Classical resolution of singularities in dilaton cosmologies

For models of dilaton-gravity with a possible exponential potential, such as the tensor-scalar sector of IIA supergravity, we show how cosmological solutions correspond to trajectories in a 2D Milne space (parametrized by the dilaton and the scale factor). Cosmological singularities correspond to points at which a trajectory meets the Milne horizon, but the trajectories can be smoothly continued through the horizon to an instanton solution of the Euclidean theory. We find some exact cosmology/instanton solutions that lift to black holes in one higher dimension. For one such solution, the singularities of a big crunch to big bang transition mediated by an instanton phase lift to the black hole and cosmological horizons of de Sitter Schwarzschild spacetimes.Comment: 24 pages, 2 figure

Cosmological D-instantons and Cyclic Universes

For models of gravity coupled to hyperbolic sigma models, such as the metric-scalar sector of IIB supergravity, we show how smooth trajectories in the `augmented target space' connect FLRW cosmologies to non-extremal D-instantons through a cosmological singularity. In particular, we find closed cyclic universes that undergo an endless sequence of big-bang to big-crunch cycles separated by instanton `phases'. We also find `big-bounce' universes in which a collapsing closed universe bounces off its cosmological singularity to become an open expanding universe.Comment: 21 pages, 4 figures. v2: minor change

Characterization of human iodothyronine sulfotransferases

Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent Km values of 3,3'-T2 and T3 [at 50 micromol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS)] were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The sulfation of 3,3'-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney

Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

Background Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. Methods Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. Results Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. Conclusion Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion

Moduli backreaction and supersymmetry breaking in string-inspired inflation models

We emphasize the importance of effects from heavy fields on supergravity models of inflation. We study, in particular, the backreaction of stabilizer fields and geometric moduli in the presence of supersymmetry breaking. Many effects do not decouple even if those fields are much heavier than the inflaton field. We apply our results to successful models of Starobinsky-like inflation and natural inflation. In most scenarios producing a plateau potential it proves difficult to retain the flatness of the potential after backreactions are taken into account. Some of them are incompatible with non-perturbative moduli stabilization. In natural inflation there exist a number of models which are not constrained by backreactions at all. In those cases the correction terms from heavy fields have the same inflaton-dependence as the uncorrected potential, so that inflation may be possible even for very large gravitino masses.Comment: 29 pages, 1 figure, comments added, subsection 2.3 added, published versio

Jordan Pairs, E6 and U-Duality in Five Dimensions

By exploiting the Jordan pair structure of U-duality Lie algebras in D = 3 and the relation to the super-Ehlers symmetry in D = 5, we elucidate the massless multiplet structure of the spectrum of a broad class of D = 5 supergravity theories. Both simple and semi-simple, Euclidean rank-3 Jordan algebras are considered. Theories sharing the same bosonic sector but with different supersymmetrizations are also analyzed.Comment: 1+41 pages, 1 Table; v2 : a Ref. and some comments adde

Waiting list mortality and the potential of donation after circulatory death heart transplantations in the Netherlands

BACKGROUND: With more patients qualifying for heart transplantation (HT) and fewer hearts being transplanted, it is vital to look for other options. To date, only organs from brain-dead donors have been used for HT in the Netherlands. We investigated waiting list mortality in all Dutch HT centres and the potential of donation after circulatory death (DCD) HT in the Netherlands. METHODS: Two different cohorts were evaluated. One cohort was defined as patients who were newly listed or were already on the waiting list for HT between January 2013 and December 2017. Follow-up continued until September 2018 and waiting list mortality was calculated. A second cohort of all DCD donors in the Netherlands (lung, liver, kidney and pancreas) between January 2013 and December 2017 was used to calculate the potential of DCD HT. RESULTS: Out of 395 patients on the waiting list for HT, 196 (50%) received transplants after a median waiting time of 2.6 years. In total, 15% died while on the waiting list before a suitable donor heart became available. We identified 1006 DCD donors. After applying exclusion criteria and an age limit of 50 years, 122 potential heart donors remained. This number increased to 220 when the age limit was extended to 57 years. CONCLUSION: Waiting list mortality in the Netherlands is high. HT using organs from DCD donors has great potential in the Netherlands and could lead to a reduction in waiting list mortality. Cardiac screening will eventually determine the true potential

Superconformal M2-branes and generalized Jordan triple systems

Three-dimensional conformal theories with six supersymmetries and SU(4) R-symmetry describing stacks of M2-branes are here proposed to be related to generalized Jordan triple systems. Writing the four-index structure constants in an appropriate form, the Chern-Simons part of the action immediately suggests a connection to such triple systems. In contrast to the previously considered three-algebras, the additional structure of a generalized Jordan triple system is associated to a graded Lie algebra, which corresponds to an extension of the gauge group. In this note we show that the whole theory with six manifest supersymmetries can be naturally expressed in terms of such a graded Lie algebra. Also the BLG theory with eight supersymmetries is included as a special case.Comment: 15 pages, v2 and v3: minor corrections and clarifications, references added, v2: section 4 extended, v3: published versio

Universal de Sitter solutions at tree-level

Type IIA string theory compactified on SU(3)-structure manifolds with orientifolds allows for classical de Sitter solutions in four dimensions. In this paper we investigate these solutions from a ten-dimensional point of view. In particular, we demonstrate that there exists an attractive class of de Sitter solutions, whose geometry, fluxes and source terms can be entirely written in terms of the universal forms that are defined on all SU(3)-structure manifolds. These are the forms J and Omega, defining the SU(3)-structure itself, and the torsion classes. The existence of such universal de Sitter solutions is governed by easy-to-verify conditions on the SU(3)-structure, rendering the problem of finding dS solutions purely geometrical. We point out that the known (unstable) solution coming from the compactification on SU(2)x SU(2) is of this kind.Comment: 20 pages, 3 figures, v2: added reference