Fourier-Laplace transform of a variation of polarized complex Hodge structure, II

We show that the limit, by rescaling, of the `new supersymmetric index' attached to the Fourier-Laplace transform of a polarized variation of Hodge structure on a punctured affine line is equal to the spectral polynomial attached to the same object. We also extend the definition by Deligne of a Hodge filtration on the de Rham cohomology of a exponentially twisted polarized variation of complex Hodge structure and prove a E_1 degeneration property for it.Comment: 51 pages, revised version, to appear in the proceedings volume of the conference `` New developments in Algebraic Geometry, Integrable Systems and Mirror symmetry", RIMS, Kyoto, Jan. 7-11, 200

Periods for flat algebraic connections

In previous work, we established a duality between the algebraic de Rham cohomology of a flat algebraic connection on a smooth quasi-projective surface over the complex numbers and the rapid decay homology of the dual connection relying on a conjecture by C. Sabbah, which has been proved recently by T. Mochizuki for algebraic connections in any dimension. In the present article, we verify that Mochizuki's results allow to generalize these duality results to arbitrary dimensions also

Allostatic load and depressive symptoms in older adults: An analysis of 12-year panel data

BACKGROUND: Whether changes in allostatic load (AL) and depressive symptoms relate over time has not been yet fully explored. This study evaluated the association between AL and depressive symptoms over 12 years among community-dwelling older adults. METHODS: Panel data from 8291 participants in the English Longitudinal Study of Ageing were analysed. Depressive symptoms were assessed with the 8-item Centre for Epidemiologic Studies Depression Scale (CES-D). The AL score was derived from nine metabolic, cardiovascular and immune biomarkers. The association between AL and depressive symptoms was modelled in a linear hybrid model adjusting for time-invariant (sex, ethnicity) and time-variant confounders (age, marital status, education, wealth, physical activity, smoking status, alcohol intake, limitations in daily living, comorbidities). RESULTS: The mean AL score was 3.1 (SD: 2.1), 3.5 (2.3), 3.2 (2.3) and 3.3 (2.5) whereas the mean CES-D score was 1.4 (SD: 1.8), 1.2 (1.8), 1.2 (1.8) and 1.2 (1.7) in waves 2, 4, 6 and 8, respectively. In the adjusted model, the between-person differences (coefficient: 0.02, 95% CI: 0.01, 0.04) but not the within-individual differences (0.01; 95% CI: −0.01, 0.03) in the AL score were associated with CES-D score. The between-person coefficient indicates that participants with greater AL scores also had slightly higher CES-D scores. The within-person coefficient indicates that changes in the AL score were not associated with changes in the CES-D score. CONCLUSION: AL was associated with depressive symptoms. However, most of the association was driven by differences in AL between individuals rather than changes in AL over time

The Abelian/Nonabelian Correspondence and Frobenius Manifolds

We propose an approach via Frobenius manifolds to the study (began in math.AG/0407254) of the relation between rational Gromov-Witten invariants of nonabelian quotients X//G and those of the corresponding ``abelianized'' quotients X//T, for T a maximal torus in G. The ensuing conjecture expresses the Gromov-Witten potential of X//G in terms of the potential of X//T. We prove this conjecture when the nonabelian quotients are partial flag manifolds.Comment: 35 pages, no figure

Long-term therapy with elamipretide normalizes activation of the mitochondrial signal transducer and activator of transcription 3 (mstat3) in of left ventricular myocardium of dogs with chronic heart failure

Introduction: The signal transducer and activator of transcription 3 (STAT3) has been identified in mitochondria (MITO) of cardiomyocytes (mSTAT3). In STAT3 -/- cells, the activities of MITO complexes I and II of the electron transport chain (ETC) were reduced suggesting that mSTAT3 is required for optimal ETC function. Deactivation of STAT3, equated with dephosphorylation of tyrosine residues, has been shown to adversely impacted MITO respiration and, consequently, oxidative phosphorylation. We previously showed that long-term (3 months) therapy with elamipretide (ELAM, previously referred to as Bendavia TM, MTP131 or SS31), a novel MITO-targeting peptide, improves LV function and normalizes MITO respiration and rate of ATP synthesis in MITO of LV myocardium of dogs with heart failure (HF). Hypothesis: This study tested the hypothesis that phosphorylation of mSTAT3 (mpSTAT3) is reduced in MITO of LV myocardium of HF dogs and is restored after long-term therapy with ELAM. Methods: LV tissue was obtained from 14 dogs with microembolization-induced HF (LV ejection fraction ∼30%) randomized to 3 months therapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or saline (Control, n=7). LV tissue from 6 normal (NL) dogs was used for comparison. Protein levels of mSTAT3 and mpSTAT3 were determined in MITO fraction by Western blotting coupled with chemiluminiscence and band intensity was quantified in densitometric units (du). Results: Protein level of mSTAT3 was 0.82±0.05 du in NL, decreased to 0.29±0.03 du in Controls (p Conclusions: mpSTAT3 level is reduced in MITO from LV of HF dogs and restored after chronic therapy with ELAM. Normalization of mpSTAT3 by ELAM likely contributed to be observed improvement in MITO function following therapy with ELAM in HF dogs

Effects of Elamipretide on Skeletal Muscle in Dogs with Experimentally Induced Heart Failure

AIMS: Elamipretide (ELAM), an aromatic-cationic tetrapeptide, interacts with cardiolipin and normalizes dysfunctional mitochondria of cardiomyocytes. This study examined the effects of ELAM on skeletal muscle mitochondria function in dogs with chronic heart failure (HF). METHODS AND RESULTS: Studies were performed in skeletal muscle biopsy specimens obtained from normal dogs (n = 7) and dogs with chronic intracoronary microembolization-induced HF (n = 14) treated with subcutaneous ELAM 0.5 mg/kg (HF + ELAM, n = 7) or vehicle (normal saline control, HF-CON, n = 7). After 3 months of therapy, triceps skeletal muscle samples were obtained from all dogs, and the proportion of type 1 and type 2 fibres was assessed. Mitochondria isolated from myofibrils of the vastus lateralis skeletal muscle exposed in vitro to ELAM for 1 h were used to assess mitochondrial function. The proportion of skeletal muscle type 1 fibres was lower in HF-CON dogs compared with normal dogs (23 ± 4 vs. 32 ± 5%, P \u3c 0.05). Treatment with ELAM restored a near-normal fibre-type composition (31 ± 7%, P \u3c 0.05 vs. HF-CON). Skeletal muscle mitochondria showed significantly lower levels of adenosine diphosphate-dependent mitochondrial respiration (100 ± 9 vs. 164 ± 15 natom O/min/mg protein, P \u3c 0.05), mitochondrial membrane potential (0.17 ± 0.03 vs. 0.53 ± 0.03 red/green fluorescence ratio, P \u3c 0.05), mitochondrial permeability transition pore (38 ± 3 vs. 62 ± 2 relative light units, P \u3c 0.05), maximum rate of adenosine triphosphate synthesis (3284 ± 418 vs. 8835 ± 423 RLU/μg protein, P \u3c 0.05), and cytochrome c oxidase activity (1390 ± 108 vs. 2459 ± 210 natom O/min/mg protein, P \u3c 0.05) compared with normal dogs. Exposure of skeletal muscle myofibrillar mitochondria from HF dogs to ELAM showed a dose-dependent improvement/normalization of all measures of mitochondrial function. In mitochondria from skeletal muscle of HF dogs exposed to 0.10 μM ELAM, adenosine diphosphate-dependent mitochondrial respiration increased to 183 ± 18 natom O/min/mg protein, membrane potential increased to 0.30 ± 0.03 red/green fluorescence ratio, mitochondrial permeability transition pore increased to 54 ± 4 RLU, maximum rate of adenosine triphosphate synthesis increased to 4423 ± 414, and cytochrome c oxidase activity increased to 2033 ± 191 natom O/min/mg protein. Exposure of skeletal muscle myofibrillar mitochondria from normal dogs to ELAM had no effect on mitochondrial function parameters. CONCLUSIONS: The results indicate that ELAM, previously shown to positively influence mitochondrial function of the failing heart, can also positively impact mitochondrial function of skeletal muscle and potentially help restore skeletal muscle function and improve exercise tolerance

tt*-geometry on the big phase space

The big phase space, the geometric setting for the study of quantum cohomology with gravitational descendents, is a complex manifold and consists of an infinite number of copies of the small phase space. The aim of this paper is to define a Hermitian geometry on the big phase space. Using the approach of Dijkgraaf and Witten, we lift various geometric structures of the small phase space to the big phase space. The main results of our paper state that various notions from tt*-geometry are preserved under such liftings