Treatments with Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have offered patients carrying cancers with mutated BRCA1 or BRCA2 genes a new and in many cases effective option for disease control. There is potentially a large patient population that may also benefit from PARP inhibitor treatment, either in monotherapy or in combination with chemotherapy. Here, we describe the multifaceted role of PARP inhibitors and discuss which treatment options could potentially be useful to gain disease control without potentiating side effects.
Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors- Pipeline Insights, 2015, provides the in-depth analysis of the pipeline assets across the Poly Adenosine Diphosphate (ADP) Ribose Polymerase (PARP) Inhibitors. The main objective of this report to track competitor pipeline molecules, related research activities, technology, collaborations, in-licensing and out-licensing deals.
Mouse monoclonal Poly (ADP-Ribose) Polymer antibody [10H]. Validated in IHC and tested in Rat, Human. Cited in 31 publication(s). Independently reviewed in 12 review(s). Immunogen corresponding to -.
Recent evidence obtained with transgenic knockout mice suggests that the enzyme poly(ADP-ribose)polymerase (PARP) does not play a direct role in DNA break processing [1, 2]. Nevertheless,...
Poly(ADP-ribose) polymerase 1 (PARP-1) and poly(ADP-ribose) glycohydrolase (PARG) regulate transcriptional activity by modifying target nuclear proteins with the addition and removal of ADP-ribose polymers, respectively. While the role of PARP-1 has been established, the exact function of PARG in the nucleus is less clear, although its assumed that PARP-1 and PARG have opposing functions in gene regulation. In this article, however, the authors show that this is not the case. Combining short hairpin RNA (shRNA) knockdown with microarray analysis in MCF-7 cells, they determined that these two enzymes often act in a similar, rather than antagonistic, manner. PARP-1 and PARG generally localized to similar target promoters, most notably in genes for stress response and metabolism, and, in about half of the genes tested, PARP-1 binding was dependent on PARG. In addition, studies using shRNA-resistant catalytic mutants revealed that enzymatic activity was not required in some target genes. So, rather ...
Conference (2017, October). Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux États-Unis avec un programme sur ... [more ▼]. Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux États-Unis avec un programme sur lintelligence artificielle dispensé par luniversité de Stanford, ces cours en ligne accessibles gratuitement font miroiter la possibilité dune démocratisation maximale des savoirs. A ce titre, les MOOC bénéficient des innovations issues du Web 2.0 : ils tirent le meilleur de la rencontre entre les nouveaux usages induits par les réseaux sociaux et les apports de la pédagogique active. Ces cinq dernières années, nous avons dispensé les travaux pratiques en Histologie aux 500 étudiants de première année détude de la faculté de Médecine de ...
Conference (2017, November). Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux Etats-Unis dans de grandes universités ... [more ▼]. Lacronyme anglophone MOOC désigne les « Massive Open Online Courses » que lon pourrait traduire par « formations en ligne massives ouvertes à tous ». Nés aux Etats-Unis dans de grandes universités, ces cours en ligne accessibles gratuitement laissent espérer une démocratisation maximale des savoirs. Ces cinq dernières années, nous avons dispensé les travaux pratiques en Histologie aux 500 étudiants de première année détude de la faculté de Médecine de lUniversité de Liège par une méthodologie hybride alliant e-learning et présentiel (Multon et al., 2015). Forte de cette expérience réussie, notre équipe a réalisé un MOOC qui fait partie intégrante du cursus de nos étudiants depuis cette ...
Ated statistic is the odds ratio (instead of fold-change). Matching 95 CIs were calculated as described . f p-values were calculated using the Fishers exact
To optimize and validate a recently developed quantitative DNA damage detection assay for high-throughput screening applications, and to compare it directly with existing techniques to show substantial improvements. Targeted improvements include superior sensitivity, specificity and ability to characterize a broader array of DNA adducts and other lesions than with currently available approaches ...
Abstract: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition. A number of strategies have been proposed to identify BRCAness, including identifying defects in other genes that modulate homologous recombination and characterizing the mutational and transcriptional signatures of BRCAness. In addition to olaparib, a number of other PARP inhibitors are in clinical development. This article reviews the development of PARP inhibitors other than olaparib, and discusses the evidence for PARP inhibitors beyond BRCA1/2-mutant ...
