Special K\"ahler-Ricci potentials on compact K\"ahler manifolds

A special K\"ahler-Ricci potential on a K\"ahler manifold is any nonconstant $C^\infty$ function $\tau$ such that $J(\nabla\tau)$ is a Killing vector field and, at every point with $d\tau\ne 0$, all nonzero tangent vectors orthogonal to $\nabla\tau$ and $J(\nabla\tau)$ are eigenvectors of both $\nabla d\tau$ and the Ricci tensor. For instance, this is always the case if $\tau$ is a nonconstant $C^\infty$ function on a K\"ahler manifold $(M,g)$ of complex dimension $m>2$ and the metric $\tilde g=g/\tau^2$, defined wherever $\tau\ne 0$, is Einstein. (When such $\tau$ exists, $(M,g)$ may be called {\it almost-everywhere conformally Einstein}.) We provide a complete classification of compact K\"ahler manifolds with special K\"ahler-Ricci potentials and use it to prove a structure theorem for compact K\"ahler manifolds of any complex dimension $m>2$ which are almost-everywhere conformally Einstein.Comment: 45 pages, AMSTeX, submitted to Journal f\"ur die reine und angewandte Mathemati

Autoimmunity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66083/1/j.1365-4362.1981.tb00393.x.pd

Intranasal administration of acetylcholinesterase inhibitors

This short review outlines the rationale, challenges, and opportunities for intranasal acetylcholinesterases, in particular galantamine. An in vitro screening model facilitated the development of a therapeutically viable formulation. In vivo testing confirmed achievement of therapeutically relevant drug levels that matched or exceeded those for oral dosing, with a dramatic reduction in undesired emetic responses. Intranasal drug delivery is an effective option for the treatment of Alzheimer's disease and other central nervous system disorders

Bounding λ2 for Kähler–Einstein metrics with large symmetry groups

We calculate an upper bound for the second non-zero eigenvalue of the scalar Laplacian, λ2, for toric-Kähler–Einstein metrics in terms of the polytope data. We also give a similar upper bound for Koiso–Sakane type Kähler–Einstein metrics. We provide some detailed examples in complex dimensions 1, 2 and 3

Hamiltonian 2-forms in Kahler geometry, III Extremal metrics and stability

This paper concerns the explicit construction of extremal Kaehler metrics on total spaces of projective bundles, which have been studied in many places. We present a unified approach, motivated by the theory of hamiltonian 2-forms (as introduced and studied in previous papers in the series) but this paper is largely independent of that theory. We obtain a characterization, on a large family of projective bundles, of those `admissible' Kaehler classes (i.e., the ones compatible with the bundle structure in a way we make precise) which contain an extremal Kaehler metric. In many cases, such as on geometrically ruled surfaces, every Kaehler class is admissible. In particular, our results complete the classification of extremal Kaehler metrics on geometrically ruled surfaces, answering several long-standing questions. We also find that our characterization agrees with a notion of K-stability for admissible Kaehler classes. Our examples and nonexistence results therefore provide a fertile testing ground for the rapidly developing theory of stability for projective varieties, and we discuss some of the ramifications. In particular we obtain examples of projective varieties which are destabilized by a non-algebraic degeneration.Comment: 40 pages, sequel to math.DG/0401320 and math.DG/0202280, but largely self-contained; partially replaces and extends math.DG/050151

Live Imaging of Xwnt5A-ROR2 Complexes

Secreted molecules of the Wnt family regulate key decisions in embryogenesis and adult tissue homeostasis by activating a complex network of Wnt signaling pathways. Although the different branches of Wnt signaling have been studied for more than 25 years, fluorophore tagged constructs for live cell imaging of Wnt molecules activating the Wnt/β-catenin pathway have become available only recently. We have generated a fluorophore tagged Wnt construct of the Xenopus Wnt5a protein (Xwnt5A) with the enhanced green fluorescent protein (EGFP), Xwnt5A-EGFP. This construct activates non-canonical Wnt pathways in an endocytosis dependent manner and is capable of compensating for the loss of endogenous Xwnt5A in Xenopus embryos. Strikingly, non-canonical Wnt pathway activation was restricted to short-range signaling while an inhibitory effect was observed in transwell cell cultures taken as long-range signaling model sytem. We used our Xwnt5A-EGFP construct to analyze in vivo binding of Wnt5A to its co-receptor ROR2 on the microscopic and on the molecular level. On the microscopic level, Xwnt5A-EGFP clusters in the membrane and recruits ROR2-mCherry to these clusters. Applying dual-colour dual-focus line-scanning fluorescence correlation spectroscopy on dorsal marginal zone explants, we identified membrane tethered Xwnt5A-EGFP molecules binding to ROR2-mCherry molecules. Our data favour a model, in which membrane-tethered Wnt-5A recruits ROR2 to form large ligand/receptor clusters and signals in an endocytosis-dependent manner

Calcium phosphate-hybridized tendon graft to enhance tendon-bone healing two years after ACL reconstruction in goats

Abstract Background We developed a novel technique to improve tendon-bone attachment by hybridizing calcium phosphate (CaP) with a tendon graft using an alternate soaking process. However, the long-term result with regard to the interface between the tendon graft and the bone is unclear. Methods We analyzed bone tunnel enlargement by computed tomography and histological observation of the interface and the tendon graft with and without the CaP hybridization 2 years after anterior cruciate ligament (ACL) reconstruction in goats using EndoButton and the postscrew technique (CaP, n = 4; control, n = 4). Results The tibial bone tunnel enlargement rates in the CaP group were lower than those in the control group (p p p Conclusions The CaP-hybridized tendon graft enhanced the tendon-bone healing 2 years after ACL reconstruction in goats. The use of CaP-hybridized tendon grafts can reduce the bone tunnel enlargement and gap area associated with the direct insertion-like formation in the interface near the joint.</p

Remission of Behcet's disease with anti-tumor necrosis factor monoclonal antibody therapy: a case report

BACKGROUND: Behcet's disease (BD) is a chronic relapsing multisystem inflammatory disorder with mucocutaneous, ocular, articular, vascular, gastrointestinal and central nervous system manifestations. Tumor necrosis factor (TNF)-alpha is believed to play a pivotal role in BD. Therapeutic blockade of the activity of TNF has been successfully given in a short course of therapy with favorable effects in patients with BD refractory to conventional immunosuppressive drugs. We aimed to find out whether a 12-month treatment with infliximab, a chimeric monoclonal antibody to TNF-alpha, had any beneficial effect in reducing relapses of a patient with long-standing BD refractory to conventional immunosuppressive drugs. CASE PRESENTATION: A 54 year-old-woman with a 35-year history of BD with orogenital ulcerations, arthritis in the right knee and retinal lesions compatible with vasculitis received infliximab, 5 mg/kg by a two-hour intravenous infusion. Symptoms improved within 24 hours and eight days later the genital and oral ulcers healed as well as the arthritis in the right knee subsided. The retinal infiltrates completely resolved within 10 days. The infusions were repeated at weeks 2, 6, 14, 22 and then every 8 weeks. The patient was able to return to her domestic daily life. No exacerbation of the mucocutaneous ocular or arthritic symptoms occurred during the treatment period. CONCLUSIONS: Previous studies have suggested that infliximab given in a short course of treatment is effective in inducing remission of severe mucocutaneous, gastrointestinal and ocular manifestations of BD. Our patient received a 12-month infliximab treatment showing a favorable effect on remission of BD manifestations. The long-term infliximab treatment appears as a new therapeutic option for patients with active BD who failed to respond to conventional immunosuppressive agents

Rubicon and PLEKHM1 Negatively Regulate the Endocytic/Autophagic Pathway via a Novel Rab7-binding Domain

Rubicon, a subunit of the Beclin 1-PI3-kinase complex and its homologue, PLEKHM1, negatively regulate endocytic pathway through the interaction with Rab7. Synchronous association with the Beclin 1–PI3-kinase complex and Rab7 is necessary for the function of Rubicon, but not PLEKHM1

Differential regulation of diacylglycerol kinase isoform in human failing hearts

Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined. In this study, we detected mRNA expressions of DGK isoforms γ, η, ε, and ζ in failing human heart samples obtained from patients undergoing cardiovascular surgery with cardiopulmonary bypass. Furthermore, we investigated modulation of DGK isoform expression in these hearts. We found that expressions of DGKη and DGKζ were increased and decreased, respectively, whereas those of DGKγ and DGKε remained unchanged. This is the first report that describes the differential regulation of DGK isoforms in normal and failing human hearts