161 research outputs found

    Evolution of cancer cell populations under cytotoxic therapy and treatment optimisation: Insight from a phenotype-structured model

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    We consider a phenotype-structured model of evolutionary dynamics in a population of cancer cells exposed to the action of a cytotoxic drug. The model consists of a nonlocal parabolic equation governing the evolution of the cell population density function. We develop a novel method for constructing exact solutions to the model equation, which allows for a systematic investigation of the way in which the size and the phenotypic composition of the cell population change in response to variations of the drug dose and other evolutionary parameters. Moreover, we address numerical optimal control for a calibrated version of the model based on biological data from the existing literature, in order to identify the drug delivery schedule that makes it possible to minimise either the population size at the end of the treatment or the average population size during the course of treatment. The results obtained challenge the notion that traditional high-dose therapy represents a "one-fits-all solution" in anticancer therapy by showing that the continuous administration of a relatively low dose of the cytotoxic drug performs more closely to i.e. the optimal dosing regimen to minimise the average size of the cancer cell population during the course of treatment

    Amphiphilic DNA nanostructures for bottom-up synthetic biology

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    DNA nanotechnology enables the construction of sophisticated biomimetic nanomachines that are increasingly central to the growing efforts of creating complex cell-like entities from the bottom-up. DNA nanostructures have been proposed as both structural and functional elements of these artificial cells, and in many instances are decorated with hydrophobic moieties to enable interfacing with synthetic lipid bilayers or regulating bulk self-organisation. In this feature article we review recent efforts to design biomimetic membrane-anchored DNA nanostructures capable of imparting complex functionalities to cell-like objects, such as regulated adhesion, tissue formation, communication and transport. We then discuss the ability of hydrophobic modifications to enable the self-assembly of DNA-based nanostructured frameworks with prescribed morphology and functionality, and explore the relevance of these novel materials for artificial cell science and beyond. Finally, we comment on the yet mostly unexpressed potential of amphiphilic DNA-nanotechnology as a complete toolbox for bottom-up synthetic biology – a figurative and literal scaffold upon which the next generation of synthetic cells could be built

    The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

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    The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

    The RIBES strategy for ex situ conservation: conventional and modern techniques for seed conservation

    Get PDF
    The Italian seed bank network (RIBES) aims to improve the quality and safety of the germplasm reserves of native plant species in Italy to ensure the long-term conservation of endangered and/or endemic flora. The strategy includes traditional methods to secure seed conservation. A comprehensive priority list for seed collection is being defined, it was prepared by crossing data of various checklists (red lists, endemics) and will soon be cross-referenced with an updated list of accessions of the whole network. A safety-backup program of duplicates will quickly be implemented to secure the conservation of the most threatened species in at least two seed banks of the network. On the other hand, the RIBES strategy also includes research by applying modern techniques. In collaboration with the Millennium Seed Bank, research on the storage behaviour of seeds and spores through thermal analysis is ongoing to inform conservation. Using the Differential Scanning Calorimetry (DSC), we could evaluate seed lipid properties such as glass transition temperature, melting, crystallization, oxidation behaviour, and thermal stability. Finally, RIBES participates as a co-funder in the LIFE Nature project SEEDFORCE, coordinating 11 seed banks of the network for collecting seeds/spores of 29 threatened species of EU interest

    OLIMPO: A few arcmin resolution survey of the sky at mm and sub-mm wavelengths

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    Abstract. OLIMPO is a 2.6 meter on-axis millimeter-wave Cassegrain telescope, mounted on an attitude controlled stratospheric balloon payload. This telescope is designed to be flown with a > 10 days Long Duration CircumPolar flight. The system contains 4 arrays of bolometers in the wavelength bands centered at 150, 220, 350, 600 GHz. The instrument will be diffraction limited at 150 GHz (3.5 arcminutes FWHM). It is currently planned to have a test flight from Trapani in 2003/4

    Anthrax Toxin Receptor Drives Protective Antigen Oligomerization and Stabilizes the Heptameric and Octameric Oligomer by a Similar Mechanism

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    Anthrax toxin is comprised of protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins are individually nontoxic; however, when PA assembles with LF and EF, it produces lethal toxin and edema toxin, respectively. Assembly occurs either on cell surfaces or in plasma. In each milieu, PA assembles into a mixture of heptameric and octameric complexes that bind LF and EF. While octameric PA is the predominant form identified in plasma under physiological conditions (pH 7.4, 37°C), heptameric PA is more prevalent on cell surfaces. The difference between these two environments is that the anthrax toxin receptor (ANTXR) binds to PA on cell surfaces. It is known that the extracellular ANTXR domain serves to stabilize toxin complexes containing the PA heptamer by preventing premature PA channel formation--a process that inactivates the toxin. The role of ANTXR in PA oligomerization and in the stabilization of toxin complexes containing octameric PA are not understood.Using a fluorescence assembly assay, we show that the extracellular ANTXR domain drives PA oligomerization. Moreover, a dimeric ANTXR construct increases the extent of and accelerates the rate of PA assembly relative to a monomeric ANTXR construct. Mass spectrometry analysis shows that heptameric and octameric PA oligomers bind a full stoichiometric complement of ANTXR domains. Electron microscopy and circular dichroism studies reveal that the two different PA oligomers are equally stabilized by ANTXR interactions.We propose that PA oligomerization is driven by dimeric ANTXR complexes on cell surfaces. Through their interaction with the ANTXR, toxin complexes containing heptameric and octameric PA oligomers are similarly stabilized. Considering both the relative instability of the PA heptamer and extracellular assembly pathway identified in plasma, we propose a means to regulate the development of toxin gradients around sites of infection during anthrax pathogenesis
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