Ceramic applications in turbine engines

Development testing activities on the 1900 F-configuration ceramic parts were completed, 2070 F-configuration ceramic component rig and engine testing was initiated, and the conceptual design for the 2265 F-configuration engine was identified. Fabrication of the 2070 F-configuration ceramic parts continued, along with burner rig development testing of the 2070 F-configuration metal combustor in preparation for 1132 C (2070 F) qualification test conditions. Shakedown testing of the hot engine simulator (HES) rig was also completed in preparation for testing of a spin rig-qualified ceramic-bladed rotor assembly at 1132 C (2070 F) test conditions. Concurrently, ceramics from new sources and alternate materials continued to be evaluated, and fabrication of 2070 F-configuration ceramic component from these new sources continued. Cold spin testing of the critical 2070 F-configuration blade continued in the spin test rig to qualify a set of ceramic blades at 117% engine speed for the gasifier turbine rotor. Rig testing of the ceramic-bladed gasifier turbine rotor assembly at 108% engine speed was also performed, which resulted in the failure of one blade. The new three-piece hot seal with the nickel oxide/calcium fluoride wearface composition was qualified in the regenerator rig and introduced to engine operation wiwth marginal success

Primary immunodeficiencies due to abnormalities of the actin cytoskeleton

PURPOSE OF REVIEW: Primary immunodeficiencies (PIDs) are inherited conditions where components of the immune system are missing or dysfunctional. Over 300 genes have been causally linked to monogenic forms of PID, including a number that regulate the actin cytoskeleton. The majority of cytoskeletal defects disrupt assembly and disassembly of filamentous actin in multiple immune cell lineages impacting functions such as cell migration and adhesion, pathogen uptake, intercellular communication, intracellular signalling, and cell division. RECENT FINDINGS: In the past 24 months, new actin defects have been identified through next generation sequencing technologies. Substantial progress has also been made in understanding the pathogenic mechanisms that contribute to immunological dysfunction, and also how the cytoskeleton participates in normal physiological immune processes. SUMMARY: This review summarises recent advances in the field, raising awareness of these conditions and our current understanding of their presentation. Description of further cases and new conditions will extend the clinical phenotype of actin relation disorders, and will promote the development of more effective and targeted therapies

Gene therapy using haematopoietic stem and progenitor cells

Haematopoietic stem and progenitor cell (HSPC) gene therapy has emerged as an effective treatment modality for monogenic disorders of the blood system such as primary immunodeficiencies and β-thalassaemia. Medicinal products based on autologous HSPCs corrected using lentiviral and gammaretroviral vectors have now been approved for clinical use, and the site-specific genome modification of HSPCs using gene editing techniques such as CRISPR–Cas9 has shown great clinical promise. Preclinical studies have shown engineered HSPCs could also be used to cross-correct non-haematopoietic cells in neurodegenerative metabolic diseases. Here, we review the most recent advances in HSPC gene therapy and discuss emerging strategies for using HSPC gene therapy for a range of diseases

Impaired bone marrow homing of cytokine-activated CD34⁺ cells in the NOD/SCID model

The reduced engraftment potential of hematopoietic stem/progenitor cells (HSPCs) after exposure to cytokines may be related to the impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short-term horning of human adult CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals. We show that the loss of engraftment ability of cytokine-activated CD34+ cells is associated with a reduction in homing of colony-forming cells (CFCs) to bone marrow (BM) at 24 hours after transplantation (from median 2.8% [range, 1.9%-6.1%] to 0.3% [0.0%-0.7%]; n = 3; P < .01), coincident with an increase in CFC accumulation in the lungs (P < .01). Impaired BM homing of cytokine-activated cells was not restored by using sorted cells in G 0G1 or by inducing cell cycle arrest at the G 1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally, we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behavior of cytokine-exposed cells. We suggest that these changes in homing and, as a consequence, engraftment result from the increased migratory capacity of infused activated cells, leading to the loss of selectivity of the homing process. © 2004 by The American Society of Hematology

Gene Editing and Genotoxicity: Targeting the Off-Targets

Gene editing technologies show great promise for application to human disease as a result of rapid developments in targeting tools notably based on ZFN, TALEN, and CRISPR-Cas systems. Precise modification of a DNA sequence is now possible in mature human somatic cells including stem and progenitor cells with increasing degrees of efficiency. At the same time new technologies are required to evaluate their safety and genotoxicity before widespread clinical application can be confidently implemented. A number of methodologies have now been developed in an attempt to predict expected and unexpected modifications occurring during gene editing. This review surveys the techniques currently available as state of the art, highlighting benefits and limitations, and discusses approaches that may achieve sufficient accuracy and predictability for application in clinical settings

A Synchronous Spin-Exchange Optically Pumped NMR-Gyroscope

Inertial navigation systems generally consist of timing, acceleration, and orientation measurement units. Although much progress has been made towards developing primary timing sources such as atomic clocks, acceleration and orientation measurement units often require calibration. Nuclear Magnetic Resonance (NMR) gyroscopes, which rely on continuous measurement of the simultaneous Larmor precession of two co-located polarized noble gases, can be configured to have scale factors that depend to first order only on fundamental constants. The noble gases are polarized by spin-exchange collisions with co-located optically pumped alkali-metal atoms. The alkali-metal atoms are also used to detect the phase of precession of the polarized noble gas nuclei. Here we present a version of an NMR gyroscope designed to suppress systematic errors from the alkali-metal atoms. We demonstrate rotation rate angle random walk (ARW) sensitivity of 16 $\mu \text{Hz}/\sqrt{\text{Hz}}$ and bias instability of $\sim$800 nHz

Should Central Banks Use Distributed Ledger Technology and Digital Currencies to Advance Financial Inclusion?

This paper examines how central banks might use distributed ledger technology (“DLT”) to improve access to safe and affordable financial products and services. We consider how central banks might use DLT to advance objectives such as Anti-Money Laundering (“AML”) compliance and discuss both central bank digital currencies (“CBDC”) and private digital currencies. We consider implementation challenges for these new approaches relating to interoperability, privacy, and efficiency. We conclude that financial inclusion is far from an assured outcome: central banks must work to ensure that any new technologies they adopt or foster do not exclude marginalized groups and instead focus with intentionality on low-income households. Moreover, difficult issues with respect to financial disintermediation, credit availability, and financial stability would need to be addressed