and stored in saline for 72 hours. The surface of the samples were roughened by diamond burs and etched with phosphoric acid; then, they were randomly divided into three groups according to the repairing process: Group 1: Silorane composite-silorane bonding agent-silorane composite; group 2: Silorane composite-silorane bonding agent-hydrophobic resin-silorane composite, and group 3: Silorane composite-silorane bonding agent-hydrophobic resin methacrylate-based composite. Repairing composite blocks measured 2.5×2.5×5mm. After repairing, the samples were stored in saline for 24 hours and thermocycled for 1500 cycles. The repair bond strength was measured at a strain rate of 1mm/min. Twenty additional cylindrical composite blocks (diameter: 2.5mm, height: 6mm) were also fabricated for measuring the cohesive strength of silorane-based composite. The data were analyzed using One-way ANOVA and the post hoc Tukey's test (α=0.05). Cohesive bond strength of silorane composite was significantly higher than the repair bond strengths in other groups (Presin layer for repair of silorane-based composite with a methacrylate-based composite enhanced the repair shear bond strength.

  12. Anaesthetic management of shoulder arthroscopic repair in Parkinson′s disease with deep brain stimulator

    Directory of Open Access Journals (Sweden)

    Ranju Gandhi

    2014-01-01

    Full Text Available We describe the anaesthetic management of arthroscopic repair for complete rotator cuff tear of shoulder in a 59-year-old female with Parkinson′s disease (PD with deep brain stimulator (DBS using a combination of general anaesthesia with interscalene approach to brachial plexus block. The DBS consists of implanted electrodes in the brain connected to the implantable pulse generator (IPG normally placed in the anterior chest wall subcutaneously. It can be programmed externally from a hand-held device placed directly over the battery stimulator unit. In our patient, IPG with its leads was located in close vicinity of the operative site with potential for DBS malfunction. Implications of DBS in a patient with PD for shoulder arthroscopy for anaesthesiologist are discussed along with a brief review of DBS.

  13. Effect of surface roughness and adhesive system on repair potential of silorane-based resin composite

    Directory of Open Access Journals (Sweden)

    Enas H. Mobarak

    2012-07-01

    Full Text Available This study was performed to evaluate the influence of surface roughness and adhesive system on the repair strength of silorane-based resin composite. Twenty-four substrate discs from silorane-based FiltekP90 were made and stored for 24 h. Half of the discs were roughened against 320 grit SiC paper while the other half was polished against 4000 grit SiC paper. All discs were etched with phosphoric acid. Repair resin composite, FiltekP90 or FiltekZ250, was bonded to the treated surfaces using their corresponding adhesive; P90 System Adhesive (SA or Adper Scotchbond Multipurpose (SBMP ending up with four repair groups. The groups were as follows: G1: Smooth + SA + FiltekP90; G2: Roughened + SA + FiltekP90; G3: Smooth + SBMP + FiltekZ250; G4: Roughened + SBMP + FiltekZ250. Additional six unrepaired discs from each resin composite (G5 and G6 were prepared to test the cohesive strength. After 24 h, discs (n = 6/group were serially sectioned to obtain sticks (n = 30/group for microtensile bond strength (μTBS testing. Scanning electron microscopic (SEM evaluation of substrates that received different treatments as well as representative substrate-repair sticks from each group were performed. Modes of failure were also determined. Two-way ANOVA with Repeated-Measures revealed that surface treatment and repair material had no significant effect on repair bond strength of silorane-based composite material. Paired t-test showed that all repair strength values were significantly lower than the cohesive strength of FiltekP90. Adhesive failure was the predominant mode of failure which was confirmed by SEM. Surface treated FiltekP90 composite showed different textures under SEM whereas phosphoric acid did not produce clear changes. An interaction layer between SBMP adhesive and FiltekZ250 repairing composite was detected. Repair of the silorane composite was successful irrespective of the surface roughness and chemistry of the repair

  14. A Review of Recent Experiments on Step-to-Step “Hand-off” of the DNA Intermediates in Mammalian Base Excision Repair Pathways1

    OpenAIRE

    Prasad, R.; Beard, W A; Batra, V. K.; Liu, Y.; Shock, D. D.; Wilson, S H

    2011-01-01

    The current “working model” for mammalian base excision repair involves two sub-pathways termed single-nucleotide base excision repair and long patch base excision repair that are distinguished by their repair patch sizes and the enzymes/co-factors involved. These base excision repair sub-pathways are designed to sequester the various DNA intermediates, passing them along from one step to the next without allowing these toxic molecules to trigger cell cycle arrest, necrotic cell death, or apo...

  15. Repair mortars based on lime. Accelerated aging tests

    Directory of Open Access Journals (Sweden)

    Martínez-Ramírez, S.

    1995-06-01

    Full Text Available The behaviour under different accelerated aging tests (freeze/thaw and crystallization cycles of a new lime mortar with biocide properties destinated to monumental repair has been studied. New mortars (which have the biocide impregnated in a clay called sepiolite have a similar behaviour to lime mortars used as a reference. After the aging tests, the biocide properties of the mortars have been tried.

    Se ha estudiado el comportamiento frente a distintos ensayos de envejecimiento acelerado (ciclos de hielo/deshielo y cristalización de sales de un nuevo mortero de cal con propiedades biocidas, destinado a la reparación monumental. Se ha comprobado que los nuevos morteros (que llevan incorporado el biocida impregnado en una arcilla denominada sepiolita tienen un comportamiento muy similar a los morteros de cal utilizados como referencia. Tras los ensayos de envejecimiento se ha visto que las propiedades biocidas de los morteros se mantienen.

  16. Repair bond strength in aged methacrylate- and silorane-based composites.

    Science.gov (United States)

    Bacchi, Atais; Consani, Rafael Leonardo; Sinhoreti, Mario Alexandre; Feitosa, Victor Pinheiro; Cavalcante, Larissa Maria; Pfeifer, Carmem Silva; Schneider, Luis Felipe

    2013-10-01

    To evaluate the tensile bond strength at repaired interfaces of aged dental composites, either dimethacrylate- or silorane-based, when subjected to different surface treatments. The composites used were Filtek P60 (methacrylate-based, 3M ESPE) and Filtek P90 (silorane-based, 3M ESPE), of which 50 slabs were stored for 6 months at 37°C. The surface of adhesion was abraded with a 600-grit silicone paper and the slabs repaired with the respective composite, according to the following surface treatment protocols: G1: no treatment; G2: adhesive application; G3: silane + adhesive; G4: sandblasting (Al2O3) + adhesive; G5: sandblasting (Al2O3) + silane + adhesive. After 24-h storage in distilled water at 37°C, tensile bond strength (TBS) was determined in a universal testing machine (Instron 4411) at a crosshead speed of 0.5 mm/min. The original data were submitted to two-way ANOVA and Tukey's test (α = 5%). The methacrylate-based composite presented a statistically significantly higher repair potential than did the silorane-based resin (p = 0.0002). Of the surface treatments for the silorane-based composite, aluminum-oxide air abrasion and adhesive (18.5 ± 3.3MPa) provided higher bond strength than only adhesive application or the control group without surface treatment. For Filtek P60, the control without treatment presented lower repair strength than all other groups with surface treatments, which were statistically similar to each other. The interaction between the factors resin composite and surface treatment was significant (p = 0.002). For aged silorane-based materials, repairs were considered successful after sandblasting (Al2O3) and adhesive application. For methacrylate resin, repair was successful with all surface treatments tested.

  17. Zinc finger nucleases for targeted mutagenesis and repair of the sickle-cell disease mutation: An in-silico study

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2012-05-01

    Full Text Available Abstract Background Sickle cell disease (or simply, SCD is an inherited hemoglobinopathy which is mostly prevalent among persons of African descent. SCD results from a monogenic (Hemoglobin, beta point-mutation (substitution of the base Adenine with Thymine at position six that leads to replacement of the amino acid glutamic acid (E with valine (V. Management of SCD within resource-poor settings is largely syndromic, since the option of cure offered by bone-marrow transplantation (BMT is risky and unaffordable by most affected individuals. Despite previous reports of repair and inhibition of the sickle beta-globin gene and messenger ribonucleic acids (mRNAs, respectively in erythrocyte precursor cells via gene-targeting using an oligomer-restriction enzyme construct and either ribozyme- or RNA-DNA chimeric oligonucleotides (or simply third strand binding, gene-therapy to treat SCD still remains largely preclinical. In the wake of the advances in target- gene- mutagenesis and repair wrought by zinc finger nuclease (ZFN technology, it was hypothesized that SCD may be cured by the same. The goal of this study thus, was constructing a database of zinc finger arrays (ZFAs and engineering ZFNs, that respectively bind and cleave within or around specific sequences in the sickle hemoglobin, beta (−βS gene. Methods and results First, using the complete 1606 genomic DNA base pair (bp sequences of the normal hemoglobin-beta (βA chain gene, and the ZiFiT-CoDA-ZFA software preset at default, 57 three-finger arrays (ZFAs that specifically bind 9 base-pair sequences within the normal hemoglobin-beta chain, were computationally assembled. Second, by serial linkage of these ZFAs to the Flavobacterium okeanokoites endonuclease Fok I― four ZFNs with unique specificity to >24 bp target-sequences at the genomic contextual positions 82, 1333, 1334, and 1413 of the βA chain-gene were constructed in-silico. Third, localizing the point-mutation of SCD at

  18. Heart valve health, disease, replacement, and repair: a 25-year cardiovascular pathology perspective.

    Science.gov (United States)

    Schoen, Frederick J; Gotlieb, Avrum I

    2016-01-01

    The past several decades have witnessed major advances in the understanding of the structure, function, and biology of native valves and the pathobiology and clinical management of valvular heart disease. These improvements have enabled earlier and more precise diagnosis, assessment of the proper timing of surgical and interventional procedures, improved prosthetic and biologic valve replacements and repairs, recognition of postoperative complications and their management, and the introduction of minimally invasive approaches that have enabled definitive and durable treatment for patients who were previously considered inoperable. This review summarizes the current state of our understanding of the mechanisms of heart valve health and disease arrived at through innovative research on the cell and molecular biology of valves, clinical and pathological features of the most frequent intrinsic structural diseases that affect the valves, and the status and pathological considerations in the technological advances in valvular surgery and interventions. The contributions of many cardiovascular pathologists and other scientists, engineers, and clinicians are emphasized, and potentially fruitful areas for research are highlighted. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Dental repair material: a resin-modified glass-ionomer bioactive ionic resin-based composite.

    Science.gov (United States)

    Croll, Theodore P; Berg, Joel H; Donly, Kevin J

    2015-01-01

    This report documents treatment and repair of three carious teeth that were restored with a new dental repair material that features the characteristics of both resin-modified glass-ionomer restorative cement (RMGI) and resin-based composite (RBC). The restorative products presented are reported by the manufacturer to be the first bioactive dental materials with an ionic resin matrix, a shock-absorbing resin component, and bioactive fillers that mimic the physical and chemical properties of natural teeth. The restorative material and base/liner, which feature three hardening mechanisms, could prove to be a notable advancement in the adhesive dentistry restorative materials continuum.

  20. Base excision repair activities differ in human lung cancer cells and corresponding normal controls

    DEFF Research Database (Denmark)

    Karahalil, Bensu; Bohr, Vilhelm A; De Souza-Pinto, Nadja C

    2010-01-01

    Oxidative damage to DNA is thought to play a role in carcinogenesis by causing mutations, and indeed accumulation of oxidized DNA bases has been observed in samples obtained from tumors but not from surrounding tissue within the same patient. Base excision repair (BER) is the main pathway...... for the repair of oxidized modifications both in nuclear and mitochondrial DNA. In order to ascertain whether diminished BER capacity might account for increased levels of oxidative DNA damage in cancer cells, the activities of BER enzymes in three different lung cancer cell lines and their non......-cancerous counterparts were measured using oligonucleotide substrates with single DNA lesions to assess specific BER enzymes. The activities of four BER enzymes, OGG1, NTH1, UDG and APE1, were compared in mitochondrial and nuclear extracts. For each specific lesion, the repair activities were similar among the three...

  1. Home-based rehabilitation in the postoperative treatment of flexor tendon repair.

    Science.gov (United States)

    Sanmartín-Fernández, M; Fernández-Bran, B; Couceiro-Otero, J

    To evaluate the results and complications of flexor tendon repair in which a home-based rehabilitation program was utilized without the assistance of a hand therapist during the first 4postoperative weeks. Between July 2009 and July 2014, a total of 21 digits in 15 patients were treated in our institution for complete laceration of the flexor tendons within the flexor pulley system (zone 1 and 2). Passive and active exercises performed by the patients themselves were started the morning after the operation. Data, as range-of-motion and complications, were collected 6months after the surgery. Fifteen digits had full recovery of flexion. One patient suffered a rupture in the fifth postoperative week. Ten of the 21 digits developed a flexion contracture of the proximal interphalangeal joint; in 5 the contracture was less or equal to 10° without impairment of function or aesthetics. Over recent decades, specialized hand therapy has been of great importance in the postoperative treatment of hand diseases. Unfortunately, these professionals are not always available in our area in the first days after surgery. With this protocol, the patient is in charge of carrying out the postoperative exercises, which could lead to a worse final result and a higher rate of complications. The home-based rehabilitation program yielded complete recovery of joint mobility in most cases with a low complication rate. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. The Mutyh base excision repair gene influences the inflammatory response in a mouse model of ulcerative colitis.

    Directory of Open Access Journals (Sweden)

    Ida Casorelli

    Full Text Available BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/- mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS. The Mutyh(-/- phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/- mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/- mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+ regulatory T cells were observed only in Mutyh(-/- mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

  3. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.

    NARCIS (Netherlands)

    B.P. Engelward (Bevin); G. Weeda (Geert); M.D. Wyatt; J.L.M. Broekhof (Jose'); J. de Wit (Jan); I. Donker (Ingrid); J.M. Allan (James); B. Gold (Bert); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

    1997-01-01

    textabstract3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA glyc

  4. Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.

    NARCIS (Netherlands)

    B.P. Engelward (Bevin); G. Weeda (Geert); M.D. Wyatt; J.L.M. Broekhof (Jose'); J. de Wit (Jan); I. Donker (Ingrid); J.M. Allan (James); B. Gold (Bert); J.H.J. Hoeijmakers (Jan); L.D. Samson (Leona)

    1997-01-01

    textabstract3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA glyc

  5. Injecting a liquid bacteria-based repair system to make porous network conrete healed

    NARCIS (Netherlands)

    Sangadji, S.; Wiktor, V.A.C.; Jonkers, H.M.; Schlangen, H.E.J.G.

    2013-01-01

    Bacteria induced calcite precipitation has been proven to be effective in making concrete structure self-healing. In Microlab TU Delft, the concept has been enhanced by developing a liquid bacteria-based concrete repair system. The solution contains calcite precipitating bacteria, nutrients and buff

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

    NARCIS (Netherlands)

    A. Campalans (Anna); R. Amouroux (Rachel); H. Menoni (Hervé); W. Vermeulen (Wim); J.P. Radicella (Pablo)

    2013-01-01

    textabstractSingle-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,

  7. Temporal-based pericranial flaps for orbitofrontal Dural repair: A technical note and Review of the literature

    Directory of Open Access Journals (Sweden)

    Esther Dupépé

    2016-03-01

    Conclusions: A temporal-based pericranial flap represents an alternative vascularized pedicle flap to the classic frontal-based pericranial flap used in orbitofrontal dural repair. In certain clinical settings, the temporal-based flap may be preferable.

  8. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

    Science.gov (United States)

    Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

    2012-03-01

    Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  9. Effect of Intermediate Agents and Preheated Composites on Repair Bond Strength of Silorane-Based Composites

    Directory of Open Access Journals (Sweden)

    Fereshteh Shafiei

    2016-05-01

    Full Text Available Objectives: Repairing composite restorations is a challenging procedure especially when two different types of composites are used. This study aimed to compare the repair strength of silorane-based composite (SC (Filtek P90 with that of preheated SC, methacrylate composite (MC(Z250, flowable MC (Filtek Supreme Plus and different adhesive/composite combinations.Materials and Methods: Eighty-four SC specimens were fabricated and randomly divided into seven groups (G. In the control group (G7, SC was bonded immediately to SC. The other specimens were water-aged for two months and were then roughened, etched and repaired with the following materials: G1 Silorane Adhesive Bond (SAB/SC;G2 Preheated SC; G3 SAB/MC; G4 Adper Single Bond (SB/MC; G5 Flowable MC/MC; G6 Preheated MC. After water storage and thermocycling, the repaired specimens were subjected to shear bond strength testing. The data were analyzed using ANOVA and Tukey’s test.Results: Preheated SC and MC, flowable MC and SAB/SC resulted in bond strength comparable to that of the control group. Preheated SC showed significantly higher bond strength when compared to SAB/MC (P=0.04 and SB/MC (P<0.001. Bond strength of SB/MC was significantly lower than that of the other groups (P<0.05, except for SAB/SC and SAB/MC.Conclusion: All repairing materials except for SB/MC resulted in bond strength values comparable to that of the control group. Repair with preheated SC yielded the highest bond strength. 

  10. The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target.

    Science.gov (United States)

    Fishel, Melissa L; Kelley, Mark R

    2007-01-01

    With our growing understanding of the pathways involved in cell proliferation and signaling, targeted therapies, in the treatment of cancer are entering the clinical arena. New and emerging targets are proteins involved in DNA repair pathways. Inhibition of various proteins in the DNA repair pathways sensitizes cancer cells to DNA damaging agents such as chemotherapy and/or radiation. We study the apurinic endonuclease 1/redox factor-1 (Ape1/Ref-1) and believe that its crucial function in DNA repair and reduction-oxidation or redox signaling make it an excellent target for sensitizing tumor cells to chemotherapy. Ape1/Ref-1 is an essential enzyme in the base excision repair (BER) pathway which is responsible for the repair of DNA caused by oxidative and alkylation damage. As importantly, Ape1/Ref-1 also functions as a redox factor maintaining transcription factors in an active reduced state. Ape1/Ref-1 stimulates the DNA binding activity of numerous transcription factors that are involved in cancer promotion and progression such as AP-1 (Fos/Jun), NFkappaB, HIF-1alpha, CREB, p53 and others. We will discuss what is known regarding the pharmacological targeting of the DNA repair activity, as well as the redox activity of Ape1/Ref-1, and explore the budding clinical utility of inhibition of either of these functions in cancer treatment. A brief discussion of the effect of polymorphisms in its DNA sequence is included because of Ape1/Ref-1's importance to maintenance and integrity of the genome. Experimental modification of Ape1/Ref-1 activity changes the response of cells and of organisms to DNA damaging agents, suggesting that Ape1/Ref-1 may also be a productive target of chemoprevention. In this review, we will provide an overview of Ape1/Ref-1's activities and explore the potential of this protein as a target in cancer treatment as well as its role in chemoprevention.

  11. Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity

    Science.gov (United States)

    Patrono, Clarice; Sterpone, Silvia; Testa, Antonella; Cozzi, Renata

    2014-01-01

    Breast cancer (BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy (RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients’ treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms (SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair (BER) genes and BC risk. We focused on X-ray repair cross complementing group 1 (XRCC1), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly (ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity. PMID:25493225

  12. Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cells

    Institute of Scientific and Technical Information of China (English)

    Muralidhar L Hegde; Tapas K Hazra; Sankar Mitra

    2008-01-01

    Base excision repair (BER) is an evolutionarily conserved process for maintaining genomic integrity by eliminating several dozen damaged (oxidized or alkylated) or inappropriate bases that are generated endogenously or induced by genotoxicants, predominantly, reactive oxygen species (ROS). BER involves 4-5 steps starting with base excision by a DNA glycosylase, followed by a common pathway usually involving an AP-endonuclease (APE) to generate 3' OH terminus at the damage site, followed by repair synthesis with a DNA polymerase and nick sealing by a DNA ligase. This pathway is also responsible for repairing DNA single-strand breaks with blocked termini directly generated by ROS. Nearly all glycosylases, far fewer than their substrate lesions particularly for oxidized bases, have broad and overlapping substrate range, and could serve as back-up enzymes in vivo. In contrast, mammalian cells encode only one APE, APEl, unlike two APEs in lower organisms. In spite of overall similarity, BER with distinct subpathways in the mammals is more complex than in E.coli. The glycosylases form complexes with downstream proteins to carry out efficient repair via distinct subpathways one of which, responsible for repair of strand breaks with 3' phosphate ter-mini generated by the NEIL family glycosylases or by ROS, requires the phosphatase activity of polynucleotide kinase instead of APEl. Different complexes may utilize distinct DNA polymerases and ligases. Mammalian glycosylases have nonconserved extensions at one of the termini, dispensable for enzymatic activity but needed for interaction with other BER and non-BER proteins for complex formation and organelle targeting. The mammalian enzymes are sometimes covalently modified which may affect activity and complex formation. The focus of this review is on the early steps in mammalian BER for oxidized damage.

  13. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    Science.gov (United States)

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age.

  14. Early Steps in the DNA Base Excision Repair Pathway of a Fission Yeast Schizosaccharomyces pombe

    Directory of Open Access Journals (Sweden)

    Kyoichiro Kanamitsu

    2010-01-01

    Full Text Available DNA base excision repair (BER accounts for maintaining genomic integrity by removing damaged bases that are generated endogenously or induced by genotoxic agents. In this paper, we describe the roles of enzymes functioning in the early steps of BER in fission yeast. Although BER is an evolutionarily conserved process, some unique features of the yeast repair pathway were revealed by genetic and biochemical approaches. AP sites generated by monofunctional DNA glycosylases are incised mainly by AP lyase activity of Nth1p, a sole bifunctional glycosylase in yeast, to leave a blocked 3′ end. The major AP endonuclease Apn2p functions predominantly in removing the 3′ block. Finally, a DNA polymerase fills the gap, and a DNA ligase seals the nick (Nth1p-dependent or short patch BER. Apn1p backs up Apn2p. In long patch BER, Rad2p endonuclease removes flap DNA containing a lesion after DNA synthesis. A UV-specific endonuclease Uve1p engages in an alternative pathway by nicking DNA on the 5′ side of oxidative damage. Nucleotide excision repair and homologous recombination are involved in repair of BER intermediates including the AP site and single-strand break with the 3′ block. Other enzymes working in 3′ end processing are also discussed.

  15. Feasibility of exercise stress echocardiography and myocardial response in patients with repaired congenital heart disease.

    Science.gov (United States)

    Hasan, Babar S; Lunze, Fatima I; Alvi, Najveen; Shafer, Keri M; Rhodes, Jonathan

    2017-06-01

    Exercise stress echocardiography (ESE) can unmask ventricular dysfunction in asymptomatic patients with congenital heart disease (CHD), but its acquisition and interpretation is often challenging, and the method has not been validated in CHD. This study aimed to evaluate the feasibility of ESE using Doppler imaging and to assess myocardial response to exercise in patients with biventricular (BiV) and univentricular (UniV) circulation after CHD repair. In this single-center prospective study, we recruited 55 participants (17 females), median age 14 years (8-22 years). Our analysis categorized participants in these three groups: with structurally normal hearts as controls (n=21), with BiV circulation (n=20) and with UniV circulation (n=14). We acquired ESE images of the systemic ventricle including pulsed-wave flow and spectral tissue Doppler imaging (TDI) of lateral free wall before and immediately after standard, symptom-limited exercise tests on an electronically braked cycle ergometer. During ESE we obtained inflow E-wave and TDI systolic (S') and early diastolic (E') velocities in 93% to 100% of participants at rest and in 90% to 100% of participants post exercise. Feasibility to obtain Doppler imaging parameter was the same across study groups. The myocardial response to exercise was increase in heart rate (HR), S' and inflow E-wave velocity in all participants. Patients with BiV circulation had preserved ventricular function at rest. While patients with UniV circulation had low S', E', and E-wave velocities at rest in comparison to controls and to BiV group (all Pincreases in HR, S' velocity and inflow E-wave velocity post exercise, with magnitudes of these increases higher in controls than in the BiV and UniV group. The S' and E' velocities were strongly associated with lower percent predicted peak oxygen consumption VO2 (rs=0.614 and rs=0.64, respectively, both Pexercise in patients after biventricular and univentricular CHD repair. Although patients with Bi

  16. Resident adult neural stem cells in Parkinson's disease--the brain's own repair system?

    Science.gov (United States)

    van den Berge, Simone A; van Strien, Miriam E; Hol, Elly M

    2013-11-05

    One important pathological process in the brain of Parkinson disease (PD) patients is the degeneration of the dopaminergic neurons in the substantia nigra, which leads to a decline in striatal dopamine levels and motor dysfunction. A major clinical problem is that this degenerative process currently cannot be stopped or reversed. Expectations from the restorative capacity of neural stem cells (NSCs) are high, as these cells can potentially replace the degenerating neurons. The discovery of the presence of NSCs in the adult human brain has instigated research into the potential of these cells as a resource to promote brain repair in neurodegenerative diseases. Neural stem and progenitor cells reside in the subventricular zone (SVZ), which is closely situated to the striatum, which is affected in PD. Therefore, restoring the dopamine levels in the striatum of PD patients through stimulating endogenous NSCs in the nearby SVZ to migrate into the striatum and differentiate into dopaminergic neurons might thus be an attractive future therapeutic approach. We will review the reported changes in NSCs in the SVZ of PD animal models and PD patients, which are due to a lack of striatal dopamine. Furthermore, we will summarise the reports that describe efforts to stimulate NSCs to replace dopaminergic cells in the SN and restore striatal dopamine levels. In our opinion, mobilizing the endogenous SVZ NSCs to replenish striatal dopamine is an attractive approach to alleviate the motor symptoms in PD patients, without the ethical and immunological challenges of transplantation of NSCs and foetal brain tissue. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Probabilistic Fatigue Life Updating for Railway Bridges Based on Local Inspection and Repair

    Science.gov (United States)

    Lee, Young-Joo; Kim, Robin E.; Suh, Wonho; Park, Kiwon

    2017-01-01

    Railway bridges are exposed to repeated train loads, which may cause fatigue failure. As critical links in a transportation network, railway bridges are expected to survive for a target period of time, but sometimes they fail earlier than expected. To guarantee the target bridge life, bridge maintenance activities such as local inspection and repair should be undertaken properly. However, this is a challenging task because there are various sources of uncertainty associated with aging bridges, train loads, environmental conditions, and maintenance work. Therefore, to perform optimal risk-based maintenance of railway bridges, it is essential to estimate the probabilistic fatigue life of a railway bridge and update the life information based on the results of local inspections and repair. Recently, a system reliability approach was proposed to evaluate the fatigue failure risk of structural systems and update the prior risk information in various inspection scenarios. However, this approach can handle only a constant-amplitude load and has limitations in considering a cyclic load with varying amplitude levels, which is the major loading pattern generated by train traffic. In addition, it is not feasible to update the prior risk information after bridges are repaired. In this research, the system reliability approach is further developed so that it can handle a varying-amplitude load and update the system-level risk of fatigue failure for railway bridges after inspection and repair. The proposed method is applied to a numerical example of an in-service railway bridge, and the effects of inspection and repair on the probabilistic fatigue life are discussed. PMID:28441768

  18. Probabilistic Fatigue Life Updating for Railway Bridges Based on Local Inspection and Repair.

    Science.gov (United States)

    Lee, Young-Joo; Kim, Robin E; Suh, Wonho; Park, Kiwon

    2017-04-24

    Railway bridges are exposed to repeated train loads, which may cause fatigue failure. As critical links in a transportation network, railway bridges are expected to survive for a target period of time, but sometimes they fail earlier than expected. To guarantee the target bridge life, bridge maintenance activities such as local inspection and repair should be undertaken properly. However, this is a challenging task because there are various sources of uncertainty associated with aging bridges, train loads, environmental conditions, and maintenance work. Therefore, to perform optimal risk-based maintenance of railway bridges, it is essential to estimate the probabilistic fatigue life of a railway bridge and update the life information based on the results of local inspections and repair. Recently, a system reliability approach was proposed to evaluate the fatigue failure risk of structural systems and update the prior risk information in various inspection scenarios. However, this approach can handle only a constant-amplitude load and has limitations in considering a cyclic load with varying amplitude levels, which is the major loading pattern generated by train traffic. In addition, it is not feasible to update the prior risk information after bridges are repaired. In this research, the system reliability approach is further developed so that it can handle a varying-amplitude load and update the system-level risk of fatigue failure for railway bridges after inspection and repair. The proposed method is applied to a numerical example of an in-service railway bridge, and the effects of inspection and repair on the probabilistic fatigue life are discussed.

  19. FACT Assists Base Excision Repair by Boosting the Remodeling Activity of RSC.

    Science.gov (United States)

    Charles Richard, John Lalith; Shukla, Manu Shubhdarshan; Menoni, Hervé; Ouararhni, Khalid; Lone, Imtiaz Nisar; Roulland, Yohan; Papin, Christophe; Ben Simon, Elsa; Kundu, Tapas; Hamiche, Ali; Angelov, Dimitar; Dimitrov, Stefan

    2016-07-01

    FACT, in addition to its role in transcription, is likely implicated in both transcription-coupled nucleotide excision repair and DNA double strand break repair. Here, we present evidence that FACT could be directly involved in Base Excision Repair and elucidate the chromatin remodeling mechanisms of FACT during BER. We found that, upon oxidative stress, FACT is released from transcription related protein complexes to get associated with repair proteins and chromatin remodelers from the SWI/SNF family. We also showed the rapid recruitment of FACT to the site of damage, coincident with the glycosylase OGG1, upon the local generation of oxidized DNA. Interestingly, FACT facilitates uracil-DNA glycosylase in the removal of uracil from nucleosomal DNA thanks to an enhancement in the remodeling activity of RSC. This discloses a novel property of FACT wherein it has a co-remodeling activity and strongly enhances the remodeling capacity of the chromatin remodelers. Altogether, our data suggest that FACT may acts in concert with RSC to facilitate excision of DNA lesions during the initial step of BER.

  20. Influence of surface treatments to repair recent fillings of silorane-and methacrylate-based composites.

    Science.gov (United States)

    Kaneko, Marina; Caldas, Ricardo Armini; Feitosa, Victor Pinheiro; Xediek Consani, Rafael Leonardo; Schneider, Luis Felipe J; Bacchi, Ataís

    2015-01-01

    The aim of this study was to evaluate the tensile bond strength (TBS) of repairs in recent fillings of methacrylate- (MBC) or silorane-based composites (SBC) subsequent to different surface treatments. Fifty slabs of Filtek P60 (3M ESPE, St Paul, USA) and Filtek P90 (3M ESPE) were stored for 10 days in distilled water at 37°C. The surface of adhesion was abraded with a 600-grit silicone paper and repaired using each respective composite: G1, no treatment (control); G2, application of adhesive; G3, application of silane and adhesive; G4, sandblasting (Al2O3) and adhesive; and G5, sandblasting (Al2O3), silane, and adhesive. Further 10 slabs of each composite were also evaluated for cohesive strength (G6). After 30 days immersion in distilled water at 37°C, the TBS was determined. TBS results were higher for MBC than for SBC (P = 0.00012). The experimental groups were similar for SBC and the TBS was 27% of its cohesive strength. For P60, sandblasting significantly improved the TBS compared to other groups. With MBC, G4 and G5, the TBS was approximately 47% of its cohesive strength. Sandblasting (Al2O3) improves the repair-strength of MBC, whilst for the SBC all treatments succeed. MBC presents higher repair strength than SBC.

  1. Tailored approach in inguinal hernia repair – Decision tree based on the guidelines

    Directory of Open Access Journals (Sweden)

    Ferdinand eKöckerling

    2014-06-01

    Full Text Available The endoscopic procedures TEP and TAPP and the open techniques Lichtenstein, Plug and Patch and PHS currently represent the gold standard in inguinal hernia repair recommended in the guidelines of the European Hernia Society, the International Endohernia Society and the European Association of Endoscopic Surgery. 82 % of experienced hernia surgeons use the tailored approach, the differentiated use of the several inguinal hernia repair techniques depending on the findings of the patient, trying to minimize the risks. The following differential therapeutic situations must be distinguished in inguinal hernia repair: unilateral in men, unilateral in women, bilateral, scrotal, after previous pelvic and lower abdominal surgery, no general anaesthesia possible, recurrence and emergency surgery. Evidence-based guidelines and consensus conferences of experts give recommendations for the best approach in the individual situation of a patient. This review tries to summarized the recommendations of the various guidelines and to transfer them into a practical dicision tree for the daily work of surgeons performing inguinal hernia repair.

  2. A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases.

    Science.gov (United States)

    Fujita, Kyota; Nakamura, Yoko; Oka, Tsutomu; Ito, Hikaru; Tamura, Takuya; Tagawa, Kazuhiko; Sasabe, Toshikazu; Katsuta, Asuka; Motoki, Kazumi; Shiwaku, Hiroki; Sone, Masaki; Yoshida, Chisato; Katsuno, Masahisa; Eishi, Yoshinobu; Murata, Miho; Taylor, J Paul; Wanker, Erich E; Kono, Kazuteru; Tashiro, Satoshi; Sobue, Gen; La Spada, Albert R; Okazawa, Hitoshi

    2013-01-01

    It is hypothesized that a common underlying mechanism links multiple neurodegenerative disorders. Here we show that transitional endoplasmic reticulum ATPase (TERA)/valosin-containing protein (VCP)/p97 directly binds to multiple polyglutamine disease proteins (huntingtin, ataxin-1, ataxin-7 and androgen receptor) via polyglutamine sequence. Although normal and mutant polyglutamine proteins interact with TERA/VCP/p97, only mutant proteins affect dynamism of TERA/VCP/p97. Among multiple functions of TERA/VCP/p97, we reveal that functional defect of TERA/VCP/p97 in DNA double-stranded break repair is critical for the pathology of neurons in which TERA/VCP/p97 is located dominantly in the nucleus in vivo. Mutant polyglutamine proteins impair accumulation of TERA/VCP/p97 and interaction of related double-stranded break repair proteins, finally causing the increase of unrepaired double-stranded break. Consistently, the recovery of lifespan in polyglutamine disease fly models by TERA/VCP/p97 corresponds well to the improvement of double-stranded break in neurons. Taken together, our results provide a novel common pathomechanism in multiple polyglutamine diseases that is mediated by DNA repair function of TERA/VCP/p97.

  3. Fuzzy Activity Based Life Cycle Costing For Repairable Equipment

    Directory of Open Access Journals (Sweden)

    Mulubrhan Freselam

    2016-01-01

    Full Text Available Life-cycle cost (LCC is the much known method used for decision making that considers all costs in the life of a system or equipment. Predicting LCCs is fraught with potential errors, owing to the uncertainty in future events, future costs, interest rates, and even hidden costs. These uncertainties have a direct impact on the decision making. Activity based LCC is used to identify the activities and cost drivers in acquisition, operation and maintenance phase. This activity based LCC is integrated with fuzzy set theory and interval mathematics to model these uncertainties. Day–Stout–Warren (DSW algorithm and the vertex method are then used to evaluate competing alternatives. A case of two pumps (Pump A and Pump B are taken and their LCC is analysed using the developed model. The equivalent annual cost of Pump B is greater than Pump A, which leads the decision maker to choose Pump A over Pump B.

  4. Optimizing paced ventricular function in patients with and without repaired congenital heart disease by contractility-guided lead implant.

    Science.gov (United States)

    Karpawich, Peter P; Singh, Harinder; Zelin, Kathleen

    2015-01-01

    This study evaluates the concept of optimizing ventricular pacing in regard to functional cardiac response. Lead implant based on physiologic variables of contractility at various sites was performed in patients with and without congenital heart disease (CHD). Since right ventricular apical pacing may adversely alter contractility and myocellular function, septal and outflow tract pacing have been advocated. However, there are few studies in the young and essentially none in those with CHD. A total of 113 consecutive patients with and without repaired CHD, aged two to 51 (median 16), some with preexisting epicardial pacemakers, underwent transvenous pacemaker implant using standard sensing/pacing indices plus measurements of pressures, QRS, and contractility responses at each of five predefined potential ventricular implant sites: apex, inflow-, low-, mid-, and infundibular/outflow-septal with each patient serving as his/her own control. Implant was at the site of best contractility with active-fixation, low-threshold steroid-eluting leads. Measured contractility indices varied up to 31% (mean 12%) between sites per patient. Septal regions (mid-, inflow-, and low-) were associated with the most optimal and right ventricular epicardial showed the worst contractility (P implant sites are patient and CHD variable. Current lead designs ensure chronic stability/performance regardless of site. Proactive contractility-guided pacing implant can optimize chronic paced ventricular function. ©2014 Wiley Periodicals, Inc.

  5. Articular Cartilage Repair Through Muscle Cell-Based Tissue Engineering

    Science.gov (United States)

    2010-03-01

    fferentiation of s tem c ells is also an i mportant i ssue t o c onsider e specially f or t he persistence of the regenerate cartilage. Based on these...tap water for 10 minutes and counterstained with nuclear fast red. Differentiation of MDSCs into chondrocytes. Pellets in OCT blocks were sectioned and...into Alcian blue solution for 30 minutes. The slides were rinsed with running tap water for 10 minutes and counterstained with nuclear fast red

  6. Differential expression of tissue repair genes in the pathogenesis of chronic obstructive pulmonary disease

    National Research Council Canada - National Science Library

    Gosselink, John V; Hayashi, Shizu; Elliott, W Mark; Xing, Li; Chan, Becky; Yang, Luojia; Wright, Claire; Sin, Don; Paré, Peter D; Pierce, John A; Pierce, Richard A; Patterson, Alex; Cooper, Joel; Hogg, James C

    2010-01-01

    .... The expression of 54 genes associated with repair of repetitively damaged tissue was measured in 136 paired samples of small bronchioles and surrounding lung tissue separated by laser capture microdissection...

  7. Databases and Bioinformatics Tools for the Study of DNA Repair

    Directory of Open Access Journals (Sweden)

    Kaja Milanowska

    2011-01-01

    Full Text Available DNA is continuously exposed to many different damaging agents such as environmental chemicals, UV light, ionizing radiation, and reactive cellular metabolites. DNA lesions can result in different phenotypical consequences ranging from a number of diseases, including cancer, to cellular malfunction, cell death, or aging. To counteract the deleterious effects of DNA damage, cells have developed various repair systems, including biochemical pathways responsible for the removal of single-strand lesions such as base excision repair (BER and nucleotide excision repair (NER or specialized polymerases temporarily taking over lesion-arrested DNA polymerases during the S phase in translesion synthesis (TLS. There are also other mechanisms of DNA repair such as homologous recombination repair (HRR, nonhomologous end-joining repair (NHEJ, or DNA damage response system (DDR. This paper reviews bioinformatics resources specialized in disseminating information about DNA repair pathways, proteins involved in repair mechanisms, damaging agents, and DNA lesions.

  8. Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes.

    Science.gov (United States)

    Dragileva, Ella; Hendricks, Audrey; Teed, Allison; Gillis, Tammy; Lopez, Edith T; Friedberg, Errol C; Kucherlapati, Raju; Edelmann, Winfried; Lunetta, Kathryn L; MacDonald, Marcy E; Wheeler, Vanessa C

    2009-01-01

    Modifying the length of the Huntington's disease (HD) CAG repeat, the major determinant of age of disease onset, is an attractive therapeutic approach. To explore this we are investigating mechanisms of intergenerational and somatic HD CAG repeat instability. Here, we have crossed HD CAG knock-in mice onto backgrounds deficient in mismatch repair genes, Msh3 and Msh6, to discern the effects on CAG repeat size and disease pathogenesis. We find that different mechanisms predominate in inherited and somatic instability, with Msh6 protecting against intergenerational contractions and Msh3 required both for increasing CAG length and for enhancing an early disease phenotype in striatum. Therefore, attempts to decrease inherited repeat size may entail a full understanding of Msh6 complexes, while attempts to block the age-dependent increases in CAG size in striatal neurons and to slow the disease process will require a full elucidation of Msh3 complexes and their function in CAG repeat instability.

  9. A quantitative model of human DNA base excision repair. I. mechanistic insights

    OpenAIRE

    Sokhansanj, Bahrad A.; Rodrigue, Garry R.; Fitch, J. Patrick; David M Wilson

    2002-01-01

    Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts conside...

  10. Apn1 AP-endonuclease is essential for the repair of oxidatively damaged DNA bases in yeast frataxin-deficient cells.

    Science.gov (United States)

    Lefevre, Sophie; Brossas, Caroline; Auchère, Françoise; Boggetto, Nicole; Camadro, Jean-Michel; Santos, Renata

    2012-09-15

    Frataxin deficiency results in mitochondrial dysfunction and oxidative stress and it is the cause of the hereditary neurodegenerative disease Friedreich ataxia (FA). Here, we present evidence that one of the pleiotropic effects of oxidative stress in frataxin-deficient yeast cells (Δyfh1 mutant) is damage to nuclear DNA and that repair requires the Apn1 AP-endonuclease of the base excision repair pathway. Major phenotypes of Δyfh1 cells are respiratory deficit, disturbed iron homeostasis and sensitivity to oxidants. These phenotypes are weak or absent under anaerobiosis. We show here that exposure of anaerobically grown Δyfh1 cells to oxygen leads to down-regulation of antioxidant defenses, increase in reactive oxygen species, delay in G1- and S-phases of the cell cycle and damage to mitochondrial and nuclear DNA. Nuclear DNA lesions in Δyfh1 cells are primarily caused by oxidized bases and single-strand breaks that can be detected 15-30 min after oxygen exposition. The Apn1 enzyme is essential for the repair of the DNA lesions in Δyfh1 cells. Compared with Δyfh1, the double Δyfh1Δapn1 mutant shows growth impairment, increased mutagenesis and extreme sensitivity to H(2)O(2). On the contrary, overexpression of the APN1 gene in Δyfh1 cells decreases spontaneous and induced mutagenesis. Our results show that frataxin deficiency in yeast cells leads to increased DNA base oxidation and requirement of Apn1 for repair, suggesting that DNA damage and repair could be important features in FA disease progression.

  11. Cartilage repair: surgical techniques and tissue engineering using polysaccharide- and collagen-based biomaterials.

    Science.gov (United States)

    Galois, L; Freyria, A M; Grossin, L; Hubert, P; Mainard, D; Herbage, D; Stoltz, J F; Netter, P; Dellacherie, E; Payan, E

    2004-01-01

    Lesions of articular cartilage have a large variety of causes among which traumatic damage, osteoarthritis and osteochondritis dissecans are the most frequent. Replacement of articular defects in joints has assumed greater importance in recent years. This interest results in large part because cartilage defects cannot adequately heal themselves. Many techniques have been suggested over the last 30 years, but none allows the regeneration of the damaged cartilage, i.e. its replacement by a strictly identical tissue. In the first generation of techniques, relief of pain was the main concern, which could be provided by techniques in which cartilage was replaced by fibrocartilage. Disappointing results led investigators to focus on more appropriate bioregenerative approaches using transplantation of autologous cells into the lesion. Unfortunately, none of these approaches has provided a perfect final solution to the problem. The latest generation of techniques, currently in the developmental or preclinical stages, involve biomaterials for the repair of chondral or osteochondral lesions. Many of these scaffolds are designed to be seeded with chondrocytes or progenitor cells. Among natural and synthetic polymers, collagen- and polysaccharide-based biomaterials have been extensively used. For both these supports, studies have shown that chondrocytes maintain their phenotype when cultured in three dimensions. In both types of culture, a glycosaminoglycan-rich deposit is formed on the surface and in the inner region of the cultured cartilage, and type II collagen synthesis is also observed. Dynamic conditions can also improve the composition of such three-dimensional constructs. Many improvements are still required, however, in a number of key aspects that so far have received only scant attention. These aspects include: adhesion/integration of the graft with the adjacent native cartilage, cell-seeding with genetically-modified cell populations, biomaterials that can be

  12. Base excision repair pathway: PARP1 genotypes as modulators of therapy response in cervical cancer patients.

    Science.gov (United States)

    Nogueira, Augusto; Assis, Joana; Faustino, Ilda; Pereira, Deolinda; Catarino, Raquel; Medeiros, Rui

    2017-02-01

    Genetic polymorphisms in genes of the base excision repair (BER) pathway appear to modulate the therapy response of cancer patients. PARP1 protein recognizes the DNA strand damage and facilitates the subsequent recruitment of BER proteins. Few studies have reported an association between PARP1 Val762Ala polymorphism (rs1136410) and cancer therapy response. The purpose of our study was to determine whether PARP1 Val762Ala polymorphism have prognostic value in patients with cervical cancer. Two hundred and sixty adult patients, with histologically confirmed cervical cancer, at FIGO-stages IB2-IVA, primarily treated with concurrent chemotherapy (cisplatin) and radiotherapy. Overall survival (OS) and disease-free survival (DFS) were the primary end points of the analysis. The PARP1 Val762Ala genetic variants were analyzed by allelic discrimination by real-time PCR. We observed that peri- and postmenopausal women carrying the C-allele present a statistically significant lower OS and DFS (log-rank test, p = 0.008 and p = 0.006, respectively) among those with early stage cervical cancer. Cox regression analysis confirmed these results, after adjustment for other prognostic factors (for OS: HR, 3.70; 95%CI, 1.32-10.38; p = 0.013 and for DFS: HR, 3.97; 95%CI, 1.59-9.93; p = 0.003). This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

  13. The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

    Directory of Open Access Journals (Sweden)

    Littlejohns David

    2011-02-01

    Full Text Available Abstract Background Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD and its location at regions undergoing restitution and regeneration. Tissue repair is essential for disease remission and we sought to determine the effects of therapeutic modalities on fascin expression and function using an in vitro model. Methods Immunohistochemistry was performed on colonic tissue from IBD patients to determine changes in fascin expression and distribution. A human colorectal epithelial cell line was treated with 5-aminosalicylate (a common treatment for IBD, or sodium butyrate to determine the effect on fascin expression and cell motility. Results Fascin overexpression was observed in both ulcerative colitis and Crohn's colitis and expression correlated with disease severity. Immunoreactivity was more intense and widespread in Crohn's compared to ulcerative colitis. Interestingly, highly expressing foci were consistently observed at the edges of ulcers where flattened, motile epithelial cells are actively involved in restitution, and also in areas of mucosal regeneration. 5-aminosalicylate reduced fascin expression in colorectal epithelial cells and inhibited their motility. Conversely, sodium butyrate increased fascin expression and stimulated cell motility in the same cells. Conclusions Our data shows that fascin is overexpressed in inflammatory bowel disease and its location is indicative of a role in tissue repair. Our in vitro studies show that different therapeutic modalities may have converse effects on fascin expression and may have significant consequences for disease remission and the clinical management of IBD.

  14. Is Early Nasal Shaping With a Limited Alar Base Incision Possible in the Repair of Cleft Lips?

    Science.gov (United States)

    Kapi, Emin; Bozkurt, Mehmet; Ozer, Torun; Celik, Mehmet Yusuf

    2016-05-01

    The repair of cleft lips has an important place in plastic and reconstructive surgery. In the treatment of these deformities, the aim was to restore the normal lip morphology in the cleft area as well as repairing any coexisting nasal deformities. Various methods are in use for this purpose. One of the most commonly employed surgical methods is Millard repair. However, this method may lead to additional scarring in the alar base on the cleft side subsequent to the incision. In this study, the results obtained from a group who have been applied alar base incisions during the modified Millard repair are compared to a group who have undergone intranasal wide dissections.The patients enrolled in the study were randomized into 2 groups. The first group were applied the modified Millard repair. In the second group, the rotation, advancement, and C-flaps were prepared according to Millard surgical repair technique; however, instead of an alar base and nasofacial groove incision on the cleft side, a nasal and maxillary supraperiosteal wide dissection was made through the incision in the mucosa of the nostril.The intranasal dissection performed during the study was observed to provide the targeted outcome and a more satisfactory cosmetic result through the modified Millard repair. In conclusion, the authors are of the opinion that the limited alar base incision and the wide supraperiosteal dissection performed in patients with cleft lips is an alternative method that can be employed in a wide range of patients.

  15. Repair approach for DMC images based on hierarchical location using edge curve

    Institute of Scientific and Technical Information of China (English)

    PAN Jun; WANG Mi; LI DeRen; FENG TianTian

    2009-01-01

    The color composite digital mapping camera (DMC) images are produced by the post-processing software of Z/I imaging. But the failure of radiometric correction in post-processing leads to residual radiometric differences between CCD images, which then affect the quality of the images in further applications. This paper, via analyzing the characters and causes of such a phenomenon, proposes a repair approach based on hierarchical location using edge curve. The approach employs a hierarchical strategy to locate the transition area and seam-line automatically and then repair the image through the global reconstruction between CCD images and the local reconstruction in the transition area. Experiments indicate that the approach proposed by this paper is feasible and can improve the quality of images effectively.

  16. Uncertain multiobjective redundancy allocation problem of repairable systems based on artificial bee colony algorithm

    Institute of Scientific and Technical Information of China (English)

    Guo Jiansheng; Wang Zutong; Zheng Mingfa; Wang Ying

    2014-01-01

    Based on the uncertainty theory, this paper is devoted to the redundancy allocation problem in repairable parallel-series systems with uncertain factors, where the failure rate, repair rate and other relative coefficients involved are considered as uncertain variables. The availability of the system and the corresponding designing cost are considered as two optimization objectives. A crisp multiobjective optimization formulation is presented on the basis of uncertainty theory to solve this resultant problem. For solving this problem efficiently, a new multiobjective artificial bee colony algorithm is proposed to search the Pareto efficient set, which introduces rank value and crowding distance in the greedy selection strategy, applies fast non-dominated sort procedure in the exploitation search and inserts tournament selection in the onlooker bee phase. It shows that the proposed algorithm outperforms NSGA-II greatly and can solve multiobjective redundancy allocation problem efficiently. Finally, a numerical example is provided to illustrate this approach.

