Design and Tests of the Silicon Sensors for the ZEUS Micro Vertex Detector

To fully exploit the HERA-II upgrade,the ZEUS experiment has installed a Micro Vertex Detector (MVD) using n-type, single-sided, silicon micro-strip sensors with capacitive charge division. The sensors have a readout pitch of 120 micrometers, with five intermediate strips (20 micrometer strip pitch). The designs of the silicon sensors and of the test structures used to verify the technological parameters, are presented. Results on the electrical measurements are discussed. A total of 1123 sensors with three different geometries have been produced by Hamamatsu Photonics K.K. Irradiation tests with reactor neutrons and Co-60 photons have been performed for a small sample of sensors. The results on neutron irradiation (with a fluence of 1 x 10^{13} 1 MeV equivalent neutrons / cm^2) are well described by empirical formulae for bulk damage. The Co-60 photons (with doses up to 2.9 kGy) show the presence of generation currents in the SiO_2-Si interface, a large shift of the flatband voltage and a decrease of the hole mobility.Comment: 33 pages, 25 figures, 3 tables, accepted for publication in NIM

Cardiovascular impairment in Shiga-toxin-2-induced experimental hemolytic-uremic syndrome: a pilot study.

INTRODUCTION: Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). Most well-known aspects of the pathophysiology are secondary to microthrombotic kidney disease including hemolytic anemia and thrombocytopenia. However, extrarenal manifestations, such as cardiac impairment, have also been reported. We have investigated whether these cardiac abnormalities can be reproduced in a murine animal model, in which administration of Stx, the main virulence factor of STEC, is used to induce HUS. METHODS: Mice received either one high or multiple low doses of Stx to simulate the (clinically well-known) different disease courses. Cardiac function was evaluated by echocardiography and analyses of biomarkers in the plasma (troponin I and brain natriuretic peptide). RESULTS: All Stx-challenged mice showed reduced cardiac output and depletion of intravascular volume indicated by a reduced end-diastolic volume and a higher hematocrit. Some mice exhibited myocardial injury (measured as increases in cTNI levels). A subset of mice challenged with either dosage regimen showed hyperkalemia with typical electrocardiographic abnormalities. DISCUSSION: Myocardial injury, intravascular volume depletion, reduced cardiac output, and arrhythmias as a consequence of hyperkalemia may be prognosis-relevant disease manifestations of HUS, the significance of which should be further investigated in future preclinical and clinical studies

Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.This study was supported by the Federal Ministry of Education and Research (BMBF, Germany, FKZ 01EO1502). This work was supported, in part, by the William Harvey Research Foundation and forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit that is supported and funded by the National Institute of Health Research. This work also contributes to the Organ Protection research theme of the Barts Centre for Trauma Sciences supported by the Barts and The London Charity (Award 753/1722). JP was supported by the German Research Foundation SFB 1039. AH was supported by the Swiss National Science Foundation

Bruton's tyrosine kinase inhibition attenuates disease progression by reducing renal immune cell invasion in mice with hemolytic-uremic syndrome

Hemolytic-uremic syndrome (HUS) can occur as a complication of an infection with Shiga-toxin (Stx)-producing Escherichia coli . Patients typically present with acute kidney injury, microangiopathic hemolytic anemia and thrombocytopenia. There is evidence that Stx-induced renal damage propagates a pro-inflammatory response. To date, therapy is limited to organ-supportive strategies. Bruton’s tyrosine kinase (BTK) plays a pivotal role in recruitment and function of immune cells and its inhibition was recently shown to improve renal function in experimental sepsis and lupus nephritis. We hypothesized that attenuating the evoked immune response by BTK-inhibitors (BTKi) ameliorates outcome in HUS. We investigated the effect of daily oral administration of the BTKi ibrutinib (30 mg/kg) and acalabrutinib (3 mg/kg) in mice with Stx-induced HUS at day 7. After BTKi administration, we observed attenuated disease progression in mice with HUS. These findings were associated with less BTK and downstream phospholipase-C-gamma-2 activation in the spleen and, subsequently, a reduced renal invasion of BTK-positive cells including neutrophils. Only ibrutinib treatment diminished renal invasion of macrophages, improved acute kidney injury and dysfunction (plasma levels of NGAL and urea) and reduced hemolysis (plasma levels of bilirubin and LDH activity). In conclusion, we report here for the first time that BTK inhibition attenuates the course of disease in murine HUS. We suggest that the observed reduction of renal immune cell invasion contributes – at least in part – to this effect. Further translational studies are needed to evaluate BTK as a potential target for HUS therapy to overcome currently limited treatment options

Bi-directional Photogoniometer for the Assessment of the Luminous Properties of Fenestration Systems

