256 research outputs found
Performance of the EUDET-type beam telescopes
Test beam measurements at the test beam facilities of DESY have been
conducted to characterise the performance of the EUDET-type beam telescopes
originally developed within the EUDET project. The beam telescopes are equipped
with six sensor planes using MIMOSA26 monolithic active pixel devices. A
programmable Trigger Logic Unit provides trigger logic and time stamp
information on particle passage. Both data acquisition framework and offline
reconstruction software packages are available. User devices are easily
integrable into the data acquisition framework via predefined interfaces.
The biased residual distribution is studied as a function of the beam energy,
plane spacing and sensor threshold. Its standard deviation at the two centre
pixel planes using all six planes for tracking in a 6\,GeV
electron/positron-beam is measured to be
(2.88\,\pm\,0.08)\,\upmu\meter.Iterative track fits using the formalism of
General Broken Lines are performed to estimate the intrinsic resolution of the
individual pixel planes. The mean intrinsic resolution over the six sensors
used is found to be (3.24\,\pm\,0.09)\,\upmu\meter.With a 5\,GeV
electron/positron beam, the track resolution halfway between the two inner
pixel planes using an equidistant plane spacing of 20\,mm is estimated to
(1.83\,\pm\,0.03)\,\upmu\meter assuming the measured intrinsic resolution.
Towards lower beam energies the track resolution deteriorates due to increasing
multiple scattering. Threshold studies show an optimal working point of the
MIMOSA26 sensors at a sensor threshold of between five and six times their RMS
noise. Measurements at different plane spacings are used to calibrate the
amount of multiple scattering in the material traversed and allow for
corrections to the predicted angular scattering for electron beams
Structure-function analysis reveals that the Pseudomonas aeruginosa Tps4 two-partner secretion system is involved in CupB5 translocation
Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, synonymous with cystic fibrosis patients, which can cause chronic infection of the lungs. This pathogen is a model organism to study biofilms: a bacterial population embedded in an extracellular matrix that provide protection from environmental pressures and lead to persistence. A number of Chaperone-Usher Pathways, namely CupA-CupE, play key roles in these processes by assembling adhesive pili on the bacterial surface. One of these, encoded by the cupB operon, is unique as it contains a nonchaperone-usher gene product, CupB5. Two-partner secretion (TPS) systems are comprised of a C-terminal integral membrane β-barrel pore with tandem N-terminal POTRA (POlypeptide TRansport Associated) domains located in the periplasm (TpsB) and a secreted substrate (TpsA). Using NMR we show that TpsB4 (LepB) interacts with CupB5 and its predicted cognate partner TpsA4 (LepA), an extracellular protease. Moreover, using cellular studies we confirm that TpsB4 can translocate CupB5 across the P. aeruginosa outer membrane, which contrasts a previous observation that suggested the CupB3 P-usher secretes CupB5. In support of our findings we also demonstrate that tps4/cupB operons are coregulated by the RocS1 sensor suggesting P. aeruginosa has developed synergy between these systems. Furthermore, we have determined the solution-structure of the TpsB4-POTRA1 domain and together with restraints from NMR chemical shift mapping and in vivo mutational analysis we have calculated models for the entire TpsB4 periplasmic region in complex with both TpsA4 and CupB5 secretion motifs. The data highlight specific residues for TpsA4/CupB5 recognition by TpsB4 in the periplasm and suggest distinct roles for each POTRA domain
Design and Test of a Forward Neutron Calorimeter for the ZEUS Experiment
A lead scintillator sandwich sampling calorimeter has been installed in the
HERA tunnel 105.6 m from the central ZEUS detector in the proton beam
direction. It is designed to measure the energy and scattering angle of
neutrons produced in charge exchange ep collisions. Before installation the
calorimeter was tested and calibrated in the H6 beam at CERN where 120 GeV
electrons, muons, pions and protons were made incident on the calorimeter. In
addition, the spectrum of fast neutrons from charge exchange proton-lucite
collisions was measured. The design and construction of the calorimeter is
described, and the results of the CERN test reported. Special attention is paid
to the measurement of shower position, shower width, and the separation of
electromagnetic showers from hadronic showers. The overall energy scale as
determined from the energy spectrum of charge exchange neutrons is compared to
that obtained from direct beam hadrons.Comment: 45 pages, 22 Encapsulated Postscript figures, submitted to Nuclear
Instruments and Method
Sinteza i antihipoksično djelovanje alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline
The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by microanalyses, IR- and 1H NMR data. Values of acute p.o. and i.p. toxicity in mice show lower toxicity compared to caffeine. Declines in spontaneous locomotor activity support the idea of depressive CNS activity of the compounds. Two compounds exhibited brain antihypoxic activity (5a and 5b against haemic and circulatory hypoxia, respectively).U radu je opisana sinteza alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline i njihova karakterizacija elementarnom analizom, IR- i 1H NMR spektroskopijom. Testiranja na miševima pokazuju da su sintetizirani spojevi primijenjeni p.o. i i.p. manje toksični od kofeina. Smanjenje lokomotoričke aktivnosti podupire ideju o njihovom depresivnom djelovanju na SŽS. Spojevi 5a i 5b djeluju antihipoksički u uvjetima krvne i cirkulacijske hipoksije u mozgu
IL-27 Regulates IL-18 Binding Protein in Skin Resident Cells
IL-18 is an important mediator involved in chronic inflammatory conditions such as cutaneous lupus erythematosus, psoriasis and chronic eczema. An imbalance between IL-18 and its endogenous antagonist IL-18 binding protein (BP) may account for increased IL-18 activity. IL-27 is a cytokine with dual function displaying pro- and anti-inflammatory properties. Here we provide evidence for a yet not described anti-inflammatory mode of action on skin resident cells. Human keratinocytes and surprisingly also fibroblasts (which do not produce any IL-18) show a robust, dose-dependent and highly inducible mRNA expression and secretion of IL-18BP upon IL-27 stimulation. Other IL-12 family members failed to induce IL-18BP. The production of IL-18BP peaked between 48–72 h after stimulation and was sustained for up to 96 h. Investigation of the signalling pathway showed that IL-27 activates STAT1 in human keratinocytes and that a proximal GAS site at the IL-18BP promoter is of importance for the functional activity of IL-27. The data are in support of a significant anti-inflammatory effect of IL-27 on skin resident cells. An important novel property of IL-27 in skin pathobiology may be to counter-regulate IL-18 activities by acting on keratinocytes and importantly also on dermal fibroblasts
Infrastructure for Detector Research and Development towards the International Linear Collider
The EUDET-project was launched to create an infrastructure for developing and
testing new and advanced detector technologies to be used at a future linear
collider. The aim was to make possible experimentation and analysis of data for
institutes, which otherwise could not be realized due to lack of resources. The
infrastructure comprised an analysis and software network, and instrumentation
infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture
The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells : Implications for COVID-19 vascular research
Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is impor-tant to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, andin heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.Peer reviewe
Activation of interferon regulatory factor-3 via toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA
U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-β (IFN-β), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-β promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A1, an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-α, indicating an anti-inflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces
- …