Possible meteoroid hazard to solid- propellant rocket motors

Meteoroid hazards to solid propellant rocket motor

Apparatus and method for control of a solid fueled rocket vehicle Patent

Solid propellant rocket vehicle thrust control method and apparatu

Structure of the Cytoplasmic Loop between Putative Helices II and III of the Mannitol Permease of Escherichia coli: A Tryptophan and 5-Fluorotryptophan Spectroscopy Study

In this work, four single tryptophan (Trp) mutants of the dimeric mannitol transporter of Escherichia coli, EIImtl, are characterized using Trp and 5-fluoroTrp (5-FTrp) fluorescence spectroscopy. The four positions, 97, 114, 126, and 133, are located in a region shown by recent studies to be involved in the mannitol translocation process. To spectroscopically distinguish between the Trp positions in each subunit of dimeric EIImtl, 5-FTrp was biosynthetically incorporated because of its much simpler photophysics compared to those of Trp. The steady-state and time-resolved fluorescence methodologies used point out that all four positions are in structured environments, both in the absence and in the presence of a saturating concentration of mannitol. The fluorescence decay of all 5-FTrp-containing mutants was highly homogeneous, suggesting similar microenvironments for both probes per dimer. However, Stern-Volmer quenching experiments using potassium iodide indicate different solvent accessibilities for the two probes at positions 97 and 133. A 5 Å two-dimensional (2D) projection map of the membrane-embedded IICmtl dimer showing 2-fold symmetry is available. The results of this work are in better agreement with a 7 Å projection map from a single 2D crystal on which no symmetry was imposed.

Old lineage on an old island : Pixibinthus, a new cricket genus endemic to New Caledonia shed light on gryllid diversification in a hotspot of biodiversity

Few studies have focused on the early colonization of New Caledonia by insects, after the re-emergence of the main island, 37 Myr ago. Here we investigate the mode and tempo of evolution of a new endemic cricket genus, Pixibinthus, recently discovered in southern New Caledonia. First we formally describe this new monotypic genus found exclusively in the open shrubby vegetation on metalliferous soils, named 'maquis minier', unique to New Caledonia. We then reconstruct a dated molecular phylogeny based on five mitochondrial and four nuclear loci in order to establish relationships of Pixibinthus within Eneopterinae crickets. Pixibinthus is recovered as thesister clade of the endemic genus Agnotecous, mostly rainforest-dwellers. Dating results show that the island colonization by their common ancestor occurred around 34.7 Myr, shortly after New Caledonia re-emergence. Pixibinthus and Agnotecous are then one of the oldest insect lineages documented so far for New Caledonia. This discovery highlights for the first time two clear-cut ecological specializations between sister clades, as Agnotecous is mainly found in rainforests with 19 species, whereas Pixibinthus is found in open habitats with a single documented species. The preference of Pixibinthus for open habitats and of Agnotecous for forest habitats nicely fits an acoustic specialization, either explained by differences in body size or in acoustic properties of their respective habitats. We hypothesize that landscape dynamics, linked to major past climatic events and recent change in fire regimes are possible causes for both present-day low diversity and rarity in genus Pixibinthus. The unique evolutionary history of this old New Caledonian lineage stresses the importance to increase our knowledge on the faunal biodiversity of 'maquis minier', in order to better understand the origin and past dynamics of New Caledonian biota

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance