Design Investigation of Lunar Water Extraction

Water is an essential resource for space exploration, for both robotic and human exploration. It is foreseen that in the future, these resources can be used to produce rocket propellant by electrolyzing water into its components Hydrogen and Oxygen or by astronauts for drinking water and breathable oxygen. This Space Resource Utilisation (SRU) would reduce the cost of spacefaring significantly. Recent discoveries have confirmed the presence of ice at the Lunar south pole. In this work, which is a continuation of the work presented in [1], the design parameters of 4 types of methods for thermal water extraction on the Moon are investigated. These methods are the in-situ surface heating method, the in-situ heated rods method, and the crucible method in different variations, as can be seen in figure 1. The goal is to find the most optimal way to extract water from the lunar surface. Additionally, this poster will present some early results from the EU LUWEX project

Review of Water Capturing Devices for Lunar ISRU

The use of resources present on celestial bodies, known as In-Situ Resource Utilization (ISRU), is becoming more and more important in space exploration due to the high cost of launching mass into orbit. ISRU would enable long-term manned operations and permanent (robotic) presence on extra-terrestrial bodies. Water is considered to be one of the most important resources for further space exploration and is currently investigated for extraction and purification on the future manned Lunar base envisioned around 2025. Previous research focused on the extraction of water from regolith but little work has been done to find ways on how to capture and liquefy the water vapour after its extraction

TLR9-Dependent and Independent Pathways Drive Activation of the Immune System by Propionibacterium Acnes

Propionibacterium acnes is usually a relatively harmless commensal. However, under certain, poorly understood conditions it is implicated in the etiology of specific inflammatory diseases. In mice, P. acnes exhibits strong immunomodulatory activity leading to splenomegaly, intrahepatic granuloma formation, hypersensitivity to TLR ligands and endogenous cytokines, and enhanced resistance to infection. All these activities reach a maximum one week after P. acnes priming and require IFN-γ and TLR9. We report here the existence of a markedly delayed (1–2 weeks), but phenotypically similar TLR9-independent immunomodulatory response to P. acnes. This alternative immunomodulation is also IFN-γ dependent and requires functional MyD88. From our experiments, a role for MyD88 in the IFN-γ-mediated P. acnes effects seems unlikely and the participation of the known MyD88-dependent receptors, including TLR5, Unc93B-dependent TLRs, IL-1R and IL-18R in the development of the alternative response has been excluded. However, the crucial role of MyD88 can partly be attributed to TLR2 and TLR4 involvement. Either of these two TLRs, activated by bacteria and/or endogenously generated ligands, can fulfill the required function. Our findings hint at an innate immune sensitizing mechanism, which is potentially operative in both infectious and sterile inflammatory disorders

Reduction of matrix interferences by the combination of chaotropic salt and DMSO in a broadly applicable target-based ELISA for pharmacokinetic studies of therapeutic monoclonal antibodies

Use of a synergistic effect of DMSO together with a chaotropic salt (NaSCN or MgCl2) allowed to drastically reduce matrix interferences in an ELISA for therapeutic monoclonal antibodies. Optimum combinations were found to be 0.4 M NaSCN together with 10.0 % DMSO, and 1.0 M MgCl2 with 15.0 % DMSO. At this optimum combination, quality controls spiked with mAb at 50.0 ng/ml in eighteen individual human sera and plasmas were quantified with an overall accuracy of 102.0 %. All of these QCs fulfilled the acceptance criteria of 80.0 - 120.0 % accuracy and precision below 20.0 %. The assay was also successfully applied to the quantification of two other mAbs in human serum. Furthermore, the use of the assay was extended to preclinical species (cynomolgus monkey and rat serum). Here, the performed validation experiments confirmed the utility of the assay and demonstrated that the assay allowed quantification of mAb from 50.0 ng/ml to 100.0 μg/ml in cynomolgus monkey serum. The method has then been applied to a pharmacokinetic study in cynomolgus monkeys. In summary, this work demonstrates the efficacy of the combination of a chaotropic salt with DMSO to minimize matrix interferences in an ELISA. The robustness thus obtained allowed the successful establishment of a cost effective, target-based ELISA format for use in pharmacokinetic studies, that is easily applicable for the quantification of mAbs in various matrices such as human, cynomolgus monkey or rat serum and plasma

Differential Contribution of Toll-Like Receptors 4 and 2 to the Cytokine Response to Salmonella enterica Serovar Typhimurium and Staphylococcus aureus in Mice

The contribution of murine Toll-like receptors 2 and 4 (TLR2 and -4, respectively) to cytokine induction by heat-killed bacteria was analyzed in vitro and in vivo. Gram-negative bacteria induced cytokines primarily via TLR4; the contribution of TLR2 was only minor. Neither TLR4 nor, surprisingly, TLR2 was required in the MyD88-dependent response to Staphylococcus aureus

Delayed development of <i>P. acnes</i> effects in primed TLR9^−/− mice.

