The XENON1T experiment aims for the direct detection of dark matter in a detector filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by ...radioactive decays inside the detector has to be sufficiently low. One major contributor is the
β
-emitter
85
Kr which is present in the xenon. For XENON1T a concentration of natural krypton in xenon
nat
Kr
/
Xe
<
200
ppq
(parts per quadrillion,
1
ppq
=
10
-
15
mol
/
mol
) is required. In this work, the design, construction and test of a novel cryogenic distillation column using the common McCabe–Thiele approach is described. The system demonstrated a krypton reduction factor of
6.4
·
10
5
with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of
nat
Kr
/
Xe
<
26
ppq
is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN.
We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber ...with a fiducial mass of (1.30±0.01) ton, resulting in a 1.0 ton yr exposure. The energy region of interest, 1.4,10.6 keV_{ee} (4.9,40.9 keV_{nr}), exhibits an ultralow electron recoil background rate of 82_{-3}^{+5}(syst)±3(stat) events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6 GeV/c^{2}, with a minimum of 4.1×10^{-47} cm^{2} at 30 GeV/c^{2} and a 90% confidence level.
Phosphatidylinositol 3-kinase-gamma (PI3Kγ) is highly expressed in leukocytes and is an attractive drug target for immune modulation. Different experimental systems have led to conflicting ...conclusions regarding inflammatory and anti-inflammatory functions of PI3Kγ. Here, we report a human patient with bi-allelic, loss-of-function mutations in PIK3CG resulting in absence of the p110γ catalytic subunit of PI3Kγ. She has a history of childhood-onset antibody defects, cytopenias, and T lymphocytic pneumonitis and colitis, with reduced peripheral blood memory B, memory CD8+ T, and regulatory T cells and increased CXCR3+ tissue-homing CD4 T cells. PI3Kγ-deficient macrophages and monocytes produce elevated inflammatory IL-12 and IL-23 in a GSK3α/β-dependent manner upon TLR stimulation. Pik3cg-deficient mice recapitulate major features of human disease after exposure to natural microbiota through co-housing with pet-store mice. Together, our results emphasize the physiological importance of PI3Kγ in restraining inflammation and promoting appropriate adaptive immune responses in both humans and mice.
•Mechanical testing of Al2024 and Al7075 specimens using various test configurations leading to different failure modes are reported.•A meticulous method for constructing the damage initiation curves ...and their implementation in the finite element framework is given.•The ingredients required to predict failure initiation using four different ductile failure criteria are computed using finite element modelling and a comparison between the different criteria is reported.•A set of independent, complex mechanical experiments that challenge the failure criteria’s prediction capabilities following initial calibration is performed.
Predicting ductile failure in engineering structural components has been an active research topic for decades. Although the micro-mechanical phenomena that govern ductile failure are well understood, and many failure criteria proposed, a leading criterion has yet to be agreed upon. In the current study, four different ductile failure criteria were implemented in the finite element framework and used to study the ductile failure process of Al2024 and Al7075 specimens. The failure criteria included stress based, energy based and strain based formulations. Several different sets of experiments were first used to determine the different model parameters required to predict failure initiation. Then these same parameters were used to predict failure initiation for a different set of experiments with different geometries and under a complex stress and strain state. A critical analysis of the performance of the different ductile failure criteria was then conducted. It is shown that, while the stress based criteria fail to provide accurate predictions for the general loading case, the energy based and strain based criteria perform well and predict both the failure load and crack location.
Abstract Background Chronic granulomatous disease (CGD) is characterized by recurrent life-threatening bacterial and fungal infections and aberrant inflammation. Mutations in CYBB cause X-linked CGD ...and account for 65%-70% of cases in western countries. Objective To understand the clinical manifestations associated with the X-linked CGD carrier state. Methods We undertook a comprehensive retrospective study of 162 affected females. We examined dihydrorhodamine oxidation (DHR) data for percent (%) X chromosome inactivation. We correlated lyonization (%DHR+) with clinical features. Where possible, we followed %DHR+ levels over time. Results Clinical data were available for 93 females: The %DHR+ was 46% (mean) and 47% (median)(SD=24). Using %DHR+ as the criterion for X inactivation, 78% of patients had levels of inactivation 20-80%, suggesting random inactivation that was independent of age. In contrast, carriers with CGD-type infections had median %DHR+ of 8% (n=14, range 0.06-48 %); those with only autoimmune or inflammatory manifestations (AIM) had median %DHR+ of 39% (n=31, range 7.4-74%). Those with both infections and autoimmunity had low %DHR+ (n=6, range=3-14%). A %DHR+ <10 % was strongly associated with infections (OR:99). Strong association persisted when the %DHR+ was <20% (OR=12) Autoimmunity was not associated with %DHR+. In two sets of identical twins the %DHR+ populations tracked closely over time. While the %DHR+ populations were very similar between sisters, those between mothers and daughters were unrelated. Conclusions A low %DHR+ strongly predicts infection risk in X-linked CGD carriers, while the carrier state itself is associated with autoimmunity.
A coupled finite element analysis in conjunction with experiments was used to investigate hot co-extrusion of a novel composite Mg AZ80/Al 1100 billet assembly. To validate the computational model, ...results from both radiography, and metallography were used.
It is demonstrated that the billet configuration proposed in this study results in a uniform composite rod, with no indication of cracks, tears, wavy interface surfaces or voids. The computational model is first validated by the experiments and then used to thoroughly study the thermo-mechanical fields that develop during the co-extrusion process. The interplay of the thermal and mechanical fields during the process is examined for different initial temperatures, die angle and ram velocity. It is demonstrated that using the proposed billet assembly, constant compressive radial stress develops across the magnesium core, leading to sound-proportional flow conditions.
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