Time Resolution of a Few Nanoseconds in Silicon Strip Detectors Using the APV25 Chip

The APV25 front-end chip for the CMS Silicon Tracker has a peaking time of 50 ns, but confines the signal to a single clock period (=bunch crossing) with its internal “deconvolution” filter. This method requires a beam-synchronous clock and thus cannot be applied to a (quasi-) continuous beam. Nevertheless, using the multi-peak mode of the APV25, where 3 (or 6,9,12,...) consecutive shaper output samples are read out, the peak time can be reconstructed externally with high precision. Thus, offtime hits can be discarded which results in significant occupancy reduction. We will describe this method, results from beam tests and the intended implementation in an upgrade of the BELLE Silicon Vertex Detector

Readout and Data Processing Electronics for the Belle-II Silicon Vertex Detector

A prototype readout system has been developed for the future Belle-II Silicon Vertex Detector at the Super-KEK-B factory in Tsukuba, Japan. It will receive raw data from double-sided sensors with a total of approximately 240,000 strips read out by APV25 chips at a trigger rate of up to 30kHz and perform strip reordering, pedestal subtraction, a two-pass common mode correction and zero suppression in FPGA firmware. Moreover, the APV25 will be operated in multi-peak mode, where (typically) six samples along the shaped waveform are used for precise hit-time reconstruction which will also be implemented in FPGAs using look-up tables

Construction and Performance of a Double-Sided Silicon Detector Module Using the Origami Concept

The APV25 front-end chip with short shaping time will be used in the Belle II Silicon Vertex Detector (SVD) in order to achive low occupancy. Since fast amplifiers are more susceptible to noise caused by their capacitive input load, they have to be placed as close to the sensor as possible. On the other hand, material budget inside the active volume has to be kept low in order to constrain multiple scattering. We built a low mass sensor module with double-sided readout, where thinned APV25 chips are placed on a single flexible circuit glued onto one side of the sensor. The interconnection to the other side is done by Kapton fanouts, which are wrapped around the edge of the sensor, hence the name Origami. Since all front-end chips are aligned in a row on the top side of the module, cooling can be done by a single aluminum pipe. The performance of the Origami module was evaluated in a beam test at CERN in August 2009, of which first results are presented here

Effect of low molecular weight proteins and dextran on renal cathepsin B and L activity

Effect of low molecular weight proteins and dextran on renal cathepsin B and L activity. Renal extraction of low molecular weight proteins (LMWP) accounts for 30% to 80% of their total metabolic clearance. Extraction includes glomerular filtration, proximal tubular uptake, and intralysosomal proteolysis. To characterize the anatomic sites and enzymes involved in digestion of reabsorbed LMWP, the lysosomal proteases, cathepsin B and L, were measured by ultramicroassay in isolated S1, S2 and S3 segments of the proximal tubule of proteinuric rats. Increased glomerular filtration and tubular uptake of LMWP were induced by i.v. and i.p. injections of myoglobin and cationic and anionic lysozyme. Both cationic lysozyme and myoglobin increased cathepsin B and L activities in the proximal tubule, while anionic lysozyme had no effect. Morphologic examination of kidney tissue suggested that proximal tubular uptake of anionic lysozyme was negligible in comparison with the cationic form. Hence, only LMWP absorbed by the proximal tubule cells stimulated cathepsin B and L activities. Proximal tubular uptake of cationic lysozyme was determined by measurement of lysozyme activities in S1, S2, and S3. S1 segments contained the highest lysozyme activity, while S2 and S3 had much lower activities, and cathepsin B and L activity following cationic lysozyme injection was stimulated only in S1 segments. These results suggest that cathepsin B and L participate in lysosomal digestion of certain LMWP. Furthermore, the activities of cathepsin B and L adapt to increased uptake of LMWP. To gain additional insight into the mechanism of cathepsin adaptation, the cathepsin B and L activities were measured following injection of dextran with a similar low molecular weight. Dextran uptake in proximal tubules was confirmed by morphologic examination of kidney tissue. Dextran increased cathepsin B and L activities in the proximal tubule. Hence, increased endocytic activity of proximal tubule cells or increased lysosomal load of macromolecules or both rather than direct protein-enzyme interaction seem to be involved in cathepsin stimulation

Characterization of the non-functional Fas ligand of gld mice

Mice homozygous for either the gld or Ipr mutation develop autoimmune diseases and progressive lymphadenopathy. The Ipr mutation Is characterized by the absence of unctional Fas, whereas gld mice exhibit an inactive FasL due to a point mutation proximal to the extracellular C-terminus. The structural repercussions of this amino acid substitution remain unknown. Here we report that FasL Is expressed at similar levels on the surface of activated T lymphocytes from gld and wild-type mice. Using a polyclonal anti-FasL antibody, Indistinguishable amounts of a 40 kDa protein are detected In both gld and wild-type splenocytes. The molecular model of FasL, based on the known structure of TNF-α, predicts that the Phe→Leu gld mutation is located at the protomer interface which Is close to the FasR Interaction site. We conclude that the gld mutation allows normal FasL biosynthesis, surface expression and ollgomerlzatlon, but induces structural alterations to the Fas binding region leading to the phenotypic changes observe

Resolution Studies on Silicon Strip Sensors with fine Pitch

In June 2008 single-sided silicon strip sensors with 50 $\mu$m readout pitch were tested in a highly energetic pion beam at the SPS at CERN. The purpose of the test was to evaluate characteristic detector properties by varying the strip width and the number of intermediate strips. The experimental setup and first results for the spatial resolution are discussed.Comment: proceeding of the International Linear Collider Workshop 2008 (LCWS08); corrected typos, added reference for section

Inhibition of death receptor signals by cellular FLIP.

The widely expressed protein Fas is a member of the tumour necrosis factor receptor family which can trigger apoptosis. However, Fas surface expression does not necessarily render cells susceptible to Fas ligand-induced death signals, indicating that inhibitors of the apoptosis-signalling pathway must exist. Here we report the characterization of an inhibitor of apoptosis, designated FLIP (for FLICE-inhibitory protein), which is predominantly expressed in muscle and lymphoid tissues. The short form, FLIPs, contains two death effector domains and is structurally related to the viral FLIP inhibitors of apoptosis, whereas the long form, FLIP(L), contains in addition a caspase-like domain in which the active-centre cysteine residue is substituted by a tyrosine residue. FLIPs and FLIP(L) interact with the adaptor protein FADD and the protease FLICE, and potently inhibit apoptosis induced by all known human death receptors. FLIP(L) is expressed during the early stage of T-cell activation, but disappears when T cells become susceptible to Fas ligand-mediated apoptosis. High levels of FLIP(L) protein are also detectable in melanoma cell lines and malignant melanoma tumours. Thus FLIP may be implicated in tissue homeostasis as an important regulator of apoptosis

Caspase Activation Is Required for T Cell Proliferation

Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade. It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity. This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors. We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity. This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval. The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation. These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner