Anti-CSF2 monoclonal antibody, clone CWE3-32D22 [PE]

Extending the range of Accelerator Mass Spectrometry (AMS) to the fission products Sr-90 and Cs-135,Cs-137 would offer numerous advantages for non-proliferation surveillance activities. A new method for suppressing the interfering isobars Zr-90 (and Y-90) and Ba-135,Ba-137 using low kinetic energy (<20 eV) gas-phase reactions in an AMS injection line can help achieving this goal in a cost effective way [1]. The reactions occur in a radiofrequency quadrupole (RFQ) cell filled with a low pressure gas, part of a device known as the Isobar Separator for Anions (ISA). Combined with fluoridematrix assisted ionization, this method greatly improves the analytical capabilities of AMS for Sr-90 and will enable the direct analysis of Cs-135,Cs-137 below sub-parts per trillion levels. The ISA alone provides interference suppression factors of 4x10(-6) for ZrF3-/SrF3- and 2x10(-5) for BaF2-/CsF2-. The general performance improvement provided by the ISA, however, critically depends on the capacity of this device to transmit the wanted anions with a high efficiency and with a stable response to the natural variations of AMS targets. Based on recent SIMION-8.1 studies and on results of a parallel study on the attenuation of other anions, we have developed a pre-commercial design for the ISA. In this design, RFQ rods and split-flow turbo molecular pumps are configured to achieve full control of reaction time, ion energy and fragmentation pathways (chemical and kinetic reactions), and to improve beam transmission through the cell. The mechanical layout will be presented in 3D models using SolidWorks; SIMION-8.1 simulations were used to illustrate the importance of optical matching of the RFQ and the front-end DC retardation section of the ISA.

The Ras family of GTPases plays an important role in signaling nodes downstream to T cell receptor and CD28 activation, potentially lowering the threshold for T-cell receptor activation by autoantigens. Somatic mutation in NRAS or KRAS may cause a rare autoimmune disorder coupled with abnormal expansion of lymphocytes. T cells from rheumatoid arthritis (RA) patients show excessive activation of Ras/MEK/ERK pathway. The small molecule farnesylthiosalicylic acid (FTS) interferes with the interaction between Ras GTPases and their prenyl-binding chaperones to inhibit proper plasma membrane localization. In the present study, we tested the therapeutic and immunomodulatory effects of FTS and its derivative 5-fluoro-FTS (F-FTS) in the rat adjuvant-induced arthritis model (AIA). We show that AIA severity was significantly reduced by oral FTS and F-FTS treatment compared to vehicle control treatment. FTS was as effective as the mainstay anti-rheumatic drug methotrexate, and combining the two drugs significantly increased efficacy compared to each drug alone. We also discovered that FTS therapy inhibited both the CFA-driven in vivo induction of Th17 and IL-17/IFN-gamma producing "double positive" as well as the upregulation of serum levels of the Th17-associated cytokines IL-17A and IL-22. By gene microarray analysis of effector CD4(+) T cells from CFA-immunized rats, re-stimulated in vitro with the mycobacterium tuberculosis heat-shock protein 65 (Bhsp65), we determined that FTS abrogated the Bhsp65-induced transcription of a large list of genes (e.g., II17a/f, II22, Ifng, Csf2, Lta, and II1a). The functional enrichment bioinformatics analysis showed significant overlap with predefined gene sets related to inflammation, immune system processes and autoimmunity. In conclusion, FTS and F-FTS display broad immunomodulatory effects in AIA with inhibition of the Th17-type response to a dominant arthritogenic antigen. Hence, targeting Ras signal-transduction cascade is a potential novel therapeutic approach for RA.