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- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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- de Jong, S, et al.
(author)
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Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder
- 2018
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1, s. 163-
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Journal article (peer-reviewed)abstract
- Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
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- Khatri, S, et al.
(author)
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CYCLIC CITRULLINATED PEPTIDE APTAMER TREATMENT ATTENUATES COLLAGEN INDUCED ARTHRITIS
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 466-466
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Conference paper (other academic/artistic)abstract
- Anti-citrullinated peptide antibodies (ACPA) appear 10–15 years before the diagnosis of rheumatoid arthritis (RA) and are associated with a more severe disease course. In previous work, we rationally designed and screened ACPA-binding peptide aptamer sequences in silico and constructed a nanoparticle with chitosan and hyaluronic acid(1). A developmental stage version of this nanoparticle was able to reduce disease activity in the collagen-induced arthritis (CIA) and the serum transfer arthritis mouse models (2).ObjectivesHere, we investigated the effect and potential toxicity of three different versions of the aptamer nanoparticle (loading of 20%, 10% and 5% aptamer, respectively) in the CIA rat model.MethodsWistar rats (males and females) were given a single intravenous dose (100 mg/kilo) of type II collagen in PBS in the tail vein. The dosing was repeated three times with one day interval, followed by blood sample collection at day 7 after the initial collagen injection. To evaluate route of administration and dosing, we injected a single intravenous and subcutaneous dose (2.5 mg/kg) of aptamer-nanoparticles (A/N ratio 20%) in PBS in the tail vein/abdomen, and plasma concentration−time profiles were followed for 2 days after dosing with weekly blood sampling. To evaluate organ uptake, rats were given a single intravenous and subcutaneous dose (2.5 mg/kg) of aptamer-nanoparticles (A/N ratio 20%) in PBS in the tail vein/abdomen. The procedure was repeated after 24 hours. Blood and urine samples were taken once a week. A group of 10 animals was sacrificed every week over a three-week period, and the organs were processed. To examine efficacy, rats were given a single subcutaneous dose (2.5 mg/kilo) of aptamer-nanoparticles and nanoparticle controls without aptamer or PBS alone in the abdomen. The procedure was repeated once a week over a course of three weeks. Weight, joint measurement, blood, and urine samples were taken once a week. Paw swelling was measured on a weekly basis. In the plasma samples we measured CPEP2 and anti-collagen II by enzyme linked immunosorbent assay (ELISA).ResultsUsing a rather high dose of collagen (100 mg/kilo) via an intravenous administration route, ACPA was measurable in all CIA rats with rapid development of RA in 82% of the included animals. Intravenous administration resulted in an immediate high plasma concentration post injection, which decreased rapidly to low levels. The s.c. administration route gave a steady, long-term aptamer release with a maximum availability 8 hours post-injection. After three aptamer-nanoparticle doses (2.5 mg/kg; either 20%, 10% or 5% aptamer), we observed a dose-dependent reduction in swollen joint count for the aptamer-nanoparticle treated groups (10 rats in each group) compared with the healthy control group (10 rats) (P-value = 2,1E-6). We observed decreased ACPA IgG levels in the rats treated with aptamer-nanoparticle. The decrease in ACPA levels correlated with the aptamer-nanoparticle having higher loading. Anti-collagen II IgG levels slightly increased towards the end of the study.ConclusionWe developed and tested a novel peptide aptamer-based drug candidate for seropositive rheumatoid arthritis in CIA rats. Over a 3-week course of treatment with subcutaneous administration of aptamer-nanoparticles, joint swelling was decreased during treatment, and completely reversed at the end of the observation period. The reduction of joint swelling was associated with decreased levels of ACPA in the blood.References[1]Khatri S, Hansen J, Mendes AC, et al. Citrullinated Peptide Epitope Targets Therapeutic Nanoparticles to Human Neutrophils. Bioconjug Chem. 2019;30(10):2584-2593. doi:10.1021/acs.bioconjchem.9b00518[2]Khatri S, Hansen J, Clausen MH, et al. LB0002 A FIRST IN CLASS THERAPEUTIC NANOPARTICLE FOR SPECIFIC TARGETING OF ANTI-CITRULLINATED PROTEIN ANTIBODY AMELIORATES SERUM TRANSFER AND COLLAGEN INDUCED ARTHRITIS. Annals of the Rheumatic Diseases 2020;79:212.Disclosure of InterestsSangita Khatri: None declared, Jonas Hansen: None declared, Nadia Pedersen: None declared, Sanne Gram-Nielsen: None declared, Ana Mendes: None declared, Ioannis Chronakis: None declared, Ulrik Keiding: None declared, Bence Réthi: None declared, Mads Hartvig Clausen Shareholder of: affiliated with IBIO TECH ApS, Tue Wenzel Kragstrup Shareholder of: affiliated with IBIO TECH ApS, Speakers bureau: TWK received speaking fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Novartis, UCB, and Abbvie., Consultant of: Consultancy fees from Bristol-Myers Squibb and Gilead, Grant/research support from: Received research grant from Gilead, Kira Astakhova Shareholder of: KA is affiliated with iBio tech.
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