Humoral autoimmunity after solid organ transplantation: Germinal ideas may not be natural

Non-HLA antibody responses following solid organ transplantation have become increasingly emphasised, with several large clinical series suggesting that such responses contribute to late graft failure. Many of the responses described recognise both recipient and donor moieties of the target antigen and thus represent auto-, rather than allo-immunity. Within this rapidly evolving field, many questions remain unanswered: what triggers the response; how innate and adaptive humoral autoimmunity integrate; and most pressingly, how autoimmunity contributes to graft damage and its relationship to other effector mechanisms of graft rejection. This review summarises recent clinical and experimental studies of humoral autoimmunity in transplant rejection, and considers some of the answers to these questions

Higher-order splitting algorithms for solving the nonlinear Schr\"odinger equation and their instabilities

Since the kinetic and the potential energy term of the real time nonlinear Schr\"odinger equation can each be solved exactly, the entire equation can be solved to any order via splitting algorithms. We verified the fourth-order convergence of some well known algorithms by solving the Gross-Pitaevskii equation numerically. All such splitting algorithms suffer from a latent numerical instability even when the total energy is very well conserved. A detail error analysis reveals that the noise, or elementary excitations of the nonlinear Schr\"odinger, obeys the Bogoliubov spectrum and the instability is due to the exponential growth of high wave number noises caused by the splitting process. For a continuum wave function, this instability is unavoidable no matter how small the time step. For a discrete wave function, the instability can be avoided only for \dt k_{max}^2{<\atop\sim}2 \pi, where $k_{max}=\pi/\Delta x$.Comment: 10 pages, 8 figures, submitted to Phys. Rev.

Forward Symplectic Integrators and the Long Time Phase Error in Periodic Motions

We show that when time-reversible symplectic algorithms are used to solve periodic motions, the energy error after one period is generally two orders higher than that of the algorithm. By use of correctable algorithms, we show that the phase error can also be eliminated two orders higher than that of the integrator. The use of fourth order forward time step integrators can result in sixth order accuracy for the phase error and eighth accuracy in the periodic energy. We study the 1-D harmonic oscillator and the 2-D Kepler problem in great details, and compare the effectiveness of some recent fourth order algorithms.Comment: Submitted to Phys. Rev. E, 29 Page

Cohomology of bundles on homological Hopf manifold

We discuss the properties of complex manifolds having rational homology of $S^1 \times S^{2n-1}$ including those constructed by Hopf, Kodaira and Brieskorn-van de Ven. We extend certain previously known vanishing properties of cohomology of bundles on such manifolds.As an application we consider degeneration of Hodge-deRham spectral sequence in this non Kahler setting.Comment: To appear in Proceedings of 2007 conference on Several complex variables and Complex Geometry. Xiamen. Chin

The K\"ahler-Ricci flow on surfaces of positive Kodaira dimension

The existence of K\"ahler-Einstein metrics on a compact K\"ahler manifold has been the subject of intensive study over the last few decades, following Yau's solution to Calabi's conjecture. The Ricci flow, introduced by Richard Hamilton has become one of the most powerful tools in geometric analysis. We study the K\"ahler-Ricci flow on minimal surfaces of Kodaira dimension one and show that the flow collapses and converges to a unique canonical metric on its canonical model. Such a canonical is a generalized K\"ahler-Einstein metric. Combining the results of Cao, Tsuji, Tian and Zhang, we give a metric classification for K\"aher surfaces with a numerical effective canonical line bundle by the K\"ahler-Ricci flow. In general, we propose a program of finding canonical metrics on canonical models of projective varieties of positive Kodaira dimension

Semliki Forest virus strongly reduces mosquito host defence signaling

The Alphavirus genus within the Togaviridae family contains several important mosquito-borne arboviruses. Other than the antiviral activity of RNAi, relatively little is known about alphavirus interactions with insect cell defences. Here we show that Semliki Forest virus (SFV) infection of Aedes albopictus-derived U4.4 mosquito cells reduces cellular gene expression. Activation prior to SFV infection of pathways involving STAT/IMD, but not Toll signaling reduced subsequent virus gene expression and RNA levels. These pathways are therefore not only able to mediate protective responses against bacteria but also arboviruses. However, SFV infection of mosquito cells did not result in activation of any of these pathways and suppressed their subsequent activation by other stimuli

Mosaic expression of Atrx in the mouse central nervous system causes memory deficits

The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX protein expression in the central nervous system attributable to the location of the gene on the X chromosome. Although the hemizygous male mice die soon after birth, heterozygous females survive to adulthood. Body growth is stunted in these animals, and they have low circulating concentrations of insulin growth factor 1. In addition, they are impaired in spatial, contextual fear and novel object recognition memory. Our findings demonstrate that mosaic loss of ATRX expression in the central nervous system leads to endocrine defects and decreased body size and has a negative impact on learning and memory

Positivity of relative canonical bundles and applications

Given a family $f:\mathcal X \to S$ of canonically polarized manifolds, the unique K\"ahler-Einstein metrics on the fibers induce a hermitian metric on the relative canonical bundle $\mathcal K_{\mathcal X/S}$. We use a global elliptic equation to show that this metric is strictly positive on $\mathcal X$, unless the family is infinitesimally trivial. For degenerating families we show that the curvature form on the total space can be extended as a (semi-)positive closed current. By fiber integration it follows that the generalized Weil-Petersson form on the base possesses an extension as a positive current. We prove an extension theorem for hermitian line bundles, whose curvature forms have this property. This theorem can be applied to a determinant line bundle associated to the relative canonical bundle on the total space. As an application the quasi-projectivity of the moduli space $\mathcal M_{\text{can}}$ of canonically polarized varieties follows. The direct images $R^{n-p}f_*\Omega^p_{\mathcal X/S}(\mathcal K_{\mathcal X/S}^{\otimes m})$, $m > 0$, carry natural hermitian metrics. We prove an explicit formula for the curvature tensor of these direct images. We apply it to the morphisms $S^p \mathcal T_S \to R^pf_*\Lambda^p\mathcal T_{\mathcal X/S}$ that are induced by the Kodaira-Spencer map and obtain a differential geometric proof for hyperbolicity properties of $\mathcal M_{\text{can}}$.Comment: Supercedes arXiv:0808.3259v4 and arXiv:1002.4858v2. To appear in Invent. mat

A new concurrent chemotherapy with vinorelbine and mitomycin C in combination with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck

Objective: The purpose of this pilot study was to evaluate the feasibility and toxicity of concurrent chemotherapy with vinorelbine and mitomycin C in combination with accelerated radiotherapy (RT) in patients with locally advanced cancer of the head and neck. Patients and Methods: Between January 2003 and March 2004, 15 patients with T4/N2-3 squamous cell carcinoma (12/15) and with N3 cervical lymph node metastases of carcinoma of unknown primary (3/15) were treated with chemotherapy and simultaneous accelerated RT. Results: 11 patients completed therapy without interruption or dose reduction. Grade 3 - 4 acute mucosal toxicity was observed in 9/15 patients, grade 4 hematologic toxicity in 6/15 patients. At a median follow-up of 7.5 months, 2 patients have died of intercurrent disease, 2 patients have experienced local relapse; 5 patients are alive with no evidence of disease at the primary tumor site. Discussion: The described regimen is highly effective, but led to remarkable side effects