145 research outputs found

    Injectable polypeptide hydrogels via methionine modification for neural stem cell delivery.

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    Injectable hydrogels with tunable physiochemical and biological properties are potential tools for improving neural stem/progenitor cell (NSPC) transplantation to treat central nervous system (CNS) injury and disease. Here, we developed injectable diblock copolypeptide hydrogels (DCH) for NSPC transplantation that contain hydrophilic segments of modified l-methionine (Met). Multiple Met-based DCH were fabricated by post-polymerization modification of Met to various functional derivatives, and incorporation of different amino acid comonomers into hydrophilic segments. Met-based DCH assembled into self-healing hydrogels with concentration and composition dependent mechanical properties. Mechanical properties of non-ionic Met-sulfoxide formulations (DCHMO) were stable across diverse aqueous media while cationic formulations showed salt ion dependent stiffness reduction. Murine NSPC survival in DCHMO was equivalent to that of standard culture conditions, and sulfoxide functionality imparted cell non-fouling character. Within serum rich environments in vitro, DCHMO was superior at preserving NSPC stemness and multipotency compared to cell adhesive materials. NSPC in DCHMO injected into uninjured forebrain remained local and, after 4 weeks, exhibited an immature astroglial phenotype that integrated with host neural tissue and acted as cellular substrates that supported growth of host-derived axons. These findings demonstrate that Met-based DCH are suitable vehicles for further study of NSPC transplantation in CNS injury and disease models

    Mapping Exoplanets

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    The varied surfaces and atmospheres of planets make them interesting places to live, explore, and study from afar. Unfortunately, the great distance to exoplanets makes it impossible to resolve their disk with current or near-term technology. It is still possible, however, to deduce spatial inhomogeneities in exoplanets provided that different regions are visible at different times---this can be due to rotation, orbital motion, and occultations by a star, planet, or moon. Astronomers have so far constructed maps of thermal emission and albedo for short period giant planets. These maps constrain atmospheric dynamics and cloud patterns in exotic atmospheres. In the future, exo-cartography could yield surface maps of terrestrial planets, hinting at the geophysical and geochemical processes that shape them.Comment: Updated chapter for Handbook of Exoplanets, eds. Deeg & Belmonte. 17 pages, including 6 figures and 4 pages of reference

    Biocatalytic Synthesis of Polymers of Precisely Defined Structures

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    The fabrication of functional nanoscale devices requires the construction of complex architectures at length scales characteristic of atoms and molecules. Currently microlithography and micro-machining of macroscopic objects are the preferred methods for construction of small devices, but these methods are limited to the micron scale. An intriguing approach to nanoscale fabrication involves the association of individual molecular components into the desired architectures by supramolecular assembly. This process requires the precise specification of intermolecular interactions, which in turn requires precise control of molecular structure

    The Complete transmission spectrum of WASP-39b with a precise water constraint

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    This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.WASP-39b is a hot Saturn-mass exoplanet with a predicted clear atmosphere based on observations in the optical and infrared. Here we complete the transmission spectrum of the atmosphere with observations in the near-infrared (NIR) over three water absorption features with the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) G102 (0.8-1.1 microns) and G141 (1.1-1.7 microns) spectroscopic grisms. We measure the predicted high amplitude H2O feature centered at 1.4 microns, and the smaller amplitude features at 0.95 and 1.2 microns, with a maximum water absorption amplitude of 2.4 planetary scale heights. We incorporate these new NIR measurements into previously published observational measurements to complete the transmission spectrum from 0.3-5 microns. From these observed water features, combined with features in the optical and IR, we retrieve a well constrained temperature Teq = 1030(+30,-20) K, and atmospheric metallicity 151 (+48,-46)x solar which is relatively high with respect to the currently established mass-metallicity trends. This new measurement in the Saturn-mass range hints at further diversity in the planet formation process relative to our solar system giants.This work is based on observations made with the NASA/ESA Hubble Space Telescope that were obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc. These observations are associated with programs GO-14169 (PI. HR Wakeford) and GO-14260 (PI. D Deming). D.K.S., H.R.W., T.E., B.D., and N.N., acknowledge funding from the European Research Council (ERC) under the European Unions Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 336792. J.G. acknowledges support from Leverhulme Trust. A.L.C. acknowledges support from the STFC. H.R.W. also acknowledges support from the Giacconi Fellowship at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc

    Liverpool telescope 2: a new robotic facility for rapid transient follow-up

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    The Liverpool Telescope is one of the world's premier facilities for time domain astronomy. The time domain landscape is set to radically change in the coming decade, with surveys such as LSST providing huge numbers of transient detections on a nightly basis; transient detections across the electromagnetic spectrum from other facilities such as SVOM, SKA and CTA; and the era of `multi-messenger astronomy', wherein events are detected via non-electromagnetic means, such as gravitational wave emission. We describe here our plans for Liverpool Telescope 2: a new robotic telescope designed to capitalise on this new era of time domain astronomy. LT2 will be a 4-metre class facility co-located with the LT at the Observatorio del Roque de Los Muchachos on the Canary island of La Palma. The telescope will be designed for extremely rapid response: the aim is that the telescope will take data within 30 seconds of the receipt of a trigger from another facility. The motivation for this is twofold: firstly it will make it a world-leading facility for the study of fast fading transients and explosive phenomena discovered at early times. Secondly, it will enable large-scale programmes of low-to-intermediate resolution spectral classification of transients to be performed with great efficiency. In the target-rich environment of the LSST era, minimising acquisition overheads will be key to maximising the science gains from any follow-up programme. The telescope will have a diverse instrument suite which is simultaneously mounted for automatic changes, but it is envisaged that the primary instrument will be an intermediate resolution, optical/infrared spectrograph for scientific exploitation of transients discovered with the next generation of synoptic survey facilities. In this paper we outline the core science drivers for the telescope, and the requirements for the optical and mechanical design

    Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

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    This article summarizes advances in the synthesis of well-defined polypeptides and block copolypeptides. Traditional methods used to polymerize α-amino acid-N-carboxyanhydrides (NCAs) are described, and limitations in the utility of these systems for the preparation of polypeptides are discussed. Improved initiators and methods that allow polypeptide synthesis with good control over chain length, chain length distribution, and chain-end functionality are also discussed. Using these methods, block and random copolypeptides of controlled dimensions (including molecular weight, sequence, composition, and molecular weight distribution) can now be prepared. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide micelles, copolypeptide vesicles, and copolypeptide hydrogels is described. Many of these assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. © Springer-Verlag Berlin Heidelberg 2013

    Stabilization of Peptide Vesicles by Introducing Inter-Peptide Disulfide Bonds

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    PURPOSE: Previously, we have shown that the amphiphilic oligopeptide SA2 (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) spontaneously self-assemble into nano-sized vesicles in aqueous environment. Relative weak individual intermolecular interactions dominate such oligopeptide assemblies. In this study we aimed at improving the stability of such peptide vesicles by covalently crosslinking the oligopeptide vesicles using disulfide bonds. Two and three cysteines were introduced in the SA2 peptide sequence to allow crosslinking (Ac-Ala-Cys-Val-Cys-Leu-(Leu/Cys)-Leu-Trp-Glu-Glu-COOH). RESULTS: Upon disulfide formation the crosslinked vesicles remained stable under conditions that disrupted the non-crosslinked peptide vesicles. The stabilized vesicles were more closely examined in terms of particle size (distribution) using atomic force microscopy, cryogenic electron microscopy, as well as dynamic light scattering analysis, showing an average particle radius in number between 15 and 20 nm. Using entrapment of calcein it was shown that intermolecular crosslinking of peptides within the vesicles did not affect the permeability for calcein. CONCLUSION: Introduction of cysteines into the hydrophobic domain of the SA2 amphiphilic oligopeptides is a feasible strategy for crosslinking the peptide vesicles. Such small crosslinked oligopeptide vesicles may hold promise for drug delivery applications

    When climate science became climate politics: British media representations of climate change in 1988

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    Climate change has become a pressing environmental concern for scientists, social commentators and politicians. Previous social science research has explored media representations of climate change in various temporal and geographical contexts. Through the lens of Social Representations Theory, this article provides a detailed qualitative thematic analysis of media representations of climate change in the 1988 British broadsheet press, given that this year constitutes an important juncture in this transition of climate change from the domain of science to that of the socio-political sphere. The following themes are outlined: (i) “Climate change: a multi-faceted threat”; (ii) “Collectivisation of threat”; (iii) “Climate change and the attribution of blame”; and (iv) “Speculative solutions to a complex socio-environmental problem.” The article provides detailed empirical insights into the “starting-point” for present-day disputes concerning climate change and lays the theoretical foundations for tracking the continuities and discontinuities characterising social representations of climate change in the future

    An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides

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    BACKGROUND: The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. METHODOLOGY/PRINCIPAL FINDINGS: We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides
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