509 research outputs found
The KATRIN Pre-Spectrometer at reduced Filter Energy
The KArlsruhe TRItium Neutrino experiment, KATRIN, will determine the mass of
the electron neutrino with a sensitivity of 0.2 eV (90% C.L.) via a measurement
of the beta-spectrum of gaseous tritium near its endpoint of E_0 =18.57 keV. An
ultra-low background of about b = 10 mHz is among the requirements to reach
this sensitivity. In the KATRIN main beam-line two spectrometers of MAC-E
filter type are used in a tandem configuration. This setup, however, produces a
Penning trap which could lead to increased background. We have performed test
measurements showing that the filter energy of the pre-spectrometer can be
reduced by several keV in order to diminish this trap. These measurements were
analyzed with the help of a complex computer simulation, modeling multiple
electron reflections both from the detector and the photoelectric electron
source used in our test setup.Comment: 22 pages, 12 figure
A pulsed, mono-energetic and angular-selective UV photo-electron source for the commissioning of the KATRIN experiment
The KATRIN experiment aims to determine the neutrino mass scale with a
sensitivity of 200 meV/c^2 (90% C.L.) by a precision measurement of the shape
of the tritium -spectrum in the endpoint region. The energy analysis of
the decay electrons is achieved by a MAC-E filter spectrometer. To determine
the transmission properties of the KATRIN main spectrometer, a mono-energetic
and angular-selective electron source has been developed. In preparation for
the second commissioning phase of the main spectrometer, a measurement phase
was carried out at the KATRIN monitor spectrometer where the device was
operated in a MAC-E filter setup for testing. The results of these measurements
are compared with simulations using the particle-tracking software
"Kassiopeia", which was developed in the KATRIN collaboration over recent
years.Comment: 19 pages, 16 figures, submitted to European Physical Journal
Group 10 metal dithiolene bis(isonitrile) complexes: synthesis, structures, properties and reactivity
The reaction of [(Ph2C2S2)2M] (M = Ni2+, Pd2+, Pt2+) with 2 equiv of RNâĄC (R = Me (a), Bn (b), Cy (c), tBu (d), 1-Ad (e), Ph (f)) yields [(Ph2C2S2)M(CâĄNR)2] (M = Ni2+, 4aâf; M = Pd2+, 5aâf; M = Pt2+, 6aâf), which are air-stable and amenable to chromatographic purification. All members have been characterized crystallographically. Structurally, progressively greater planarity tends to be manifested as M varies from Ni to Pt, and a modest decrease in the CâĄN bond length of coordinated CâĄNR appears in moving from Ni toward Pt. Vibrational spectroscopy (CH2Cl2 solution) reveals ÎœCâĄN frequencies for [(Ph2C2S2)M(CâĄNR)2] that are substantially higher than those for free CâĄNR and increase as M ranges from Ni to Pt. This trend is interpreted as arising from an increasingly positive charge at M that stabilizes the linear, charge-separated resonance form of the ligand over the bent form with lowered CâN bond order. UVâvis spectra reveal lowest energy transitions that are assigned as HOMO (dithiolene Ï) â LUMO (MâL Ï*) excitations. One-electron oxidations of [(Ph2C2S2)M(CâĄNR)2] are observed at âŒ+0.5 V due to Ph2C2S22â â Ph2C2SâSâą + eâ. Chemical oxidation of [(Ph2C2S2)Pt(CâĄNtBu)2] with [(Br-p-C6H4)3N][SbCl6] yields [(Ph2C2SâSâą)Pt(CâĄNtBu)2]+, identified spectroscopically, but in the crystalline state [[(Ph2C2SâSâą)Pt(CâĄNtBu)2]2]2+ prevails, which forms via axial Pt···S interactions and pyramidalization at the metal. Complete substitution of MeNC from [(Ph2C2S2)Ni(CâĄNMe)2] by 2,6-Me2py under forcing conditions yields [(2,6-Me2py)Ni(ÎŒ2-η1,η1-SâČ,η1-Sâł-S2C2Ph2)]2 (8), which features a folded Ni2S2 core. In most cases, isocyanide substitution from [(Ph2C2S2)M(CâĄNMe)2] with monodentate ligands (L = phosphine, CNâ, carbene) leads to [(Ph2C2S2)M(L)(CâĄNMe)]n (n = 0, 1â), wherein ÎœCâĄN varies according to the relative Ï-donating power of L (9â21). The use of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) provides [(Ph2C2S2)M(IPr)(CâĄNMe)] for M = Ni (18), Pd (19), but for Pt, attack by IPr at the isocyanide carbon occurs to yield the unusual η1,ÎșC-ketenimine complex [(Ph2C2S2)Pt(C(NMe)(IPr))(CâĄNMe)] (20)
Effect of a sweeping conductive wire on electrons stored in the Penning trap between the KATRIN spectrometers
The KATRIN experiment is going to search for the mass of the electron
antineutrino down to 0.2 eV/c^2. In order to reach this sensitivity the
background rate has to be understood and minimised to 0.01 counts per second.
One of the background sources is the unavoidable Penning trap for electrons due
to the combination of the electric and magnetic fields between the pre- and the
main spectrometer at KATRIN. In this article we will show that by sweeping a
conducting wire periodically through such a particle trap stored particles can
be removed, an ongoing discharge in the trap can be stopped, and the count rate
measured with a detector looking at the trap is reduced.Comment: Final version published in EPJ A, 14 pages, 19 figures (21 files
FMLP- and TNF-stimulated monoclonal Lym-1 antibody-dependent lysis of B lymphoblastoid tumour targets by neutrophils
Asthma and gender impact accumulation of T cell subtypes
<p>Abstract</p> <p>Background</p> <p>The "Th2 hypothesis for asthma" asserts that an increased ratio of Th2:Th1 cytokine production plays an important pathogenic role in asthma. Although widely embraced, the hypothesis has been challenged by various empirical observations and has been described as overly simplistic. We sought to establish whether CD3+CD28-mediated and antigen-independent accumulation of type 1 and type 2 T cells differs significantly between nonasthmatic and asthmatic populations.</p> <p>Methods</p> <p>An ex vivo system was used to characterize the regulation of IFN-Îł-producing (type 1) and IL-13-producing (type 2) T cell accumulation in response to CD3+CD28 and IL-2 stimulation by flow cytometry.</p> <p>Results</p> <p>IL-13-producing T cells increased in greater numbers in response to antigen-independent stimulation in peripheral blood lymphocytes from female atopic asthmatic subjects compared with male asthmatics and both male and female atopic non-asthmatic subjects. IFN-Îł<sup>+ </sup>T cells increased in greater numbers in response to either antigen-independent or CD3+CD28-mediated stimulation in peripheral blood lymphocytes from atopic asthmatic subjects compared to non-asthmatic subjects, regardless of gender.</p> <p>Conclusions</p> <p>We demonstrate that T cells from asthmatics are programmed for increased accumulation of both type 2 and type 1 T cells. Gender had a profound effect on the regulation of type 2 T cells, thus providing a mechanism for the higher frequency of adult asthma in females.</p
Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET
A bispecific antibody (BsAb) targeting the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) pathways represents a novel approach to overcome resistance to targeted therapies in patients with nonsmall cell lung cancer. In this study, we sequentially screened a panel of BsAbs in a combinatorial approach to select the optimal bispecific molecule. The BsAbs were derived from different EGFR and MET parental monoclonal antibodies. Initially, molecules were screened for EGFR and MET binding on tumor cell lines and lack of agonistic activity toward MET. Hits were identified and further screened based on their potential to induce untoward cell proliferation and crossphosphorylation of EGFR by MET via receptor colocalization in the absence of ligand. After the final step, we selected the EGFR and MET arms for the lead BsAb and added low fucose Fc engineering to generate amivantamab (JNJ-61186372). The crystal structure of the anti-MET Fab of amivantamab bound to MET was solved, and the interaction between the two molecules in atomic details was elucidated. Amivantamab antagonized the hepatocyte growth factor (HGF)-induced signaling by binding to MET Sema domain and thereby blocking HGF beta-chain-Sema engagement. The amivantamab EGFR epitope was mapped to EGFR domain III and residues K443, K465, I467, and S468. Furthermore, amivantamab showed superior antitumor activity over small molecule EGFR and MET inhibitors in the HCC827-HGF in vivo model. Based on its unique mode of action, amivantamab may provide benefit to patients with malignancies associated with aberrant EGFR and MET signaling.Transplantation and autoimmunit
Commissioning of the vacuum system of the KATRIN Main Spectrometer
The KATRIN experiment will probe the neutrino mass by measuring the
beta-electron energy spectrum near the endpoint of tritium beta-decay. An
integral energy analysis will be performed by an electro-static spectrometer
(Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a
volume of 1240 m^3, and a complex inner electrode system with about 120000
individual parts. The strong magnetic field that guides the beta-electrons is
provided by super-conducting solenoids at both ends of the spectrometer. Its
influence on turbo-molecular pumps and vacuum gauges had to be considered. A
system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter
strips has been deployed and was tested during the commissioning of the
spectrometer. In this paper the configuration, the commissioning with bake-out
at 300{\deg}C, and the performance of this system are presented in detail. The
vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is
demonstrated that the performance of the system is already close to these
stringent functional requirements for the KATRIN experiment, which will start
at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure
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