Staphylococcus aureus α-Toxin Triggers the Synthesis of B-Cell Lymphoma 3 by Human Platelets

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced αIIbβ3-dependent aggregation (EC50 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis

Digitalisierung beruflicher Lern- und Arbeitsprozesse. Impulse aus der Bauwirtschaft und anderen gewerblich-technischen Sektoren

Der Sammelband stellt aktuelle Ansätze zum digital unterstützten beruflichen Lernen dar. Die Beiträge geben Einblicke in die dynamische Entwicklung der Schnittstellen von Erwerbsarbeit und beruflicher Aus-, Fort- und Weiterbildung im Kontext der Digitalisierung Arbeits- und Lernmitteln. Der Band schließt damit an die 2019 ebenfalls im Universitätsverlag der Technischen Universität Berlin erschienene Publikation „Berufsbildung am Bau digital“ (hrsg. von Bernd Mahrin und Johannes Meyser) an. Das erste Kapitel erörtert grundsätzliche didaktische Fragen zu digital unterstütztem Lernen und Arbeiten einschließlich der Rahmenbedingungen. Im zweiten Kapitel schließen sich Beiträge zur Kapazitätsentwicklung, zu Standards und zu digitalen Werkzeugen an. Das dritte Kapitel widmet sich konkreten Einzellösungen mit starkem Praxisbezug und hohem Transferpotenzial zum digitalisierten Arbeiten und Lernen im Bausektor und im Metallbereich. Das abschließende vierte Kapitel präsentiert übergreifend nutzbare und frei zugängliche Online-Angebote wie einen Medienpool für Bildungszwecke, eine Lernmedien-Datenbank und ein hybrides Lernsystem mit virtuellem 3D-Gebäudemodell. Das Buch ist entstanden im Rahmen des durch das Bundesministerium für Bildung und Forschung und den Europäischen Sozialfonds geförderten Projektes DigiBAU – Digitales Bauberufliches Lernen und Arbeiten. (DIPF/Orig.)The anthology presents current approaches to digitally supported professional learning. The articles provide insights into the dynamic development of the interfaces between gainful employment and vocational training and further education in the context of digitization of work and learning aids. The volume is thus connected to the publication “Berufsbildung am Bau digital” (edited by Bernd Mahrin and Johannes Meyser), which was published in 2019 by the University Press of the Technische Universität Berlin. The first chapter discusses fundamental didactic questions about digitally supported learning and working, including the framework conditions. The second chapter picks contributions on capacity development, standards, and digital tools out as central themes. The third chapter is dedicated to concrete specific solutions with strong practical relevance and high transfer potential for digitized work and learning in the construction sector and in the metal sector. The final fourth chapter presents comprehensive and freely accessible online offers such as a media pool for educational purposes, a learning media database and a hybrid learning system with a virtual 3D building model. The book was created as part of the DigiBAU project - digital vocational learning and working in the field of construction - funded by the German Federal Ministry of Education and Research and the European Social Fund. (DIPF/Orig.

Impact of improved attenuation correction on 18F-FDG PET/MR hybrid imaging of the heart.

PURPOSE:The aim of this study was to evaluate and quantify the effect of improved attenuation correction (AC) including bone segmentation and truncation correction on 18F-Fluordesoxyglucose cardiac positron emission tomography/magnetic resonance (PET/MR) imaging. METHODS:PET data of 32 cardiac PET/MR datasets were reconstructed with three different AC-maps (1. Dixon-VIBE only, 2. HUGE truncation correction and bone segmentation, 3. MLAA). The Dixon-VIBE AC-maps served as reference of reconstructed PET data. 17-segment short-axis polar plots of the left ventricle were analyzed regarding the impact of each of the three AC methods on PET quantification in cardiac PET/MR imaging. Non-AC PET images were segmented to specify the amount of truncation in the Dixon-VIBE AC-map serving as a reference. All AC-maps were evaluated for artifacts. RESULTS:Using HUGE + bone AC results in a homogeneous gain of ca. 6% and for MLAA 8% of PET signal distribution across the myocardium of the left ventricle over all patients compared to Dixon-VIBE AC only. Maximal relative differences up to 18% were observed in segment 17 (apex). The body volume truncation of -12.7 ± 7.1% compared to the segmented non-AC PET images using the Dixon-VIBE AC method was reduced to -1.9 ± 3.9% using HUGE and 7.8 ± 8.3% using MLAA. In each patient, a systematic overestimation in AC-map volume was observed when applying MLAA. Quantitative impact of artifacts showed regional differences up to 6% within single segments of the myocardium. CONCLUSIONS:Improved AC including bone segmentation and truncation correction in cardiac PET/MR imaging is important to ensure best possible diagnostic quality and PET quantification. The results exhibited an overestimation of AC-map volume using MLAA, while HUGE resulted in a more realistic body contouring. Incorporation of bone segmentation into the Dixon-VIBE AC-map resulted in homogeneous gain in PET signal distribution across the myocardium. The majority of observed AC-map artifacts did not significantly affect the quantitative assessment of the myocardium

Coordination of Metabolism and Virulence Factors Expression of Extraintestinal Pathogenic Escherichia coli Purified from Blood Cultures of Patients with Sepsis

One of the trademarks of extraintestinal pathogenic Escherichia coli is adaptation of metabolism and basic physiology to diverse host sites. However, little is known how this common human pathogen adapts to permit survival and growth in blood. We used label-free quantitative proteomics to characterize five E. coli strains purified from clinical blood cultures associated with sepsis and urinary tract infections. Further comparison of proteome profiles of the clinical strains and a reference uropathogenic E. coli strain 536 cultivated in blood culture and on two different solid media distinguished cellular features altered in response to the pathogenically relevant condition. The analysis covered nearly 60% of the strains predicted proteomes, and included quantitative description based on label-free intensity scores for 90% of the detected proteins. Statistical comparison of anaerobic and aerobic blood cultures revealed 32 differentially expressed proteins (1.5% of the shared proteins), mostly associated with acquisition and utilization of metal ions critical for anaerobic or aerobic respiration. Analysis of variance identified significantly altered amounts of 47 proteins shared by the strains (2.7%), including proteins involved in vitamin B6 metabolism and virulence. Although the proteomes derived from blood cultures were fairly similar for the investigated strains, quantitative proteomic comparison to the growth on solid media identified 200 proteins with substantially changed levels (11% of the shared proteins). Blood culture was characterized by up-regulation of anaerobic fermentative metabolism and multiple virulence traits, including cell motility and iron acquisition. In a response to the growth on solid media there were increased levels of proteins functional in aerobic respiration, catabolism of medium-specific carbon sources and protection against oxidative and osmotic stresses. These results demonstrate on the expressed proteome level that expression of extraintestinal virulence factors and overall cellular metabolism closely reflects specific growth conditions

Improving the CT (140 kVp) to PET (511 keV) conversion in PET/MR Hardware Component Attenuation Correction

PurposeToday, attenuation correction (AC) of positron emission tomography/magnetic resonance (PET/MR) hardware components is performed by using an established method from PET/CT hybrid imaging. As shown in previous studies, the established mathematical conversion from computed tomography (CT) to PET attenuation coefficients may, however, lead to incorrect results in PET quantification when applied to AC of hardware components in PET/MR. The purpose of this study is to systematically investigate the attenuating properties of various materials and electronic components frequently used in the context of PET/MR hybrid imaging. The study, thus, aims at improving hardware component attenuation correction in PET/MR.Materials and methodsOverall, 38 different material samples were collected; a modular phantom was used to for CT, PET, and PET/MR scanning of all samples. Computed tomography‐scans were acquired with a tube voltage of 140 kVp to determine Hounsfield Units (HU). PET transmission scans were performed with 511 keV to determine linear attenuation coefficients (LAC) of all materials. The attenuation coefficients were plotted to obtain a HU to LAC correlation graph, which was then compared to two established conversions from literature. Hardware attenuation maps of the different materials were created and applied to PET data reconstruction following a phantom validation experiment. From these measurements, PET difference maps were calculated to validate and compare all three conversion methods.ResultsFor each material, the HU and corresponding LAC could be determined and a bi‐linear HU to LAC conversion graph was derived. The corresponding equation was urn:x-wiley:00942405:media:mp14091:mp14091-math-0001 . While the two established conversions lead to a mean quantification PET bias of 4.69% ± 0.27% and −2.84% ± 0.72% in a phantom experiment, PET difference measurements revealed only 0.5 % bias in PET quantification when applying the new conversion resulting from this study.ConclusionsAn optimized method for the conversion of CT to PET attenuation coefficients has been derived by systematic measurement of 38 different materials. In contrast to established methods, the new conversion also considers highly attenuating materials, thus improving attenuation correction of hardware components in PET/MR hybrid imaging

Towards fast whole-body PET/MR: Investigation of PET image quality versus reduced PET acquisition times.

PURPOSE:The trend towards faster acquisition protocols in whole-body positron emission tomography/magnetic resonance (PET/MR) arises the question of whether short PET data acquisition protocols in a whole-body multi-station context allow for reduced PET acquisition times while providing adequate PET image quality and accurate quantification parameters. The study goal is to investigate how reducing PET acquisition times affects PET image quality and quantification in whole-body PET/MR in patients with oncologic findings. METHODS:Fifty-one patients with different oncologic findings underwent a clinical whole-body 18F-Fluorodeoxyglucose PET/MR examination. PET data was reconstructed with 4, 3, 2, and 1 min/bed time intervals for each patient to simulate the effect of reduced PET acquisition times. The 4-minute PET reconstructions served as reference standard. All whole-body PET data sets were analyzed regarding image quality, lesion detectability, PET quantification and standardized uptake values. RESULTS:A total of 91 lesions were detected in the 4-minute PET reconstructions. The same number of congruent lesions was also noticed in the 3 and 2 minutes-per-bed (mpb) reconstructed images. A total of 2 lesions in 2 patients was not detected in the 1 minute PET data reconstructions due to poor image quality. Image noise in the blood pool increased from 22.2% (4 mpb) to 42.1% (1 mpb). Signal-to-noise ratio declined with shorter timeframes from 13.1 (4 mpb) to 9.3 (1 mpb). SUVmean and SUVmax showed no significant changes between 4 and 1 mpb reconstructed timeframes. CONCLUSIONS:Reconstruction of PET data with different time intervals has shown that 2 minutes acquisition time per bed position instead of 4 minutes is sufficient to provide accurate lesion detection and adequate image quality in a clinical setting, despite the trends to lower image quality with shorter PET acquisition times. This provides latitude for potential reduction of PET acquisition times in fast PET/MR whole-body examinations

Interdisciplinary engineering of cyber-physical production systems

In the context of cross-disciplinary and cross-company cooperation, several challenges in developing manufacturing systems are revealed through industrial use cases. To tackle these challenges, two propositions are used in parallel. First, coupling technical models representing different content areas facilitates the detection of boundary crossing consequences, either by using a posteriori or a priori connection. Second, it is necessary to enrich these coupled technical models with team and organizational models as interventions focusing on the collaboration between individuals and teams within broader organizational conditions. Accordingly, a combined interdisciplinary approach is proposed. The feasibility and benefits of the approach is proven with an industrial use case. The use case shows that inconsistencies among teams can be identified by coupling engineering models and that an integrated organizational model can release the modelling process from communication barriers