Poly(ADP-ribose) polymerase activity in nuclei isolated from differentiating cardiac muscle of the rat has been characterized and its activity measured during development. Optimum enzyme activity is observed at pH 8.5. Poly(ADP-ribose) polymerase is inhibited by ATP, thymidine, nicotinamide, theophylline, 3-isobutyl-1-methylxanthine and caffeine and stimulated by actinomycin D. The activity measured under optimal assay conditions increases during differentiation of cardiac muscle and is inversely related to the rate of DNA synthesis and to the activities of DNA polymerase α and thymidine kinase. When DNA synthesis and the activity of DNA polymerase α are inhibited in cardiac muscle of the 1-day-old neonatal rat by dibutyryl cyclic AMP or isoproterenol, the specific activity of poly(ADP-ribose) polymerase measured in isolated nuclei is increased. The concentration of NAD+ in cardiac muscle increases during postnatal development. In the adult compared with the 1-day-old neonatal rat the ...
Poly(ADP-ribosylation) is a post-translational modification of nuclear proteins involved in several cellular events as well as in processes that characterize the infective cycle of some viruses. In the present study, we investigated the role of poly(ADP-ribosylation) on Epstein-Barr Virus (EBV) lytic cycle activation. Inhibition of PARP-1 by 3-aminobenzamide (3-ABA) during EBV induction, diminished cell damage and apoptosis in the non-productive Raji cell line while markedly reducing the release of viral particles in the productive Jijoye cells. Furthermore, incubation with 3-ABA up-regulated the levels of LMP1 and EBNA2 latent viral proteins. At the same time, it slightly affected the expression of the immediate early BZLF1 gene, but largely down-regulated the levels of the early BFRF1 protein. The modulation of the expression of both latent and lytic EBV genes appeared to be post-transcriptionally regulated. Taken together the data indicate that PARP-1 plays a role in the progression of EBV lytic
IL-4 is survival factor for lymphocytes and other hematopoietic cells. Whether there are mechanisms of pro-survival signaling induced by IL-4 apart from PI3K-Akt activation is not fully clear. Our laboratory identified PARP-14, a poly-ADP-ribose polymerase subfamily member, as a Stat6-interacting protein. PARP-14 is highly expressed in lymphoid organs, influences B cell subset ratios as well as the IgA response to antigen, and has intrinsic ADP-ribosyltransferase activity. ADP-ribosyltransferases and PARPs catalyze mono- and poly-ADP-ribosylation, transferring ADP from NAD+ to target proteins. ADP-ribosylation is a post-translational modification used by bacterial exotoxins to impact signal transduction, or, in the case of the mammalian PARP-1, to influence gene transcription and DNA repair or trigger apoptosis. Almost nothing is known about biological roles or mechanisms of action of other mammalian PARPs. We now show that PARP-14 is essential for full survival signaling despite normal Akt ...
The second recently approved drug is olaparib, which is indicated as monotherapy for women who have germline BRCA mutations and have been treated with 3 or more lines of previous chemotherapy. Olaparib is an inhibitor of the enzyme poly(adenosine diphosphate-ribose) polymerase (PARP). Approval in December 2014 was based on a trial by Kaufman and colleagues that included patients with ovarian cancer and germline BRCA mutations. The final publication included 193 patients with a median of 4 prior regimens; all were considered platinum resistant or not suitable for further platinum therapy. Using single-agent olaparib, the response rate was 31% with a 225-day median duration of response. Generally, toxicities were mild to moderate and included fatigue, nausea and vomiting, and anemia. One concern about olaparib is the potentially increased rate of myelodysplastic syndrome and acute myeloid leukemia (2% in this trial).. H&O Are there any more angiogenesis inhibitors in current or recent clinical ...
article{1cb77357-aca8-4b11-9d70-6a2e46c89bc9, abstract = {We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval ...
The Poly (ADP-Ribose) Antibody is an anti-poly (ADP-ribose) antibody raised in mouse and can be used for Western blot, IHC, and ICC detection.
The Poly (ADP-Ribose) Antibody is an anti-poly (ADP-ribose) antibody raised in mouse and can be used for Western blot, IHC, and ICC detection.
