Blocking the PCNA/NKp44 Checkpoint to Stimulate NK Cell Responses to Multiple Myeloma

Simple SummaryMembrane-associated PCNA is expressed on the surface of human MM cell lines and primary MM cells. Mab 14-25-9 interacts with membrane-associated PCNA and blocks its binding to NK-expressed NKp44, thus activating NK function. We showed that mAb 14-25-9 can serve as an immune checkpoint blocker, enhancing the function of NK cells on target human MM cell lines and primary cells.AbstractMultiple Myeloma (MM) is a devastating malignancy that evades immune destruction using multiple mechanisms. The NKp44 receptor interacts with PCNA (Proliferating Cell Nuclear Antigen) and may inhibit NK cells’ functions. Here we studied in vitro the expression and function of PCNA on MM cells. First, we show that PCNA is present on the cell membrane of five out of six MM cell lines, using novel anti-PCNA mAb developed to recognize membrane-associated PCNA. Next, we stained primary bone marrow (BM) mononuclear cells from MM patients and showed significant staining of membrane-associated PCNA in the fraction of CD38⁺CD138⁺ BM cells that contain the MM cells. Importantly, blocking of the membrane PCNA on MM cells enhanced the activity of NK cells, including IFN-γ-secretion and degranulation. Our results highlight the possible blocking of the NKp44-PCNA immune checkpoint by the mAb 14-25-9 antibody to enhance NK cell responses against MM, providing a novel treatment option.     

Thermal stability of CeO<Subscript>2</Subscript>/ZrO<Subscript>2</Subscript> multilayer thin films prepared by pulsed laser deposition

Multilayers of CeO₂/ZrO₂ thin films were deposited on Si (100) substrates using pulsed laser deposition at an optimized oxygen partial pressure of 3×10⁻² mbar and at room temperature. The CeO₂ layer thickness was 10 nm, while the ZrO₂ layer thickness was varied as 10, 20 and 30 nm. CeO₂ and ZrO₂ layers were deposited alternately to obtain 25 bilayers. High temperature x-ray diffraction (HTXRD) results showed that the multilayer films had cubic ceria and tetragonal ZrO₂. Thermal expansion coefficients were calculated for CeO₂ and t-ZrO₂ and found to increase with the decrease of ZrO₂ layer thickness. The cross sectional transmission electron microscopy (XTEM) of CeO₂/ZrO₂ multilayer also indicated that ceria was found to be in cubic phase while zirconia contained predominantly tetragonal phase along with cubic phase in thermally annealed specimen.     

Stability boundary analysis of the dynamic voltage restorer in weak systems with dynamic loads

In this contribution, a stability analysis for a dynamic voltage restorer (DVR) connected to a weak ac system containing a dynamic load is presented using continuation techniques and bifurcation theory. The system dynamics are explored through the continuation of periodic solutions of the associated dynamic equations. The switching process in the DVR converter is taken into account to trace the stability regions through a suitable mathematical representation of the DVR converter. The stability regions in the Thevenin equivalent plane are computed. In addition, the stability regions in the control gains space, as well as the contour lines for different Floquet multipliers, are computed. Besides, the DVR converter model employed in this contribution avoids the necessity of developing very complicated iterative map approaches as in the conventional bifurcation analysis of converters. The continuation method and the DVR model can take into account dynamics and nonlinear loads and any network topology since the analysis is carried out directly from the state space equations. The bifurcation approach is shown to be both computationally efficient and robust, since it eliminates the need for numerically critical and long‐lasting transient simulations. Copyright © 2011 John Wiley & Sons, Ltd.     

Midwavelength Infrared Avalanche Photodiode Using InAs–GaSb Strain Layer Superlattice

InAs-GaSb strain layer superlattice p⁺-n^--n avalanche photodiodes (APDs) are fabricated using a newly introduced electron-beam aided zinc sulfide deposition. Temperature-dependent measurements were performed on 300 times 300 mum² mesa etched APDs. The effect of passivation was also studied on the diode characteristics and APD performances. Temperature-dependent gain strongly correlates with avalanche mechanism.     

Channel Assignment Strategies for Multiradio Wireless Mesh Networks: Issues and Solutions

Next-generation wireless mobile communications will be driven by converged networks that integrate disparate technologies and services. The wireless mesh network is envisaged to be one of the key components in the converged networks of the future, providing flexible high- bandwidth wireless backhaul over large geographical areas. While single radio mesh nodes operating on a single channel suffer from capacity constraints, equipping mesh routers with multiple radios using multiple nonoverlap- ping channels can significantly alleviate the capacity problem and increase the aggregate bandwidth available to the network. However, the assignment of channels to the radio interfaces poses significant challenges. The goal of channel assignment algorithms in multiradio mesh networks is to minimize interference while improving the aggregate network capacity and maintaining the connectivity of the network. In this article we examine the unique constraints of channel assignment in wireless mesh networks and identify the key factors governing assignment schemes, with particular reference to interference, traffic patterns, and multipath connectivity. After presenting a taxonomy of existing channel assignment algorithms for WMNs, we describe a new channel assignment scheme called MesTiC, which incorporates the mesh traffic pattern together with connectivity issues in order to minimize interference in multi- radio mesh networks.     

Control of Three-Phase, Four-Wire PWM Rectifier

This paper presents the analysis, design, and control of a four-wire rectifier system using split-capacitor topology. The proposed controller does not require any complex transformation or input voltage sensing. A detailed analysis of the distortions in the line and the neutral currents is presented. It is shown that the single-carrier-based, conventional sine-triangle PWM (CSPWM) scheme results in a peak-to-peak neutral current ripple, which is greater than the peak-to-peak ripple of any of the line currents. Also, for the same operating condition, the distortions in the line and the neutral currents increase considerably, when a three-limb boost inductor is used instead of three single-phase inductors. A three-carrier-based SPWM scheme is proposed in this paper. Compared to CSPWM, the proposed scheme significantly reduces the neutral current ripple when three single-phase inductors are used, and reduces both line and neutral current ripples when a three-limb inductor is used. The control scheme is verified through Matlab simulation. It is implemented on an field-programmable gate-array (FPGA)-based digital controller and tested on a prototype. Simulation and experimental results are presented.     

Sleepy keeper style based Low Power VLSI Architecture of a Viterbi Decoder applying for the Wireless LAN Operation sustainability

Analog Integrated Circuits and Signal Processing - Remarkable progress in the field of wireless communication has created a research interest for Viterbi decoder with long duration of battery life,...     

Optimal actuation of micro-cantilevers by laser radiation pressure

Singly-clamped cantilevers actuated by optical radiation pressure exerted by a laser are analysed. An expression for optimum point of actuation giving the maximum amount of deflection is obtained.