<p>Groups of WT and TLR9^−/− mice (15–20 animals/group) were primed with heat-killed <i>P. acnes</i> (20 µg/g b.w.) i.v. or remained untreated (controls; day 0). <b>A. Hypersensitivity to LPS:</b> At indicated time points after priming the animals were challenged with LPS from <i>S.a.e.</i> (0.01 µg/g b.w.), i.v. One hour and 4 h later, plasma was collected for determination of TNF-α and IFN-γ, respectively. Before challenge with LPS no detectable TNF-α or IFN-γ was found in plasma of <i>P. acnes</i>-treated mice of either one of the groups (not shown). Cumulative data of 3 different experiments are shown. *:p-value<0.05 and ***:p-value<0.001 WT compared to TLR9^−/− mice, and <i>P. acnes</i>-treated WT or <i>P. acnes</i>-treated TLR9^−/− at the indicated time point compared to untreated controls. <b>B. Splenomegaly:</b> Spleens were removed and weighted at indicated time points after treatment. Cumulative data from 4–5 experiments are shown. *:p-value<0.05 and **:p-value<0.01. <b>C. Enhanced resistance to serovar Typhimurium infection is delayed in TLR9^−/− mice:</b> 7 or 21 days after priming, the animals were infected with <i>Salmonella</i> serovar Typhimurium (200 CFU/0.2 ml PBS/i.v.). Bacterial counts in liver of unprimed and primed animals were determined 4 days after infection. One representative experiment of three is shown. *:p-value<0.05 and **:p-value<0.01.</p

LPS sensitivity of <i>P. acnes</i> primed TLR2/TLR4/TLR9^−/− mice after.

<p>Groups of TLR9^−/− and TLR2/TLR4/TLR9^−/− mice were primed with heat-killed <i>P. acnes</i> (20 µg/g b.w.) i.v. or remained untreated. Each mouse was challenged 21 days after priming with a mixture of murine recombinant IL-12 (25 ng) and murine recombinant IL-18 (100 ng). Four hours after challenge, plasma was collected for determination of IFN-γ. Before challenge, no detectable IFN-γ was found in plasma of <i>P. acnes</i>-treated mice of either one of the groups (not shown). One representative experiment of two is shown. *:p-value<0.05 and **:p-value<0.01 as compared to only rIL-12+rIL-18-treated controls.</p

Effective 'Activated PI3Kd Syndrome' -targeted therapy with PI3Kd inhibitor leniolisib

Background Gain-of-function mutations driving PI3K (phosphoinositide 3-kinase delta) enzyme activity lead to accumulation of senescent T cells, lymphadenopathy and immune-deficiency (PASLI disease), also known as Activated PI3K Syndrome (APDS). Inhibition of PI3K is a new therapeutic approach for the treatment of APDS. Methods We assessed leniolisib (CDZ173), a potent and selective PI3K inhibitor, in vitro for its effect on PI3K pathway activation induced by four APDS-causative p110δ variants in cell lines and in T cell blasts from patients. We then conducted a clinical trial with six APDS patients who completed a 12-week, open-label, multi-site, within-subject dose-escalation study of leniolisib to assess safety, pharmacokinetics and effects on lymphoproliferation and immune dysregulation. Results Expression of APDS mutant p110δ in cell lines and patient-derived lymphocytes led to increased pathway activity, measured as phosphorylation of AKT or S6, which was suppressed by leniolisib in a concentration dependent way. Oral leniolisib led to a dose-dependent reduction in PI3K/AKT pathway activity assessed ex vivo and resolved the immune dysregulation with normalization of circulating transitional and naïve B cells and reduction in PD-1+CD4+ and senescent CD57+CD8+ T cells. After 12 weeks of treatment, all patients showed amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean, range 26-57%) and 40% (mean, range: 13-65%), respectively. Conclusions Targeting hyperactive p110 in APDS patients using leniolisib was well tolerated and showed consistent laboratory and clinical improvement, including reduction in cellular immune dysfunction and lymphoproliferation (Funded by Novartis and NIAID DIR; ClinicalTrials.gov number, NCT02435173)