Results Decreased expression of PARP1 was detected by immunohistochemistry in skin sections of SSc patients, particularly in fibroblasts. Inhibition of PARylation by 3AB augmented the stimulatory effects of TGFβ on fibroblasts in vitro. PARP1 inhibition increased Smad dependent transcription in reporter assays and promoted the transcription of TGFβ/Smad target genes. Treatment with 3AB also stimulated the collagen release and fostered the expression of contractile proteins with increased expression of α-smooth muscle actin (α-SMA) and enhanced formation of stress fiber formation compared to fibroblasts stimulated with TGFβ alone. Inhibition of PARylation also exacerbated experimental fibrosis in vivo. Treatment with 3AB induced a more severe fibrotic response to bleomycin with increased dermal thickening by up to 103% (p,0.0001), hydroxyproline contents and myofibroblast counts compared to control mice (p,0.0001 and p=0.0059). Inhibition of PARylation also strongly exacerbated fibrosis in ...
There is a need to improve treatments for metastatic breast cancer. Here we show activation of the phosphoinositide 3-kinase (PI3K) and MAP kinase (MAPK) pathways in a MMTV-CreBRCA1f/fp53+/- mouse model of breast cancer. When treated with the pan-Class IA PI3K-inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK-pathway at the "pushing margin". Surprisingly, PI3K-inhibition increased indicators of DNA damage, poly-ADP-ribosylation and γH2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. PARP-inhibitor Olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and Olaparib delayed tumor doubling to more than 70 days in the mouse model and over 50 days in xenotransplants from human BRCA1-related tumors, suggesting ...
Genetic Instability is an enabling cancer phenotype associated with nearly all tumours. Sheffield has a strong tradition in basic research that aims to uncover the fundamental mechanisms through which DNA integrity is maintained, and to subsequently discover how their dysregulation contributes to cancer.. The work of several PIs is integrated in the YCR Institute for Cancer Studies in the Department of Oncology, where the groups of Dr Helen Bryant, Dr Spencer Collis, Professor Mark Meuth and Dr Cyril Sanders investigate the molecular mechanisms of DNA replication and remodelling, DNA damage detection and repair, while cancer-associated protein kinases that control cell cycle checkpoints are the subject of pre-clinical work in Dr Patrick Eyers lab. Elsewhere in the University this work is complemented by the research groups of Dr Alastair Goldman, Professor Stuart Wilson, Dr Karen Sisley and Professor Carl Smythe, who each investigate how distinct normal and cancer cell types maintain genomic ...
Background: Poly (ADP-ribosyl) polymerase 1 (PARP1) is important in maintaining genomic stability, repairing DNA damage, and regulating transcriptional processe
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Haughton, G; Lanier, L L.; Babcock, G F.; Lynes, D M.; and willexploit, N., "Ation of the surface idiotype as tumor specific antigen." (1978). Subject Strain Bibliography 1978. 2066 ...
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This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008 ...
|p|BYK 49187 is a potent inhibitor of PARP-1 and PARP-2 with pIC50 value pIC50 values of 8.36 and 7.50 for cell-free recombinant PARP-1 and murine PARP-2 respectively [1].|br /|Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a numb
View mouse Macrod2 Chr2:140395309-142392966 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
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A Membrane-bound or cytosolic enzyme that catalyzes the synthesis of Cyclic ADP-Ribose (cADPR) from Nicotinamide Adenine Dinucleotide (NAD). This enzyme generally catalyzes the Hydrolysis of cADPR to ADP-Ribose, as well, and sometimes the synthesis of Cyclic ADP-Ribose 2 phosphate (2-P-cADPR) from NADP ...
Nowadays it has become evident that a chronic systemic inflammation is present in patients suffering from chronic obstructive pulmonary disease (COPD).. The role of the nuclear enzyme poly(adenosine diphosphate-ribose)polymerase (PARP) as a key mediator within these systemic inflammatory processes as well as in COPD associated exercise intolerance and muscle weakness could recently been identified. The attenuating effect of dietary ingredients with PARP inhibiting activity on systemic inflammation was supported by data from in vitro and in vivo studies, from other groups as well as from our own lab. We identified several caffeine metabolites as potent inhibitors of the most abundant PARP-isoform PARP-1 in-vitro, in animal models as well as in ex-vivo experiments with whole blood from COPD patients.. However, clinical data with respect to their anti-inflammatory effects in COPD patients are currently not available for none of these substances. Therefore, the current clinical pilot study is ...
