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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2024)

Materials with strong coupling between structural and electronic degrees of freedom (charge, orbital and spin) are of interest for a wide array of functional applications. Localized electronic states resulting from point defects and bound-excitons in ionic materials influence functional behavior of these materials. We explore the consequences of such couplings on defect properties and excited states, for cases where intrinsic charge and structural disorder give rise to a variety of local environments. Using Density Functional Theory (DFT) with Hubbard U correction and hybrid density functional theory levels of theory, we study how local distortions and chemical disorder influence the localized electronic states determining bulk properties such as defect thermodynamics and scintillation. The work presented in this thesis focuses on two illustrative cases.We investigate the energetics underlying charge ordering, defect formation and clustering in iron oxides. For magnetite (Fe3O4), we study the energetics underlying the ordering of Fe2+ and Fe3+ cations, and the effect of this ordering on point defect energetics and electronic structure. The calculations reveal strong variations in anion and cation vacancy formation energetics and stable charge states with changes in local environment. We also extend this study to oxygen-iron vacancy complexes in magnetite (Fe3O4) and hematite (Fe2O3) and find a significant thermodynamic driving force for oxygen and iron vacancies to bind. The results have potentially important implications for ionic transport, as the low energy defect configurations in certain local chemical environments can lead to percolating networks of low-energy migration pathways. In the second topic, we consider the nature of localized exciton states in Tl2LiYCl6, a promising candidate for commercial scintillator applications such as γ-ray detection. The driving forces for structural distortions away from the idealized cubic elpasolite crystal structure are discussed as originating from maximizing the energy lowering interactions of Tl and Cl orbitals. These distortions influence the bulk electronic structure and lead to different stable and metastable exciton configurations. Comparison of electron-hole binding energies of exciton configurations show that the Tl+ centered exciton exhibits the best agreement with the broad peak, as observed in the measured emission spectra. Collectively, this work explores complexities of simulating localized defect and exciton electronic states in materials with variations in the coupled local structural and chemical environments. This research motivates further studies into developing approaches for sampling defect and exciton configurations generated by coupling of localized electronic states with structural and chemical order in the bulk.

    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2021)
    The soft, dynamic lattice of inorganic lead halide perovskite CsPbX3 (X = Cl-, Br-, I-) leads to the emergence of many interesting photophysical and optoelectronic phenomena. However, probing their lattice dynamics with vibrational spectroscopy remains challenging. The influence of the fundamental octahedral building block in the perovskite lattice can be better resolved in zero-dimensional (0D) vacancy-ordered double perovskites of form A2BX6. Here we study Cs2TeX6 (X = Cl-, Br-, I-) single crystals to yield detailed insight into the fundamental octahedral building block and to explore the effect that its isolation in the crystal structure has on structural and electronic properties. The isolated [TeX6]2- octahedral units serve as the vibrational, absorbing, and emitting centers within the crystal. Serving as the vibrational centers, the isolated octahedra inform the likelihood of a random distribution of 10 octahedral symmetries within the mixed-halide spaces, as well as the presence of strong exciton-phonon coupling and anharmonic lattice dynamics. Serving as the absorbing and emitting centers, the isolated octahedra exhibit compositionally tunable absorption (1.50-3.15 eV) and emission (1.31-2.11 eV) energies. Due to greater molecular orbital overlap between neighboring octahedra with increasing halide anion size, there is a transition from a more molecule-like electronic structure in Cs2TeCl6 and Cs2TeBr6-as expected from the effective 0D nature of these single crystals-to a dispersive electronic structure in Cs2TeI6, typical of three-dimensional (3D) bulk single crystals.
      Cover page: Lattice Dynamics and Optoelectronic Properties of Vacancy-Ordered Double Perovskite Cs2TeX6 (X = Cl–, Br–, I–) Single Crystals
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2014)
      Immunostimulatory cytokines can enhance anti-tumor immunity and are part of the therapeutic armamentarium for cancer treatment. We have previously reported that post-transplant lymphoma patients have an acquired deficiency of signal transducer and activator of transcription 4, which results in defective IFNγ production during clinical immunotherapy. With the goal of further improving cytokine-based immunotherapy, we examined the effects of a soybean peptide called lunasin that synergistically works with cytokines on natural killer (NK) cells. Peripheral blood mononuclear cells of healthy donors and post-transplant lymphoma patients were stimulated with or without lunasin in the presence of IL-12 or IL-2. NK activation was evaluated, and its tumoricidal activity was assessed using in vitro and in vivo tumor models. Chromatin immunoprecipitation assay was performed to evaluate the histone modification of gene loci that are regulated by lunasin and cytokine. Adding lunasin to IL-12- or IL-2-stimulated NK cells demonstrated synergistic effects in the induction of IFNG and GZMB involved in cytotoxicity. The combination of lunasin and cytokines (IL-12 plus IL-2) was capable of restoring IFNγ production by NK cells from post-transplant lymphoma patients. In addition, NK cells stimulated with lunasin plus cytokines displayed higher tumoricidal activity than those stimulated with cytokines alone using in vitro and in vivo tumor models. The underlying mechanism responsible for the effects of lunasin on NK cells is likely due to epigenetic modulation on target gene loci. Lunasin represents a different class of immune modulating agent that may augment the therapeutic responses mediated by cytokine-based immunotherapy.
        Cover page: Soypeptide lunasin in cytokine immunotherapy for lymphoma
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2023)
        Calculations of point defect energetics with Density Functional Theory (DFT) can provide valuable insight into several optoelectronic, thermodynamic, and kinetic properties. These calculations commonly use methods ranging from semi-local functionals with a-posteriori corrections to more computationally intensive hybrid functional approaches. For applications of DFT-based high-throughput computation for data-driven materials discovery, point defect properties are of interest, yet are currently excluded from available materials databases. This work presents a benchmark analysis of automated, semi-local point defect calculations with a-posteriori corrections, compared to 245 “gold standard” hybrid calculations previously published. We consider three different a-posteriori correction sets implemented in an automated workflow, and evaluate the qualitative and quantitative differences among four different categories of defect information: thermodynamic transition levels, formation energies, Fermi levels, and dopability limits. We highlight qualitative information that can be extracted from high-throughput calculations based on semi-local DFT methods, while also demonstrating the limits of quantitative accuracy.
          Cover page: High-throughput calculations of charged point defect properties with semi-local density functional theory—performance benchmarks for materials screening applicationsCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2016)

          Purpose

          Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity of nivolumab in a hypothesis-generating prospective mRCC trial.

          Experimental design

          Nivolumab was administered intravenously every 3 weeks at 0.3, 2, or 10 mg/kg to previously treated patients and 10 mg/kg to treatment-naïve patients with mRCC. Baseline and on-treatment biopsies and blood were obtained. Clinical activity, tumor-associated lymphocytes, PD-L1 expression (Dako immunohistochemistry; ≥5% vs. <5% tumor membrane staining), tumor gene expression (Affymetrix U219), serum chemokines, and safety were assessed.

          Results

          In 91 treated patients, median overall survival [95% confidence interval (CI)] was 16.4 months [10.1 to not reached (NR)] for nivolumab 0.3 mg/kg, NR for 2 mg/kg, 25.2 months (12.0 to NR) for 10 mg/kg, and NR for treatment-naïve patients. Median percent change from baseline in tumor-associated lymphocytes was 69% (CD3+), 180% (CD4+), and 117% (CD8+). Of 56 baseline biopsies, 32% had ≥5% PD-L1 expression, and there was no consistent change from baseline to on-treatment biopsies. Transcriptional changes in tumors on treatment included upregulation of IFNγ-stimulated genes (e.g., CXCL9). Median increases in chemokine levels from baseline to C2D8 were 101% (CXCL9) and 37% (CXCL10) in peripheral blood. No new safety signals were identified.

          Conclusions

          Immunomodulatory effects of PD-1 inhibition were demonstrated through multiple lines of evidence across nivolumab doses. Biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. These data may inform potential combinations. Clin Cancer Res; 22(22); 5461-71. ©2016 AACR.
            Cover page: Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2022)
            The CBFA2T3-GLIS2 (C/G) fusion is a product of a cryptic translocation primarily seen in infants and early childhood and is associated with dismal outcome. Here, we demonstrate that the expression of the C/G oncogenic fusion protein promotes the transformation of human cord blood hematopoietic stem and progenitor cells (CB HSPCs) in an endothelial cell coculture system that recapitulates the transcriptome, morphology, and immunophenotype of C/G acute myeloid leukemia (AML) and induces highly aggressive leukemia in xenograft models. Interrogating the transcriptome of C/G-CB cells and primary C/G AML identified a library of C/G-fusion-specific genes that are potential targets for therapy. We developed chimeric antigen receptor (CAR) T cells directed against one of the targets, folate receptor α (FOLR1), and demonstrated their preclinical efficacy against C/G AML using in vitro and xenograft models. FOLR1 is also expressed in renal and pulmonary epithelium, raising concerns for toxicity that must be addressed for the clinical application of this therapy. Our findings underscore the role of the endothelial niche in promoting leukemic transformation of C/G-transduced CB HSPCs. Furthermore, this work has broad implications for studies of leukemogenesis applicable to a variety of oncogenic fusion-driven pediatric leukemias, providing a robust and tractable model system to characterize the molecular mechanisms of leukemogenesis and identify biomarkers for disease diagnosis and targets for therapy.
              Cover page: CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target
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