Development of an integrated heat pipe-thermal storage system for a solar receiver

The Organic Rankine Cycle (ORC) Solar Dynamic Power System (SDPS) is one of the candidates for Space Station prime power application. In the low Earth orbit of the Space Station approximately 34 minutes of the 94-minute orbital period is spent in eclipse with no solar energy input to the power system. For this period the SDPS will use thermal energy storage (TES) material to provide a constant power output. An integrated heat-pipe thermal storage receiver system is being developed as part of the ORC-SDPS solar receiver. This system incorporates potassium heat pipe elements to absorb and transfer the solar energy within the receiver cavity. The heat pipes contain the TES canisters within the potassium vapor space with the toluene heater tube used as the condenser region of the heat pipe. During the insolation period of the Earth orbit, solar energy is delivered to the heat pipe in the ORC-SDPS receiver cavity. The heat pipe transforms the non-uniform solar flux incident in the heat pipe surface within the receiver cavity to an essentially uniform flux at the potassium vapor condensation interface in the heat pipe. During solar insolation, part of the thermal energy is delivered to the heater tube and the balance is stored in the TES units. During the eclipse period of the orbit, the balance stored in the TES units is transferred by the potassium vapor to the toluene heater tube

Abundant and equipotent founder cells establish and maintain acute lymphoblastic leukaemia

High frequencies of blasts in primary acute lymphoblastic leukaemia (ALL) samples have the potential to induce leukaemia and to engraft mice. However, it is unclear how individual ALL cells each contribute to drive leukaemic development in a bulk transplant and the extent to which these blasts vary functionally. We used cellular barcoding as a fate mapping tool to track primograft ALL blasts in vivo. Our results show that high numbers of ALL founder cells contribute at similar frequencies to leukaemic propagation over serial transplants, without any clear evidence of clonal succession. These founder cells also exhibit equal capacity to home and engraft to different organs, although stochastic processes may alter the composition in restrictive niches. Our findings enhance the stochastic stem cell model of ALL by demonstrating equal functional abilities of singular ALL blasts and show that successful treatment strategies must eradicate the entire leukaemic cell population

The Niemann-Pick C1 and caveolin-1 proteins interact to modulate efflux of low density lipoprotein-derived cholesterol from late endocytic compartments

The Niemann-Pick C1 (NPC1) protein has a central role in regulating the efflux of lipoprotein-derived cholesterol from late endosomes/lysosomes and transport to other cellular compartments. Since the NPC1 protein has been shown to regulate the transport of cholesterol to cellular compartments enriched with the ubiquitous cholesterol-binding and transport protein caveolin-1, the present study was performed to determine whether the NPC1 and caveolin-1 proteins interact and function to modulate efflux of low density lipoprotein (LDL)-derived cholesterol from endocytic compartments. To perform these studies, normal human fibroblasts were grown in media with lipoprotein-deficient serum (LPDS) or media with LPDS supplemented with purified human LDL. The results indicated reciprocal co-immunoprecipitation and partial co-localization of the NPC1 and caveolin-1 proteins that was decreased when fibroblasts were grown in media with LDL. Consistent with interaction of the NPC1 and caveolin-1 proteins, a highly conserved caveolin-binding motif was identified within a cytoplasmic loop located adjacent to the sterol-sensing domain (SSD) of the NPC1 protein. To examine the functional relevance of this interaction, fibroblasts were transfected with caveolin-1 siRNA and found to accumulate increased amounts of LDL-derived cholesterol within late endosomes/lysosomes. Together, this report presents novel results demonstrating that the NPC1 and caveolin-1 proteins interact to modulate efflux of LDL-derived cholesterol from late endocytic compartments

Disruption of a Yeast ADE6 Gene Homolog in Ustilago maydis

A putative homolog of the Sacharromyces cereviseae ADE6 and Escherichia coli purL genes is identified near a multigenic complex, which contains two genes, sid1 and sid2, involved in a siderophore biosynthetic pathway inUstilago maydis. The putative ADE6 homolog was mutated by targeted gene disruption. The resulting mutant strains demonstrated a requirement for exogenous adenine, indicating that the U. maydis ade6 homolog is required for purine biosynthesis

The MLL-Menin Interaction is a Therapeutic Vulnerability in <em>NUP98</em>-rearranged AML

\ua9 2023 Wolters Kluwer Health. All rights reserved. Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin-MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors

Systems biological and mechanistic modelling of radiation-induced cancer

This paper summarises the five presentations at the First International Workshop on Systems Radiation Biology that were concerned with mechanistic models for carcinogenesis. The mathematical description of various hypotheses about the carcinogenic process, and its comparison with available data is an example of systems biology. It promises better understanding of effects at the whole body level based on properties of cells and signalling mechanisms between them. Of these five presentations, three dealt with multistage carcinogenesis within the framework of stochastic multistage clonal expansion models, another presented a deterministic multistage model incorporating chromosomal aberrations and neoplastic transformation, and the last presented a model of DNA double-strand break repair pathways for second breast cancers following radiation therapy