Poly (ADP-ribose) polymerases (PARPs) are a family of related enzymes that catalyze the transfer of ADP-ribose onto target proteins. PAR synthesis and subsequent degradation by poly-(ADP-ribose) glycohydrolase (PARG) are important roles in DNA repair. The discovery that certain tumors are defective in homologous recombination repair and depend on PARP-mediated DNA repair for survival suggests PARP and PARG as potential targets in cancer therapy. In addition, Tankyrase 1 (PARP 5a) plays an important role in telomere elongation. Screening tools for potential PARP, PARG and Tankyrase inhibitors are important for drug discovery.. Trevigen offers kits including purified enzymes, antibodies and reagents to measure PARP 1, Tankyrase 1, PARG and PAR. These assays are well suited for the large-scale screening of compound libraries, IC50 determination of potential PARP inhibitors, and measurement of the in vivo activity in cell extracts or peripheral blood mononuclear cells. In addition, monoclonal and ...
Although hyperthermia offers clinical appeal to sensitize cells to chemotherapy, this approach has been limited in terms of long-term outcome as well as economic and technical burden. Thus, a more detailed knowledge about how hyperthermia exerts its effects on chemotherapy may illuminate ways to improve the approach. Here, we asked whether hyperthermia alters the response to chemotherapy-induced DNA damage and whether this mechanism is involved in its sensitizing effect in BRCA-competent models of ovarian and colon cancer. Notably, we found that hyperthermia delayed the repair of DNA damage caused by cisplatin or doxorubicin, acting upstream of different repair pathways to block histone polyADP-ribosylation (PARylation), a known effect of chemotherapy. Furthermore, hyperthermia blocked this histone modification as efficiently as pharmacologic inhibitors of PARP (PARPi), producing comparable delay in DNA repair, induction of double-strand breaks (DSB), and cell cytotoxicity after chemotherapy. ...
Removes ADP-ribose from asparatate and glutamate residues in proteins bearing a single ADP-ribose moiety. Inactive towards proteins bearing poly-ADP-ribose. Deacetylates O-acetyl-ADP ribose, a signaling molecule generated by the deacetylation of acetylated lysine residues in histones and other proteins. Plays a role in estrogen signaling. Binds to androgen receptor (AR) and amplifies the transactivation function of AR in response to androgen. May play an important role in carcinogenesis and/or progression of hormone-dependent cancers by feed-forward mechanism that activates ESR1 transactivation. Could be an ESR1 coactivator, providing a positive feedback regulatory loop for ESR1 signal transduction. Could be involved in invasive growth by down-regulating CDH1 in endometrial cancer cells. Enhances ESR1-mediated transcription activity.
Mammalian cells have developed complex mechanisms to identify DNA damage and activate the required response to maintain genome integrity. Those mechanisms include DNA damage detection, DNA repair, cell cycle arrest and apoptosis which operate together to protect the conceptus from DNA damage origina …
ABT-737 is an orally available inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, ABT-767 selectively binds to PARP 1 and 2, thereby preventing repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. ABT-767 may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance.
The gene PADPRP codes for a nuclear enzyme Poly (ADP-ribose) polymerase. This enzyme is a DNA binding protein that modulates chromatin structure adjacent to DNA strand breaks (Smulson and Sugimura...
Boccardi, S., Calla, D. B., Malfense Fierro, G. P., Ciampa, F. and Meo, M., 2016. Nonlinear damage detection and localization using a time domain approach. In: Yu, T., Gyekenyesi, A. L., Shull, P. J. and Wu, H. F., eds. Nondestructive Characterization and Monitoring of Advanced Materials, Aerospace, and Civil Infrastructure 2016 ...
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Use: Roller blinds. Number of colours: 6 (Show all) Material: 100% PLF CS. Fabric width: 300 cm/118 inch/3.28 yard. Max. width of the system: 250 cm/98 inch/2.73 yard. Max. height of the system: 300 cm/118 inch/3.28 yard. Weight: 125 g/m². Sound absorption: αw 0.40. ...
