Publications

Four-fold increase in epoxide polymerization rate with change of alkyl-substitution on mono-mu-oxo-dialuminum initiators

by Ferrier, RC; Imbrogno, J; Rodriguez, CG; Chwatko, M; Meyer, PW; Lynd, NA

POLYMER CHEMISTRY; Volume: 8; Issue: 31; Pages: 4503-4511; DOI: 10.1039/c7py00894e

We present an improvement in the rate, utility, and mechanistic understanding of mono-mu-oxo-dialuminum initiators for epoxide ring-opening polymerization based on investigation of a homologous series of trialkylaluminum adducts of (2-dibenzylamino) ethoxy-dialkylaluminum (TAxEDA) [(AlR3)center dot(O(AlR2) CH2CH2N(Bn)(2)), with R = Me, Et, iBu]. Using in situ FTIR spectroscopy of neat AGE polymerizations, we determined that the isobutyl-substituted TAxEDA (iBu-TAxEDA) exhibited a propagation rate constant (k(p)) of 1.100 +/- 0.022 x 10(-3) M-1 s(-1), which was twice that of the methyl-functional TAxEDA (Me-TAxEDA) (k(p) = 0.500 +/- 0.011 x 10(-3) M-1 s(-1)) and four times that of ethyl-functional TAxEDA (Et-TAxEDA) (k(p) = 0.270 +/- 0.003 x 10(-3) M-1 s(-1)). The dative R3Al-O bond length in the mono-mu-oxo-dialuminum was longest for the iBu-TAxEDA (1.93 angstrom) and shortest for the Et-TAxEDA (1.88 angstrom). Consistent with a previously proposed mechanism for TAxEDA-initiated polymerization, the increased Al-O bond length may accommodate more-facile coordination and enchainment of the monomer by separation of the Al-O interaction leading to an increased polymerization rate. The generality of the improved iBu-TAxEDA was supported by polymerization of a range of monomer substrates such as propylene oxide (PO), butylene oxide (BO), epichlorohydrin (ECH), allyl glycidyl ether (AGE), propargyl glycidyl ether (PGE), and adamantylmethyl glycidyl ether (AMGE). In all cases investigated, the triisobutyl-functional TAxEDA (iBu-TAxEDA) represented an improved initiator for epoxide polymerization.

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A Conversation with John McKetta

by McKetta, JJ; Truskett, TM

ANNUAL REVIEW OF CHEMICAL AND BIOMOLECULAR ENGINEERING, VOL 8; Book Series: Annual Review of Chemical and Biomolecular Engineering; Volume: 8; Pages: 1-11; DOI: 10.1146/annurev-chembioeng-060816-101315

John J. McKetta, Jr. is a foundational figure in chemical engineering education and energy policy in the United States. An authority on the thermodynamic properties of hydrocarbons and an energy adviser to several US presidents, McKetta helped to educate and mentor thousands of students at the University of Texas at Austin for over 40 years, many of whom became leading figures in the energy and petrochemical industries, as well as in academia. As dean of the College of Engineering, McKetta helped to establish a bioengineering program, which later became the Biomedical Engineering Department, at the University of Texas at Austin, and was a tireless advocate for excellence and a focus on the student. At age 100, McKetta recalls the challenges and opportunities he faced in childhood, his memories of the emergence of petrochemical engineering, and his views on chemical engineering education and the people it has impacted in the United States over the past 100 years.

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Epitaxial Growth of Perovskite Strontium Titanate on Germanium via Atomic Layer Deposition.

by Lin EL, Edmondson BI, Hu S, Ekerdt JG

J Vis Exp. 2016 Jul 26;(113). doi: 10.3791/54268.

Atomic layer deposition (ALD) is a commercially utilized deposition method for electronic materials. ALD growth of thin films offers thickness control and conformality by taking advantage of self-limiting reactions between vapor-phase precursors and the growing film. Perovskite oxides present potential for next-generation electronic materials, but to-date have mostly been deposited by physical methods. This work outlines a method for depositing SrTiO3 (STO) on germanium using ALD. Germanium has higher carrier mobilities than silicon and therefore offers an alternative semiconductor material with faster device operation. This method takes advantage of the instability of germanium’s native oxide by using thermal deoxidation to clean and reconstruct the Ge (001) surface to the 2×1 structure. 2-nm thick, amorphous STO is then deposited by ALD. The STO film is annealed under ultra-high vacuum and crystallizes on the reconstructed Ge surface. Reflection high-energy electron diffraction (RHEED) is used during this annealing step to monitor the STO crystallization. The thin, crystalline layer of STO acts as a template for subsequent growth of STO that is crystalline as-grown, as confirmed by RHEED. In situ X-ray photoelectron spectroscopy is used to verify film stoichiometry before and after the annealing step, as well as after subsequent STO growth. This procedure provides framework for additional perovskite oxides to be deposited on semiconductors via chemical methods in addition to the integration of more sophisticated heterostructures already achievable by physical methods.

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Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX.

by Horava SD, Peppas NA

Ann Biomed Eng. 2016 Jun;44(6):1970-82. doi: 10.1007/s10439-016-1566-x.

The oral administration of hematological factor IX (FIX) can offer a convenient prophylactic treatment for hemophilia B patients. pH-Responsive hydrogels based on poly(methacrylic acid)-grafted-poly(ethylene glycol) (P(MAA-g-EG)) have been engineered as delivery vehicles for FIX. In oral delivery, such hydrogel carriers protected FIX from the gastric environment and released it under intestinal conditions as demonstrated by evaluation of the loading and release of FIX. Tailoring of the hydrogel networks improved the loading of FIX within the microcarriers, which is critical for minimizing protein degradation. Optimizing the loading conditions by increasing the incubation time and using a reduced ionic strength buffer further improved the delivery potential of the microcarriers. The presence of the microcarriers significantly enhanced the oral absorption of FIX in vitro. As shown in this work, P(MAA-g-EG) microcarriers are promising candidates for the oral delivery of FIX.

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Normalized Synergy Predicts That CD8 Co-Receptor Contribution to T Cell Receptor (TCR) and pMHC Binding Decreases As TCR Affinity Increases in Human Viral-Specific T Cells.

by Williams CM, Schonnesen AA, Zhang SQ, Ma KY, He C, Yamamoto T, Eckhardt SG, Klebanoff CA, Jiang N

Front Immunol. 2017 Jul 28;8:894. doi: 10.3389/fimmu.2017.00894

The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8+ T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands. CD8 contribution in a native human antigen-specific T cell response remains elusive. Here, using Hepatitis C Virus-specific precursor CTLs spanning a large range of TCR affinities, we discovered that the functional responsiveness of any given TCR correlated with the contribution of CD8 to TCR/pMHC binding. Furthermore, we found that CD8 contribution to TCR/pMHC binding in the two-dimensional (2D) system was more accurately reflected by normalized synergy (CD8 cooperation normalized by total TCR/pMHC bonds) rather than synergy (total CD8 cooperation) alone. While synergy showed an increasing trend with TCR affinity, normalized synergy was demonstrated to decrease with the increase of TCR affinity. Critically, normalized synergy was shown to correlate with CTL functionality and peptide sensitivity, corroborating three-dimensional (3D) analysis of CD8 contribution with respect to TCR affinity. In addition, we identified TCRs that were independent of CD8 for TCR/pMHC binding. Our results resolve the current discrepancy between 2D and 3D analysis on CD8 contribution to TCR/pMHC binding, and demonstrate that naturally occurring high-affinity TCRs are more capable of CD8-independent interactions that yield greater functional responsiveness even with CD8 blocking. Taken together, our data suggest that addition of the normalized synergy parameter to our previously established TCR discovery platform using 2D TCR affinity and sequence test would allow for selection of TCRs specific to any given antigen with the desirable attributes of high TCR affinity, CD8 co-receptor independence and functional superiority. Utilizing TCRs with less CD8 contribution could be beneficial for adoptive cell transfer immunotherapies using naturally occurring or genetically engineered T cells against viral or cancer-associated antigens.

