Published in Annu Rev Immunol on October 04, 2001
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol (2005) 6.18
The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med (2003) 4.20
B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A (2003) 2.66
Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Proc Natl Acad Sci U S A (2005) 2.49
Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci U S A (2004) 1.95
Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis. Immunity (2008) 1.77
Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses. Proc Natl Acad Sci U S A (2008) 1.77
The B7 family of immune-regulatory ligands. Genome Biol (2005) 1.74
Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection. J Clin Invest (2004) 1.71
Functional classification of immune regulatory proteins. Structure (2013) 1.49
Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov (2013) 1.46
Lymphocytes from patients with type 1 diabetes display a distinct profile of chromatin histone H3 lysine 9 dimethylation: an epigenetic study in diabetes. Diabetes (2008) 1.46
BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation. J Immunol (2006) 1.45
DC-HIL is a negative regulator of T lymphocyte activation. Blood (2007) 1.37
PILAR is a novel modulator of human T-cell expansion. Blood (2008) 1.33
Immune gene networks of mycobacterial vaccine-elicited cellular responses and immunity. J Infect Dis (2006) 1.30
The immune regulatory protein B7-H3 promotes osteoblast differentiation and bone mineralization. Proc Natl Acad Sci U S A (2004) 1.30
The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity. J Clin Invest (2003) 1.26
Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. Yale J Biol Med (2011) 1.23
B7-H5 costimulates human T cells via CD28H. Nat Commun (2013) 1.19
B7-h2 is a costimulatory ligand for CD28 in human. Immunity (2011) 1.17
No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory regulator of human T cell activation. Eur J Immunol (2006) 1.13
The quantal theory of how the immune system discriminates between "self and non-self" Med Immunol (2004) 1.13
CD80 and CD86 control antiviral CD8+ T-cell function and immune surveillance of murine gammaherpesvirus 68. J Virol (2006) 1.11
The complex role of B7 molecules in tumor immunology. Trends Mol Med (2008) 1.09
CTLA4 expression is an indicator and regulator of steady-state CD4+ FoxP3+ T cell homeostasis. J Immunol (2008) 1.08
Induction of Th17 cellular immunity with a novel nanoemulsion adjuvant. Crit Rev Immunol (2010) 1.07
Immune escape mechanisms of intraocular tumors. Prog Retin Eye Res (2009) 1.07
Multicolor fate mapping of Langerhans cell homeostasis. J Exp Med (2013) 1.06
FOXM1 promotes allergen-induced goblet cell metaplasia and pulmonary inflammation. Mol Cell Biol (2012) 1.04
The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression. Nat Immunol (2013) 1.04
Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol (2007) 1.03
Inducible costimulator is required for type 2 antibody isotype switching but not T helper cell type 2 responses in chronic nematode infection. Proc Natl Acad Sci U S A (2005) 1.00
Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation. J Immunol (2011) 1.00
Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. Cancers (Basel) (2011) 0.99
DC-HIL/glycoprotein Nmb promotes growth of melanoma in mice by inhibiting the activation of tumor-reactive T cells. Cancer Res (2010) 0.99
Immunosupportive therapies in aging. Clin Interv Aging (2007) 0.97
Colonic epithelial cell mediated suppression of CD4 T cell activation. Gut (2004) 0.97
PD-L1: PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro. Invest Ophthalmol Vis Sci (2008) 0.96
Escherichia coli prevents phagocytosis-induced death of macrophages via classical NF-kappaB signaling, a link to T-cell activation. Infect Immun (2006) 0.96
Early treatment of NOD mice with B7-H4 reduces the incidence of autoimmune diabetes. Diabetes (2011) 0.96
Expression of immunosuppresive B7-H3 ligand by hormone-treated prostate cancer tumors and metastases. Clin Cancer Res (2009) 0.96
Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4. J Exp Med (2003) 0.95
Dual opposing roles of adaptive immunity in hypertension. Eur Heart J (2014) 0.95
Modulation of NKT cell development by B7-CD28 interaction: an expanding horizon for costimulation. PLoS One (2008) 0.94
NKG2D receptor signaling enhances cytolytic activity by virus-specific CD8+ T cells: evidence for a protective role in virus-induced encephalitis. J Virol (2007) 0.94
Disruption of the ICOS-B7RP-1 costimulatory pathway leads to enhanced hepatic immunopathology and increased gamma interferon production by CD4 T cells in murine schistosomiasis. Infect Immun (2003) 0.94
Processing and presentation of exogenous HLA class I peptides by dendritic cells from human immunodeficiency virus type 1-infected persons. J Virol (2005) 0.94
Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice. J Exp Med (2005) 0.93
Increased PRAME-specific CTL killing of acute myeloid leukemia cells by either a novel histone deacetylase inhibitor chidamide alone or combined treatment with decitabine. PLoS One (2013) 0.92
Regulation of Trypanosoma cruzi-induced myocarditis by programmed death cell receptor 1. Infect Immun (2011) 0.92
Chronic antigenic stimuli as a possible explanation for the immunodepression caused by liver cirrhosis. Clin Exp Immunol (2009) 0.91
Targeting of myelin protein zero in a spontaneous autoimmune polyneuropathy. J Immunol (2008) 0.91
Antigen receptor signaling in the rheumatic diseases. Arthritis Res Ther (2009) 0.91
CD28 Costimulation: From Mechanism to Therapy. Immunity (2016) 0.90
CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. PLoS Pathog (2014) 0.90
Suppression of activation and costimulatory signaling in splenic CD4+ T cells after trauma-hemorrhage reduces T-cell function: a mechanism of post-traumatic immune suppression. Am J Pathol (2009) 0.89
Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma. Sci Rep (2016) 0.88
Bystander activation and anti-tumor effects of CD8+ T cells following Interleukin-2 based immunotherapy is independent of CD4+ T cell help. PLoS One (2014) 0.88
The programmed death-1 and interleukin-10 pathways play a down-modulatory role in LP-BM5 retrovirus-induced murine immunodeficiency syndrome. J Virol (2007) 0.88
TGF-beta1 on osteoimmunology and the bone component cells. Cell Biosci (2013) 0.88
T regulatory cells are markers of disease activity in multiple sclerosis patients. PLoS One (2011) 0.88
Foreign body-type multinucleated giant cells induced by interleukin-4 express select lymphocyte co-stimulatory molecules and are phenotypically distinct from osteoclasts and dendritic cells. Exp Mol Pathol (2011) 0.88
The CD154/CD40 interaction required for retrovirus-induced murine immunodeficiency syndrome is not mediated by upregulation of the CD80/CD86 costimulatory molecules. J Virol (2002) 0.87
Transcription regulation from a TATA and INR-less promoter: spatial segregation of promoter function. EMBO J (2006) 0.87
Expression and function of inducible co-stimulator in patients with systemic lupus erythematosus: possible involvement in excessive interferon-gamma and anti-double-stranded DNA antibody production. Arthritis Res Ther (2006) 0.87
ERK and not p38 pathway is required for IL-12 restoration of T cell IL-2 and IFN-gamma in a rodent model of alcohol intoxication and burn injury. J Immunol (2009) 0.86
Distinct pathways of humoral and cellular immunity induced with the mucosal administration of a nanoemulsion adjuvant. J Immunol (2014) 0.86
Alcohol exposure impairs myeloid dendritic cell function in rhesus macaques. Alcohol Clin Exp Res (2009) 0.86
Inhibitors of mitogen-activated protein kinases differentially regulate costimulated T cell cytokine production and mouse airway eosinophilia. Respir Res (2005) 0.86
Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nat Commun (2016) 0.86
Differential capacity of human skin dendritic cells to polarize CD4+ T cells into IL-17, IL-21 and IL-22 producing cells. PLoS One (2012) 0.85