  17. Exact-Repair Minimum Bandwidth Regenerating Codes Based on Evaluation of Linearized Polynomials

    CERN Document Server

    Xie, Hongmei

    2012-01-01

    In this paper, we propose two new constructions of exact-repair minimum storage regenerating (exact-MBR) codes. Both constructions obtain the encoded symbols by first treating the message vector over GF(q) as a linearized polynomial and then evaluating it over an extension field GF(q^m). The evaluation points are chosen so that the encoded symbols at any node are conjugates of each other, while corresponding symbols of different nodes are linearly dependent with respect to GF(q). These properties ensure that data repair can be carried out over the base field GF(q), instead of matrix inversion over the extension field required by some existing exact-MBR codes. To the best of our knowledge, this approach is novel in the construction of exact-MBR codes. One of our constructions leads to exact-MBR codes with arbitrary parameters. These exact-MBR codes have higher data reconstruction complexities but lower data repair complexities than their counterparts based on the product-matrix approach; hence they may be suit...

  18. A national Vascular Quality Initiative database comparison of hybrid and open repair for aortoiliac-femoral occlusive disease.

    Science.gov (United States)

    Zavatta, Marco; Mell, Matthew W

    2017-08-16

    We sought to analyze the outcomes of revascularization for aortoiliac-femoral occlusive disease by comparing hybrid repair by endovascular revascularization and open common femoral endarterectomy (ER-CFE) with open aortoiliac reconstruction and CFE (OR-CFE). Using the national Society for Vascular Surgery Vascular Quality Initiative database from 2009 to 2015, we identified all patients receiving open or endovascular revascularization of the aortoiliac system and who additionally underwent CFE. Patients with concomitant infrainguinal procedures were excluded, as were procedures performed at centers with CFE group and 1472 in the ER-CFE group with follow-up of at least 9 months. Patients with ER-CFE were older (68 ± 9 years vs 63 ± 9 years; P CFE were more likely to have received a previous inflow procedure (27% vs 21%; P CFE (5.2 ± 1.6 vs 2.9 ± 1.0; P CFE was associated with lower 30-day mortality (1.8% vs 3.4%; P = .01), shorter length of stay (median 3 vs 7 days; P CFE had greater ABI improvement at long-term follow-up (0.39 ± 0.37 vs 0.26 ± 0.23; P CFE appeared to have improved short-term outcomes and equivalent freedom from major amputation compared with open surgical repair with CFE. Conversely, open repair with CFE was associated with better long-term improvement in ABI and ambulatory status. Open repair should therefore be considered for patients with aortoiliac-femoral occlusive disease and reasonable surgical risk. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  19. REPAIR OF LARGE SKULL BASE DEFECT FOLLOWING EXCISION OF BASALOID SQUAMOUS CELL CARCINOMA OF MAXILLO - ETHMOID REGION : A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Monoj Mukherjee

    2015-02-01

    Full Text Available AIM: To present a case of basaloid squamous cell carcinoma of maxillo - ethmoid region with intracranial extradural extention and its surgical management including repair of the skull base defect. MATERIAL : A 30 year female presented with progressive bilateral nasal obstruction, facial deformity for 5 years duration. She developed blindness in last 6 months. Recent CT s can showed large heterogeneous enhancing soft tissue mass in right maxillary sinus, nasal cavity and right ethmoid sinus invading the skull base . INTERVENTION : She underwent excision of the mass by modified weber ferguson incision and repair of skull base defect with temporalis muscle flap. Skin defect over the face and nose was repaired by median forehead flap. RESULT : There was total tumor clearance and no CSF leakage following surgery. CONCLUSION : Sinonasal malignancy with intracranial extradural extenti on is not a contraindication for successful surgical management. Resultant skull base defect can be repaired by a temporalis muscle flap to prevent CSF leak and intracranial infection

  20. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Directory of Open Access Journals (Sweden)

    Ricardo Mouro Pinto

    2013-10-01

    Full Text Available The Huntington's disease gene (HTT CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111 mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111 than on a 129 background (129.Hdh(Q111 . Linkage mapping in (B6x129.Hdh(Q111 F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111 mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111 somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3 complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3. The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest

  1. Mismatch repair genes Mlh1 and Mlh3 modify CAG instability in Huntington's disease mice: genome-wide and candidate approaches.

    Science.gov (United States)

    Pinto, Ricardo Mouro; Dragileva, Ella; Kirby, Andrew; Lloret, Alejandro; Lopez, Edith; St Claire, Jason; Panigrahi, Gagan B; Hou, Caixia; Holloway, Kim; Gillis, Tammy; Guide, Jolene R; Cohen, Paula E; Li, Guo-Min; Pearson, Christopher E; Daly, Mark J; Wheeler, Vanessa C

    2013-10-01

    The Huntington's disease gene (HTT) CAG repeat mutation undergoes somatic expansion that correlates with pathogenesis. Modifiers of somatic expansion may therefore provide routes for therapies targeting the underlying mutation, an approach that is likely applicable to other trinucleotide repeat diseases. Huntington's disease Hdh(Q111) mice exhibit higher levels of somatic HTT CAG expansion on a C57BL/6 genetic background (B6.Hdh(Q111) ) than on a 129 background (129.Hdh(Q111) ). Linkage mapping in (B6x129).Hdh(Q111) F2 intercross animals identified a single quantitative trait locus underlying the strain-specific difference in expansion in the striatum, implicating mismatch repair (MMR) gene Mlh1 as the most likely candidate modifier. Crossing B6.Hdh(Q111) mice onto an Mlh1 null background demonstrated that Mlh1 is essential for somatic CAG expansions and that it is an enhancer of nuclear huntingtin accumulation in striatal neurons. Hdh(Q111) somatic expansion was also abolished in mice deficient in the Mlh3 gene, implicating MutLγ (MLH1-MLH3) complex as a key driver of somatic expansion. Strikingly, Mlh1 and Mlh3 genes encoding MMR effector proteins were as critical to somatic expansion as Msh2 and Msh3 genes encoding DNA mismatch recognition complex MutSβ (MSH2-MSH3). The Mlh1 locus is highly polymorphic between B6 and 129 strains. While we were unable to detect any difference in base-base mismatch or short slipped-repeat repair activity between B6 and 129 MLH1 variants, repair efficiency was MLH1 dose-dependent. MLH1 mRNA and protein levels were significantly decreased in 129 mice compared to B6 mice, consistent with a dose-sensitive MLH1-dependent DNA repair mechanism underlying the somatic expansion difference between these strains. Together, these data identify Mlh1 and Mlh3 as novel critical genetic modifiers of HTT CAG instability, point to Mlh1 genetic variation as the likely source of the instability difference in B6 and 129 strains and suggest that MLH1

  2. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Dhollander, A.A.M., E-mail: Aad.Dhollander@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Huysse, W.C.J., E-mail: Wouter.Huysse@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, P.C.M., E-mail: pverdonk@yahoo.co [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verstraete, K.L., E-mail: Koenraad.Verstraete@Ugent.b [Department of Radiology, Ghent University Hospital, De Pintelaan 185, -1K12 IB, B9000 Gent (Belgium); Verdonk, R., E-mail: Rene.Verdonk@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium); Verbruggen, G., E-mail: Gust.Verbruggen@Ugent.b [Laboratory of Connective Tissue Biology, Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Almqvist, K.F., E-mail: Fredrik.Almqvist@Ugent.b [Department of Orthopaedic Surgery and Traumatology, Ghent University Hospital, De Pintelaan 185, 1P5, B9000 Gent (Belgium)

    2010-07-15

    Aim: The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects of the knee. MRI was used for the morphological analysis of cartilage repair. The correlation between MRI findings and clinical outcome was also studied. Methods: A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of symptomatic chondral and osteochondral lesions in the knee. Twenty-one patients were prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9 and 12 months of follow-up. Of the 21 patients, 12 had consented to follow the postoperative MRI evaluation protocol. MRI data were analyzed based on the original MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) and modified MOCART scoring system. The correlation between the clinical outcome and MRI findings was evaluated. Results: A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 12 months of follow-up. One of the two MRI scoring systems that were used, showed a statistically significant deterioration of the repair tissue at 1 year of follow-up. Twelve months after the operation complete filling or hypertrophy was found in 41.6%. Bone-marrow edema and effusion were seen in 41.7% and 25% of the study patients, respectively. We did not find a consistent correlation between the MRI criteria and the clinical results. Discussion: The present study confirmed the primary role of MRI in the evaluation of cartilage repair. Two MOCART-based scoring systems were used in a longitudinal fashion and allowed a practical and morphological evaluation of the repair tissue. However, the correlation between clinical outcome and MRI findings was poor. Further

  3. Chromatin remodelling complex RSC promotes base excision repair in chromatin of Saccharomyces cerevisiae.

    Science.gov (United States)

    Czaja, Wioletta; Mao, Peng; Smerdon, Michael J

    2014-04-01

    The base excision repair (BER) pathway is a conserved DNA repair system required to maintain genomic integrity and prevent mutagenesis in all eukaryotic cells. Nevertheless, how BER operates in vivo (i.e. in the context of chromatin) is poorly understood. We have investigated the role of an essential ATP-dependent chromatin remodelling (ACR) complex RSC (Remodels the Structure of Chromatin) in BER of intact yeast cells. We show that depletion of STH1, the ATPase subunit of RSC, causes enhanced sensitivity to the DNA alkylating agent methyl methanesulfonate (MMS) and results in a substantial inhibition of BER, at the GAL1 locus and in the genome overall. Consistent with this observation, the DNA in chromatin is less accessible to micrococcal nuclease digestion in the absence of RSC. Quantitative PCR results indicate that repair deficiency in STH1 depleted cells is not due to changes in the expression of BER genes. Collectively, our data indicates the RSC complex promotes efficient BER in chromatin. These results provide, for the first time, a link between ATP-dependent chromatin remodelling and BER in living cells.

  4. Influence of surface preparation on fracture load of resin composite-based repairs

    Science.gov (United States)

    Mateos-Palacios, Rocío; Román-Rodríguez, Juan-Luis; Solá-Ruíz, María-Fernanda; Fons-Font, Antonio

    2015-01-01

    The purpose of the present study is to evaluate the fracture load of composite-based repairs to fractured zirconium oxide (Z) crowns and to ceramic-fused-to-metal (CM) crowns, comparing different mechanical surface preparation methods. A total of 75 crowns were repaired; samples then underwent dynamic loading and thermocycling. Final fracture load values for failure of the repaired crowns were measured and the type of fracture registered. Group I: CM: Surface preparation with a diamond bur + 9.5% Hydrofluoric Acid (HF) etching; Group II): CM: air-particle (Al2O3) + 9.5% HF; Group III: CM: Silica coating (SiO2); Group IV): Z: air-particle (Al2O3) + HF 9.5%; Group V) Z: Silica coating (SiO2). Of the three CM groups, Group I (CM-diamond bur) showed the highest mean failure value, with significant difference in comparison with Group III (CM-silica coating). For the zirconia groups, the highest value was obtained by Group V (silica coating). Key words:Crown, ceramic-fused-to-metal, zirconia, resin-composite, ceramic covering. PMID:25810848

  5. Influence of surface preparation on fracture load of resin composite-based repairs.

    Science.gov (United States)

    Agustín-Panadero, Rubén; Mateos-Palacios, Rocío; Román-Rodríguez, Juan-Luis; Solá-Ruíz, María-Fernanda; Fons-Font, Antonio

    2015-02-01

    The purpose of the present study is to evaluate the fracture load of composite-based repairs to fractured zirconium oxide (Z) crowns and to ceramic-fused-to-metal (CM) crowns, comparing different mechanical surface preparation methods. A total of 75 crowns were repaired; samples then underwent dynamic loading and thermocycling. Final fracture load values for failure of the repaired crowns were measured and the type of fracture registered. Group I: CM: Surface preparation with a diamond bur + 9.5% Hydrofluoric Acid (HF) etching; Group II): CM: air-particle (Al2O3) + 9.5% HF; Group III: CM: Silica coating (SiO2); Group IV): Z: air-particle (Al2O3) + HF 9.5%; Group V) Z: Silica coating (SiO2). Of the three CM groups, Group I (CM-diamond bur) showed the highest mean failure value, with significant difference in comparison with Group III (CM-silica coating). For the zirconia groups, the highest value was obtained by Group V (silica coating). Key words:Crown, ceramic-fused-to-metal, zirconia, resin-composite, ceramic covering.

  6. Deoxyribonucleic acid repair gene X-ray repair cross-complementing group 1 polymorphisms and non-carcinogenic disease risk in different populations: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Bagher Larijani

    2013-01-01

    Full Text Available Purpose: This study aims to assess a meta-analysis of the association of X-ray repair cross-complementing group 1 (XRCC1 polymorphisms with the risk of various non-carcinogenic diseases in different population. Materials and Methods: This meta-analysis was performed by critically reviewing reveals 38 studies involving 10043 cases and 11037 controls. Among all the eligible studies, 14 focused on Arg194Trp polymorphism, 33 described the Arg399Gln and three articles investigated on Arg280His. Populations were divided into three different ethnic subgroups include Caucasians, Asians and other (Turkish and Iranian. Results: Pooled results showed no correlation between Arg194Trp and non-carcinogenic disease. There was only weak relation in the recessive (odds ratio [OR] =1.11, 95% confidence interval [CI]: 0.86-1.44 model in Asian population and dominant (OR = 1.04, 95% CI: 0.66-1.63 model of other populations. In Arg399Gln polymorphism, there was no relation with diseases of interest generally. In the pooled analysis, there were weak relation in the dominant (OR = 1.08, 95% CI: 0.86-1.35 model of Asian population and quite well-correlation with recessive (OR = 1.49, 95% CI: 1.19-1.88, dominant (OR = 1.23, 95% CI: 0.94-1.62, and additive (OR = 1.23, 95% CI: 0.94-1.62 models of other subgroup. For Arg280His, there was a weak relation only in the dominant model (OR = 1.06, 95% CI: 0.74-1.51. Conclusion: The present meta-analysis correspondingly shows that Arg399Gln variant to be associated with increased non-carcinogenic diseases risk through dominant and recessive modes among Iranian and Turkish population. It also suggests a trend of dominant and recessive effect of Arg280His variant in all population and its possible protective effect on non-carcinogenic diseases.

  7. DNA repair diseases: what do they tell us about cancer and aging?

    Directory of Open Access Journals (Sweden)

    Carlos FM Menck

    2014-01-01

    Full Text Available The discovery of DNA repair defects in human syndromes, initially in xeroderma pigmentosum (XP but later in many others, led to striking observations on the association of molecular defects and patients' clinical phenotypes. For example, patients with syndromes resulting from defective nucleotide excision repair (NER or translesion synthesis (TLS present high levels of skin cancer in areas exposed to sunlight. However, some defects in NER also lead to more severe symptoms, such as developmental and neurological impairment and signs of premature aging. Skin cancer in XP patients is clearly associated with increased mutagenesis and genomic instability, reflecting the defective repair of DNA lesions. By analogy, more severe symptoms observed in NER-defective patients have also been associated with defective repair, likely involving cell death after transcription blockage of damaged templates. Endogenously induced DNA lesions, particularly through oxidative stress, have been identified as responsible for these severe pathologies. However, this association is not that clear and alternative explanations have been proposed. Despite high levels of exposure to intense sunlight, patients from tropical countries receive little attention or care, which likely also reflects the lack of understanding of how DNA damage causes cancer and premature aging.

  8. Rehabilitation after Rotator Cuff Repair.

    Science.gov (United States)

    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.

  9. Base excision repair activities in organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation.

    Science.gov (United States)

    Rolseth, Veslemøy; Rundén-Pran, Elise; Neurauter, Christine Gran; Yndestad, Arne; Luna, Luisa; Aukrust, Pål; Ottersen, Ole Petter; Bjørås, Magnar

    2008-06-01

    The capacity for DNA repair is likely to be one of the factors that determine the vulnerability of neurons to ischemic stress and may influence the pathological outcome of stroke. In this report, initiation of base excision repair (BER) was assessed by analysis of enzyme activity and gene expression level of DNA glycosylases and AP-endonucleases in rat organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation (OGD) - an in vitro model of stroke. Under basal conditions, AP-endonuclease activity and base removal of ethenoadenine and 8-oxoguanine (8-oxoG) were higher (by approximately 20-35 %) in CA3/fascia dentata (FD) than in CA1. Base removal of uracil did not differ between the two hippocampal regions, while removal of 5-hydroxyuracil (5-OHU) was slightly less efficient in CA3/FD than in CA1. Analyses performed immediately after 30 min of OGD revealed a decreased AP-endonuclease activity (by approximately 20%) in CA1 as well as CA3/FD, and an increased ethenoadenine activity (by approximately 25%) in CA1. Activities for 8-oxoG, 5-OHU and uracil showed no significant changes at this time point. At 8h after OGD, none of the enzyme activities differed from control values. Real-time RT-PCR showed that transcription of DNA glycosylases, including Ogg1, Nth1, Ung, Aag, Neil1 and Neil2 were not changed in response to OGD treatment (t=0 h). The hippocampal expression of Neil2 was low compared with the other DNA glycosylases. These data indicate that CA1 has a lower capacity than CA3/FD for removal of base lesions under basal conditions. The relatively low capacity for BER in basal conditions and the apparent failure to upregulate repair of oxidative damage after OGD might contribute to the high vulnerability of CA1 to ischemic injury.

  10. Multi-Cultural Competency-Based Vocational Curricula. Auto Body Repair. Multi-Cultural Competency-Based Vocational/Technical Curricula Series.

    Science.gov (United States)

    Hepburn, Larry; Shin, Masako

    This document, one of eight in a multi-cultural competency-based vocational/technical curricula series, is on auto body repair. This program is designed to run 40 weeks and cover 7 instructional areas: use of basic repair tools; metal bumping (theory and practice); metal refinishing (theory and practice); panel replacement; glass work; spot…

  11. A Web-Based Rapid Prototyping Workflow Management Information System for Computer Repair and Maintenance

    Directory of Open Access Journals (Sweden)

    A. H. El-Mousa

    2008-01-01

    Full Text Available Problem statement: Response to paper-based requests for computer and peripheral repair and maintenance has become very troublesome and slow due to the large demand and expansion at the University of Jordan. The objectives of this study were to: (i investigate the current system processes associated with the paper-based workflow system. (ii design and implement, using a suitable workflow management approach, a totally electronic alterative to improve performance. Approach: The methodology followed in the transform of the business processes from the paper to the electronic-based was using the rapid prototyping workflow management approach. This approach is seen to be especially effective in such cases where there is direct continuous interaction and involvement between the different stakeholders during the lifecycle of the project. Results: The system had been implemented and tested with the result that efficiency, accountability and response time have greatly improved in handling repair and maintenance orders. The transform from paper to electronic resulted in greatly enhanced user satisfaction especially since the developed system provided automatic feedback regarding order status. Conclusion: The design process and results provide a working blueprint for easy and quick various similar university-based business processes to be transformed to electronic. This should highly motivate internal in-house restructuring of business process to utilize technology and IT to enhance performance and accountability.

  12. Investigation of Phosphate Cement-based Binder with Super High Early Strength for Repair of Concrete

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Magnesium phosphate cement-based binder (MPB) for repair of concrete was prepared by proportionally mixing over burned MgO powder (M) with NHH2PO4 powder (P) and set modifying admixtures. It is characteristic by excellent properties such as rapid setting,high strength and high bond strength to old concrete.. The study is focused on the key factors influencing the setting time and strength of MPB, the bond property of MPB to old concrete and the kinetic feature of the hydration of MPB.

  13. APE1, the DNA base excision repair protein, regulates the removal of platinum adducts in sensory neuronal cultures by NER

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Suk [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Guo, Chunlu; Thompson, Eric L. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Jiang, Yanlin [Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States); Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Department of Pediatrics and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indianapolis, IN 46202 (United States); Lee, Suk-Hee, E-mail: slee@iu.edu [Department of Biochemistry and Molecular Biology, Indianapolis, IN 46202 (United States)

    2015-09-15

    Peripheral neuropathy is one of the major side effects of treatment with the anticancer drug, cisplatin. One proposed mechanism for this neurotoxicity is the formation of platinum adducts in sensory neurons that could contribute to DNA damage. Although this damage is largely repaired by nuclear excision repair (NER), our previous findings suggest that augmenting the base excision repair pathway (BER) by overexpressing the repair protein APE1 protects sensory neurons from cisplatin-induced neurotoxicity. The question remains whether APE1 contributes to the ability of the NER pathway to repair platinum-damage in neuronal cells. To examine this, we manipulated APE1 expression in sensory neuronal cultures and measured Pt-removal after exposure to cisplatin. When neuronal cultures were treated with increasing concentrations of cisplatin for two or three hours, there was a concentration-dependent increase in Pt-damage that peaked at four hours and returned to near baseline levels after 24 h. In cultures where APE1 expression was reduced by ∼80% using siRNA directed at APE1, there was a significant inhibition of Pt-removal over eight hours which was reversed by overexpressing APE1 using a lentiviral construct for human wtAPE1. Overexpressing a mutant APE1 (C65 APE1), which only has DNA repair activity, but not its other significant redox-signaling function, mimicked the effects of wtAPE1. Overexpressing DNA repair activity mutant APE1 (226 + 177APE1), with only redox activity was ineffective suggesting it is the DNA repair function of APE1 and not its redox-signaling, that restores the Pt-damage removal. Together, these data provide the first evidence that a critical BER enzyme, APE1, helps regulate the NER pathway in the repair of cisplatin damage in sensory neurons.

  14. Rev1 is a base excision repair enzyme with 5′-deoxyribose phosphate lyase activity

    Science.gov (United States)

    Prasad, Rajendra; Poltoratsky, Vladimir; Hou, Esther W.; Wilson, Samuel H.

    2016-01-01

    Rev1 is a member of the Y-family of DNA polymerases and is known for its deoxycytidyl transferase activity that incorporates dCMP into DNA and its ability to function as a scaffold factor for other Y-family polymerases in translesion bypass events. Rev1 also is involved in mutagenic processes during somatic hypermutation of immunoglobulin genes. In light of the mutation pattern consistent with dCMP insertion observed earlier in mouse fibroblast cells treated with a base excision repair-inducing agent, we questioned whether Rev1 could also be involved in base excision repair (BER). Here, we uncovered a weak 5′-deoxyribose phosphate (5′-dRP) lyase activity in mouse Rev1 and demonstrated the enzyme can mediate BER in vitro. The full-length Rev1 protein and its catalytic core domain are similar in their ability to support BER in vitro. The dRP lyase activity in both of these proteins was confirmed by NaBH4 reduction of the Schiff base intermediate and kinetics studies. Limited proteolysis, mass spectrometry and deletion analysis localized the dRP lyase active site to the C-terminal segment of Rev1's catalytic core domain. These results suggest that Rev1 could serve as a backup polymerase in BER and could potentially contribute to AID-initiated antibody diversification through this activity. PMID:27683219

  15. [Molecular bases of prion diseases].

    Science.gov (United States)

    Pokrovskiĭ, V I; Kiselev, O I

    1998-01-01

    The paper briefly analyzes the origin of priones and their association with the cellular gene and homologous protein of diseases in man and animals. There is evidence for a direct relationship of the agents that cause spongious encephalitis in the cattle and a new type of Creutzfeldt-Jacob disease in man. The molecular organization of priones and the conformational cellular protein changes underlying the infectious activation of the cell homologue of priones. Emphasis is first laid on the capacity of the cell homologue of priones and their infectiously active derivative to bind to DNA or RNA. In the context of concepts of the priones yeasts an attempt was made to explain the reproduction through the altered control of translation of mRNA that encodes the cellular homologue of priones, which accounts for the duration of the incubation period of the disease. The infections caused by priones are referred to as the so-called slow infections. But in the context of the proposed hypothesis, an infective process in the tissues did not really have some typical signs of infection and resembles accumulation diseases more without the replicative burst typical of infectious processes. The paper gives data on the vital cycle of priones in infected animals and changes in the accumulation of an infective agent. This assesses the currently available diagnostic methods and gives preference to the methods which will be based on the use of monoclonal antibodies that specifically recognize the conformationally altered form of an infectious prione or on the identification of primary oligomeric forms which manifest the onset of amyloidization of the damaged tissues. The main conclusion of the paper is that protein prionization is a common biological phenomenon and the diseases caused by these processes will increase in number in the near future, which makes it necessary to develop diagnostic methods and universal treatments of diseases, such as bacterial infections by using antibiotics.

  16. Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair

    DEFF Research Database (Denmark)

    Akbari, Mansour; Keijzers, Guido; Maynard, Scott

    2014-01-01

    slower than the preceding mitochondrial BER steps. Overexpression of DNA ligase III in mitochondria improved the rate of overall BER, increased cell survival after menadione induced oxidative stress and reduced autophagy following the inhibition of the mitochondrial electron transport chain complex I...... by rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidative stress, and removal of dysfunctional......Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disrupt mitochondrial...

  17. Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors.

    Science.gov (United States)

    Goglia, Alexander G; Delsite, Robert; Luz, Antonio N; Shahbazian, David; Salem, Ahmed F; Sundaram, Ranjini K; Chiaravalli, Jeanne; Hendrikx, Petrus J; Wilshire, Jennifer A; Jasin, Maria; Kluger, Harriet M; Glickman, J Fraser; Powell, Simon N; Bindra, Ranjit S

    2015-02-01

    Most cancer therapies involve a component of treatment that inflicts DNA damage in tumor cells, such as double-strand breaks (DSBs), which are considered the most serious threat to genomic integrity. Complex systems have evolved to repair these lesions, and successful DSB repair is essential for tumor cell survival after exposure to ionizing radiation (IR) and other DNA-damaging agents. As such, inhibition of DNA repair is a potentially efficacious strategy for chemo- and radiosensitization. Homologous recombination (HR) and nonhomologous end-joining (NHEJ) represent the two major pathways by which DSBs are repaired in mammalian cells. Here, we report the design and execution of a high-throughput, cell-based small molecule screen for novel DSB repair inhibitors. We miniaturized our recently developed dual NHEJ and HR reporter system into a 384-well plate-based format and interrogated a diverse library of 20,000 compounds for molecules that selectively modulate NHEJ and HR repair in tumor cells. We identified a collection of novel hits that potently inhibit DSB repair, and we have validated their functional activity in a comprehensive panel of orthogonal secondary assays. A selection of these inhibitors was found to radiosensitize cancer cell lines in vitro, which suggests that they may be useful as novel chemo- and radio sensitizers. Surprisingly, we identified several FDA-approved drugs, including the calcium channel blocker mibefradil dihydrochloride, that demonstrated activity as DSB repair inhibitors and radiosensitizers. These findings suggest the possibility for repurposing them as tumor cell radiosensitizers in the future. Accordingly, we recently initiated a phase I clinical trial testing mibefradil as a glioma radiosensitizer.

  18. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Shikazono, Naoya, E-mail: shikazono.naoya@jaea.go.jp [Japan Atomic Energy Agency, Advanced Research Science Center, 2-4 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki 319-1195 (Japan); O' Neill, Peter [Gray Institute for Radiation Oncology and Biology, University of Oxford, Roosevelt Drive, Oxford OX3 7DQ (United Kingdom)

    2009-10-02

    Clustered DNA damage induced by a single radiation track is a unique feature of ionizing radiation. Using a plasmid-based assay in Escherichia coli, we previously found significantly higher mutation frequencies for bistranded clusters containing 7,8-dihydro-8-oxoguanine (8-oxoG) and 5,6-dihydrothymine (DHT) than for either a single 8-oxoG or a single DHT in wild type and in glycosylase-deficient strains of E. coli. This indicates that the removal of an 8-oxoG from a clustered damage site is most likely retarded compared to the removal of a single 8-oxoG. To gain further insights into the processing of bistranded base lesions, several potential repair intermediates following 8-oxoG removal were assessed. Clusters, such as DHT + apurinic/apyrimidinic (AP) and DHT + GAP have relatively low mutation frequencies, whereas clusters, such as AP + AP or GAP + AP, significantly reduce the number of transformed colonies, most probably through formation of a lethal double strand break (DSB). Bistranded AP sites placed 3' to each other with various interlesion distances also blocked replication. These results suggest that bistranded base lesions, i.e., single base lesions on each strand, but not clusters containing only AP sites and strand breaks, are repaired in a coordinated manner so that the formation of DSBs is avoided. We propose that, when either base lesion is initially excised from a bistranded base damage site, the remaining base lesion will only rarely be converted into an AP site or a single strand break in vivo.

  19. Corrosion considerations in the brazing repair of cobalt-based partial dentures.

    Science.gov (United States)

    Luthy, H; Marinello, C P; Reclaru, L; Scharer, P

    1996-05-01

    Cobalt-based alloys (Co-Cr-Mo) are usually used in dentistry as frameworks for removable partial dentures. In their basic form these structures function successfully. However, modifications or repairs of the frameworks may reduce their resistance to corrosion and, as a consequence, may provoke biologic reactions in the soft tissues. These reactions may be the result of different types of alloys that contact each other and, in the presence of saliva (based on potential differences), produce a galvanic cell. In this study, a clinical situation after repair of a removable partial denture was examined. The metallographic study of the prosthesis revealed a brazed zone where a gold braze was joining the Co-Cr-Mo framework with a Co-Cr-Ni type alloy (without Mo). The latter revealed signs of corrosion. Various electrochemical parameters (Ecorr, Ecouple, icorr, icouple) of these alloys were analyzed in the laboratory. The Co-Cr-Ni alloy had the lowest nobility and underwent galvanic corrosion in a galvanic couple with gold braze.

  20. Nationwide prevalence of groin hernia repair.

    Directory of Open Access Journals (Sweden)

    Jakob Burcharth

    Full Text Available INTRODUCTION: Groin hernia repair is a commonly performed surgical procedure in the western world but large-scaled epidemiologic data are sparse. Large-scale data on the occurrence of groin hernia repair may provide further understanding to the pathophysiology of groin hernia development. This study was undertaken to investigate the age and gender dependent prevalence of groin hernia repair. METHODS: In a nationwide register-based study, using data from the Civil Registration System covering all Danish citizens, we established a population-based cohort of all people living in Denmark on December 31(st, 2010. Within this population all groin hernia repairs during the past 5 years were identified using data from the ICD 10(th edition in the Danish National Hospital Register. RESULTS: The study population covered n = 5,639,885 persons. During the five years study period 46,717 groin hernia repairs were performed (88.6% males, 11.4% females. Inguinal hernias comprised 97% of groin hernia repairs (90.2% males, 9.8% females and femoral hernias 3% of groin hernia repairs (29.8% males, 70.2% females. Patients between 0-5 years and 75-80 years constituted the two dominant groups for inguinal hernia repair. In contrast, the age-specific prevalence of femoral hernia repair increased steadily throughout life peaking at age 80-90 years in both men and women. CONCLUSION: The age distribution of inguinal hernia repair is bimodal peaking at early childhood and old age, whereas the prevalence of femoral hernia repair increased steadily throughout life. This information can be used to formulate new hypotheses regarding disease etiology with regard to age and gender specifications.

  1. Enhanced base excision repair capacity in carotid atherosclerosis may protect nuclear DNA but not mitochondrial DNA

    DEFF Research Database (Denmark)

    Skarpengland, Tonje; B. Dahl, Tuva; Skjelland, Mona

    2016-01-01

    Lesional and systemic oxidative stress has been implicated in the pathogenesis of atherosclerosis, potentially leading to accumulation of DNA base lesions within atherosclerotic plaques. Although base excision repair (BER) is a major pathway counteracting oxidative DNA damage, our knowledge on BER...... and accumulation of DNA base lesions in clinical atherosclerosis is scarce. Here, we evaluated the transcriptional profile of a wide spectrum of BER components as well as DNA damage accumulation in atherosclerotic and non-atherosclerotic arteries. BER gene expression levels were analyzed in 162 carotid plaques, 8...... genes in atherosclerosis may contribute to lesional nuclear DNA stability but appears insufficient to maintain mtDNA integrity, potentially influencing mitochondrial function in cells within the atherosclerotic lesion....

  2. DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

    2014-08-05

    Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

  3. Factors Influencing Adaptation and Performance at Physical Exercise in Complex Congenital Heart Diseases after Surgical Repair

    Directory of Open Access Journals (Sweden)

    P. P. Bassareo

    2014-01-01

    Full Text Available In the last thirty years, steady progress in the diagnostic tools and care of subjects affected by congenital heart diseases (CHD has resulted in a significant increase in their survival to adulthood, even for those affected by complex CHD. Based on these premises, a number of teenagers and adults affected by corrected (surgically or through interventional techniques CHD ask to be allowed to undertake sporting activities, both at a recreational and competitive level. The purpose of this review is to examine the mechanisms influencing the adaption at physical exercise of patients suffering from complex CHD. The conclusion is that even if there are some modest risks with exercise, they should be seen in perspective, and the life-long benefits of regular exercise on general health, mood, and well-being should be emphasized.

  4. Development of repair mechanism of FSX-414 based 1st stage nozzle of gas turbine

    Science.gov (United States)

    Rahman, Md. Tawfiqur

    2017-06-01

    This paper describes the failure mechanism and repair technology of 1st stage nozzle or vane of industrial gas turbine which is made of cobalt based super alloy FSX-414. 1st stage nozzles or vanes are important stationery components of gas turbine based power plant. Those are the parts of hot gas path components of gas turbine and their manufacturing process is casting. At present, it is widely accepted that gas turbine based combined cycle power plant is the most efficient and cost effective solution to generate electricity. One of the factors of high efficiency of this type of gas turbine is the increase of its turbine inlet temperature. As an effect of this factor and in conjunction with some other factors, the 1st stage nozzle of gas turbine operates under extremely high temperature and thermal stresses. As a result, the design lifetime of these components becomes limited. Furthermore, attention on nozzles or vanes is required in order to achieve their design lifetime. However, due to unfriendly operational condition and environmental effect, anytime failure can occur on these heat resistant alloy based components which may lead to severe damage of gas turbine. To mitigate these adverse effects, schedule maintenance is performed on a predetermined time interval of hot gas path components of gas turbine based power plant. This paper addresses common failures in gas turbine's 1st stage nozzles or vanes. Usually these are repaired by using ADH process but for several reasons ADH process is not used here. Hence the challenging task is performed using gas tungsten arc welding which is presented in this article systematically.

  5. Laser Engineered Net Shape (LENS) Technology for the Repair of Ni-Base Superalloy Turbine Components

    Science.gov (United States)

    Liu, Dejian; Lippold, John C.; Li, Jia; Rohklin, Stan R.; Vollbrecht, Justin; Grylls, Richard

    2014-09-01

    The capability of the laser engineered net shape (LENS) process was evaluated for the repair of casting defects and improperly machined holes in gas turbine engine components. Various repair geometries, including indentations, grooves, and through-holes, were used to simulate the actual repair of casting defects and holes in two materials: Alloy 718 and Waspaloy. The influence of LENS parameters, including laser energy density, laser scanning speed, and deposition pattern, on the repair of these defects and holes was studied. Laser surface remelting of the substrate prior to repair was used to remove machining defects and prevent heat-affected zone (HAZ) liquation cracking. Ultrasonic nondestructive evaluation techniques were used as a possible approach for detecting lack-of-fusion in repairs. Overall, Alloy 718 exhibited excellent repair weldability, with essentially no defects except for some minor porosity in repairs representative of deep through-holes and simulated large area casting defects. In contrast, cracking was initially observed during simulated repair of Waspaloy. Both solidification cracking and HAZ liquation cracking were observed in the repairs, especially under conditions of high heat input (high laser power and/or low scanning speed). For Waspaloy, the degree of cracking was significantly reduced and, in most cases, completely eliminated by the combination of low laser energy density and relatively high laser scanning speeds. It was found that through-hole repairs of Waspaloy made using a fine powder size exhibited excellent repair weldability and were crack-free relative to repairs using coarser powder. Simulated deep (7.4 mm) blind-hole repairs, representative of an actual Waspaloy combustor case, were successfully produced by the combination use of fine powder and relatively high laser scanning speeds.

  6. A quantitative model of human DNA base excision repair. I. Mechanistic insights.

    Science.gov (United States)

    Sokhansanj, Bahrad A; Rodrigue, Garry R; Fitch, J Patrick; Wilson, David M

    2002-04-15

    Base excision repair (BER) is a multistep process involving the sequential activity of several proteins that cope with spontaneous and environmentally induced mutagenic and cytotoxic DNA damage. Quantitative kinetic data on single proteins of BER have been used here to develop a mathematical model of the BER pathway. This model was then employed to evaluate mechanistic issues and to determine the sensitivity of pathway throughput to altered enzyme kinetics. Notably, the model predicts considerably less pathway throughput than observed in experimental in vitro assays. This finding, in combination with the effects of pathway cooperativity on model throughput, supports the hypothesis of cooperation during abasic site repair and between the apurinic/apyrimidinic (AP) endonuclease, Ape1, and the 8-oxoguanine DNA glycosylase, Ogg1. The quantitative model also predicts that for 8-oxoguanine and hydrolytic AP site damage, short-patch Polbeta-mediated BER dominates, with minimal switching to the long-patch subpathway. Sensitivity analysis of the model indicates that the Polbeta-catalyzed reactions have the most control over pathway throughput, although other BER reactions contribute to pathway efficiency as well. The studies within represent a first step in a developing effort to create a predictive model for BER cellular capacity.

  7. Nucleotide excision repair and recombination are engaged in repair of trans-4-hydroxy-2-nonenal adducts to DNA bases in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Beata Janowska, Marek Komisarski, Paulina Prorok, Beata Sokołowska, Jarosław Kuśmierek, Celina Janion, Barbara Tudek

    2009-01-01

    Full Text Available One of the major products of lipid peroxidation is trans-4-hydroxy-2-nonenal (HNE. HNE forms highly mutagenic and genotoxic adducts to all DNA bases. Using M13 phage lacZ system, we studied the mutagenesis and repair of HNE treated phage DNA in E. coli wild-type or uvrA, recA, and mutL mutants. These studies revealed that: (i nucleotide excision and recombination, but not mismatch repair, are engaged in repair of HNE adducts when present in phage DNA replicating in E. coli strains; (ii in the single uvrA mutant, phage survival was drastically decreased while mutation frequency increased, and recombination events constituted 48 % of all mutations; (iii in the single recA mutant, the survival and mutation frequency of HNE-modified M13 phage was slightly elevated in comparison to that in the wild-type bacteria. The majority of mutations in recA- strain were G:C → T:A transversions, occurring within the sequence which in recA+ strains underwent RecA-mediated recombination, and the entire sequence was deleted; (iv in the double uvrA recA mutant, phage survival was the same as in the wild-type although the mutation frequency was higher than in the wild-type and recA single mutant, but lower than in the single uvrA mutant. The majority of mutations found in the latter strain were base substitutions, with G:C → A:T transitions prevailing. These transitions could have resulted from high reactivity of HNE with G and C, and induction of SOS-independent mutations.

  8. Mucocele after transnasal endoscopic repair of traumatic anterior skull base fistula in children.

    Science.gov (United States)

    Verillaud, Benjamin; Genty, Erwan; Leboulanger, Nicolas; Zerah, Michel; Garabédian, Erea Noël; Roger, Gilles

    2011-09-01

    To report the long-term sinonasal complications after endoscopic repair of anterior skull base fractures in children. This study describes mucocele formation in 6 patients treated endoscopically for posttraumatic CSF fistulae. We aim to address possible etiologic factors, specific treatments and follow-up modalities. 12 children, mean age 5.8 years (3-10), treated endoscopically at our institution between 2004 and 2010 for an anterior cranial base fracture complicated by a CSF fistula. An iatrogenic mucocele was observed in 6 cases. A retrospective review of the files of these 6 patients was carried out demonstrating demographic characteristics, presenting signs/symptoms, site of skull base defect, repair technique, timing and onset of the mucoceles, their presentation and management. A systematic CT-scan and/or MRI was carried out at 3 months, 1 year and then annually. 3 patients presented after cranial trauma with persistent CSF nasal leak, and 4 with meningitis. Posttraumatic defects reached the posterior wall of the frontal sinus and the junction of ethmoid and frontal bone in 3 cases, and the cribriform plate in 3 cases. Endoscopic closure was performed in all cases, with the middle turbinate as an overlay patch. No recurrence of a CSF leak was observed. After a mean period of 16 months, a single iatrogenic mucocele was observed in 4 patients (radiological detection only), and multiple mucoceles in 2 patients. Surgical treatment was advocated in cases of proptosis, quick expansion of the mucocele leading to sinus bony wall remodelling or erosion (2 cases), and meningitis related to an erosion of the cribriform plate by the mucocele. Three mucoceles were successfully treated endoscopically, and 1 required an external approach. Mucocele incidence after endoscopic repair of skull base fractures in children is not insignificant (50% in our 12 patients series). Paediatric anatomical features, cranial trauma, and the transethmoidal approach may play a role in

  9. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Aderbal R T Silva

    Full Text Available Alzheimer's disease (AD is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles. Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX, DNA repair (p53, BRCA1, PTEN, and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1 through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA composed of three groups: I "clinical-pathological AD" (CP-AD--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C and clinical dementia (CDR ≥ 2, IQCODE>3.8; II "pathological AD" (P-AD--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C and without cognitive impairment (CDR 0, IQCODE<3.2; and III "normal aging" (N--subjects without neuropathological AD (Braak ≤ II and CERAD 0 or A and with normal cognitive function (CDR 0, IQCODE<3.2. Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.

  10. Ricinus communis-based biopolymer and epidermal growth factor regulations on bone defect repair: A rat tibia model

    Science.gov (United States)

    Mendoza-Barrera, C.; Meléndez-Lira, M.; Altuzar, V.; Tomás, S. A.

    2003-01-01

    We report the effect of the addition of an epidermal growth factor to a Ricinus communis-based biopolymer in the healing of a rat tibia model. Bone repair and osteointegration after a period of three weeks were evaluated employing photoacoustic spectroscopy and x-ray diffraction. A parallel study was performed at 1, 2, 3, 4, 5, 6, 7, and 8 weeks with energy dispersive x-ray spectroscopy. We conclude that the use of an epidermal growth factor (group EGF) in vivo accelerates the process of bony repair in comparison with other groups, and that the employment of the Ricinus communis-based biopolymer as a bone substitute decreases bone production.

  11. A new theoretical formula for fractionated radiotherapy based on a saturable cellular repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez-Reyes, A. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain)); Farrus, B. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain)); Biete, A. (Servicio de Radioterapia, Hospital Clinico y Provincial de Barcelona (Spain))

    1993-01-01

    Recently we have published a new model of survival cellular response to radiation based on the existence of a saturable cellular repair mechanism. In the present paper we extend the predictions of this model of calculating the change in total dose necessary to achieve an equal response in a tissue when the dose per fraction in a radiotherapy fractionation schedule is varied. The model provides a new explanation of the difference between late and early radiation reactions. Results obtained from the model for different tissues and standard fractionation schedules are approximately equal to those obtained by the L.Q. (linear-quadratic) model. The model is compatible with in vitro survival curves that are straight at high doses. (orig.).

  12. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    Science.gov (United States)

    Zhu, Kai; Lai, Hao; Guo, Changfa; Li, Jun; Wang, Yulin; Wang, Lingyan; Wang, Chunsheng

    2014-01-01

    Mesenchymal stem cell (MSC) transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2) silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine) (Arg-G4) nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. PMID:25429216

  13. Restoring the balance between disease and repair in multiple sclerosis: insights from mouse models

    OpenAIRE

    Robert H. Miller; Fyffe-Maricich, Sharyl L.

    2010-01-01

    Multiple sclerosis (MS) is considered an autoimmune-mediated demyelinating disease that targets the central nervous system (CNS). Despite considerable research efforts over multiple decades, our understanding of the basic biological processes that are targeted in the disease and the mechanisms of pathogenesis are poorly understood. Consequently, current therapies directed at controlling the progression of the disease are limited in their effectiveness. Historically, the primary focus of MS re...

  14. Straight line repair of unilateral cleft lip: new operative method based on 25 years experience.

    Science.gov (United States)

    Nakajima, T; Tamada, I; Miyamoto, J; Nagasao, T; Hikosaka, M

    2008-08-01

    The resultant scar in the primary repair of unilateral cleft lip should ideally be straight and the mirror image of the philtrum on the non-cleft side. In 1993, we reported a new operative technique for unilateral cleft lip, in which we designed a straight line for the incision on the white lip. In order to produce the nostril floor, we used the white lip tissue in the area between the alar base and alveolus at the cleft side as a flap. We also used a small triangular flap above the white skin roll to prevent Cupid's peak from being drawn up. Unlike the rotation-advancement method, our technique does not leave a transverse scar at the alar base. Instead, it leaves a scar only along the line coincident with the natural philtral ridge. However, during observations of our patients, we noticed that the small triangular flap designed to be 1.5mm tended to become a conspicuous angular scar as the patients grew older. In addition, drooping of Cupid's peak on the cleft side was often observed with this small triangular flap. To make it less conspicuous, we made some modifications to the small flap above the white skin roll. With this new technique, we designed a semi-circular flap (1.5 x 3mm) above the white skin roll, instead of the small triangular flap. The suture line of our refined procedure draws a gentle curve, which looks almost straight because of skin elasticity. Moreover, the semi-circular flap causes less drooping of the upper lip than the triangular flap. We believe that revising the shape of the small flap on the white skin roll greatly improves patients' appearance. In this report, we present our refined techniques of primary repair of unilateral cleft lip.

  15. Semantic Trouble Sources and Their Repair in Conversations Affected by Parkinson's Disease

    Science.gov (United States)

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background: It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these…

  16. Semantic Trouble Sources and Their Repair in Conversations Affected by Parkinson's Disease

    Science.gov (United States)

    Saldert, Charlotta; Ferm, Ulrika; Bloch, Steven

    2014-01-01

    Background: It is known that dysarthria arising from Parkinson's disease may affect intelligibility in conversational interaction. Research has also shown that Parkinson's disease may affect cognition and cause word-retrieval difficulties and pragmatic problems in the use of language. However, it is not known whether or how these…

  17. Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model

    Science.gov (United States)

    He, Aijuan; Liu, Lina; Luo, Xusong; Liu, Yu; Liu, Yi; Liu, Fangjun; Wang, Xiaoyun; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-01-01

    Functional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability of in vivo cartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed an in vitro cartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involved in vitro cartilage engineering, repair of osteochondral defects, and evaluation of in vivo repair efficacy. The results demonstrated that BMSC engineered cartilage in vitro (BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated that in vitro cartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs. PMID:28084417

  18. Comparative Study of Co-based Alloys in Repairing Low Cr-Mo steel Components by Laser Cladding

    Science.gov (United States)

    Díaz, E.; Amado, J. M.; Montero, J.; Tobar, M. J.; Yáñez, A.

    Refurbishment of damaged components is nowadays a useful solution to save maintenance costs. Laser cladding is one of the most advantageous solutions to fulfill this kind of repair. With the aim of reusing deteriorated steam circuit parts of thermal power stations, a laser cladding process has been developed. Different Co-based alloys of Stellite® and Tribaloy® families, which offer good resistance against impact, corrosion and erosive wear at high temperatures, were used as coating materials to improve the durability of this repair. A comparative study of morphology, structure and hardness of the deposited layers with optimized parameters has been carried out.

  19. A New Powerful Method for Site-Specific Transgene Stabilization Based on Chromosomal Double-Strand Break Repair

    Science.gov (United States)

    Kravchuk, Oksana; Savitsky, Mikhail

    2011-01-01

    Transgenic insects are a promising tool in sterile insect techniques and population replacement strategies. Such transgenic insects can be created using nonautonomous transposons, which cannot be transferred without a transposase source. In biocontrol procedures where large numbers of insects are released, there is increased risk of transgene remobilization caused by external transposase sources that can alter the characteristics of the transgenic organisms lead horizontal transgene transfer to other species. Here we describe a novel, effective method for transgene stabilization based on the introduction of directed double-strand breaks (DSB) into a genome-integrated sequence and their subsequent repair by the single-strand annealing (SSA) pathway. Due to the construct's organization, the repair pathway is predictable, such that all transposon and marker sequences can be deleted, while preserving integration of exogenous DNA in the genome. The exceptional conservation of DNA repair pathways makes this method suitable for a broad range of organisms. PMID:22022613

  20. A new powerful method for site-specific transgene stabilization based on chromosomal double-strand break repair.

    Directory of Open Access Journals (Sweden)

    Artem Tkachuk

    Full Text Available Transgenic insects are a promising tool in sterile insect techniques and population replacement strategies. Such transgenic insects can be created using nonautonomous transposons, which cannot be transferred without a transposase source. In biocontrol procedures where large numbers of insects are released, there is increased risk of transgene remobilization caused by external transposase sources that can alter the characteristics of the transgenic organisms lead horizontal transgene transfer to other species. Here we describe a novel, effective method for transgene stabilization based on the introduction of directed double-strand breaks (DSB into a genome-integrated sequence and their subsequent repair by the single-strand annealing (SSA pathway. Due to the construct's organization, the repair pathway is predictable, such that all transposon and marker sequences can be deleted, while preserving integration of exogenous DNA in the genome. The exceptional conservation of DNA repair pathways makes this method suitable for a broad range of organisms.

