15 research outputs found
A molecular dynamics study of plasticiser migration in nitrocellulose binders
The migration of the energetic plasticisers 1-nitramino-2,3-dinitroxypropane; 2,4-dinitroethylbenzene; and 2,4,6-trinitroethylbenzene in two nitrocellulose binder mixtures has been investigated by the calculation of diffusion coefficients and activation energies of diffusion from molecular dynamics simulations. The study included parameterisation of force fields for nitrocellulose; 1-nitramino-2,3-dinitroxypropane; the stabilizer ethyl centralite; and the overall nitrocellulose binder mixtures. Simulated densities obtained were in very good agreement with experimental densities. The diffusion coefficients compare favourably with experimental values available for similar systems, when differences such as the proportions of plasticisers are taken into consideration. Examination of the plasticiser diffusion rates suggests that 1-nitramino-2,3-dinitroxypropane migrates more slowly from a nitrocellulose binder than 2,4-dinitroethylbenzene for the nitrocellulose and plasticiser proportions used in this study. Understanding plasticiser migration is essential for the long-term storage of energetic material formulations without significant changes occurring in their properties or compositions
Targeting intermediary metabolism enhances the efficacy of BH3 mimetic therapy in haematological malignancies.
BH3 mimetics are novel targeted drugs with remarkable specificity and potency and enormous potential to improve cancer therapy. However, acquired resistance is an emerging problem. We report the rapid development of resistance in chronic lymphocytic leukemia cells isolated from patients exposed to increasing doses of Navitoclax (ABT-263), a BH3 mimetic. To mimic such rapid development of chemoresistance, we have developed simple resistance models to three different BH3 mimetics, targeting BCL-2 (ABT-199), BCL-XL (A-1331852) or MCL-1 (A-1210477), in relevant haematological cancer cell lines. In these models, resistance could be attributed neither to consistent changes in expression levels of the anti-apoptotic proteins nor interactions among different pro- and anti-apoptotic BCL-2 family members. Using genetic silencing, pharmacological inhibition and metabolic supplementation, we report that targeting of glutamine uptake and its downstream signalling pathways, namely glutaminolysis, reductive carboxylation, lipogenesis, cholesterogenesis and mTOR signalling result in marked sensitisation of the chemoresistant cells to BH3 mimetic-mediated apoptosis. Furthermore, our findings highlight the possibility of repurposing widely used drugs, such as statins, to target intermediary metabolism and improve the efficacy of BH3 mimetic therapy
Theoretical Calculations of the Structures of Some Prostaglandins and Inhibitors of Lipoxygenase
The economy of nature: the structure of evolution in Linnaeus, Darwin, and the modern synthesis
Marine Sclerobiofacies: Encrusting and Endolithic Communities on Shells Through Time and Space
Marine Sclerobiofacies: Encrusting and Endolithic Communities on Shells Through Time and Space
The concept of sclerobiofacies is defined herein as suites of sclerobiont encrusters and endiont borers (collectively sclerobionts) preserved on skeletons that characterize particular facies/environments. Skeletal components provide biologically standardized substrates; when possible, comparison of encrusting assemblages on fossil shells of the same or closely related eurytopic species provides a degree of substrate control comparable to modern experimentally deployed shells. Taxonomic composition of sclerobiont suites varies rather predictably among marine environments (e.g., based upon depth) but is primarily useful for comparisons of environments within local areas and limited time frames. Parameters that may be used to compare sclerobiofacies across broader spatial and temporal dimensions include: per shell and cumulative species richness (diversity), frequency of encrustation, areal coverage, and guild structure of encrusting taxa. Herein, we summarize characteristic sclerobiofacies in a series of Recent and ancient examples. Modern subtropical marine encrusters, documented on experimentally deployed molluscan shells at sites ranging from 15 to over 200 m, show high biont richness in shallow subtidal areas. Maximal areal coverages in Bahamian samples occur at about 20–30 m, whereas species richness increases downward to the deeper euphotic zone (∼75–80 m). Below this level, rapid decline in both richness and percent coverage results in deeper Dysphotic–Aphotic zone samples yielding only a few species with coverage rarely exceeding 5%. Burial is also a key factor such that rapidly buried shells in the Shallow Euphotic zone have species coverages, richnesses, and taxonomic compositions resembling long-exposed shells in deeper areas below the euphotic zone. Shelly substrates from the Cambrian to Early Ordovician exhibit only minor encrustation by solitary attached taxa, especially echinoderms; however, by the Late Ordovician various solitary (e.g., cornulitids, craniid brachiopods) and colonial forms (e.g., trepostome and tubuliporate bryozoans) form distinctive sclerobiofacies. Photic zone-related environments, judged independently on the basis of microendoliths, show overall lower taxonomic richness than modern counterparts. However, they also show common patterns, including a general decrease of richness and percent encrustation from Shallow Euphotic to Dysphotic/Aphotic zones. Comparable trends are seen in Middle Devonian exemplars from New York State. Not only were there consistent trends toward lowered diversity/coverage into deep-water settings but also an additional factor related to turbidity and/or sedimentation rate was identified from assemblages at comparable depths arrayed along a distal to proximal gradient with respect to siliciclastic input sources. Carboniferous sclerobiont suites from varied sites in North America show many of the same traits as their Devonian counterparts, although detailed depth zonations are not documented at present. The Permo-Triassic extinctions appear to have had a strong impact on the taxonomic composition of marine sclerobiofacies, although a paucity of studies obscures details of Mesozoic and Cenozoic sclerobiofacies. In general, they appear to have taxonomic compositions and patterns similar to those observed in the Recent. The concept of sclerobiofacies provides another tool for paleoenvironmental analysis. Together with litho-, ichno-, bio-, and taphofacies, the properties of shell encrusting assemblages will yield detailed further insights into ancient environmental gradients