Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.Cataloged from PDF version of thesis.Includes bibliographical references.Assembly of functional nanocomponents offers promising applications in drug delivery to solid tumors and bottom-up synthesis and integration of nanodevices. This thesis presents a novel multistage nanoparticle delivery system consisting of an assembly of nanoparticles that can change its size to facilitate transport into solid tumors. Current FDA-approved nanotherapeutics, which function based on the enhanced permeation and retention (EPR) effect, suffer from poor penetration into the extravascular regions of the tumor due to the dense collagen matrix, resulting in heterogeneous therapeutic effects and likely contributing to tumor regression and development of resistance. We propose a multistage nanoparticle system that "shrinks" when it extravasates into the tumor and is exposed to the tumor microenvironment, allowing enhanced penetration into the tumor parenchyma. This "shrinkage" is preferentially triggered in the tumor through cleavage by MMPs, proteases highly expressed in the tumor microenvironment. A multistage nanoparticle system allows us to engineer the size and surface properties of each stage independently for preferential transvascular transport into tumors and high diffusion in the tumor's interstitial space. To our knowledge, this work is the first demonstration of a size-changing nanoparticle delivery system in vivo. Multistage nanoparticle delivery systems provide a promising approach to improving the delivery of anticancer agents into solid tumors and as a result the enhancement of the drug's therapeutic efficacy. Another area that necessitates the controlled assembly of nanocomponents is in the integration of nanodevices and nanocircuitry. We have developed a method of combining the synthesis and assembly of semiconducting nanowires in a single step using electrically controlled catalytic nanowire growth. Our results demonstrate electric field-modulated nanowire growth that can be used as a simple and inexpensive method for fabricating and integrating nanoscale devices.by Cliff R. Wong.Ph.D

Avidin as a model for charge driven transport into cartilage and drug delivery for treating early stage post-traumatic osteoarthritis

Local drug delivery into cartilage remains a challenge due to its dense extracellular matrix of negatively charged proteoglycans enmeshed within a collagen fibril network. The high negative fixed charge density of cartilage offers the unique opportunity to utilize electrostatic interactions to augment transport, binding and retention of drug carriers. With the goal of developing particle-based drug delivery mechanisms for treating post-traumatic osteoarthritis, our objectives were, first, to determine the size range of a variety of solutes that could penetrate and diffuse through normal cartilage and enzymatically treated cartilage to mimic early stages of OA, and second, to investigate the effects of electrostatic interactions on particle partitioning, uptake and binding within cartilage using the highly positively charged protein, Avidin, as a model. Results showed that solutes having a hydrodynamic diameter ≤10 nm can penetrate into the full thickness of cartilage explants while larger sized solutes were trapped in the tissue's superficial zone. Avidin had a 400-fold higher uptake than its neutral same-sized counterpart, NeutrAvidin, and >90% of the absorbed Avidin remained within cartilage explants for at least 15 days. We report reversible, weak binding (K[subscript D] ~ 150 μm) of Avidin to intratissue sites in cartilage. The large effective binding site density (N[subscript T] ~ 2920 μm) within cartilage matrix facilitates Avidin's retention, making its structure suitable for particle based drug delivery into cartilage

Crop Updates 2000 - Cereals part 1

This session covers eleven papers from different authors: PLENARY PAPERS 1. New Wheat for a Secure, Sustainable Future, Timothy G. Reeves, Sanjaya Rajaram, Maarten van Ginkel, Richard Trethowan, Hans-Joachim Braun, and Kelly Cassaday, International Maize and Wheat Improvement Centre (CIMMYT) 2. Managing Cereal Rusts - a National Perspective, R.A. McIntosh, University of Sydney Plant Breeding Institute, New South Wales 3. Managing Cereal Rusts in 2000 - a regional imperative, R. Loughman, Agriculture Western Australia 4. Is nutrition the answer to wheat after canola problems?Ross Brennan1, Bill Bowden1, Mike Bolland1, Zed Rengel2 and David Isbister2 1 Agriculture Western Australia 2University of Western Australia 5. Improved Sandplain Cropping Systems by Controlled Traffic, Dr Paul Blackwell, Agriculture Western Australia 6. Raised bed farming for improved cropping of waterlogged soils, Derk Bakker, Greg Hamilton, David Houlbrooke, Cliff Spann and Doug Rowe, Agriculture Western Australia 7. Banded Urea increased wheat yields, Patrick Gethin, Stephen Loss, Frank Boetel, and Tim O’Dea, CSBP futurefarm 8. Flexi N is as effective as Urea on wheat and canola, Frank Boetel, Stephen Loss, Patrick Gethin, and Tim O’Dea CSBP futurefarm 9. Why potassium may reduce cereal leaf disease, Noeleen Edwards, Agriculture Western Australia 10, Trace elements, Wayne Pluske CSBP futurefarm, and Ross BrennanAgriculture Western Australia 11. Historical Nutrient Balance at Paddock and Whole Farm scales for typical wheatbelt farms in the Dowerin - Wongan Hills area, M.T.F. Wong, K. Wittwer and H. Zhang Precision Agriculture Research Group, CSIRO Land and Wate