  1. An in vitro DNA double-strand break repair assay based on end-joining of defined duplex oligonucleotides.

    Science.gov (United States)

    Datta, Kamal; Purkayastha, Shubhadeep; Neumann, Ronald D; Winters, Thomas A

    2012-01-01

    DNA double-strand breaks (DSBs) are caused by endogenous cellular processes such as oxidative metabolism, or by exogenous events like exposure to ionizing radiation or other genotoxic agents. Repair of these DSBs is essential for the maintenance of cellular genomic integrity. In human cells, and cells of other higher eukaryotes, DSBs are primarily repaired by the nonhomologous end-joining (NHEJ) DSB repair pathway. Most in vitro assays that have been designed to measure NHEJ activity employ linear plasmid DNA as end-joining substrates, and such assays have made significant contributions to our understanding of the biochemical mechanisms of NHEJ. Here we describe an in vitro end-joining assay employing linear oligonucleotides that has distinct advantages over plasmid-based assays for the study of structure-function relationships between the proteins of the NHEJ pathway and synthetic DNA end-joining substrates possessing predetermined DSB configurations and chemistries.

  2. Tridimensional quantitative porosity characterization of three set calcium silicate-based repair cements for endodontic use.

    Science.gov (United States)

    De Souza, Erika Thuanne Gonçalves; Nunes Tameirão, Michele Dias; Roter, Juliana Marins; De Assis, Joaquim Teixeira; De Almeida Neves, Aline; De-Deus, Gustavo André

    2013-10-01

    The aim of the this study was to quantitatively evaluate in three-dimensional (3D), the porosity degree of three improved silicate-based endodontic repair cements (iRoot BP Plus®, Biodentine®, and Ceramicrete) compared to a gold-standard calcium silicate bioactive cement (Pro Root® MTA). From each tested cement, four samples were prepared by a single operator following the manufacturer's instructions in terms of proportion, time, and mixing method, using cylindrical plastic split-ring moulds. The moulds were lubricated and the mixed cements were inserted with the aid of a cement spatula. The samples were scanned using a compact micro-CT device (Skyscan 1174, Bruker micro-CT, Kontich, Belgium) and the projection images were reconstructed into cross-sectional slices (NRecon v.1.6.9, Bruker micro-CT). From the stack of images, 3D models were rendered and the porosity parameters of each tested material were obtained after threshold definition by comparison with standard porosity values of Biodentine®. No statistically significant differences in the porosity parameters among the different materials were seen. Regarding total porosity, iRoot BP Plus® showed a higher percentage of total porosity (9.58%), followed by Biodentine® (7.09%), Pro Root® MTA (6.63%), and Ceramicrete (5.91%). Regarding closed porosity, Biodentine® presented a slight increase in these numbers compared to the other sealers. No significant difference in porosity between iRoot BP Plus®, Biodentine®, and Ceramicrete were seen. In addition, no significant difference in porosity between the new calcium silicate-containing repair cements and the gold-standard MTA were found.

  3. A soft self-repairing for FBG sensor network in SHM system based on PSO-SVR model reconstruction

    Science.gov (United States)

    Zhang, Xiaoli; Wang, Peng; Liang, Dakai; Fan, Chunfeng; Li, Cailing

    2015-05-01

    Structural health monitoring (SHM) system takes advantage of an array of sensors to continuously monitor a structure and provide an early prediction such as the damage position and damage degree etc. Such a system requires monitoring the structure in any conditions including bad condition. Therefore, it must be robust and survivable, even has the self-repairing ability. In this study, a model reconstruction predicting algorithm based on particle swarm optimization-support vector regression (PSO-SVR) is proposed to achieve the self-repairing of the Fiber Bragg Grating (FBG) sensor network in SHM system. Furthermore, an eight-point FBG sensor SHM system is experimented in an aircraft wing box. For the damage loading position prediction on the aircraft wing box, six kinds of disabled modes are experimentally studied to verify the self-repairing ability of the FBG sensor network in the SHM system, and the predicting performance are compared with non-reconstruction based on PSO-SVR model. The research results indicate that the model reconstruction algorithm has more excellence than that of non-reconstruction model, if partial sensors are invalid in the FBG-based SHM system, the predicting performance of the model reconstruction algorithm is almost consistent with that no sensor is invalid in the SHM system. In this way, the self-repairing ability of the FBG sensor is achieved for the SHM system, such the reliability and survivability of the FBG-based SHM system is enhanced if partial FBG sensors are invalid.

  4. A community-based long-term follow up of women undergoing obstetric fistula repair in rural Ethiopia

    DEFF Research Database (Denmark)

    Nielsen, H S; Lindberg, L; Nygaard, U

    2009-01-01

    still suffering from fistula no change was seen (P = 0.1). Four women became pregnant following their surgery, among which there was one maternal death, three stillbirths and one re-occurrence of fistula. CONCLUSION: Community-based, long-term follow up after fistula repair succeeded in Western rural...

  5. Nanovector-based prolyl hydroxylase domain 2 silencing system enhances the efficiency of stem cell transplantation for infarcted myocardium repair

    Directory of Open Access Journals (Sweden)

    Zhu K

    2014-11-01

    Full Text Available Kai Zhu,1,2 Hao Lai,1,2 Changfa Guo,1,2 Jun Li,1,2 Yulin Wang,1,2 Lingyan Wang,3 Chunsheng Wang1,2 1Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Cardiovascular Disease, Shanghai, People’s Republic of China; 3Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Mesenchymal stem cell (MSC transplantation has attracted much attention in myocardial infarction therapy. One of the limitations is the poor survival of grafted cells in the ischemic microenvironment. Small interfering RNA-mediated prolyl hydroxylase domain protein 2 (PHD2 silencing in MSCs holds tremendous potential to enhance their survival and paracrine effect after transplantation. However, an efficient and biocompatible PHD2 silencing system for clinical application is lacking. Herein, we developed a novel PHD2 silencing system based on arginine-terminated generation 4 poly(amidoamine (Arg-G4 nanoparticles. The system exhibited effective and biocompatible small interfering RNA delivery and PHD2 silencing in MSCs in vitro. After genetically modified MSC transplantation in myocardial infarction models, MSC survival and paracrine function of IGF-1 were enhanced significantly in vivo. As a result, we observed decreased cardiomyocyte apoptosis, scar size, and interstitial fibrosis, and increased angiogenesis in the diseased myocardium, which ultimately attenuated ventricular remodeling and improved heart function. This work demonstrated that an Arg-G4 nanovector-based PHD2 silencing system could enhance the efficiency of MSC transplantation for infarcted myocardium repair. Keywords: nanoparticles, PHD2, siRNA delivery, mesenchymal stem cells, myocardial infarction

  6. Prediction of Combine Economic Life Based on Repair and Maintenance Costs Model

    Directory of Open Access Journals (Sweden)

    A Rohani

    2014-09-01

    Full Text Available Farm machinery managers often need to make complex economic decisions on machinery replacement. Repair and maintenance costs can have significant impacts on this economic decision. The farm manager must be able to predict farm machinery repair and maintenance costs. This study aimed to identify a regression model that can adequately represent the repair and maintenance costs in terms of machine age in cumulative hours of use. The regression model has the ability to predict the repair and maintenance costs for longer time periods. Therefore, it can be used for the estimation of the economic life. The study was conducted using field data collected from 11 John-Deer 955 combine harvesters used in several western provinces of Iran. It was found that power model has a better performance for the prediction of combine repair and maintenance costs. The results showed that the optimum replacement age of John-Deer 955 combine was 54300 cumulative hours.

  7. Influence of incorporation of ZrO2 nanoparticles on the repair strength of polymethyl methacrylate denture bases.

    Science.gov (United States)

    Gad, Mohammed M; Rahoma, Ahmed; Al-Thobity, Ahmad M; ArRejaie, Aws S

    Repeated fracture of the denture base is a common problem in prosthodontics, and it represents a nuisance and a time sink for the clinician. Therefore, the possibility of increasing repair strength using new reinforcement materials is of great interest to prosthodontists. This study aimed to evaluate the effects of incorporation of zirconia nanoparticles (nano-ZrO2) on the flexural strength and impact strength of repaired polymethyl methacrylate (PMMA) denture bases. One hundred eighty specimens of heat-polymerized acrylic resin were fabricated (90 for each test) and divided into three main groups: one control group (intact specimens) and two groups divided according to surface design (45° bevels and butt joints), in which specimens were prepared in pairs to create 2.5 mm gaps. Nano-ZrO2 was added to repair resin in 2.5 wt%, 5 wt%, and 7.5 wt% concentrations of acrylic powder. A three-point bending test was used to measure flexural strength, and a Charpy-type test was used to measure impact strength. Scanning electron microscopy was used to analyze the fracture surfaces and nano-ZrO2 distribution. The results were analyzed with a paired sample t-test and an unpaired t-test, with a P-value of ≤0.05 being significant. Incorporation of nano-ZrO2 into the repair resin significantly increased flexural strength (P<0.05). The highest value was found in the bevel group reinforced with 7.5% nano-ZrO2, whereas the lowest value was found in the butt group reinforced with 2.5% nano-ZrO2. The impact strength values of all repaired groups were significantly lower than those of the control group (P<0.05). Among repaired groups, the higher impact strength value was seen in the butt group reinforced with 2.5% nano-ZrO2. The bevel joint demonstrated mainly cohesive failure, whereas the butt joint demonstrated mainly adhesive failure. Incorporation of nano-ZrO2 into the repair resin improved the flexural strength of repaired denture bases, whereas it decreased impact strength

  8. Isolation of a small molecule inhibitor of DNA base excision repair.

    Science.gov (United States)

    Madhusudan, Srinivasan; Smart, Fiona; Shrimpton, Paul; Parsons, Jason L; Gardiner, Laurence; Houlbrook, Sue; Talbot, Denis C; Hammonds, Timothy; Freemont, Paul A; Sternberg, Michael J E; Dianov, Grigory L; Hickson, Ian D

    2005-01-01

    The base excision repair (BER) pathway is essential for the removal of DNA bases damaged by alkylation or oxidation. A key step in BER is the processing of an apurinic/apyrimidinic (AP) site intermediate by an AP endonuclease. The major AP endonuclease in human cells (APE1, also termed HAP1 and Ref-1) accounts for >95% of the total AP endonuclease activity, and is essential for the protection of cells against the toxic effects of several classes of DNA damaging agents. Moreover, APE1 overexpression has been linked to radio- and chemo-resistance in human tumors. Using a newly developed high-throughput screen, several chemical inhibitors of APE1 have been isolated. Amongst these, CRT0044876 was identified as a potent and selective APE1 inhibitor. CRT0044876 inhibits the AP endonuclease, 3'-phosphodiesterase and 3'-phosphatase activities of APE1 at low micromolar concentrations, and is a specific inhibitor of the exonuclease III family of enzymes to which APE1 belongs. At non-cytotoxic concentrations, CRT0044876 potentiates the cytotoxicity of several DNA base-targeting compounds. This enhancement of cytotoxicity is associated with an accumulation of unrepaired AP sites. In silico modeling studies suggest that CRT0044876 binds to the active site of APE1. These studies provide both a novel reagent for probing APE1 function in human cells, and a rational basis for the development of APE1-targeting drugs for antitumor therapy.

  9. Android Platform Based Smartphones for a Logistical Remote Association Repair Framework

    Directory of Open Access Journals (Sweden)

    Shao-Fan Lien

    2014-06-01

    Full Text Available The maintenance of large-scale systems is an important issue for logistics support planning. In this paper, we developed a Logistical Remote Association Repair Framework (LRARF to aid repairmen in keeping the system available. LRARF includes four subsystems: smart mobile phones, a Database Management System (DBMS, a Maintenance Support Center (MSC and wireless networks. The repairman uses smart mobile phones to capture QR-codes and the images of faulty circuit boards. The captured QR-codes and images are transmitted to the DBMS so the invalid modules can be recognized via the proposed algorithm. In this paper, the Linear Projective Transform (LPT is employed for fast QR-code calibration. Moreover, the ANFIS-based data mining system is used for module identification and searching automatically for the maintenance manual corresponding to the invalid modules. The inputs of the ANFIS-based data mining system are the QR-codes and image features; the output is the module ID. DBMS also transmits the maintenance manual back to the maintenance staff. If modules are not recognizable, the repairmen and center engineers can obtain the relevant information about the invalid modules through live video. The experimental results validate the applicability of the Android-based platform in the recognition of invalid modules. In addition, the live video can also be recorded synchronously on the MSC for later use.

  10. Android Platform Based Smartphones for a Logistical Remote Association Repair Framework

    Science.gov (United States)

    Lien, Shao-Fan; Wang, Chun-Chieh; Su, Juhng-Perng; Chen, Hong-Ming; Wu, Chein-Hsing

    2014-01-01

    The maintenance of large-scale systems is an important issue for logistics support planning. In this paper, we developed a Logistical Remote Association Repair Framework (LRARF) to aid repairmen in keeping the system available. LRARF includes four subsystems: smart mobile phones, a Database Management System (DBMS), a Maintenance Support Center (MSC) and wireless networks. The repairman uses smart mobile phones to capture QR-codes and the images of faulty circuit boards. The captured QR-codes and images are transmitted to the DBMS so the invalid modules can be recognized via the proposed algorithm. In this paper, the Linear Projective Transform (LPT) is employed for fast QR-code calibration. Moreover, the ANFIS-based data mining system is used for module identification and searching automatically for the maintenance manual corresponding to the invalid modules. The inputs of the ANFIS-based data mining system are the QR-codes and image features; the output is the module ID. DBMS also transmits the maintenance manual back to the maintenance staff. If modules are not recognizable, the repairmen and center engineers can obtain the relevant information about the invalid modules through live video. The experimental results validate the applicability of the Android-based platform in the recognition of invalid modules. In addition, the live video can also be recorded synchronously on the MSC for later use. PMID:24967603

  11. Guidelines for the Design and Conduct of Clinical Studies in Knee Articular Cartilage Repair: International Cartilage Repair Society Recommendations Based on Current Scientific Evidence and Standards of Clinical Care.

    Science.gov (United States)

    Mithoefer, Kai; Saris, Daniel B F; Farr, Jack; Kon, Elizaveta; Zaslav, Kenneth; Cole, Brian J; Ranstam, Jonas; Yao, Jian; Shive, Matthew; Levine, David; Dalemans, Wilfried; Brittberg, Mats

    2011-04-01

    To summarize current clinical research practice and develop methodological standards for objective scientific evaluation of knee cartilage repair procedures and products. A comprehensive literature review was performed of high-level original studies providing information relevant for the design of clinical studies on articular cartilage repair in the knee. Analysis of cartilage repair publications and synopses of ongoing trials were used to identify important criteria for the design, reporting, and interpretation of studies in this field. Current literature reflects the methodological limitations of the scientific evidence available for articular cartilage repair. However, clinical trial databases of ongoing trials document a trend suggesting improved study designs and clinical evaluation methodology. Based on the current scientific information and standards of clinical care, detailed methodological recommendations were developed for the statistical study design, patient recruitment, control group considerations, study endpoint definition, documentation of results, use of validated patient-reported outcome instruments, and inclusion and exclusion criteria for the design and conduct of scientifically sound cartilage repair study protocols. A consensus statement among the International Cartilage Repair Society (ICRS) and contributing authors experienced in clinical trial design and implementation was achieved. High-quality clinical research methodology is critical for the optimal evaluation of current and new cartilage repair technologies. In addition to generally applicable principles for orthopedic study design, specific criteria and considerations apply to cartilage repair studies. Systematic application of these criteria and considerations can facilitate study designs that are scientifically rigorous, ethical, practical, and appropriate for the question(s) being addressed in any given cartilage repair research project.

  12. An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Mirta M L Sousa

    Full Text Available Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs. Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ pathway of double-strand break (DSB repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel

  13. Presence of base excision repair enzymes in the wheat aleurone and their activation in cells undergoing programmed cell death.

    Science.gov (United States)

    Bissenbaev, Amangeldy K; Ishchenko, Alexander A; Taipakova, Sabira M; Saparbaev, Murat K

    2011-10-01

    Cereal aleurone cells are specialized endosperm cells that produce enzymes to hydrolyze the starchy endosperm during germination. Aleurone cells can undergo programmed cell death (PCD) when incubated in the presence of gibberellic acid (GA) in contrast to abscisic acid (ABA) which inhibits the process. The progression of PCD in aleurone layer cells of wheat grain is accompanied by an increase in deoxyribonuclease (DNase) activities and the internucleosomal degradation of nuclear DNA. Reactive oxygen species (ROS) are increased during PCD in the aleurone cells owing to the β-oxidation of triglycerides and inhibition of the antioxidant enzymes possibly leading to extensive oxidative damage to DNA. ROS generate mainly non-bulky DNA base lesions which are removed in the base excision repair (BER) pathway, initiated by the DNA glycosylases. At present, very little is known about oxidative DNA damage repair in cereals. Here, we study DNA repair in the cell-free extracts of wheat aleurone layer incubated or not with phytohormones. We show, for the first time, the presence of 8-oxoguanine-DNA and ethenoadenine-DNA glycosylase activities in wheat aleurone cells. Interestingly, the DNA glycosylase and AP endonuclease activities are strongly induced in the presence of GA. Based on these data we propose that GA in addition to activation of nuclear DNases also induces the DNA repair activities which remove oxidized DNA bases in the BER pathway. Potential roles of the wheat DNA glycosylases in GA-induced oligonucleosomal fragmentation of DNA and metabolic activation of aleurone layer cells via repair of transcribed regions are discussed.

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

    Science.gov (United States)

    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

  15. Endovascular repair for a huge vertebral artery pseudoaneurysm caused by Behcet's disease

    Institute of Scientific and Technical Information of China (English)

    DONG Zhi-hui; FU Wei-guo; GUO Da-qiao; XU Xin; CHEN Bin; JIANG Jun-hao; YANG Jue; SHI Zheng-yu; WANG Yu-qi

    2006-01-01

    @@ Behcet's disease (BD), a multisystem chronic autoimmune process of unknown etiology,usually leads to arterial impairment. Isolated case reports have described BD-related arterial dissections, pseudoaneurysms or aneurysms.1-4 Recently, we successfully treated a huge vertebral artery pseudoaneurysm (VAPA) in a patient with BD by stent-grafting with preservation of the affected vertebral artery.

  16. Multiple Repair Sequences in Everyday Conversations Involving People with Parkinson's Disease

    Science.gov (United States)

    Griffiths, Sarah; Barnes, Rebecca; Britten, Nicky; Wilkinson, Ray

    2015-01-01

    Background: Features of dysarthria associated with Parkinson's disease (PD), such as low volume, variable rate of speech and increased pauses, impact speaker intelligibility. Those affected report restricted interactional participation, although this area is under explored. Aims: To examine naturally occurring instances of problems with…

  17. Decreased DNA repair capacity in familial, but not in sporadic Alzheimer's disease

    NARCIS (Netherlands)

    M.E.T.I. Boerrigter; C.M. van Duijn (Cock); E. Mullaart; P. Eikelenboom (Piet); C.M.A. van der Togt; D.L. Knook; J. Vijg (Jan); A. Hofman (Albert)

    1991-01-01

    textabstractUsing the alkaline filter elution technique we determined the induction and disappearance of DNA single-strand breaks (SSB) in freshly isolated peripheral blood lymphocytes (PBL) from 43 Alzheimer's disease (AD) patients and 48 normal, healthy age- and sex-matched control subjects

  18. Simultaneous repair of pectus excavatum associated with congenital heart disease%漏斗胸合并先心病同期手术治疗14例

    Institute of Scientific and Technical Information of China (English)

    胡庆华; 龙隆; 罗万俊; 蒋海河; 张卫星; 陈胜喜

    2014-01-01

    Objective To summarize clinical experience and effects of simultaneous repair of pectus ex-cavatum associated with congenital heart disease. Methods From 2000 to 2012,we repaired pectus excava-tum and congenital heart defects simultaneously in 14 children ,aged from 3 years to 14 years old,10 male and 4 female,using 3 different surgical procedures.Surgical approaches,complications,postoperative effects and follow -up results were retrospectively analyzed. Results All operations went well,and there were no major complications except pleural effusion in one patient and delayed wound healing in another one.Patients were followed up 6 months to 5 years,and their clinical results were quite satisfactory. Conclusion Choosing ap-propriate surgical procedures based on patients'conditions and wishes as well as operator's experience,simulta-neous repair of pectus excavatum and heart defects can be done with minimal complications and satisfactory long-term results.%目的总结同期手术矫治漏斗胸合并先心病的临床经验和疗效。方法2000年至2012年我们采用3种不同术式同期手术矫治漏斗胸合并先心病患儿14例,其中男10例,女4例,年龄3~14岁。回顾性分析患儿手术方法、并发症、术后疗效及随访情况。结果14例患儿手术顺利,术后除1例胸腔积液和1例伤口延期愈合外,无其它并发症,随访6个月至5年,心内修补和漏斗胸矫治均疗效满意。结论根据患儿病情、意愿和术者经验选择合理的手术方式,同期矫治漏斗胸合并先心病,并发症少,远期疗效满意。

  19. Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity.

    Science.gov (United States)

    Cho, Seung-Ju; Kim, So-Yeon; Jeong, Ho-Chang; Cheong, Hyeonsik; Kim, Doseok; Park, Soon-Jung; Choi, Jong-Jin; Kim, Hyongbum; Chung, Hyung-Min; Moon, Sung-Hwan; Cha, Hyuk-Jin

    2015-12-01

    Stem-toxic small molecules have been developed to induce selective cell death of pluripotent stem cells (PSCs) to lower the risk of teratoma formation. However, despite their high efficacies, chemical-based approaches may carry unexpected toxicities on specific differentiated cell types. Herein, we took advantage of KillerRed (KR) as a suicide gene, to selectively induce phototoxicity using visible light via the production of reactive oxygen species. PSCs in an undifferentiated state that exclusively expressed KR (KR-PSCs) were eliminated by a single exposure to visible light. This highly selective cell death in KR-PSCs was exploited to successfully inhibit teratoma formation. In particular, endothelial cells from KR-mPSCs remained fully functional in vitro and sufficient to repair ischemic injury in vivo regardless of light exposure, suggesting that a genetic approach in which KR is expressed in a tightly controlled manner would be a viable strategy to inhibit teratoma formation for future safe PSC-based therapies.

  20. An HPLC-tandem mass spectrometry method for simultaneous detection of alkylated base excision repair products.

    Science.gov (United States)

    Mullins, Elwood A; Rubinson, Emily H; Pereira, Kevin N; Calcutt, M Wade; Christov, Plamen P; Eichman, Brandt F

    2013-11-01

    DNA glycosylases excise a broad spectrum of alkylated, oxidized, and deaminated nucleobases from DNA as the initial step in base excision repair. Substrate specificity and base excision activity are typically characterized by monitoring the release of modified nucleobases either from a genomic DNA substrate that has been treated with a modifying agent or from a synthetic oligonucleotide containing a defined lesion of interest. Detection of nucleobases from genomic DNA has traditionally involved HPLC separation and scintillation detection of radiolabeled nucleobases, which in the case of alkylation adducts can be laborious and costly. Here, we describe a mass spectrometry method to simultaneously detect and quantify multiple alkylpurine adducts released from genomic DNA that has been treated with N-methyl-N-nitrosourea (MNU). We illustrate the utility of this method by monitoring the excision of N3-methyladenine (3 mA) and N7-methylguanine (7 mG) by a panel of previously characterized prokaryotic and eukaryotic alkylpurine DNA glycosylases, enabling a comparison of substrate specificity and enzyme activity by various methods. Detailed protocols for these methods, along with preparation of genomic and oligonucleotide alkyl-DNA substrates, are also described.

  1. Repair of Ischemic Injury by Pluripotent Stem Cell Based Cell Therapy without Teratoma through Selective Photosensitivity

    Directory of Open Access Journals (Sweden)

    Seung-Ju Cho

    2015-12-01

    Full Text Available Stem-toxic small molecules have been developed to induce selective cell death of pluripotent stem cells (PSCs to lower the risk of teratoma formation. However, despite their high efficacies, chemical-based approaches may carry unexpected toxicities on specific differentiated cell types. Herein, we took advantage of KillerRed (KR as a suicide gene, to selectively induce phototoxicity using visible light via the production of reactive oxygen species. PSCs in an undifferentiated state that exclusively expressed KR (KR-PSCs were eliminated by a single exposure to visible light. This highly selective cell death in KR-PSCs was exploited to successfully inhibit teratoma formation. In particular, endothelial cells from KR-mPSCs remained fully functional in vitro and sufficient to repair ischemic injury in vivo regardless of light exposure, suggesting that a genetic approach in which KR is expressed in a tightly controlled manner would be a viable strategy to inhibit teratoma formation for future safe PSC-based therapies.

  2. Effect of Mechanical Surface Treatment on the Repair Bond Strength of the Silorane-based Composite Resin

    Directory of Open Access Journals (Sweden)

    Parnian Alizadeh Oskoee

    2014-06-01

    Full Text Available Background and aims. A proper bond must be created between the existing composite resin and the new one for successful repair. The aim of this study was to compare the effect of three mechanical surface treatments, using diamond bur, air abrasion, and Er,Cr:YSGG laser, on the repair bond strength of the silorane-based composite resin. Materials and methods. Sixty cylindrical composite resin specimens (Filtek Silorane were fabricated and randomly divided into four groups according to surface treatment: group 1 (control group without any mechanical surface treatment, groups 24 were treated with air abrasion, Er,Cr:YSGG laser, and diamond bur, respectively. In addition, a positive control group was assigned in order to measure the cohesive strength. Silorane bonding agent was used in groups 14 before adding the new composite resin. Then, the specimens were subjected to a shear bond strength test and data was analyzed using one-way ANOVA and post hoc Tukey tests at a significance level of P < 0.05. The topographical effects of surface treatments were characterized under a scanning electron microscope. Results. There were statistically significant differences in the repair bond strength values between groups 1 and 2 and groups 3 and 4 (P < 0.001. There were no significant differences between groups 1 and 2 (P = 0.98 and groups 3 and 4 (P = 0.97. Conclusion. Surface treatment using Er,Cr:YSGG laser and diamond bur were effective in silorane-based composite resin repair.

  3. Early Incorporation of an Evidence-Based Aquatic-Assisted Approach to Arthroscopic Rotator Cuff Repair Rehabilitation: Prospective Case Study.

    Science.gov (United States)

    Burmaster, Chris; Eckenrode, Brian J; Stiebel, Matthew

    2016-01-01

    Both traditional and progressive rotator cuff repair rehabilitation protocols often delay active motion of the shoulder for 6 weeks or more. The early inclusion of a comprehensive aquatic-assisted exercise program presents a unique approach to postoperative management. The purpose of this case study is to describe a comprehensive evidence-based, aquatic-assisted rehabilitation program following arthroscopic rotator cuff repair. A 73-year-old woman with a nonretracted, medium-size, full-thickness tear (2.5 cm) of the supraspinatus tendon underwent arthroscopic rotator cuff repair and was referred for postoperative physical therapy. The rehabilitation program was initiated at 2 weeks postoperatively and consisted of concurrent land- and aquatic-based interventions over 6 weeks for a total of 18 physical therapy visits. Improvements were made in all 5 patient-reported outcome measures that were recorded weekly over the course of care. Improvements reached or exceeded minimal detectable change levels for the Shoulder Pain and Disability Index and the Penn Shoulder Score. Her numeric pain rating scale score at rest decreased from 4/10 at the initial evaluation to 2/10 at 8 weeks postoperatively and with activity decreased from 9/10 to 6/10. Shoulder strength and range of motion values also exhibited improvement over the course of care. No adverse events occurred during the case study. This case study illustrates the safe inclusion of low-stress aquatic exercises as an early adjunct to traditional land-based rotator cuff repair rehabilitation programs in small- to medium-size repairs. Further studies are needed to determine the long-term effectiveness of adding aquatic therapy to traditional postoperative programs. © 2016 American Physical Therapy Association.

  4. Long-term outcome in dogs after surgical repair of cranial cruciate ligament disease

    OpenAIRE

    MölsÀ, Sari

    2014-01-01

    Cranial cruciate ligament (CCL) disease is one of the most common causes of lameness in dogs. Surgical treatment is recommended to stabilize the stifle joint, alleviate pain, and delay the progression of osteoarthritis (OA). A variety of surgical techniques has been introduced and can be broken down into the more traditional intracapsular ligament replacement and extracapsular suture techniques and the newer neutralizing dynamic osteotomy techniques. Although an enormous amount of literature ...

  5. Formulation and Evaluation of Exotic Fat Based Cosmeceuticals for Skin Repair

    OpenAIRE

    Mandawgade S; Patravale Vandana

    2008-01-01

    Mango butter was explored as a functional, natural supplement and active skin ingredient in skin care formulations. A foot care cream was developed with mango butter to evaluate its medicinal value and protective function in skin repair. Qualitative comparison and clinical case studies of the product were carried out. Wound healing potential of foot care cream was investigated on the rat excision and incision wound models. Results of the clinical studies demonstrated complete repair of worn a...

  6. Tailored Approach in Inguinal Hernia Repair – Decision Tree Based on the Guidelines

    OpenAIRE

    2014-01-01

    The endoscopic procedures TEP and TAPP and the open techniques Lichtenstein, Plug and Patch, and PHS currently represent the gold standard in inguinal hernia repair recommended in the guidelines of the European Hernia Society, the International Endohernia Society, and the European Association of Endoscopic Surgery. Eighty-two percent of experienced hernia surgeons use the “tailored approach,” the differentiated use of the several inguinal hernia repair techniques depending on the findings of ...

  7. Tissue Engineering for Rotator Cuff Repair: An Evidence-Based Systematic Review

    Directory of Open Access Journals (Sweden)

    Nicola Maffulli

    2012-01-01

    Full Text Available The purpose of this systematic review was to address the treatment of rotator cuff tears by applying tissue engineering approaches to improve tendon healing, specifically platelet rich plasma (PRP augmentation, stem cells, and scaffolds. Our systematic search was performed using the combination of the following terms: “rotator cuff”, “shoulder”, “PRP”, “platelet rich plasma”, “stemcells”, “scaffold”, “growth factors”, and “tissue engineering”. No level I or II studies were found on the use of scaffolds and stem cells for rotator cuff repair. Three studies compared rotator cuff repair with or without PRP augmentation. All authors performed arthroscopic rotator cuff repair with different techniques of suture anchor fixation and different PRP augmentation. The three studies found no difference in clinical rating scales and functional outcomes between PRP and control groups. Only one study showed clinical statistically significant difference between the two groups at the 3-month followup. Any statistically significant difference in the rates of tendon rerupture between the control group and the PRP group was found using the magnetic resonance imaging. The current literature on tissue engineering application for rotator cuff repair is scanty. Comparative studies included in this review suggest that PRP augmented repair of a rotator cuff does not yield improved functional and clinical outcome compared with non-augmented repair at a medium and long-term followup.

  8. Cartilage repair surgery: outcome evaluation by using noninvasive cartilage biomarkers based on quantitative MRI techniques?

    Science.gov (United States)

    Jungmann, Pia M; Baum, Thomas; Bauer, Jan S; Karampinos, Dimitrios C; Erdle, Benjamin; Link, Thomas M; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J; Woertler, Klaus; Welsch, Goetz H

    2014-01-01

    New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

  9. Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

    Directory of Open Access Journals (Sweden)

    Pia M. Jungmann

    2014-01-01

    Full Text Available Background. New quantitative magnetic resonance imaging (MRI techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, and diffusion weighted imaging (DWI are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair.

  10. Metal inhibition of human alkylpurine-DNA-N-glycosylase activityin base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ping; Guliaev, Anton B.; Hang, Bo

    2006-02-28

    Cadmium (Cd{sup 2+}), nickel (Ni{sup 2+}) and cobalt (Co{sup 2+}) are human and/or animal carcinogens. Zinc (Zn{sup 2+}) is not categorized as a carcinogen, and rather an essential element to humans. Metals were recently shown to inhibit DNA repair proteins that use metals for their function and/or structure. Here we report that the divalent ions Cd{sup 2+}, Ni{sup 2+}, and Zn{sup 2+} can inhibit the activity of a recombinant human N-methylpurine-DNA glycosylase (MPG) toward a deoxyoligonucleotide with ethenoadenine (var epsilonA). MPG removes a variety of toxic/mutagenic alkylated bases and does not require metal for its catalytic activity or structural integrity. At concentrations starting from 50 to 1000 {micro}M, both Cd{sup 2+} and Zn{sup 2+} showed metal-dependent inhibition of the MPG catalytic activity. Ni{sup 2+} also inhibited MPG, but to a lesser extent. Such an effect can be reversed with EDTA addition. In contrast, Co{sup 2+} and Mg{sup 2+} did not inhibit the MPG activity in the same dose range. Experiments using HeLa cell-free extracts demonstrated similar patterns of inactivation of the var epsilonA excision activity by the same metals. Binding of MPG to the substrate was not significantly affected by Cd{sup 2+}, Zn{sup 2+}, and Ni{sup 2+} at concentrations that show strong inhibition of the catalytic function, suggesting that the reduced catalytic activity is not due to altered MPG binding affinity to the substrate. Molecular dynamics (MD) simulations with Zn{sup 2+} showed that the MPG active site has a potential binding site for Zn{sup 2+}, formed by several catalytically important and conserved residues. Metal binding to such a site is expected to interfere with the catalytic mechanism of this protein. These data suggest that inhibition of MPG activity may contribute to metal genotoxicity and depressed repair of alkylation damage by metals in vivo.

  11. Delayed recovery due to exaggerated acid, base and electrolyte imbalance in prolonged laparoscopic repair of diaphragmatic hernia

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2011-01-01

    Full Text Available The acid, base and electrolyte changes are usually observed in the perioperative settings. We report a case of prolonged laparoscopic repair of left-sided diaphragmatic hernia which involved a lot of tissue handling and fluid replacement leading to acid, base and electrolyte imbalance. A 42-year-old male underwent prolonged laparoscopic repair under general anesthesia. Intraoperatively, surgeon reported that contents of hernia includes bowel along with mesentery, spleen and lot of fatty tissue The blood loss was about 2 L which was replaced with 1 L of colloid and 7.5 L of lactated ringer. Near the end of surgery arterial blood gas analysis revealed metabolic acidosis, hyperkalemia, and hypocalcemia leading to delayed recovery. We conclude prolonged laparoscopic surgery involving lot of tissue handling including gut and fat should be monitored for acid, base, electrolyte imbalance and corrected timely to have uneventful rapid recovery.

  12. Tendon repair

    Science.gov (United States)

    Repair of tendon ... Tendon repair can be performed using: Local anesthesia (the immediate area of the surgery is pain-free) ... a cut on the skin over the injured tendon. The damaged or torn ends of the tendon ...

  13. Configuration model of partial repairable spares under batch ordering policy based on inventory state

    Institute of Scientific and Technical Information of China (English)

    Ruan Minzhi; Luo Yi; Li Hua

    2014-01-01

    Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost (LCC). With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the (s-1, s) and (R, Q) inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets:one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model’s correctness, method’s validity as well as optimization project’s rationality are proved to a certain extent.

  14. Configuration model of partial repairable spares under batch ordering policy based on inventory state

    Directory of Open Access Journals (Sweden)

    Ruan Minzhi

    2014-06-01

    Full Text Available Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost (LCC. With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and consumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the (s−1, s and (R, Q inventory policy, the spares resupply model is established under the batch ordering policy based on inventory state, and the optimization analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets: one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation; therefore, the model’s correctness, method’s validity as well as optimization project’s rationality are proved to a certain extent.

  15. Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair.

    Science.gov (United States)

    Akbari, Mansour; Keijzers, Guido; Maynard, Scott; Scheibye-Knudsen, Morten; Desler, Claus; Hickson, Ian D; Bohr, Vilhelm A

    2014-04-01

    Base excision repair (BER) is the most prominent DNA repair pathway in human mitochondria. BER also results in a temporary generation of AP-sites, single-strand breaks and nucleotide gaps. Thus, incomplete BER can result in the generation of DNA repair intermediates that can disrupt mitochondrial DNA replication and transcription and generate mutations. We carried out BER analysis in highly purified mitochondrial extracts from human cell lines U2OS and HeLa, and mouse brain using a circular DNA substrate containing a lesion at a specific position. We found that DNA ligation is significantly slower than the preceding mitochondrial BER steps. Overexpression of DNA ligase III in mitochondria improved the rate of overall BER, increased cell survival after menadione induced oxidative stress and reduced autophagy following the inhibition of the mitochondrial electron transport chain complex I by rotenone. Our results suggest that the amount of DNA ligase III in mitochondria may be critical for cell survival following prolonged oxidative stress, and demonstrate a functional link between mitochondrial DNA damage and repair, cell survival upon oxidative stress, and removal of dysfunctional mitochondria by autophagy.

  16. Detecting and Correcting Speech Repairs

    CERN Document Server

    Heeman, P A; Heeman, Peter; Allen, James

    1994-01-01

    Interactive spoken dialog provides many new challenges for spoken language systems. One of the most critical is the prevalence of speech repairs. This paper presents an algorithm that detects and corrects speech repairs based on finding the repair pattern. The repair pattern is built by finding word matches and word replacements, and identifying fragments and editing terms. Rather than using a set of prebuilt templates, we build the pattern on the fly. In a fair test, our method, when combined with a statistical model to filter possible repairs, was successful at detecting and correcting 80\\% of the repairs, without using prosodic information or a parser.

  17. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function.

    Science.gov (United States)

    Ontaneda, Daniel; Thompson, Alan J; Fox, Robert J; Cohen, Jeffrey A

    2016-11-23

    Multiple sclerosis is a major cause of neurological disability, which accrues predominantly during progressive forms of the disease. Although development of multifocal inflammatory lesions is the underlying pathological process in relapsing-remitting multiple sclerosis, the gradual accumulation of disability that characterises progressive multiple sclerosis seems to result more from diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti-inflammatory drugs that have regulatory approval for treatment of relapsing-remitting multiple sclerosis have little or no efficacy in progressive multiple sclerosis without inflammatory lesion activity. Effective therapies for progressive multiple sclerosis that prevent worsening, reverse damage, and restore function are a major unmet need. In this Series paper we summarise the current status of therapy for progressive multiple sclerosis and outline prospects for the future.

  18. DNA polymerases beta and lambda mediate overlapping and independent roles in base excision repair in mouse embryonic fibroblasts.

    Directory of Open Access Journals (Sweden)

    Elena K Braithwaite

    Full Text Available Base excision repair (BER is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol beta is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol lambda, was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol beta and pol lambda. Neutral red viability assays demonstrated that pol lambda and pol beta double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol lambda to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol lambda and pol beta interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.

  19. Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice

    DEFF Research Database (Denmark)

    Skarpengland, Tonje; Holm, Sverre; Scheffler, Katja

    2016-01-01

    an atherogenic lipid profile, increased hepatic triglyceride levels and attenuated macrophage cholesterol efflux capacity. Apoe-/- Neil3-/- mice showed marked alterations in several pathways affecting hepatic lipid metabolism, but no genotypic alterations in genome integrity or genome-wide accumulation...... of oxidative DNA damage. These results suggest a novel role for the DNA glycosylase Neil3 in atherogenesis in balancing lipid metabolism and macrophage function, potentially independently of genome-wide canonical base excision repair of oxidative DNA damage....

  20. Influence of incorporation of ZrO2 nanoparticles on the repair strength of polymethyl methacrylate denture bases

    Directory of Open Access Journals (Sweden)

    Gad MM

    2016-10-01

    Full Text Available Mohammed M Gad,1 Ahmed Rahoma,2,3 Ahmad M Al-Thobity,1 Aws S ArRejaie4 1Department of Substitutive Dental Sciences, 2Department of Restorative Dental Sciences, College of Dentistry, University of Dammam, Dammam, Saudi Arabia; 3Department of Dental Materials, College of Dentistry, Al-Azhar University, Assiut, Egypt; 4Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia Background: Repeated fracture of the denture base is a common problem in prosthodontics, and it represents a nuisance and a time sink for the clinician. Therefore, the possibility of increasing repair strength using new reinforcement materials is of great interest to prosthodontists.Aim of the study: This study aimed to evaluate the effects of incorporation of zirconia nanoparticles (nano-ZrO2 on the flexural strength and impact strength of repaired polymethyl methacrylate (PMMA denture bases.Materials and methods: One hundred eighty specimens of heat-polymerized acrylic resin were fabricated (90 for each test and divided into three main groups: one control group (intact specimens and two groups divided according to surface design (45° bevels and butt joints, in which specimens were prepared in pairs to create 2.5 mm gaps. Nano-ZrO2 was added to repair resin in 2.5 wt%, 5 wt%, and 7.5 wt% concentrations of acrylic powder. A three-point bending test was used to measure flexural strength, and a Charpy-type test was used to measure impact strength. Scanning electron microscopy was used to analyze the fracture surfaces and nano-ZrO2 distribution. The results were analyzed with a paired sample t-test and an unpaired t-test, with a P-value of ≤0.05 being significant.Results: Incorporation of nano-ZrO2 into the repair resin significantly increased flexural strength (P<0.05. The highest value was found in the bevel group reinforced with 7.5% nano-ZrO2, whereas the lowest value was found in the butt group reinforced with 2.5% nano

  1. Removal of uracil by uracil DNA glycosylase limits pemetrexed cytotoxicity: overriding the limit with methoxyamine to inhibit base excision repair

    Science.gov (United States)

    Bulgar, A D; Weeks, L D; Miao, Y; Yang, S; Xu, Y; Guo, C; Markowitz, S; Oleinick, N; Gerson, S L; Liu, L

    2012-01-01

    Uracil DNA glycosylase (UDG) specifically removes uracil bases from DNA, and its repair activity determines the sensitivity of the cell to anticancer agents that are capable of introducing uracil into DNA. In the present study, the participation of UDG in the response to pemetrexed-induced incorporation of uracil into DNA was studied using isogenic human tumor cell lines with or without UDG (UDG+/+/UDG−/−). UDG−/− cells were very sensitive to pemetrexed. Cell killing by pemetrexed was associated with genomic uracil accumulation, stalled DNA replication, and catastrophic DNA strand breaks. By contrast, UDG+/+ cells were >10 times more resistant to pemetrexed due to the rapid removal of uracil from DNA by UDG and subsequent repair of the resultant AP sites (abasic sites) via the base excision repair (BER). The resistance to pemetrexed in UDG+/+ cells could be reversed by the addition of methoxyamine (MX), which binds to AP sites and interrupts BER pathway. Furthermore, MX-bound AP sites induced cell death was related to their cytotoxic effect of dual inactivation of UDG and topoisomerase IIα, two genes that are highly expressed in lung cancer cells in comparison with normal cells. Thus, targeting BER-based therapy exhibits more selective cytotoxicity on cancer cells through a synthetic lethal mechanism. PMID:22237209

  2. Double-strand break repair based on short-homology regions is suppressed under terminal deoxynucleotidyltransferase expression, as revealed by a novel vector system for analysing DNA repair by nonhomologous end joining.

    Science.gov (United States)

    Maezawa, So; Nakano, Saori; Kuniya, Takaaki; Koiwai, Osamu; Koiwai, Kotaro

    2016-01-01

    We have constructed a novel, nonhomologous end-joining (NHEJ) assay vector (NAV), containing mKate2, Venus and ccdB genes. Cotransfection of NAV with a construct expressing the restriction enzyme I-SceI generated a double-strand break (DSB) in NAV that excised mKate2 and ccdB. Repair of this DSB produced an intact vector that expressed Venus, a green fluorescent protein. Because cells bearing the repaired NAV lacked the ccdB gene which slows cell proliferation, the cultures were enriched in cells containing repaired DSBs. DNA sequence analysis of the DSB junctions indicated that the repair was carried out mainly by using the closest homology sequence. Use of the NAV yielded rapid results within 3 days after transfection. We then used the NAV to analyse NHEJ in cells overexpressing terminal deoxynucleotidyltransferase (TdT). The results indicated that TdT suppresses DNA repair that is based on short (one- or two-base) homology regions, to efficiently add deoxynucleotides during VDJ recombination in lymphoid cells.

  3. Smoking, DNA Adducts and Number of Risk DNA Repair Alleles in Lung Cancer Cases, in Subjects with Benign Lung Diseases and in Controls

    Directory of Open Access Journals (Sweden)

    Marco Peluso

    2010-01-01

    Full Text Available Smoke constituents can induce DNA adducts that cause mutations and lead to lung cancer. We have analyzed DNA adducts and polymorphisms in two DNA repair genes, for example, XRCC1 Arg194Trp and Arg399Gln genes and XRCC3 Thr241Met gene, in 34 lung cancer cases in respect to 30 subjects with benign lung cancer disease and 40 healthy controls. When the study population was categorized in base to the number of risk alleles, adducts were significantly increased in individuals bearing 3-4 risk alleles (OR=4.1 95% C.I. 1.28–13.09, P=.009. A significant association with smoking was noticed in smokers for more than 40 years carrying 3-4 risk alleles (OR=36.38, 95% C.I. 1.17–1132.84, P=.040. A not statistically significant increment of lung cancer risk was observed in the same group (OR=4.54, 95% C.I. 0.33–62.93, P=.259. Our results suggest that the analysis of the number of risk alleles predicts the interindividual variation in DNA adducts of smokers and lung cancer cases.

  4. Prediction of Repair Work Duration for Gas Transport Systems Based on Small Data Samples

    DEFF Research Database (Denmark)

    Lesnykh, Valery; Litvin, Yuri; Kozin, Igor

    2016-01-01

    Prediction of the duration of a repair and maintenance project of a gas transport system is an important part of planning activities. There exist numerous sources of uncertainties that may result in time overruns possibly leading to multiple negative consequences. Our experience in planning...... this work suggests that accepting the stochastic nature of the project duration is a constructive step towards the preparedness to contingencies and defining penalties for repair companies. To support this approach, one needs to construct probability distributions of the durations of the projects...

  5. DiseaseConnect: a comprehensive web server for mechanism-based disease-disease connections.

    Science.gov (United States)

    Liu, Chun-Chi; Tseng, Yu-Ting; Li, Wenyuan; Wu, Chia-Yu; Mayzus, Ilya; Rzhetsky, Andrey; Sun, Fengzhu; Waterman, Michael; Chen, Jeremy J W; Chaudhary, Preet M; Loscalzo, Joseph; Crandall, Edward; Zhou, Xianghong Jasmine

    2014-07-01

    The DiseaseConnect (http://disease-connect.org) is a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. The traditional disease classification system groups diseases with similar clinical symptoms and phenotypic traits. Thus, diseases with entirely different pathologies could be grouped together, leading to a similar treatment design. Such problems could be avoided if diseases were classified based on their molecular mechanisms. Connecting diseases with similar pathological mechanisms could inspire novel strategies on the effective repositioning of existing drugs and therapies. Although there have been several studies attempting to generate disease connectivity networks, they have not yet utilized the enormous and rapidly growing public repositories of disease-related omics data and literature, two primary resources capable of providing insights into disease connections at an unprecedented level of detail. Our DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease-disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug-disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments.

  6. Potential of cardiac stem/progenitor cells and induced pluripotent stem cells for cardiac repair in ischaemic heart disease

    OpenAIRE

    Wang, Wei Eric; Chen, Xiongwen; Houser, Steven R.; Zeng, Chunyu

    2013-01-01

    Stem cell therapy has emerged as a promising strategy for cardiac and vascular repair. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. CS/PCs (cardiac stem/progenitor cells) are one type of adult stem cell with the potential to differentiate into cardiac lineages (cardiomyocytes, smooth muscle cells and endothelial cells). iPSCs (induced pluripotent stem cells) also ha...

  7. Repairs of composite structures

    Science.gov (United States)

    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

  8. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... Bladder exstrophy repair involves two surgeries. The first surgery is to repair the bladder and the second one is to attach ...

  9. Acetylation regulates WRN catalytic activities and affects base excision DNA repair

    DEFF Research Database (Denmark)

    Muftuoglu, Meltem; Kusumoto, Rika; Speina, Elzbieta

    2008-01-01

    The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone...

  10. Preferred mesh-based inguinal hernia repair in a teaching setting: results of a randomized study.

    NARCIS (Netherlands)

    Nienhuijs, S.W.; Kortmann, B.B.M.; Boerma, M.; Strobbe, L.J.; Rosman, C.

    2004-01-01

    HYPOTHESIS: Surgeons' preferences for any of 3 methods of inguinal hernia repair are comparable in terms of operating time, incision length, perceived difficulty, and surgeon's satisfaction. DESIGN: Randomized patient-blinded study. SETTING: Teaching hospital. PATIENTS: A total of 334 patients rando

  11. The mitochondrial transcription factor A functions in mitochondrial base excision repair

    DEFF Research Database (Denmark)

    Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V

    2010-01-01

    Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected i...

  12. Functional articular cartilage repair: here, near, or is the best approach not yet clear?

    NARCIS (Netherlands)

    Mastbergen, S.C.; Saris, D.B.F.; Lafeber, F.P.J.G.

    2013-01-01

    In this Review we describe three approaches for cartilage tissue repair at the rheumatology–orthopaedics interface: disease-modifying osteoarthritis (OA) drug (DMOAD) treatment; cell-based therapies, and intrinsic cartilage repair by joint distraction. DMOADs can slow the progression of joint damage

  13. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. In vitro tensile bond strength of denture repair acrylic resins to primed base metal alloys using two different processing techniques.

    Science.gov (United States)

    Banerjee, Sarmistha; Engelmeier, Robert L; O'Keefe, Kathy L; Powers, John M

    2009-12-01

    Approximately 38% of removable partial denture (RPD) failures involve fracture at the alloy/acrylic interface. Autopolymerizing resin is commonly used to repair RPDs. Poor chemical bonding of repair acrylic to base metal alloys can lead to microleakage and failure of the bond. Therefore, ideal repair techniques should provide a strong, adhesive bond. This investigation compared the tensile bond strength between cobalt-chromium (Super Cast, Pentron Laboratory Technologies, Llc., Wallingford, CT) and nickel-chromium (Rexalloy, Pentron Laboratory Technologies, Llc.) alloys and autopolymerized acrylic resin (Dentsply Repair Material, Dentsply Int, Inc, York, Pa) using three primers containing different functional monomers [UBar (UB), Sun Medical Co., Ltd., Shiga, Japan: Alloy Primer (AP) Kuraray Medical Inc., Okayama, Japan; and MR Bond (MRB) Tokyuyama Dental Corp., Tokyo, Japan] and two processing techniques (bench cure and pressure-pot cure). One hundred and twenty eight base metal alloy ingots were polished, air abraded, and ultrasonically cleaned. The control group was not primed. Specimens in the test groups were primed with one of the three metal primers. Autopolymerized acrylic resin material was bonded to the metal surfaces. Half the specimens were bench cured, and the other half were cured in a pressure pot. All specimens were stored in distilled water for 24 hours at 37 degrees C. The specimens were debonded under tension at a crosshead speed of 0.05 cm/min. The forces at which the bond failed were noted. Data were analyzed using ANOVA. Fisher's PLSD post hoc test was used to determine significant differences (p effect on bond strength of all specimens except Co-Cr alloy primed with UB. The highest bond strength was observed for both Co-Cr and Ni-Cr alloys that were sandblasted, primed with MRB, and pressure-pot cured. Co-Cr alloys primed with UB had the lowest bond strength whether bench cured or pressure-pot cured. Primed specimens generally experienced

  15. SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner

    Science.gov (United States)

    Xu, Zhu; Zhang, Lei; Zhang, Wenjun; Meng, Du; Zhang, Hongxia; Jiang, Ying; Xu, Xiaojun; Van Meter, Michael; Seluanov, Andrei; Gorbunova, Vera; Mao, Zhiyong

    2015-01-01

    In principle, a decline in base excision repair (BER) efficiency with age should lead to genomic instability and ultimately contribute to the onset of the aging phenotype. Although multiple studies have indicated a negative link between aging and BER, the change of BER efficiency with age in humans has not been systematically analyzed. Here, with foreskin fibroblasts isolated from 19 donors between 20 and 64 y of age, we report a significant decline of BER efficiency with age using a newly developed GFP reactivation assay. We further observed a very strong negative correlation between age and the expression levels of SIRT6, a factor which is known to maintain genomic integrity by improving DNA double strand break (DSB) repair. Our mechanistic study suggests that, similar to the regulatory role that SIRT6 plays in DNA DSB repair, SIRT6 regulates BER in a PARP1-depdendent manner. Moreover, overexpression of SIRT6 rescues the decline of BER in aged fibroblasts. In summary, our results uncovered the regulatory mechanisms of BER by SIRT6, suggesting that SIRT6 reactivation in aging tissues may help delay the process of aging through improving BER. PMID:25607651

  16. A Subcutaneous Alar Base (SCAB) flap to restore symmetry of the ala in primary cleft-lip nose repair.

    Science.gov (United States)

    Sherif, Mahmoud Magdi

    2014-12-01

    Primary surgical correction of cleft-lip nose deformity is now well accepted. Despite various surgical techniques proposed, perfect nasal symmetry has not been persistently attained. The main reason is that the maxillary deficiency is frequently overlooked.This paper presents 62 cases of unilateral cleft lip repaired over the last 20 years by using the author's modification of the Millard primary lip nose repair. Each of these patients had a minimum follow-up of 1 year (range 1-12 years).The technique consists of raising a small subcutaneous alar base flap (SCAB) from the nasolabial region. The flap is turned over like a book page to add bulk to the deficient maxilla and to elevate the depressed ala. It also controls alar rotation and permits its permanent fixation to the anterior nasal spine.The results show that this modification has improved the alar contour and symmetry in patients undergoing primary cleft-lip nasal repair. There was minimal increase in the operating time and the final scar is similar to the original Millard technique.

  17. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    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. Formulation and evaluation of exotic fat based cosmeceuticals for skin repair

    Directory of Open Access Journals (Sweden)

    Mandawgade S

    2008-01-01

    Full Text Available Mango butter was explored as a functional, natural supplement and active skin ingredient in skin care formulations. A foot care cream was developed with mango butter to evaluate its medicinal value and protective function in skin repair. Qualitative comparison and clinical case studies of the product were carried out. Wound healing potential of foot care cream was investigated on the rat excision and incision wound models. Results of the clinical studies demonstrated complete repair of worn and cracked skin in all the human volunteers. Furthermore, foot care cream exhibited significant healing response in both the wound models. The project work could be concluded as establishment of high potential for mango butter to yield excellent emolliency for better skin protection. Improving the product features and medicinal functionality further validate mango butter as a specialty excipient in development of cosmeceuticals and has an immense value for its commercialization.

  19. Prediction of Repair Work Duration for Gas Transport Systems Based on Small Data Samples

    DEFF Research Database (Denmark)

    Lesnykh, Valery; Litvin, Yuri; Kozin, Igor

    2016-01-01

    Prediction of the duration of a repair and maintenance project of a gas transport system is an important part of planning activities. There exist numerous sources of uncertainties that may result in time overruns possibly leading to multiple negative consequences. Our experience in planning...... this work suggests that accepting the stochastic nature of the project duration is a constructive step towards the preparedness to contingencies and defining penalties for repair companies. To support this approach, one needs to construct probability distributions of the durations of the projects...... of concurrently running subprojects. Following this, guidance is provided on how to decide about what duration should define the deadline for completion of the whole work. A simple example is provided....

  20. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    OpenAIRE

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng; Guo, Changfa; Wang, Chunsheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The inject...

  1. Recovery of spermatogenesis after microsurgical subinguinal varicocele repair in azoospermic men based on testicular histology

    Directory of Open Access Journals (Sweden)

    Sandro C. Esteves

    2005-12-01

    Full Text Available OBJECTIVE: Analyze whether testicular histologic patterns from a group of azoospermic men with varicocele is predictive of treatment outcome after subinguinal microsurgical varicocele repair. MATERIALS AND METHODS: Seventeen azoospermic men underwent bilateral open single testis biopsy and microsurgical subinguinal repair of clinical varicoceles. RESULTS: Histopathology of testicular biopsies revealed hypospermatogenesis (HYPO in 6 men, maturation arrest (MA in 5, and Sertoli cell-only (SCO in 6. Overall, presence of spermatozoa in the ejaculates was achieved in 47% (8/17 of men after varicocele repair, but only 35% (6/17 of them had motile sperm in their ejaculates. Only men with testicular histology revealing HYPO (5/6 or maturation arrest (3/5 had improvement after surgery. Median (25% - 75% percentile postoperative motile sperm count for both groups were 0.9 X 106/mL (0.1-1.8 X 106/mL and 0.7 X 106/mL (0.1-1.1, respectively (p = 0.87. The mean time for appearance of spermatozoa in the ejaculates was 5 months (3 to 9 months. One (HYPO of 8 (12.5% men who improved after surgery contributed to an unassisted pregnancy. Postoperative testicular biopsies obtained from patients who had no improvement after surgery revealed that testicular histology diagnosis remained unchanged. Successful testicular sperm retrieval for intracytoplasmic sperm injection (ICSI was achieved in 4 of 9 (44.4% individuals who did not improve after surgery, including 1 man with testicular histology exhibiting SCO. CONCLUSION: Microsurgical varicocele repair in nonobstructive azoospermic men with clinical varicoceles can result in sperm appearance in the ejaculate when hypospermatogenesis or maturation arrest is found on testicular histology diagnosis.

  2. Characterization of the Micro-Welding Process for Repair of Nickel Base Superalloys

    Science.gov (United States)

    Durocher, J.; Richards, N. L.

    2007-12-01

    Micro-welding is a low-heat input process whereby a metal or cermet, is deposited by the generation of a low-power arc between a consumable electrode and a substrate. The low-heat input of this process offers unique advantages over more common welding processes such as gas tungsten arc, plasma arc, laser, and electron beam welding. At present, the repair of turbine blades and vanes commonly involves gas tungsten arc welding and these components are susceptible to heat affected zone cracking during the weld repair process; vacuum brazing is also used but mainly on low-stress components such as stators. In this study, the low-heat input characteristic of micro-welding has been utilized to simulate repair of Inconel (Trade Mark of Special Metals) 625, Inconel 718, and Inconel 722 filler alloys to a cast Inconel 738 substrate. The effect of micro-welding process parameters on the deposition rate, coating quality, and substrate has been investigated.

  3. Evaluation of the Low Heat Input Process for Weld Repair of Nickel-Base Superalloys

    Science.gov (United States)

    Durocher, J.; Richards, N. L.

    2011-10-01

    The repair of turbine blades and vanes commonly involves gas tungsten arc welding or an equivalent process, but unfortunately these components are often susceptible to heat-affected zone (HAZ) cracking during the weld repair process. This is a major problem especially in cast alloys due to their coarse-grain size and where the (Al + Ti) contents is in excess of 3-4%; vacuum brazing is also used but mainly on low stress non-rotating components such as vanes. Micro-welding has the potential to deposit small amounts of filler at low heat input levels with minimum HAZ and thus is an attractive process for depositing a quality weld. As with conventional fusion processes, the filler alloy is deposited by the generation of a low power arc between a consumable electrode and the substrate. The low heat input of this process offers unique advantages over more common welding processes such as gas tungsten arc, plasma arc, laser, and electron beam welding. In this study, the low heat input characteristic of micro-welding has been used to simulate weld repair using Inconel (IN) (Inconel and IN are trademarks of INCO Alloys International) 625, Rene (Rene is a trademark of General Electric Company) 41, Nimonic (Nimonic is a trademark of INCO Alloys International) 105 and Inconel 738LC filler alloys, to a cast Inconel 738LC substrate. The effect of micro-welding process parameters on the deposition rate, coating quality, and substrate has been investigated.

  4. Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity.

    Directory of Open Access Journals (Sweden)

    Debra A Cockayne

    Full Text Available The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV(1, FEV(1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO grouped together to form a cluster associated with FEV(1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α formed another cluster associated with both DLCO and FEV(1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV(1/FVC were stronger in patients without metabolic syndrome (r  =  -0.52, p  =  0.005 and r  =  -0.61, p =  0.023, respectively compared to patients with coexisting metabolic syndrome (r  =  -0.25, p  =  0.47 and r  =  -0.15, p  =  0.96, respectively, and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV(1, FEV(1/FVC and DLCO. These data highlight systemic

  5. Use of a molecular beacon to track the activity of base excision repair protein OGG1 in live cells.

    Science.gov (United States)

    Mirbahai, Leda; Kershaw, Rachael M; Green, Richard M; Hayden, Rachel E; Meldrum, Rosalind A; Hodges, Nikolas J

    2010-02-01

    An abundant form of DNA damage caused by reactive oxygen species is 8-oxo-7,8-dihydroguanine for which the base excision repair protein 8-oxoguanine-DNA glycosylase 1 (OGG1) is a major repair enzyme. To assess the location and intracellular activity of the OGG1 protein in response to oxidative stress, we have utilised a fluorescence-quench molecular beacon switch containing a 8-oxo-dG:C base pair and a fluorescent and quencher molecule at opposite ends of a hairpin oligonucleotide. Oxidative stress was induced by treatment with potassium bromate. Flow cytometry demonstrated a concentration-dependent increase in the activity of OGG1 that was detected by the fluorescence produced when the oligonucleotide was cleaved in the cells treated with potassium bromate. This signal is highly specific and not detectable in OGG1 knock out cells. Induction of OGG1 activity is not a result of induction of OGG1 gene expression as assessed by qPCR suggesting a role for protein stabilisation or increased OGG1 catalytic activity. High resolution confocal microscopy pinpointed the location of the fluorescent molecular beacon in live cells to perinuclear regions that were identified as mitochondria by co-staining with mitotracker dye. There is no evidence of cut beacon within the nuclear compartment of the cell. Control experiments with a positive control beacon (G:C base pair and lacking the DAB quencher) did not result in mitochondrial localisation of fluorescence signal indicating that the dye does not accumulate in mitochondria independent of OGG1 activity. Furthermore, faint nuclear staining was apparent confirming that the beacon structure is able to enter the nucleus. In conclusion, these data indicate that the mitochondria are the major site for OGG1 repair activity under conditions of oxidative stress.

  6. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

    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

  7. 'Failure limited' data and TTT-based trend tests in multiple repairable systems

    Energy Technology Data Exchange (ETDEWEB)

    Caroni, C., E-mail: ccar@math.ntua.g [Department of Mathematics, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), 9 Iroon Polytechniou, Zografou 157 80, Athens (Greece)

    2010-06-15

    Tests for trend in multiple repairable systems based on the total time on test (introduced by Kvaloy and Lindqvist) are valid for data that end at a failure time only if data collection was planned to continue until a predetermined number of failures had occurred. They are not valid for a commoner form of data that end with the last of a random number of failures within a predetermined observation period. The necessary modification to the analysis is given here and appropriate terminology is suggested.

  8. Optimum repair-level analysis (ORLA) and life cycle cost (LCC) models for the base and installation security system (BISS)

    Energy Technology Data Exchange (ETDEWEB)

    York, A.A.; Chipchak, J.S.

    1979-03-01

    Models for Optimum Repair-Level Analysis (ORLA) and Life Cycle Cost (LCC) analysis for Base and Installation Security System (BISS) equipment are described. The ORLA model determines the costs of alternative maintenance approaches for selection of the most economic maintenance approach. The LCC model determines the total cost to the Government for the development, acquisition, initial logistics support, and recurring support of a system over the projected inventory usage period. A unique feature of these models is the marriage of ORLA and ICC which enables LCC to utilize completely the most economic ORLA decision costs. This significantly reduces the overall LCC effort.

  9. Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay--a methodological overview.

    Science.gov (United States)

    Azqueta, Amaya; Langie, Sabine A S; Slyskova, Jana; Collins, Andrew R

    2013-11-01

    There is an increasing demand for phenotyping assays in the field of human functional genetics. DNA repair activity is representative of this functional approach, being seen as a valuable biomarker related to cancer risk. Repair activity is evaluated by incubating a cell extract with a DNA substrate containing lesions specific for the DNA repair pathway of interest. Enzymic incision at the lesion sites can be measured by means of the comet assay (single cell gel electrophoresis). The assay is particularly applicable for evaluation of base and nucleotide excision repair pathways (BER and NER). Substrate DNA containing oxidised purines gives a measure of BER, while UV-induced photolesions are the substrate for NER. While applications of comet-based DNA repair assays continue to increase, there are no commonly accepted standard protocols, which complicates inter-laboratory comparisons of results. Here we provide a comprehensive summary of protocols for the comet-based BER- and NER-specific in vitro DNA repair assays that can be applied to a wide spectrum of biological material--cultured cell lines, blood cells, animal tissue samples and human biopsies. Our intention is to provide a detailed and user-friendly account of the assays, including practical tips and recommendations to help in setting them up. By proposing standard protocols, we hope to facilitate comparison of results obtained in different laboratories.

  10. Mice with DNA repair gene Ercc1 deficiency in a neural crest lineage are a model for late-onset Hirschsprung disease.

    Science.gov (United States)

    Selfridge, Jim; Song, Liang; Brownstein, David G; Melton, David W

    2010-06-04

    The Ercc1 gene is essential for nucleotide excision repair and is also important in recombination repair and the repair of interstrand crosslinks. We have previously used a floxed Ercc1 allele with a keratinocyte-specific Cre recombinase transgene to inactivate Ercc1 in the epidermal layer of the skin and so generate a mouse model for UV-induced non-melanoma skin cancer. Now, in an attempt to generate a model for UV-induced melanoma, we have used the floxed Ercc1 allele in combination with a Cre transgene under the control of the tyrosinase gene promoter to produce mice with Ercc1-deficient melanocytes that are hypersensitive to UV irradiation. These animals developed normally, but died when 4-6 months old with severe colonic obstruction. Melanocytes are derived from the neural crest and the tyrosinase promoter is also expressed in additional neural crest-derived lineages, including the progenitors of the parasympathetic nervous system that innervates the gastrointestinal tract and controls gut peristalsis. A functional enteric nervous system developed in floxed Ercc1 mice with the tyrosinase Cre transgene, but was found to have degenerated in the colons of affected mice. We suggest that accumulating unrepaired endogenous DNA damage in the Ercc1-deficient colonic parasympathetic ganglia leads to the degeneration of this network and results in a colonic obstructive disorder that resembles late-onset Hirschsprung disease in man.

  11. Grey Repairable System Analysis

    Institute of Scientific and Technical Information of China (English)

    Renkuan Guo; Charles Ernie Love

    2006-01-01

    In this paper, we systematically discuss the basic concepts of grey theory, particularly the grey differential equation and its mathematical foundation, which is essentially unknown in the reliability engineering community. Accordingly,we propose a small-sample based approach to estimate repair improvement effects by partitioning system stopping times into intrinsic functioning times and repair improvement times. An industrial data set is used for illustrative purposes in a stepwise manner.

  12. Blood-based biomarkers for Parkinson's disease.

    Science.gov (United States)

    Chahine, Lama M; Stern, Matthew B; Chen-Plotkin, Alice

    2014-01-01

    There is a pressing need for biomarkers to diagnose Parkinson's disease (PD), assess disease severity, and prognosticate course. Various types of biologic specimens are potential candidates for identifying biomarkers--defined here as surrogate indicators of physiological or pathophysiological states--but blood has the advantage of being minimally invasive to obtain. There are, however, several challenges to identifying biomarkers in blood. Several candidate biomarkers identified in other diseases or in other types of biological fluids are being pursued as blood-based biomarkers in PD. In addition, unbiased discovery is underway using techniques including metabolomics, proteomics, and gene expression profiling. In this review, we summarize these techniques and discuss the challenges and successes of blood-based biomarker discovery in PD. Blood-based biomarkers that are discussed include α-synuclein, DJ-1, uric acid, epidermal growth factor, apolipoprotein-A1, and peripheral inflammatory markers.

  13. Resolution of Chronic Aspiration Pneumonitis Following Endoscopic Endonasal Repair of Spontaneous Cerebrospinal Fluid Fistula of the Skull Base.

    Science.gov (United States)

    Seltzer, Justin; Babadjouni, Arash; Wrobel, Bozena B; Zada, Gabriel

    2016-06-01

    Spontaneous cerebrospinal fluid (CSF) rhinorrhea due to a skull base defect requires prompt diagnosis and treatment. Multiple surgical options are available for repairing the fistula, including the two-layer "fascial apposition" method and use of a pedicled nasal-septal flap. A 44-year-old obese woman presented with 4 months of progressive cough, exertional dyspnea, hoarseness, and intermittent fluid drainage from the right nostril. Chest computed tomography (CT) imaging and bronchoscopy showed chronic pneumonitis, which was confirmed by pulmonary wedge resection. CT and magnetic resonance imaging of the skull base, as well as laboratory analysis of the nasal fluid for β2-transferrin, confirmed a skull base defect causing CSF rhinorrhea. During surgery, insertion of a lumbar drain with the intrathecal fluorescein administration was performed, followed by endoscopic endonasal repair using an autologous fascial apposition graft and pedicled nasal-septal flap. Both the CSF leak and the pulmonary complications resolved following the operation with no symptoms at 11-month follow-up. This is the first reported case of spontaneous CSF rhinorrhea complicated by chronic aspiration and pneumonitis. Increased diagnostic complexity due to chronic pulmonary complications resulted in unnecessary interventions and treatment delays. Prompt recognition of spontaneous CSF leaks is essential to prevent potentially harmful complications.

  14. The Base Excision Repair system of Salmonella enterica serovar typhimurium counteracts DNA damage by host nitric oxide.

    Directory of Open Access Journals (Sweden)

    Anthony R Richardson

    2009-05-01

    Full Text Available Intracellular pathogens must withstand nitric oxide (NO. generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS and possesses multiple systems to detoxify NO.. Consequently, the level of NO. stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO. sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO. fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO.-dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO.. These observations demonstrate that host-derived NO. damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity.

  15. Monte Carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. I. Model properties and predicted trends

    Energy Technology Data Exchange (ETDEWEB)

    Semenenko, Vladimir; Stewart, Robert D.; Ackerman, Eric J.

    2005-12-31

    Single-cell irradiators and new experimental assays are rapidly expanding our ability to quantify the molecular mechanisms responsible for phenomena such as toxicant-induced adaptations in DNA repair and signal-mediated changes to the genome stability of cells not directly damaged by radiation (i.e., bystander cells). To advance our understanding of, and ability to predict and mitigate, the potentially harmful effects of radiological agents, effective strategies must be devised to incorporate information from molecular and cellular studies into mechanism-based, hierarchical models. A key advantage of the hierarchical modeling approach is that information from DNA repair and other in vitro assays can be systematically integrated into higher-level cell transformation and, eventually, carcinogenesis models. This presentation will outline the hierarchical modeling strategy used to integrate information from in vitro studies into the Virtual Cell (VC) radiobiology software (see Endnote). A new multi-path genomic instability model will be introduced and used to link biochemical processing of double strand breaks (DSBs) to neoplastic cell transformation. Bystander and directly damaged cells are treated explicitly in the model using a microdosimetric approach, although many of the details of the bystander response model are of a necessarily preliminary nature. The new model will be tested against several published radiobiological datasets. Results illustrating how hypothesized bystander mechanisms affect the shape of dose-response curves for neoplastic transformation as a function of Linear Energy Transfer (LET) will be presented. EndNote: R.D. Stewart, Virtual Cell (VC) Radiobiology Software. PNNL-13579, July 2001. Available at http://www.pnl.gov/berc/kbem/vc/ The DNA repair model used in the VC computer program is based on the Two-Lesion Kinetic (TLK) model [Radiat. Res. 156(4), 365-378 October 2001].

  16. Quantitative computer-based assessment of lip symmetry following cleft lip repair.

    Science.gov (United States)

    McKearney, Richard M; Williams, John V; Mercer, Nigel S

    2013-03-01

    Objective : To demonstrate an objective method of measuring lip symmetry after cleft lip repair by comparing patients with unilateral cleft lip (UCL) to non-cleft lip controls using the SymNose computer program. Design : Retrospective cohort study comparing several parameters of lip symmetry between UCL cases and controls. Participants were represented by digital photographs that were traced using SymNose. Setting : This study was performed at the South West Cleft Unit, Bristol, U.K. Participants : Forty-four participants aged 10 years (±1 year) were recruited into and completed the study. A consecutive case series of 22 patients with UCL ± palate had previously undergone primary repair. Twenty-two age-matched controls were recruited from a local primary school. Main Outcome Measures : Lip symmetry, expressed as the percentage mismatch of an overlaying of the left upper lip area and upper vermillion border area over the right, horizontal lip tilt, and lateral deviation of the lips. Results : A significant increase in labial asymmetry was seen in the UCL group in the following parameters: upper lip mismatch and upper vermillion border mismatch. No significant differences were observed in horizontal lip tilt or lateral lip deviation. Conclusion : This study supports the use of SymNose for the objective quantitative assessment of lip symmetry as an outcome measure of surgery following cleft lip repair. It allows comparison of surgical techniques and can be used to perform audits. It is a time-efficient process, relatively inexpensive, and straightforward to use.

  17. Accelerated rehabilitation following Achilles tendon repair after acute rupture - Development of an evidence-based treatment protocol.

    Science.gov (United States)

    Brumann, Mareen; Baumbach, Sebastian F; Mutschler, Wolf; Polzer, Hans

    2014-11-01

    The acute rupture of the Achilles tendon is a protracted injury. Surgery is only the beginning of a long rehabilitation period. Therefore, the rehabilitation protocol is an integral aspect to restore the pre-injury activity level. Despite several trials available comparing different treatment regimes, there is still no consensus regarding the optimal protocol. Consequently, the aim of our study was to systematically search the evidence available and define a precise rehabilitation programme after operative repair of acute Achilles tendon rupture based on the trials with the highest level of evidence. We performed a systematic literature search in Medline, Embase and Cochrane library. We identified twelve randomized controlled trials comparing different treatment regimes after operative repair of the Achilles tendon. Five trials compared full to non weight bearing, all applying immobilization in equinus. Immediate full weight bearing led to significant higher patient satisfaction, earlier ambulation and return to pre-injury activity. Four trials compared early ankle mobilization to immobilization. All trials found mobilization to be superior as it shortens time to return to work and sports significantly. Three trials compared the combination of full weight bearing and early ankle mobilization to immobilization. This combination was most beneficial. Patients showed significantly higher satisfaction, less use of rehabilitation resources, earlier return to pre-injury activities and further demonstrated significantly increased calf muscle strength, reduced atrophy and tendon elongation. No study found an increased rerupture rate for the more progressive treatment. In conclusion, the rehabilitation protocol after Achilles tendon repair should allow immediate full weight bearing. After the second postoperative week controlled ankle mobilization by free plantar flexion and limited dorsiflexion at 0° should be applied. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Mesenchymal stem cells delivered in a microsphere-based engineered skin contribute to cutaneous wound healing and sweat gland repair.

    Science.gov (United States)

    Huang, Sha; Lu, Gang; Wu, Yan; Jirigala, Enhe; Xu, Yongan; Ma, Kui; Fu, Xiaobing

    2012-04-01

    Bone-marrow-derived mesenchymal stem cells (BM-MSCs) can contribute to wound healing after skin injury. However, the role of BM-MSCs on repairing skin appendages in renewal tissues is incompletely explored. Moreover, most preclinical studies suggest that the therapeutic effects afforded by BM-MSCs transplantation are short-lived and relatively unstable. To assess whether engrafted bone-marrow-derived mesenchymal stem cells via a delivery system can participate in cutaneous wound healing and sweat-gland repair in mice. For safe and effective delivery of BM-MSCs to wounds, epidermal growth factor (EGF) microspheres were firstly developed to both support cells and maintain appropriate stimuli, then cell-seeded microspheres were incorporated with biomimetic scaffolds and thus fabricated an engineered skin construct with epithelial differentiation and proliferative potential. The applied efficacy was examined by implanting them into excisional wounds on both back and paws of hind legs in mice. After 3 weeks, BM-MSC-engineered skin (EGF loaded) treated wounds exhibited accelerated healing with increased re-epithelialization rates and less skin contraction. Furthermore, histological and immunofluorescence staining analysis revealed sweat glands-like structures became more apparent in BM-MSC-engineered skin (EGF loaded) treated wounds but the number of implanted BM-MSCs were decreased gradually in later phases of healing progression. Our study suggests that BM-MSCs delivered by this EGF microspheres-based engineered skin model may be a promising strategy to repair sweat glands and improve cutaneous wound healing after injury and success in this study might provide a potential benefit for BM-MSCs administration clinically. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Hypospadias repair

    Science.gov (United States)

    ... the problem. If the repair is not done, problems may occur later on such as: Difficulty controlling and directing urine stream A curve in the penis during erection Decreased fertility Embarrassment about appearance of penis Surgery ...

  20. Risk based surveillance for vector borne diseases

    DEFF Research Database (Denmark)

    Bødker, Rene

    of samples and hence early detection of outbreaks. Models for vector borne diseases in Denmark have demonstrated dramatic variation in outbreak risk during the season and between years. The Danish VetMap project aims to make these risk based surveillance estimates available on the veterinarians smart phones...

  1. Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Lavínia Almeida Cruz

    2012-01-01

    Full Text Available Eukaryotic cells have developed mechanisms to prevent genomic instability, such as DNA damage detection and repair, control of cell cycle progression and cell death induction. The bifunctional compound furocumarin 8-methoxy-psoralen (8-MOP is widely used in the treatment of various inflammatory skin diseases. In this review, we summarize recent data about the role of chromatin remodeling in the repair of DNA damage induced by treatment with 8-methoxypsoralen plus UVA (8-MOP+UVA, focusing on repair proteins in budding yeast Saccharomyces cerevisiae, an established model system for studying DNA repair pathways. The interstrand crosslinks (ICL formed by the 8-MOP+UVA treatment are detrimental lesions that can block transcription and replication, leading to cell death if not repaired. Current data show the involvement of different pathways in ICL processing, such as nucleotide excision repair (NER, base excision repair (BER, translesion repair (TLS and double-strand break repair. 8-MOP+UVA treatment in yeast enhances the expression of genes involved in the DNA damage response, double strand break repair by homologous replication, as well as genes related to cell cycle regulation. Moreover, alterations in the expression of subtelomeric genes and genes related to chromatin remodeling are consistent with structural modifications of chromatin relevant to DNA repair. Taken together, these findings indicate a specific profile in 8-MOP+UVA responses related to chromatin remodeling and DNA repair.

  2. Genetic variants involved in oxidative stress, base excision repair, DNA methylation, and folate metabolism pathways influence myeloid neoplasias susceptibility and prognosis.

    Science.gov (United States)

    Gonçalves, Ana Cristina; Alves, Raquel; Baldeiras, Inês; Cortesão, Emília; Carda, José Pedro; Branco, Claudia C; Oliveiros, Bárbara; Loureiro, Luísa; Pereira, Amélia; Nascimento Costa, José Manuel; Sarmento-Ribeiro, Ana Bela; Mota-Vieira, Luisa

    2017-01-01

    Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) share common features: elevated oxidative stress, DNA repair deficiency, and aberrant DNA methylation. We performed a hospital-based case-control study to evaluate the association in variants of genes involved in oxidative stress, folate metabolism, DNA repair, and DNA methylation with susceptibility and prognosis of these malignancies. To that end, 16 SNPs (one per gene: CAT, CYBA, DNMT1, DNMT3A, DNMT3B, GPX1, KEAP1, MPO, MTRR, NEIL1, NFE2F2, OGG1, SLC19A1, SOD1, SOD2, and XRCC1) were genotyped in 191 patients (101 MDS and 90 AML) and 261 controls. We also measured oxidative stress (reactive oxygen species/total antioxidant status ratio), DNA damage (8-hydroxy-2'-deoxyguanosine), and DNA methylation (5-methylcytosine) in 50 subjects (40 MDS and 10 controls). Results showed that five genes (GPX1, NEIL1, NFE2L2, OGG1, and SOD2) were associated with MDS, two (DNMT3B and SLC19A1) with AML, and two (CYBA and DNMT1) with both diseases. We observed a correlation of CYBA TT, GPX1 TT, and SOD2 CC genotypes with increased oxidative stress levels, as well as NEIL1 TT and OGG1 GG genotypes with higher DNA damage. The 5-methylcytosine levels were negatively associated with DNMT1 CC, DNMT3A CC, and MTRR AA genotypes, and positively with DNMT3B CC genotype. Furthermore, DNMT3A, MTRR, NEIL1, and OGG1 variants modulated AML transformation in MDS patients. Additionally, DNMT3A, OGG1, GPX1, and KEAP1 variants influenced survival of MDS and AML patients. Altogether, data suggest that genetic variability influence predisposition and prognosis of MDS and AML patients, as well AML transformation rate in MDS patients. © 2016 Wiley Periodicals, Inc.

  3. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation.

    Science.gov (United States)

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng; Guo, Changfa; Wang, Chunsheng

    2015-05-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation.

  4. Enhanced infarct myocardium repair mediated by thermosensitive copolymer hydrogel-based stem cell transplantation

    Science.gov (United States)

    Xia, Yu; Zhu, Kai; Lai, Hao; Lang, Meidong; Xiao, Yan; Lian, Sheng

    2015-01-01

    Mesenchymal stem cell (MSC) transplantation by intramyocardial injection has been proposed as a promising therapy strategy for cardiac repair after myocardium infarction. However, low retention and survival of grafted MSCs hinder its further application. In this study, copolymer with N-isopropylacrylamide/acrylic acid/2-hydroxylethyl methacrylate-poly(ɛ-caprolactone) ratio of 88:9.6:2.4 was bioconjugated with type I collagen to construct a novel injectable thermosensitive hydrogel. The injectable and biocompatible hydrogel-mediated MSC transplantation could enhance the grafted cell survival in the myocardium, which contributed to the increased neovascularization, decreased interstitial fibrosis, and ultimately improved heart function to a significantly greater degree than regular MSC transplantation. We suggest that this novel hydrogel has the potential for future stem cell transplantation. PMID:25432986

  5. On the effectiveness of recoding-based repair in network coded distributed storage

    DEFF Research Database (Denmark)

    Sipos, Marton A.; Braun, Patrik J.; Roetter, Daniel Enrique Lucani

    2017-01-01

    recovery node gets connected to a given subset of the operating nodes and receives a part of the stored data. The objective of this paper is to investigate data survival for Random Linear Network Coding (RLNC) as a function of topology and communication overhead, dened by the number of connections...... and the number of transmitted packets to the recovery node, respectively. The paper includes two main contributions. First, a sufficient set of conditions for quasi-infinite longevity of the stored data is derived. Second, a comparison using experimental results shows that RLNC can be up to 50% more effective......High capacity storage systems distribute less across several storage devices (nodes) and apply an erasure code to meet availability and reliability requirements. Since devices can lose network connectivity or fail permanently, a dynamic repair mechanism must be put in place. In such cases a new...

  6. A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats.

    Science.gov (United States)

    Pei, Ming; Li, Jingting; McConda, David B; Wen, Sijin; Clovis, Nina B; Danley, Suzanne S

    2015-09-01

    Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly(lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici's collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats.

  7. Repairing the sickle cell mutation. I. Specific covalent binding of a photoreactive third strand to the mutated base pair.

    Science.gov (United States)

    Broitman, S; Amosova, O; Dolinnaya, N G; Fresco, J R

    1999-07-30

    A DNA third strand with a 3'-psoralen substituent was designed to form a triplex with the sequence downstream of the T.A mutant base pair of the human sickle cell beta-globin gene. Triplex-mediated psoralen modification of the mutant T residue was sought as an approach to gene repair. The 24-nucleotide purine-rich target sequence switches from one strand to the other and has four pyrimidine interruptions. Therefore, a third strand sequence favorable to two triplex motifs was used, one parallel and the other antiparallel to it. To cope with the pyrimidine interruptions, which weaken third strand binding, 5-methylcytosine and 5-propynyluracil were used in the third strand. Further, a six residue "hook" complementary to an overhang of a linear duplex target was added to the 5'-end of the third strand via a T(4) linker. In binding to the overhang by Watson-Crick pairing, the hook facilitates triplex formation. This third strand also binds specifically to the target within a supercoiled plasmid. The psoralen moiety at the 3'-end of the third strand forms photoadducts to the targeted T with high efficiency. Such monoadducts are known to preferentially trigger reversion of the mutation by DNA repair enzymes.

  8. The role of the PHP domain associated with DNA polymerase X from Thermus thermophilus HB8 in base excision repair.

    Science.gov (United States)

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2012-11-01

    Base excision repair (BER) is one of the most commonly used DNA repair pathways involved in genome stability. X-family DNA polymerases (PolXs) play critical roles in BER, especially in filling single-nucleotide gaps. In addition to a polymerase core domain, bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain with phosphoesterase activity which is also required for BER. However, the role of the PHP domain of PolX in bacterial BER remains unresolved. We found that the PHP domain of Thermus thermophilus HB8 PolX (ttPolX) functions as two types of phosphoesterase in BER, including a 3'-phosphatase and an apurinic/apyrimidinic (AP) endonuclease. Experiments using T. thermophilus HB8 cell lysates revealed that the majority of the 3'-phosphatase and AP endonuclease activities are attributable to the another phosphoesterase in T. thermophilus HB8, endonuclease IV (ttEndoIV). However, ttPolX possesses significant 3'-phosphatase activity in ΔttendoIV cell lysate, indicating possible complementation. Our experiments also reveal that there are only two enzymes that display the 3'-phosphatase activity in the T. thermophilus HB8 cell, ttPolX and ttEndoIV. Furthermore, phenotypic analysis of ΔttpolX, ΔttendoIV, and ΔttpolX/ΔttendoIV using hydrogen peroxide and sodium nitrite supports the hypothesis that ttPolX functions as a backup for ttEndoIV in BER.

  9. A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy.

    Science.gov (United States)

    Owens, Daniel J; Sharples, Adam P; Polydorou, Ioanna; Alwan, Nura; Donovan, Timothy; Tang, Jonathan; Fraser, William D; Cooper, Robert G; Morton, James P; Stewart, Claire; Close, Graeme L

    2015-12-15

    Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (45 ± 25 nmol/l). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors, with peak torque measured over the following 7 days of recovery. Parallel experimentation using isolated human skeletal muscle-derived myoblast cells from biopsies of 14 males with low serum 25(OH)D (37 ± 11 nmol/l) were subjected to mechanical wound injury, which enabled corresponding in vitro studies of muscle repair, regeneration, and hypertrophy in the presence and absence of 10 or 100 nmol 1α,25(OH)2D3. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. In vitro, 10 nmol 1α,25(OH)2D3 improved muscle cell migration dynamics and resulted in improved myotube fusion/differentiation at the biochemical, morphological, and molecular level together with increased myotube hypertrophy at 7 and 10 days postdamage. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy. Copyright © 2015 the American Physiological Society.

  10. Nanoparticle-based therapy for respiratory diseases

    Directory of Open Access Journals (Sweden)

    ADRIANA L. DA SILVA

    2013-03-01

    Full Text Available Nanotechnology is an emerging science with the potential to create new materials and strategies involving manipulation of matter at the nanometer scale (<100 nm. With size-dependent properties, nanoparticles have introduced a new paradigm in pharmacotherapy – the possibility of cell-targeted drug delivery with minimal systemic side effects and toxicity. The present review provides a summary of published findings, especially regarding to nanoparticle formulations for lung diseases. The available data have shown some benefits with nanoparticle-based therapy in the development of the disease and lung remodeling in respiratory diseases. However, there is a wide gap between the concepts of nanomedicine and the published experimental data and clinical reality. In addition, studies are still required to determine the potential of nanotherapy and the systemic toxicity of nanomaterials for future human use.

  11. Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies.

    Science.gov (United States)

    Schmalz, Gottfried; Smith, Anthony J

    2014-04-01

    The traditional concept of replacing diseased tooth/pulp tissues by inert materials (restoration) is being challenged by recent advances in pulp biology leading to regenerative strategies aiming at the generation of new vital tissue. New tissue formation in the pulp chamber can be observed after adequate infection control and the formation of a blood clot. However, differentiation of true odontoblasts is still more speculative, and the approach is largely limited to immature teeth with open apices. A more systematic approach may be provided by the adoption of the tissue engineering concepts of using matrices, suitable (stem) cells, and signaling molecules to direct tissue events. With these tools, pulplike constructs have already been generated in experimental animals. However, a number of challenges still remain for clinical translation of pulp regeneration (eg, the cell source [resident vs nonresident stem cells, the latter associated with cell-free approaches], mechanisms of odontoblast differentiation, the pulp environment, the role of infection and inflammation, dentin pretreatment to release fossilized signaling molecules from dentin, and the provision of suitable matrices). Transition as a process, defined by moving from one form of "normal" to another, is based not only on the progress of science but also on achieving change to established treatment concepts in daily practice. However, it is clear that the significant recent achievements in pulp biology are providing an exciting platform from which clinical translation of dental pulp regeneration can advance. Copyright © 2014. Published by Elsevier Inc.

  12. INTERNAL REPAIR OF PIPELINES

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-04-12

    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) 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.

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

    Science.gov (United States)

    Lindahl, Tomas; Modrich, Paul; Sancar, Aziz

    2016-01-01

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

  14. Urban seismic risk assessment: statistical repair cost data and probable structural losses based on damage scenario—correlation analysis

    Science.gov (United States)

    Eleftheriadou, Anastasia K.; Baltzopoulou, Aikaterini D.; Karabinis, Athanasios I.

    2016-06-01

    The current seismic risk assessment is based on two discrete approaches, actual and probable, validating afterwards the produced results. In the first part of this research, the seismic risk is evaluated from the available data regarding the mean statistical repair/strengthening or replacement cost for the total number of damaged structures (180,427 buildings) after the 7/9/1999 Parnitha (Athens) earthquake. The actual evaluated seismic risk is afterwards compared to the estimated probable structural losses, which is presented in the second part of the paper, based on a damage scenario in the referring earthquake. The applied damage scenario is based on recently developed damage probability matrices (DPMs) from Athens (Greece) damage database. The seismic risk estimation refers to 750,085 buildings situated in the extended urban region of Athens. The building exposure is categorized in five typical structural types and represents 18.80 % of the entire building stock in Greece. The last information is provided by the National Statistics Service of Greece (NSSG) according to the 2000-2001 census. The seismic input is characterized by the ratio, a g/ a o, where a g is the regional peak ground acceleration (PGA) which is evaluated from the earlier estimated research macroseismic intensities, and a o is the PGA according to the hazard map of the 2003 Greek Seismic Code. Finally, the collected investigated financial data derived from different National Services responsible for the post-earthquake crisis management concerning the repair/strengthening or replacement costs or other categories of costs for the rehabilitation of earthquake victims (construction and function of settlements for earthquake homeless, rent supports, demolitions, shorings) are used to determine the final total seismic risk factor.

  15. Is There a Role for Base Excision Repair in Estrogen/Estrogen Receptor-Driven Breast Cancers?

    Science.gov (United States)

    Abdel-Fatah, Tarek M.A.; Perry, Christina; Arora, Arvind; Thompson, Nicola; Doherty, Rachel; Moseley, Paul M.; Green, Andrew R.; Chan, Stephen Y.T.; Ellis, Ian O.

    2014-01-01

    Abstract Estrogen and estrogen metabolite-induced reactive oxygen species generation can promote oxidative DNA base damage. If unrepaired, base damaging lesions could accelerate mutagenesis, leading to a “mutator phenotype” characterized by aggressive behavior in estrogen-estrogen receptor (ER)-driven breast cancer. To test this hypothesis, we investigated 1406 ER+ early-stage breast cancers with 20 years' long-term clinical follow-up data for DNA polymerase β (pol β), flap endonuclease 1 (FEN1), AP endonuclease 1 (APE1), X-ray cross-complementation group 1 protein (XRCC1), single-strand monofunctional uracil glycosylase-1 (SMUG1), poly (ADP-ribose) polymerase 1 (PARP1), ataxia telangiectasia mutated and Rad3 related (ATR), ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Chk1, Chk2, p53, breast cancer susceptibility gene 1 (BRCA1), and topoisomerase 2 (TOPO2) expression. Multivariate Cox proportional hazards model was used to calculate a DNA repair prognostic index and correlated to clinicopathological variables and survival outcomes. Key base excision repair (BER) proteins, including XRCC1, APE1, SMUG1, and FEN1, were independently associated with poor breast cancer-specific survival (BCSS) (ps≤0.01). Multivariate Cox model stratified patients into four distinct prognostic sub-groups with worsening BCSS (ps<0.01). In addition, compared with prognostic sub-group 1, sub-groups 2, 3, and 4 manifest increasing tumor size, grade, mitosis, pleomorphism, differentiation, lymphovascular invasion, high Ki67, loss of Bcl-2, luminal B phenotype (ps≤0.01), and poor survival, including in patients who received tamoxifen adjuvant therapy (p<0.00001). Our observation supports the hypothesis that BER-directed stratification could inform appropriate therapies in estrogen-ER-driven breast cancers. Antioxid. Redox Signal. 21, 2262–2268. PMID:25111287

  16. Femoral hernia repair

    Science.gov (United States)

    Femorocele repair; Herniorrhaphy; Hernioplasty - femoral ... During surgery to repair the hernia, the bulging tissue is pushed back in. The weakened area is sewn closed or strengthened. This repair ...

  17. Undescended testicle repair

    Science.gov (United States)

    Orchidopexy; Inguinal orchidopexy; Orchiopexy; Repair of undescended testicle; Cryptorchidism repair ... first year of life without treatment. Undescended testicle repair surgery is recommended for patients whose testicles do ...

  18. Skin-Based DNA Repair Phenotype for Cancer Risk from GCR in Genetically Diverse Populations

    Science.gov (United States)

    Guiet, Elodie; Viger, Louise; Snijders, Antoine; Costes, Sylvian V.

    2017-01-01

    Predicting cancer risk associated with cosmic radiation remains a mission-critical challenge for NASA radiation health scientists and mission planners. Epidemiological data are lacking and risk methods do not take individual radiation sensitivity into account. In our approach we hypothesize that genetic factors strongly influence risk of cancer from space radiation and that biomarkers reflecting DNA damage and cell death are ideal tools to predict risk and monitor potential health effects post-flight. At this workshop, we will be reporting the work we have done over the first 9 months of this proposal. Skin cells from 15 different strains of mice already characterized for radiation-induced cancer sensitivity (B6C3F; BALB/cByJ, C57BL/6J, CBA/CaJ, C3H/HeMsNrsf), and 10 strains from the DOE collaborative cross-mouse model were expanded from ear biopsy and cultivated until Passage 3. On average, 3 males and 3 females for each strain were expanded and frozen for further characterization at the NSRL beam line during the NSRL16C run for three LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and two ion fluences (1 and 3 particles per cell). The mice work has established new metrics for the usage of Radiation Induced Foci as a marker for various aspect of DNA repair deficiencies. In year 2, we propose to continue characterization of the mouse lines with low LET to identify loci specific to high- versus low- LET and establish genetic linkage for the various DNA repair biomarkers. Correlation with cancer risk from each animals strain and gender will also be investigated. On the human side, we will start characterizing the DNA damage response induced ex-vivo in 200 human's blood donors for radiation sensitivity with a tentative 500 donors by the end of this project. All ex-vivo phenotypic data will be correlated to genetic characterization of each individual human donors using SNP arrays characterization as done for mice. Similarly, ex-vivo phenotypic features from mice will

  19. DNA repair in neurons: So if they don't divide what's to repair?

    Energy Technology Data Exchange (ETDEWEB)

    Fishel, Melissa L. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States); Vasko, Michael R. [Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States); Kelley, Mark R. [Department of Pediatrics (Section of Hematology/Oncology), Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States) and Department of Pharmacology and Toxicology, Indiana University School of Medicine, 1044 W. Walnut St., Indianapolis, IN 46202 (United States) and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1044 W. Walnut, Room 302C, Indianapolis, IN 46202 (United States)]. E-mail: mkelley@iupui.edu

    2007-01-03

    Neuronal DNA repair remains one of the most exciting areas for investigation, particularly as a means to compare the DNA repair response in mitotic (cancer) vs. post-mitotic (neuronal) cells. In addition, the role of DNA repair in neuronal cell survival and response to aging and environmental insults is of particular interest. DNA damage caused by reactive oxygen species (ROS) such as generated by mitochondrial respiration includes altered bases, abasic sites, and single- and double-strand breaks which can be prevented by the DNA base excision repair (BER) pathway. Oxidative stress accumulates in the DNA of the human brain over time especially in the mitochondrial DNA (mtDNA) and is proposed to play a critical role in aging and in the pathogenesis of several neurological disorders including Parkinson's disease, ALS, and Alzheimer's diseases. Because DNA damage accumulates in the mtDNA more than nuclear DNA, there is increased interest in DNA repair pathways and the consequence of DNA damage in the mitochondria of neurons. The type of damage that is most likely to occur in neuronal cells is oxidative DNA damage which is primarily removed by the BER pathway. Following the notion that the bulk of neuronal DNA damage is acquired by oxidative DNA damage and ROS, the BER pathway is a likely area of focus for neuronal studies of DNA repair. BER variations in brain aging and pathology in various brain regions and tissues are presented. Therefore, the BER pathway is discussed in greater detail in this review than other repair pathways. Other repair pathways including direct reversal, nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination and non-homologous end joining are also discussed. Finally, there is a growing interest in the role that DNA repair pathways play in the clinical arena as they relate to the neurotoxicity and neuropathy associated with cancer treatments. Among the numerous side effects of cancer treatments, major

  20. Long-Standing Motor and Sensory Recovery following Acute Fibrin Sealant Based Neonatal Sciatic Nerve Repair

    Directory of Open Access Journals (Sweden)

    Natalia Perussi Biscola

    2016-01-01

    Full Text Available Brachial plexus lesion results in loss of motor and sensory function, being more harmful in the neonate. Therefore, this study evaluated neuroprotection and regeneration after neonatal peripheral nerve coaptation with fibrin sealant. Thus, P2 neonatal Lewis rats were divided into three groups: AX: sciatic nerve axotomy (SNA without treatment; AX+FS: SNA followed by end-to-end coaptation with fibrin sealant derived from snake venom; AX+CFS: SNA followed by end-to-end coaptation with commercial fibrin sealant. Results were analyzed 4, 8, and 12 weeks after lesion. Astrogliosis, microglial reaction, and synapse preservation were evaluated by immunohistochemistry. Neuronal survival, axonal regeneration, and ultrastructural changes at ventral spinal cord were also investigated. Sensory-motor recovery was behaviorally studied. Coaptation preserved synaptic covering on lesioned motoneurons and led to neuronal survival. Reactive gliosis and microglial reaction decreased in the same groups (AX+FS, AX+CFS at 4 weeks. Regarding axonal regeneration, coaptation allowed recovery of greater number of myelinated fibers, with improved morphometric parameters. Preservation of inhibitory synaptic terminals was accompanied by significant improvement in the motor as well as in the nociceptive recovery. Overall, the present data suggest that acute repair of neonatal peripheral nerves with fibrin sealant results in neuroprotection and regeneration of motor and sensory axons.

