Readout system and testbeam results of the RD50-MPW2 HV-CMOS pixel chip

The RD50-CMOS group aims to design and study High Voltage CMOS (HVCMOS) chips for use in a high radiation environment. Currently, measurements are performed on RD50-MPW2 chip, the second prototype developed by this group. The active matrix of the prototype consists of 8x8 pixels with analog front end. Details of the analog front end and simulations have been already published earlier. This contribution focuses on the Caribou based readout system of the active matrix. Each pixel of the active matrix can be readout one after the other. Relevant aspects of hardware, firmware and software are introduced. As a first stage, firmware for a standalone setup is introduced and details on data flow are given. Afterwards, a second stage of the firmware capable of synchronizing with other detectors and accepting triggers is presented, focusing on operation of the chip in combination with a tracking telescope to measure efficiency and residuals.Comment: Published under licence in Journal of Physics: Conference Series by IOP Publishing Ltd. CC-BY Content from this work may be used under the terms of the Creative Commons Attribution 4.0 International licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DO

A Proton Computed Tomography Demonstrator for Stopping Power Measurements

Particle therapy is an established method to treat deep-seated tumours using accelerator-produced ion beams. For treatment planning, the precise knowledge of the relative stopping power (RSP) within the patient is vital. Conversion errors from x-ray computed tomography (CT) measurements to RSP introduce uncertainties in the applied dose distribution. Using a proton computed tomography (pCT) system to measure the SP directly could potentially increase the accuracy of treatment planning. A pCT demonstrator, consisting of double-sided silicon strip detectors (DSSD) as tracker and plastic scintillator slabs coupled to silicon photomultipliers (SiPM) as a range telescope, was developed. After a significant hardware upgrade of the range telescope, a 3D tomogram of an aluminium stair phantom was recorded at the MedAustron facility in Wiener Neustadt, Austria. In total, 80 projections with 6.5x10^5 primary events were acquired and used for the reconstruction of the RSP distribution in the phantom. After applying a straight-line approximation for the particle path inside the phantom, the most probable value (MPV) of the RSP distribution could be measured with an accuracy of 0.59%. The RSP resolution inside the phantom was only 9.3% due to a limited amount of projections and measured events per projection.Comment: Preprint submitted to the open-access Journal of Physics: Conference Series. (TIPP2021 conference proceedings). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Feasibility study of a proton CT system based on 4D-tracking and residual energy determination via time-of-flight

For dose calculations in ion beam therapy, it is vital to accurately determine the relative stopping power (RSP) distribution within the treated volume. Currently, RSP values are extrapolated from Hounsfield units (HU), measured with x-ray computed tomography (CT), which entails RSP inaccuracies due to conversion errors. A suitable method to improve the treatment plan accuracy is proton computed tomography (pCT). A typical pCT system consists of a tracking system and a separate residual energy (or range) detector to measure the RSP distribution directly. This paper introduces a novel pCT system based on a single detector technology, namely low gain avalanche detectors (LGADs). LGADs are fast 4D-tracking detectors, which can be used to simultaneously measure the particle position and time with precise timing and spatial resolution. In contrast to standard pCT systems, the residual energy is determined via a time-of-flight (TOF) measurement between different 4D-tracking stations. The design parameters for a realistic proton computed tomography system based on 4D-tracking detectors were studied and optimized using Monte Carlo simulations. The RSP accuracy and RSP resolution were measured inside the inserts of the CTP404 phantom to estimate the performance of the pCT system. After introducing a dedicated calibration procedure for the TOF calorimeter, RSP accuracies < 0.6 % could be achieved. Furthermore, the design parameters with the strongest impact on the RSP resolution were identified and a strategy to improve RSP resolution is proposed.Comment: Preprint submitted to Physics in Medicine and Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

