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Novel concepts employing autologous, ex vivo expanded natural regulatory T cells (nTreg) for adoptive transfer has potential to prevent organ rejection after kidney transplantation. However, the impact of dialysis and maintenance immunosuppression on the nTreg phenotype and peripheral survival is not well understood, but essential when assessing patient eligibility. The current study investigates regulatory T-cells in dialysis and kidney transplanted patients and the feasibility of generating a clinically useful nTreg product from these patients. Heparinized blood from 200 individuals including healthy controls, dialysis patients with end stage renal disease and patients 1, 5, 10, 15, 20 years after kidney transplantation were analyzed. Differentiation and maturation of nTregs were studied by flow cytometry in order to compare dialysis patients and kidney transplanted patients under maintenance immunosuppression to healthy controls. CD127 expressing CD4(+)CD25(high)FoxP3(+) nTregs were detectable at increased frequencies in dialysis patients with no negative impact on the nTreg end product quality and therapeutic usefulness of the ex vivo expanded nTregs. Further, despite that immunosuppression mildly altered nTreg maturation, neither dialysis nor pharmacological immunosuppression or previous acute rejection episodes impeded nTreg survival in vivo. Accordingly, the generation of autologous, highly pure nTreg products is feasible and qualifies patients awaiting or having received allogenic kidney transplantation for adoptive nTreg therapy. Thus, our novel treatment approach may enable us to reduce the incidence of organ rejection and reduce the need of long-term immunosuppression.
Ein Deutschunterricht, der die Alltags- und Medienkultur der Schüler und Schülerinnen ernst nimmt, darf Sporttexte nicht unberücksichtigt lassen. Zu sehr ist der Sport in all seinen Facetten Teil der Lebenswelt vieler Schülerinnen und Schüler geworden. Die Frage ist nicht mehr, ob der Deutschunterricht darauf zu reagieren hat, die Frage ist vielmehr, wie er dies tun und welche Sporttexte er dabei nutzen kann.
Auch wenn die Suche nach sinnvollen Bezügen zwischen Sport und Deutschunterricht schon seit längerem intensiv betrieben wird, offenbart das vielschichtige Kulturphänomen „Sport“ immer wieder neue interessante Seiten, die es lohnen, fachdidaktisch behandelt zu werden.
Die zehn Beiträge in diesem Band verstehen sich als Unterrichtsanregungen für den kompetenzorientierten Deutschunterricht. Sie bedienen Betrachtungen zum Sport aus literarischer, sprachlicher und medialer Perspektive. Die theoretisch-begrifflichen Aspekte der jeweiligen Themen werden soweit behandelt, wie sie für das Verständnis erforderlich sind. Im Zentrum vieler Beiträge stehen Unterrichtsszenarien mit kommentierten Texten und Aufgaben, die für die Unterrichtsvorbereitung oder für den Unterricht selbst genutzt werden können.
A seismological network was operated at the junction of the aseismic Walvis Ridge with the northwestern Namibian coast. We mapped crustal thickness and bulk V-p/V-s ratio by the H-k analysis of receiver functions. In the Damara Belt, the crustal thickness is similar to 35km with a V-p/V-s ratio of <1.75. The crust is similar to 30km thick at the coast in the Kaoko Belt. Strong variations in crustal thickness and V-p/V-s ratios are found at the landfall of the Walvis Ridge. Here and at similar to 150km northeast of the coast, the crustal thickness increases dramatically reaching 44km and the V-p/V-s ratios are extremely high (similar to 1.89). These anomalies are interpreted as magmatic underplating produced by the mantle plume during the breakup of Gondwana. The area affected by the plume is smaller than 300km in diameter, possibly ruling out the existence of a large plume head under the continent during the breakup.
PaRDeS. Zeitschrift der Vereinigung für Jüdische Studien e. V., möchte die fruchtbare und facettenreiche Kultur des Judentums sowie seine Berührungspunkte zur Umwelt in den unterschiedlichen Bereichen dokumentieren. Daneben dient die Zeitschrift als Forum zur Positionierung der Fächer Jüdische Studien und Judaistik innerhalb des wissenschaftlichen Diskurses sowie zur Diskussion ihrer historischen und gesellschaftlichen Verantwortung.