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

    Science.gov (United States)

    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

  2. In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing.

    Science.gov (United States)

    Zhou, Jie; Wang, Hui; Zhao, Shichang; Zhou, Nai; Li, Le; Huang, Wenhai; Wang, Deping; Zhang, Changqing

    2016-03-01

    Full-thickness skin defects represent urgent clinical problem nowadays. Wound dressing materials are hotly needed to induce dermal reconstruction or to treat serious skin defects. In this study, the borate bioactive glass (BG) micro-fibers were fabricated and compared with the traditional material 45S5 Bioglass(®) (SiG) micro-fibers. The morphology, biodegradation and bioactivity of BG and SiG micro-fibers were investigated in vitro. The wound size reduction and angiogenic effects of BG and SiG micro-fibers were evaluated by the rat full-thickness skin defect model and Microfil technique in vivo. Results indicated that the BG micro-fibers showed thinner fiber diameter (1 μm) and better bioactivity than the SiG micro-fibers did. The ionic extracts of BG and SiG micro-fibers were not toxic to human umbilical vein endothelial cells (HUVECs). In vivo, the BG micro-fiber wound dressings obviously enhanced the formation of blood vessel, and resulted in a much faster wound size reduction than the SiG micro-fibers, or than the control groups, after 9 days application. The good skin defect reconstruction ability of BG micro-fibers contributed to the B element in the composition, which results in the better bioactivity and angiogenesis. As shown above, the novel bioactive borate glass micro-fibers are expected to provide a promising therapeutic alternative for dermal reconstruction or skin defect repair.

  3. Intervention-based stochastic disease eradication.

    Directory of Open Access Journals (Sweden)

    Lora Billings

    Full Text Available Disease control is of paramount importance in public health, with infectious disease extinction as the ultimate goal. Although diseases may go extinct due to random loss of effective contacts where the infection is transmitted to new susceptible individuals, the time to extinction in the absence of control may be prohibitively long. Intervention controls are typically defined on a deterministic schedule. In reality, however, such policies are administered as a random process, while still possessing a mean period. Here, we consider the effect of randomly distributed intervention as disease control on large finite populations. We show explicitly how intervention control, based on mean period and treatment fraction, modulates the average extinction times as a function of population size and rate of infection spread. In particular, our results show an exponential improvement in extinction times even though the controls are implemented using a random Poisson distribution. Finally, we discover those parameter regimes where random treatment yields an exponential improvement in extinction times over the application of strictly periodic intervention. The implication of our results is discussed in light of the availability of limited resources for control.

  4. DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers

    Science.gov (United States)

    Abdel-Fatah, Tarek M.A.; Arora, Arvind; Moseley, Paul M.; Perry, Christina; Rakha, Emad A.; Green, Andrew R.; Chan, Stephen Y.T.; Ellis, Ian O.; Madhusudan, Srinivasan

    2015-01-01

    Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β, FEN1, APE1, XRCC1, SMUG1, PARP1, BRCA1, ATR, ATM, DNA-PKcs, Chk1, Chk2, p53, and TOPO2. Multivariate Cox proportional hazards models (with backward stepwise exclusion of these factors, using a criterion of p < 0.05 for retention of factors in the model) were used to identify factors that were independently associated with clinical outcomes. XRCC1 (p = 0.002), pol β (p = 0.032) FEN1 (p = 0.001) and BRCA1 (p = 0.040) levels were independently associated with poor BCSS. Subsequently, DNA repair index prognostic (DRPI) scores for breast cancer specific survival (BCSS) were calculated and two prognostic groups (DRPI-PGs) were identified. Patients in prognostic group 2 (DRPI-PG2) have higher risk of death (p < 0.001). Furthermore, in DRPI-PG2 patients, exposure to anthracycline reduced the risk of death [(HR (95% CI) = 0.79 (0.64–0.98), p = 0.032) by 21–26%. In addition, DRPI-PG2 patients have adverse clinicopathological features including higher grade, lympho-vascular invasion, Her-2 positive phenotype, compared to those in DRPI-PG1 (p < 0.01). Receiver operating characteristic (ROC) curves indicated that the DRPI outperformed the currently used prognostic factors and adding DRPI to lymph node stage significantly improved their performance as a predictor for BCSS [p < 0.00001, area under curve (AUC) = 0.70]. BER strongly influences pathogenesis of ER- and TNBCs. The DRPI accurately predicts BCSS and can also serve as a valuable prognostic and predictive tool for TNBCs. PMID:26267318

  5. Production, Purification, and Characterization of 15N-Labeled DNA Repair Proteins as Internal Standards for Mass Spectrometric Measurements

    Science.gov (United States)

    Jaruga, Pawel; Nelson, Bryant C.; Lowenthal, Mark S.; Jemth, Ann-Sofie; Loseva, Olga; Coskun, Erdem; Helleday, Thomas

    2016-01-01

    Oxidatively induced DNA damage is caused in living organisms by a variety of damaging agents, resulting in the formation of a multiplicity of lesions, which are mutagenic and cytotoxic. Unless repaired by DNA repair mechanisms before DNA replication, DNA lesions can lead to genomic instability, which is one of the hallmarks of cancer. Oxidatively induced DNA damage is mainly repaired by base excision repair pathway with the involvement of a plethora of proteins. Cancer tissues develop greater DNA repair capacity than normal tissues by overexpressing DNA repair proteins. Increased DNA repair in tumors that removes DNA lesions generated by therapeutic agents before they became toxic is a major mechanism in the development of therapy resistance. Evidence suggests that DNA repair capacity may be a predictive biomarker of patient response. Thus, knowledge of DNA–protein expressions in disease-free and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. Our laboratory has developed methodologies that use mass spectrometry with isotope dilution for the measurement of expression of DNA repair proteins in human tissues and cultured cells. For this purpose, full-length 15N-labeled analogs of a number of human DNA repair proteins have been produced and purified to be used as internal standards for positive identification and accurate quantification. This chapter describes in detail the protocols of this work. The use of 15N-labeled proteins as internal standards for the measurement of several DNA repair proteins in vivo is also presented. PMID:26791985

  6. Intestinal obstruction repair

    Science.gov (United States)

    Repair of volvulus; Intestinal volvulus - repair; Bowel obstruction - repair ... Intestinal obstruction repair is done while you are under general anesthesia . This means you are asleep and DO NOT feel pain. ...

  7. Aortic aneurysm repair - endovascular

    Science.gov (United States)

    EVAR; Endovascular aneurysm repair - aorta; AAA repair - endovascular; Repair - aortic aneurysm - endovascular ... Endovascular aortic repair is done because your aneurysm is very large, growing quickly, or is leaking or bleeding. You may have ...

  8. Motorcycle Repair.

    Science.gov (United States)

    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…

  9. Superomniphobic and easily repairable coatings on copper substrates based on simple immersion or spray processes.

    Science.gov (United States)

    Rangel, Thomaz C; Michels, Alexandre F; Horowitz, Flávio; Weibel, Daniel E

    2015-03-24

    Textures that resemble typical fern or bracken plant species (dendrite structures) were fabricated for liquid repellency by dipping copper substrates in a single-step process in solutions containing AgNO3 or by a simple spray liquid application. Superhydrophobic surfaces were produced using a solution containing AgNO3 and trimethoxypropylsilane (TMPSi), and superomniphobic surfaces were produced by a two-step procedure, immersing the copper substrate in a AgNO3 solution and, after that, in a solution containing 1H,1H,2H,2H-perfluorodecyltriethoxysilane (PFDTES). The simple functionalization processes can also be used when the superomniphobic surfaces were destroyed by mechanical stress. By immersion of the wrecked surfaces in the above solutions or by the spray method and soft heating, the copper substrates could be easily repaired, regenerating the surfaces' superrepellency to liquids. The micro- and nanoroughness structures generated on copper surfaces by the deposition of silver dendrites functionalized with TMPSi presented apparent contact angles greater than 150° with a contact angle hysteresis lower than 10° when water was used as the test liquid. To avoid total wettability with very low surface tension liquids, such as rapeseed oil and hexadecane, a thin perfluorinated coating of poly(tetrafluoroethylene) (PTFE), produced by physical vapor deposition, was used. A more efficient perfluorinated coating was obtained when PFDTES was used. The superomniphobic surfaces produced apparent contact angles above 150° with all of the tested liquids, including hexadecane, although the contact angle hysteresis with this liquid was above 10°. The coupling of dendritic structures with TMPSi/PTFE or directly by PFDTES coatings was responsible for the superrepellency of the as-prepared surfaces. These simple, fast, and reliable procedures allow the large area, and cost-effective scale fabrication of superrepellent surfaces on copper substrates for various industrial

  10. Decision making based on analysis of benefit versus costs of preventive retrofit versus costs of repair after earthquake hazards

    Science.gov (United States)

    Bostenaru Dan, M.

    2012-04-01

    In this presentation interventions on seismically vulnerable early reinforced concrete skeleton buildings, from the interwar time, at different performance levels, from avoiding collapse up to assuring immediate post-earthquake functionality are considered. Between these two poles there are degrees of damage depending on the performance aim set. The costs of the retrofit and post-earthquake repair differ depending on the targeted performance. Not only an earthquake has impact on a heritage building, but also the retrofit measure, for example on its appearance or its functional layout. This way criteria of the structural engineer, the investor, the architect/conservator/urban planner and the owner/inhabitants from the neighbourhood are considered for taking a benefit-cost decision. Benefit-cost analysis based decision is an element in a risk management process. A solution must be found on how much change to accept for retrofit and how much repairable damage to take into account. There are two impact studies. Numerical simulation was run for the building typology considered for successive earthquakes, selected in a deterministic way (1977, 1986 and two for 1991 from Vrancea, Romania and respectively 1978 Thessaloniki, Greece), considering also the case when retrofit is done between two earthquakes. The typology of buildings itself was studied not only for Greece and Romania, but for numerous European countries, including Italy. The typology was compared to earlier reinforced concrete buildings, with Hennebique system, in order to see to which amount these can belong to structural heritage and to shape the criteria of the architect/conservator. Based on the typology study two model buildings were designed, and for one of these different retrofit measures (side walls, structural walls, steel braces, steel jacketing) were considered, while for the other one of these retrofit techniques (diagonal braces, which permits adding also active measures such as energy

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Photographic-Based Optical Evaluation of Tissues and Biomaterials Used for Corneal Surface Repair: A New Easy-Applied Method.

    Directory of Open Access Journals (Sweden)

    Miguel Gonzalez-Andrades

    Full Text Available Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM for measuring functional optical blurring and transparency in corneal surface grafts.Plastic compressed collagen scaffolds (PCCS and multilayered amniotic membranes (AM samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD technique, which is the gold standard method.All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR value of 80.3 ± 2.8%, with a blurring index (BI of 50.6 ± 4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6| with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005. The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring.This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair.

  13. Demonstrating mood repair with a situation-based measure of self-compassion and self-criticism.

    Science.gov (United States)

    Falconer, Caroline J; King, John A; Brewin, Chris R

    2015-12-01

    The clinical significance of self-criticism and self-compassion has prompted the development of questionnaires assessing these constructs. However, there is a lack of measures assessing their interaction within specific contexts and potential involvement in mood repair processes. To rectify this, we developed the Self-Compassion and Self-Criticism Scales (SCCS), based on responses to specific scenarios, and examined its psychometric properties in an online survey and an experimental situation. In study 1, standard psychometric procedures were used to investigate the reliability and validity of the SCCS. In study 2, an experimental challenge involving a difficult language task was used to test its sensitivity to change. In study 1, exploratory factor analysis (n = 413) showed a clear two-factor structure of the SCCS denoting two orthogonal scales, with high internal validity (α ≥ .87). Correlations between the SCCS and existing measures also demonstrated appropriate convergent validity. Study 2 (n = 90) provided preliminary evidence that the SCCS can detect changes in self-appraisals. Participants receiving no performance feedback from the challenge task showed reduced state self-criticism and increased state self-compassion, demonstrating mood repair. The SCCS has promise as a situational measure of self-compassion and self-criticism. In the context of specific problem situations, clients' levels of self-criticism and self-compassion may well be orthogonal and can be assessed with the SCCS. In setting treatment goals and assessing treatment outcome, it may be helpful to target both self-compassion and self-criticism separately. © 2015 The Authors. Psychology and Psychotherapy published by John Wiley & Sons Ltd on behalf of the British Psychological Society.

  14. DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers

    DEFF Research Database (Denmark)

    Osorio, Ana; Milne, Roger L; Kuchenbaecker, Karoline

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of th...

  15. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    Osorio, Ana; Milne, Roger L.; Kuchenbaecker, Karoline; Vaclova, Tereza; Pita, Guillermo; Alonso, Rosario; Peterlongo, Paolo; Blanco, Ignacio; de la Hoya, Miguel; Duran, Mercedes; Diez, Orland; Ramon y Cajal, Teresa; Konstantopoulou, Irene; Martinez-Bouzas, Cristina; Conejero, Raquel Andres; Soucy, Penny; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Arver, Brita; Rantala, Johanna; Loman, Niklas; Ehrencrona, Hans; Olopade, Olufunmilayo I.; Beattie, Mary S.; Domchek, Susan M.; Nathanson, Katherine; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; John, Esther M.; Whittemore, Alice S.; Daly, Mary B.; Southey, Melissa; Hopper, John; Terry, Mary B.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Steele, Linda; Neuhausen, Susan L.; Ding, Yuan Chun; Hansen, Thomas V. O.; Jonson, Lars; Ejlertsen, Bent; Gerdes, Anne-Marie; Infante, Mar; Herraez, Belen; Moreno, Leticia Thais; Weitzel, Jeffrey N.; Herzog, Josef; Weeman, Kisa; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Bonanni, Bernardo; Mariette, Frederique; Volorio, Sara; Viel, Alessandra; Varesco, Liliana; Papi, Laura; Ottini, Laura; Tibiletti, Maria Grazia; Radice, Paolo; Yannoukakos, Drakoulis; Garber, Judy; Ellis, Steve; Frost, Debra; Platte, Radka; Fineberg, Elena; Evans, Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Cole, Trevor; Eccles, Diana; Cook, Jackie; Hodgson, Shirley; Brewer, Carole; Tischkowitz, Marc; Douglas, Fiona; Porteous, Mary; Side, Lucy; Walker, Lisa; Morrison, Patrick; Donaldson, Alan; Kennedy, John; Foo, Claire; Godwin, Andrew K.; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hans Joerg; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Damiola, Francesca; Poppe, Bruce; Claes, Kathleen; Piedmonte, Marion; Tucker, Kathy; Backes, Floor; Rodriguez, Gustavo; Brewster, Wendy; Wakeley, Katie; Rutherford, Thomas; Caldes, Trinidad; Nevanlinna, Heli; Aittomaki, Kristiina; Rookus, Matti A.; van Os, Theo A. M.; van der Kolk, Lizet; de Lange, J. L.; Meijers-Heijboer, Hanne E. J.; van der Hout, A. H.; van Asperen, Christi J.; Gomez Garcia, Encarna B.; Hoogerbrugge, Nicoline; Collee, J. Margriet; van Deurzen, Carolien H. M.; van der Luijt, Rob B.; Devilee, Peter; Olah, Edith; Lazaro, Conxi; Teule, Alex; Menendez, Mireia; Jakubowska, Anna; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Johannsson, Oskar Th; Maugard, Christine; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R.; Healey, Sue; Olswold, Curtis; Guidugli, Lucia; Lindor, Noralane; Slager, Susan; Szabo, Csilla I.; Vijai, Joseph; Robson, Mark; Kauff, Noah; Zhang, Liying; Rau-Murthy, Rohini; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Lejbkowicz, Flavio; Andrulis, Irene; Mulligan, Anna Marie; Glendon, Gord; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Friedman, Eitan; Laitman, Yael; Shimon, Shani Paluch; Simard, Jacques; Easton, Douglas F.; Offit, Kenneth; Couch, Fergus J.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Benitez, Javier

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the c

  16. DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    Osorio, Ana; Milne, Roger L.; Kuchenbaecker, Karoline; Vaclova, Tereza; Pita, Guillermo; Alonso, Rosario; Peterlongo, Paolo; Blanco, Ignacio; de la Hoya, Miguel; Duran, Mercedes; Diez, Orland; Ramon y Cajal, Teresa; Konstantopoulou, Irene; Martinez-Bouzas, Cristina; Conejero, Raquel Andres; Soucy, Penny; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Arver, Brita; Rantala, Johanna; Loman, Niklas; Ehrencrona, Hans; Olopade, Olufunmilayo I.; Beattie, Mary S.; Domchek, Susan M.; Nathanson, Katherine; Rebbeck, Timothy R.; Arun, Banu K.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; John, Esther M.; Whittemore, Alice S.; Daly, Mary B.; Southey, Melissa; Hopper, John; Terry, Mary B.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Steele, Linda; Neuhausen, Susan L.; Ding, Yuan Chun; Hansen, Thomas V. O.; Jonson, Lars; Ejlertsen, Bent; Gerdes, Anne-Marie; Infante, Mar; Herraez, Belen; Moreno, Leticia Thais; Weitzel, Jeffrey N.; Herzog, Josef; Weeman, Kisa; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Bonanni, Bernardo; Mariette, Frederique; Volorio, Sara; Viel, Alessandra; Varesco, Liliana; Papi, Laura; Ottini, Laura; Tibiletti, Maria Grazia; Radice, Paolo; Yannoukakos, Drakoulis; Garber, Judy; Ellis, Steve; Frost, Debra; Platte, Radka; Fineberg, Elena; Evans, Gareth; Lalloo, Fiona; Izatt, Louise; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Cole, Trevor; Eccles, Diana; Cook, Jackie; Hodgson, Shirley; Brewer, Carole; Tischkowitz, Marc; Douglas, Fiona; Porteous, Mary; Side, Lucy; Walker, Lisa; Morrison, Patrick; Donaldson, Alan; Kennedy, John; Foo, Claire; Godwin, Andrew K.; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hans Joerg; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.; Mazoyer, Sylvie; Damiola, Francesca; Poppe, Bruce; Claes, Kathleen; Piedmonte, Marion; Tucker, Kathy; Backes, Floor; Rodriguez, Gustavo; Brewster, Wendy; Wakeley, Katie; Rutherford, Thomas; Caldes, Trinidad; Nevanlinna, Heli; Aittomaki, Kristiina; Rookus, Matti A.; van Os, Theo A. M.; van der Kolk, Lizet; de Lange, J. L.; Meijers-Heijboer, Hanne E. J.; van der Hout, A. H.; van Asperen, Christi J.; Gomez Garcia, Encarna B.; Hoogerbrugge, Nicoline; Collee, J. Margriet; van Deurzen, Carolien H. M.; van der Luijt, Rob B.; Devilee, Peter; Olah, Edith; Lazaro, Conxi; Teule, Alex; Menendez, Mireia; Jakubowska, Anna; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Johannsson, Oskar Th; Maugard, Christine; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R.; Healey, Sue; Olswold, Curtis; Guidugli, Lucia; Lindor, Noralane; Slager, Susan; Szabo, Csilla I.; Vijai, Joseph; Robson, Mark; Kauff, Noah; Zhang, Liying; Rau-Murthy, Rohini; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Berger, Andreas; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Lejbkowicz, Flavio; Andrulis, Irene; Mulligan, Anna Marie; Glendon, Gord; Toland, Amanda Ewart; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Friedman, Eitan; Laitman, Yael; Shimon, Shani Paluch; Simard, Jacques; Easton, Douglas F.; Offit, Kenneth; Couch, Fergus J.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Benitez, Javier

    2014-01-01

    Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the c

  17. Archaeal DNA Polymerase-B as a DNA Template Guardian: Links between Polymerases and Base/Alternative Excision Repair Enzymes in Handling the Deaminated Bases Uracil and Hypoxanthine

    Directory of Open Access Journals (Sweden)

    Javier Abellón-Ruiz

    2016-01-01

    Full Text Available In Archaea repair of uracil and hypoxanthine, which arise by deamination of cytosine and adenine, respectively, is initiated by three enzymes: Uracil-DNA-glycosylase (UDG, which recognises uracil; Endonuclease V (EndoV, which recognises hypoxanthine; and Endonuclease Q (EndoQ, (which recognises both uracil and hypoxanthine. Two archaeal DNA polymerases, Pol-B and Pol-D, are inhibited by deaminated bases in template strands, a feature unique to this domain. Thus the three repair enzymes and the two polymerases show overlapping specificity for uracil and hypoxanthine. Here it is demonstrated that binding of Pol-D to primer-templates containing deaminated bases inhibits the activity of UDG, EndoV, and EndoQ. Similarly Pol-B almost completely turns off EndoQ, extending earlier work that demonstrated that Pol-B reduces catalysis by UDG and EndoV. Pol-B was observed to be a more potent inhibitor of the enzymes compared to Pol-D. Although Pol-D is directly inhibited by template strand uracil, the presence of Pol-B further suppresses any residual activity of Pol-D, to near-zero levels. The results are compatible with Pol-D acting as the replicative polymerase and Pol-B functioning primarily as a guardian preventing deaminated base-induced DNA mutations.

  18. Advanced cell-based cardiac repair: How to mend a broken heart

    NARCIS (Netherlands)

    R. de Jong (Renate)

    2014-01-01

    markdownabstract__Abstract__ Cardiovascular disease is still the leading cause of death worldwide, accounting for approximately 13 million deaths a year.1 It is estimated that this number will double in the upcoming 15 years due to aging of the population in combination with an increase of risk fac

  19. Advanced cell-based cardiac repair: How to mend a broken heart

    NARCIS (Netherlands)

    R. de Jong (Renate)

    2014-01-01

    markdownabstract__Abstract__ Cardiovascular disease is still the leading cause of death worldwide, accounting for approximately 13 million deaths a year.1 It is estimated that this number will double in the upcoming 15 years due to aging of the population in combination with an increase of risk

  20. [New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

    Science.gov (United States)

    Fu, X B

    2016-01-01

    Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

  1. Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases.

    Science.gov (United States)

    Woods, Ryan D; O'Shea, Valerie L; Chu, Aurea; Cao, Sheng; Richards, Jody L; Horvath, Martin P; David, Sheila S

    2016-01-29

    MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new-for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer.

  2. Damaged anal canal as a cause of fecal incontinence after surgical repair for Hirschsprung disease - a preventable and under-reported complication.

    Science.gov (United States)

    Bischoff, Andrea; Frischer, Jason; Knod, Jennifer Leslie; Dickie, Belinda; Levitt, Marc A; Holder, Monica; Jackson, Lyndsey; Peña, Alberto

    2017-04-01

    Fecal incontinence after the surgical repair of Hirschsprung disease is a potentially preventable complication that carries a negative impact on patient's quality of life. Patients that were previously operated for Hirschsprung disease and presented to our bowel management clinic with the complaint of fecal incontinence were retrospectively reviewed. All patients underwent a rectal examination under anesthesia looking for anatomic explanations for their incontinence. One hundred three patients were identified. 54 patients had a damaged anal canal. 22 patients also had a patulous anus. The operative reports mentioned the pectinate line in 32 patients, in 12 it was not mentioned, and in 10 patients the operative report was not available. All patients with a damaged anal canal suffered from true fecal incontinence; 45 of them are on daily enemas (41 are clean and 4 are still having "accidents"), 7 are not doing bowel management due to noncompliance and 2 patients have a permanent ileostomy. 49 patients did not have a damaged anal canal, 25 of those responded to changes in diet and medication and are having voluntary bowel movements. Fecal incontinence may occur after an operation for Hirschsprung disease. When the anal canal is damaged, incontinence is always present, severe, and probably permanent. The preservation of the anal canal may avoid this complication. Copyright © 2017. Published by Elsevier Inc.

  3. Evaluation of cartilage repair tissue after matrix-associated autologous chondrocyte transplantation using a hyaluronic-based or a collagen-based scaffold with morphological MOCART scoring and biochemical T2 mapping: preliminary results.

    Science.gov (United States)

    Welsch, Goetz Hannes; Mamisch, Tallal Charles; Zak, Lukas; Blanke, Matthias; Olk, Alexander; Marlovits, Stefan; Trattnig, Siegfried

    2010-05-01

    In cartilage repair, bioregenerative approaches using tissue engineering techniques have tried to achieve a close resemblance to hyaline cartilage, which might be visualized using advanced magnetic resonance imaging. To compare cartilage repair tissue at the femoral condyle noninvasively after matrix-associated autologous chondrocyte transplantation using Hyalograft C, a hyaluronic-based scaffold, to cartilage repair tissue after transplantation using CaReS, a collagen-based scaffold, with magnetic resonance imaging using morphologic scoring and T2 mapping. Cohort study; Level of evidence, 3. Twenty patients after matrix-associated autologous chondrocyte transplantation (Hyalograft C, n = 10; CaReS, n = 10) underwent 3-T magnetic resonance imaging 24 months after surgery. Groups were matched by age and defect size/localization. For clinical outcome, the Brittberg score was assessed. Morphologic analysis was applied using the magnetic resonance observation of cartilage repair tissue score, and global and zonal biochemical T2 mapping was performed to reflect biomechanical properties with regard to collagen matrix/content and hydration. The clinical outcome was comparable in each group. The magnetic resonance observation of cartilage repair tissue score showed slightly but not significantly (P= .210) better results in the CaReS group (76.5) compared to the Hyalograft C group (70.0), with significantly better (P= .004) constitution of the surface of the repair tissue in the CaReS group. Global T2 relaxation times (milliseconds) for healthy surrounding cartilage were comparable in both groups (Hyalograft C, 49.9; CaReS, 51.9; P= .398), whereas cartilage repair tissue showed significantly higher results in the CaReS group (Hyalograft C, 48.2; CaReS, 55.5; P= .011). Zonal evaluation showed no significant differences (P > or = .05). Most morphologic parameters provided comparable results for both repair tissues. However, differences in the surface and higher T2 values for

  4. A Comparison of Weld-Repaired and Base Metal for Inconel 718 and CRES 321 at Cryogenic and Room Temperatures

    Science.gov (United States)

    Newman, John A.; Smith, Stephen W.; Willard, Scott A.; Piascik, Robert S.

    2004-01-01

    Fatigue crack growth tests were conducted to characterize the performance of Inconel 718 and CRES 321 welds, weld heat-affect-zone and parent metal at room temperature laboratory air and liquid nitrogen (-196oC) environments. The results of this study were required to predict the damage tolerance behavior of proposed orbiter main engine hydrogen fuel liner weld repairs. Experimental results show that the room and cryogenic temperature fatigue crack growth characteristics of both alloys are not significantly degraded by the weld repair process. However, both Inconel 718 and CRES 321 exhibited lower apparent toughness within the weld repair region compared to the parent metal.

  5. Quantifying the contributions of base selectivity, proofreading and mismatch repair to nuclear DNA replication in Saccharomyces cerevisiae.

    Science.gov (United States)

    St Charles, Jordan A; Liberti, Sascha E; Williams, Jessica S; Lujan, Scott A; Kunkel, Thomas A

    2015-07-01

    Mismatches generated during eukaryotic nuclear DNA replication are removed by two evolutionarily conserved error correction mechanisms acting in series, proofreading and mismatch repair (MMR). Defects in both processes are associated with increased susceptibility to cancer. To better understand these processes, we have quantified base selectivity, proofreading and MMR during nuclear DNA replication in Saccharomyces cerevisiae. In the absence of proofreading and MMR, the primary leading and lagging strand replicases, polymerase ɛ and polymerase δ respectively, synthesize DNA in vivo with somewhat different error rates and specificity, and with apparent base selectivity that is more than 100 times higher than measured in vitro. Moreover, leading and lagging strand replication fidelity rely on a different balance between proofreading and MMR. On average, proofreading contributes more to replication fidelity than does MMR, but their relative contributions vary from nearly all proofreading of some mismatches to mostly MMR of other mismatches. Thus accurate replication of the two DNA strands results from a non-uniform and variable balance between error prevention, proofreading and MMR.

  6. When is mesh fixation in TAPP-repair of primary inguinal hernia repair necessary? The register-based analysis of 11,230 cases.

    Science.gov (United States)

    Mayer, F; Niebuhr, H; Lechner, M; Dinnewitzer, A; Köhler, G; Hukauf, M; Fortelny, R H; Bittner, R; Köckerling, F

    2016-10-01

    Whereas for TEP the guidelines do not recommend mesh fixation on the basis of meta-analyses regardless of the defect size, for TAPP mesh fixation can be omitted only up to a defect size of 3 cm because of the paucity of studies on this topic. Hence, this study now seeks to explore this subject on the basis of prospective data from the Herniamed Hernia Registry. In the period September 01, 2009, to January 31, 2014, 11,228 male patients were operated on with the TAPP technique for a primary unilateral inguinal hernia and were followed up for 1 year. Mesh fixation was used for 7422 (66.1 %) of these patients and no mesh fixation for 3806 patients (33.9 %). Unadjusted analysis did not find any significant difference in the recurrence rate (0.88 % with fixation vs. 1.1 % without fixation; p = 0.259). Multivariable analysis of all potential influence factors (age, ASA, BMI, risk factors, defect size, mesh fixation, localization of defect, mesh size) did not identify any factor that impacted recurrence on 1-year follow-up. Only for medial and combined defect localization versus lateral localization was a highly significant effect identified (p < 0.001). With mesh fixation and larger mesh size, it was possible to significantly reduce the recurrence rate for larger medial hernias in this series (p = 0.046). For TAPP repair of an inguinal hernia, mesh fixation is not necessary in a significant number of patients. Patients with a medial and combined hernia are at higher risk of recurrence. In the patient series analyzed, it was possible to significantly reduce the recurrence rate with mesh fixation and larger mesh size for medial defects.

  7. OpenCV Based Disease Identification of Mango Leaves

    Directory of Open Access Journals (Sweden)

    Jayaprakash Sethupathy

    2016-10-01

    Full Text Available This paper aims in classifying and identifying the diseases of mango leaves for Indian agriculture. K-means algorithm is chosen for the disease segmentation, and the disease classification and identification is carried out using the SVM classifier. Disease identification based on analysis of patches or discoloring of leaf will hold good for some of the plant diseases, but some other diseases which will deform the leaf shape cannot be identified based on the same method. In this case leaf shape based disease identification has to be performed. Based on this analysis two topics are addressed in this research paper. (1 Disease identification using the OpenCV libraries (2 Leaf shape based disease identification.

  8. Hemodynamic effects of sustained postoperative cardiac resynchronization therapy in infants after repair of congenital heart disease: Results of a randomized clinical trial.

    Science.gov (United States)

    Friedberg, Mark K; Schwartz, Steven M; Zhang, Hargen; Chiu-Man, Christine; Manlhiot, Cedric; Ilina, Maria V; Arsdell, Glen Van; Kirsh, Joel A; McCrindle, Brian W; Stephenson, Elizabeth A

    2017-02-01

    It is unknown whether continuous cardiac resynchronization therapy (CRT) can lead to sustained improvement in hemodynamics after surgery for congenital heart disease (CHD). We investigated whether CRT improves cardiac index (CI) and blood pressure in infants after biventricular repair of CHD. We randomized infants younger than 4 months after biventricular CHD surgery to standard care or standard care plus CRT for 48 hours or until extubation if sooner. Change in the primary outcome of CI and blood pressure over time was compared between groups. For subgroup analysis, QRS duration was considered prolonged if greater than the 98th percentile. Forty-two patients were randomized: 21 controls and 21 patients receiving CRT (median weight 4 kg). There were no identified adverse events from pacing. The change in CI over time was not different between patients receiving CRT and controls, but trended toward improvement in patients with wide QRS who received CRT (n = 9) vs controls with wide QRS (n = 8) (+1.65 (0.86) L/(min·m(2)); P = .06). Controls with wide QRS experienced the smallest increase in CI (0.33 L/(min·m(2))). Blood pressure was significantly higher in infants with wide QRS who received CRT than in controls (+7.14 (3.08) mm Hg; P = .02). Serum lactate level, catecholamine use, ventilation time, and length of intensive care unit stay were similar between the 2 groups. CRT improved blood pressure and a trend toward higher CI in infants after repair of biventricular CHD with prolonged QRS duration. These findings warrant further study of CRT to improve postoperative recovery in infants with electrical dyssynchrony. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. Register-based studies of cardiovascular disease

    DEFF Research Database (Denmark)

    Abildstrøm, Steen Z; Torp-Pedersen, Christian; Madsen, Mette

    2011-01-01

    Introduction: The use of the unique personal identification number in the Nordic database systems enables the researchers to link the registers at the individual level. The registers can be used for both defining specific patient populations and to identify later events during follow-up. This rev...... the hospitalisation rate and treatment of cardiovascular disease. The risk of unmeasured factors affecting the results calls for cautious interpretation of the results.......-up. This review gives three examples within cardiovascular epidemiology to illustrate the use of the national administrative registers available to all researchers upon request. Research topics: The hospitalisation rate of acute myocardial infarction (AMI) was expected to be increased and case-fatality rate......-based treatment increased significantly over time and adherence to treatment was high. Finally, use of specific nonsteroidal antiinflammatory drugs by healthy subjects was associated with a dose-dependent increase in cardiovascular risk. CONCLUSION: The nationwide registers have proven very useful in monitoring...

  10. Final Environmental Assessment Airfield Storm Drainage System Repair Joint Base Andrews-Naval Air Facility Washington, MD

    Science.gov (United States)

    2015-06-01

    eastern cottontail (Sylvilagus floridanus). Reptiles occasionally found on the airfield include the eastern garter snake (Thamnophis sirtalis...and Noise Control. Acoustical Society of America . Sewickley, PA. HDR (HDR Engineering, Inc.). 2014. Design Analysis. Design for Repair/Replacement of

  11. Development and Evaluation of Cement-Based Materials for Repair of Corrosion-Damaged Reinforced Concrete Slabs

    OpenAIRE

    Liu, Rongtang; Olek, J.

    2001-01-01

    In this study, the results of an extensive laboratory investigation conducted to evaluate the properties of concrete mixes used as patching materials to repair reinforced concrete slabs damaged by corrosion are reported. Seven special concrete mixes containing various combinations of chemical or mineral admixtures were developed and used as a patching material to improve the durability of the repaired slabs. Physical and mechanical properties of these mixes, such as compressive strength, stat...

  12. Mismatch repair in Streptococcus pneumoniae: relationship between base mismatches and transformation efficiencies.

    Science.gov (United States)

    Claverys, J P; Méjean, V; Gasc, A M; Sicard, A M

    1983-10-01

    Genetic transformation in Streptococcus pneumoniae involves the insertion of single-stranded pieces of donor DNA into a recipient genome. Efficiencies of transformation strongly depend on the mutations (markers) carried by donor DNA. Markers are classified according to their transforming efficiencies into very high, high, intermediate, and low efficiency. The last is approximately 1/20th as efficient as the first. This marker effect is under the control of the Hex system, which is thought to correct mismatches at the donor-recipient heteroduplex stage in transformation. To investigate this effect, wild type, mutant, and revertant DNA sequences at five genetic sites within the amiA locus were determined. The results show that low-efficiency markers arise from transitional changes A . T to G . C. The transversion A . T to T . A corresponds to an intermediate-efficiency marker. Transversions G . C to T . A and G . C to C . G lead to high-efficiency markers. Among the eight possible mismatches that could exist transiently at the heteroduplex stage in transformation, only two--namely, A/G and C/C--are not corrected by the Hex system. It is noteworthy that the four possible base pairs (A . T, T . A, G . C, and C . G) have been encountered at the very same site (amiA6 site), which constitutes a good illustration of the marker effect. DNA sequence analysis also reveals that short deletions (33 or 34 bases long) are integrated with very high efficiencies. These results confirm that the Hex system corrects point mismatches harbored in donor-recipient heteroduplexes thousands of bases long. The correction pattern of the Hex system toward multiple-base mismatches has also been investigated. Its behavior toward double-base mismatches is complex, suggesting that neighboring sequences may affect the detection of mispaired bases.

  13. Near-Infrared Radiation Based Composite Repair Using Thermoplastics as Adhesives

    Science.gov (United States)

    2007-12-01

    thermoplastics based on their adhesive strength. Amongst other, a Na+-based ionomer S1856 and an adhesion promoter Ethylene Metacrylic Acid (EMAA) have shown...the air to flow when vacuum is drawn, and gives a certain roughness to the surface finish of the panel after curing. The S- glass fibers are used as...panel. The glass fibers provide a path for the excess resin to flow, and is by then called a bleeder. The more layers of S- glass fibers, the more

  14. CrowdAidRepair: A Crowd-Aided Interactive Data Repairing Method

    KAUST Repository

    Zhou, Jian

    2016-03-25

    Data repairing aims at discovering and correcting erroneous data in databases. Traditional methods relying on predefined quality rules to detect the conflict between data may fail to choose the right way to fix the detected conflict. Recent efforts turn to use the power of crowd in data repairing, but the crowd power has its own drawbacks such as high human intervention cost and inevitable low efficiency. In this paper, we propose a crowd-aided interactive data repairing method which takes the advantages of both rule-based method and crowd-based method. Particularly, we investigate the interaction between crowd-based repairing and rule-based repairing, and show that by doing crowd-based repairing to a small portion of values, we can greatly improve the repairing quality of the rule-based repairing method. Although we prove that the optimal interaction scheme using the least number of values for crowd-based repairing to maximize the imputation recall is not feasible to be achieved, still, our proposed solution identifies an efficient scheme through investigating the inconsistencies and the dependencies between values in the repairing process. Our empirical study on three data collections demonstrates the high repairing quality of CrowdAidRepair, as well as the efficiency of the generated interaction scheme over baselines.

  15. Minimally disruptive schedule repair for MCM missions

    Science.gov (United States)

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

    2015-05-01

    Mine countermeasures (MCM) missions entail planning and operations in very dynamic and uncertain operating environments, which pose considerable risk to personnel and equipment. Frequent schedule repairs are needed that consider the latest operating conditions to keep mission on target. Presently no decision support tools are available for the challenging task of MCM mission rescheduling. To address this capability gap, we have developed the CARPE system to assist operation planners. CARPE constantly monitors the operational environment for changes and recommends alternative repaired schedules in response. It includes a novel schedule repair algorithm called Case-Based Local Schedule Repair (CLOSR) that automatically repairs broken schedules while satisfying the requirement of minimal operational disruption. It uses a case-based approach to represent repair strategies and apply them to new situations. Evaluation of CLOSR on simulated MCM operations demonstrates the effectiveness of case-based strategy. Schedule repairs are generated rapidly, ensure the elimination of all mines, and achieve required levels of clearance.

  16. The role of base excision repair in the development of primary open angle glaucoma in the Polish population

    Energy Technology Data Exchange (ETDEWEB)

    Cuchra, Magda; Markiewicz, Lukasz; Mucha, Bartosz [Department of Clinical Chemistry and Biochemistry, Medical University of Lodz (Poland); Pytel, Dariusz [The Abramson Family Cancer Research Institute, Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 (United States); Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425 (United States); Szymanek, Katarzyna [Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw (Poland); Szemraj, Janusz [Department of Medical Biochemistry, Medical University of Lodz, Lodz (Poland); Szaflik, Jerzy; Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw, SPKSO Hospital, Warsaw (Poland); Majsterek, Ireneusz, E-mail: ireneusz.majsterek@umed.lodz.pl [Department of Clinical Chemistry and Biochemistry, Medical University of Lodz (Poland)

    2015-08-15

    Highlights: • We suggested the association of XRCC1 gene with the increase risk of POAG development. • We indicated the association of clinical factor and XRCC1, MUTYH, ADPRT and APE1 genes with POAG progression. • We postulated the increase level of oxidative DNA damage in group of patients with POAG in relation to healthy controls. • We suggested the slightly decrease ability to repair of oxidative DNA damage. • This is the first data that showed the role of BER mechanism in POAG pathogenesis. - Abstract: Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients. The aim of our study was to evaluate an association of BER gene polymorphism with a risk of POAG. Moreover, an association of clinical parameters was examined including cup disk ratio (c/d), rim area (RA) and retinal nerve fiber layer (RNFL) with glaucoma progression according to BER gene polymorphisms. Our research included 412 patients with POAG and 454 healthy controls. Gene polymorphisms were analyzed by PCR-RFLP. Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. The 399Arg/Gln genotype of the XRCC1 gene (OR 1.38; 95% CI 1.02–1.89 p = 0.03) was associated with an increased risk of POAG occurrence. It was indicated that the 399Gln/Gln XRCC1 genotype might increase the risk of POAG progression according to the c/d ratio (OR 1.67; 95% CI 1.07–2.61 P = 0.02) clinical parameter. Moreover, the association of VF factor with 148Asp/Glu of APE1 genotype distribution and POAG progression (OR 2.25; 95% CI 1.30–3.89) was also found. Additionally, the analysis of the 324Gln/His MUTYH polymorphism gene distribution in the patient group according to RNFL factor showed that it might

  17. Assessment of the functionality of bacteria-based repair system for concrete through ESEM analysis

    NARCIS (Netherlands)

    Wiktor, V.; Jonkers, H.M.

    2015-01-01

    Biodeposition, a method by which calcium carbonate (CaCO3) precipitation is induced by bacteria, has been proposed as an interesting approach to protect building materials. The liquid-based system presented in this paper aims at the sealing of cracks and decrease of the porosity due to the productio

  18. Environmental Assessment: 13th Street Bridge Emergency Repair and Retrofit Vandenberg Air Force Base California

    Science.gov (United States)

    2003-06-23

    23-1 Acres on Vandenberg Air Force Base. Robert 0. Gibson, Archaeologist, Paso Robles, California. Submitted toURS Corporation, Santa Barbara...Timbrook (editors). 1977. The Eye (?f the Flute: Chwnash Traditional History and Ritual, as told by Fernando Librado Kitsepmvit to John P. Harrington

  19. Holliday junction affinity of the base excision repair factor Endo III contributes to cholera toxin phage integration.

    Science.gov (United States)

    Bischerour, Julien; Spangenberg, Claudia; Barre, François-Xavier

    2012-09-12

    Toxigenic conversion of Vibrio cholerae bacteria results from the integration of a filamentous phage, CTX phage. Integration is driven by the bacterial Xer recombinases, which catalyse the exchange of a single pair of strands between the phage single-stranded DNA and the host double-stranded DNA genomes; replication is thought to convert the resulting pseudo-Holliday junction (HJ) intermediate into the final recombination product. The natural tendency of the Xer recombinases to recycle HJ intermediates back into substrate should thwart this integration strategy, which prompted a search for additional co-factors aiding directionality of the process. Here, we show that Endo III, a ubiquitous base excision repair enzyme, facilitates CTX phage-integration in vivo. In vitro, we show that it prevents futile Xer recombination cycles by impeding new rounds of strand exchanges once the pseudo-HJ is formed. We further demonstrate that this activity relies on the unexpected ability of Endo III to bind to HJs even in the absence of the recombinases. These results explain how tandem copies of the phage genome can be created, which is crucial for subsequent virion production.

  20. Fabrication of silk mesh with enhanced cytocompatibility: preliminary in vitro investigation toward cell-based therapy for hernia repair.

    Science.gov (United States)

    Guillaume, O; Park, J; Monforte, X; Gruber-Blum, S; Redl, H; Petter-Puchner, A; Teuschl, A H

    2016-02-01

    Recent studies have demonstrated that combining cells with meshes prior to implantation successfully enhanced hernia repair. The idea is to create a biologic coating surrounding the mesh with autologous cells, before transplantation into the patient. However, due to the lack of a prompt and robust cell adhesion to the meshes, extensive in vitro cultivation is required to obtain a homogenous cell layer covering the mesh. In this context, the objective of this publication is to manufacture meshes made of silk fibres and to enhance the cytoadhesion and cytocompatibility of the biomaterial by surface immobilization of a pro-adhesive wheat germ agglutinin (lectin WGA). We first investigated the affinity between the glycoprotein WGA and cells, in solution and then after covalent immobilization of WGA on silk films. Then, we manufactured meshes made of silk fibres, tailored them with WGA grafting and finally evaluated the cytocompatibility and the inflammatory response of silk and silk-lectin meshes compared to common polypropylene mesh, using fibroblasts and peripheral blood mononuclear cells, respectively. The in vitro experiments revealed that the cytocompatibility of silk can be enhanced by surface immobilization with lectin WGA without exhibiting negative response in terms of pro-inflammatory reaction. Grafting lectin to silk meshes could bring advantages to facilitate cell-coating of meshes prior to implantation, which is an imperative prerequisite for abdominal wall tissue regeneration using cell-based therapy.

  1. Hematopoietic tissue repair under chronic low daily dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.

    1994-12-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3{minus}26.3 cGy d{sup {minus}1}). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 & 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity.

  2. Inhibition of DNA repair by Pentoxifylline and related methylxanthine derivatives.

    Science.gov (United States)

    Böhm, Lothar; Roos, Wynand Paul; Serafin, Antonio Mendes

    2003-11-15

    The methylxanthine drug Pentoxifylline is reviewed for new properties which have emerged only relatively recently and for which clinical applications can be expected. After a summary on the established systemic effects of Pentoxifylline on the microcirculation and reduction of tumour anoxia, the role of the drug in the treatment of vasoocclusive disorders, cerebral ischemia, infectious diseases, septic shock and acute respiratory distress, the review focuses on another level of drug action which is based on in vitro observations in a variety of cell lines. Pentoxifylline and the related drug Caffeine are known radiosensitizers especially in p53 mutant cells. The explanation that the drug abrogates the G2 block and shortens repair in G2 by promoting early entry into mitosis is not anymore tenable because enhancement of radiotoxicity requires presence of the drug during irradiation and fails when the drug is added after irradiation at the G2 maximum. Repair assays by measurement of recovery ratios and by delayed plating experiments indeed strongly suggested a role in repair which is now confirmed for Pentoxifylline by constant field gel electrophoresis (CFGE) measurements and for Pentoxifylline and for Caffeine by use of a variety of repair mutants. The picture now emerging shows that Caffeine and Pentoxifylline inhibit homologous recombination by targeting members of the PIK kinase family (ATM and ATR) which facilitate repair in G2. Pentoxifylline induced repair inhibition between irradiation dose fractions to counter interfraction repair has been successfully applied in a model for stereotactic surgery. Another realistic avenue of application of Pentoxifylline in tumour therapy comes from experiments which show that repair events in G2 can be targeted directly by addition of cytotoxic drugs and Pentoxifylline at the G2 maximum. Under these conditions massive dose enhancement factors of up to 80 have been observed suggesting that it may be possible to realise

  3. Repairing Learned Knowledge Using Experience

    Science.gov (United States)

    1990-05-01

    It necessar and Identify by’ 6109h nii be) learning precedent-based learning knowledge repair explanation-based learning near - miss groups 20. ABSTRACT...can a program use explanations to repair a recollection, preventing further misapplication? Near - Miss Groups Isolate Suspicious Relations If a metal...pail differs from a porcelain cup only in the position of handle attachment, then we would say that the pail is a near miss . Unfortunately, there are

  4. Current developments in cell- and biomaterial-based approaches for stroke repair.

    Science.gov (United States)

    Jendelová, Pavla; Kubinová, Šárka; Sandvig, Ioanna; Erceg, Slaven; Sandvig, Axel; Syková, Eva

    2016-01-01

    Stroke is one of the most devastating diseases and a leading cause of mortality worldwide. So far, clinical management of stroke involves surgical clot retrieval or thrombolytic treatment inducing reperfusion of the occluded vessels in the cerebral infarcted area, which is dependent on early intervention following insult. New treatment strategies involve the promotion of angiogenesis and neuroplasticity, stimulation of endogenous neurogenesis, remyelinization, and immunomodulation by means of cell transplantation and sustained drug delivery. This review describes different types of stem cells (endogenous and exogenous neural progenitors, pluripotent stem cell derivatives, mesenchymal stem cells [MSCs], olfactory ensheathing cells) and biomaterials, their routes of administration, means of noninvasive imaging, and the prerequisites and hurdles for the successful translation of the cell therapies to the clinic. Neural precursors (NPs) derived from pluripotent stem cells, unlike MSCs, can not only remodel the CNS by promoting neuroplasticity, angiogenesis, and immunomodulation, but also replace damaged cells. To transfer NPs into the clinic, step by step guidelines for researchers are identified and discussed.

  5. Recent advances in cell-based therapy for Parkinson disease

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Cooper, Oliver; Vinuela, Angel

    2008-01-01

    In this review, the authors discuss recent advances in the field of cell therapy for Parkinson disease (PD). They compare and contrast recent clinical trials using fetal dopaminergic neurons. They attribute differences in cell preparation techniques, cell type specification, and immunosuppression...... as reasons for variable outcome and for some of the side effects observed in these clinical trials. To address ethical, practical, and technical issues related to the use of fetal cell sources, alternative sources of therapeutic dopaminergic neurons are being developed. The authors describe the progress...... in enrichment and purification strategies of stem cell-derived dopaminergic midbrain neurons. They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease....

  6. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

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

    2011-01-01

    : 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......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...

  7. Lime-based repair mortars with water-repellent admixtures: laboratory durability assessment

    OpenAIRE

    Nunes, C.; Slížková, Z. (Zuzana)

    2015-01-01

    Conservation of architectural structures using lime binders is currently an important research topic aiming compatibility, durability and sustainability. In this study, lime (L) and lime-metakaolin (LM) mortars were prepared with the addition of water-repellent admixtures: linseed oil, stand oil and a silane based water-repellent. Experimental results demonstrate that oil imparts higher hydrophobicity to both L and LM mixtures. Durability was assessed through freeze-thaw and NaCl crystal...

  8. Environmental Assessment: Construction of Consolidated Fuel Overhaul and Repair Facility at Tinker Air Force Base, Oklahoma

    Science.gov (United States)

    2007-10-01

    the base, the Hennessey Group overlies the aquifer and acts as a confining layer because it is typical clay -rich, low-permeability shale. The...archaeological materials such as chipped ~·:one tools, pottery , bone, historic crockery, glass, metal items or building materials, this agency should be...materials such as chipped stone, tools, pottery , bone, historic crockery, glass, metal items or building materials, this agency should be contacted

  9. Cell-based therapies for cardiac repair : a meeting report on scientific observations and European regulatory viewpoints

    NARCIS (Netherlands)

    Schüssler-Lenz, Martina; Beuneu, Claire; Menezes-Ferreira, Margarida; Jekerle, Veronika; Bartunek, Jozef; Chamuleau, Steven; Celis, Patrick; Doevendans, Pieter; O'Donovan, Maura; Hill, Jonathan; Hystad, Marit; Jovinge, Stefan; Kyselovič, Ján; Lipnik-Stangelj, Metoda; Maciulaitis, Romaldas; Prasad, Krishna; Samuel, Anthony; Tenhunen, Olli; Tonn, Torsten; Rosano, Giuseppe; Zeiher, Andreas; Salmikangas, Paula

    2016-01-01

    In the past decade, novel cell-based products have been studied in patients with acute and chronic cardiac disease to assess whether these therapies are efficacious in improving heart function and preventing the development of end-stage heart failure. Cardiac indications studied include acute myocar

  10. Cell-based therapies for cardiac repair : a meeting report on scientific observations and European regulatory viewpoints

    NARCIS (Netherlands)

    Schüssler-Lenz, Martina; Beuneu, Claire; Menezes-Ferreira, Margarida; Jekerle, Veronika; Bartunek, Jozef; Chamuleau, Steven|info:eu-repo/dai/nl/236454161; Celis, Patrick; Doevendans, Pieter|info:eu-repo/dai/nl/164248366; O'Donovan, Maura; Hill, Jonathan; Hystad, Marit; Jovinge, Stefan; Kyselovič, Ján; Lipnik-Stangelj, Metoda; Maciulaitis, Romaldas; Prasad, Krishna; Samuel, Anthony; Tenhunen, Olli; Tonn, Torsten; Rosano, Giuseppe; Zeiher, Andreas; Salmikangas, Paula

    2016-01-01

    In the past decade, novel cell-based products have been studied in patients with acute and chronic cardiac disease to assess whether these therapies are efficacious in improving heart function and preventing the development of end-stage heart failure. Cardiac indications studied include acute myocar

  11. Disease Compass- a navigation system for disease knowledge based on ontology and linked data techniques.

    Science.gov (United States)

    Kozaki, Kouji; Yamagata, Yuki; Mizoguchi, Riichiro; Imai, Takeshi; Ohe, Kazuhiko

    2017-06-19

    Medical ontologies are expected to contribute to the effective use of medical information resources that store considerable amount of data. In this study, we focused on disease ontology because the complicated mechanisms of diseases are related to concepts across various medical domains. The authors developed a River Flow Model (RFM) of diseases, which captures diseases as the causal chains of abnormal states. It represents causes of diseases, disease progression, and downstream consequences of diseases, which is compliant with the intuition of medical experts. In this paper, we discuss a fact repository for causal chains of disease based on the disease ontology. It could be a valuable knowledge base for advanced medical information systems. We developed the fact repository for causal chains of diseases based on our disease ontology and abnormality ontology. This section summarizes these two ontologies. It is developed as linked data so that information scientists can access it using SPARQL queries through an Resource Description Framework (RDF) model for causal chain of diseases. We designed the RDF model as an implementation of the RFM for the fact repository based on the ontological definitions of the RFM. 1554 diseases and 7080 abnormal states in six major clinical areas, which are extracted from the disease ontology, are published as linked data (RDF) with SPARQL endpoint (accessible API). Furthermore, the authors developed Disease Compass, a navigation system for disease knowledge. Disease Compass can browse the causal chains of a disease and obtain related information, including abnormal states, through two web services that provide general information from linked data, such as DBpedia, and 3D anatomical images. Disease Compass can provide a complete picture of disease-associated processes in such a way that fits with a clinician's understanding of diseases. Therefore, it supports user exploration of disease knowledge with access to pertinent information

  12. Environmental Assessment: Construction of Consolidated Fuel Overhaul and Repair Facility at Tinker Air Force Base, Oklahoma

    Science.gov (United States)

    2007-10-01

    Historic Preservation Officer MH:bh Oklahoma Archeological Survey March 23, 2007 Trudi Logan Department of the Air Force 72 Air Base Wing (AFMC...Fox Larry Ci’l AETC CONS/LGCK; McKee John M Civ OC-ALC/FMA; King Thelma J Civ OC-ALC/FMC; Powell Paul A Civ 72 ABW/CECED; Powell Paul A Civ 72 ABW...L CIV OC-ALC/FMC Grimes Jim D Civ OC-ALC/FMC; Tomlinson Deborah L Civ OC-ALC/FMC; Fox Larry Civ AETC CONS/LGCK; McKee John M Civ OC-ALC/FMA; King

  13. In vivo and in vitro cellular response to PEG-based hydrogels for wound repair

    Science.gov (United States)

    Waldeck, Heather

    Biomaterials are continuously being explored as a means to support, improve, or influence wound healing processes. Understanding the determining factors controlling the host response to biomaterials is crucial in developing strategies to employ materials for biomedical uses. In order to evaluate the host response to poly(ethylene glycol) (PEG)-based hydrogels, both in vivo and in vitro studies were performed to determine its efficacy as a dermal wound treatment and to investigate the mechanisms controlling cell-material interaction, respectively. The results of an in vivo study using a full thickness wound in a rat model demonstrated that both soluble and immobilized bioactive factors could be incorporated into a PEG-based semi-interpenetrating network (sIPN) to enhance the rate and the quality of dermal wound healing. To gain a better understanding of the results observed in vivo, in vitro studies were then conducted to examine the dynamics and mechanisms of the cell-material interaction. Degradation of the sIPN was explored as an influential factor in both mediating cellular response and controlling solute transport from the material. As degradation through gelatin dissolution could be influenced by simple alterations to the material formulation, these results provide facile guidelines to control the delivery of high molecular weight compounds. Further investigation of the cellular response to PEG-based biomaterials focused on key factors influencing cell-material interaction. Specifically, the role of the beta1 integrin subunit and several serum proteins (TGF-aalpha, IL-1beta and PDGF-BB) in mediating cellular response was explored. As cell-material interactions are based on commonly occurring interfaces between cells and molecules of the native extracellular environment, these studies provided insight into the mechanisms controlling the observed cellular response. Finally, the inflammatory response of primary monocytes to biomaterials was examined. Monocytes

  14. Impact of aortic repair based on flow field computer simulation within the thoracic aorta.

    Science.gov (United States)

    Filipovic, Nenad; Milasinovic, Danko; Zdravkovic, Nebojsa; Böckler, Dittmar; von Tengg-Kobligk, Hendrik

    2011-03-01

    Purpose of this computational study is to examine the hemodynamic parameters of velocity fields and shear stress in the thoracic aorta with and without aneurysm, based on an individual patient case and virtual surgical intervention. These two cases, case I (with aneurysm) and II (without aneurysm), are analyzed by computational fluid dynamics. The 3D Navier-Stokes equations and the continuity equation are solved with an unsteady stabilized finite element method. The vascular geometries are reconstructed based on computed tomography angiography images to generate a patient-specific 3D finite element mesh. The input data for the flow waveforms are derived from MR phase contrast flow measurements of a patient before surgical intervention. The computed results show velocity profiles skewed towards the inner aortic wall for both cases in the ascending aorta and in the aortic arch, while in the descending aorta these velocity profiles are skewed towards the outer aortic wall. Computed streamlines indicate that flow separation occurs at the proximal edge of the aneurysm, i.e. computed flow enters the aneurysm in the distal region, and that there is essentially a single, slowly rotating, vortex within the aneurysm during most of the systole. In summary, after virtual surgical intervention in case II higher shear stress distribution along the descending aorta could be found, which may produce more healthy reactions in the endothelium and benefit of vascular reconstruction of an aortic aneurysm at this particular location.

  15. A situated reasoning architecture for space-based repair and replace tasks

    Science.gov (United States)

    Bloom, Ben; Mcgrath, Debra; Sanborn, Jim

    1989-01-01

    Space-based robots need low level control for collision detection and avoidance, short-term load management, fine-grained motion, and other physical tasks. In addition, higher level control is required to focus strategic decision making as missions are assigned and carried out. Reasoning and control must be responsive to ongoing changes in the environment. Research aimed at bridging the gap between high level artificial intelligence (AI) planning techniques and task-level robot programming for telerobotic systems is described. Situated reasoning is incorporated into AI and Robotics systems in order to coordinate a robot's activity within its environment. An integrated system under development in a component maintenance domain is described. It is geared towards replacing worn and/or failed Orbital Replacement Units (ORUs) designed for use aboard NASA's Space Station Freedom based on the collection of components available at a given time. High level control reasons in component space in order to maximize the number operational component-cells over time, while the task-level controls sensors and effectors, detects collisions, and carries out pick and place tasks in physical space. Situated reasoning is used throughout the system to cope with component failures, imperfect information, and unexpected events.

  16. Structural biology of disease-associated repetitive DNA sequences and protein-DNA complexes involved in DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, G.; Santhana Mariappan, S.V.; Chen, X.; Catasti, P.; Silks, L.A. III; Moyzis, R.K.; Bradbury, E.M.; Garcia, A.E.

    1997-07-01

    This project is aimed at formulating the sequence-structure-function correlations of various microsatellites in the human (and other eukaryotic) genomes. Here the authors have been able to develop and apply structure biology tools to understand the following: the molecular mechanism of length polymorphism microsatellites; the molecular mechanism by which the microsatellites in the noncoding regions alter the regulation of the associated gene; and finally, the molecular mechanism by which the expansion of these microsatellites impairs gene expression and causes the disease. Their multidisciplinary structural biology approach is quantitative and can be applied to all coding and noncoding DNA sequences associated with any gene. Both NIH and DOE are interested in developing quantitative tools for understanding the function of various human genes for prevention against diseases caused by genetic and environmental effects.

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

    Science.gov (United States)

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

    2013-01-01

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

  18. Eye muscle repair - discharge

    Science.gov (United States)

    ... 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 ...

  19. Ventral hernia repair

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007661.htm Ventral hernia repair To use the sharing features on this page, please enable JavaScript. Ventral hernia repair is surgery to repair a ventral hernia. ...

  20. Brain aneurysm repair

    Science.gov (United States)

    ... 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 ...

  1. [Inguinal and femoral hernia repair].

    Science.gov (United States)

    Geissler, B; Anthuber, M

    2011-05-01

    With an incidence of 200,000 new cases per year in Germany, inguinal hernia has a significant socioeconomic impact. The 2009 guidelines from the European Hernia Society established treatment recommendations. Hernia repair is based on reinforcing the posterior wall of the inguinal canal by suture or mesh repair by an anterior or posterior approach. Lightweight mesh reduces recurrence rates and is the treatment of choice even in primary hernias. Laparoscopic hernia repair is associated with specific risks but is superior in postoperative pain and earlier return to work.

  2. Recommendations for the repair, the lining or the strengthening of concrete slabs or pavements with bonded cement-based material overlays

    OpenAIRE

    Courard, Luc; Bissonnette, Benoît; Beushausen, Hans; Fowler,David; Trevino, Manuel; Alex, Vaysburd; Johan, Silfwerbrand

    2013-01-01

    The recommendations presented in this publication are inspired by the State of the Art Report edited by the RILEM technical committee TC 193 RLS Bonded cement-based material overlays for the repair, the lining or the strengthening of slabs and pavements. The objective is to lay out all the practical aspects to be considered in the design of concrete overlays: bonded concrete overlay process, assessment of the existing structure, surface preparation, overlay materials, design methods, construc...

  3. Photoinduced reductive repair of thymine glycol: implications for excess electron transfer through DNA containing modified bases.

    Science.gov (United States)

    Ito, Takeo; Kondo, Akiko; Terada, Satoru; Nishimoto, Sei-Ichi

    2006-08-23

    Photoinduced reduction of thymine glycol in oligodeoxynucleotides was investigated using either a reduced form of flavin adenine dinucleotide (FADH(-)) as an intermolecular electron donor or covalently linked phenothiazine (PTZ) as an intramolecular electron donor. Intermolecular electron donation from photoexcited flavin (FADH(-)) to free thymidine glycol generated thymidine in high yield, along with a small amount of 6-hydroxy-5,6-dihydrothymidine. In the case of photoreduction of 4-mer long single-stranded oligodeoxynucleotides containing thymine glycol by *FADH(-), the restoration yield of thymine was varied depending on the sequence of oligodeoxynucleotides. Time-resolved spectroscopic study on the photoreduction by laser-excited N,N-dimethylaniline (DMA) suggested elimination of a hydroxyl ion from the radical anion of thymidine glycol with a rate constant of approximately 10(4) s(-1) generates 6-hydroxy-5,6-dihydrothymidine (6-HOT(*)) as a key intermediate, followed by further reduction of 6-HOT(*) to thymidine or 6-hydroxy-5,6-dihydrothymdine (6-HOT). On the other hand, an excess electron injected into double-stranded DNA containing thymine glycol was not trapped at the lesion but was further transported along the duplex. Considering redox properties of the nucleobases and PTZ, competitive excess electron trapping at pyrimidine bases (thymine, T and cytosine, C) which leads to protonation of the radical anion (T(-)(*), C(-)(*)) or rapid back electron transfer to the radical cation of PTZ (PTZ(+)(*)), is presumably faster than elimination of the hydroxyl ion from the radical anion of thymine glycol in DNA.

  4. Cell-based technologies for Huntington's disease

    Directory of Open Access Journals (Sweden)

    Mônica Santoro Haddad

    Full Text Available ABSTRACT Huntington's disease (HD is a fatal genetic disorder, which causes the progressive breakdown of neurons in the human brain. HD deteriorates human physical and mental abilities over time and has no cure. Stem cell-based technologies are promising novel treatments, and in HD, they aim to replace lost neurons and/or to prevent neural cell death. Herein we discuss the use of human fetal tissue (hFT, neural stem cells (NSCs of hFT origin or embryonic stem cells (ESCs and induced pluripotent stem cells (IPSCs, in clinical and pre-clinical studies. The in vivo use of mesenchymal stem cells (MSCs, which are derived from non-neural tissues, will also be discussed. All these studies prove the potential of stem cells for transplantation therapy in HD, demonstrating cell grafting and the ability to differentiate into mature neurons, resulting in behavioral improvements. We claim that there are still many problems to overcome before these technologies become available for HD patient treatment, such as: a safety regarding the use of NSCs and pluripotent stem cells, which are potentially teratogenic; b safety regarding the transplantation procedure itself, which represents a risk and needs to be better studied; and finally c technical and ethical issues regarding cells of fetal and embryonic origin.

  5. Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor Tendon Repairs.

    Science.gov (United States)

    Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A

    2017-04-01

    The aim of the study was to compare biomechanical strength, repair times, and repair values for zone II core flexor tendon repairs. A total of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index through small finger and randomized into one of 5 repair groups: 4-stranded cross-stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double-stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided suture). Repairs were measured in situ and their repair times were measured. Tendons were linearly loaded to failure and multiple biomechanical values were measured. The repair value was calculated based on operating room costs, repair times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc statistical analysis were used to compare repair data. The braided cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the 4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to perform. The total repair value was the highest for braided cruciate ( P > .05) compared with all other repairs. Barbed suture did not outperform any repairs in any categories. The braided cruciate was the strongest of the tested flexor tendon repairs. The 2-mm gapping and maximum load to failure for this repair approached similar historical strength of other 6- and 8-stranded repairs. In this study, suture cost was negligible in the overall repair cost and should be not a determining factor in choosing a repair.

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

    Science.gov (United States)

    de Semir, David; Aran, Josep M

    2006-08-01

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

  7. Monte carlo simulation of base and nucleotide excision repair of clustered DNA damage sites. II. Comparisons of model predictions to measured data.

    Science.gov (United States)

    Semenenko, V A; Stewart, R D

    2005-08-01

    Clustered damage sites other than double-strand breaks (DSBs) have the potential to contribute to deleterious effects of ionizing radiation, such as cell killing and mutagenesis. In the companion article (Semenenko et al., Radiat. Res. 164, 180-193, 2005), a general Monte Carlo framework to simulate key steps in the base and nucleotide excision repair of DNA damage other than DSBs is proposed. In this article, model predictions are compared to measured data for selected low-and high-LET radiations. The Monte Carlo model reproduces experimental observations for the formation of enzymatic DSBs in Escherichia coli and cells of two Chinese hamster cell lines (V79 and xrs5). Comparisons of model predictions with experimental values for low-LET radiation suggest that an inhibition of DNA backbone incision at the sites of base damage by opposing strand breaks is active over longer distances between the damaged base and the strand break in hamster cells (8 bp) compared to E. coli (3 bp). Model estimates for the induction of point mutations in the human hypoxanthine guanine phosphoribosyl transferase (HPRT) gene by ionizing radiation are of the same order of magnitude as the measured mutation frequencies. Trends in the mutation frequency for low- and high-LET radiation are predicted correctly by the model. The agreement between selected experimental data sets and simulation results provides some confidence in postulated mechanisms for excision repair of DNA damage other than DSBs and suggests that the proposed Monte Carlo scheme is useful for predicting repair outcomes.

  8. Production, Purification, and Characterization of ¹⁵N-Labeled DNA Repair Proteins as Internal Standards for Mass Spectrometric Measurements.

    Science.gov (United States)

    Reddy, Prasad T; Jaruga, Pawel; Nelson, Bryant C; Lowenthal, Mark S; Jemth, Ann-Sofie; Loseva, Olga; Coskun, Erdem; Helleday, Thomas; Dizdaroglu, Miral

    2016-01-01

    Oxidatively induced DNA damage is caused in living organisms by a variety of damaging agents, resulting in the formation of a multiplicity of lesions, which are mutagenic and cytotoxic. Unless repaired by DNA repair mechanisms before DNA replication, DNA lesions can lead to genomic instability, which is one of the hallmarks of cancer. Oxidatively induced DNA damage is mainly repaired by base excision repair pathway with the involvement of a plethora of proteins. Cancer tissues develop greater DNA repair capacity than normal tissues by overexpressing DNA repair proteins. Increased DNA repair in tumors that removes DNA lesions generated by therapeutic agents before they became toxic is a major mechanism in the development of therapy resistance. Evidence suggests that DNA repair capacity may be a predictive biomarker of patient response. Thus, knowledge of DNA-protein expressions in disease-free and cancerous tissues may help predict and guide development of treatments and yield the best therapeutic response. Our laboratory has developed methodologies that use mass spectrometry with isotope dilution for the measurement of expression of DNA repair proteins in human tissues and cultured cells. For this purpose, full-length (15)N-labeled analogs of a number of human DNA repair proteins have been produced and purified to be used as internal standards for positive identification and accurate quantification. This chapter describes in detail the protocols of this work. The use of (15)N-labeled proteins as internal standards for the measurement of several DNA repair proteins in vivo is also presented.

  9. DiseaseConnect: a comprehensive web server for mechanism-based disease–disease connections

    Science.gov (United States)

    Liu, Chun-Chi; Tseng, Yu-Ting; Li, Wenyuan; Wu, Chia-Yu; Mayzus, Ilya; Rzhetsky, Andrey; Sun, Fengzhu; Waterman, Michael; Chen, Jeremy J. W.; Chaudhary, Preet M.; Loscalzo, Joseph; Crandall, Edward; Zhou, Xianghong Jasmine

    2014-01-01

    The DiseaseConnect (http://disease-connect.org) is a web server for analysis and visualization of a comprehensive knowledge on mechanism-based disease connectivity. The traditional disease classification system groups diseases with similar clinical symptoms and phenotypic traits. Thus, diseases with entirely different pathologies could be grouped together, leading to a similar treatment design. Such problems could be avoided if diseases were classified based on their molecular mechanisms. Connecting diseases with similar pathological mechanisms could inspire novel strategies on the effective repositioning of existing drugs and therapies. Although there have been several studies attempting to generate disease connectivity networks, they have not yet utilized the enormous and rapidly growing public repositories of disease-related omics data and literature, two primary resources capable of providing insights into disease connections at an unprecedented level of detail. Our DiseaseConnect, the first public web server, integrates comprehensive omics and literature data, including a large amount of gene expression data, Genome-Wide Association Studies catalog, and text-mined knowledge, to discover disease–disease connectivity via common molecular mechanisms. Moreover, the clinical comorbidity data and a comprehensive compilation of known drug–disease relationships are additionally utilized for advancing the understanding of the disease landscape and for facilitating the mechanism-based development of new drug treatments. PMID:24895436

  10. Patterns of prefrontal dysfunction in alcoholics with and without Korsakoff's syndrome, patients with Parkinson's disease, and patients with rupture and repair of the anterior communicating artery.

    Science.gov (United States)

    Dirksen, Courtney L; Howard, Julie A; Cronin-Golomb, Alice; Oscar-Berman, Marlene

    2006-09-01

    This study compared patterns of frontal-lobe dysfunction in alcoholics with Korsakoff's syndrome (KS: n = 9), non-Korsakoff alcoholics (AL: n = 28), patients with Parkinson's disease (PD: n = 18), and patients with rupture and repair of the anterior communicating artery (ACoA: n = 4) relative to healthy non-neurological control (NC) participants (n = 70). The tests administered were sensitive to functions of dorsolateral prefrontal and orbito-frontal subsystems. Measures included perseverative errors on the Wisconsin Card Sorting Test (WCST-pe), errors on object alternation (OA), errors on Trails B, number of words generated on the Controlled Oral Word Association Test (COWAT), and number of categories completed on the WCST (WCST-cc). KS patients were as impaired as AL participants on orbitofrontal measures and, on dorsolateral prefrontal measures, were impaired relative to AL participants, whose performance did not differ from controls. Patients with PD also were impaired on tests of orbitofrontal and dorsolateral prefrontal functioning but to a lesser extent than the KS patients. Moreover, most of the PD deficits were driven by the impaired performance of patients whose initial symptoms were on the right side of the body. The ACoA patients were significantly impaired on tests of orbitofrontal but not dorsolateral prefrontal functioning relative to the control group. Together, the results confirm different patterns of frontal-system impairments in patient groups having compromised frontal lobe functioning consequent to varying etiologies.

  11. Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair.

    Science.gov (United States)

    Zhang, Shuning; Ma, Xin; Yao, Kang; Zhu, Hong; Huang, Zheyong; Shen, Li; Qian, Juying; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

    2014-06-01

    Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.

  12. How to repair an episiotomy.

    Science.gov (United States)

    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 .

  13. DNA repair in Chromobacterium violaceum.

    Science.gov (United States)

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

    2004-03-31

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

  14. The role of base excision repair in the development of primary open angle glaucoma in the Polish population.

    Science.gov (United States)

    Cuchra, Magda; Markiewicz, Lukasz; Mucha, Bartosz; Pytel, Dariusz; Szymanek, Katarzyna; Szemraj, Janusz; Szaflik, Jerzy; Szaflik, Jacek P; Majsterek, Ireneusz

    2015-08-01

    Glaucoma is a leading cause of irreversible blindness in developing countries. Previous data have shown that progressive loss of human TM cells may be connected with chronic exposure to oxidative stress. This hypothesis may suggest a role of the base excision repair (BER) pathway of oxidative DNA damage in primary open angle glaucoma (POAG) patients. The aim of our study was to evaluate an association of BER gene polymorphism with a risk of POAG. Moreover, an association of clinical parameters was examined including cup disk ratio (c/d), rim area (RA) and retinal nerve fiber layer (RNFL) with glaucoma progression according to BER gene polymorphisms. Our research included 412 patients with POAG and 454 healthy controls. Gene polymorphisms were analyzed by PCR-RFLP. Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. The 399 Arg/Gln genotype of the XRCC1 gene (OR 1.38; 95% CI 1.02-1.89 p = 0.03) was associated with an increased risk of POAG occurrence. It was indicated that the 399 Gln/Gln XRCC1 genotype might increase the risk of POAG progression according to the c/d ratio (OR 1.67; 95% CI 1.07-2.61 P = 0.02) clinical parameter. Moreover, the association of VF factor with 148 Asp/Glu of APE1 genotype distribution and POAG progression (OR 2.25; 95% CI 1.30-3.89) was also found. Additionally, the analysis of the 324 Gln/His MUTYH polymorphism gene distribution in the patient group according to RNFL factor showed that it might decrease the progression of POAG (OR 0.47; 95% CI 0.30-0.82 P = 0.005). We suggest that the 399 Arg/Gln polymorphism of the XRCC1 gene may serve as a predictive risk factor of POAG.

  15. 基于Petri网的模型偏差域识别与模型修正%Petri Nets Based Recognition of Model Deviation Domains and Model Repair

    Institute of Scientific and Technical Information of China (English)

    杜玉越; 孙亚男; 刘伟

    2016-01-01

    Process mining techniques can be used to discover process models from event logs .Event logs and process model can be contrasted by conformance checking techniques . And conformance checking techniques can be used to detect the deviations between observed behaviors and process model .However ,existing techniques of process mining concern with discovering these deviations ,but not support to repair the process model easily and make the process model more related to the real process .So in this paper we propose a token‐based identification method of model deviation domains and a token‐based technique of model repair (static model repair and dynamic model repair ) through techniques of conformance checking and dynamic behaviors of workflow net .Model deviation domains can be identified effectively though the flow direction of token .We can repair process model according to model deviation domains .And we also can repair the real complex process accurately which has the structures of complicated circulation and choice .In this paper ,the effectiveness and the correctness of techniques are illustrated through contrast experiment and analysis with other techniques .%过程挖掘技术能够通过事件日志建立过程模型,一致性检测技术能够发现过程模型和观察行为间的偏差。然而,现有的过程挖掘技术着重于发现偏差,不易于修正偏差。因此,利用一致性检测技术和工作流网模型的动态特性,提出一种基于Petri网的模型偏差域识别方法和模型修正技术(静态模型修正和动态模型修正)。通过跟踪token流向,有效地识别模型偏差域,并对其进行修正,特别是能够正确修正具有循环结构、选择结构的复杂实际流程。最后,通过与其他方法的对比实验和分析,验证了本文方法的有效性和正确性。

  16. Mitral valve repair in acquired dextrocardia.

    Science.gov (United States)

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

    2015-10-01

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

  17. Targeted gene repair – in the arena

    OpenAIRE

    2003-01-01

    The development of targeted gene repair is under way and, despite some setbacks, shows promise as an alternative form of gene therapy. This approach uses synthetic DNA molecules to activate and direct the cell’s inherent DNA repair systems to correct inborn errors. The progress of this technique and its therapeutic potential are discussed in relation to the treatment of genetic diseases.

  18. Validation of the Algorithms for Base Exchangeable Repair Costs (Engine) and Base Exchangeable Modification Costs (Engine) for the Component Support Cost System (D160B).

    Science.gov (United States)

    2014-09-26

    REPORTING 010 03 NUMBER. ITEM IDENTIFICATION Oil 03 NOMENCLATURE . ITEM 012 03 PRICE. STANDARD INVENTORY 013 03 CODE, WEAPON SYSTEM SUPPORT 014 05 CODE...elements not used in calculation of standard depot repair prices (* sales prices"). ISI affirms the congruence of the definitions of repair prices as

  19. 基于规则的网站信息检测与修复方法%Rule-based website verification and repairing approach

    Institute of Scientific and Technical Information of China (English)

    朱菁菁; 杨小虎

    2011-01-01

    为了给网站管理员提供有效的、半自动化的工具,帮助他们处理一些可能预见的问题,提出了一种采用逻辑语言实现自动推理验证网站信息的半自动化方法,并用逻辑编程语言prolog实现.基于用户最初制定的规则来检测网站所发布的信息,同时做出相应的处理,力求能最大限度地自动修复、完整网页内容.实验结果验证了该方法的有效性.%Verifying and repairing website content for its correctness and completeness is a challenging research issue. In order to provide web administrators with an effective and semi-automatic mechanism to assist them in fixing every possible expected problem, an approach for semi-automatically is proposed to verify website information based on the logic programming, and is realized by logic programming language prolog. This approach based on the rules given by users at first, and will semi-automatically repair and audit website when any problem is captured and is dealt with. The result shows it give support to automated website verification and repair.

  20. Unilateral cleft lip/nose repair using an equal bows /straight line advancement technique - A preliminary report and postoperative symmetry-based anthropometry.

    Science.gov (United States)

    Hakim, Samer George; Aschoff, Horst Heinrich; Jacobsen, Hans-Christian; Sieg, Peter

    2014-04-01

    In the evolution of cleft lip repair there has been continuous attempt to minimize local trauma, improve lip and nasal appearance and, especially, prevent conspicuous scars. The surgical technique presented meets these criteria, resulting in an appropriate scar course in children with a specific philtral ridge shape. Postoperative digital anthropometry was performed in 18 patients who underwent unilateral cleft lip repair using the equal bows/straight line advancement technique and in matched healthy control individuals. Symmetry values were assessed for lip length, philtral ridge length, vermilion height, width of the alar base, nasocanthal length, circumference of the nostrils, nostril width and height in both cleft and control groups. Evaluation revealed no significant differences in the symmetry values between cleft patients and control group (lip length: p = 0.71, philtral ridge length: p = 0.52, vermilion height: p = 0.23, alar base width: p = 0.69, nasocanthal length: p = 0.25, nostril circumference: p = 0.17, nostril width: p = 0.34, nostril height: p = 0.33). Principles of cleft lip repair can be achieved using the described technique which provides adequate lip length and natural nasal appearance in patients with a parallel-shaped philtral ridge.

  1. DNA excision-repair defect of xeroderma pigmentosum prevents removal of a class of oxygen free radical-induced base lesions.

    Science.gov (United States)

    Satoh, M S; Jones, C J; Wood, R D; Lindahl, T

    1993-07-01

    Plasmid DNA was gamma-irradiated or treated with H2O2 in the presence of Cu2+ to generate oxygen free radical-induced lesions. Open circular DNA molecules were removed by ethidium bromide/CsCl density gradient centrifugation. The closed circular DNA fraction was treated with the Escherichia coli reagent enzymes endonuclease III (Nth protein) and Fpg protein. This treatment converted DNA molecules containing the major base lesions pyrimidine hydrates and 8-hydroxyguanine to a nicked form. Remaining closed circular DNA containing other oxygen radical-induced base lesions was used as a substrate for nucleotide excision-repair in a cell-free system. Extracts from normal human cells, but not extracts from xeroderma pigmentosum cells, catalyzed repair synthesis in this DNA. The repair defect in the latter extracts could be specifically corrected by in vitro complementation. The data suggest that accumulation of endogenous oxidative damage in cellular DNA from xeroderma pigmentosum patients contributes to the increased frequency of internal cancers and the neural degeneration occurring in serious cases of the syndrome.

  2. Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.

    Science.gov (United States)

    Oliveira, Marcela Silva; Carmona, Fabio; Vicente, Walter V A; Manso, Paulo H; Mata, Karina M; Celes, Mara Rúbia; Campos, Erica C; Ramos, Simone G

    2017-04-01

    Surgeries to correct congenital heart diseases are increasing in Brazil and worldwide. However, even with the advances in surgical techniques and perfusion, some cases, especially the more complex ones, can develop heart failure and death. A retrospective study of patients who underwent surgery for correction of congenital heart diseases with cardiopulmonary bypass (CPB) in a university tertiary-care hospital that died, showed infarction in different stages of evolution and scattered microcalcifications in the myocardium, even without coronary obstruction. CPB is a process routinely used during cardiac surgery for congenital heart disease. However, CPB has been related to increased endogenous catecholamines that can lead to major injuries in cardiomyocytes. The mechanisms involved are not completely understood. The aim of this study was to evaluate the alterations induced in the β-adrenergic receptors and GRK-2 present in atrial cardiomyocytes of infants with congenital heart disease undergoing surgical repair with CPB and correlate the alterations with functional and biochemical markers of ischemia/myocardial injury. The study consisted of right atrial biopsies of infants undergoing surgical correction in HC-FMRPUSP. Thirty-three cases were selected. Atrial biopsies were obtained at the beginning of CPB (group G1) and at the end of CPB (group G2). Real-time PCR, Western blotting, and immunofluorescence analysis were conducted to evaluate the expression of β1, β2-adrenergic receptors, and GRK-2 in atrial myocardium. Cardiac function was evaluated by echocardiography and biochemical analysis (N-terminal pro-brain natriuretic peptide (NT-ProBNP), lactate, and cardiac troponin I). We observed an increase in serum lactate, NT-proBNP, and troponin I at the end of CPB indicating tissue hypoxia/ischemia. Even without major clinical consequences in cardiac function, these alterations were followed by a significant increase in gene expression of β1 and β2 receptors and

  3. Alkylation base damage is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease.

    Directory of Open Access Journals (Sweden)

    Wenjian Ma

    2011-04-01

    Full Text Available DNA double-strand breaks (DSBs are potent sources of genome instability. While there is considerable genetic and molecular information about the disposition of direct DSBs and breaks that arise during replication, relatively little is known about DSBs derived during processing of single-strand lesions, especially for the case of single-strand breaks (SSBs with 3'-blocked termini generated in vivo. Using our recently developed assay for detecting end-processing at random DSBs in budding yeast, we show that single-strand lesions produced by the alkylating agent methyl methanesulfonate (MMS can generate DSBs in G2-arrested cells, i.e., S-phase independent. These derived DSBs were observed in apn1/2 endonuclease mutants and resulted from aborted base excision repair leading to 3' blocked single-strand breaks following the creation of abasic (AP sites. DSB formation was reduced by additional mutations that affect processing of AP sites including ntg1, ntg2, and, unexpectedly, ogg1, or by a lack of AP sites due to deletion of the MAG1 glycosylase gene. Similar to direct DSBs, the derived DSBs were subject to MRX (Mre11, Rad50, Xrs2-determined resection and relied upon the recombinational repair genes RAD51, RAD52, as well as on the MCD1 cohesin gene, for repair. In addition, we identified a novel DNA intermediate, detected as slow-moving chromosomal DNA (SMD in pulsed field electrophoresis gels shortly after MMS exposure in apn1/2 cells. The SMD requires nicked AP sites, but is independent of resection/recombination processes, suggesting that it is a novel structure generated during processing of 3'-blocked SSBs. Collectively, this study provides new insights into the potential consequences of alkylation base damage in vivo, including creation of novel structures as well as generation and repair of DSBs in nonreplicating cells.

  4. New insights in the removal of the hydantoins, oxidation product of pyrimidines, via the base excision and nucleotide incision repair pathways.

    Science.gov (United States)

    Redrejo-Rodríguez, Modesto; Saint-Pierre, Christine; Couve, Sophie; Mazouzi, Abdelghani; Ishchenko, Alexander A; Gasparutto, Didier; Saparbaev, Murat

    2011-01-01

    Oxidative damage to DNA, if not repaired, can be both miscoding and blocking. These genetic alterations can lead to mutations and/or cell death, which in turn cause cancer and aging. Oxidized DNA bases are substrates for two overlapping repair pathways: base excision (BER) and nucleotide incision repair (NIR). Hydantoin derivatives such as 5-hydroxyhydantoin (5OH-Hyd) and 5-methyl-5-hydroxyhydantoin (5OH-5Me-Hyd), major products of cytosine and thymine oxidative degradation pathways, respectively, have been detected in cancer cells and ancient DNA. Hydantoins are blocking lesions for DNA polymerases and excised by bacterial and yeast DNA glycosylases in the BER pathway. However little is known about repair of pyrimidine-derived hydantoins in human cells. Here, using both denaturing PAGE and MALDI-TOF MS analyses we report that the bacterial, yeast and human AP endonucleases can incise duplex DNA 5' next to 5OH-Hyd and 5OH-5Me-Hyd thus initiating the NIR pathway. We have fully reconstituted the NIR pathway for these lesions in vitro using purified human proteins. Depletion of Nfo in E. coli and APE1 in HeLa cells abolishes the NIR activity in cell-free extracts. Importantly, a number of redundant DNA glycosylase activities can excise hydantoin residues, including human NTH1, NEIL1 and NEIL2 and the former protein being a major DNA glycosylase activity in HeLa cells extracts. This study demonstrates that both BER and NIR pathways can compete and/or back-up each other to remove hydantoin DNA lesions in vivo.

  5. New insights in the removal of the hydantoins, oxidation product of pyrimidines, via the base excision and nucleotide incision repair pathways.

    Directory of Open Access Journals (Sweden)

    Modesto Redrejo-Rodríguez

    Full Text Available BACKGROUND: Oxidative damage to DNA, if not repaired, can be both miscoding and blocking. These genetic alterations can lead to mutations and/or cell death, which in turn cause cancer and aging. Oxidized DNA bases are substrates for two overlapping repair pathways: base excision (BER and nucleotide incision repair (NIR. Hydantoin derivatives such as 5-hydroxyhydantoin (5OH-Hyd and 5-methyl-5-hydroxyhydantoin (5OH-5Me-Hyd, major products of cytosine and thymine oxidative degradation pathways, respectively, have been detected in cancer cells and ancient DNA. Hydantoins are blocking lesions for DNA polymerases and excised by bacterial and yeast DNA glycosylases in the BER pathway. However little is known about repair of pyrimidine-derived hydantoins in human cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, using both denaturing PAGE and MALDI-TOF MS analyses we report that the bacterial, yeast and human AP endonucleases can incise duplex DNA 5' next to 5OH-Hyd and 5OH-5Me-Hyd thus initiating the NIR pathway. We have fully reconstituted the NIR pathway for these lesions in vitro using purified human proteins. Depletion of Nfo in E. coli and APE1 in HeLa cells abolishes the NIR activity in cell-free extracts. Importantly, a number of redundant DNA glycosylase activities can excise hydantoin residues, including human NTH1, NEIL1 and NEIL2 and the former protein being a major DNA glycosylase activity in HeLa cells extracts. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that both BER and NIR pathways can compete and/or back-up each other to remove hydantoin DNA lesions in vivo.

  6. Alkylation base damage is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease.

    Directory of Open Access Journals (Sweden)

    Wenjian Ma

    2011-04-01

    Full Text Available DNA double-strand breaks (DSBs are potent sources of genome instability. While there is considerable genetic and molecular information about the disposition of direct DSBs and breaks that arise during replication, relatively little is known about DSBs derived during processing of single-strand lesions, especially for the case of single-strand breaks (SSBs with 3'-blocked termini generated in vivo. Using our recently developed assay for detecting end-processing at random DSBs in budding yeast, we show that single-strand lesions produced by the alkylating agent methyl methanesulfonate (MMS can generate DSBs in G2-arrested cells, i.e., S-phase independent. These derived DSBs were observed in apn1/2 endonuclease mutants and resulted from aborted base excision repair leading to 3' blocked single-strand breaks following the creation of abasic (AP sites. DSB formation was reduced by additional mutations that affect processing of AP sites including ntg1, ntg2, and, unexpectedly, ogg1, or by a lack of AP sites due to deletion of the MAG1 glycosylase gene. Similar to direct DSBs, the derived DSBs were subject to MRX (Mre11, Rad50, Xrs2-determined resection and relied upon the recombinational repair genes RAD51, RAD52, as well as on the MCD1 cohesin gene, for repair. In addition, we identified a novel DNA intermediate, detected as slow-moving chromosomal DNA (SMD in pulsed field electrophoresis gels shortly after MMS exposure in apn1/2 cells. The SMD requires nicked AP sites, but is independent of resection/recombination processes, suggesting that it is a novel structure generated during processing of 3'-blocked SSBs. Collectively, this study provides new insights into the potential consequences of alkylation base damage in vivo, including creation of novel structures as well as generation and repair of DSBs in nonreplicating cells.

  7. Treatment and Controversies in Paraesophageal Hernia Repair

    Directory of Open Access Journals (Sweden)

    P. Marco eFisichella

    2015-04-01

    Full Text Available Background: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair.Methods: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron deficiency anemia, Nissen fundoplication, sac excision, mesh, mesh repair. Results: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.

  8. Location of recurrent groin hernias at TEP after Lichtenstein repair: a study based on the Swedish Hernia Register.

    Science.gov (United States)

    Bringman, S; Holmberg, H; Österberg, J

    2016-06-01

    To investigate which type of hernia that has the highest risk of a recurrence after a primary Lichtenstein repair. Male patients operated on with a Lichtenstein repair for a primary direct or indirect inguinal hernia and with a TEP for a later recurrence, with both operations recorded in the Swedish Hernia Register (SHR), were included in the study. The study period was 1994-2014. Under the study period, 130,037 male patients with a primary indirect or direct inguinal hernia were operated on with a Lichtenstein repair. A second operation in the SHR was registered in 2236 of these patients (reoperation rate 1.7 %). TEP was the chosen operation in 737 in this latter cohort. The most likely location for a recurrence was the same as the primary location. If the recurrences change location from the primary place, we recognized that direct hernias had a RR of 1.51 to having a recurrent indirect hernia compared to having a direct recurrence after an indirect primary hernia repair. Recurrent hernias after Lichtenstein are more common on the same location as the primary one, compared to changing the location.

  9. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents

    DEFF Research Database (Denmark)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier

    2015-01-01

    BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas o...

  10. Cardiac MRI in children and adolescents who have undergone surgical repair of right-sided congenital heart disease. Automated left ventricular volumes and function analysis and effects of different manual adjustments

    Energy Technology Data Exchange (ETDEWEB)

    Rompel, O.; Janka, R.; May, M.S.; Lell, M.M.; Uder, M.; Hammon, M. [University Hospital Erlangen (Germany). Dept. of Radiology; Gloeckler, M.; Dittrich, S. [University Hospital Erlangen (Germany). Dept. of Pediatric Cardiology; Cesnjevar, R. [University Hospital Erlangen (Germany). Dept. of Pediatric Cardiac Surgery

    2015-12-15

    To evaluate automated segmentation and the effects of different manual adjustments regarding left ventricular parameter quantification in cardiac magnetic resonance (MR) data on children and adolescents who have undergone surgical repair of right-sided congenital heart disease (CHD). Dedicated software (syngo.via, Siemens AG) was used to automatically segment and/or manually adjust the end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), myocardial mass (MM) and ejection fraction (EF) before/after manual apex/base adjustment (ADJ-step 1) and after manual apex/base/myocardial contour adjustment (ADJ-step 2; reference standard). MR data of 40 patients (13.1 ± 3.1y, 4-17y) with repaired CHD with decreased pulmonary blood flow (CHD-DPBF) were evaluated. Intra- and inter-rater reliability was determined for 10 randomly selected patients. The software correctly detected the left ventricle in 38/40 (95 %) patients. EDV after automated segmentation: 119.1 ± 44.0ml; after ADJ-step 1: 115.8 ± 39.5 ml; after ADJ-step 2: 116.2 ± 39.4 ml. The corresponding results for ESV were 52.0 ± 18.5/49.6 ± 16.9/49.7 ± 16.4 ml; for SV 67.1 ± 28.5/66.2 ± 25.4/66.5 ± 25.5 ml; for EF 55.5 ± 7.3/56.7 ± 6.6/56.7 ± 6.3%; for MM 83.7 ± 35.9/76.2 ± 28.3/74.6 ± 27.2 g. Significant differences were found for ESV/MM/EF comparing the automated segmentation results with these after ADJ-step 1 and ADJ-step 2. No significant differences were found when comparing all results of ADJ-step 1 and ADJ-step 2 or when comparing EDV/SV results. Intra- and inter-rater reliability was excellent. The mean time effort was 63.4 ± 6.9 s for the automated segmentation, 74.2 ± 8.9 s for ADJ-step 1 and 269.5 ± 39.4 s for ADJ-step 2. Automated left ventricular volumes and function analysis in children and adolescents with surgically treated CHD proved to be feasible with excellent intra- and inter-rater reliability. Automated segmentation with manual apex/base adjustment provided

  11. Patterns of prefrontal dysfunction in alcoholics with and without Korsakoff’s syndrome, patients with Parkinson’s disease, and patients with rupture and repair of the anterior communicating artery

    OpenAIRE

    Dirksen, Courtney L; Howard, Julie A.; Cronin-Golomb, Alice; Oscar-Berman, Marlene

    2006-01-01

    This study compared patterns of frontal-lobe dysfunction in alcoholics with Korsakoff’s syndrome (KS: n = 9), non-Korsakoff alcoholics (AL: n = 28), patients with Parkinson’s disease (PD: n = 18), and patients with rupture and repair of the anterior communicating artery (ACoA: n = 4) relative to healthy non-neurological control (NC) participants (n = 70). The tests administered were sensitive to functions of dorsolateral prefrontal and orbito-frontal subsystems. Measures included perseverativ...

  12. Risk of Morbidity, Mortality, and Recurrence After Parastomal Hernia Repair

    DEFF Research Database (Denmark)

    Helgstrand, Frederik; Rosenberg, Jacob; Kehlet, Henrik

    2013-01-01

    Surgical outcome results after repair for parastomal hernia are sparsely reported and based on small-scale studies.......Surgical outcome results after repair for parastomal hernia are sparsely reported and based on small-scale studies....

  13. Mitochondrial DNA repair: a novel therapeutic target for heart failure.

    Science.gov (United States)

    Marín-García, José

    2016-09-01

    Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS) and Ca(2+) handling to stress responses, cell survival and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular, cancer, premature aging and cardiovascular diseases (CVD), including myocardial ischemia, cardiomyopathy and heart failure (HF). Mitochondria contain their own genome organized into DNA-protein complexes, called "mitochondrial nucleoids," along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription and repair. Although the mammalian organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to various types of mtDNA damage. These include accumulation of mtDNA point mutations and/or deletions and decreased mtDNA copy number, which will impair mitochondrial function and finally, may lead to CVD including HF.

  14. Cancer TARGETases: DSB repair as a pharmacological target.

    Science.gov (United States)

    Samadder, Pounami; Aithal, Rakesh; Belan, Ondrej; Krejci, Lumir

    2016-05-01

    Cancer is a disease attributed to the accumulation of DNA damages due to incapacitation of DNA repair pathways resulting in genomic instability and a mutator phenotype. Among the DNA lesions, double stranded breaks (DSBs) are the most toxic forms of DNA damage which may arise as a result of extrinsic DNA damaging agents or intrinsic replication stress in fast proliferating cancer cells. Accurate repair of DSBs is therefore paramount to the cell survival, and several classes of proteins such as kinases, nucleases, helicases or core recombinational proteins have pre-defined jobs in precise execution of DSB repair pathways. On one hand, the proper functioning of these proteins ensures maintenance of genomic stability in normal cells, and on the other hand results in resistance to various drugs employed in cancer therapy and therefore presents a suitable opportunity for therapeutic targeting. Higher relapse and resistance in cancer patients due to non-specific, cytotoxic therapies is an alarming situation and it is becoming more evident to employ personalized treatment based on the genetic landscape of the cancer cells. For the success of personalized treatment, it is of immense importance to identify more suitable targetable proteins in DSB repair pathways and also to explore new synthetic lethal interactions with these pathways. Here we review the various alternative approaches to target the various protein classes termed as cancer TARGETases in DSB repair pathway to obtain more beneficial and selective therapy.

  15. Biomarker-based dissection of neurodegenerative diseases.

    Science.gov (United States)

    Olsson, Bob; Zetterberg, Henrik; Hampel, Harald; Blennow, Kaj

    2011-12-01

    The diagnosis of neurodegenerative diseases within neurology and psychiatry are hampered by the difficulty in getting biopsies and thereby validating the diagnosis by pathological findings. Biomarkers for other types of disease have been readily adopted into the clinical practice where for instance troponins are standard tests when myocardial infarction is suspected. However, the use of biomarkers for neurodegeneration has not been fully incorporated into the clinical routine. With the development of cerebrospinal fluid (CSF) biomarkers that reflect pathological events within the central nervous system (CNS), important clinical diagnostic tools are becoming available. This review summarizes the most promising biomarker candidates that may be used to monitor different types of neurodegeneration and protein inclusions, as well as different types of metabolic changes, in living patients in relation to the clinical phenotype and disease progression over time. Our aim is to provide the reader with an updated lexicon on currently available biomarker candidates, how far they have come in development and how well they reflect pathogenic processes in different neurodegenerative diseases. Biomarkers for specific pathogenetic processes would also be valuable tools both to study disease pathogenesis directly in patients and to identify and monitor the effect of novel treatment strategies.

