Interval training normalizes cCardiomyocyte function, diastolic Ca²⁺ control, and SR Ca²⁺ release synchronicity in a mouse model of diabetic cardiomyopathy

In the present study we explored the mechanisms behind excitation-contraction (EC)-coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db), and determined whether 13-weeks of aerobic interval training could restore cardiomyocyte Ca2+ cycling and EC-coupling. Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca2+ leak, reduced synchrony of Ca2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca2+ and caffeine-induced Ca2+ release. Additionally, the rate of SR Ca2+ ATPase (SERCA2a)-mediated Ca2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca2+ release indicated increased Na+/Ca2+- exchanger (NCX) activity. The increased SR-Ca2+ leak was attributed to increased Ca2+-calmodulindependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca2+ leak upon inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca2+ release synchronicity, T-tubule density, twitch Ca2+ amplitude, SERCA2a and NCX activities, and SR-Ca2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A (PKA) inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca2+ load when compared with the sedentary db/db mice. EC-coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition. These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type (WT)

Black Holes in Supergravity: the non-BPS Branch

We construct extremal, spherically symmetric black hole solutions to 4D supergravity with charge assignments that preclude BPS-saturation. In particular, we determine the ground state energy as a function of charges and moduli. We find that the mass of the non-BPS black hole remains that of a marginal bound state of four basic constituents throughout the entire moduli space and that there is always a non-zero gap above the BPS bound.Comment: 29 pages, one appendix, no figures; v2. few comments and references added and a missing sign included; v3. further references adde

Holographic Gravitational Anomalies

In the AdS/CFT correspondence one encounters theories that are not invariant under diffeomorphisms. In the boundary theory this is a gravitational anomaly, and can arise in 4k+2 dimensions. In the bulk, there can be gravitational Chern-Simons terms which vary by a total derivative. We work out the holographic stress tensor for such theories, and demonstrate agreement between the bulk and boundary. Anomalies lead to novel effects, such as a nonzero angular momentum for global AdS(3). In string theory such Chern-Simons terms are known with exact coefficients. The resulting anomalies, combined with symmetries, imply corrections to the Bekenstein-Hawking entropy of black holes that agree exactly with the microscopic counting.Comment: 25 page

First-order flow equations for extremal black holes in very special geometry

We construct interpolating solutions describing single-center static extremal non-supersymmetric black holes in four-dimensional N=2 supergravity theories with cubic prepotentials. To this end, we derive and solve first-order flow equations for rotating electrically charged extremal black holes in a Taub-NUT geometry in five dimensions. We then use the connection between five- and four-dimensional extremal black holes to obtain four-dimensional flow equations and we give the corresponding solutions.Comment: 21 pages. v2: Summary section adde

Development of Eosinophilic Airway Inflammation and Airway Hyperresponsiveness in Mast Cell–deficient Mice

Mast cells are the main effector cells of immediate hypersensitivity and anaphylaxis. Their role in the development of allergen-induced airway hyperresponsiveness (AHR) is controversial and based on indirect evidence. To address these issues, mast cell–deficient mice (W/W  v) and their congenic littermates were sensitized to ovalbumin (OVA) by intraperitoneal injection and subsequently challenged with OVA via the airways. Comparison of OVA-specific immunoglobulin E (IgE) levels in the serum and numbers of eosinophils in bronchoalveolar lavage fluid or lung digests showed no differences between the two groups of mice. Further, measurements of airway resistance and dynamic compliance at baseline and after inhalation of methacholine were similar. These data indicate that mast cells or IgE–mast cell activation is not required for the development of eosinophilic inflammation and AHR in mice sensitized to allergen via the intraperitoneal route and challenged via the airways

Entropy Function for Non-extremal D1D5 and D2D6NS5-branes

We apply the entropy function formalism to non-extremal D1D5 and D2D6NS5-branes whose throat approximation is given by the Schwarzschild black hole in AdS_3\times S^3\times T^4 and AdS_3\times S^2\times S^1\times T^4, respectively. We find the Bekenstein-Hawking entropy and the (alpha')^3R^4 corrections from the value of the entropy function at its saddle point. While the higher derivative terms have no effect on the temperature, they decrease the value of the entropy.Comment: 17 Pages, Latex file; Minor additions, version published in JHE

One entropy function to rule them all

We study the entropy of extremal four dimensional black holes and five dimensional black holes and black rings is a unified framework using Sen's entropy function and dimensional reduction. The five dimensional black holes and black rings we consider project down to either static or stationary black holes in four dimensions. The analysis is done in the context of two derivative gravity coupled to abelian gauge fields and neutral scalar fields. We apply this formalism to various examples including $U(1)^3$ minimal supergravity.Comment: 29 pages, 2 figures, revised version for publication, details adde

A Note on Exact Solutions and Attractor Mechanism for Non-BPS Black Holes

We obtain two extremal, spherically symmetric, non-BPS black hole solutions to 4D supergravity, one of which carries D2-D6 charges and the other carries D0-D2-D4 charges. For the D2-D6 case, rather than solving the equations of motion directly, we assume the form of the solution and then find that the assumption satisfies the equations of motion and the constraint. Our D2-D6 solution is manifestly dual to the solution presented in 0710.4967. The D0-D2-D4 solution is obtained by performing certain $[SL(2,{\bf Z})]^{3}$ duality transformations on the D0-D4 solution in 0710.4967.Comment: 20 pages, LaTe

On R**2 Corrections for 5D Black Holes

We study higher order corrections to extremal black holes/black string in five dimensions. These higher order corrections are due to supersymmetric completion of R**2 term in five dimensions. By making use of the results we extend the notion of very special geometry when higher derivative terms are also taken into account. This can be used to make a connection between total bundle space of near horizon wrapped M2's and wrapped M5's in the presence of higher order corrections. We also show how the corrected geometry removes the singularity of a small black hole.Comment: 16 pages, latex file, V3: typos corrected, refs added, V4; minor corrections, few comments added, refs adde

Extremal black holes in D=5: SUSY vs. Gauss-Bonnet corrections

We analyse near-horizon solutions and compare the results for the black hole entropy of five-dimensional spherically symmetric extremal black holes when the N=2 SUGRA actions are supplied with two different types of higher-order corrections: (1) supersymmetric completion of gravitational Chern-Simons term, and (2) Gauss-Bonnet term. We show that for large BPS black holes lowest order \alpha' corrections to the entropy are the same, but for non-BPS are generally different. We pay special attention to the class of prepotentials connected with K3\times T^2 and T^6 compactifications. For supersymmetric correction we find beside BPS also a set of non-BPS solutions. In the particular case of T^6 compactification (equivalent to the heterotic string on $T^4\times S^1$) we find the (almost) complete set of solutions (with exception of some non-BPS small black holes), and show that entropy of small black holes is different from statistical entropy obtained by counting of microstates of heterotic string theory. We also find complete set of solutions for K3\times T^2 and T^6 case when correction is given by Gauss-Bonnet term. Contrary to four-dimensional case, obtained entropy is different from the one with supersymmetric correction. We show that in Gauss-Bonnet case entropy of small ``BPS'' black holes agrees with microscopic entropy in the known cases.Comment: 28 pages; minor changes, version to appear in JHE