Performance of the LHC Arc Superconducting Quadrupoles Towards the End of their Series Fabrication

The fabrication of the 408 main arc quadrupole magnets and their cold masses will come to an end in summer 2006. A rich collection of measurement and test data has been accumulated and their analysis is presented in this paper. These data cover the fabrication and the efficiency in the use of the main components, the geometrical measurements and the achieved dimensional precision, the warm magnetic measurements in the factory and the performance at cold conditions, especially the training behaviour. The scrap rate of the Nb-Ti/Cu conductor as well as that of other components turned out to be acceptably low and the quench performance measured was in general very good. Most quadrupoles measured so far exceeded the operating field gradient with one or no quench. The multipole content at cold was measured for a limited number of quadrupoles in order to verify the warm-to-cold correlation. From the point of view of field quality, all quadrupoles could be accepted for the machine. The measures taken to overcome the problem of a too high permeability of a batch of collars are discussed

Ras oncogene-independent activation of RALB signaling is a targetable mechanism of escape from NRAS(V12) oncogene addiction in acute myeloid leukemia.

Somatic mutations that lead to constitutive activation of NRAS and KRAS proto-oncogenes are among the most common in human cancer and frequently occur in acute myeloid leukemia (AML). An inducible NRAS(V12)-driven AML mouse model has established a critical role for continued NRAS(V12) expression in leukemia maintenance. In this model genetic suppression of NRAS(V12) expression results in rapid leukemia remission, but some mice undergo spontaneous relapse with NRAS(V12)-independent (NRI) AMLs providing an opportunity to identify mechanisms that bypass the requirement for Ras oncogene activity and drive leukemia relapse. We found that relapsed NRI AMLs are devoid of NRAS(V12) expression and signaling through the major oncogenic Ras effector pathways, phosphatidylinositol-3-kinase and mitogen-activated protein kinase, but express higher levels of an alternate Ras effector, Ralb, and exhibit NRI phosphorylation of the RALB effector TBK1, implicating RALB signaling in AML relapse. Functional studies confirmed that inhibiting CDK5-mediated RALB activation with a clinically relevant experimental drug, dinaciclib, led to potent RALB-dependent antileukemic effects in human AML cell lines, induced apoptosis in patient-derived AML samples in vitro and led to a 2-log reduction in the leukemic burden in patient-derived xenograft mice. Furthermore, dinaciclib potently suppressed the clonogenic potential of relapsed NRI AMLs in vitro and prevented the development of relapsed AML in vivo. Our findings demonstrate that Ras oncogene-independent activation of RALB signaling is a therapeutically targetable mechanism of escape from NRAS oncogene addiction in AML

A 12 GHZ RF Power source for the CLIC study

The CLIC RF frequency has been changed in 2008 from the initial 30 GHz to the European X-band 11.9942 GHz permitting beam independent power production using klystrons for CLIC accelerating structure testing. A design and fabrication contract for five klystrons at that frequency has been signed by different parties with SLAC. France (IRFU, CEA Saclay) is contributing a solid state modulator purchased in industry and specific 12 GHz RF network components to the CLIC study. RF pulses over 120 MW peak at 230 ns length will be obtained by using a novel SLED-I type pulse compression scheme designed and fabricated by IAP, Nizhny Novgorod, Russia. The X-band power test stand is being installed in the CLIC Test Facility CTF3 for independent structure and component testing in a bunker, but allowing, in a later stage, for powering RF components in the CTF3 beam lines. The design of the facility, results from commissioning of the RF power source and the expected performance of the Test Facility are reported