  16. Base excision repair efficiency and mechanism in nuclear extracts are influenced by the ratio between volume of nuclear extraction buffer and nuclei-Implications for comparative studies

    DEFF Research Database (Denmark)

    Akbari, Mansour; Krokan, Hans E

    2012-01-01

    The base excision repair (BER) pathway corrects many different DNA base lesions and is important for genomic stability. The mechanism of BER cannot easily be investigated in intact cells and therefore in vitro methods that reflect the in vivo processes are in high demand. Reconstitution of BER...... using purified proteins essentially mirror properties of the proteins used, and does not necessarily reflect the mechanism as it occurs in the cell. Nuclear extracts from cultured cells have the capacity to carry out complete BER and can give important information on the mechanism. Furthermore...

  17. A Self-repairing Minefield Strategy Based on Intelligent Agent%基于智能代理的雷场自修复策略

    Institute of Scientific and Technical Information of China (English)

    梁聪聪; 焦国太; 张可; 陈建文

    2011-01-01

    This paper presented a new strategy based on intelligent agent for the problem of minefield inefficient self-repairing which caused by node multiple jumps. This strategy used distributed algorithm and adopted intelligent agent technology,each node was an intelligent agent in the minefield, using "blackboard model" message transfer mechanism to complete information fusion, produced a minefield self-repairing strategy of strategy driving and multiple nodes collaboration. Simulation results showed that this strategy could make a rapid response to minefield gap, and plan a global repairing, which averted node multiple jumps.%针对多次跳跃引起的雷场自修复效率问题,提出一种基于智能代理(Agent)的雷场自修复策略.该策略采用分布式算法,引入智能Agent体系,将雷场每个节点看做一个智能Agent,利用“黑板模型”消息传递机制进行信息融合,形成了一种以策略驱动Agent,多Agent节点协作的自修复策略.仿真结果表明:该修复策略能对缺口信息作出快速反应,进行全局规划修复,避免了修复节点的多次跳跃.

  18. Cutoff value of Japanese Orthopaedic Association shoulder score in patients with rotator cuff repair: Based on the University of California at Los Angeles shoulder score.

    Science.gov (United States)

    Imai, Takaki; Gotoh, Masafumi; Tokunaga, Tsuyoshi; Kawakami, Jyunichi; Mitsui, Yasuhiro; Fukuda, Keiji; Ogino, Misa; Okawa, Takahiro; Shiba, Naoto

    2017-05-01

    The Japanese Orthopaedic Association shoulder score cutoff values were calculated in patients with rotator cuff repair using the University of California at Los Angeles shoulder score. Overall, 175 patients with rotator cuff repair were subjects in this study. The University of California at Los Angeles and Japanese Orthopaedic Association shoulder scores were evaluated before surgery and at 3, 6, 9, and 12 months after surgery. The cutoff value of the Japanese Orthopaedic Association shoulder score was determined using the 4-stage criteria of the University of California at Los Angeles shoulder score and a University of California at Los Angeles shoulder score of 28 points, which is the boundary between an excellent/good group and a fair/poor group. Both the JOA shoulder and UCLA shoulder scores showed significant improvement at 6, 9, and 12 months from the preoperative scores (p values of the two scores (r = 0.85, p value of the Japanese Orthopaedic Association shoulder score based on the highest accuracy from receiver operating characteristic curve analysis was 83 points. A Japanese Orthopaedic Association shoulder score cutoff value of 83 was equivalent to a University of California at Los Angeles shoulder score cutoff value of 28 for distinguishing between excellent/good and fair/poor outcomes after rotator cuff repair. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  19. Human ribosomal protein S3 interacts with DNA base excision repair proteins hAPE/Ref-1 and hOGG1.

    Science.gov (United States)

    Hegde, Vijay; Wang, Mu; Deutsch, Walter A

    2004-11-09

    The human ribosomal protein S3 (hS3) possesses associated activities that suggest alternative roles beyond its participation in protein translation. For example, it is capable of cleaving apurinic/apyrimidinic (AP) DNA via a beta-elimination reaction, an activity that is missing in partially purified extracts of xeroderma pigmentosum group-D fibroblasts. In a recent study, we showed by surface plasmon resonance (SPR) that hS3 also has a very high apparent binding affinity for 7,8-dihydro-8-oxoguanine (8-oxoG) and AP sites in DNA. Using the same SPR technology, it is shown here that hS3 positively interacts with the human base excision repair (BER) enzymes N-glycosylase/AP lyase OGG1 and APE/Ref-1. Using a DNA substrate that allows for the detection of 8-oxoG repair, we also show that hOGG1 N-glycosylase activity becomes increasingly more robust in the presence of hS3. Human S3 was found to co-immunoprecipitate with both hOGG1 and APE/Ref-1, indicating that these proteins physically interact with one another. These results raise the possibility that hS3 not only functions as a ribosomal protein but, in addition, may influence repair activities at sites of DNA damage.

  20. Bypass of a 5',8-cyclopurine-2'-deoxynucleoside by DNA polymerase β during DNA replication and base excision repair leads to nucleotide misinsertions and DNA strand breaks.

    Science.gov (United States)

    Jiang, Zhongliang; Xu, Meng; Lai, Yanhao; Laverde, Eduardo E; Terzidis, Michael A; Masi, Annalisa; Chatgilialoglu, Chryssostomos; Liu, Yuan

    2015-09-01

    5',8-Cyclopurine-2'-deoxynucleosides including 5',8-cyclo-dA (cdA) and 5',8-cyclo-dG (cdG) are induced by hydroxyl radicals resulting from oxidative stress such as ionizing radiation. 5',8-cyclopurine-2'-deoxynucleoside lesions are repaired by nucleotide excision repair with low efficiency, thereby leading to their accumulation in the human genome and lesion bypass by DNA polymerases during DNA replication and base excision repair (BER). In this study, for the first time, we discovered that DNA polymerase β (pol β) efficiently bypassed a 5'R-cdA, but inefficiently bypassed a 5'S-cdA during DNA replication and BER. We found that cell extracts from pol β wild-type mouse embryonic fibroblasts exhibited significant DNA synthesis activity in bypassing a cdA lesion located in replication and BER intermediates. However, pol β knock-out cell extracts exhibited little DNA synthesis to bypass the lesion. This indicates that pol β plays an important role in bypassing a cdA lesion during DNA replication and BER. Furthermore, we demonstrated that pol β inserted both a correct and incorrect nucleotide to bypass a cdA at a low concentration. Nucleotide misinsertion was significantly stimulated by a high concentration of pol β, indicating a mutagenic effect induced by pol β lesion bypass synthesis of a 5',8-cyclopurine-2'-deoxynucleoside. Moreover, we found that bypass of a 5'S-cdA by pol β generated an intermediate that failed to be extended by pol β, resulting in accumulation of single-strand DNA breaks. Our study provides the first evidence that pol β plays an important role in bypassing a 5',8-cyclo-dA during DNA replication and repair, as well as new insight into mutagenic effects and genome instability resulting from pol β bypassing of a cdA lesion.

  1. DNA repair. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Setlow, R.

    1978-01-01

    Some topics discussed are as follows: difficulty in extrapolating data from E. coli to mammalian systems; mutations caused by UV-induced changes in DNA; mutants deficient in excision repair; other postreplication mechanisms; kinds of excision repair systems; detection of repair by biochemical or biophysical means; human mutants deficient in repair; mutagenic effects of UV on XP cells; and detection of UV-repair defects among XP individuals. (HLW)

  2. Biologics for tendon repair.

    Science.gov (United States)

    Docheva, Denitsa; Müller, Sebastian A; Majewski, Martin; Evans, Christopher H

    2015-04-01

    Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

  3. Use of nerve conduits for peripheral nerve injury repair A Web of Science-based literature analysis

    Institute of Scientific and Technical Information of China (English)

    Jinniang Nan; Xuguang Hu; Hongxiu Li; Xiaonong Zhang; Renjing Piao

    2012-01-01

    OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair.SELECTION CRITERIA: Inclusion criteria: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. Exclusion criteria: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers.MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers.CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

  4. Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium

    Science.gov (United States)

    Li, Jun; Zhu, Kai; Yang, Shan; Wang, Yulin; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury. PMID:25767192

  5. Robot based three-dimensional welding for jet engine blade repair and rapid prototyping of small components

    Science.gov (United States)

    Thukaram, Santosh Kumar

    Aero engines are made up of a large number of blades which are subject to wear and damage. They are expensive and must be repaired wherever possible. Engines also have small components which are required in small numbers that need to be developed rapidly. The first part of this research work focuses on developing a robust automated blade repair method using robotic welding. Optimal weld parameters were developed for build-up of edges having different thicknesses. Samples with varying Current and varying travel speed were produced and their micro hardness values were compared. Blade profiles were welded upon. The second part involves a methodology for producing small components using rapid prototyping (RP) techniques. This part involves use of 3D robotic welding for layered manufacturing. Tensile samples produced using the metal RP method were tested and results were found to be well above the minimum cast specifications for the given material.

  6. Constraint satisfaction and optimization for space station short-term mission planning based on an iterative conflict-repair method

    Science.gov (United States)

    Bu, Hui-Jiao; Zhang, Jin; Luo, Ya-Zhong

    2016-10-01

    This article studies the optimization of space station short-term mission planning (STMP) problems. The domain knowledge including description and the concept definitions of the STMP problem are presented, an STMP constraint satisfaction model is developed, and then an iterative conflict-repair method with the resolving strategies is proposed to satisfy complicated constraints. A genetic algorithm (GA) is adopted to optimize the STMP problem. The proposed approach is evaluated using a test case with 15 missions, 13 devices and three astronauts. The results show that the established STMP constraint satisfaction model is effective, and the iterative conflict-repair method can make the plan satisfy all constraints considered and can effectively improve the optimization performance of the GA.

  7. Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium

    OpenAIRE

    Li, Jun; Zhu, Kai; Yang, Shan; WANG, YULIN; Guo, Changfa; Yin, Kanhua; Wang, Chunsheng; Lai, Hao

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothe...

  8. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mayara H. Paula

    2016-02-01

    Full Text Available BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5; 1.96 (SD=0.56 and 1.65 (SD=0.52; 1.51 (SD=0.62, respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings.

  9. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial.

    Science.gov (United States)

    Paula, Mayara H; Barbosa, Rafael I; Marcolino, Alexandre M; Elui, Valéria M C; Rosén, Birgitta; Fonseca, Marisa C R

    2016-01-01

    Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings.

  10. Early sensory re-education of the hand after peripheral nerve repair based on mirror therapy: a randomized controlled trial

    Science.gov (United States)

    Paula, Mayara H.; Barbosa, Rafael I.; Marcolino, Alexandre M.; Elui, Valéria M. C.; Rosén, Birgitta; Fonseca, Marisa C. R.

    2016-01-01

    BACKGROUND: Mirror therapy has been used as an alternative stimulus to feed the somatosensory cortex in an attempt to preserve hand cortical representation with better functional results. OBJECTIVE: To analyze the short-term functional outcome of an early re-education program using mirror therapy compared to a late classic sensory program for hand nerve repair. METHOD: This is a randomized controlled trial. We assessed 20 patients with median and ulnar nerve and flexor tendon repair using the Rosen Score combined with the DASH questionnaire. The early phase group using mirror therapy began on the first postoperative week and lasted 5 months. The control group received classic sensory re-education when the protective sensation threshold was restored. All participants received a patient education booklet and were submitted to the modified Duran protocol for flexor tendon repair. The assessments were performed by the same investigator blinded to the allocated treatment. Mann-Whitney Test and Effect Size using Cohen's d score were used for inter-group comparisons at 3 and 6 months after intervention. RESULTS: The primary outcome (Rosen score) values for the Mirror Therapy group and classic therapy control group after 3 and 6 months were 1.68 (SD=0.5); 1.96 (SD=0.56) and 1.65 (SD=0.52); 1.51 (SD=0.62), respectively. No between-group differences were observed. CONCLUSION: Although some clinical improvement was observed, mirror therapy was not shown to be more effective than late sensory re-education in an intermediate phase of nerve repair in the hand. Replication is needed to confirm these findings. PMID:26786080

  11. Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Kang, Lingzhi [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Meng, Qing-Yuan [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Wang, Zhaoliang [Jinan Military General Hospital of PLA, Jinan 250031 (China); Guo, Zhongwu, E-mail: zwguo@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2014-12-01

    The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials.

  12. Improvement of adhesion performance of mortar-repair interface with inducing crack path into repair

    Directory of Open Access Journals (Sweden)

    A. Satoh

    2015-10-01

    Full Text Available The most important performance for repair materials is adhesion to the substrate. The authors experimentally find out that high modulus fine aggregates in repair material enhance strength of it as well as the strength of the interface repaired with it, compared to the ordinary repair without fine aggregates. This paper elaborates the mechanisms for that with fractographic observation and FEM analysis based on the results of experiment. Also the authors discuss the ways for enhancing the strength and ductility of the repaired mortar

  13. Endonuclease IV Is the Main Base Excision Repair Enzyme Involved in DNA Damage Induced by UVA Radiation and Stannous Chloride

    Directory of Open Access Journals (Sweden)

    Ellen S. Motta

    2010-01-01

    Full Text Available Stannous chloride (SnCl2 and UVA induce DNA lesions through ROS. The aim of this work was to study the toxicity induced by UVA preillumination, followed by SnCl2 treatment. E. coli BER mutants were used to identify genes which could play a role in DNA lesion repair generated by these agents. The survival assays showed (i The nfo mutant was the most sensitive to SnCl2; (ii lethal synergistic effect was observed after UVA pre-illumination, plus SnCl2 incubation, the nfo mutant being the most sensitive; (iii wild type and nfo mutants, transformed with pBW21 plasmid (nfo+ had their survival increased following treatments. The alkaline agarose gel electrophoresis assays pointed that (i UVA induced DNA breaks and fpg mutant was the most sensitive; (ii SnCl2-induced DNA strand breaks were higher than those from UVA and nfo mutant had the slowest repair kinetics; (iii UVA+SnCl2 promoted an increase in DNA breaks than SnCl2 and, again, nfo mutant displayed the slowest repair kinetics. In summary, Nfo protects E. coli cells against damage induced by SnCl2 and UVA+ SnCl2.

  14. Evidence for Base Substitutions and Repair of DNA Mismatch Damage Induced by Low Energy N+ Ion Beam Implantation in E. coli

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Ever since the low energy N+ ion beam has been accepted, the mutations of ionizing radiation are attributable mainly to avoidance of DNA damages repair. Evidences based on in vivo proof results are limited. Using the E.coli wild type and mutator strains, the mutant frequencies suggest that base substitutions in rpoB gene are induced by the N+ implantation. A highly conserved region is selected to get the direct evidence for base substitutions by sequence of the high fidelity PCR amplification products in mutants. Most of the mutants (90.9%, 40/44) have at least one base substitution in the amplification region. The evidences for CG to TA (55%, 22/40), AT to GC (20%, 8/40) and TA to CG (5%, 2/40) transitions are identified. The transversions are AT to TA (15%, 6/40) and GC to CG (5%, 2/40). It is suggested that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N+ implantation by analysis of the mutant frequencies of mutator strains.

  15. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    Science.gov (United States)

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.

  16. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes

    Directory of Open Access Journals (Sweden)

    Rutter Joni L

    2004-03-01

    Full Text Available Abstract Background Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs in eight genes involved in base excision repair (XRCC1, APEX, POLD1, BRCA1 protein interaction (BRIP1, ZNF350, BRCA2, and growth regulation (TGFß1, IGFBP3 were evaluated. Methods Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748 identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Results Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR = 2.3; 95% CI 1.3–3.8; XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1–3.9; and BRIP1 (or BACH1 P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6–29.3. The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFß1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1 1845C>T, L66P, R501S, and S472P. Conclusion Some variants in genes within the base-excision repair pathway (XRCC1 and

  17. A heart team's perspective on interventional mitral valve repair

    DEFF Research Database (Denmark)

    Treede, Hendrik; Schirmer, Johannes; Rudolph, Volker

    2012-01-01

    Surgical mitral valve repair carries an elevated perioperative risk in the presence of severely reduced ventricular function and relevant comorbidities. We sought to assess the feasibility of catheter-based mitral valve repair using a clip-based percutaneous edge-to-edge repair system in selected...

  18. Injury and repair of nephron microvasculature endothelium in chronic renal disease%慢性肾脏病肾单位毛细血管内皮细胞损伤及修复研究进展

    Institute of Scientific and Technical Information of China (English)

    王琰; 余毅

    2011-01-01

    The function of the vascular endothelium plays a very important role in chronic renal disease. The block of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring in patients with chronic progressive renal disease. Recent research found that the angiotensin Ⅱ receptor antagonist (ARB), angiotensinconverting enzyme inhibitor (ACEI) and anti-oxidations may be benificial to endothelial cell repair and to delay the progression of renal disease. This review describes the injury and repair of nephron microvasculature endothelium in chronic renal disease.%血管内皮功能在慢性肾病中的作用非常显著.慢性进展性肾脏病患者,肾小球和肾间质瘢痕形成,微脉管系统发生进行性闭塞.血管紧张素Ⅱ受体拮抗剂(ARB)、血管紧张素转化酶抑制剂(ACEI)和抗氧化药物等可促进内皮细胞损伤的修复,达到延缓慢性进展性肾病肾功能恶化的作用.本文综述慢性肾脏病肾单位毛细血管内皮细胞损伤及其修复.

  19. CardioGenBase: A Literature Based Multi-Omics Database for Major Cardiovascular Diseases.

    Directory of Open Access Journals (Sweden)

    Alexandar V

    Full Text Available Cardiovascular diseases (CVDs account for high morbidity and mortality worldwide. Both, genetic and epigenetic factors are involved in the enumeration of various cardiovascular diseases. In recent years, a vast amount of multi-omics data are accumulated in the field of cardiovascular research, yet the understanding of key mechanistic aspects of CVDs remain uncovered. Hence, a comprehensive online resource tool is required to comprehend previous research findings and to draw novel methodology for understanding disease pathophysiology. Here, we have developed a literature-based database, CardioGenBase, collecting gene-disease association from Pubmed and MEDLINE. The database covers major cardiovascular diseases such as cerebrovascular disease, coronary artery disease (CAD, hypertensive heart disease, inflammatory heart disease, ischemic heart disease and rheumatic heart disease. It contains ~1,500 cardiovascular disease genes from ~2,4000 research articles. For each gene, literature evidence, ontology, pathways, single nucleotide polymorphism, protein-protein interaction network, normal gene expression, protein expressions in various body fluids and tissues are provided. In addition, tools like gene-disease association finder and gene expression finder are made available for the users with figures, tables, maps and venn diagram to fit their needs. To our knowledge, CardioGenBase is the only database to provide gene-disease association for above mentioned major cardiovascular diseases in a single portal. CardioGenBase is a vital online resource to support genome-wide analysis, genetic, epigenetic and pharmacological studies.

  20. Acid-base and potassium disorders in liver disease.

    Science.gov (United States)

    Ahya, Shubhada N; José Soler, Maria; Levitsky, Josh; Batlle, Daniel

    2006-11-01

    Acid-base and potassium disorders occur frequently in the setting of liver disease. As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acid-base disorders ensue. The most common acid-base disorder is respiratory alkalosis. Metabolic acidosis alone or in combination with respiratory alkalosis also is common. Acid-base disorders in patients with liver disease are complex. The urine anion gap may help to distinguish between chronic respiratory alkalosis and hyperchloremic metabolic acidosis when a blood gas is not available. A negative urine anion gap helps to rule out chronic respiratory alkalosis. In this disorder a positive urine anion gap is expected owing to suppressed urinary acidification. Distal renal tubular acidosis occurs in autoimmune liver disease such as primary biliary cirrhosis, but often is a functional defect from impaired distal sodium delivery. Potassium disorders are often the result of the therapies used to treat advanced liver disease.

  1. Nuclear translocation contributes to regulation of DNA excision repair activities

    DEFF Research Database (Denmark)

    Knudsen, Nina Østergaard; Andersen, Sofie Dabros; Lützen, Anne;

    2009-01-01

    , it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M......DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA.......T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also...

  2. Pectus excavatum repair

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002949.htm Pectus excavatum repair To use the sharing features on this page, please enable JavaScript. Pectus excavatum repair is surgery to correct pectus excavatum . This ...

  3. Radio-adaptive response of base excision repair genes and proteins in human peripheral blood mononuclear cells exposed to gamma radiation.

    Science.gov (United States)

    Toprani, Sneh M; Das, Birajalaxmi

    2015-09-01

    Radio-adaptive response is a mechanism whereby a low-dose exposure (priming dose) induces resistance to a higher dose (challenging dose) thus significantly reducing its detrimental effects. Radiation-induced DNA damage gets repaired through various DNA repair pathways in human cells depending upon the type of lesion. The base excision repair (BER) pathway repairs radiation-induced base damage, abasic sites and single-strand breaks in cellular DNA. In the present study, an attempt has been made to investigate the involvement of BER genes and proteins in the radio-adaptive response in human resting peripheral blood mononuclear cells (PBMC). Venous blood samples were collected from 20 randomly selected healthy male individuals with written informed consent. PBMC were isolated and irradiated at a priming dose of 0.1 Gy followed 4h later with a challenging dose of 2.0 Gy (primed cells). Quantitation of DNA damage was done using the alkaline comet assay immediately and expression profile of BER genes and proteins were studied 30 min after the challenging dose using real-time quantitative polymerase chain reaction and western blot, respectively. The overall result showed significant (P ≤ 0.05) reduction of DNA damage in terms of percentage of DNA in tail (%T) with a priming dose of 0.1 Gy followed by a challenging dose of 2.0 Gy after 4 h. Twelve individuals showed significant (P ≤ 0.05) reduction in %T whereas eight individuals showed marginal reduction in DNA damage that was not statistically significant. However, at the transcriptional level, BER genes such as APE1, FEN1 and LIGASE1 showed significant (P ≤ 0.05) up-regulation in both groups. Significant (P ≤ 0.05) up-regulation was also observed at the protein level for OGG1, APE1, MBD4, FEN1 and LIGASE1 in primed cells. Up-regulation of some BER genes and proteins such as APE1, FEN1 and LIGASE1 in primed cells of resting PBMC is suggestive of active involvement of the BER pathway in radio-adaptive response.

  4. A trans-well-based cellular model for the rapid pre-evaluation of tympanic membrane repair materials.

    Science.gov (United States)

    Hung, Shih-Han; Su, Chin-Hui; Tseng, How

    2016-08-01

    It is important to have a standardized tympanic membrane (TM) perforation platform to evaluate the various myringoplasty materials that have been studied and developed extensively during recent years. However, currently there are no cellular models specifically designed for this purpose, and animal models remain unsatisfactory. The purpose of this study is to propose an inexpensive, readily available, well-controlled, and easy-to-create cellular model as a substitute for use in the evaluation of TM repairing materials. A trans-well model was created using a cell culture insert with a round hole created at the center of the polycarbonate membrane. HaCaT cells were cultured on the fenestrated culture insert, and the desired myringoplasty graft was placed at the center of the window for one week and observed by fluorescent microscopy under vital staining. Under this cellular model, there was notable migration of HaCaT cells onto the positive control graft (rabbit fascia), while only a few cell clusters were observed on the negative control graft (paper). Model validation showed that the cell migration ratio for the PLLA + 1% hyaluronic acid (HA) graft is significantly higher than using myringoplasty paper, poly L-lactide (PLLA), or PLLA + 0.5% HA (p model might be a useful pre-evaluation platform for the evaluation of TM repairing materials. The model is inexpensive, readily available, easy to create, and standardized for use.

  5. Parkinson's disease detection based on dysphonia measurements

    Science.gov (United States)

    Lahmiri, Salim

    2017-04-01

    Assessing dysphonic symptoms is a noninvasive and effective approach to detect Parkinson's disease (PD) in patients. The main purpose of this study is to investigate the effect of different dysphonia measurements on PD detection by support vector machine (SVM). Seven categories of dysphonia measurements are considered. Experimental results from ten-fold cross-validation technique demonstrate that vocal fundamental frequency statistics yield the highest accuracy of 88 % ± 0.04. When all dysphonia measurements are employed, the SVM classifier achieves 94 % ± 0.03 accuracy. A refinement of the original patterns space by removing dysphonia measurements with similar variation across healthy and PD subjects allows achieving 97.03 % ± 0.03 accuracy. The latter performance is larger than what is reported in the literature on the same dataset with ten-fold cross-validation technique. Finally, it was found that measures of ratio of noise to tonal components in the voice are the most suitable dysphonic symptoms to detect PD subjects as they achieve 99.64 % ± 0.01 specificity. This finding is highly promising for understanding PD symptoms.

  6. Modelling in Optimal Inspection and Repair

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Rackwitz, R.; Faber, M.H.;

    1991-01-01

    A model for reliability based optimal inspection and repair strategies is described. The total expected costs in the lifetime is minimized with the number of inspections, the inspection times and efforts, the repair crack size limit and a design parameter as optimization variables. The equivalenc...

  7. Repairing VLSI/WSI Redundant Memories with Minimum Cost

    Institute of Scientific and Technical Information of China (English)

    黄维康; F.Lombardi

    1990-01-01

    A new approach to repair memory chips with redundancy is proposed.This approach s based on the minimization of the repair cost.Algorithms for cost driven repair are presented.The algorithms can be executed either on -line(concurrently with the testing of the memory),or off-lin(at completion of testing).Analytical expressions for the repair cost under both circumstances are given.The presented algorithms are also perfect in the sense that they can correctly diagnose a repairable/unrepairable memory and find the optimal repair-solution.

  8. Inferring drug-disease associations based on known protein complexes.

    Science.gov (United States)

    Yu, Liang; Huang, Jianbin; Ma, Zhixin; Zhang, Jing; Zou, Yapeng; Gao, Lin

    2015-01-01

    Inferring drug-disease associations is critical in unveiling disease mechanisms, as well as discovering novel functions of available drugs, or drug repositioning. Previous work is primarily based on drug-gene-disease relationship, which throws away many important information since genes execute their functions through interacting others. To overcome this issue, we propose a novel methodology that discover the drug-disease association based on protein complexes. Firstly, the integrated heterogeneous network consisting of drugs, protein complexes, and disease are constructed, where we assign weights to the drug-disease association by using probability. Then, from the tripartite network, we get the indirect weighted relationships between drugs and diseases. The larger the weight, the higher the reliability of the correlation. We apply our method to mental disorders and hypertension, and validate the result by using comparative toxicogenomics database. Our ranked results can be directly reinforced by existing biomedical literature, suggesting that our proposed method obtains higher specificity and sensitivity. The proposed method offers new insight into drug-disease discovery. Our method is publicly available at http://1.complexdrug.sinaapp.com/Drug_Complex_Disease/Data_Download.html.

  9. Blood based proteomic biomarkers of Alzheimer’s disease pathology

    Directory of Open Access Journals (Sweden)

    Alison Louise Baird

    2015-11-01

    Full Text Available The complexity of Alzheimer’s disease (AD and its long prodromal phase poses challenges for early diagnosis and yet allows for the possibility of the development of disease modifying treatments for secondary prevention. It is therefore of importance to develop biomarkers, in particular in the preclinical or early phases that reflect the pathological characteristics of the disease and moreover could be of utility in triaging subjects for preventative therapeutic clinical trials. Much research has sought biomarkers for diagnostic purposes by comparing affected people to unaffected controls. However, given that AD pathology precedes disease onset, a pathology endophenotype design for biomarker discovery creates the opportunity for detection of much earlier markers of disease. Blood based biomarkers potentially provide a minimally invasive option for this purpose and research in the field has adopted various omics approaches in order to achieve this. This review will therefore examine the current literature regarding blood based proteomic biomarkers of AD and its associated pathology.

  10. Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases.

    Science.gov (United States)

    Ahmadi, Majid; Gharibi, Tohid; Dolati, Sanam; Rostamzadeh, Davood; Aslani, Saeed; Baradaran, Behzad; Younesi, Vahid; Yousefi, Mehdi

    2017-03-01

    Recent genome-wide association studies have documented a number of genetic variants to explain mechanisms underlying autoimmune diseases. However, the precise etiology of autoimmune diseases remains largely unknown. Epigenetic mechanisms like alterations in the post-translational modification of histones and DNA methylation may potentially cause a breakdown of immune tolerance and the perpetuation of autoreactive responses. Recently, several studies both in experimental models and clinical settings proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in autoimmune diseases, in some cases based on mechanistical observations. Epigenetic therapy already being employed in hematopoietic malignancies may also be associated with beneficial effects in autoimmune diseases. In this review, we will discuss on what we know and expect about the treatment of autoimmune disease based on epigenetic aberrations.

  11. When "Other" Initiate Repair.

    Science.gov (United States)

    Schegloff, Emanuel A.

    2000-01-01

    Elaborates on the locus of other-initiated repair, and reports on a number of environments in which others initiate repair turns later than the one directly following the trouble-source turn. Describes several ways that other initiation of repair, which occurs in next-turn position, may be delayed within that position. (Author/VWL)

  12. Wound repair in Pocillopora

    Science.gov (United States)

    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.

  13. Changes in DNA repair during aging

    Science.gov (United States)

    Gorbunova, Vera; Seluanov, Andrei; Mao, Zhiyong; Hine, Christpher

    2007-01-01

    DNA is a precious molecule. It encodes vital information about cellular content and function. There are only two copies of each chromosome in the cell, and once the sequence is lost no replacement is possible. The irreplaceable nature of the DNA sets it apart from other cellular molecules, and makes it a critical target for age-related deterioration. To prevent DNA damage cells have evolved elaborate DNA repair machinery. Paradoxically, DNA repair can itself be subject to age-related changes and deterioration. In this review we will discuss the changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excision repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age. Mutations in DNA repair genes and premature aging phenotypes they cause have been reviewed extensively elsewhere, therefore the focus of this review is on the comparison of DNA repair mechanisms in young versus old. PMID:17913742

  14. Initial steps of the base excision repair pathway within the nuclear architecture; Les etapes initiales du mecanisme de reparation par excision de bases au sein de l'architecture nucleaire

    Energy Technology Data Exchange (ETDEWEB)

    Amouroux, R

    2009-09-15

    Oxidative stress induced lesions threaten aerobic organisms by representing a major cause of genomic instability. A common product of guanine oxidation, 8-oxo-guanine (8- oxoG) is particularly mutagenic by provoking G to T transversions. Removal of oxidised bases from DNA is initiated by the recognition and excision of the damaged base by a DNA glycosylase, initiating the base excision repair (BER) pathway. In mammals, 8-oxoG is processed by the 8-oxoG-DNA-glycosylase I (OGG1), which biochemical mechanisms has been well characterised in vitro. However how and where this enzyme finds the modified base within the complex chromatin architecture is not yet understood. We show that upon induction of 8-oxoG, OGG1, together with at least two other proteins involved in BER, is recruited from a soluble fraction to chromatin. Formation kinetics of this patches correlates with 8-oxoG excision, suggesting a direct link between presence of this chromatin-associated complexes and 8-oxoG repair. More precisely, these repair patches are specifically directed to euchromatin regions, and completely excluded from heterochromatin regions. Inducing of artificial chromatin compaction results in a complete inhibition of the in vivo repair of 8-oxoG, probably by impeding the access of OGG1 to the lesion. Using OGG1 mutants, we show that OGG1 direct recognition of 8-oxoG did not trigger its re-localisation to the chromatin. We conclude that in response to the induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions. (author)

  15. Is Trust for Sale? The Effectiveness of Financial Compensation for Repairing Competence- versus Integrity-Based Trust Violations.

    Science.gov (United States)

    Haesevoets, Tessa; Reinders Folmer, Chris; Van Hiel, Alain

    2015-01-01

    Despite the popularity of financial compensation as a means for addressing trust violations, the question whether (more) money can indeed buy trust back remains largely unexplored. In the present research, we focus on the role of violation type and compensation size. The results of a scenario study and a laboratory experiment show that financial compensation can effectively promote the restoration of trust for transgressions that indicate a lack of competence. Conversely, for transgressions which signal a lack of integrity, financial compensation is not an effective tool to repair trust. Moreover, our findings indicate that for both violation types, overcompensation has no positive effects on top of the impact of equal compensation. These findings therefore show that when it comes to trust, money cannot buy everything.

  16. Imperfect repair and lifesaving in heterogeneous populations

    Energy Technology Data Exchange (ETDEWEB)

    Finkelstein, Maxim [Department of Mathematical Statistics, University of the Free State, PO Box 339, 9300 Bloemfontein (South Africa) and Max Planck Institute for Demographic Research, Rostock (Germany)]. E-mail: FinkelM.SCl@mail.uovs.ac.za

    2007-12-15

    In this theoretical paper we generalize the notion of minimal repair to the heterogeneous case, when the lifetime distribution function can be modeled by continuous or a discrete mixture of distributions. The statistical (black box) minimal repair and the minimal repair based on information just before the failure of an object are considered. The corresponding failure (intensity) rate processes are defined and analyzed. Demographic lifesaving model is also considered: each life is saved (cured) with some probability (or equivalently a proportion of individuals who would have died are now resuscitated and given another chance). Those who are saved experience the statistical minimal repair. Both of these models are based on the Poisson or non-homogeneous Poisson processes of underlying events, which allow for considering heterogeneity. We also consider the new model of imperfect repair in the homogeneous case and present generalizations to the heterogeneous setting.

  17. Small Crater Expedient Repair Test.

    Science.gov (United States)

    1980-08-01

    Force Base, New Mexico , October 1975. 3. Rollings, Raymond S., Laboratory Evaluation of Expedient Pavement Repair Materials, CEEDO-TR-7-44, Civil and...blank) APPENDIX A EQUIPMENT PERFORMANCE SP6WCIFICATIONS Performance specit’ications are included i.n tl is appe udi \\ tor the following equipment: 1

  18. Microwave Oven Repair. Teacher Edition.

    Science.gov (United States)

    Smreker, Eugene

    This competency-based curriculum guide for teachers addresses the skills a technician will need to service microwave ovens and to provide customer relations to help retain the customer's confidence in the product and trust in the service company that performs the repair. The guide begins with a task analysis, listing 20 cognitive tasks and 5…

  19. Is the Oxidative DNA Damage Level of Human Lymphocyte Correlated with the Antioxidant Capacity of Serum or the Base Excision Repair Activity of Lymphocyte?

    Directory of Open Access Journals (Sweden)

    Yi-Chih Tsai

    2013-01-01

    Full Text Available A random screening of human blood samples from 24 individuals of nonsmoker was conducted to examine the correlation between the oxidative DNA damage level of lymphocytes and the antioxidant capacity of serum or the base excision repair (BER activity of lymphocytes. The oxidative DNA damage level was measured with comet assay containing Fpg/Endo III cleavage, and the BER activity was estimated with a modified comet assay including nuclear extract of lymphocytes for enzymatic cleavage. Antioxidant capacity was determined with trolox equivalent antioxidant capacity assay. We found that though the endogenous DNA oxidation levels varied among the individuals, each individual level appeared to be steady for at least 1 month. Our results indicate that the oxidative DNA damage level is insignificantly or weakly correlated with antioxidant capacity or BER activity, respectively. However, lymphocytes from carriers of Helicobacter pylori (HP or Hepatitis B virus (HBV tend to give higher levels of oxidative DNA damage (P<0.05. Though sera of this group of individuals show no particular tendency with reduced antioxidant capacity, the respective BER activities of lymphocytes are lower in average (P<0.05. Thus, reduction of repair activity may be associated with the genotoxic effect of HP or HBV infection.

  20. Speeding disease gene discovery by sequence based candidate prioritization

    Directory of Open Access Journals (Sweden)

    Porteous David J

    2005-03-01

    Full Text Available Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

  1. Percutaneous mitral valve repair.

    Science.gov (United States)

    Gillinov, A Marc; Liddicoat, John R

    2006-01-01

    Surgical mitral valve repair is the procedure of choice to treat mitral regurgitation of all etiologies. Whereas annuloplasty is the cornerstone of mitral valve repair, a variety of other surgical techniques are utilized to correct dysfunction of the leaflets and subvalvular apparatus; in most cases, surgical repair entails application of multiple repair techniques in each patient. Preclinical studies and early human experience have demonstrated that some of these surgical repair techniques can be performed using percutaneous approaches. Specifically, there has been great progress in the development of novel technology to facilitate percutaneous annuloplasty and percutaneous edge-to-edge repair. The objectives of this report were to (1) discuss the surgical foundations for these percutaneous approaches; (2) review device design and experimental and clinical results of percutaneous valve repair; and (3) address future directions, including the key challenges of patient selection and clinical trial design.

  2. 32 CFR 174.14 - Maintenance and repair.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Maintenance and repair. 174.14 Section 174.14... REVITALIZING BASE CLOSURE COMMUNITIES AND ADDRESSING IMPACTS OF REALIGNMENT Maintenance and Repair § 174.14 Maintenance and repair. (a) Facilities and equipment located on installations being closed are often...

  3. T-style keratoprosthesis based on surface-modified poly (2-hydroxyethyl methacrylate) hydrogel for cornea repairs

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Jun [Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); Sun, Jianguo [Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); State Key Laboratory of Molecular Engineering of Polymers, Fudan University (China); Hong, Jiaxu [Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); Wang, Wentao [Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); Wei, Anji [Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); Le, Qihua [Research Center, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China); Xu, Jianjiang, E-mail: jianjiang-xu@163.com [Department of Ophthalmology, Eye & ENT Hospital, Shanghai Medical College, Fudan University (China); Key Laboratory of Myopia, Ministry of Health, Fudan University (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University (China)

    2015-05-01

    Corneal disease is a common cause of blindness, and keratoplasty is considered as an effective treatment method. However, there is a severe shortage of donor corneas worldwide. This paper presents a novel T-style design of a keratoprosthesis and its preparation methods, in which a mechanically and structurally effective artificial cornea is made based on a poly(2-hydroxyethyl methacrylate) hydrogel. The porous skirt was modified with hyaluronic acid and cationized gelatin, and the bottom of the optical column was coated with poly(ethylene glycol). The physical properties of the T-style Kpro were analyzed using ultraviolet and visible spectrophotometry and electron scanning microscopy. The surface chemical properties were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface modification in the spongy skirt promoted cell adhesion and produced a firm bond between the corneal tissue and the implant device, while the surface modification in the optic column resisted cell adhesion and prevented retroprosthetic membrane formation. Through improved surgical techniques, the novel T-style keratoprosthesis provides enough mechanical stability to facilitate long-term biointegration with the host environment. In vivo implantation experiments showed that the T-style keratoprosthesis is a promising cornea alternative for patients with severe limbal stem cell deficiency and corneal opacity. - Highlights: • T-style keratoprosthesis was designed and prepared based on a PHEMA hydrogel. • Selective surface modifications effectively regulated cells' selective adhesion. • T-style keratoprosthesis provides enough mechanical stability to facilitate long-term biointegration with host tissues.

  4. Integrated Knowledge Based Expert System for Disease Diagnosis System

    Science.gov (United States)

    Arbaiy, Nureize; Sulaiman, Shafiza Eliza; Hassan, Norlida; Afizah Afip, Zehan

    2017-08-01

    The role and importance of healthcare systems to improve quality of life and social welfare in a society have been well recognized. Attention should be given to raise awareness and implementing appropriate measures to improve health care. Therefore, a computer based system is developed to serve as an alternative for people to self-diagnose their health status based on given symptoms. This strategy should be emphasized so that people can utilize the information correctly as a reference to enjoy healthier life. Hence, a Web-based Community Center for Healthcare Diagnosis system is developed based on expert system technique. Expert system reasoning technique is employed in the system to enable information about treatment and prevention of the diseases based on given symptoms. At present, three diseases are included which are arthritis, thalassemia and pneumococcal. Sets of rule and fact are managed in the knowledge based system. Web based technology is used as a platform to disseminate the information to users in order for them to optimize the information appropriately. This system will benefit people who wish to increase health awareness and seek expert knowledge on the diseases by performing self-diagnosis for early disease detection.

  5. Pathway-based analysis tools for complex diseases: a review.

    Science.gov (United States)

    Jin, Lv; Zuo, Xiao-Yu; Su, Wei-Yang; Zhao, Xiao-Lei; Yuan, Man-Qiong; Han, Li-Zhen; Zhao, Xiang; Chen, Ye-Da; Rao, Shao-Qi

    2014-10-01

    Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehensive understanding of the molecular mechanisms underlying complex diseases. Extensive studies utilizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods-the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available pathway-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are discussed. This review will provide a useful guide to dissect complex diseases.

  6. Collagen based film with well epithelial and stromal regeneration as corneal repair materials: Improving mechanical property by crosslinking with citric acid

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Xuan; Liu, Yang; Li, Weichang; Long, Kai; Wang, Lin; Liu, Sa; Wang, Yingjun [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China); Ren, Li, E-mail: psliren@scut.edu.cn [School of Materials Science and Engineering, South China University of Technology, Guangzhou (China); National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou (China)

    2015-10-01

    Corneal disease can lead to vision loss. It has become the second greatest cause of blindness in the world, and keratoplasty is considered as an effective treatment method. This paper presents the crosslinked collagen (Col)–citric acid (CA) films developed by making use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The results showed that the Col–CA films had necessary optical performance, water content. The collagenase resistance of CA crosslinked films was superior to that of EDC crosslinked films. And CA5 film (Col:CA:EDC:NHS = 60:3:10:10) had the best mechanical properties. Cell experiments showed that CA5 film was non-cytotoxic and human corneal epithelial cells could proliferate well on the films. Lamellar keratoplasty showed that the CA5 film could be sutured in the rabbit eyes and was epithelialized completely in about 10 days, and the transparency was restored quickly in 30 ± 5 days. No inflammation and corneal neovascularization were observed at 6 months. Corneal stroma had been repaired; stromal cells and neo-stroma could be seen in the area of operation from the hematoxylin–eosin stained histologic sections and anterior segment optical coherence tomography images. These results indicated that Col–CA films were highly promising biomaterials that could be used in corneal tissue engineering and a variety of other tissue engineering applications. - Highlights: • Adding different amounts of citric acid could change the properties of films. • The crosslinked films had better mechanical property than non-modified films. • Crosslinked collagen–citric acid films could tolerate suture during operation. • The films showed good ability of epithelial and stromal repair.

  7. Rapid Set Materials for Advanced Spall Repair

    Science.gov (United States)

    2010-08-01

    cement -based polymer- cement mortar and concrete • Magnesium -ammonium- phosphate - cement mortar and concrete • Polymer-based mortar and concrete...material or lodged debris from the joint or crack. • Place a small bead of caulk over the joint or crack. • If using a cement -based repair material, soak...placement equipment immediately after use. • When using cement repair materials, either wet cure or apply curing compound. • Remove the compressible spacer

  8. Neural stem cell-based treatment for neurodegenerative diseases.

    Science.gov (United States)

    Kim, Seung U; Lee, Hong J; Kim, Yun B

    2013-10-01

    Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury. © 2013 Japanese Society of Neuropathology.

  9. Validation of hospital register-based diagnosis of Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, Lene; Lassen, Christina Funch; Himmerslev, Liselotte;

    2012-01-01

    (PD) is a neurodegenerative disorder and only 75-80% of patients with parkinsonism will have idiopathic PD (iPD). It is necessary to follow patients in order to determine if some of them will develop other neurodegenerative diseases and a one-time-only diagnostic code for iPD reported in the register......Denmark has a long-standing tradition of maintaining one of the world's largest health science specialized register data bases as the National Hospital Register (NHR). To estimate the prevalence and incidence of diseases, the correctness of the diagnoses recorded is critical. Parkinson's disease...

  10. Validation of hospital register-based diagnosis of Parkinson's disease

    DEFF Research Database (Denmark)

    Wermuth, Lene; Lassen, Christina Funch; Himmerslev, Liselotte

    2012-01-01

    Denmark has a long-standing tradition of maintaining one of the world's largest health science specialized register data bases as the National Hospital Register (NHR). To estimate the prevalence and incidence of diseases, the correctness of the diagnoses recorded is critical. Parkinson's disease...... (PD) is a neurodegenerative disorder and only 75-80% of patients with parkinsonism will have idiopathic PD (iPD). It is necessary to follow patients in order to determine if some of them will develop other neurodegenerative diseases and a one-time-only diagnostic code for iPD reported in the register...

  11. Embryonic template-based generation and purification of pluripotent stem cell-derived cardiomyocytes for heart repair

    NARCIS (Netherlands)

    Dierickx, P.; Doevendans, P.A.; Geijsen, N.; van Laake, L.W.

    2012-01-01

    Cardiovascular disease remains a leading cause of death in Western countries. Many types of cardiovascular diseases are due to a loss of functional cardiomyocytes, which can result in irreversible cardiac failure. Since the adult human heart has limited regenerative potential, cardiac transplantatio

  12. Synchronized valve repair in patients with various valvular disease%同期瓣膜成形术治疗共存的不同原因瓣膜疾病

    Institute of Scientific and Technical Information of China (English)

    朱亚彬; 朱兵; 李星海; 毛宝根; 王宁夫; 杨岷

    2011-01-01

    目的:探讨对不同原因的瓣膜疾病行瓣膜成形术的特点和技巧.方法:回顾性分析2004年10月至2010年12月142例不同原因的瓣膜疾病患者行各种瓣膜成形手术的临床资料以及临床随访的情况,总结各种瓣膜成形的技术要点和经验.结果:142例患者中风湿性心脏病联合瓣膜病变42例,先天性心脏病56例,冠心病4例,单纯二尖瓣退行性病变35例,二尖瓣barlow氏综合征5例.术中低心排不能脱机死亡1例,30 d住院死亡2例,其余均顺利出院.临床随访126例,随访率90.6%,平均随访时间490 d.随访显示,残余三尖瓣轻度返流5例,三尖瓣中度返流3例,肺动脉瓣轻度返流5例,肺动脉瓣轻度狭窄3例,二尖瓣返流轻到中度1例,主动脉瓣轻到中度返流1例,目前均无须再次手术.结论:瓣膜成形手术具有血流动力学稳定、安全性高、术后并发症少的特点,可以避免瓣膜置换的抗凝并发症,近中期效果满意,长期效果需要进一步随访.%Objective: To summarize the data of 142 cases who received combined valve repair in our heart centre from 2004. Oct. to 2010 and to explore the opportunity, applicability and feasibility of valve repair in various valvular diseases. Methods: The data of 142 patients who suhfered from congenital heart disease, rheumatic heart disease or degenerative heart disease, were collect retrospectively and received various valve repair operation as well as other cardiac manipulation. Among them, rheumatic combined heart disease 42 cases, complex congenital heart disease 56 cases, coronary heart disease 4 cases, degenerative valve disease 35 cases, and Barlow's syndrome 5 cases. Different techniques in different patients and attention in perioperative treatment were analyzed. Results:One patient died of low cardiac output syndrome in hospital not weaning off cardio-pulmonary bypass, two patients died of postoperative concurrent symptoms, other 139 cases recovered and 126 cases

  13. Clinical Relevance of Classifying Massive Rotator Cuff Tears: Results Based on Functional and Radiological Findings After Arthroscopic Repair.