RD50-MPW3: A fully monolithic digital CMOS sensor for future tracking detectors

The CERN-RD50 CMOS working group develops the RD50-MPWseries of monolithic high-voltage CMOS pixel sensors for potential use in future high luminosity experiments such as the HL-LHC and FCC-hh. In this contribution, the design of the latest prototype in this series, RD50-MPW3, is presented. An overview of its pixel matrix and digital readout periphery is given, with discussion of the new structures implemented in the chip and the problems they aim to solve. The main analog and digital features of the sensor are already tested and initial laboratory characterisation of the chip is presented

Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling

The mesodiencephalic dopaminergic (mdDA) neurons, including the nigrostriatal subset that preferentially degenerates in Parkinson's Disease (PD), strongly depend on an accurately balanced Wingless-type MMTV integration site family member 1 (WNT1)/beta-catenin signaling pathway during their development. Loss of this pathway abolishes the generation of these neurons, whereas excessive WNT1/b-catenin signaling prevents their correct differentiation. The identity of the cells responding to this pathway in the developing mammalian ventral midbrain (VM) as well as the precise progression of WNT/b-catenin action in these cells are still unknown. We show that strong WNT/b-catenin signaling inhibits the differentiation of WNT/b-catenin-responding mdDA progenitors into PITX3(+) and TH+ mdDA neurons by repressing the Pitx3 gene in mice. This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. LEF1 expression is restricted to a caudolateral mdDA progenitor subset that preferentially responds to WNT/b-catenin signaling and gives rise to a fraction of all mdDA neurons. Our data indicate that an attenuation of WNT/b-catenin signaling in mdDA progenitors is essential for their correct differentiation into specific mdDA neuron subsets. This is an important consideration for stem cell-based regenerative therapies and in vitro models of neuropsychiatric diseases

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Publisher Copyright: © 2021, The Author(s).Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change.Peer reviewe

Global data on earthworm abundance, biomass, diversity and corresponding environmental properties

Earthworms are an important soil taxon as ecosystem engineers, providing a variety of crucial ecosystem functions and services. Little is known about their diversity and distribution at large spatial scales, despite the availability of considerable amounts of local-scale data. Earthworm diversity data, obtained from the primary literature or provided directly by authors, were collated with information on site locations, including coordinates, habitat cover, and soil properties. Datasets were required, at a minimum, to include abundance or biomass of earthworms at a site. Where possible, site-level species lists were included, as well as the abundance and biomass of individual species and ecological groups. This global dataset contains 10,840 sites, with 184 species, from 60 countries and all continents except Antarctica. The data were obtained from 182 published articles, published between 1973 and 2017, and 17 unpublished datasets. Amalgamating data into a single global database will assist researchers in investigating and answering a wide variety of pressing questions, for example, jointly assessing aboveground and belowground biodiversity distributions and drivers of biodiversity change

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Upgrade studies for the Belle silicon vertex detector