A study to better understand the association between a group of thrombotic and inflammatory biomarkers and the MetS. by Aldi T Kraja, Michael A Province, D
Poly(ADP-ribosyl)ation of proteins is an important switch in cellular processes including differentiation. In particular, recent advances reveal emerging role in differentiation of cancer cells. Here we described the effect of poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide on a morphological feature of differentiation in transformed endothelial cells GM7373. Exposed to this drug, the cells displayed a 40% growth inhibition due to apoptosis, valued by time-lapse videomicroscopy and TUNEL assay. At the same time, cells showed enhanced motility and, when cultured on Matrigel enriched with FGF2 plus 3-aminobenzamide, began to organize a capillary network, in an Akt phosphorylation dependent manner, accompanied by a cyclooxygenase-2 induction. These results validate the role of poly(ADP-ribose) polymerase activity in cell differentiation and confirm the hypothesis that PARP may be a useful target for anticancer drugs.. ...
Carcinoid neuroendocrine tumors (CNETs) are resistant to chemotherapy and the higher level doses of single or combination chemotherapy that are effective against these cancers also cause significant side-effects to the surrounding healthy tissues; therefore it is necessary to potentiate chemotherapy of these cancers. In the advanced clinical trials for different cancers, the pharmacological inhibitors of the DNA damage-responsive nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1 or PARP) have shown a significant promise either as monotherapy or as potentiators of other chemotherapeutic agents. Here, we examined whether PARP-inhibitor PJ-34 can potentiate the therapy of CNETs by streptozotocin (STZ), because STZ causes DNA damage that is repaired by base excision repair pathway in which PARP-1 is known to play a significant role. We used the CNDT2.5 as model NET cells to show that treatment of cells with 1 μM PJ-34 could effectively block the activation of PARP in response to 0.5 and 1 mg/ml ...
This is probably the most appropriate time for the development of robust and reliable structural damage detection systems as aging civil engineering structures, such as bridges, are being used past their life expectancy and beyond their original design loads. Often, when a significant damage to the structure is discovered, the deterioration has already progressed far and required repair is substantial. This is both expensive and has negative impact on the environment and traffic during replacement. For the exposed reasons the demand for efficient Structural Health Monitoring techniques is currently extremely high. This licentiate thesis presents a two-stage model-free damage detection approach based on Machine Learning. The method is applied to data gathered in a numerical experiment using a three-dimensional finite element model of a railway bridge. The initial step in this study consists in collecting the structural dynamic response that is simulated during the passage of a train, considering ...
adshelp[at]cfa.harvard.edu The ADS is operated by the Smithsonian Astrophysical Observatory under NASA Cooperative Agreement NNX16AC86A ...
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Ation, properties . Upon cytosolic entry, A-components mono-ADP-ribosylate globular (G)-actin at arginine-177 that then inhibits actin filament formation and
Ion-ele ctron re a ction b ased fr agment ation methods (ExD) in t andem m ass spe ctrometr y (MS), su ch as ele ctron c apture disso ci ation (ECD) and ele ctron tr ansfer disso ci ation (ETD) repres
GenDR A curated database of genes associated with dietary restriction in model organisms either from genetic manipulation experiments or gene expression profiling.. ...
1. F. Abdenur, C. Bonatti, S. Crovisier, Global dominated splittings and the C1 Newhouse phenomenon, Proc. Amer. Math. Soc., 134 (2006), 2229-2237 , MR 2213695 , Zbl 1088.37013 2. F. Abdenur, C. Bonatti, S. Crovisier, L. Díaz, Generic diffeomorphisms on compact surfaces, Fundam. Math., 187 (2005), 127-159 , MR 2214876 , Zbl 1089.37032 3. F. Abdenur and L. Díaz, Pseudo-orbit shadowing in the C1-topology, to appear in Discrete Cont. Dyn. Syst. , MR 2257429 , Zbl 1132.37014 4. R. Abraham, S. Smale, Nongenericity of Ω-stability, Global analysis I, Proc. Symp. Pure Math. AMS, 14 (1970), 5-8 , Zbl 0215.25102 5. M.-C. Arnaud, Création de connexions en topologie C1 , Ergodic Theory Dyn. Syst., 21 (2001), 339-381 , MR 1827109 , Zbl 0997.37007 6. M.-C. Arnaud, Approximation des ensembles ω-limites des difféomorphismes par des orbites périodiques, Ann. Sci. Éc. Norm. Supér., IV. Sér., 36 (2003), 173-190 , Numdam , Zbl 1024.37011 7. M.-C. Arnaud, C. Bonatti, S. Crovisier, Dynamiques symplectiques ...