776 research outputs found
E11, generalised space-time and equations of motion in four dimensions
We construct the non-linear realisation of the semi-direct product of E11 and
its first fundamental representation at low levels in four dimensions. We
include the fields for gravity, the scalars and the gauge fields as well as the
duals of these fields. The generalised space-time, upon which the fields
depend, consists of the usual coordinates of four dimensional space-time and
Lorentz scalar coordinates which belong to the 56-dimensional representation of
E7. We demand that the equations of motion are first order in derivatives of
the generalised space-time and then show that they are essentially uniquely
determined by the properties of the E11 Kac-Moody algebra and its first
fundamental representation. The two lowest equations correctly describe the
equations of motion of the scalars and the gauge fields once one takes the
fields to depend only on the usual four dimensional space-time
N = 2 supersymmetric sigma-models and duality
For two families of four-dimensional off-shell N = 2 supersymmetric nonlinear
sigma-models constructed originally in projective superspace, we develop their
formulation in terms of N = 1 chiral superfields. Specifically, these theories
are: (i) sigma-models on cotangent bundles T*M of arbitrary real analytic
Kaehler manifolds M; (ii) general superconformal sigma-models described by
weight-one polar supermultiplets. Using superspace techniques, we obtain a
universal expression for the holomorphic symplectic two-form \omega^{(2,0)}
which determines the second supersymmetry transformation and is associated with
the two complex structures of the hyperkaehler space T*M that are complimentary
to the one induced from M. This two-form is shown to coincide with the
canonical holomorphic symplectic structure. In the case (ii), we demonstrate
that \omega^{(2,0)} and the homothetic conformal Killing vector determine the
explicit form of the superconformal transformations. At the heart of our
construction is the duality (generalized Legendre transform) between off-shell
N = 2 supersymmetric nonlinear sigma-models and their on-shell N = 1 chiral
realizations. We finally present the most general N = 2 superconformal
nonlinear sigma-model formulated in terms of N = 1 chiral superfields. The
approach developed can naturally be generalized in order to describe 5D and 6D
superconformal nonlinear sigma-models in 4D N = 1 superspace.Comment: 31 pages, no figures; V2: reference and comments added, typos
corrected; V3: more typos corrected, published versio
On the perturbative S-matrix of generalized sine-Gordon models
Motivated by its relation to the Pohlmeyer reduction of AdS_5 x S^5
superstring theory we continue the investigation of the generalized sine-Gordon
model defined by SO(N+1)/SO(N) gauged WZW theory with an integrable potential.
Extending our previous work (arXiv:0912.2958) we compute the one-loop
two-particle S-matrix for the elementary massive excitations. In the N = 2 case
corresponding to the complex sine-Gordon theory it agrees with the charge-one
sector of the quantum soliton S-matrix proposed in hep-th/9410140. In the case
of N > 2 when the gauge group SO(N) is non-abelian we find a curious anomaly in
the Yang-Baxter equation which we interpret as a gauge artifact related to the
fact that the scattered particles are not singlets under the residual global
subgroup of the gauge group
Off-shell supergravity-matter couplings in three dimensions
We develop the superspace geometry of N-extended conformal supergravity in
three space-time dimensions. General off-shell supergravity-matter couplings
are constructed in the cases N=1,2,3,4.Comment: 73 pages; V5: typos in eqs. (3.4b), (3.17) and (4.24) correcte
Background independent action for double field theory
Double field theory describes a massless subsector of closed string theory
with both momentum and winding excitations. The gauge algebra is governed by
the Courant bracket in certain subsectors of this double field theory. We
construct the associated nonlinear background-independent action that is
T-duality invariant and realizes the Courant gauge algebra. The action is the
sum of a standard action for gravity, antisymmetric tensor, and dilaton fields
written with ordinary derivatives, a similar action for dual fields with dual
derivatives, and a mixed term that is needed for gauge invariance.Comment: 45 pages, v2: minor corrections, refs. added, to appear in JHE
On duality symmetry in perturbative quantum theory
Non-compact symmetries of extended 4d supergravities involve duality
rotations of vectors and thus are not manifest off-shell invariances in
standard "second-order" formulation. To study how such symmetries are realised
in the quantum theory we consider examples in 2 dimensions where vector-vector
duality is replaced by scalar-scalar one. Using a "doubled" formulation, where
fields and their momenta are treated on an equal footing and the duality
becomes a manifest symmetry of the action (at the expense of Lorentz symmetry),
we argue that the corresponding on-shell quantum effective action or S-matrix
are duality symmetric as well as Lorentz invariant. The simplest case of
discrete Z_2 duality corresponds to a symmetry of the S-matrix under flipping
the sign of the negative-chirality scalars in 2 dimensions or phase rotations
of chiral (definite-helicity) parts of vectors in 4 dimensions. We also briefly
discuss some 4d models and comment on implications of our analysis for extended
supergravities.Comment: 21 pages, Latex v2: comments and references added v3: references and
minor comments adde
Off-shell superconformal nonlinear sigma-models in three dimensions
We develop superspace techniques to construct general off-shell N=1,2,3,4
superconformal sigma-models in three space-time dimensions. The most general
N=3 and N=4 superconformal sigma-models are constructed in terms of N=2 chiral
superfields. Several superspace proofs of the folklore statement that N=3
supersymmetry implies N=4 are presented both in the on-shell and off-shell
settings. We also elaborate on (super)twistor realisations for (super)manifolds
on which the three-dimensional N-extended superconformal groups act
transitively and which include Minkowski space as a subspace.Comment: 67 pages; V2: typos corrected, one reference added, version to appear
on JHE
Darolutamide does not interfere with OATP-mediated uptake of docetaxel
The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drugâdrug interaction was identified
Darolutamide does not interfere with OATP-mediated uptake of docetaxel
The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drugâdrug interaction was identified
How Clinical Integration of Pharmacists in General Practice has Impact on Medication Therapy Management: A Theory-oriented Evaluation.
Background: Data on medication-related hospital admissions suggest that there is an opportunity for improved pharmaceutical care. Hence, concerns about medication-related hospital admissions is a driver to extend and integrate the role of community pharmacists in general practice. Aim: The aim of this paper is to give a systematic description of 1) what integrating a non-dispensing pharmacist (NDP) in general practice entails and 2) how this integrated care model is expected to contribute to patientsâ medication therapy management. Methods: Based on ethnographic data collected by NDPs in general practices in the Netherlands, we conducted a theory evaluation. Results: The impact of NDPs providing integrated care can be explained by 1) the specific expertise NDPs bring into general practice and the tailored solutions they offer for individual patients, including deviation from medical protocols when necessary, 2) the reconciliation of interprofessional tensions caused by overlapping tasks with practice nurses, which results in a distinct patient population, 3) the conduct of clinical medication reviews aligned to the work processes of the GP practice and 4) the integration of quality management work into clinical work. Conclusion: The success of integrated pharmaceutical care is dependent on how NDPs collaborate with GPs and practice nurses. NDPs need to mobilize clinical pharmaceutical expertise into general practice. Yet, integrating quality management into clinical work is key to integrate pharmaceutical care. Paradoxically, full integration requires from NDPs to develop a distinct role in general practice
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