Oncogenic signaling: new insights and controversies from chronic myeloid leukemia

Chronic myeloid leukemia (CML), which is caused by the BCR–ABL fusion tyrosine kinase, is one of the most intensively studied human cancers. ABL kinase inhibitors have been spectacularly successful in treating CML, but disease persistence and acquired drug resistance can prevent eradication and cure of the leukemia. The development of better therapies will depend on a full understanding of signaling pathways in CML, facilitated by model studies using mutant mice

Ring resonator-based Tunable Optical Delay Line in LPCVD Waveguide Technology

Optical circuits providing a time delay to signals modulated on optical carriers are considered important for optical communication systems and phased array antennas. A continuously tunable optical delay line is demonstrated in low-cost CMOS compatible LPCVD planar waveguide technology. The device consists of three cascaded ringresonator all-pass filters with fixed circumference of 2 cm (delay of 0.12 ns and FSR of 8.4 GHz). The measured group delay ranges from 0 ns up to 1.2 ns with a bandwidth of 500 MHz and delay ripple smaller than 1 ps, which is in accordance with the calculations

Ring resonator-based single-chip 1x8 optical beam forming network in LPCVD waveguide technology

Optical ring resonators (ORRs) are good candidates to provide continuously tunable delay in beam forming networks (BFNs) for phased array antenna systems. \ud Delay and splitting/combining elements can be integrated on a single optical chip to form an OBFN. A state-of-the-art 1×8 OBFN chip has been fabricated in LPCVD waveguide technology.\ud It is designed with 1 input and 8 outputs, between which a binary-tree topology is used. A different number of ORRs (up to 7) are cascaded for each output.\ud In this paper, the principle of operation is explained and demonstrated by presenting measurements on the 1×8 OBFN chip

JAKing up hematopoietic proliferation

Mutations that deregulate proliferation and survival pathways have emerged as a common molecular theme in the pathogenesis of myeloproliferative disorders (MPDs). Three studies now report an amino acid substitution in the JAK2 kinase in most patients with polycythemia vera as well as in some cases of essential thrombocythemia and chronic idiopathic myelofibrosis. Functional analysis demonstrates that this mutation confers erythropoietin-independent growth in vitro, deregulates signaling pathways downstream of JAK2, and causes polycythemia in mice. These results open new avenues for diagnosing and classifying patients with these disorders, and identify a new molecular target for drug discovery

Optical beam forming for phased-array antennas

The activities of the Telecommunication Engineering (TE) group span the communications spectrum from copper cables, optical fibres, microwaves, radio and electromagnetic compatibility. Our research concentrates on optical signal processing and networks, mobile communications, microwave techniques and radiation from ICs and PCBs [1]. A considerable (and particularly interesting) part of it is related to optical beam forming for phased array antennas, using optical ring resonators.\ud In this article the theoretical basics and practical challenges of this interesting research topic will be summarized.\u

Phased array antenna steering using a ring resonator-based optical beam forming network

A novel beam steering mechanism for a phased array antenna receiver system is introduced. The core of the system is a ring resonator-based integrated optical beam forming network chip. Its principles are explained and demonstrated by presenting some measurement results. The system architecture around the chip is based on a combination of frequency down conversion, filter-based optical single sideband modulation and balanced coherent detection. It is proven that such an architecture has significant advantages with respect to a straightforward architecture using double sideband modulation and direct detection, namely relaxed bandwidth requirements on the optical modulators and detectors, reduced complexity and optical losses of the beam forming chip, and enhanced dynamic range

Broadband phased array antenna steering by means of coherent signal combining in an integrated ring resonator-based optical beamformer

A squint-free, continuously tunable optical beamformer for broadband phased array receive antennas is proposed. The complete system is demonstrated, including E/O and O/E conversions, and optical signal processing. The latter involves delay synchronization and coherent optical combining, which is performed in an integrated ring resonator-based optical beam forming network, realized in low-loss, CMOScompatible TriPleX technology. Successful combination of four beamformer input channels has been demonstrated by means of RF-to-RF measurements

Novel ring resonator-based optical beamformer system and experimental results

A novel squint-free, continuously tunable beamformer mechanism for a phased array antenna system is proposed. It consists of filter-based optical single-sideband suppressed-carrier modulation, a fully integrated optical beam forming network using cascades of optical ring resonators as tunable delay elements, and balanced coherent optical detection. The proposed system brings advantages in optical bandwidth requirement, system complexity, and dynamic range, without introducing the problem of beam squint or limited tuning resolution. Some experimental results are presented in order to demonstrate the feasibility of the proposed concept

Optical phase synchronization in coherent optical beamformers for phased array receive antennas

An optical phase synchronization system using a power feedback loop technique is experimentally demonstrated. The system allows coherent combining of signals modulated on the same optical carrier in a hybrid optical beam forming system setup

The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity

The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have been shown by indirect immunofluorescence to associate with F-actin stress fibers in fibroblasts. Analysis of deletion mutants of c-Abl stably expressed in fibroblasts maps the domain responsible for this interaction to the extreme COOH-terminus of Abl. This domain mediates the association of a heterologous protein with F-actin filaments after microinjection into NIH 3T3 cells, and directly binds to F-actin in a cosedimentation assay. Microinjection and cosedimentation assays localize the actin-binding domain to a 58 amino acid region, including a charged motif at the extreme COOH-terminus that is important for efficient binding. F-actin binding by Abl is calcium independent, and Abl competes with gelsolin for binding to F- actin. In addition to the F-actin binding domain, the COOH-terminus of Abl contains a proline-rich region that mediates binding and sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to bundle F-actin filaments in vitro. The COOH terminus of Abl thus confers several novel localizing functions upon the protein, including actin binding, nuclear localization, and DNA binding. Abl may modify and receive signals from the F-actin cytoskeleton in vivo, and is an ideal candidate to mediate signal transduction from the cell surface and cytoskeleton to the nucleus