Solid organ transplant (SOT) recipients receive therapeutic immunosuppression that compromises their immune response to infections and vaccines. For this reason, SOT patients have a high risk of developing severe coronavirus disease 2019 (COVID-19) and an increased risk of death from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Moreover, the efficiency of immunotherapies and vaccines is reduced due to the constant immunosuppression in this patient group. Here, we propose adoptive transfer of SARS-CoV-2-specific T cells made resistant to a common immunosuppressant, tacrolimus, for optimized performance in the immunosuppressed patient. Using a ribonucleoprotein approach of CRISPR-Cas9 technology, we have generated tacrolimus-resistant SARS-CoV-2-specific T cell products from convalescent donors and demonstrate their specificity and function through characterizations at the single-cell level, including flow cytometry, single-cell RNA (scRNA) Cellular Indexing of Transcriptomes and Epitopes (CITE), and T cell receptor (TCR) sequencing analyses. Based on the promising results, we aim for clinical validation of this approach in transplant recipients. Additionally, we propose a combinatory approach with tacrolimus, to prevent an overshooting immune response manifested as bystander T cell activation in the setting of severe COVID-19 immunopathology, and tacrolimus-resistant SARS-CoV-2-specific T cell products, allowing for efficient clearance of viral infection. Our strategy has the potential to prevent severe COVID-19 courses in SOT or autoimmunity settings and to prevent immunopathology while providing viral clearance in severe non-transplant COVID-19 cases.
Das 11. Herbsttreffen Patholinguistik mit dem Schwerpunktthema »Gut gestimmt: Diagnostik und Therapie bei Dysphonie« fand am 18.11.2017 in Potsdam statt. Das Herbsttreffen wird seit 2007 jährlich vom Verband für Patholinguistik e.V. (vpl) durchgeführt. Der vorliegende Tagungsband beinhaltet die Hauptvorträge zum Schwerpunktthema sowie Beiträge zu den Kurzvorträgen »Spektrum Patholinguistik« und der Posterpräsentationen zu weiteren Themen aus der sprachtherapeutischen Forschung und Praxis.
The 2010 very high energy gamma-ray flare and 10 years ofmulti-wavelength oservations of M 87
(2012)
The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
Background:
From birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family's socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration.
Method:
We used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children's school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high)
Results:
Family SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation.
Conclusion:
Family SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course.
Purpose
Kettle holes are small inland water bodies known to be dominated by terrigenous material; however, the processes and structures that drive the enrichment and depletion of specific geochemical elements in the water column and kettle hole sediment remain unclear. We hypothesized that the mobile elements (Ca, Fe, K, P) behave different from each other in their transport, intermediate soil retention, and final accumulation in the kettle hole sediment.
Methods
Topsoils from transects spanning topographic positions from erosional to depositional areas, sediment cores, shallow groundwater, and kettle hole water of two glacial kettle holes in NE Germany (Rittgarten (RG) and Kraatz (KR)) were collected. The Fe, Ca, K, and total P (TP) concentrations were quantified and additionally the major anions in shallow groundwater and kettle hole water. The element-specific mobilization, relocation, and, finally, accumulation in the sediment were investigated by enrichment factors. Furthermore, a piper diagram was used to estimate groundwater flow directions and pond-internal processes.
Results
At KR only, the upper 10 cm of the kettle hole sediment reflected the relative element composition of the eroded terrestrial soils. The sediment from both kettle holes was enriched in Ca, Fe, K, and P compared to topsoils, indicating several possible processes including the input of clay and silt sized particles enriched in these elements, fertilizer input, and pond-internal processes including biogenic calcite and hydroxyapatite precipitation, Fe-P binding (KR), FeSx formation (RG), and elemental fixation and deposition via floating macrophytes (RG). High Ca concentrations in the kettle hole water indicated a high input of Ca from shallow groundwater inflow, while Ca precipitation in the kettle hole water led to lower Ca concentration in groundwater outflow.
Conclusions
The considerable element losses in the surrounding soils and the inputs into the kettle holes should be addressed by comprehensive soil and water protection measures, i.e., avoiding tillage, fertilizing conservatively, and creating buffer zones.