    Science.gov (United States)

    Ok, Hyun Soo; Kim, Byung Guk; Choi, Won Chul; Hong, Chul Gie; Kim, Jee Woong; Kim, Jae Hwa

    2017-01-01

    Studies on the results of arthroscopic repair of massive rotator cuff tears have reported widely varied prognoses. Among other factors, the sizable discrepancy can be attributable to the fact that the current definition of massive rotator cuff tears covers an extensive area of tendons. Functional and radiological results according to subgroups would show significant inter-subgroup differences preoperatively and postoperatively. Cohort study; Level of evidence, 2. A total of 104 patients who required arthroscopic repair for massive rotator cuff tears were prospectively evaluated. The patients were allocated into 3 groups according to tendon involvement as diagnosed by preoperative magnetic resonance imaging: group 1 (anterosuperior type involving the subscapularis and supraspinatus), group 2 (posterosuperior type involving the infraspinatus and supraspinatus), and group 3 (anteroposterior type involving the subscapularis, supraspinatus, and infraspinatus). We compared functional results (at 2 years postoperatively) and radiological findings (at 1 year postoperatively) for each group. There were 34 patients in group 1, 54 in group 2, and 16 in group 3. In all 3 groups, functional results significantly improved after surgery. There were no statistically significant intergroup differences in functional results among the 3 groups. On the radiological evaluations, each group (groups 1, 2, and 3) showed a significantly different result in the preoperative acromiohumeral distance (AHD) (7.19, 5.44, and 5.22 mm, respectively), tear size (38.8, 39.3, and 46.4 mm, respectively), extent of retraction (33.9, 40.0, and 41.4 mm, respectively), postoperative AHD (8.92, 7.37, and 6.71 mm, respectively), and retear rate (23.5%, 51.9%, and 56.2%, respectively) ( P rotator cuff tears can be divided into 3 types: anterosuperior (group 1), posterosuperior (group 2), and anteroposterior (group 3). Each group has distinctive characteristics and shows different results in the preoperative

  14. Hiatal hernia repair with biologic mesh reinforcement reduces recurrence rate in small hiatal hernias.

    Science.gov (United States)

    Schmidt, E; Shaligram, A; Reynoso, J F; Kothari, V; Oleynikov, D

    2014-01-01

    The utility of mesh reinforcement for small hiatal hernia found especially during antireflux surgery is unknown. Initial reports for the use of biological mesh for crural reinforcement during repair for defects greater than 5 cm have been shown to decrease recurrence rates. This study compares patients with small hiatal hernias who underwent onlay biologic mesh buttress repair versus those with suture cruroplasty alone. This is a single-institution retrospective review of all patients undergoing repair of hiatal hernia measuring 1-5 cm between 2002 and 2009. The patients were evaluated based on surgical repair: one group undergoing crural reinforcement with onlay biologic mesh and other group with suture cruroplasty only. Seventy patients with hiatal hernia measuring 1-5 cm were identified. Thirty-eight patients had hernia repair with biologic mesh, and 32 patients had repair with suture cruroplasty only. Recurrence rate at 1 year was 16% (5/32) in patients who had suture cruroplasty only and 0% (0/38) in the group with crural reinforcement with absorbable mesh (statistically significant, P = 0.017). Suture cruroplasty alone appears to be inadequate for hiatal hernias measuring 1-5 cm with significant recurrence rate and failure of antireflux surgery. Crural reinforcement with absorbable mesh may reduce hiatal hernia recurrence rate in small hiatal hernias. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  15. Human Disease Insight: An integrated knowledge-based platform for disease-gene-drug information.

    Science.gov (United States)

    Tasleem, Munazzah; Ishrat, Romana; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-01-01

    The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com.

  16. Cell culture-based profiling across mammals reveals DNA repair and metabolism as determinants of species longevity

    Science.gov (United States)

    Ma, Siming; Upneja, Akhil; Galecki, Andrzej; Tsai, Yi-Miau; Burant, Charles F; Raskind, Sasha; Zhang, Quanwei; Zhang, Zhengdong D; Seluanov, Andrei; Gorbunova, Vera; Clish, Clary B; Miller, Richard A; Gladyshev, Vadim N

    2016-01-01

    Mammalian lifespan differs by >100 fold, but the mechanisms associated with such longevity differences are not understood. Here, we conducted a study on primary skin fibroblasts isolated from 16 species of mammals and maintained under identical cell culture conditions. We developed a pipeline for obtaining species-specific ortholog sequences, profiled gene expression by RNA-seq and small molecules by metabolite profiling, and identified genes and metabolites correlating with species longevity. Cells from longer lived species up-regulated genes involved in DNA repair and glucose metabolism, down-regulated proteolysis and protein transport, and showed high levels of amino acids but low levels of lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns were recapitulated by further analyses of primate and bird fibroblasts. The study suggests that fibroblast profiling captures differences in longevity across mammals at the level of global gene expression and metabolite levels and reveals pathways that define these differences. DOI: http://dx.doi.org/10.7554/eLife.19130.001 PMID:27874830

  17. The effect of rotator cuff repair on early overhead shoulder function: a study in 1600 consecutive rotator cuff repairs.

    Science.gov (United States)

    Robinson, Hayden A; Lam, Patrick H; Walton, Judie R; Murrell, George A C

    2017-01-01

    Rotator cuff tears are often surgically repaired, generally with good results. However, repairs not infrequently retear, and how important repair integrity is with respect to early functional outcomes after rotator cuff repair is unclear. Thus, the purpose of this study was to determine the effect of a retear on overhead activities in a large cohort of patients after rotator cuff repair. This was a retrospective cohort study of prospectively collected data from 1600 consecutive rotator cuff repairs. Outcomes were based on patient responses to the L'Insalata Shoulder Questionnaire and findings on examination preoperatively and at 6 months of follow-up. Repair integrity was determined by ultrasound imaging at the 6-month follow-up visit. The 1600 patients (885 men, 715 women) were a mean age of 58 years. Postoperative ultrasound imaging found 13% (211 of 1600) of repairs had retorn. Significant improvements were seen irrespective of rotator cuff integrity in pain levels with overhead activity (P rotation strength (P rotator cuff repair integrity on shoulder function. Patients who had an arthroscopic rotator cuff repair reported significant improvements in overhead pain levels irrespective of the repair integrity at 6 months. Repair integrity influenced supraspinatus and external rotation power, where patients with intact repairs were stronger than those with a retear. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  18. 游戏化汽车维修学习软件的开发研究%Research and development of automobile repair game-based learning software

    Institute of Scientific and Technical Information of China (English)

    聂淼

    2014-01-01

    The common automotive repair knowledge is selected as the main content in this study. The car owners and car major students are taken as the target population to develop games-based learning software by means of Flash game engine. The game-based learning software has transcended the old onefold teaching method which only adopts the introductory content such as characters,images,etc. It use Flash technology to make a virtual auto repair factory in which learners can learn vehicle main-tenance knowledge intuitively. Meanwhile the enjoyment of the game makes learners more actively to achieve better learning out-come.%该研究选取常见的汽车维修知识为主要内容,以有车一族和汽车专业学习者为目标人群,利用Flash游戏引擎开发游戏化学习软件。在该游戏化学习软件中,突破了以往仅仅是文字、图片等介绍性为主的单一教学方式,通过Flash技术让现实中的汽车修理厂再现,让学习者能够在创设的虚拟情景中直观地学习汽车维修知识。同时游戏的趣味性能够让学习者在学习中更加主动,取得较好的学习效果。

  19. Novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a synovium-based pool of meniscoprogenitor cells.

    Science.gov (United States)

    Hunziker, Ernst B; Lippuner, Kurt; Keel, Marius J B; Shintani, Nahoko

    2016-09-01

    Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait, and obesity. Sixty percent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-β1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically, for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1588-1596, 2016.

  20. Enfermedades de base genética Genetically based diseases

    Directory of Open Access Journals (Sweden)

    D. González-Lamuño

    2008-01-01

    significant degree of disability they generate, the social impact of hereditary diseases is enormous, due to their potentially recurrent character in the same family and the high socio-health cost deriving from the enormous care burden they require. The diagnosis of hereditary diseases presents very significant differentiating characteristics since the result of a genetic diagnosis has effects not only on the patient but also on related individuals. Thus the unit of study in genetic diagnosis is the family and the whole process of diagnosis involves family research. It is also useful to bear in mind that the protocols of diagnosis are developed in parallel with the basic research and in general are hardly standardised. The results obtained in genetic studies and the type of information provided to the patient and his family must be qualified within the process of "genetic counselling".

  1. Systems Maintenance Automated Repair Tasks (SMART)

    Science.gov (United States)

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

    2010-01-01

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

  2. Optimality in DNA repair.

    Science.gov (United States)

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

    2012-01-07

    DNA within cells is subject to damage from various sources. Organisms have evolved a number of mechanisms to repair DNA damage. The activity of repair enzymes carries its own risk, however, because the repair of two nearby lesions may lead to the breakup of DNA and result in cell death. We propose a mathematical theory of the damage and repair process in the important scenario where lesions are caused in bursts. We use this model to show that there is an optimum level of repair enzymes within cells which optimises the cell's response to damage. This optimal level is explained as the best trade-off between fast repair and a low probability of causing double-stranded breaks. We derive our results analytically and test them using stochastic simulations, and compare our predictions with current biological knowledge.

  3. Chronic pediatric pulmonary disease and primary humoral antibody based immune disease.

    Science.gov (United States)

    Dosanjh, A

    2011-04-01

    Chronic inflammation of the larger airways is a common occurrence in children. A number of factors such as younger age, premature birth, male gender, exposure to environmental smoke or pollution, and crowded housing can increase a child's susceptibility to chronic lung disease. Chronic bronchitis may be caused by an underlying humoral immunodeficiency if the clinical course is recurrent or prolonged. Primary humoral immunodeficiency accounts for approximately 70% of all immunodeficiencies. The differential of chronic bronchitis also includes Cystic Fibrosis, ciliary defects and immune cellular and phagocytic defects. This review will summarize the most common humoral antibody based immune based deficiencies associated with chronic pulmonary disease.

  4. Metabolic biomarkers and gallstone disease - a population-based study

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Skaaby, Tea; Sørensen, Lars Tue

    2017-01-01

    OBJECTIVES: The objectives for this study were to examine the associations between metabolic biomarkers of obesity including insulin resistance, vascular dysfunction, systemic inflammation, genetic susceptibility and ultrasound proven gallstone disease or cholecystectomy in a population-based cross......). RESULTS: Gallstone disease was associated with fasting glucose (OR 1.14, 95% CI [1.05;1.24]), fasting insulin (OR 1.03, 95% CI [1.01;1.05]), homeostasis model assessment insulin resistance (OR 1.18, 95% CI [1.02;1.36]), the metabolic syndrome (OR 1.51, 95% CI [1.16;1.96]), white blood cell count (OR 1......-sectional study. MATERIAL AND METHODS: A total of 2650 participants were included, of whom 422 had gallstone disease. Associations between selected metabolic biomarkers and gallstone disease were estimated by multivariable logistic regression models and expressed as odds ratio (OR) and 95% confidence interval (CI...

  5. Hirschsprung's disease prevalence in Europe. A register based study

    DEFF Research Database (Denmark)

    Best, Kate E; Addor, Marie-Claude; Arriola, Larraitz;

    2014-01-01

    BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence......, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number...... of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence...

  6. Metabolism, Genomics, and DNA Repair in the Mouse Aging Liver

    Directory of Open Access Journals (Sweden)

    Michel Lebel

    2011-01-01

    Full Text Available The liver plays a pivotal role in the metabolism of nutrients, drugs, hormones, and metabolic waste products, thereby maintaining body homeostasis. The liver undergoes substantial changes in structure and function within old age. Such changes are associated with significant impairment of many hepatic metabolic and detoxification activities, with implications for systemic aging and age-related disease. It has become clear, using rodent models as biological tools, that genetic instability in the form of gross DNA rearrangements or point mutations accumulate in the liver with age. DNA lesions, such as oxidized bases or persistent breaks, increase with age and correlate well with the presence of senescent hepatocytes. The level of DNA damage and/or mutation can be affected by changes in carcinogen activation, decreased ability to repair DNA, or a combination of these factors. This paper covers some of the DNA repair pathways affecting liver homeostasis with age using rodents as model systems.

  7. Pregnancy after biventricular repair for pulmonary atresia with ventricular septal defect.

    NARCIS (Netherlands)

    Drenthen, W.; Pieper, P.G.; Zoon, N.; Roos-Hesselink, J.W.; Voors, A.A.; Mulder, B.J.M.; Dijk, A.P.J. van; Sollie, K.M.; Vliegen, H.W.; Ebels, T.; Veldhuisen, D.J. van

    2006-01-01

    Information on pregnancy and delivery in women with biventricular repair for isolated noncomplex pulmonary atresia with a ventricular septal defect (PAVSD) is limited. Using a nationwide congenital heart disease registry (CONgenital CORvitia [CONCOR]), 9 women with biventricular repair for PAVSD

  8. Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae.

    Science.gov (United States)

    Mániková, Dominika; Vlasáková, Danusa; Loduhová, Jana; Letavayová, Lucia; Vigasová, Dana; Krascsenitsová, Eva; Vlcková, Viera; Brozmanová, Jela; Chovanec, Miroslav

    2010-03-01

    Selenium (Se) belongs to nutrients that are essential for human health. Biological activity of this compound, however, mainly depends on its dose, with a potential of Se to induce detrimental effects at high doses. Although mechanisms lying behind detrimental effects of Se are poorly understood yet, they involve DNA damage induction. Consequently, DNA damage response and repair pathways may play a crucial role in cellular response to Se. Using Saccharomyces cerevisiae we showed that sodium selenite (SeL), an inorganic form of Se, can be toxic and mutagenic in this organism due to its ability to induce DNA double-strand breaks (DSBs). Moreover, we reported that a spectrum of mutations induced by this compound in the stationary phase of growth is mainly represented by 1-4 bp deletions. Consequently, we proposed that SeL acts as an oxidizing agent in yeast producing oxidative damage to DNA. As short deletions could be anticipated to arise as a result of action of non-homologous end-joining (NHEJ) and oxidative damage to DNA is primarily coped with base excision repair (BER), a contribution of these two pathways towards survival, DSB induction, mutation frequency and types of mutations following SeL exposure was examined in present study. First, we show that while NHEJ plays no role in repairing toxic DNA lesions induced by SeL, cells with impairment in BER are sensitized towards this compound. Of BER activities examined, those responsible for processing of 3'-blocking DNA termini seem to be the most crucial for manifestation of the toxic effects of SeL in yeast. Second, an impact of NHEJ and BER on DSB induction after SeL exposure turned to be inappreciable, as no increase in DNA double-strand breakage in NHEJ and BER single or NHEJ BER double mutant upon SeL exposure was observed. Finally, we demonstrate that impairment in both these pathways does not importantly change mutation frequency after SeL exposure and that NHEJ is not responsible for generation of short

  9. Classification of multiple diseases based on wavelet features

    Directory of Open Access Journals (Sweden)

    Nalini Bodasingi

    2017-03-01

    Full Text Available This study presents an efficient disease classification approach based on medical images. The approach is more efficient as it reduces the computational complexity. The implementation uses only two wavelet filters in selecting the texture features as compared with five filters used in the earlier research works. The computed average and energy features are fed to feed-forward neural network (FFNN and support vector machine (SVM classifiers. The SVM is proved as a better classifier than the FFNN for all the three diseases related to skin, breast and retina with an improved accuracies of 89%, 92% and 100%, respectively. Also, a graphical user interface is developed useful for various disease classification based on the whole dataset of size 100.

  10. Network Medicine: A Network-based Approach to Human Diseases

    Science.gov (United States)

    Ghiassian, Susan Dina

    With the availability of large-scale data, it is now possible to systematically study the underlying interaction maps of many complex systems in multiple disciplines. Statistical physics has a long and successful history in modeling and characterizing systems with a large number of interacting individuals. Indeed, numerous approaches that were first developed in the context of statistical physics, such as the notion of random walks and diffusion processes, have been applied successfully to study and characterize complex systems in the context of network science. Based on these tools, network science has made important contributions to our understanding of many real-world, self-organizing systems, for example in computer science, sociology and economics. Biological systems are no exception. Indeed, recent studies reflect the necessity of applying statistical and network-based approaches in order to understand complex biological systems, such as cells. In these approaches, a cell is viewed as a complex network consisting of interactions among cellular components, such as genes and proteins. Given the cellular network as a platform, machinery, functionality and failure of a cell can be studied with network-based approaches, a field known as systems biology. Here, we apply network-based approaches to explore human diseases and their associated genes within the cellular network. This dissertation is divided in three parts: (i) A systematic analysis of the connectivity patterns among disease proteins within the cellular network. The quantification of these patterns inspires the design of an algorithm which predicts a disease-specific subnetwork containing yet unknown disease associated proteins. (ii) We apply the introduced algorithm to explore the common underlying mechanism of many complex diseases. We detect a subnetwork from which inflammatory processes initiate and result in many autoimmune diseases. (iii) The last chapter of this dissertation describes the

  11. Efficacy and Safety of Augmenting the Preclose Technique with a Collagen-Based Closure Device for Percutaneous Endovascular Aneurysm Repair

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Rafiuddin, E-mail: rafiuddin.patel@ouh.nhs.uk [Oxford University Hospitals NHS Trust, Department of Radiology, John Radcliffe Hospital (United Kingdom); Juszczak, Maciej T. [Oxford University Hospitals NHS Trust, Department of Vascular Surgery, John Radcliffe Hospital (United Kingdom); Bratby, Mark J. [Oxford University Hospitals NHS Trust, Department of Radiology, John Radcliffe Hospital (United Kingdom); Sideso, Ediri [Oxford University Hospitals NHS Trust, Department of Vascular Surgery, John Radcliffe Hospital (United Kingdom); Anthony, Susan; Tapping, Charles R. [Oxford University Hospitals NHS Trust, Department of Radiology, John Radcliffe Hospital (United Kingdom); Handa, Ashok; Darby, Christopher R.; Perkins, Jeremy [Oxford University Hospitals NHS Trust, Department of Vascular Surgery, John Radcliffe Hospital (United Kingdom); Uberoi, Raman [Oxford University Hospitals NHS Trust, Department of Radiology, John Radcliffe Hospital (United Kingdom)

    2015-08-15

    PurposeTo report our experience of selectively augmenting the preclose technique for percutaneous endovascular aneurysm repair (p-EVAR) with an Angio-Seal device as a haemostatic adjunct in cases of significant bleeding after tensioning the sutures of the suture-mediated closure devices.Materials and MethodsProspectively collected data for p-EVAR patients at our institute were analysed. Outcomes included technical success and access site complications. A logistic regression model was used to analyse the effects of sheath size, CFA features and stent graft type on primary failure of the preclose technique necessitating augmentation and also on the development of complications.Resultsp-EVAR was attempted via 122 CFA access sites with a median sheath size of 18-French (range 12- to 28-French). Primary success of the preclose technique was 75.4 % (92/122). Angio-Seal augmentation was utilised as an adjunct to the preclose technique in 20.5 % (25/122). The overall p-EVAR success rate was 95.1 % (116/122). There was a statistically significant relationship (p = 0.0093) between depth of CFA and primary failure of preclose technique. CFA diameter, calcification, type of stent graft and sheath size did not have significant effects on primary preclose technique failure. Overall 4.9 % (6/122) required surgical conversion but otherwise there were no major complications.ConclusionAugmentation with an Angio-Seal device is a safe and effective adjunct to increase the success rate of the preclose technique in p-EVAR.

  12. Repair and regeneration in endodontics.

    Science.gov (United States)

    Lin, L M; Rosenberg, P A

    2011-10-01

    The ideal objective of treatment of established diseases, including irreversible pulpitis and apical periodontitis, is to achieve wound healing. Wound healing can result in repair or regeneration. The ultimate goal of wound healing is to restore the original architecture and biological function of the injured tissue or organ. Although humans are equipped with powerful innate and adaptive immune defence mechanisms, many intrinsic and extrinsic factors can affect wound healing. Complete regeneration following injury in humans can occur only in the pre-natal foetus within 24 weeks of gestation. Post-natal wounds including irreversible pulpitis or apical periodontitis always heal by repair or by a combination of repair and regeneration. Somatic cells, such as fibroblasts, macrophages, cementoblasts and osteoblasts, in the pulp and periapical tissues have limited potential for regeneration following injury and lack of telomerase. Wound healing of irreversible pulpitis and apical periodontitis requires recruitment and differentiation of progenitor/stem cells into tissue-committed somatic cells. Stem cell differentiation is regulated by intrinsic factors and extrinsic micro-environmental cues. Functionality of stem cells appears to show an age-related decline because of the change in intrinsic properties and diminished signals within the extrinsic local and systemic environment that modulate the function of stem cells or their progeny. Infection induces an immuno-inflammatory response and tissue destruction, which hinders the potential of tissue regeneration. Therefore, prevention, early detection and treatment of inflammation/infection of pulpal and periapical disease can enhance regeneration and minimize the repair of pulpal and periapical tissues after endodontic therapy. © 2011 International Endodontic Journal.

  13. Morphological and biochemical T2 evaluation of cartilage repair tissue based on a hybrid double echo at steady state (DESS-T2d) approach.

    Science.gov (United States)

    Welsch, Goetz H; Mamisch, Tallal C; Zak, Lukas; Mauerer, Andreas; Apprich, Sebastian; Stelzeneder, David; Marlovits, Stefan; Trattnig, Siegfried

    2011-10-01

    To use a new approach which provides, based on the widely used three-dimensional double-echo steady-state (DESS) sequence, in addition to the morphological information, the generation of biochemical T2 maps in one hybrid sequence. In 50 consecutive MRIs at 3.0 Tesla (T) after matrix-associated autologous chondrocyte transplantation (MACT) of the knee, by the use this new DESS-T2d approach, the morphological Magnetic resonance Observation of CArtilage Repair Tissue (MOCART) score, as well as biochemical T2d values were assessed. Furthermore, these results were correlated to standard morphological sequences as well as to standard multi-echo spin-echo T2 mapping. The MOCART score correlated (Pearson:0.945; P < 0.001) significantly as assessed with standard morphological sequences (68.8 ± 13.2) and the morphological images of the DESS T2d sequence (68.7 ± 12.6). T2 and T2d relaxation times (ms) were comparable in between the control cartilage (T2: 52.5 ± 11.4; T2d: 46.6 ± 10.3) and the repair tissue (T2: 54.4 ± 11.4; T2d: 47.5 ± 13.0) (T2: P = 0.157; T2d: P = 0.589). As expected, T2d values were lower than the standard-T2 values, however, both functional relaxation times correlated significantly (Pearson:0.429; P < 0.001). The presented hybrid approach provides the possibility to combine morphological and biochemical MRI in one fast 3D sequence, and thus, may attract for the clinical use of biochemical MRI. Copyright © 2011 Wiley-Liss, Inc.

  14. Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging

    NARCIS (Netherlands)

    Y. Kamenisch (York); M.I. Fousteri (Maria); J. Knoch (Jennifer); A.K. Von Thaler (Anna Katherina); B. Fehrenbacher (Birgit); H. Kato (Hiroki); T. Becker (Tim); M.E.T. Dollé (Martijn); R. Kuiper (Ruud); M. Majora (Marc); M. Schaller (Martin); G.T.J. van der Horst (Gijsbertus); H. van Steeg (Harry); M. Röcken (Martin); D. Rapaport (Doron); J. Krutmann (Jean); L.H.F. Mullenders (Leon); M. Berneburg (Mark)

    2010-01-01

    textabstractDefects in the DNA repair mechanism nucleotide excision repair (NER) may lead to tumors in xeroderma pigmentosum (XP) or to premature aging with loss of subcutaneous fat in Cockayne syndrome (CS). Mutations of mitochondrial (mt)DNA play a role in aging, but a link between the

  15. Thirty-day outcome and quality of life after endovascular abdominal aortic aneurysm repair in octogenarians based on the Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE)

    NARCIS (Netherlands)

    Pol, Robert A.; Zeebregts, Clark J.; van Sterkenburg, Steven M. M.; Reijnen, Michel M. P. J.

    Objectives: To determine 30-day outcome and quality of life after elective endovascular abdominal aortic aneurysm repair in octogenarians. Methods: From March 2009 to May 2011, 1200 patients with abdominal aortic aneurysms were treated with endovascular aneurysm repair (EVAR) using the Endurant

  16. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature

    DEFF Research Database (Denmark)

    Vilmar, A.; Sorensen, J.B.

    2009-01-01

    BACKGROUND: Patients diagnosed with advanced non-small cell lung cancer have a dismal prognosis and are often relative resistant to chemotherapy. A need for markers has emerged based on tumour biology in order to predict which patients will respond to treatment. Excision repair cross-complementat...

  17. Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA.

    Science.gov (United States)

    Hata, Kuniki; Urushibara, Ayumi; Yamashita, Shinichi; Lin, Mingzhang; Muroya, Yusa; Shikazono, Naoya; Yokoya, Akinari; Fu, Haiying; Katsumura, Yosuke

    2015-01-01

    Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 10(8) dm(3) mol(-1) s(-1) and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10-1000 μmol dm(-3)) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid.

  18. Atopic dermatitis, and the role for a ceramide-dominant, physiologic lipid-based barrier repair emulsion.

    Science.gov (United States)

    Kircik, Leon; Hougeir, Firas; Bikowski, Joseph

    2013-09-01

    Over the last half century, and especially over the last 15 years, understanding of the structure and function of the stratum corneum has evolved tremendously. Once conceptualized as an inactive film formed by lifeless, disintegrating keratinocytes, the stratum corneum is now recognized as a viable, functional structure that plays an important role in maintaining skin health and possibly mediating cutaneous diseases. Researchers and clinicians have also come to realize that the barrier functions not only to prevent the entry of exogenous factors, such as irritants or allergens, but that it also can mediate disease. We had already realized that dysfunction of the barrier may itself directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis. More specifically, evidence shows that epidermal barrier dysfunction is likely to be a precursor of cutaneous inflammation.

  19. Recombinant protein-based viral disease diagnostics in veterinary medicine.

    Science.gov (United States)

    Balamurugan, Vinayagamurthy; Venkatesan, Gnanavel; Sen, Arnab; Annamalai, Lakshmanan; Bhanuprakash, Veerakyathappa; Singh, Raj Kumar

    2010-09-01

    Identification of pathogens or antibody response to pathogens in human and animals modulates the treatment strategies for naive population and subsequent infections. Diseases can be controlled and even eradicated based on the epidemiology and effective prophylaxis, which often depends on development of efficient diagnostics. In addition, combating newly emerging diseases in human as well as animal healthcare is challenging and is dependent on developing safe and efficient diagnostics. Detection of antibodies directed against specific antigens has been the method of choice for documenting prior infection. Other than zoonosis, development of inexpensive vaccines and diagnostics is a unique problem in animal healthcare. The advent of recombinant DNA technology and its application in the biotechnology industry has revolutionized animal healthcare. The use of recombinant DNA technology in animal disease diagnosis has improved the rapidity, specificity and sensitivity of various diagnostic assays. This is because of the absence of host cellular proteins in the recombinant derived antigen preparations that dramatically decrease the rate of false-positive reactions. Various recombinant products are used for disease diagnosis in veterinary medicine and this article discusses recombinant-based viral disease diagnostics currently used for detection of pathogens in livestock and poultry.

  20. Therapeutics for Alzheimer's disease based on the metal hypothesis.

    Science.gov (United States)

    Bush, Ashley I; Tanzi, Rudolph E

    2008-07-01

    Alzheimer's disease is the most common form of dementia in the elderly, and it is characterized by elevated brain iron levels and accumulation of copper and zinc in cerebral beta-amyloid deposits (e.g., senile plaques). Both ionic zinc and copper are able to accelerate the aggregation of Abeta, the principle component of beta-amyloid deposits. Copper (and iron) can also promote the neurotoxic redox activity of Abeta and induce oxidative cross-linking of the peptide into stable oligomers. Recent reports have documented the release of Abeta together with ionic zinc and copper in cortical glutamatergic synapses after excitation. This, in turn, leads to the formation of Abeta oligomers, which, in turn, modulates long-term potentiation by controlling synaptic levels of the NMDA receptor. The excessive accumulation of Abeta oligomers in the synaptic cleft would then be predicted to adversely affect synaptic neurotransmission. Based on these findings, we have proposed the "Metal Hypothesis of Alzheimer's Disease," which stipulates that the neuropathogenic effects of Abeta in Alzheimer's disease are promoted by (and possibly even dependent on) Abeta-metal interactions. Increasingly sophisticated pharmaceutical approaches are now being implemented to attenuate abnormal Abeta-metal interactions without causing systemic disturbance of essential metals. Small molecules targeting Abeta-metal interactions (e.g., PBT2) are currently advancing through clinical trials and show increasing promise as disease-modifying agents for Alzheimer's disease based on the "metal hypothesis."

  1. Potential of neural stem cell-based therapies for Alzheimer's disease.

    Science.gov (United States)

    Li, Xue-Yuan; Bao, Xin-Jie; Wang, Ren-Zhi

    2015-09-01

    Alzheimer's disease (AD), known to be a leading cause of dementia that causes heavy social and financial burdens worldwide, is characterized by progressive loss of neurons and synaptic connectivity after depositions of amyloid-β (Aβ) protein. Current therapies for AD patients can only alleviate symptoms but cannot deter the neural degeneration, thus providing no long-term recovery. Neural stem cells (NSCs), capable of self-renewal and of differentiation into functional neurons and glia, have been shown to repair damaged networks and reverse memory and learning deficits in animal studies, providing new hope for curing AD patients by cell transplantation. Under AD pathology, the microenvironment also undergoes great alterations that affect the propagation of NSCs and subsequent therapeutic efficiency, calling for measures to improve the hostile environment for cell transplantation. This article reviews the therapeutic potential of both endogenous and exogenous NSCs in the treatment of AD and the challenges to application of stem cells in AD treatment, particularly those from the microenvironmental alterations, in the hope of providing more information for future research in exploiting stem cell-based therapies for AD. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  2. Content-Related Repairing of Inconsistencies in Distributed Data

    Institute of Scientific and Technical Information of China (English)

    Yue-Feng Du; De-Rong Shen; Tie-Zheng Nie; Yue Kou; Ge Yu

    2016-01-01

    Conditional functional dependencies (CFDs) are a critical technique for detecting inconsistencies while they may ignore some potential inconsistencies without considering the content relationship of data. Content-related conditional functional dependencies (CCFDs) are a type of special CFDs, which combine content-related CFDs and detect potential inconsistencies by putting content-related data together. In the process of cleaning inconsistencies, detection and repairing are interactive: 1) detection catches inconsistencies, 2) repairing corrects caught inconsistencies while may bring new incon-sistencies. Besides, data are often fragmented and distributed into multiple sites. It consequently costs expensive shipment for inconsistencies cleaning. In this paper, our aim is to repair inconsistencies in distributed content-related data. We propose a framework consisting of an inconsistencies detection method and an inconsistencies repairing method, which work iteratively. The detection method marks the violated CCFDs for computing the inconsistencies which should be repaired preferentially. Based on the repairing-cost model presented in this paper, we prove that the minimum-cost repairing using CCFDs is NP-complete. Therefore, the repairing method heuristically repairs the inconsistencies with minimum cost. To improve the efficiency and accuracy of repairing, we propose distinct values and rules sequences. Distinct values make less data shipments than real data for communication. Rules sequences determine appropriate repairing sequences to avoid some incorrect repairs. Our solution is proved to be more effective than CFDs by empirical evaluation on two real-life datasets.

  3. The first large population based twin study of coeliac disease

    Science.gov (United States)

    Greco, L; Romino, R; Coto, I; Di Cosmo, N; Percopo, S; Maglio, M; Paparo, F; Gasperi, V; Limongelli, M G; Cotichini, R; D'Agate, C; Tinto, N; Sacchetti, L; Tosi, R; Stazi, M A

    2002-01-01

    Background and aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1–134), independent of the DQ at risk genotype. Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region. PMID:11950806

  4. DESARDA’S NO MESH REPAIR VERSUS LICHTENSTEIN’S OPEN MESH REPAIR OF INGUINAL HERNIA: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Zaheer

    2015-09-01

    Full Text Available BACKGROUND : The tissue - based techniques are still acceptable for primary inguinal hernia repair according to the European Hernia Society guidelines. Desarda’s no mesh technique, introduced in 2001, is a hernia repair method using an undetached strip of external oblique Apo neurosis . This study compared outcomes after hernia repair with Desarda (D and mesh - based Lichtenstein (L techniques. METHODS : A total of 100 patients were randomly assigned to the D or L group (50 each. The primary outcomes measured were post - operative pain ( D ay1 and day 7, mean hospital stay (in days, return to basic activity (in days and recurrence. RESULTS : During the follow - up, no recurrences were observed in each group (p = 1.000. Average duration of the Desarda’s repair was 65.64 minutes, while the Lichtenstein repair lasted for 65.76 minutes. Mean VAS on 1 st post - operative day was significantly less in Desarda’s repair (2.86 than Lichenstein’s repair (3.50, (p=0.0004. Mean hospital stay was less in Desarda’s repair (2.58 days versus Lichtenstein’s repair (3.90 days p=0.0001. Return to basic physical activity was earlier in Desarda’s repair (7.04 days than Lichenstein’s repair (11.30 days, (p=<0.0001. However there was no recurrence in either group in 18 months follow up. CONCLUSIONS : The Desarda’s and Lichtenstein’s methods of primary inguinal hernia repair do not differ in the means of procedure complexity, surgery time and complication profile. However the return to basic physical activity was earlier in Desarda’s repair. Desarda’s no mesh repair is equally safe and more cost effective than Lichtenstein’s repair. The technique may potentially increase the number of tissue - based methods a vailable for treating inguinal hernias.

  5. Estimation of incidences of infectious diseases based on antibody measurements

    DEFF Research Database (Denmark)

    Simonsen, J; Mølbak, K; Falkenhorst, G

    2009-01-01

    Owing to under-ascertainment it is difficult if not impossible to determine the incidence of a given disease based on cases notified to routine public health surveillance. This is especially true for diseases that are often present in mild forms as for example diarrhoea caused by foodborne...... bacterial infections. This study presents a Bayesian approach for obtaining incidence estimates by use of measurements of serum antibodies against Salmonella from a cross-sectional study. By comparing these measurements with antibody measurements from a follow-up study of infected individuals...

  6. Workshop on DNA repair.

    NARCIS (Netherlands)

    A.R. Lehmann (Alan); J.H.J. Hoeijmakers (Jan); A.A. van Zeeland (Albert); C.M.P. Backendorf (Claude); B.A. Bridges; A. Collins; R.P.D. Fuchs; G.P. Margison; R. Montesano; E. Moustacchi; A.T. Natarajan; M. Radman; A. Sarasin; E. Seeberg; C.A. Smith; M. Stefanini (Miria); L.H. Thompson; G.P. van der Schans; C.A. Weber (Christine); M.Z. Zdzienika

    1992-01-01

    textabstractA workshop on DNA repair with emphasis on eukaryotic systems was held, under the auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout (The Netherlands) 14-19 April 1991. The local organization of the meeting was done under the auspices of the Medical Genetic C

  7. Laparoscopic lumbar hernia repair.

    Science.gov (United States)

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

    2006-04-01

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

  8. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  9. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  10. Disease Related Knowledge Summarization Based on Deep Graph Search

    Directory of Open Access Journals (Sweden)

    Xiaofang Wu

    2015-01-01

    Full Text Available The volume of published biomedical literature on disease related knowledge is expanding rapidly. Traditional information retrieval (IR techniques, when applied to large databases such as PubMed, often return large, unmanageable lists of citations that do not fulfill the searcher’s information needs. In this paper, we present an approach to automatically construct disease related knowledge summarization from biomedical literature. In this approach, firstly Kullback-Leibler Divergence combined with mutual information metric is used to extract disease salient information. Then deep search based on depth first search (DFS is applied to find hidden (indirect relations between biomedical entities. Finally random walk algorithm is exploited to filter out the weak relations. The experimental results show that our approach achieves a precision of 60% and a recall of 61% on salient information extraction for Carcinoma of bladder and outperforms the method of Combo.

  11. Shuttle Repair Tools Automate Vehicle Maintenance

    Science.gov (United States)

    2013-01-01

    that it could apply to ongoing maintenance work. According to Schuh, "SMART standardized and streamlined many shuttle repair processes, saving time and money while increasing safety and the quality of repairs." Maintenance technicians and engineers now had a tool that kept them in the field, and because SMART is capable of continually evolving, each time an engineer put it to use, it would enrich the Agency-wide knowledge base. "If an engineer sees something in the work environment that they could improve, a repair process or a procedure, SMART can incorporate that data for use in future operations," says Belson.

  12. New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites%组织修复与再生的新挑战:实现多种组织在损伤部位的同步修复与再生

    Institute of Scientific and Technical Information of China (English)

    付小兵

    2016-01-01

    Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years.However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases.Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

  13. Management and outcomes of colovesical fistula repair.

    Science.gov (United States)

    Lynn, Elizabeth T; Ranasinghe, Nalin E; Dallas, Kai B; Divino, Celia M

    2012-05-01

    This large retrospective study presents the largest colovesical fistula (CVF) series to date. We report on recurrence risk factors and patient satisfaction based on quality of life after CVF repair. Approval was obtained from The Mount Sinai School of Medicine Institutional Review Board, and a retrospective review was performed from 2003 to 2010 involving 72 consecutive patients who underwent a colovesical fistula repair. The CVF recurrence rate was 11 per cent. Ten percent of our patients who had a history of radiation therapy were at a significantly higher risk of developing a recurrence. Noted recurrence rates were significantly higher in advanced bladder repairs compared with simple repair (P = 0.022). The modified (Gastrointestinal Quality of Life Index) surveys showed overall patient satisfaction score was 3.6, out of a maximum score of 4, regardless of the type of repair or any postoperative complications. Our study found the CVF recurrence rate to be 11 per cent. Patients at higher risk of recurrence include those needing advanced bladder repair, those with "complex" CVF, and those whose fistulas involve the urethra. Patient satisfaction was found to be more closely linked to the resolution of CVF symptoms, irrespective of the type of repair performed or development of postoperative complications.

  14. Establishment of Kawasaki disease database based on metadata standard.

    Science.gov (United States)

    Park, Yu Rang; Kim, Jae-Jung; Yoon, Young Jo; Yoon, Young-Kwang; Koo, Ha Yeong; Hong, Young Mi; Jang, Gi Young; Shin, Soo-Yong; Lee, Jong-Keuk

    2016-07-01

    Kawasaki disease (KD) is a rare disease that occurs predominantly in infants and young children. To identify KD susceptibility genes and to develop a diagnostic test, a specific therapy, or prevention method, collecting KD patients' clinical and genomic data is one of the major issues. For this purpose, Kawasaki Disease Database (KDD) was developed based on the efforts of Korean Kawasaki Disease Genetics Consortium (KKDGC). KDD is a collection of 1292 clinical data and genomic samples of 1283 patients from 13 KKDGC-participating hospitals. Each sample contains the relevant clinical data, genomic DNA and plasma samples isolated from patients' blood, omics data and KD-associated genotype data. Clinical data was collected and saved using the common data elements based on the ISO/IEC 11179 metadata standard. Two genome-wide association study data of total 482 samples and whole exome sequencing data of 12 samples were also collected. In addition, KDD includes the rare cases of KD (16 cases with family history, 46 cases with recurrence, 119 cases with intravenous immunoglobulin non-responsiveness, and 52 cases with coronary artery aneurysm). As the first public database for KD, KDD can significantly facilitate KD studies. All data in KDD can be searchable and downloadable. KDD was implemented in PHP, MySQL and Apache, with all major browsers supported.Database URL: http://www.kawasakidisease.kr.

  15. Localized Knowledge based System for Human Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    Adane Nega Tarekegn

    2016-03-01

    Full Text Available —Knowledge based system can be designed to solve complex medical problems. It incorporates the expert‟s knowledge that has been coded into facts, rules, heuristics and procedures. Incorporation of local languages with the knowledge based system allows endusers communicate with the system in a simpler and easier way. In this study a localized knowledge based system is developed for TB disease diagnosis using Ethiopian national language. To develop the localized knowledge based system, tacit knowledge is acquired from domain experts using interviewing techniques and explicit knowledge is captured from documented sources using relevant documents analysis method. Then the acquired knowledge is modeled using decision tree structure that represents concepts and procedures involved in diagnosis of disease. Production rules are used to represent domain knowledge. The localized knowledge based system is developed using SWI Prolog version 6.4.1 programming language. Prolog supports natural language processing feature to localize the system. As a result, the system is implemented using Amharic language (the national language of Ethiopia user interface. With Localization, users at remote areas and users who are not good in foreign languages are benefited enormously. The system is tested and evaluated to ensure that whether the performance of the system is accurate and the system is usable by physicians and patients. The average performance of the localized knowledge based system has registered 81.5%.

  16. Three-dimensional echocardiographic assessment of the repaired mitral valve.

    Science.gov (United States)

    Maslow, Andrew; Mahmood, Feroze; Poppas, Athena; Singh, Arun

    2014-02-01

    This study examined the geometric changes of the mitral valve (MV) after repair using conventional and three-dimensional echocardiography. Prospective evaluation of consecutive patients undergoing mitral valve repair. Tertiary care university hospital. Fifty consecutive patients scheduled for elective repair of the mitral valve for regurgitant disease. Intraoperative transesophageal echocardiography. Assessments of valve area (MVA) were performed using two-dimensional planimetry (2D-Plan), pressure half-time (PHT), and three-dimensional planimetry (3D-Plan). In addition, the direction of ventricular inflow was assessed from the three-dimensional imaging. Good correlations (r = 0.83) and agreement (-0.08 +/- 0.43 cm(2)) were seen between the MVA measured with 3D-Plan and PHT, and were better than either compared to 2D-Plan. MVAs were smaller after repair of functional disease repaired with an annuloplasty ring. After repair, ventricular inflow was directed toward the lateral ventricular wall. Subgroup analysis showed that the change in inflow angle was not different after repair of functional disease (168 to 171 degrees) as compared to those presenting with degenerative disease (168 to 148 degrees; p<0.0001). Three-dimensional imaging provides caregivers with a unique ability to assess changes in valve function after mitral valve repair. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Nucleotide excision repair syndromes: molecular basis and clinical symptoms.

    NARCIS (Netherlands)

    D. Bootsma (Dirk); G. Weeda (Geert); W. Vermeulen (Wim); H. van Vuuren; C. Troelstra (Christine); J.H.J. Hoeijmakers (Jan); P.J. van der Spek (Peter)

    1995-01-01

    textabstractThe phenotypic consequences of a nucleotide excision repair (NER) defect in man are apparent from three distinct inborn diseases characterized by hypersensitivity of the skin to ultraviolet light and a remarkable clinical and genetic heterogeneity. These are the prototype repair

  18. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne)

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in

  19. A Novel Approach to Stimulate Cartilage Repair: Targeting Collagen Turnover

    NARCIS (Netherlands)

    Y.M. Bastiaansen-Jenniskens (Yvonne)

    2009-01-01

    textabstractOA is a complex disease of which the ethiopathology is not completely known and therapies to repair cartilage are still under investigation. The increase of collagen type II expression in osteoarthritic cartilage suggests an activated repair mechanism that is however ineffective in repai

  20. Mitral Valve Repair: The Chordae Tendineae

    Directory of Open Access Journals (Sweden)

    Carlos-A Mestres

    2015-10-01

    Full Text Available Repair of the mitral valve is the treatment of choice for mitral valve regurgitation when the anatomy is favorable. It is well known that mitral valve repair enjoys better clinical and functional results than any other type of valve substitute. This fact is beyond doubt regardless of the etiology of the valve lesion and is of particular importance in degenerative diseases.This review analyzes the most important advances in the knowledge of the anatomy, pathophysiology, and chordal function of the mitral valve as well as the different alternatives in the surgical repair and clinical results of the most prevalent diseases of the mitral valve. An attempt has been made to organize the acquired information available in a practical way.

  1. PETROBAS amazon gas pipeline - repair logistics evaluation study

    Energy Technology Data Exchange (ETDEWEB)

    Faertes, Denise [Petrobas, Rio de Janeiro, (Brazil); Domingues, Joaquim [DNV, Rio de Janeiro, (Brazil)

    2010-07-01

    Repair logistics is often a challenge in the pipeline industry because of extreme operating conditions. This paper presents an evaluation of the repair logistics at the Urucu-Coari-Manaus gas pipeline in Brazil. This study establishes strategies for each identified failure scenario, classified by type of repair, logistics, resources and costs. Several meetings and brain-storming workshops, bringing together experienced teams from PETROBRAS took place. They provided an analysis of operating conditions for different pipeline sections and an evaluation of the best practices and strategies to be adopted for pipeline repair. Different repair strategies and logistics options were compared with a base case crisis scenario to evaluate gains in terms of repair time reductions. A cost analysis was then done to prioritize these strategies. This study provided important support to the decision making process, with respect to different repair resources and logistics options. It provided formal and innovative solutions.

  2. Repair of Electronics for Long Duration Spaceflight

    Science.gov (United States)

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

    2007-01-01

    , Langley Research Center, Johnson Space Center, the National Center for Space Exploration Research, and the U.S. Navy. The project goals are 1) develop and demonstrate a manually-operated electronics repair capability to be conducted in a spacecraft environment; and 2) develop guidelines for designs of electronics that facilitates component-level repair for future space exploration efforts. This multi-faceted program utilizes a cross-disciplinary approach to examine pre- and post-repair diagnostics, conformal coating removal and replacement, component soldering, and electronics design for supportability. These areas are investigated by a combination of trade studies, ground based testing, reduced gravity aircraft testing, and actual spaceflight testing on the International Space Station (ISS) in multiple experiments. This paper details the efforts of this program, with emphasis on early trade study results, ground-based efforts, and two upcoming ISS experiments.

  3. Tree-based disease classification using protein data.

    Science.gov (United States)

    Zhu, Hongtu; Yu, Chang-Yung; Zhang, Heping

    2003-09-01

    A reliable and precise classification of diseases is essential for successful diagnosis and treatment. Using mass spectrometry from clinical specimens, scientists may find the protein variations among disease and use this information to improve diagnosis. In this paper, we propose a novel procedure to classify disease status based on the protein data from mass spectrometry. Our new tree-based algorithm consists of three steps: projection, selection and classification tree. The projection step aims to project all observations from specimens into the same bases so that the projected data have fixed coordinates. Thus, for each specimen, we obtain a large vector of 'coefficients' on the same basis. The purpose of the selection step is data reduction by condensing the large vector from the projection step into a much lower order of informative vector. Finally, using these reduced vectors, we apply recursive partitioning to construct an informative classification tree. This method has been successfully applied to protein data, provided by the Department of Radiology and Chemistry at Duke University.

  4. Diverless pipeline repair system for deep water

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Carlo M. [Eni Gas and Power, Milan (Italy); Fabbri, Sergio; Bachetta, Giuseppe [Saipem/SES, Venice (Italy)

    2009-07-01

    SiRCoS (Sistema Riparazione Condotte Sottomarine) is a diverless pipeline repair system composed of a suite of tools to perform a reliable subsea pipeline repair intervention in deep and ultra deep water which has been on the ground of the long lasting experience of Eni and Saipem in designing, laying and operating deep water pipelines. The key element of SiRCoS is a Connection System comprising two end connectors and a repair spool piece to replace a damaged pipeline section. A Repair Clamp with elastomeric seals is also available for pipe local damages. The Connection System is based on pipe cold forging process, consisting in swaging the pipe inside connectors with suitable profile, by using high pressure seawater. Three swaging operations have to be performed to replace the damaged pipe length. This technology has been developed through extensive theoretical work and laboratory testing, ending in a Type Approval by DNV over pipe sizes ranging from 20 inches to 48 inches OD. A complete SiRCoS system has been realised for the Green Stream pipeline, thoroughly tested in workshop as well as in shallow water and is now ready, in the event of an emergency situation.The key functional requirements for the system are: diverless repair intervention and fully piggability after repair. Eni owns this technology and is now available to other operators under Repair Club arrangement providing stand-by repair services carried out by Saipem Energy Services. The paper gives a description of the main features of the Repair System as well as an insight into the technological developments on pipe cold forging reliability and long term duration evaluation. (author)

  5. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5-15 years (mean 4.5. Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50% with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

  6. Evidence-based therapy for sleep disorders in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    LIU Ling

    2013-08-01

    Full Text Available Objective To evaluate the effectiveness of the treatments for sleep disorders in neurodegenerative diseases so as to provide the best therapeutic regimens for the evidence-based treatment. Methods Search PubMed, MEDLINE, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases with "sleep disorder or sleep disturbance", "neurodegenerative diseases", "Parkinson's disease or PD", "Alzheimer's disease or AD", "multiple system atrophy or MSA" as retrieval words. The quality of the articles were evaluated with Jadad Scale. Results A total of 35 articles, including 2 systematic reviews, 5 randomized controlled trials, 13 clinical controlled trials, 13 case series and 2 epidemiological investigation studies were included for evaluation, 13 of which were high grade and 22 were low grade articles. Clinical evidences showed that: 1 advice on sleep hygiene, careful use of dopaminergic drugs and hypnotic sedative agents should be considered for PD. Bright light therapy (BLT may improve circadian rhythm sleep disorders and clonazepam may be effective for rapid eye movement sleep behavior disorder (RBD. However, to date, very few controlled studies are available to make a recommendation for the management of sleep disorders in PD; 2 treatments for sleep disorders in AD include drug therapy (e.g. melatonin, acetylcholinesterase inhibitors, antipsychotic drugs, antidepressants and non-drug therapy (e.g. BLT, behavior therapy, but very limited evidence shows the effectiveness of these treatments; 3 the first line treatment for sleep-related breathing disorder in MSA is nasal continuous positive airway pressure (nCPAP, and clonazepam is effective for RBD in MSA; 4 there is rare evidence related to the treatment of sleep disorders in dementia with Lewy body (DLB and amyotrophic lateral sclerosis (ALS. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment in neurodegenerative

  7. Stem cells for cardiac repair: an introduction

    Institute of Scientific and Technical Information of China (English)

    Bastiaan C du Pr(e); Pieter A Doevendans; Linda W van Laake

    2013-01-01

    Cardiovascular disease is a major cause of morbidity and mortality throughout the world. Most cardiovascular diseases, such as ischemic heart disease and cardiomyopathy, are associated with loss of functional cardiomyocytes. Unfortunately, the heart has a limited regenerative capacity and is not able to replace these cardiomyocytes once lost. In recent years, stem cells have been put forward as a potential source for cardiac regeneration. Pre-clinical studies that use stem cell-derived cardiac cells show promising results. The mechanisms, though, are not well understood, results have been variable, sometimes transient in the long term, and often without a mechanistic explanation. There are still several major hurdles to be taken. Stem cell-derived cardiac cells should resemble original cardiac cell types and be able to integrate in the damaged heart. Integration requires ad