Cpd-1 Null Mice Display a Subtle Neurological Phenotype

CPD1 (also known as ANP32-E) belongs to a family of evolutionarily conserved acidic proteins with leucine rich repeats implicated in a variety of cellular processes regulating gene expression, vesicular trafficking, intracellular signaling and apoptosis. Because of its spatiotemporal expression pattern, CPD1 has been proposed to play an important role in brain morphogenesis and synaptic development.We have generated CPD1 knock-out mice that we have subsequently characterized. These mice are viable and fertile. However, they display a subtle neurological clasping phenotype and mild motor deficits.CPD1 is not essential for normal development; however, it appears to play a role in the regulation of fine motor functions. The minimal phenotype suggests compensatory biological mechanisms

Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells

One of the ultimate goals in transplantation is to develop novel therapeutic methods for induction of donor-specific tolerance to reduce the side effects caused by the generalized immunosuppression associated to the currently used pharmacologic regimens. Interaction or phagocytosis of cells in early apoptosis exerts potent anti-inflammatory and immunosuppressive effects on antigen (Ag)-presenting cells (APC) like dendritic cells (DC) and macrophages. This observation led to the idea that apoptotic cell-based therapies could be employed to deliver donor-Ag in combination with regulatory signals to recipient’s APC as therapeutic approach to restrain the anti-donor response. This review describes the multiple mechanisms by which apoptotic cells down-modulate the immuno-stimulatory and pro-inflammatory functions of DC and macrophages, and the role of the interaction between apoptotic cells and APC in self-tolerance and in apoptotic cell-based therapies to prevent/treat allograft rejection and graft-versus-host disease in murine experimental systems and in humans. It also explores the role that in vivo-generated apoptotic cells could have in the beneficial effects of extracorporeal photopheresis, donor-specific transfusion, and tolerogenic DC-based therapies in transplantation

Small-Signal Modeling of Phase-Shifted Digital PWM in Interleaved and Multilevel Converters

In this article, small-signal modeling of digital pulsewidth modulators (DPWMs) used in multicell voltage source converters (VSCs) is addressed. In addition to sampling and computation, DPWM introduces delay, which impairs VSC's dynamic performance and robustness. In order to take into account the influence of modulation delay, an accurate small-signal representation of DPWM is necessary. Here, modeling of multisampled bipolar and unipolar phase-shifted DPWMs for single-, double-, and multi-update strategies is presented. The simplest multilevel modulation of single-cell full-bridge VSCs, unipolar DPWM, is also covered by the analysis. The derived operating-point-dependent small-signal DPWM models are verified using simulated and experimental frequency response measurements up to four times the Nyquist frequency. Comparisons are also made with the models conventionally considered in the literature. Additionally, an approximate method is presented to model the influence of dead time on DPWM's small-signal dynamics. For the purposes of showcasing the importance of the proposed DPWM models, high-frequency admittance of a VSC employing multisampled multiupdate unipolar DPWM is modeled and verified in simulations and experiments

Accurate High-Frequency Modeling of the Input Admittance of PWM Grid-Connected VSCs

This article addresses high-frequency admittance modeling of current-controlled voltage source converters (VSCs). Recent studies have shown that harmonic instability may also occur at frequencies above the Nyquist frequency. To form an accurate multiple-frequency model in this frequency range, sidebands that originate from modulation and sampling must be examined. In this article, an accurate small-signal model is developed taking into account an adequate digital pulsewidth modulator (DPWM) representation, which allows to predict dependence of the frequency response on the steady-state dc (SS-dc) operating point. It is shown that when center-pulse sampling is implemented, pulsewidth modulation sidebands do not create additional loops leaving only sampling sidebands to be considered. Using the same approach as for SS-dc operation, a model that accurately represents admittance measurements during sinusoidal ac (S-ac) operation is developed. Its basis is a novel DPWM model suitable for S-ac regime, which allows to predict dependence of the VSC’s input admittance on the grid voltage magnitude. Experimental and simulated admittance measurements, performed on a single-phase two-level VSC during various SS-dc and S-ac regimes, match with the proposed models up to twice the sampling frequency