129 research outputs found
IIA Ten-forms and the Gauge Algebras of Maximal Supergravity Theories
We show that IIA supergravity can be extended with two independent 10-form
potentials. These give rise to a single BPS IIA 9-brane. We investigate the
bosonic gauge algebra of both IIA and IIB supergravity in the presence of
10-form potentials and point out an intriguing relation with the symmetry
algebra , which has been conjectured to be the underlying symmetry of
string theory/M-theory.Comment: 18 pages, section on IIA 9-branes added, references added; version to
be publishe
Probabilistic Bisimulation: Naturally on Distributions
In contrast to the usual understanding of probabilistic systems as stochastic
processes, recently these systems have also been regarded as transformers of
probabilities. In this paper, we give a natural definition of strong
bisimulation for probabilistic systems corresponding to this view that treats
probability distributions as first-class citizens. Our definition applies in
the same way to discrete systems as well as to systems with uncountable state
and action spaces. Several examples demonstrate that our definition refines the
understanding of behavioural equivalences of probabilistic systems. In
particular, it solves a long-standing open problem concerning the
representation of memoryless continuous time by memory-full continuous time.
Finally, we give algorithms for computing this bisimulation not only for finite
but also for classes of uncountably infinite systems
Duality Symmetries and G^{+++} Theories
We show that the non-linear realisations of all the very extended algebras
G^{+++}, except the B and C series which we do not consider, contain fields
corresponding to all possible duality symmetries of the on-shell degrees of
freedom of these theories. This result also holds for G_2^{+++} and we argue
that the non-linear realisation of this algebra accounts precisely for the form
fields present in the corresponding supersymmetric theory. We also find a
simple necessary condition for the roots to belong to a G^{+++} algebra.Comment: 35 pages. v2: 2 appendices added, other minor corrections. v3: tables
corrected, other minor changes, one appendix added, refs. added. Version
published in Class. Quant. Gra
The effective action of D6-branes in N=1 type IIA orientifolds
We use a Kaluza-Klein reduction to compute the low-energy effective action
for the massless modes of a spacetime-filling D6-brane wrapped on a special
Lagrangian 3-cycle of a type IIA Calabi-Yau orientifold. The modifications to
the characteristic data of the N=1 bulk orientifold theory in the presence of a
D6-brane are analysed by studying the underlying Type IIA supergravity coupled
to the brane worldvolume in the democratic formulation and performing a
detailed dualisation procedure. The N=1 chiral coordinates are found to be in
agreement with expectations from mirror symmetry. We work out the Kahler
potential for the chiral superfields as well as the gauge kinetic functions for
the bulk and the brane gauge multiplets including the kinetic mixing between
the two. The scalar potential resulting from the dualisation procedure can be
formally interpreted in terms of a superpotential. Finally, the gauging of the
Peccei-Quinn shift symmetries of the complex structure multiplets reproduces
the D-term potential enforcing the calibration condition for special Lagrangian
3-cycles.Comment: 48 pages, v2: typos corrected, references adde
Fluxes and Warping for Gauge Couplings in F-theory
We compute flux-dependent corrections in the four-dimensional F-theory
effective action using the M-theory dual description. In M-theory the 7-brane
fluxes are encoded by four-form flux and modify the background geometry and
Kaluza-Klein reduction ansatz. In particular, the flux sources a warp factor
which also depends on the torus directions of the compactification fourfold.
This dependence is crucial in the derivation of the four-dimensional action,
although the torus fiber is auxiliary in F-theory. In M-theory the 7-branes are
described by an infinite array of Taub-NUT spaces. We use the explicit metric
on this geometry to derive the locally corrected warp factor and M-theory
three-from as closed expressions. We focus on contributions to the 7-brane
gauge coupling function from this M-theory back-reaction and show that terms
quadratic in the internal seven-brane flux are induced. The real part of the
gauge coupling function is modified by the M-theory warp factor while the
imaginary part is corrected due to a modified M-theory three-form potential.
The obtained contributions match the known weak string coupling result, but
also yield additional terms suppressed at weak coupling. This shows that the
completion of the M-theory reduction opens the way to compute various
corrections in a genuine F-theory setting away from the weak string coupling
limit.Comment: 46 page
Rational F-Theory GUTs without exotics
We construct F-theory GUT models without exotic matter, leading to the MSSM
matter spectrum with potential singlet extensions. The interplay of engineering
explicit geometric setups, absence of four-dimensional anomalies, and realistic
phenomenology of the couplings places severe constraints on the allowed local
models in a given geometry. In constructions based on the spectral cover we
find no model satisfying all these requirements. We then provide a survey of
models with additional U(1) symmetries arising from rational sections of the
elliptic fibration in toric constructions and obtain phenomenologically
appealing models based on SU(5) tops. Furthermore we perform a bottom-up
exploration beyond the toric section constructions discussed in the literature
so far and identify benchmark models passing all our criteria, which can serve
as a guideline for future geometric engineering.Comment: 27 Pages, 1 Figur
In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials
Background aims Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell–based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice–conforming, MSC-based advanced-therapy medicinal product. Methods To support the development of ABCB5+ MSCs for potential therapeutic topical, intramuscular and intravenous administration, we have tested our product in a series of Good Laboratory Practice–compliant nonclinical in-vivo studies addressing all relevant aspects of biosafety, including potential long-term persistence and proliferation, distribution to nontarget tissues, differentiation into undesired cell types, ectopic tissue formation, tumor formation and local tissue reaction. Results (i) Subcutaneous application of 1 × 107 ABCB5+ MSCs/animal and intravenous application of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice did not result in safety-relevant biodistribution, persistence or proliferation of the cells; (ii) three monthly subcutaneous injections of ABCB5+ MSCs at doses ranging from 1 × 105 to 1 × 107 cells/animal and three biweekly intravenous injections of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice were nontoxic and revealed no tumorigenic potential; and (iii) intramuscular injection of 5 × 106 ABCB5+ MSCs/animal to immunocompromised mice was locally well tolerated. Discussion The present preclinical in vivo data demonstrate the local and systemic safety and tolerability of a novel advanced-therapy medicinal product based on human skin-derived ABCB5+ MSCs
Massive Abelian Gauge Symmetries and Fluxes in F-theory
F-theory compactified on a Calabi-Yau fourfold naturally describes
non-Abelian gauge symmetries through the singularity structure of the elliptic
fibration. In contrast Abelian symmetries are more difficult to study because
of their inherently global nature. We argue that in general F-theory
compactifications there are massive Abelian symmetries, such as the uplift of
the Abelian part of the U(N) gauge group on D7-branes, that arise from
non-Kahler resolutions of the dual M-theory setup. The four-dimensional
F-theory vacuum with vanishing expectation values for the gauge fields
corresponds to the Calabi-Yau limit. We propose that fluxes that are turned on
along these U(1)s are uplifted to non-harmonic four-form fluxes. We derive the
effective four-dimensional gauged supergravity resulting from F-theory
compactifications in the presence of the Abelian gauge factors including the
effects of possible fluxes on the gauging, tadpoles and matter spectrum.Comment: 49 page
Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as good manufacturing practice-compliant autologous advanced therapy medicinal product for clinical use: Process validation and first in-human data
© 2020 International Society for Cell & Gene Therapy Background aim: Mesenchymal stromal cells (MSCs) hold promise for the treatment of tissue damage and injury. However, MSCs comprise multiple subpopulations with diverse properties, which could explain inconsistent therapeutic outcomes seen among therapeutic attempts. Recently, the adenosine triphosphate-binding cassette transporter ABCB5 has been shown to identify a novel dermal immunomodulatory MSC subpopulation. Methods: The authors have established a validated Good Manufacturing Practice (GMP)-compliant expansion and manufacturing process by which ABCB5+ MSCs can be isolated from skin tissue and processed to generate a highly functional homogeneous cell population manufactured as an advanced therapy medicinal product (ATMP). This product has been approved by the German competent regulatory authority to be tested in a clinical trial to treat therapy-resistant chronic venous ulcers. Results: As of now, 12 wounds in nine patients have been treated with 5 × 105 autologous ABCB5+ MSCs per cm2 wound area, eliciting a median wound size reduction of 63% (range, 32–100%) at 12 weeks and early relief of pain. Conclusions: The authors describe here their GMP- and European Pharmacopoeia-compliant production and quality control process, report on a pre-clinical dose selection study and present the first in-human results. Together, these data substantiate the idea that ABCB5+ MSCs manufactured as ATMPs could deliver a clinically relevant wound closure strategy for patients with chronic therapy-resistant wounds
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