Abstract The selection of low-radioactive construction materials is of utmost importance for the success of low-energy rare event search experiments. Besides radioactive contaminants in the bulk, the ...emanation of radioactive radon atoms from material surfaces attains increasing relevance in the effort to further reduce the background of such experiments. In this work, we present the $$^{222}$$ 222 Rn emanation measurements performed for the XENON1T dark matter experiment. Together with the bulk impurity screening campaign, the results enabled us to select the radio-purest construction materials, targeting a $$^{222}$$ 222 Rn activity concentration of $$10\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ 10 μ Bq / kg in $$3.2\,\mathrm{t}$$ 3.2 t of xenon. The knowledge of the distribution of the $$^{222}$$ 222 Rn sources allowed us to selectively eliminate problematic components in the course of the experiment. The predictions from the emanation measurements were compared to data of the $$^{222}$$ 222 Rn activity concentration in XENON1T. The final $$^{222}$$ 222 Rn activity concentration of $$(4.5\pm 0.1)\,\mathrm{\,}\upmu \mathrm{Bq}/\mathrm{kg}$$ ( 4.5 ± 0.1 ) μ Bq / kg in the target of XENON1T is the lowest ever achieved in a xenon dark matter experiment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Silicon Photomultipliers as photosensors for liquid xenon detectors are an attractive alternative to photomultiplier tubes: liquid xenon detectors employed in low background experiments or compact ...Compton cameras can take advantage of the small sensor mass and dimensions, the larger light collection coming from a more packed tiling of the readout plane, and possibly a smaller cost per area. We investigate the operation in liquid xenon of samples developed by Ketek GmbH. To provide sensitivity to the liquid xenon scintillation light wavelength, 178 nm, the inactive entrance layer of the device has been thinned. The operation of such devices at temperatures as low as -100°C has been verified, characterizing dark count rate and after-pulsing as well. In order to not deteriorate the liquid xenon purity, we selected a substrate and a bonding adhesive measuring the outgassing properties of the parts. Finally, we realized a test station to assess the photon detection efficiency at a wavelength of 178 nm. In a cryogenic vacuum-insulated vessel an 241 Am α-source and up to four samples are immersed in liquid xenon, allowing an event-by-event comparison of the response of three Silicon Photomultipliers and a 1" Photomultiplier Tube used as reference.
An internal tandem duplication in the fms-like tyrosine kinase 3 gene (FLT3/ITD) is associated with poor prognosis in acute myeloid leukemia (AML), but the impact of mutant level, size, and ...interaction with nucleophosmin 1 (NPM1) mutations remains controversial. We evaluated these characteristics in a large cohort of young adult AML patients. There was a highly significant trend for worsening in relapse risk (RR) and overall survival (OS) with increasing FLT3/ITD mutant level (P < .001 for both), and even in the low level mutant group (1%-24% of total FLT3 alleles), RR was significantly worse than in the FLT3 wild-type (WT) group (P < .001). In multivariate analysis, mutant level was the most powerful prognostic factor for RR. Mutant size and number had no significant impact on outcome. The beneficial impact of an NPM1 mutation on RR and OS was seen in FLT3/ITD+ as well as FLT3/WT patients; both markers were highly significant independent predictors of outcome (P < .001). Stratification using both markers identified 3 prognostic groups: good (FLT3/ITD−NPM1+), intermediate (FLT3/ITD−NPM1− or FLT3/ITD+NPM1+), and poor (FLT3/ITD+NPM1−). Patients with high FLT3/ITD mutant level (greater than 50%) or FLT3/ITD+ in the absence of an NPM1 mutation may be good candidates for more experimental therapeutic approaches.