Zsfassung in dt. Sprachehttp://www.hephy.at/fileadmin/user_upload/Publikationen/diploma_thesis_irmler.pdfTeilchenstrahlen in Beschleunigeranlagen entstehen, verwendet werden. Ein Beispiel ist der Belle-Detektor, der sich um den Kollissionspunkt des Elektron-Positron-Beschleunigers der High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan, befindet.Der derzeit im Belle-Experiment installierte Silicon Vertex Detector (SVD) leidet unter der immer großer werdenden Occupancy (darunter versteht man den Anteil der Streifen, die zu einem beliebigen Zeitpunkt ein Signal ungleich Null liefern) der innersten Lage. Diese Diplomarbeit beschäftigt sich mit Methoden zur Reduktion der Occupancy von Silizium-Detektor-Systemen. Um dies zu erreichen, besteht eine Möglichkeit darin, die Streifenlänge und somit die sensitive Fläche der Silizium-Sensoren zu reduzieren, was aber zwingend zu einer Erhöhung der auszulesenden Kanäle führt. Ein anderer Ansatz ist es, die derzeitige Ausleseelektronik durch ein System mit kürzerer Integrationszeit zu ersetzen, wodurch das sensitive Zeitfenster verringert wird.In dieser Arbeit wird gezeigt, wie der schnelle und moderne Auslesechip APV25, welcher ursprünglich für den Silicon Strip Tracker des Compact-Muon-Solenid-Projekts (CMS) am CERN (Genf, CH) entwickelt wurde, unter den Bedingungen des Belle-Experiments eingesetzt werden kann. Im Gegensatz zu CMS, wo einseitige Sensoren verwendet werden, arbeitet der Belle-SVD mit doppelseitigen Silizium-Streifen-Detektoren (DSSD), was umfassende Änderungen des Auslesesystems erfordert.Die Hauptaufgabe des Projekts bestand darin, einen Prototypen einer solchen Ausleseelektronik zu entwerfen und die Software zur Datennahme und -analyse an die neuen Erfordernisse anzupassen. Weiters wurde eine verbesserte Methode der Datenauswertung unter Verwendung des APV25 in die Software implementiert, welche es ermöglicht, den wahren Durchtrittszeitpunkt eines Teilchens mit bisher nicht erreichter Genauigkeit zu rekonstruieren.Abschließend wurde die Funktion des Protoypen, der Software und der modifizierten Datenanalyse durch mehrere Messreihen in Teilchenstrahlen (Beam Tests) am KEK und am Paul Scherer Institut (PSI, Villigen, CH) evaluiert. Die dabei gewonnen, hervorragenden Ergebnisse waren ausschlaggebend dafür, dass bereits an einer Implementierung des Nachfolgers des derzeitigen Belle-SVDs gearbeitet wird, wobei der APV25 und andere Teile des neu entworfenen Auslesesystems zum Einsatz kommen werden.Diese Diplomarbeit umfasst nur die Anfänge meiner im Jahr 2004 begonnenen Tätigkeit für das Institut für Hochenergiephysik der österreichischen Akademie der Wissenschaften (HEPHY). Weiterführende Themen werden im Kapitel ``Summary and Outlook'' kurz vorgestellt. Da die Entwicklungsarbeit zu diesem Projekt weiterläuft, kann zum jetzigen Zeitpunkt noch kein abschließender Bericht verfasst werden.Today silicon microstrip detectors are very important for the research of high energy physics, because in virtually every experiment they are used to measure the tracks of charged particles which are produced by colliding particle beams. Such an experiment is the Belle detector, which is located around the collision point of the electron positron accelerator of the High Energy Accelerator Research Organization (KEK) in Tsukuba, Japan.The currently installed Silicon Vertex Detector (SVD) of the Belle experiment suffers from the increasing occupancy (fraction of hit channels with non-zero signal at any random moment) of its innermost layer. This diploma thesis describes methods to reduce the occupancy of such a detector system. One possible improvement is to shorten the strips of the silicon sensors and thus reduce their active area, but this implies an increase of the total number of readout channels.Another method is to replace the currently installed readout electronics by one with a shorter integration period, which reduces the sensitive time window.It will be shown how the fast and modern readout chip APV25, which was originally developed for the Silicon Strip Tracker of the Compact Muon Solenoid (CMS) project at CERN (Geneva, CH), can be used in the environment of the Belle experiment.In contrast to CMS, which uses single-sided sensors, the Belle SVD employs double-sided silicon strip detectors (DSSDs) which require significant modifications to the readout system.The main task of this thesis was the development of a prototype of such a readout system and the revision of the data acquisition and analysis software to meet the new requirements.Furthermore, an advanced data processing method which can be applied using the APV25 was implemented into the software. With this method it is possible to reconstruct the time when the particle traversed the sensor with unprecedented precision.Finally the readout system, the software and the improved data acquisition method were evaluated in several particle beam tests at the KEK and the Paul Scherer Institut (PSI, Villigen, CH) with excellent results. Since the requirements are easily met, it was decided to initiate the re\-placement of whole the Belle SVD, using the APV25 and other components of the new readout system.This thesis covers only the earlier part of my work for the Institute of High Energy Physics of the Austrian Academy of Sciences (HEPHY), which i started in 2004. Additional topics are briefly introduced in the chapter ``Summary and Outlook''. As work is ongoing, it is too early to give a final report.10