Published in Biochemistry on December 13, 2005
Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res (2006) 6.42
G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res (2006) 5.84
Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res (2006) 3.87
Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov (2011) 3.54
Human telomere, oncogenic promoter and 5'-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics. Nucleic Acids Res (2007) 3.49
A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene. Biochemistry (2006) 2.62
Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie (2008) 2.38
Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence. Nucleic Acids Res (2007) 2.23
NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nucleic Acids Res (2006) 2.03
The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression. J Med Chem (2009) 2.03
Polymorphism of human telomeric quadruplex structures. Biochimie (2008) 1.89
A sequence-independent study of the influence of short loop lengths on the stability and topology of intramolecular DNA G-quadruplexes. Biochemistry (2007) 1.75
Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein. J Biol Chem (2009) 1.72
A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res (2008) 1.49
Structural insights into G-quadruplexes: towards new anticancer drugs. Future Med Chem (2010) 1.44
Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. Nucleic Acids Res (2009) 1.44
The proximal promoter region of the human vascular endothelial growth factor gene has a G-quadruplex structure that can be targeted by G-quadruplex-interactive agents. Mol Cancer Ther (2008) 1.44
Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands. J Am Chem Soc (2009) 1.42
Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription. Genome Res (2007) 1.39
QuadBase: genome-wide database of G4 DNA--occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes. Nucleic Acids Res (2007) 1.35
Intramolecular DNA quadruplexes with different arrangements of short and long loops. Nucleic Acids Res (2007) 1.30
Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma. Nucleic Acids Res (2010) 1.30
Targeting MYC Expression through G-Quadruplexes. Genes Cancer (2010) 1.29
Exon array analyses across the NCI-60 reveal potential regulation of TOP1 by transcription pausing at guanosine quartets in the first intron. Cancer Res (2010) 1.24
Solution structure of a 2:1 quindoline-c-MYC G-quadruplex: insights into G-quadruplex-interactive small molecule drug design. J Am Chem Soc (2011) 1.17
Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb. Clin Cancer Res (2012) 1.17
Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. Methods Mol Biol (2010) 1.16
Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene. Nucleic Acids Res (2008) 1.16
Structural polymorphism within a regulatory element of the human KRAS promoter: formation of G4-DNA recognized by nuclear proteins. Nucleic Acids Res (2008) 1.12
Interaction of human telomeric DNA with N-methyl mesoporphyrin IX. Nucleic Acids Res (2012) 1.11
Greglist: a database listing potential G-quadruplex regulated genes. Nucleic Acids Res (2007) 1.07
The dynamic character of the BCL2 promoter i-motif provides a mechanism for modulation of gene expression by compounds that bind selectively to the alternative DNA hairpin structure. J Am Chem Soc (2014) 1.06
Molecular cloning of the human platelet-derived growth factor receptor beta (PDGFR-beta) promoter and drug targeting of the G-quadruplex-forming region to repress PDGFR-beta expression. Biochemistry (2010) 1.06
The relationship of potential G-quadruplex sequences in cis-upstream regions of the human genome to SP1-binding elements. Nucleic Acids Res (2008) 1.06
A sequence-independent analysis of the loop length dependence of intramolecular RNA G-quadruplex stability and topology. Biochemistry (2011) 1.04
The i-motif in the bcl-2 P1 promoter forms an unexpectedly stable structure with a unique 8:5:7 loop folding pattern. J Am Chem Soc (2009) 1.04
Predictive modelling of topology and loop variations in dimeric DNA quadruplex structures. Nucleic Acids Res (2006) 1.02
RTEF-1, an upstream gene of hypoxia-inducible factor-1α, accelerates recovery from ischemia. J Biol Chem (2011) 0.98
Genome-wide colonization of gene regulatory elements by G4 DNA motifs. Nucleic Acids Res (2009) 0.97
The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells. Nucleic Acids Res (2012) 0.97
HIF-1alpha and HIF-2alpha play a central role in stretch-induced but not shear-stress-induced angiogenesis in rat skeletal muscle. J Physiol (2007) 0.96
The role of hypoxia-inducible factor 1α in determining the properties of castrate-resistant prostate cancers. PLoS One (2013) 0.94
The role of G-quadruplex/i-motif secondary structures as cis-acting regulatory elements. Pure Appl Chem (2010) 0.94
U3 region in the HIV-1 genome adopts a G-quadruplex structure in its RNA and DNA sequence. Biochemistry (2014) 0.92
Investigating a quadruplex-ligand interaction by unfolding kinetics. J Am Chem Soc (2006) 0.91
G-quadruplex structures formed at the HOX11 breakpoint region contribute to its fragility during t(10;14) translocation in T-cell leukemia. Mol Cell Biol (2013) 0.91
The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K+ solution. J Am Chem Soc (2014) 0.90
Solution structure of the major G-quadruplex formed in the human VEGF promoter in K+: insights into loop interactions of the parallel G-quadruplexes. Nucleic Acids Res (2013) 0.90
Evidence for G-quadruplex in the promoter of vegfr-2 and its targeting to inhibit tumor angiogenesis. Nucleic Acids Res (2013) 0.90
Solution-state structure of an intramolecular G-quadruplex with propeller, diagonal and edgewise loops. Nucleic Acids Res (2012) 0.88
Polymorphism and resolution of oncogene promoter quadruplex-forming sequences. Org Biomol Chem (2011) 0.85
Sequence, stability, and structure of G-quadruplexes and their interactions with drugs. Curr Protoc Nucleic Acid Chem (2012) 0.85
Inhibition of the hypoxia-inducible factor pathway by a G-quadruplex binding small molecule. Sci Rep (2013) 0.85
A cis-element with mixed G-quadruplex structure of NPGPx promoter is essential for nucleolin-mediated transactivation on non-targeting siRNA stress. Nucleic Acids Res (2012) 0.84
An exonuclease I hydrolysis assay for evaluating G-quadruplex stabilization by small molecules. Nucleic Acids Res (2007) 0.84
End-stacking of copper cationic porphyrins on parallel-stranded guanine quadruplexes. J Biol Inorg Chem (2007) 0.84
Solution structure of all parallel G-quadruplex formed by the oncogene RET promoter sequence. Nucleic Acids Res (2011) 0.83
"One ring to bind them all"-part I: the efficiency of the macrocyclic scaffold for g-quadruplex DNA recognition. J Nucleic Acids (2010) 0.83
Not all G-quadruplexes are created equally: an investigation of the structural polymorphism of the c-Myc G-quadruplex-forming sequence and its interaction with the porphyrin TMPyP4. Org Biomol Chem (2012) 0.82
DNA G-quadruplex and its potential as anticancer drug target. Sci China Chem (2014) 0.81
Recognition and discrimination of DNA quadruplexes by acridine-peptide conjugates. Org Biomol Chem (2008) 0.81
Inhibition of cancer cell migration and invasion through suppressing the Wnt1-mediating signal pathway by G-quadruplex structure stabilizers. J Biol Chem (2014) 0.81
Metal Cations in G-Quadruplex Folding and Stability. Front Chem (2016) 0.79
Calculation of hydrodynamic properties for G-quadruplex nucleic acid structures from in silico bead models. Top Curr Chem (2013) 0.79
An improved model for the hTERT promoter quadruplex. PLoS One (2014) 0.78
Ion-dependent conformational switching by a DNA aptamer that induces remyelination in a mouse model of multiple sclerosis. Nucleic Acids Res (2012) 0.78
Induction of senescence in cancer cells by the G-quadruplex stabilizer, BMVC4, is independent of its telomerase inhibitory activity. Br J Pharmacol (2012) 0.77
Resolution of quadruplex polymorphism by size-exclusion chromatography. Curr Protoc Nucleic Acid Chem (2011) 0.77
An RNA-binding Protein, Lin28, Recognizes and Remodels G-quartets in the MicroRNAs (miRNAs) and mRNAs It Regulates. J Biol Chem (2015) 0.77
General cell-binding activity of intramolecular G-quadruplexes with parallel structure. PLoS One (2013) 0.77
Aptamer selection based on G4-forming promoter region. PLoS One (2013) 0.76
Possible regulatory roles of promoter g-quadruplexes in cardiac function-related genes - human TnIc as a model. PLoS One (2013) 0.76
