The discoidin domain receptor (DDR1) is characterized by a discoidin I motif in the extracellular domain, an unusually long cytoplasmic juxtamembrane (JM) region, and a kinase domain that is 45% ...identical to that of the NGF receptor, TrkA. DDR1 also has a major splice form, which has a 37 amino acid insert in the JM region with a consensus Shc PTB site that is lacking in the shorter receptor. One class of ligands for the DDR receptors has recently been identified as being derived from the collagen family, but neither native PC12 cells, which express modest amounts of DDR1, nor trans‐fected PC12 cells, which express much larger amounts of DDR1, respond to this ligand. A chimeric receptor, containing the extracellular domain of hPDGFRβ fused to the transmembrane and intracel‐lular regions of DDR1, also fails to mediate neuro‐nal‐like differentiation in stably transfected PC12 cells and is only weakly autophosphorylated. However, chimeric receptors, which are composed of combinations of intracellular regions from DDR1 and TrkA (with the extracellular domain of hPDGFRβ), in some cases provided ligand (PDGF)‐inducible receptor responses. Those with the TrkA kinase domain and the DDR1 JM regions were able to produce differentiation to varying degrees, whereas the opposite combination did not. Analysis of the signaling responses of the two chimeras with DDR1 JM sequences (with and without the insert) indicated that the shorter sequence bound and activated FRS2 whereas the insert‐containing form activated Shc instead. Both activated PLC γ through the carboxyl‐terminal tyrosine of the TrkA domain (Y785 in TrkA residue numbering). Mutation of this site (Y3 F) eliminated PLC7 activation (indicating there are no other cryptic binding sites for PLC γ in the DDR1 sequences) and markedly reduced the differ‐entiative activity of the receptor. This is in contrast to TrkA (or PDGFRβ/TrkA chimeras), where ablation of this pathway has no notable effect on PC12 cell morphogenic responses. Thus, the activation of FRS2 and Shc (leading to MAPK activation) is weaker in the DDR1/TrkA chimeras than in TrkA alone, and the PLC7 contribution becomes essential for full response. Nonetheless, both DDR1 JM regions contain potentially usable signaling sites, albeit they apparently are not activated directly in DDR1 (or DDR1 chimeras) in a ligand‐dependent fashion. These findings suggest that the DDR1 receptors do have signaling capacity but may require additional components or altered conditions to fully activate their kinase domains and/or sustain the activation of the JM sites.—Foehr, E. D., Tatavos, A., Tanabe, E., Raffioni, S., Goetz, S., DiMarco, E., De Luca, M., Bradshaw, R. A. Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of jux‐tamembrane domains in PDGFR/DDR/TrkA chi‐meric receptors. FASEB J. 14, 973–981 (2000)
The US-LHC accelerator research program (LARP) built and tested the first 3.7-m long Nb{sub 3}Sn quadrupole model of LQ series with a 90 mm bore diameter and a target field gradient of 200 T/m. The ...LQ series, developed in collaboration among FNAL, LBNL and BNL, is a scale up of the previously tested 1-m long technology quadrupoles of TQ series based on similar coils and two different mechanical structures (shell-based TQS and collar-based TQC), with a primary goal of demonstrating the Nb{sub 3}Sn accelerator magnet technology for the luminosity upgrade of LHC interaction regions. In this paper, we present the field quality measurements in the first 3.7-m long LQS01 model based on the modified TQS mechanical structure. The results are compared to the expectations from the magnet geometry and magnetic properties of coils and iron yoke. Moreover, we present a comparison between this magnet and the short models previously measured.
Expression of the human interferon gamma receptor (IFN-gamma R) in mouse cells is not sufficient to confer biological responsiveness to human IFN-gamma and vice versa. An additional species-specific ...component is required for signal transduction. We identified this cofactor by expression cloning in simian COS cells stably transfected with the nonfunctional murine IFN-gamma R and a IFN-gamma-inducible reporter construct encoding the human Tac antigen (interleukin-2 receptor alpha chain, CD25). A cDNA clone was obtained that, upon stable transfection, rendered human HEp-2 cells expressing the murine IFN-gamma R fully responsive to murine IFN-gamma. This cDNA encodes a novel 332 amino acid type I transmembrane protein that belongs to the IFN receptor family and that we designate IFN-gamma R beta chain.
