C-Peptide and Atherogenesis: C-Peptide as a Mediator of Lesion Development in Patients with Type 2 Diabetes Mellitus?

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential role of C-peptide in atherogenesis in patients with type 2 diabetes

The Real Topological String on a local Calabi-Yau

We study the topological string on local P2 with O-plane and D-brane at its real locus, using three complementary techniques. In the A-model, we refine localization on the moduli space of maps with respect to the torus action preserved by the anti-holomorphic involution. This leads to a computation of open and unoriented Gromov-Witten invariants that can be applied to any toric Calabi-Yau with involution. We then show that the full topological string amplitudes can be reproduced within the topological vertex formalism. We obtain the real topological vertex with trivial fixed leg. Finally, we verify that the same results derive in the B-model from the extended holomorphic anomaly equation, together with appropriate boundary conditions. The expansion at the conifold exhibits a gap structure that belongs to a so far unidentified universality class.Comment: 37 pages, 4 figure

Proinflammatory Effects of C-Peptide in Different Tissues

Atherosclerosis is well known as an inflammatory disease that can lead to clinical complications such as heart attack or stroke. C-peptide as a cleavage product of proinsulin is in the last few decades known as an active peptide with a number of different effects on microvascular and macrovascular complications in type 2 diabetic patients. Patients with insulin resistance and early type 2 diabetes show elevated levels of C-peptide in blood. Several last findings demonstrated deposition of C-peptide in the vessel wall in ApoE-deficient mice and induction of local inflammation. Besides that, C-peptide has proliferative effects on human mesangial cells. This review discusses recently published proinflammatory effects of C-peptide in different tissues

C-Peptide: A New Mediator of Atherosclerosis in Diabetes

Diabetes type 2 and insulin resistance are the risk factors for cardiovascular disease. It is already known that atherosclerosis is an inflammatory disease, and a lot of different factors are involved in its onset. C-peptide is a cleavage product of proinsulin, an active substance with a number of effects within different complications of diabetes. In this paper we discuss the role of C-peptide and its effects in the development of atherosclerosis in type 2 diabetic patients

Real Mirror Symmetry for One-parameter Hypersurfaces

We study open string mirror symmetry for one-parameter Calabi-Yau hypersurfaces in weighted projective space. We identify mirror pairs of D-brane configurations, derive the corresponding inhomogeneous Picard-Fuchs equations, and solve for the domainwall tensions as analytic functions over moduli space. Our calculations exemplify several features that had not been seen in previous work on the quintic or local Calabi-Yau manifolds. We comment on the calculation of loop amplitudes.Comment: 42 pages, 2 figure

Ivabradine Reduces Chemokine-Induced CD4-Positive Lymphocyte Migration

Aims. Migration of CD4-positive lymphocytes into the vessel wall is a critical step in atherogenesis. Recent data suggest that ivabradine, a selective I(f)-channel blocker, reduces atherosclerotic plaque formation in apolipoprotein E-deficient mice, hitherto nothing is known about the mechanism by which ivabradine modulates plaque formation. Therefore, the present study investigated whether ivabradine regulates chemokine-induced migration of lymphocytes. Methods and results. Stimulation of CD4-positive lymphocytes with SDF-1 leads to a 2.0 ± 0.1 fold increase in cell migration (P < .01; n = 7). Pretreatment of cells with ivabradine reduces this effect to a maximal 1.2 ± 0.1 fold induction at 0.1 µmol/L ivabradine (P < .01 compared to SDF-1-treated cells, n = 7). The effect of ivabradine on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity as determined by PI-3 kinase activity assays. Downstream, ivabradine inhibits activation of the small GTPase Rac and phosphorylation of the Myosin Light Chain (MLC). Moreover, ivabradine treatment reduces f-actin formation as well as ICAM3 translocation to the uropod of the cell, thus interfering with two important steps in T cell migration. Conclusion. Ivabradine inhibits chemokine-induced migration of CD4-positive lymphocytes. Given the crucial importance of chemokine-induced T-cell migration in early atherogenesis, ivabradine may be a promising tool to modulate this effect

Extended Holomorphic Anomaly in Gauge Theory

The partition function of an N=2 gauge theory in the Omega-background satisfies, for generic value of the parameter beta=-eps_1/eps_2, the, in general extended, but otherwise beta-independent, holomorphic anomaly equation of special geometry. Modularity together with the (beta-dependent) gap structure at the various singular loci in the moduli space completely fixes the holomorphic ambiguity, also when the extension is non-trivial. In some cases, the theory at the orbifold radius, corresponding to beta=2, can be identified with an "orientifold" of the theory at beta=1. The various connections give hints for embedding the structure into the topological string.Comment: 25 page

ABCD of Beta Ensembles and Topological Strings

We study beta-ensembles with Bn, Cn, and Dn eigenvalue measure and their relation with refined topological strings. Our results generalize the familiar connections between local topological strings and matrix models leading to An measure, and illustrate that all those classical eigenvalue ensembles, and their topological string counterparts, are related one to another via various deformations and specializations, quantum shifts and discrete quotients. We review the solution of the Gaussian models via Macdonald identities, and interpret them as conifold theories. The interpolation between the various models is plainly apparent in this case. For general polynomial potential, we calculate the partition function in the multi-cut phase in a perturbative fashion, beyond tree-level in the large-N limit. The relation to refined topological string orientifolds on the corresponding local geometry is discussed along the way.Comment: 33 pages, 1 figur