Vibrational Microfeeding of Polymer and Metal Powders for Locally Graded Properties in Powder-Based Additive Manufacturing

Subject of this work is the contact mechanical properties and flowability of polymer and metal powders when they are dispensed on the surface of a powder bed for use in laser-based powder bed fusion in additive manufacturing. Generating local part properties in metal as well as polymer-based powder bed fusion processes is of high interest, so an approach is made to locally add additives by a vibrational microfeeding system for metal and polymer powders. To realize a controlled powder discharge, the behavior of additives, which are dropped on a surface and on a powder bed is analyzed. Influencing factors for mass flow of the powders will be excitation frequency, excitation amplitude and capillary diameter on the side of experimental setup as well as particle size distribution and physical properties on the material side

Long-term observation reveals high-frequency engraftment of human acute myeloid leukemia in immunodeficient mice

Repopulation of immunodeficient mice remains the primary method for functional assessment of human acute myeloid leukemia. Published data report engraftment in ~40-66% of cases, mostly of intermediate- or poor-risk subtypes. Here we report that extending follow-up beyond the standard analysis endpoints of 10 to 16 weeks after transplantation permitted leukemic engraftment from nearly every case of xenotransplanted acute myeloid leukemia (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune pheno-types and genetic signatures when compared to corresponding pre-transplant cells and, furthermore, were able to induce leukemia in re-transplantation assays. Importantly, bone marrow biopsies taken at standardized time points failed to detect leukemic cells in 11/18 of cases that later showed robust engraftment (61%, termed "long-latency engrafters"), indicating that leukemic cells can persist over months at undetectable levels without losing disease-initiating properties. Cells from favorable-risk leukemia subtypes required longer to become detectable in NOD/SCID/IL2Rγ; null; mice (27.5±9.4 weeks) than did cells from intermediate-risk (21.9±9.4 weeks,; P; <0.01) or adverse-risk (17±7.6 weeks;; P; <0.0001) subtypes, explaining why the engraftment of the first was missed with previous protocols. Mechanistically, leukemic cells engrafting after a prolonged latency showed inferior homing to the bone marrow. Finally, we applied our model to favorable-risk acute myeloid leukemia with inv(16); here, we showed that CD34; +; (but not CD34; -; ) blasts induced robust, long-latency engraftment and expressed enhanced levels of stem cell genes. In conclusion, we provide a model that allows; in vivo; mouse studies with a wide range of molecular subtypes of acute myeloid leukemia subtypes which were previously considered not able to engraft, thus enabling novel insights into leukemogenesis

Automating compositional safety analysis using a failure type taxonomy for component fault trees

Safety assurance is a major challenge in the design of today's complex embedded systems and future Cyber-physical systems. Changes in a system's architectural design invalidate former safety analyses and require a manual adaptation of related safety analysis models in order to restore consistency. In this work, we present an approach for automating the compositional assembly of Component Fault Trees by automatically generating mappings between their input and output failure modes. Therefore, we propose a taxonomy of failure types for annotating model elements and deriving a model of the failure propagation. This way, automatic and system-wide safety analyses can be executed and easily repeated after making modifications to the system's architecture. We demonstrate the feasibility of our approach using an example ethylene vaporization unit from an industrial domain

Structural and optical characterization of Si quantumdots in a SiC matrix

Amorphous hydrogenated Si1-xCx / SiC multilayers consisting of alternating Si1-xCx and stoichiometric SiC layers were prepared using Plasma Enhanced Chemical Vapour Deposition (PECVD). Annealing at temperatures up to 1100°C was done targeting the size controlled crystallization of Si nanocrystals (NCs) in a SiC matrix. The influence of annealing temperature on the nanostructure of the multilayers was studied using Glancing Incidence X-ray Diffraction (GIXRD), Raman spectroscopy and Transmission Electron Microscopy (TEM). GIXRD reveal the crystallization of Si and SiC, when annealing temperatures exceed 900°C. The crystallization of Si and SiC was confirmed by TEM bright field imaging and electron diffraction. Annealing at 900°C, leads to the formation of Si NCs with a size of 3 nm, whereas the SiC NCs also have a size of 3 nm. However, a large amount of Si is still amorphous as shown by Raman spectroscopy. Annealing at temperatures exceeding 900°C reduces the amorphous phase and a further growth of Si NCs occurs

Photocatalytic Arylation of P4 and PH3: Reaction Development Through Mechanistic Insight

Detailed 31P{1H} NMR spectroscopic investigations provide deeper insight into the complex, multi-step mechanisms involved in the recently reported photocatalytic arylation of white phosphorus (P4). Specifically, these studies have identified a number of previously unrecognized side products, which arise from an unexpected non-innocent behavior of the commonly employed terminal reductant Et3N. The different rate of formation of these products explains discrepancies in the performance of the two most effective catalysts, [Ir(dtbbpy)(ppy)2][PF6] (dtbbpy=4,4′-di-tert-butyl-2,2′-bipyridine) and 3DPAFIPN. Inspired by the observation of PH3 as a minor intermediate, we have developed the first catalytic procedure for the arylation of this key industrial compound. Similar to P4 arylation, this method affords valuable triarylphosphines or tetraarylphosphonium salts depending on the steric profile of the aryl substituents

Advances in component fault trees

Component Fault Trees (CFTs) were invented in 2003 as a compositional extension to fault trees to better reflect the technical architecture of a system in its safety analysis model. Since then, a lot of research has been contributed regarding semantic extensions, evaluation techniques, and tighter linking between system and safety models. This paper addresses three main objectives. First, we summarize the most important contributions and shape a vision of better integrated system modeling and safety analysis. Second, we push forward standardization and sketch a new evaluation scheme for quantitative analysis using mdd. Lastly, an outlook on future improvement ideas is given to make CFTs a viable technique for loosely coupled systems and Cyber-Physical Systems

Long-term observation reveals high-frequency engraftment of human acute myeloid leukemia in immunodeficient mice

Repopulation of immunodeficient mice remains the primary method for functional assessment of human acute myeloid leukemia. Published data report engraftment in ~40-66% of cases, mostly of intermediate- or poor-risk subtypes. Here we report that extending follow-up beyond the standard analysis endpoints of 10 to 16 weeks after transplantation permitted leukemic engraftment from nearly every case of xenotransplanted acute myeloid leukemia (18/19, ~95%). Xenogeneic leukemic cells showed conserved immune pheno-types and genetic signatures when compared to corresponding pre-transplant cells and, furthermore, were able to induce leukemia in re-transplantation assays. Importantly, bone marrow biopsies taken at standardized time points failed to detect leukemic cells in 11/18 of cases that later showed robust engraftment (61%, termed "long-latency engrafters"), indicating that leukemic cells can persist over months at undetectable levels without losing disease-initiating properties. Cells from favorable-risk leukemia subtypes required longer to become detectable in NOD/SCID/IL2Rγ; null; mice (27.5±9.4 weeks) than did cells from intermediate-risk (21.9±9.4 weeks,; P; <0.01) or adverse-risk (17±7.6 weeks;; P; <0.0001) subtypes, explaining why the engraftment of the first was missed with previous protocols. Mechanistically, leukemic cells engrafting after a prolonged latency showed inferior homing to the bone marrow. Finally, we applied our model to favorable-risk acute myeloid leukemia with inv(16); here, we showed that CD34; +; (but not CD34; -; ) blasts induced robust, long-latency engraftment and expressed enhanced levels of stem cell genes. In conclusion, we provide a model that allows; in vivo; mouse studies with a wide range of molecular subtypes of acute myeloid leukemia subtypes which were previously considered not able to engraft, thus enabling novel insights into leukemogenesis

Retained functional normal and preleukemic HSCs at diagnosis are associated to good prognosis in DNMT3Amut NPM1mut AMLs

AML is a heterogeneous disease characterized by high rate of relapse and mortality. While chemotherapies may eradicate blasts, they are less effective in eliminating relapse-causing Leukemic Stem Cells (LSCs). Although LSCs are usually identified as CD34+CD38- cells, there is significant heterogeneity in surface marker expression and CD34- LSCs exist particularly in NPM1mut AMLs. By analyzing diagnostic primary DNMT3AmutNPM1mut AML samples, we suggest a novel flow cytometry sorting strategy particularly useful for CD34neg AML subtypes. To enrich for LSCs independently of CD34 status, positive selection for GPR56 and negative selection for NKG2D-Ligands are employed. We demonstrate that the functional reconstitution capacity of CD34- and CD34+ LSCs as well as their transcriptomes are very similar supporting phenotypic plasticity. Furthermore, we show that while CD34+ subpopulations can contain next to LSCs also normal and/or pre-leukemic Hematopoietic Stem Cells (HSCs), this is not the case in CD34-GPR56+NKG2DL- enriched LSCs which thus can be isolated with high purity. Finally, we show that AML patients, who retain at time of diagnosis a reserve of normal and/or preleukemic HSCs in their bone marrow able to reconstitute immunocompromised mice, have significant longer relapse-free and overall survival compared to AML patients in whom functional HSCs are no longer detectable