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System-size effects in ionic fluids under periodic boundary conditions.

by Thompson JP, Sanchez IC

J Chem Phys. 2016 Dec 7;145(21):214103. doi: 10.1063/1.4968040

We investigate the system-size dependence of the thermodynamic properties of ionic fluids under periodic boundary conditions. Following an approach previously developed in the context of quantum Monte Carlo simulations of many-electron systems, we show that the leading-order finite-size artifact in the Coulomb energy per particle of a classical fluid of N structureless ions at given density and temperature is simply -kBT(2N)-1. Analytical approximations for the periodicity-induced size dependence of the excess thermodynamic properties of the fluid in the weak-coupling regime are obtained within the linearized Debye-Hückel theory. Theoretical results are compared with published simulations of the one-component plasma and our own simulations of a primitive-model electrolyte solution. Our work is directly relevant to estimating finite-size corrections in simulations of charged fluids comprising structureless ions embedded in continuous media. We outline in the Appendix how some of our formal results may be generalized to molecular fluids with mobile ions; e.g., electrolyte solutions with explicit solvent.

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The Regulation of Inherently Autoreactive VH4-34-Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa.

by Hart GT, Akkaya M, Chida AS, Wei C, Jenks SA, Tipton C, He C, Wendel BS, Skinner J, Arora G, Kayentao K, Ongoiba A, Doumbo O, Traore B, Narum DL, Jiang N, Crompton PD, Sanz I, Pierce SK

J Immunol. 2016 Nov 15;197(10):3841-3849

Plasmodium falciparum malaria is a deadly infectious disease in which Abs play a critical role in naturally acquired immunity. However, the specificity and nature of Abs elicited in response to malaria are only partially understood. Autoreactivity and polyreactivity are common features of Ab responses in several infections and were suggested to contribute to effective pathogen-specific Ab responses. In this article, we report on the regulation of B cells expressing the inherently autoreactive VH4-34 H chain (identified by the 9G4 mAb) and 9G4+ plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+ peripheral blood CD19+ B cells was similar in United States adults and African adults and children; however, more 9G4+ B cells appeared in classical and atypical memory B cell compartments in African children and adults compared with United States adults. The levels of 9G4+ IgG increased following acute febrile malaria but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case, even though a portion of 9G4+ B cells acquired phenotypes of atypical and classical memory B cells and 9G4+ IgG contained equivalent numbers of somatic hypermutations compared with all other VHs, a characteristic of secondary Ab repertoire diversification in response to Ag stimulation. Determining the origin and function of 9G4+ B cells and 9G4+ IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.

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Rational Modular RNA Engineering Based on In Vivo Profiling of Structural Accessibility.

by Leistra AN, Amador P, Buvanendiran A, Moon-Walker A, Contreras LM

ACS Synth Biol. 2017 Aug 10. doi: 10.1021/acssynbio.7b00185.

Bacterial small RNAs (sRNAs) have been established as powerful parts for controlling gene expression. However, development and application of engineered sRNAs has primarily focused on regulating novel synthetic targets. In this work, we demonstrate a rational modular RNA engineering approach that uses in vivo structural accessibility measurements to tune the regulatory activity of a multisubstrate sRNA for differential control of its native target network. Employing the CsrB global sRNA regulator as a model system, we use published in vivo structural accessibility data to infer the contribution of its local structures (substructures) to function and select a subset for engineering. We then modularly recombine the selected substructures, differentially representing those of presumed high or low functional contribution, to build a library of 21 CsrB variants. Using fluorescent translational reporter assays, we demonstrate that the CsrB variants achieve a 5-fold gradient of control of well-characterized Csr network targets. Interestingly, results suggest that less conserved local structures within long, multisubstrate sRNAs may represent better targets for rational engineering than their well-conserved counterparts. Lastly, mapping the impact of sRNA variants on a signature Csr network phenotype indicates the potential of this approach for tuning the activity of global sRNA regulators in the context of metabolic engineering applications.

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Template-Free Mesoporous Electrochromic Films on Flexible Substrates from Tungsten Oxide Nanorods.

by Heo S, Kim J, Ong GK, Milliron DJ

Nano Lett. 2017 Aug 8. doi: 10.1021/acs.nanolett.7b02730.

Low-temperature processed mesoporous nanocrystal thin films are platforms for fabricating functional composite thin films on flexible substrates. Using a random arrangement of anisotropic nanocrystals can be a facile solution to generate pores without templates. However, the tendency for anisotropic particles to spontaneously assemble into a compact structure must be overcome. Here, we present a method to achieve random networking of nanorods during solution phase deposition by switching their ligand-stabilized colloidal nature into a charge-stabilized nature by a ligand-stripping chemistry. Ligand-stripped tungsten suboxide (WO2.72) nanorods result in uniform mesoporous thin films owing to repulsive electrostatic forces preventing nanorods from densely packing. Porosity and pore size distribution of thin films are controlled by changing the aspect ratio of the nanorods. This template-free mesoporous structure, achieved without annealing, provides a framework for introducing guest components, therefore enabling our fabrication of inorganic nanocomposite electrochromic films on flexible substrates. Following infilling of niobium polyoxometalate clusters into pores and successive chemical condensation, a WOx-NbOx composite film is produced that selectively controls visible and near-infrared light transmittance without any annealing required. The composite shows rapid switching kinetics and can be stably cycled between optical states over 2000 times. This simple strategy of using anisotropic nanocrystals gives insight into mesoporous thin film fabrication with broader applications for flexible devices.

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Normalized Synergy Predicts That CD8 Co-Receptor Contribution to T Cell Receptor(TCR) and pMHC Binding Decreases As TCR Affinity Increases in Human Viral-Specific T Cells

by Williams, CM; Schonnesen, AA; Zhang, SQ ; Ma, KY; He, CF; Yamamoto, T; Eckhardt, SG; Klebanoff, CA; Jiang, N

FRONTIERS IN IMMUNOLOGY; Volume: 8; Pages: 1-14; Article Number: 894; DOI: 10.3389/fimmu.2017.00894

The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands. CD8 contribution in a native human antigen-specific T cell response remains elusive. Here, using Hepatitis C Virus-specific precursor CTLs spanning a large range of TCR affinities, we discovered that the functional responsiveness of any given TCR correlated with the contribution of CD8 to TCR/pMHC binding. Furthermore, we found that CD8 contribution to TCR/pMHC binding in the two-dimensional (2D) system was more accurately reflected by normalized synergy (CD8 cooperation normalized by total TCR/pMHC bonds) rather than synergy (total CD8 cooperation) alone. While synergy showed an increasing trend with TCR affinity, normalized synergy was demonstrated to decrease with the increase of TCR affinity. Critically, normalized synergy was shown to correlate with CTL functionality and peptide sensitivity, corroborating three-dimensional (3D) analysis of CD8 contribution with respect to TCR affinity. In addition, we identified TCRs that were independent of CD8 for TCR/pMHC binding. Our results resolve the current discrepancy between 2D and 3D analysis on CD8 contribution to TCR/pMHC binding, and demonstrate that naturally occurring high-affinity TCRs are more capable of CD8-independent interactions that yield greater functional responsiveness even with CD8 blocking. Taken together, our data suggest that addition of the normalized synergy parameter to our previously established TCR discovery platform using 2D TCR affinity and sequence test would allow for selection of TCRs specific to any given antigen with the desirable attributes of high TCR affinity, CD8 co-receptor independence and functional superiority. Utilizing TCRs with less CD8 contribution could be beneficial for adoptive cell transfer immunotherapies using naturally occurring or genetically engineered T cells against viral or cancer-associated antigens.

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