Compact Biocompatible Quantum Dots via RAFT-Mediated Synthesis of Imidazole-Based Random Copolymer Ligand

We present a new class of polymeric ligands for quantum dot (QD) water solubilization to yield biocompatible and derivatizable QDs with compact size (~10-12 nm diameter), high quantum yields (>50%), excellent stability across a large pH range (pH 5-10.5), and low nonspecific binding. To address the fundamental problem of thiol instability in traditional ligand exchange systems, the polymers here employ a stable multidentate imidazole binding motif to the QD surface. The polymers are synthesized via reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization to produce molecular weight controlled monodisperse random copolymers from three types of monomers that feature imidazole groups for QD binding, polyethylene glycol (PEG) groups for water solubilization, and either primary amines or biotin groups for derivatization. The polymer architecture can be tuned by the monomer ratios to yield aqueous QDs with targeted surface functionalities. By incorporating amino-PEG monomers, we demonstrate covalent conjugation of a dye to form a highly efficient QD-dye energy transfer pair as well as covalent conjugation to streptavidin for high-affinity single molecule imaging of biotinylated receptors on live cells with minimal non-specific binding. The small size and low serum binding of these polymer-coated QDs also allow us to demonstrate their utility for in-vivo imaging of the tumor microenvironment in live mice.Chemistry and Chemical Biolog

Translations equations to compare ActiGraph GT3X and Actical accelerometers activity counts

Background: This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Methods: Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R2 were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. Results: The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R2 range: 0.514 to 0.989 and average: 0.822) and full data set (R2 = 0.865). Conclusions: The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraphvertical component can be confidently performed between data sets and might allow further synthesis of information between studies

Encoding of Temporal Information by Timing, Rate, and Place in Cat Auditory Cortex

A central goal in auditory neuroscience is to understand the neural coding of species-specific communication and human speech sounds. Low-rate repetitive sounds are elemental features of communication sounds, and core auditory cortical regions have been implicated in processing these information-bearing elements. Repetitive sounds could be encoded by at least three neural response properties: 1) the event-locked spike-timing precision, 2) the mean firing rate, and 3) the interspike interval (ISI). To determine how well these response aspects capture information about the repetition rate stimulus, we measured local group responses of cortical neurons in cat anterior auditory field (AAF) to click trains and calculated their mutual information based on these different codes. ISIs of the multiunit responses carried substantially higher information about low repetition rates than either spike-timing precision or firing rate. Combining firing rate and ISI codes was synergistic and captured modestly more repetition information. Spatial distribution analyses showed distinct local clustering properties for each encoding scheme for repetition information indicative of a place code. Diversity in local processing emphasis and distribution of different repetition rate codes across AAF may give rise to concurrent feed-forward processing streams that contribute differently to higher-order sound analysis

A study of CP violation in the decays B±→[K+K-π+π-]Dh± (h= K, π) and B±→[π+π-π+π-]Dh±

The first study of CP violation in the decay mode B±→[K+K-π+π-]Dh± , with h= K, π , is presented, exploiting a data sample of proton–proton collisions collected by the LHCb experiment that corresponds to an integrated luminosity of 9 \,fb - 1 . The analysis is performed in bins of phase space, which are optimised for sensitivity to local CP asymmetries. CP -violating observables that are sensitive to the angle γ of the Unitarity Triangle are determined. The analysis requires external information on charm-decay parameters, which are currently taken from an amplitude analysis of LHCb data, but can be updated in the future when direct measurements become available. Measurements are also performed of phase-space integrated observables for B±→[K+K-π+π-]Dh± and B±→[π+π-π+π-]Dh± decays

Measurement of antiproton production from antihyperon decays in pHe collisions at √sNN=110GeV

The interpretation of cosmic antiproton flux measurements from space-borne experiments is currently limited by the knowledge of the antiproton production cross-section in collisions between primary cosmic rays and the interstellar medium. Using collisions of protons with an energy of 6.5 TeV incident on helium nuclei at rest in the proximity of the interaction region of the LHCb experiment, the ratio of antiprotons originating from antihyperon decays to prompt production is measured for antiproton momenta between 12 and 110GeV\!/c . The dominant antihyperon contribution, namely Λ¯ → p¯ π+ decays from promptly produced Λ¯ particles, is also exclusively measured. The results complement the measurement of prompt antiproton production obtained from the same data sample. At the energy scale of this measurement, the antihyperon contributions to antiproton production are observed to be significantly larger than predictions of commonly used hadronic production models

Measurement of τL using the Bs0 →J/ψη decay mode

Using a proton–proton collision data sample collected by the LHCb detector and corresponding to an integrated luminosity of 5.7fb-1 , the lifetime of the light Bs0 mass eigenstate, τL , is measured using the Bs0→J/ψη decay mode to be τL=1.445±0.016(stat)±0.008(syst)ps. A combination of this result with a previous LHCb analysis using an independent dataset corresponding to 3 fb - 1 of integrated luminosity gives τL=1.452±0.014±0.007±0.002ps, where the first uncertainty is statistical, the second due to the uncorrelated part of the systematic uncertainty and the third due to the correlated part of the systematic uncertainty

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages