Generalized E(7(7)) coset dynamics and D=11 supergravity

The hidden on-shell E(7(7)) symmetry of maximal supergravity is usually discussed in a truncation from D=11 to four dimensions. In this article, we reverse the logic and start from a theory with manifest off-shell E(7(7)) symmetry inspired by West's coset construction. Following de Wit's and Nicolai's idea that a 4+56 dimensional "exceptional geometry" underlies maximal supergravity, we construct the corresponding Lagrangian and the supersymmetry variations for the 56 dimensional subsector. We prove that both the dynamics and the supersymmetry coincide with D=11 supergravity in a truncation to d=7 in the expected way.Comment: 42 pages, v2: references adde

K(E10), Supergravity and Fermions

We study the fermionic extension of the E10/K(E10) coset model and its relation to eleven-dimensional supergravity. Finite-dimensional spinor representations of the compact subgroup K(E10) of E(10,R) are studied and the supergravity equations are rewritten using the resulting algebraic variables. The canonical bosonic and fermionic constraints are also analysed in this way, and the compatibility of supersymmetry with local K(E10) is investigated. We find that all structures involving A9 levels 0,1 and 2 nicely agree with expectations, and provide many non-trivial consistency checks of the existence of a supersymmetric extension of the E10/K(E10) coset model, as well as a new derivation of the `bosonic dictionary' between supergravity and coset variables. However, there are also definite discrepancies in some terms involving level 3, which suggest the need for an extension of the model to infinite-dimensional faithful representations of the fermionic degrees of freedom.Comment: 50 page

SO(5,5) duality in M-theory and generalized geometry

We attempt to reformulate eleven dimensional supergravity in terms of an object that unifies the three-form and the metric and makes the M-theory duality group manifest. This short note deals with the case of where the U-duality group SO(5,5) acts in five spatial dimensions.Comment: 7 pages, LaTex, v2: typos corrected and reference adde

Combined PARP and Dual Topoisomerase Inhibition Potentiates Genome Instability and Cell Death in Ovarian Cancer

Although ovarian cancer is a rare disease, it constitutes the fifth leading cause of cancer death among women. It is of major importance to develop new therapeutic strategies to improve survival. Combining P8-D6, a novel dual topoisomerase inhibitor with exceptional anti-tumoral properties in ovarian cancer and compounds in preclinical research, and olaparib, a PARP inhibitor targeting DNA damage repair, is a promising approach. P8-D6 induces DNA damage that can be repaired by base excision repair or homologous recombination in which PARP plays a major role. This study analyzed benefits of combining P8-D6 and olaparib treatment in 2D and 3D cultures with ovarian cancer cells. Measurement of viability, cytotoxicity and caspase activity were used to assess therapy efficacy and to calculate the combination index (CI). Further DNA damage was quantified using the biomarkers RAD51 and γH2A.X. The combinational treatment led to an increased caspase activity and reduced viability. CI values partially show synergisms in combinations at 100 nM and 500 nM P8-D6. More DNA damage accumulated, and spheroids lost their membrane integrity due to the combinational treatment. While maintaining the same therapy efficacy as single-drug therapy, doses of P8-D6 and olaparib can be reduced in combinational treatments. Synergisms can be seen in some tested combinations. In summary, the combination therapy indicates benefits and acts synergistic at 100 nM and 500 nM P8-D6

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

Generalized Geometry and M theory

We reformulate the Hamiltonian form of bosonic eleven dimensional supergravity in terms of an object that unifies the three-form and the metric. For the case of four spatial dimensions, the duality group is manifest and the metric and C-field are on an equal footing even though no dimensional reduction is required for our results to hold. One may also describe our results using the generalized geometry that emerges from membrane duality. The relationship between the twisted Courant algebra and the gauge symmetries of eleven dimensional supergravity are described in detail.Comment: 29 pages of Latex, v2 References added, typos fixed, v3 corrected kinetic term and references adde

The local symmetries of M-theory and their formulation in generalised geometry

In the doubled field theory approach to string theory, the T-duality group is promoted to a manifest symmetry at the expense of replacing ordinary Riemannian geometry with generalised geometry on a doubled space. The local symmetries are then given by a generalised Lie derivative and its associated algebra. This paper constructs an analogous structure for M-theory. A crucial by-product of this is the derivation of the physical section condition for M-theory formulated in an extended space.Comment: 20 pages, v2: Author Name corrected, v3: typos correcte

Duality Invariant Actions and Generalised Geometry

We construct the non-linear realisation of the semi-direct product of E(11) and its first fundamental representation at lowest order and appropriate to spacetime dimensions four to seven. This leads to a non-linear realisation of the duality groups and introduces fields that depend on a generalised space which possess a generalised vielbein. We focus on the part of the generalised space on which the duality groups alone act and construct an invariant action.Comment: 59 pages (typos fixed and added comments

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)