Cytotoxic T lymphocyte antigen 4 immunoglobulin modified dendritic cells attenuate allergic airway inflammation and hyperresponsiveness by regulating the development of T helper type 1 (Th1)/Th2 and Th2/regulatory T cell subsets in a murine model of asthma. Clin Exp Immunol (2011) 0.85
Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis. Clin Exp Immunol (2005) 0.85
Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection. Immunology (2013) 0.85
Enforced expression of roquin protein in T cells exacerbates the incidence and severity of experimental arthritis. J Biol Chem (2012) 0.85
Optimizing dendritic cell-based immunotherapy: tackling the complexity of different arms of the immune system. Mediators Inflamm (2012) 0.85
Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity. World J Gastroenterol (2016) 0.84
Stimulation of human CD4⁺ T lymphocytes via TLR3, TLR5 and TLR7/8 up-regulates expression of costimulatory and modulates proliferation. Open Microbiol J (2009) 0.83
Mechanisms of ganglioside inhibition of APC function. J Immunol (2003) 0.83
CD40-associated TRAF 6 signaling is required for disease induction in a retrovirus-induced murine immunodeficiency. J Virol (2004) 0.83
The immunostimulatory effects of retinoblastoma cell supernatant on dendritic cells. Protein Cell (2014) 0.83
Oral Treatment with Extract of Agaricus blazei Murill Enhanced Th1 Response through Intestinal Epithelial Cells and Suppressed OVA-Sensitized Allergy in Mice. Evid Based Complement Alternat Med (2010) 0.83
Tumor-specific oncolytic adenoviruses expressing granulocyte macrophage colony-stimulating factor or anti-CTLA4 antibody for the treatment of cancers. Cancer Gene Ther (2014) 0.83
Immunological weapons against acute myeloid leukaemia. Immunology (2002) 0.82
CTLA4-Ig inhibits allergic airway inflammation by a novel CD28-independent, nitric oxide synthase-dependent mechanism. Eur J Immunol (2010) 0.82
Crystallization and preliminary X-ray crystallographic study of the extracellular domain of the 4-1BB ligand, a member of the TNF family. Acta Crystallogr Sect F Struct Biol Cryst Commun (2005) 0.82
Antigen processing and CD24 expression determine antigen presentation by splenic CD4+ and CD8+ dendritic cells. Immunology (2007) 0.81
DC-HIL-expressing myelomonocytic cells are critical promoters of melanoma growth. J Invest Dermatol (2014) 0.81
Infiltration of m2 tumor-associated macrophages in oral squamous cell carcinoma correlates with tumor malignancy. Cancers (Basel) (2011) 0.81
Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes. Br J Pharmacol (2006) 0.80
The CTLA-4 -1661A/G and -1772T/C dimorphisms in Japanese patients with systemic sclerosis. Rheumatol Int (2007) 0.80
Differential requirements for CD80/86-CD28 costimulation in primary and memory CD4 T cell responses to vaccinia virus. Cell Immunol (2010) 0.80
CTLA-4 gene polymorphism and the risk of systemic lupus erythematosus in the Chinese population. J Biomed Biotechnol (2011) 0.80
Characterization of phenotypes of immune cells and cytokines associated with chronic exposure to Premolis semirufa caterpillar bristles extract. PLoS One (2013) 0.79
Polymorphic sites at the immunoregulatory CTLA-4 gene are associated with chronic chagas disease and its clinical manifestations. PLoS One (2013) 0.79
Programmed death-1 ligands-transfected dendritic cells loaded with glutamic acid decarboxylase 65 (GAD65) inhibit both the alloresponse and the GAD65-reactive lymphocyte response. Clin Exp Immunol (2007) 0.79
Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med (2006) 13.74
CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity (2002) 8.28
Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science (2011) 6.19
IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest (2008) 4.12
PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol (2002) 3.78
The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest (2006) 3.33
IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity (2002) 3.17
Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J Immunol (2004) 3.15
Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med (2003) 2.71
IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol (2007) 2.71
Abrogation of Ref1 retrovirus restriction in human cells. J Virol (2002) 2.60
Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. J Exp Med (2003) 2.54
An IL-17F/A heterodimer protein is produced by mouse Th17 cells and induces airway neutrophil recruitment. J Immunol (2007) 2.46
Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells. J Exp Med (2002) 2.28
Putting evidence into practice: evidence-based interventions for chemotherapy-induced peripheral neuropathy. Clin J Oncol Nurs (2007) 2.17
Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum (2007) 2.10
Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J Biol Chem (2007) 2.06
KSHV vFLIP binds to IKK-gamma to activate IKK. J Cell Sci (2003) 2.04
Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses. J Immunol (2003) 1.93
The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J Immunol (2008) 1.82
Duplication of primate and rodent B7-H3 immunoglobulin V- and C-like domains: divergent history of functional redundancy and exon loss. Genomics (2003) 1.81
Th17 cytokines and their emerging roles in inflammation and autoimmunity. Immunol Rev (2008) 1.75
IL-21 induces the apoptosis of resting and activated primary B cells. J Immunol (2003) 1.67
Continuous high-titer HIV-1 vector production. Nat Biotechnol (2003) 1.58
Activation of antigen-presenting cells by microbial products breaks self tolerance and induces autoimmune disease. J Clin Invest (2004) 1.57
IL-21 activates both innate and adaptive immunity to generate potent antitumor responses that require perforin but are independent of IFN-gamma. J Immunol (2003) 1.55
Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. J Immunol (2010) 1.53
PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol (2006) 1.52
Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis. J Invest Dermatol (2011) 1.51
Crystal structure of a vFlip-IKKgamma complex: insights into viral activation of the IKK signalosome. Mol Cell (2008) 1.46
HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. J Virol (2010) 1.44
IL-22 induces an acute-phase response. J Immunol (2010) 1.40
Use of an objective tool to assess platelet inhibition prior to off-pump coronary surgery to reduce blood usage. J Invasive Cardiol (2012) 1.40
Nurse case management improves blood pressure, emotional distress and diabetes complication screening. Diabetes Res Clin Pract (2005) 1.30
PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells. EMBO Mol Med (2011) 1.27
Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen. J Immunol (2005) 1.26
A phagocytic cell line markedly improves survival of infected neutropenic mice. J Leukoc Biol (2005) 1.23
IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice. J Clin Invest (2008) 1.17
Pilot evaluation of citalopram for the treatment of hot flashes in women with inadequate benefit from venlafaxine. J Palliat Med (2005) 1.17
Cloning and functional characterization of the Rhizopus oryzae high affinity iron permease (rFTR1) gene. FEMS Microbiol Lett (2004) 1.11
Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts. J Leukoc Biol (2006) 1.11
Tumor necrosis factor alpha blockade exacerbates murine psoriasis-like disease by enhancing Th17 function and decreasing expansion of Treg cells. Arthritis Rheum (2010) 1.10
Selective ERK activation differentiates mouse and human tolerogenic dendritic cells, expands antigen-specific regulatory T cells, and suppresses experimental inflammatory arthritis. Arthritis Rheum (2011) 1.08
IL-21 receptor is critical for the development of memory B cell responses. J Immunol (2010) 1.05
Murine leukemia virus particle assembly quantitated by fluorescence microscopy: role of Gag-Gag interactions and membrane association. J Virol (2003) 1.05
BTLA: a new inhibitory receptor with a B7-like ligand. Trends Immunol (2003) 1.04
Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A. J Immunol (2002) 1.04
Selective functional inhibition of JAK-3 is sufficient for efficacy in collagen-induced arthritis in mice. Arthritis Rheum (2010) 1.03
IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL/MpJ-Fas(lpr/lpr)/J mice. J Immunol (2012) 1.02
IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis. Exp Neurol (2007) 0.98
Autoreactive T cells mediate NK cell degeneration in autoimmune disease. J Immunol (2006) 0.97
A strabismus susceptibility locus on chromosome 7p. Proc Natl Acad Sci U S A (2003) 0.97
IL-22R, IL-10R2, and IL-22BP binding sites are topologically juxtaposed on adjacent and overlapping surfaces of IL-22. J Mol Biol (2008) 0.97
DNA vaccines encoding retrovirus-based virus-like particles induce efficient immune responses without adjuvant. Vaccine (2005) 0.97
Effect of the internal promoter on insertional gene activation by lentiviral vectors with an intact HIV long terminal repeat. J Virol (2010) 0.95
The β-globin locus control region in combination with the EF1α short promoter allows enhanced lentiviral vector-mediated erythroid gene expression with conserved multilineage activity. Mol Ther (2012) 0.93
Enhanced GITR/GITRL interactions augment IL-27 expression and induce IL-10-producing Tr-1 like cells. Eur J Immunol (2012) 0.92
IL-21 effects on human IgE production in response to IL-4 or IL-13. Cell Immunol (2005) 0.90
Growth factors improve gene expression after lentiviral transduction in human adult and fetal hepatocytes. J Gene Med (2007) 0.90
Gene transfer to repopulating human CD34+ cells using amphotropic-, GALV-, or RD114-pseudotyped HIV-1-based vectors from stable producer cells. Mol Ther (2005) 0.89
Therapeutic opportunities in the B7/CD28 family of ligands and receptors. Curr Opin Pharmacol (2005) 0.88
Insertional mutagenesis by retroviral vectors: current concepts and methods of analysis. Curr Gene Ther (2013) 0.87
Safer, silencing-resistant lentiviral vectors: optimization of the ubiquitous chromatin-opening element through elimination of aberrant splicing. J Virol (2012) 0.86
A FLIPR-based assay to assess potency and selectivity of inhibitors of the TEC family kinases Btk and Itk. Assay Drug Dev Technol (2007) 0.84
Tumor cells secreting IL-13 but not IL-13Ralpha2 fusion protein have reduced tumorigenicity in vivo. Int Immunol (2004) 0.83
Conjugation of lentivirus to paramagnetic particles via nonviral proteins allows efficient concentration and infection of primary acute myeloid leukemia cells. J Virol (2005) 0.82
Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy. Cancer Immunol Immunother (2005) 0.82
Comparable in vivo efficacy of CD28/B7, ICOS/GL50, and ICOS/GL50B costimulatory pathways in murine tumor models: IFNgamma-dependent enhancement of CTL priming, effector functions, and tumor specific memory CTL. Cell Immunol (2003) 0.81
Cell-surface and cytokine biomarkers in autoimmune and inflammatory diseases. Drug Discov Today (2006) 0.81
DNA fusion vaccine designs to induce tumor-lytic CD8+ T-cell attack via the immunodominant cysteine-containing epitope of NY-ESO 1. Int J Cancer (2013) 0.81
Unexpected targets and triggers of autoimmunity. J Clin Immunol (2014) 0.80
Dehydroepiandrosterone for the treatment of hot flashes: a pilot study. Support Cancer Ther (2006) 0.80
Targeting lentiviral vectors for cancer immunotherapy. Curr Cancer Ther Rev (2011) 0.80
The pathology and immunology of atopic dermatitis. Inflamm Allergy Drug Targets (2011) 0.80
Pilot evaluation of aprepitant for the treatment of hot flashes. Support Cancer Ther (2006) 0.78
The DTH effector response and IL-2 are unaffected by cyclosporine A in autoimmune B6D2F1 mice. Cell Immunol (2010) 0.78
Cytosolic phospholipase A2α blockade abrogates disease during the tissue-damage effector phase of experimental autoimmune encephalomyelitis by its action on APCs. J Immunol (2011) 0.77
Distinct in vitro binding properties of the anti-CD20 small modular immunopharmaceutical 2LM20-4 result in profound and sustained in vivo potency in cynomolgus monkeys. Rheumatology (Oxford) (2011) 0.75
Geriatric trauma G-60 falls with hip fractures: A pilot study of acute pain management using femoral nerve fascia iliac blocks. J Trauma Acute Care Surg (2015) 0.75