Review of Particle Physics
The European physical journal. C, Particles and fields,
03/1998, Letnik:
3, Številka:
1-4
Journal Article
Recenzirano
Odprti dostop
This biennial Review summarizes much of Particle Physics. Using data from previous editions, plus 1600 new measurements from 550 papers, we list, evaluate, and average measured properties of gauge ...bosons, leptons, quarks, mesons, and baryons. We also summarize searches for hypothetical particles such as Higgs bosons, heavy neutrinos, and supersymmetric particles. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as the Standard Model, particle detectors, probability, and statistics. A booklet is available containing the Summary Tables and abbreviated versions of some of the other sections of this full Review. All tables, listings, and reviews (and errata) are also available on the Particle Data Group website: http: //pdg. lbl. gov.
Abstract
Background
Integrins play a key role in facilitating immune cell trafficking throughout the body and represent an important receptor family for therapeutic intervention. In particular, the ...α4β7 integrin is a clinically validated target for the treatment of inflammatory bowel diseases (IBD), as exemplified by the humanised monoclonal antibody vedolizumab, which blocks the interactions between α4β7-expressing lymphocytes and its ligand MAdCAM-1. This blockade leads to the inhibition of these circulating lymphocytes from exiting the bloodstream and entering intestinal mucosal tissues resulting in a decrease in mucosal inflammation in patients. While oral inhibitors of the α4β7 integrin are advantageous over biologics, the efforts have been impeded by challenges to achieve desired selectivity and optimal DMPK properties. The aim of this study was to develop and characterise orally bioavailable small-molecule inhibitors of the α4β7 integrin and to determine their therapeutic potential.
Methods
Oral small-molecule inhibitors targeting the α4β7 integrin were discovered using Morphic Integrin Technology (MInT) platform. These small-molecule inhibitors were tested for potency and selectivity against a broad panel of integrin family members in multiple biochemical and cell-based functional assays in a ligand-competitive fashion. An acute PD assay with CFSE-labelled lymphocytes was developed to evaluate the activity of the small-molecule compounds in blocking lymphocyte trafficking to gut-associated lymphoid tissues in mice. The in vivo activity was also examined through changes in circulating α4β7+ CD4+ T memory cells in a relevant non-human primate model.
Results
Key drug candidate small molecules demonstrated over 1000-fold selectivity in vitro against a broad panel of integrin family members, including the α4β1 integrin. These compounds effectively blocked lymphocyte trafficking to mesenteric lymph nodes and Peyer’s patches in the gut in a dose-dependent manner, similar to an α4β7-specific antibody, in an acute gut-homing assay in mice. Additionally, these inhibitors also demonstrated effective occlusion of immune trafficking in a relevant non-human primate model. The lead compound has favourable DMPK properties, good oral bioavailability and is projected to have sufficient exposure in humans to effectively block α4β7-expressing immune cells in circulation.
Conclusion
Potent, selective, oral small-molecule inhibitors of α4β7 integrin have been discovered that demonstrate on-target, mechanistic efficacy in two animal models relevant to human IBD. It has the potential to be an effective and safe therapeutic in monotherapy as well as serving as a backbone for combination with other IBD drugs.
A comprehensive as of November 2003 and evaluated data compilation on
sigma_tot(e+ e- --> hadrons) was used to estimate the lowest order hadronic
contribution to the muon anomalous magnetic moment. ...The preliminary result is
a_mu(had, LO) = (699.6 +- 1.9(rad) +- 2.0(proc) +- 8.5(e+e-)) * 10^-10 The
Standard Model value of the muon magnetic anomaly calculated by updated SM
formulae published or e-printed by November 2003 then reads a_mu = (1 165 918
3.5 +- 8.7(had) +- 4.0(LbL) +- 0.3(QED) +- 0.2(EW)) * 10^-10. This result
deviates from the current experimental world average of a_mu by (-19.5 +-
9.6(theor) +- 8.0(exp)) * 10^-10, i.e. at 1.5 sigma level.
Overview of the COMPETE Program Ezhela, V. V; Cudell, J. R; Gauron, P ...
arXiv (Cornell University),
12/2002
Journal Article
Odprti dostop
Nowadays, scientific databases have become the bread-and-butter of particle
physicists. These databases must be maintained and checked repeatedly to insure
the accuracy of their content. The COMPETE ...collaboration aims at motivating
data maintenance via the interfacing of theory and experiment at the database
level. The database concept then needs to be supplemented by a "model-base".
Such an object enables one not only to decide what the best description may be,
but also to discern what potential problems exist in the data. The
systematization of such a cross-fertilization between models and data results
in the "object of knowledge" that is the point at which all existing
information resources on a given problem could converge. There are many
advantages to such a global approach. First of all, the maintenance of a data
set is not a static task: it needs to be motivated by physics. The second
advantage is that one can have a common testing ground for theories and models.
Thirdly, an extensive theoretical database can be used to plan new experiments
and to predict various quantities. Finally, as new data come in, one can very
quickly decide on their theoretical impact, and hence immediately evaluate the
need for new physics ideas.
As we want to treat a large amount of data and many models, computer
technology constitutes an important part of our activity. We have concentrated
on the elaboration of artificial intelligence decision-making algorithms, as
well as on the delivery of computer tools for the end-user. Further linkage
with existing databases, such as PDG, COMPAS, and HEPDATA is being developed or
planned.
PDF
