High resolution pixel detectors for e+e- linear colliders

The physics goals at the future e+e- linear collider require high performance vertexing and impact parameter resolution. Two possible technologies for the vertex detector of an experimental apparatus are outlined in the paper: an evolution of the Hybrid Pixel Sensors already used in high energy physics experiments and a new detector concept based on the monolithic CMOS sensors.Comment: 8 pages, to appear on the Proceedings of the International Workshop on Linear Colliders LCWS99, Sitges (Spain), April 28 - May 5, 199

Variational Approach to Hard Sphere Segregation Under Gravity

It is demonstrated that the minimization of the free energy functional for hard spheres and hard disks yields the result that excited granular materials under gravity segregate not only in the widely known "Brazil nut" fashion, i.e. with the larger particles rising to the top, but also in reverse "Brazil nut" fashion. Specifically, the local density approximation is used to investigate the crossover between the two types of segregation occurring in the liquid state, and the results are found to agree qualitatively with previously published results of simulation and of a simple model based on condensation.Comment: 10 pages, 3 figure

Aberrant Autophagic Response in The Muscle of A Knock-in Mouse Model of Spinal and Bulbar Muscular Atrophy

Spinal and bulbar muscular atrophy (SBMA) is characterized by loss of motoneurons and sensory neurons, accompanied by atrophy of muscle cells. SBMA is due to an androgen receptor containing a polyglutamine tract (ARpolyQ) that misfolds and aggregates, thereby perturbing the protein quality control (PQC) system. Using SBMA AR113Q mice we analyzed proteotoxic stress-induced alterations of HSPB8-mediated PQC machinery promoting clearance of misfolded proteins by autophagy. In muscle of symptomatic AR113Q male mice, we found expression upregulation of Pax-7, myogenin, E2-ubiquitin ligase UBE2Q1 and acetylcholine receptor (AchR), but not of MyoD, and of two E3-ligases (MuRF-1 and Cullin3). TGF beta 1 and PGC-1 alpha were also robustly upregulated. We also found a dramatic perturbation of the autophagic response, with upregulation of most autophagic markers (Beclin-1, ATG10, p62/SQSTM1, LC3) and of the HSPB8-mediated PQC response. Both HSPB8 and its co-chaperone BAG3 were robustly upregulated together with other specific HSPB8 interactors (HSPB2 and HSPB3). Notably, the BAG3: BAG1 ratio increased in muscle suggesting preferential misfolded proteins routing to autophagy rather than to proteasome. Thus, mutant ARpolyQ induces a potent autophagic response in muscle cells. Alteration in HSPB8-based PQC machinery may represent muscle-specific biomarkers useful to assess SBMA progression in mice and patients in response to pharmacological treatments

High Resolution Hybrid Pixel Sensors for the e+e- TESLA Linear Collider Vertex Tracker

In order to fully exploit the physics potential of a future high energy e+e- linear collider, a Vertex Tracker, providing high resolution track reconstruction, is required. Hybrid Silicon pixel sensors are an attractive option, for the sensor technology, due to their read-out speed and radiation hardness, favoured in the high rate environment of the TESLA e+e- linear collider design but have been so far limited by the achievable single point space resolution. In this paper, a conceptual design of the TESLA Vertex Tracker, based on a novel layout of hybrid pixel sensors with interleaved cells to improve their spatial resolution, is presented.Comment: 12 pages, 5 figures, to appear in the Proceedings of the Vertex99 Workshop, Texel (The Netherlands), June 199

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast mil

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast mil

The certification of anti-myeloperoxidase immunoglobulin G in human serum ERM® - DA476/IFCC

This report describes the production and certification of ERM-DA476/IFCC, a new serum protein reference material intended for the standardisation of measurements of anti-myeloperoxidase immunoglobulin G (anti-MPO IgG) antibodies. The material was produced according to ISO Guide 34:2009. The raw material used to prepare ERM-DA476/IFCC was a plasmapheresis material containing a high concentration of anti-MPO IgG. After a thorough commutability study lyophilised serum was selected as the format for the candidate reference material. Serum processing was performed based on the procedure used for the reference material ERM-DA470k/IFCC. The plasma was converted into serum which was then delipidated. After the addition of preservatives the processed serum was diluted with plasmapheresis solution containing albumin, prior to the transfer of 1 mL aliquots to glass vials. The serum was then lyophilised and the vials closed with rubber stoppers and screw caps under nitrogen atmosphere prior to storage at -70 °C. The between unit-homogeneity was quantified and stability during dispatch and storage were assessed in accordance with ISO Guide 35:2006. The material was characterised by an inter-laboratory comparison exercise performed by laboratories of demonstrated competence and with adherence to ISO/IEC 17025 , using a purified anti-MPO IgG preparation as calibrant. This was achieved using a value transfer protocol previously used in the characterisation of ERM-DA470k/IFCC. Technically invalid results were removed. However no other outliers were eliminated on statistical grounds only. Uncertainties of the certified values were calculated in accordance to the Guide to the Expression of Uncertainty in Measurement (GUM) and include uncertainties relating to possible lack of homogeneity, instability and characterisation. The material is intended for the calibration of methods and quality control. As any reference material, it can also be used for control charts or validation studies. The CRM is available in glass vials containing the lyophilised residue of 1 g serum. The minimum amount of reconstituted sample to be used is 10 μL. The CRM was accepted as European Reference Material (ERM®) after peer evaluation by the partners of the European Reference Materials consortium