In vitro footprinting of promoter regions within supercoiled plasmid DNA. Methods Mol Biol (2010) 0.76
Separation of Quadruplex Polymorphism in DNA Sequences by Reversed-Phase Chromatography. Curr Protoc Nucleic Acid Chem (2015) 0.75
Formation and stabilization of the telomeric antiparallel G-quadruplex and inhibition of telomerase by novel benzothioxanthene derivatives with anti-tumor activity. Sci Rep (2015) 0.75
In silico identification of novel ligands for G-quadruplex in the c-MYC promoter. J Comput Aided Mol Des (2014) 0.75
Downregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complex. Sci Rep (2016) 0.75
The Role of PALB2 in the DNA Damage Response and Cancer Predisposition. Int J Mol Sci (2017) 0.75
A novel G-quadruplex motif in the Human MET promoter region. Biosci Rep (2017) 0.75
Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med (2013) 18.08
Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc Natl Acad Sci U S A (2002) 9.60
Centromere-specific assembly of CENP-a nucleosomes is mediated by HJURP. Cell (2009) 4.22
Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat Rev Drug Discov (2011) 3.54
The dynamic character of the G-quadruplex element in the c-MYC promoter and modification by TMPyP4. J Am Chem Soc (2004) 3.19
Facilitation of a structural transition in the polypurine/polypyrimidine tract within the proximal promoter region of the human VEGF gene by the presence of potassium and G-quadruplex-interactive agents. Nucleic Acids Res (2005) 3.01
The cationic porphyrin TMPyP4 down-regulates c-MYC and human telomerase reverse transcriptase expression and inhibits tumor growth in vivo. Mol Cancer Ther (2002) 2.39
Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie (2008) 2.38
NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region. Nucleic Acids Res (2006) 2.03
The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression. J Med Chem (2009) 2.03
Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter. J Am Chem Soc (2006) 1.93
Telomestatin and diseleno sapphyrin bind selectively to two different forms of the human telomeric G-quadruplex structure. J Am Chem Soc (2005) 1.87
Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J Am Chem Soc (2002) 1.82
Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein. J Biol Chem (2009) 1.72
The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics. Nat Rev Cancer (2009) 1.71
Clinical evidence in guardianship of older adults is inadequate: findings from a tri-state study. Gerontologist (2007) 1.67
Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4. Nucleic Acids Res (2007) 1.66
Formation of pseudosymmetrical G-quadruplex and i-motif structures in the proximal promoter region of the RET oncogene. J Am Chem Soc (2007) 1.53
A novel G-quadruplex-forming GGA repeat region in the c-myb promoter is a critical regulator of promoter activity. Nucleic Acids Res (2008) 1.49
The proximal promoter region of the human vascular endothelial growth factor gene has a G-quadruplex structure that can be targeted by G-quadruplex-interactive agents. Mol Cancer Ther (2008) 1.44
Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands. J Am Chem Soc (2009) 1.42
Design and synthesis of an expanded porphyrin that has selectivity for the c-MYC G-quadruplex structure. J Am Chem Soc (2005) 1.40
Feedback control in sensing chromosome biorientation by the Aurora B kinase. Curr Biol (2011) 1.40
Replacement of histone H3 with CENP-A directs global nucleosome array condensation and loosening of nucleosome superhelical termini. Proc Natl Acad Sci U S A (2011) 1.33
The c-MYC NHE III(1): function and regulation. Annu Rev Pharmacol Toxicol (2010) 1.31
Targeting MYC Expression through G-Quadruplexes. Genes Cancer (2010) 1.29
Looking at the sunny side of life: age-related change in an event-related potential measure of the negativity bias. Psychol Sci (2007) 1.26
Telomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma. Mol Cancer Ther (2003) 1.26
How much choice is too much? The case of the Medicare prescription drug benefit. Health Serv Res (2009) 1.25
The different biological effects of telomestatin and TMPyP4 can be attributed to their selectivity for interaction with intramolecular or intermolecular G-quadruplex structures. Cancer Res (2003) 1.25
Structure of the biologically relevant G-quadruplex in the c-MYC promoter. Nucleosides Nucleotides Nucleic Acids (2006) 1.21
Telomerase inhibition and cell growth arrest after telomestatin treatment in multiple myeloma. Clin Cancer Res (2004) 1.21
Biophysical studies of the c-MYC NHE III1 promoter: model quadruplex interactions with a cationic porphyrin. Biophys J (2006) 1.20
NM23-H2 may play an indirect role in transcriptional activation of c-myc gene expression but does not cleave the nuclease hypersensitive element III(1). Mol Cancer Ther (2009) 1.19
Solution structure of a 2:1 quindoline-c-MYC G-quadruplex: insights into G-quadruplex-interactive small molecule drug design. J Am Chem Soc (2011) 1.17
Telomere inhibition and telomere disruption as processes for drug targeting. Annu Rev Pharmacol Toxicol (2002) 1.17
Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. Methods Mol Biol (2010) 1.16
Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene. Nucleic Acids Res (2008) 1.16
Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma is directly mediated through the promoter G-quadruplex. J Biol Chem (2011) 1.14
Telomeres and telomerases as drug targets. Curr Opin Pharmacol (2002) 1.14
Epigenetic centromere specification directs aurora B accumulation but is insufficient to efficiently correct mitotic errors. J Cell Biol (2010) 1.13
Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer. Cancer Res (2006) 1.11
Risky decision making in younger and older adults: the role of learning. Psychol Aging (2011) 1.11
The cationic porphyrin TMPyP4 destabilizes the tetraplex form of the fragile X syndrome expanded sequence d(CGG)n. Nucleic Acids Res (2003) 1.09
The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity. Biochemistry (2010) 1.07
The dynamic character of the BCL2 promoter i-motif provides a mechanism for modulation of gene expression by compounds that bind selectively to the alternative DNA hairpin structure. J Am Chem Soc (2014) 1.06
Molecular cloning of the human platelet-derived growth factor receptor beta (PDGFR-beta) promoter and drug targeting of the G-quadruplex-forming region to repress PDGFR-beta expression. Biochemistry (2010) 1.06
Choosing the right medicare prescription drug plan: the effect of age, strategy selection, and choice set size. Health Psychol (2011) 1.06
The i-motif in the bcl-2 P1 promoter forms an unexpectedly stable structure with a unique 8:5:7 loop folding pattern. J Am Chem Soc (2009) 1.04
Heterogeneous nuclear ribonucleoprotein K and nucleolin as transcriptional activators of the vascular endothelial growth factor promoter through interaction with secondary DNA structures. Biochemistry (2011) 1.03
Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and refolds by parallel pathways via cooperative or sequential events. J Am Chem Soc (2012) 1.02
The transcriptional complex between the BCL2 i-motif and hnRNP LL is a molecular switch for control of gene expression that can be modulated by small molecules. J Am Chem Soc (2014) 1.02
The design, synthesis, and evaluation of 8 hybrid DFG-out allosteric kinase inhibitors: a structural analysis of the binding interactions of Gleevec, Nexavar, and BIRB-796. Bioorg Med Chem (2010) 1.01
UA62784, a novel inhibitor of centromere protein E kinesin-like protein. Mol Cancer Ther (2009) 1.01
Characterization of DNA damage induced by a natural product antitumor antibiotic leinamycin in human cancer cells. Chem Res Toxicol (2010) 1.00
The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching. J Cell Biol (2008) 0.97
Retracted Mutations in the G-quadruplex silencer element and their relationship to c-MYC overexpression, NM23 repression, and therapeutic rescue. Proc Natl Acad Sci U S A (2004) 0.97
Orally active alpha-tocopheryloxyacetic acid suppresses tumor growth and multiplicity of spontaneous murine breast cancer. Mol Cancer Ther (2009) 0.95
The role of G-quadruplex/i-motif secondary structures as cis-acting regulatory elements. Pure Appl Chem (2010) 0.94
The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer. BMC Cancer (2011) 0.93
