The MuPix Telescope: A Thin, high Rate Tracking Telescope

The MuPix Telescope is a particle tracking telescope, optimized for tracking low momentum particles and high rates. It is based on the novel High-Voltage Monolithic Active Pixel Sensors (HV-MAPS), designed for the Mu3e tracking detector. The telescope represents a first application of the HV-MAPS technology and also serves as test bed of the Mu3e readout chain. The telescope consists of up to eight layers of the newest prototypes, the MuPix7 sensors, which send data self-triggered via fast serial links to FPGAs, where the data is time-ordered and sent to the PC. A particle hit rate of 1 MHz per layer could be processed. Online tracking is performed with a subset of the incoming data. The general concept of the telescope, chip architecture, readout concept and online reconstruction are described. The performance of the sensor and of the telescope during test beam measurements are presented.Comment: Proceedings TWEPP 2016, 8 pages, 7 figure

Irradiation study of a fully monolithic HV-CMOS pixel sensor design in AMS 180 nm

High-Voltage Monolithic Active Pixel Sensors (HV-MAPS) based on the 180 nm HV-CMOS process have been proposed to realize thin, fast and highly integrated pixel sensors. The MuPix7 prototype, fabricated in the commercial AMS H18 process, features a fully integrated on-chip readout, i.e. hit-digitization, zero suppression and data serialization. It is the first fully monolithic HV-CMOS pixel sensor that has been tested for the use in high irradiation environments like HL-LHC. We present results from laboratory and test beam measurements of MuPix7 prototypes irradiated with neutrons (up to $5.0\cdot10^{15}{\,\rm{n}_{\rm{eq}}/cm^2}$) and protons (up to $7.8\cdot 10^{15} \,\rm{protons}/cm^2$) and compare the performance with non-irradiated sensors. Efficiencies well above 90 % at noise rates below 200 Hz per pixel are measured. A time resolution better than 22 ns is measured for all tested settings and sensors, even at the highest irradiation fluences. The data transmission at 1.25 Gbit/s and the on-chip PLL remain fully functional

MuPix7 - A fast monolithic HV-CMOS pixel chip for Mu3e

The MuPix7 chip is a monolithic HV-CMOS pixel chip, thinned down to 50 \mu m. It provides continuous self-triggered, non-shuttered readout at rates up to 30 Mhits/chip of 3x3 mm^2 active area and a pixel size of 103x80 \mu m^2. The hit efficiency depends on the chosen working point. Settings with a power consumption of 300 mW/cm^2 allow for a hit efficiency >99.5%. A time resolution of 14.2 ns (Gaussian sigma) is achieved. Latest results from 2016 test beam campaigns are shown.Comment: Proceedingsfor the PIXEL2016 conference, submitted to JINST A dangling reference has been removed from this version, no other change

Deep phenotyping of the unselected COPSAC2010 birth cohort study

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008–2010 to a novel unselected ‘COPSAC(2010)’ cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high‐dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty‐eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over‐representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC(2010) birth cohort study provides longitudinal clinical follow‐up with highly specific end‐points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle‐related chronic inflammatory disorders such as asthma

MuPix and ATLASPix -- Architectures and Results

High Voltage Monolithic Active Pixel Sensors (HV-MAPS) are based on a commercial High Voltage CMOS process and collect charge by drift inside a reversely biased diode. HV-MAPS represent a promising technology for future pixel tracking detectors. Two recent developments are presented. The MuPix has a continuous readout and is being developed for the Mu3e experiment whereas the ATLASPix is being developed for LHC applications with a triggered readout. Both variants have a fully monolithic design including state machines, clock circuitries and serial drivers. Several prototypes and design variants were characterised in the lab and in testbeam campaigns to measure efficiencies, noise, time resolution and radiation tolerance. Results from recent MuPix and ATLASPix prototypes are presented and prospects for future improvements are discussed.Comment: 10 pages, proceedings, The 28th International Workshop on Vertex Detectors (VERTEX 2019), 13 - 18 Oct 2019, Lopud Island, Croati

Interleukin-8 Is Activated in Patients with Chronic Liver Diseases and Associated with Hepatic Macrophage Accumulation in Human Liver Fibrosis

BACKGROUND: Interleukin-8 (IL-8, CXCL8) is a potent chemoattractant for neutrophils and contributes to acute liver inflammation. Much less is known about IL-8 in chronic liver diseases (CLD), but elevated levels were reported from alcoholic and hepatitis C-related CLD. We investigated the regulation of IL-8, its receptors CXCR1 and CXCR2 and possible IL-8 responding cells in CLD patients. METHODOLOGY: Serum IL-8 levels were measured in CLD patients (n = 200) and healthy controls (n = 141). Intrahepatic IL-8, CXCR1 and CXCR2 gene expression was quantified from liver samples (n = 41), alongside immunohistochemical neutrophil (MPO) and macrophage (CD68) stainings. CXCR1 and CXCR2 expression was analyzed on purified monocytes from patients (n = 111) and controls (n = 31). In vitro analyses explored IL-8 secretion by different leukocyte subsets. PRINCIPAL FINDINGS: IL-8 serum levels were significantly increased in CLD patients, especially in end-stage cirrhosis. Interestingly, patients with cholestatic diseases exhibited highest IL-8 serum concentrations. IL-8 correlated with liver function, inflammatory cytokines and non-invasive fibrosis markers. Intrahepatically, IL-8 and CXCR1 expression were strongly up-regulated. However, intrahepatic IL-8 could only be associated to neutrophil infiltration in patients with primary biliary cirrhosis (PBC). In non-cholestatic cirrhosis, increased IL-8 and CXCR1 levels were associated with hepatic macrophage accumulation. In line, CXCR1, but not CXCR2 or CXCR3, expression was increased on circulating monocytes from cirrhotic patients. Moreover, monocyte-derived macrophages from CLD patients, especially the non-classical CD16⁺ subtype, displayed enhanced IL-8 secretion in vitro. CONCLUSIONS: IL-8 is strongly activated in CLD, thus likely contributing to hepatic inflammation. Our study suggests a novel role of IL-8 for recruitment and activation of hepatic macrophages via CXCR1 in human liver cirrhosis

Elevated Flt3L predicts long-term survival in patients with high-grade gastroenteropancreatic neuroendocrine neoplasms

BACKGROUND: The clinical management of high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) is challenging due to disease heterogeneity, illustrating the need for reliable biomarkers facilitating patient stratification and guiding treatment decisions. FMS-like tyrosine kinase 3 ligand (Flt3L) is emerging as a prognostic or predictive surrogate marker of host tumoral immune response and might enable the stratification of patients with otherwise comparable tumor features. METHODS: We evaluated Flt3L gene expression in tumor tissue as well as circulating Flt3L levels as potential biomarkers in a cohort of 54 patients with GEP-NEN. RESULTS: We detected a prominent induction of Flt3L gene expression in individual G2 and G3 NEN, but not in G1 neuroendocrine tumors (NET). Flt3L mRNA expression levels in tumor tissue predicted the disease-related survival of patients with highly proliferative G2 and G3 NEN more accurately than the conventional criteria of grading or NEC/NET differentiation. High level Flt3L mRNA expression was associated with the increased expression of genes related to immunogenic cell death, lymphocyte effector function and dendritic cell maturation, suggesting a less tolerogenic (more proinflammatory) phenotype of tumors with Flt3L induction. Importantly, circulating levels of Flt3L were also elevated in high grade NEN and correlated with patients' progression-free and disease-related survival, thereby reflecting the results observed in tumor tissue. CONCLUSIONS: We propose Flt3L as a prognostic biomarker for high grade GEP-NEN, harnessing its potential as a marker of an inflammatory tumor microenvironment. Flt3L measurements in serum, which can be easily be incorporated into clinical routine, should be further evaluated to guide patient stratification and treatment decisions