16 research outputs found

    Utilization of Aqueous RAFT Prepared Copolymers to Improve Anticancer Drug Efficacy

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    The advent of controlled radical polymerization (CRP) techniques, along with advancements in facile conjugation chemistry, now allow synthetic tailoring of precise, polymeric architectures necessary for drug/gene delivery. Reversible addition- fragmentation chain transfer (RAFT) polymerization and its aqueous counterpart (aRAFT) afford quantitative control over key synthetic parameters including block length, microstructure, and placement of structo-pendent and structo-terminal functionality for conjugation of active agents and targeting moieties. The relevance of water-soluble and amphiphilic (co)polymers synthesized by RAFT for in vitro delivery of therapeutics in biological fluids is an especially attractive feature. In many cases, polymerization, binding, conjugation, and stimulus-induced release can be accomplished directly in aqueous media. However, specific problems, barriers, and challenges regarding rational design of polymeric delivery systems for therapeutic siRNA still exist. This dissertation focuses on RAFT synthesized (co)polymers as vectors and functional constructs to overcome delivery challenges. In section I, a modular copolymer consisting of HPMA and glutamic acid was synthesized to overcome hurdles of endosomal escape. Glutamic acid undergoes a coil-to-helix transition at endosomal pH- values, and these helices were stabilized with HPMA. As a proof-of-concept, the pH- responsive constructs demonstrated membrane disruption via red blood cell hemolysis and dye release from fluorescein-loaded POPC vesicles. In section II, hydrophilic-block-cationic copolymers were complexed with siRNA to ascertain the structure-property relationships governing siRNA release from block ionomer complexes (BICs). It was determined that the stability of the complexes, which increases with increasing cationic block length, delayed the time required to achieve gene suppression. These results indicated that decomplexation was facilitated via an ion exchange/substitution mechanism. In section III, AS1411, an anticancer biologic, was delivered utilizing hydrophilic-block-cationic copolymers. The prepared BICs were found to be monodisperse (PDIs \u3c 0.1) and charge neutral (i.e., N:P = 1). The anti-proliferative ability of AS1411 was then assessed utilizing hydrophilic-block-cationic copolymers as delivery vehicles. After 72 h, AS1411 demonstrated successful cellular inhibition; however, negligible anti-proliferative activity was witnessed when AS1411 was delivered utilizing hydrophilic-block-cationic copolymers. This reduction in drug activity was attributed to reduction of available drug caused by increased BIC stability as was determined in Section II

    Block Ionomer Complexes Consisting of siRNA and \u3ci\u3ea\u3c/i\u3eRAFT-Synthesized Hydrophilic-\u3ci\u3eBlock\u3c/i\u3e-Cationic Copolymers II: The Influence of Cationic Block Charge Density on Gene Suppression

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    Block ionomer complex (BIC)–siRNA interactions and effectiveness in cell transfection are reported. Aqueous RAFT polymerization was used to prepare a series of hydrophilic-block-cationic copolymers in which the cationic block statistically incorporates increasing amounts of neutral, hydrophilic monomer such that the number of cationic groups remains unchanged but the cationic charge density is diluted along the polymer backbone. Reduced charge density decreases the electrostatic binding strength between copolymers and siRNA with the goal of improving siRNA release after targeted cellular delivery. However, lower binding strength resulted in decreased transfection and RNA interference pathway activation, leading to reduced gene knockdown. Enzymatic siRNA degradation studies with BICs indicated lowered binding strength increases susceptibility to RNases, which is the likely cause for poor gene knockdown

    The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

    Fusion Learning Conference 2023 - proceedings

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    Welcome to the 3rd annual Fusion Learning Conference at BU. The event provides a hub for the exchange of knowledge, pedagogical innovations, and cutting-edge research that shape the landscape of our learning and teaching. This year we are hosting the largest number of submissions to the conference and look forward to an exciting line up of guest speaker from IBM presenting on the influence of Artificial Intelligence on higher education; a BU panel of experts sharing their insight about some of the emerging themes in our learning and teaching and preparing our students for future of work; staff presentations and discussions including, student engagement, digital transformation, academic integrity, inclusive and sustainability in the curriculum design. I hope that you find this selection of posters and abstracts to be enlightening

    The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

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    The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V

    HawkTour (semester 2 of unknown), IPRO 305: HawkTour IPRO 305 Final Report F04

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    The team will be focusing on the challenge of integrating Pervasive Computing into a specific aspect of the IIT campus. The overall vision of the IPRO 305 team is to continue efforts to develop an application called HawkTour – a virtual Illinois Institute of Technology tour guide. HawkTour will provide a completely new approach to the campus tour at IIT.Deliverable

    HawkTour (semester 2 of unknown), IPRO 305: HawkTour IPRO 305 Project Plan F04

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    The team will be focusing on the challenge of integrating Pervasive Computing into a specific aspect of the IIT campus. The overall vision of the IPRO 305 team is to continue efforts to develop an application called HawkTour – a virtual Illinois Institute of Technology tour guide. HawkTour will provide a completely new approach to the campus tour at IIT.Deliverable

    HawkTour (semester 2 of unknown), IPRO 305: HawkTour IPRO 305 Midterm Report F04

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    The team will be focusing on the challenge of integrating Pervasive Computing into a specific aspect of the IIT campus. The overall vision of the IPRO 305 team is to continue efforts to develop an application called HawkTour – a virtual Illinois Institute of Technology tour guide. HawkTour will provide a completely new approach to the campus tour at IIT.Deliverable
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