Most energy saving applications of advanced fenestration systems (solar blinds, novel types of glazing and daylight redirecting devices) require a precise knowledge of their directional light transmission features. These photometric properties can be described by a Bi-directional Transmission Distribution Function (BTDF) whose experimental assessment requires appropriate equipment. A novel bi-directional transmission photogoniometer, based on digital imaging techniques, was designed and set up for that purpose. The apparatus takes advantage of a modern video image capturing device (CCD digital camera) as well as of powerful image analysis software (pattern recognition) to considerably reduce the scanning time of a BTDF measurement, in comparison to existing devices that use a conventional approach (mobile photometer). A detailed calibration and validation procedure was used to obtain optimal experimental accuracy for the device during the assessment of BTDF data. It included a spectral, a photometric and a geometrical calibration of the digital video system, as well as several additional corrections, leading to an overall relative accuracy better than 11% for BTDF data. A special effort was made to improve the user-friendliness of BTDF measurement by facilitating the data acquisition and treatment (definition of a data acquisition and electronic data format) and by offering different possibilities of BTDF visualisation (hemispherical representation, axonometric view of photometric solids, C-planes). Overall, the photometric equipment was used to assess the BTDFs of more than 20 novel fenestration products of the industrial partner of the project (Baumann-Hüppe Storen AG). The experimental data produced was successfully used by the company to optimise the visual and energy saving performance of their products, which confirms the adequacy of the novel bi-directional photogoniometer for practical building applications

Inhibition of the JAK/STAT Pathway with Baricitinib Reduces the Multiple Organ Dysfunction Caused by Hemorrhagic Shock in Rats.

OBJECTIVE: The aim of this study was to investigate (a) the effects of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway inhibitor (baricitinib) on the MODS in a rat model of hemorrhagic shock (HS) and (b) whether treatment with baricitinib attenuates the activation of JAK/STAT, NF-κB and NLRP3 caused by HS. BACKGROUND: Post-traumatic MODS, which is in part due to excessive systemic inflammation, is associated with high morbidity and mortality. The JAK/STAT pathway is a regulator of numerous growth factor and cytokine receptors and, hence, is considered a potential master regulator of many inflammatory signaling processes. However, its role in trauma-hemorrhage is unknown. METHODS: An acute HS rat model was performed to determine the effect of baricitinib on MODS. The activation of JAK/STAT, NF-κB and NLRP3 pathways were analyzed by western blotting in the kidney and liver. RESULTS: We demonstrate here for the first time that treatment with baricitinib (during resuscitation following severe hemorrhage) attenuates the organ injury and dysfunction and the activation of JAK/STAT, NF-κB and NLRP3 pathways caused by HS in the rat. CONCLUSIONS: Our results point to a role of the JAK/STAT pathway in the pathophysiology of the organ injury and dysfunction caused by trauma/hemorrhage and indicate that JAK inhibitors, such as baricitinib, may be repurposed for the treatment of the MODS after trauma and/or hemorrhage

Beam Test of Silicon Strip Sensors for the ZEUS Micro Vertex Detector

For the HERA upgrade, the ZEUS experiment has designed and installed a high precision Micro Vertex Detector (MVD) using single sided micro-strip sensors with capacitive charge division. The sensors have a readout pitch of 120 microns, with five intermediate strips (20 micron strip pitch). An extensive test program has been carried out at the DESY-II testbeam facility. In this paper we describe the setup developed to test the ZEUS MVD sensors and the results obtained on both irradiated and non-irradiated single sided micro-strip detectors with rectangular and trapezoidal geometries. The performances of the sensors coupled to the readout electronics (HELIX chip, version 2.2) have been studied in detail, achieving a good description by a Monte Carlo simulation. Measurements of the position resolution as a function of the angle of incidence are presented, focusing in particular on the comparison between standard and newly developed reconstruction algorithms.Comment: 41 pages, 21 figures, 2 tables, accepted for publication in NIM

Global long-term monitoring of the ozone layer - a prerequisite for predictions

Although the Montreal Protocol now controls the production and emission of ozone depleting substances, the timing of ozone recovery is unclear. There are many other factors affecting the ozone layer, in particular climate change is expected to modify the speed of re-creation of the ozone layer. Therefore, long-term observations are needed to monitor the further evolution of the stratospheric ozone layer. Measurements from satellite instruments provide global coverage and are supplementary to selective ground-based observations. The combination of data derived from different space-borne instruments is needed to produce homogeneous and consistent long-term data records. They are required for robust investigations including trend analysis. For the first time global total ozone columns from three European satellite sensors GOME (ERS-2), SCIAMACHY (ENVISAT), and GOME-2 (METOP-A) are combined and added up to a continuous time series starting in June 1995. On the one hand it is important to monitor the consequences of the Montreal Protocol and its amendments; on the other hand multi-year observations provide the basis for the evaluation of numerical models describing atmospheric processes, which are also used for prognostic studies to assess the future development. This paper gives some examples of how to use satellite data products to evaluate model results with respective data derived from observations, and to disclose the abilities and deficiencies of atmospheric models. In particular, multi-year mean values derived from the Chemistry-Climate Model E39C-A are used to check climatological values and the respective standard deviations