PNA-nitrogen mustard conjugates are effective suppressors of HER-2/neu and biological tools for recognition of PNA/DNA interactions. Bioconjug Chem (2006) 0.92
Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells. Mol Cancer Ther (2006) 0.91
Voreloxin, a first-in-class anticancer quinolone derivative, in relapsed/refractory solid tumors: a report on two dosing schedules. Clin Cancer Res (2010) 0.91
Peptide nucleic acid conjugates: synthesis, properties and applications. Curr Top Med Chem (2005) 0.90
Binding of G-quadruplex-interactive agents to distinct G-quadruplexes induces different biological effects in MiaPaCa cells. Nucleosides Nucleotides Nucleic Acids (2005) 0.89
Anticancer activity and cellular repression of c-MYC by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on direct targeting of the G-quadruplex in the c-MYC promoter. J Med Chem (2012) 0.89
A comprehensive strategy to combat colon cancer targeting the adenomatous polyposis coli tumor suppressor gene. Ann N Y Acad Sci (2005) 0.87
Molecular modeling and biophysical analysis of the c-MYC NHE-III1 silencer element. J Mol Model (2007) 0.86
Cellular response and molecular mechanism of antitumor activity by leinamycin in MiaPaCa human pancreatic cancer cells. Anticancer Drugs (2004) 0.86
Determination of the importance of the stereochemistry of psorospermin in topoisomerase II-induced alkylation of DNA and in vitro and in vivo biological activity. Mol Cancer Ther (2005) 0.85
I-motif structures formed in the human c-MYC promoter are highly dynamic--insights into sequence redundancy and I-motif stability. PLoS One (2010) 0.85
Identification of a novel inhibitor of urokinase-type plasminogen activator. Mol Cancer Ther (2007) 0.84
Identification of a lead small-molecule inhibitor of the Aurora kinases using a structure-assisted, fragment-based approach. Mol Cancer Ther (2006) 0.84
Characterization of novel diaryl oxazole-based compounds as potential agents to treat pancreatic cancer. J Pharmacol Exp Ther (2009) 0.84
Structure of a quinobenzoxazine--G-quadruplex complex by REDOR NMR. Biochemistry (2004) 0.84
A direct and nondestructive approach to determine the folding structure of the I-motif DNA secondary structure by NMR. J Am Chem Soc (2009) 0.83
One fish, two fish, red fish, blue fish: effects of price frames, brand names, and choice set size on Medicare Part D insurance plan decisions. Med Care Res Rev (2012) 0.83
Design, synthesis, and biological evaluation of a series of fluoroquinoanthroxazines with contrasting dual mechanisms of action against topoisomerase II and G-quadruplexes. J Med Chem (2003) 0.83
Modulating the functional contributions of c-Myc to the human endothelial cell cyclic strain response. J Vasc Res (2009) 0.82
Synthesis and characterization of a small analogue of the anticancer natural product leinamycin. Bioorg Med Chem (2012) 0.81
DNA acting like RNA. Biochem Soc Trans (2011) 0.80
DNA structure: Visualizing the quadruplex. Nat Chem (2013) 0.80
DNA cleavage induced by antitumor antibiotic leinamycin and its biological consequences. Bioorg Med Chem (2012) 0.80
Targeting and regulation of the HER-2/neu oncogene promoter with bis-peptide nucleic acids. Oligonucleotides (2005) 0.80
Subjective numeracy scale as a tool for assessing statistical numeracy in older adult populations. Gerontology (2013) 0.79
The macrocycle of leinamycin imparts hydrolytic stability to the thiol-sensing 1,2-dithiolan-3-one 1-oxide unit of the natural product. Bioorg Med Chem Lett (2012) 0.79
A bis-alkylating triplex forming oligonucleotide inhibits intracellular reporter gene expression and prevents triplex unwinding due to helicase activity. Biochemistry (2003) 0.77
Gaining insights into the small molecule targeting of the G-quadruplex in the c-MYC promoter using NMR and an allele-specific transcriptional assay. Top Curr Chem (2013) 0.77
Thiol-dependent DNA cleavage by aminomethylated Beaucage's reagent. Org Biomol Chem (2010) 0.77
Statutory reform is associated with improved court practice: results of a tri-state comparison. Behav Sci Law (2007) 0.76
Tolerability, safety and pharmacokinetics of ridaforolimus in combination with bicalutamide in patients with asymptomatic, metastatic castration-resistant prostate cancer (CRPC). Cancer Chemother Pharmacol (2013) 0.76