JACoW IPAC2024 (2024) THYN1 The Large Hadron Collider will soon undergo an upgrade to increase its
luminosity by a factor of ~10 1. A crucial part of this upgrade will be
replacement of the NbTi ...focusing magnets with Nb3Sn magnets that achieve a ~50%
increase in the field strength. This will be the first ever large-scale
implementation of Nb3Sn magnets in a particle accelerator. The High-Luminosity
LHC Upgrade, HL-LHC is a CERN project with a world-wide collaboration. It is
under construction and utilizes Nb3Sn Magnets (named MQXF) as key ingredients
to increase tenfold the integrated luminosity delivered to the CMS and ATLAS
experiments in the next decade.
The HL-LHC AUP is the US effort to contribute approximately 50% of the
low-beta focusing magnets and crab cavities for the HL-LHC.
This paper will present the program to fabricate the Nb3Sn superconducting
magnets. We are reporting the status of the HL-LHC AUP project present the
results from horizontal tests of the first fully assembled cryo-assembly.
Mechanisms responsible for atrioventricular (AV) block during acute inferior myocardial infarction are only partially understood. Increased parasympathetic tone is the factor usually postulated; ...however, persistence of AV block after atropine administration is frequently observed. Adenosine, an endogenous ischemic metabolite, has well established depressant effects on AV node con- auction. In this report, an episode of atropine-resistant AV block was reversed by aminophylline, a competitive adenosine antagonist, in a patient with an acute inferior myocardial infarction. This observation suggests a role for adenosine in the mediation of ischemia-induced AV node block.
The response of metals and their microstructures under extreme dynamic
conditions can be markedly different from that under quasistatic conditions.
Traditionally, high strain rates and shock stresses ...are measured using
cumbersome and expensive methods such as the Kolsky bar or large spall
experiments. These methods are low throughput and do not facilitate
high-fidelity microstructure-property linkages. In this work, we combine two
powerful small-scale testing methods, custom nanoindentation, and laser-driven
micro-flyer shock, to measure the dynamic and spall strength of metals. The
nanoindentation system is configured to test samples from quasistatic to
dynamic strain rate regimes (10$^{-3}$ s$^{-1}$ to 10$^{+4}$ s$^{-1}$). The
laser-driven micro-flyer shock system can test samples through impact loading
between 10$^{+5}$ s$^{-1}$ to 10$^{+7}$ s$^{-1}$ strain rates, triggering spall
failure. The model material used for testing is Magnesium alloys, which are
lightweight, possess high-specific strengths and have historically been
challenging to design and strengthen due to their mechanical anisotropy. Here,
we modulate their microstructure by adding or removing precipitates to
demonstrate interesting upticks in strain rate sensitivity and evolution of
dynamic strength. At high shock loading rates, we unravel an interesting
paradigm where the spall strength of these materials converges, but the failure
mechanisms are markedly different. Peak aging, considered to be a standard
method to strengthen metallic alloys, causes catastrophic failure, faring much
worse than solutionized alloys. Our high throughput testing framework not only
quantifies strength but also teases out unexplored failure mechanisms at
extreme strain rates, providing valuable insights for the rapid design and
improvement of metals for extreme environments.
HINS Linac Front End Focusing System R D Apollinari, G; Carcagno, R H; Dimarco, J ...
IEEE transactions on applied superconductivity,
06/2009, Letnik:
19, Številka:
3
Journal Article
Recenzirano
This report summarizes current status of an R&D program to develop a focusing system for the front end of a superconducting RF linac. Superconducting solenoids will be used as focusing lenses in the ...low energy accelerating sections of the abstract truncated by publisher.
Accelerator magnet test facilities frequently need to measure different magnets on differently equipped test stands and with different instrumentation. Designing a modular and highly reusable system ...that combines flexibility built-in at the architectural level as well as on the component level addresses this need. Specification of the backbone of the system, with the interfaces and dataflow for software components and core hardware modules, serves as a basis for building such a system. The design process and implementation of an extensible magnetic measurement data acquisition and control system are described, including techniques for maximizing the reuse of software. The discussion is supported by showing the application of this methodology to constructing two dissimilar systems for rotating coil measurements, both based on the same architecture and sharing core hardware modules and many software components. The first system is for production testing 10 m long cryo-assemblies containing two MQXFA quadrupole magnets for the high-luminosity upgrade of the Large Hadron Collider and the second for testing IQC conventional quadrupole magnets in support of the accelerator system at Fermilab.
PDF