IntroductionThe pathogenesis of atopic diseases is highly complex, and the exact mechanisms leading to atopic dermatitis (AD) onset in infants remain mostly enigmatic. In addition to an ...interdependent network of components of skin development in young age and skin barrier dysfunction underlying AD development that is only partially understood, a complex interplay between environmental factors and lifestyle habits with skin barrier and immune dysregulation is suspected to contribute to AD onset. This study aims to comprehensively evaluate individual microbiome and immune responses in the context of environmental determinants related the risk of developing AD in the first 4 years of a child’s life.Methods and analysesThe ‘Munich Atopic Prediction Study’ is a comprehensive clinical and biological investigation of a prospective birth cohort from Munich, Germany. Information on pregnancy, child development, environmental factors, parental exposures to potential allergens and acute or chronic diseases of children and parents are collected by questionnaires together with a meticulous clinical examination by trained dermatologists focusing on allergies, skin health, and in particular signs of AD at 2 months after birth and then every 6 months. In addition, skin barrier functions are assessed through cutometry, corneometry and transepidermal water loss at every visit. These measurements are completed with allergy diagnostics and extensive microbiome analyses from stool and skin swabs as well as transcriptome analyses using skin microbiopsies.The aim is to assess the relevance of different known and yet unknown risk factors of AD onset and exacerbations in infants and to identify possible accessible and robust biomarkers.Ethics and disseminationThe study is approved by the Ethical Committee of the Medical Faculty of the Technical University of Munich (reference 334/16S). All relevant study results will be presented at national and international conferences and in peer-reviewed journals.
The apparition of adaptive immunity in
correlates with the expansion of the E-protein family to encompass E2-2, HEB, and E2A. Within the family, E2-2 and HEB are more closely evolutionarily related ...but their concerted action in hematopoiesis remains to be explored. Here we show that the combined disruption of E2-2 and HEB results in failure to express the early lymphoid program in Common lymphoid precursors (CLPs) and a near complete block in B-cell development. In the thymus, Early T-cell progenitors (ETPs) were reduced and T-cell development perturbed, resulting in reduced CD4 T- and increased γδ T-cell numbers. In contrast, hematopoietic stem cells (HSCs), erythro-myeloid progenitors, and innate immune cells were unaffected showing that E2-2 and HEB are dispensable for the ancestral hematopoietic lineages. Taken together, this E-protein dependence suggests that the appearance of the full
E-protein repertoire was critical to reinforce the gene regulatory circuits that drove the emergence and expansion of the lineages constituting humoral immunity.
Abstract
The Phase-I trigger readout electronics upgrade of the ATLAS
Liquid Argon calorimeters enhances the
physics reach of the experiment during the upcoming operation at
increasing Large Hadron ...Collider luminosities.
The new system, installed during the second Large Hadron Collider Long Shutdown,
increases the trigger readout granularity by up to a factor of ten
as well as its precision and range.
Consequently, the background rejection at trigger level is improved
through enhanced filtering algorithms utilizing the additional information
for topological discrimination of electromagnetic and hadronic shower shapes.
This paper presents the final designs of the new electronic elements,
their custom electronic devices, the procedures
used to validate their proper functioning, and the performance achieved
during the commissioning of this system.
The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, ...transcriptional regulators maintaining Foxp3 transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression. Under homeostatic conditions, Treg cells expressed high levels of the E47 antagonist Id3, thus restricting E47 activity and maintaining Foxp3 expression. In contrast, stimulation of Id3-deficient or E47-overexpressing Treg cells resulted in the loss of Foxp3 expression in a subset of Treg cells in vivo and in vitro. Mechanistic analysis indicated that E47 activated expression of the transcription factor Spi-B and the suppressor of cytokine signaling 3 (SOCS3), which both downregulated Foxp3 expression. These findings demonstrate that the balance of Id3 and E47 controls the maintenance of Foxp3 expression in Treg cells and, thus, contributes to Treg cell plasticity.
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•Id3−/− Treg cells lose expression of Foxp3 upon stimulation•The balance of Id3 and E47 controls Foxp3 transcription in established Treg cells•High E47 activity increases Spib and Socs3 transcription in Treg cells•Spi-B and SOCS3 repress Foxp3 expression
Stable Foxp3 expression is instrumental for Treg cell function. Rauch et al. found that the transcriptional regulator Id3 maintains Foxp3 transcription in established Treg cells by restricting E47 transcription factor activity. They suggest that a dynamic modulation of the Id3-E47 balance could transiently alter Treg cell function during immune responses.
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