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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2017)

Scientists and engineers have investigated various types of stable and accurate optical synthesizers, where mode-locked laser based optical frequency comb synthesizers have been widely investigated. These frequency combs bridge the frequencies from optical domain to microwave domain with orders of magnitude difference, providing a metrological tool for various platforms. The demand for highly robust, scalable, compact and cost-effective femtosecond-laser synthesizers, however, are of great importance for applications in air- or space-borne platforms, where low cost and rugged packaging are particularly required. This has been afforded in the past several years due to breakthroughs in chip-scale nanofabrication, bringing advances in optical frequency combs down to semiconductor chips. These platforms, with significantly enhanced light-matter interaction, provide a fertile sandbox for research rich in nonlinear dynamics, and offer a reliable route towards low-phase noise photonic oscillators, broadband optical frequency synthesizers, miniaturized optical clockwork, and coherent terabit communications.

The dissertation explores various types of optical frequency comb synthesizers based on nonlinear microresonators. Firstly, the fundamental mechanism of mode-locking in a high-quality factor microresonator is examined, supported by ultrafast optical characterizations, analytical closed-form solutions and numerical modeling. In the evolution of these frequency microcombs, the key nonlinear dynamical effect governing the comb state coherence is rigorously analyzed. Secondly, a prototype of chip-scale optical frequency synthesizer is demonstrated, with the laser frequency comb stabilized down to instrument-limited 50-mHz RF frequency inaccuracies and 10-16 fractional frequency inaccuracies, near the fundamental limits. Thirdly, a globally stable Turing pattern is achieved and characterized in these nonlinear resonators with high-efficiency conversion, subsequently generating coherent high-power terahertz radiation via plasmonic photomixers. Finally, a new universal modality of frequency combs is discussed, including satellite states, dynamical tunability, and high efficiency conversion towards direct chip-scale optical frequency synthesis at the precision metrology frontiers.

    Cover page: Chip-Scale Architectures for Precise Optical Frequency Synthesis
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2016)

    Background

    The dual role of B cells as drivers and suppressors of the immune responses have underscored the need to trace the fate of B cells recognizing donor major histocompatibility complex class I and class II after allograft transplantation.

    Methods

    In this study, we used donor class II tetramers to trace the fate of I-E-specific B cells after immunization with BALB/c spleen cells or cardiac transplantation, in naive or sensitized C57BL/6 recipients. We combined this approach with genetic lineage tracing of memory B cells in activation-induced cytidine deaminase regulated Cre transgenic mice crossed to the ROSA26-enhanced yellow fluorescent protein reporter mice to track endogenous I-E-specific memory B cell generation.

    Results

    Immunization with BALB/c splenocytes or heart transplantation induced an expansion and differentiation of I-E-specific B cells into germinal center B cells, whereas BALB/c heart transplantation into sensitized recipients induced the preferential differentiation into antibody-secreting cells. A 10.8-fold increase in the frequency of I-E-specific memory B cells was observed by day 42 postimmunization. Treatment with CTLA4-Ig starting on day 0 or day 7 postimmunization abrogated I-E-specific memory B cell generation and sensitized humoral responses, but not if treatment commenced on day 14.

    Conclusions

    The majority of donor-specific memory B cells are generated between days 7 and 14 postimmunization, thus revealing a flexible timeframe whereby delayed CTLA4-Ig administration can inhibit sensitization and the generation of memory graft-reactive B cells.
      Cover page: Tracing Donor-MHC Class II Reactive B cells in Mouse Cardiac Transplantation
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2020)
      The absence of alloantibodies is a feature of transplantation tolerance. Although the lack of T cell help has been evoked to explain this absence, herein we provide evidence for B cell-intrinsic tolerance mechanisms. Using a murine model of heart tolerance, we showed that alloreactive B cells were not deleted but rapidly lost their ability to differentiate into germinal center B cells and secrete donor-specific antibodies. We inferred that tolerant alloreactive B cells retained their ability to sense alloantigen because they continued to drive T cell maturation into CXCR5+PD-1+ T follicular helper cells. Unexpectedly, dysfunctional alloreactive B cells acquired the ability to inhibit antibody production by new naive B cells in an antigen-specific manner. Thus, tolerant alloreactive B cells contribute to transplantation tolerance by foregoing germinal center responses while retaining their ability to function as antigen-presenting cells and by actively suppressing de novo alloreactive B cell responses.
        Cover page: Transplantation tolerance modifies donor-specific B cell fate to suppress de novo alloreactive B cells
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2017)
        Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients. Continuous CTLA4-Ig treatment was unexpectedly efficacious at inhibiting endogenous graft-reactive T cell expansion but was unable to inhibit late CD4+ and CD8+ T cell infiltration into the allografts, and rejection was observed in 50% of recipients by day 35 after transplantation. When CTLA4-Ig was combined with the sphingosine 1-phosphate receptor-1 (S1PR1) functional antagonist FTY720, alloantibody production was inhibited and donor-specific IFN-γ-producing T cells were reduced to levels approaching nonsensitized tolerant recipients. Late T cell recruitment into the graft was also restrained, and graft survival improved with this combination therapy. These observations suggest that a rational strategy consisting of inhibiting memory T cell expansion and trafficking into the allograft with CTLA4-Ig and FTY720 can promote allograft survival in allosensitized recipients.
          Cover page: CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2017)
          Chaos has revolutionized the field of nonlinear science and stimulated foundational studies from neural networks, extreme event statistics, to physics of electron transport. Recent studies in cavity optomechanics provide a new platform to uncover quintessential architectures of chaos generation and the underlying physics. Here, we report the generation of dynamical chaos in silicon-based monolithic optomechanical oscillators, enabled by the strong and coupled nonlinearities of two-photon absorption induced Drude electron-hole plasma. Deterministic chaotic oscillation is achieved, and statistical and entropic characterization quantifies the chaos complexity at 60 fJ intracavity energies. The correlation dimension D2 is determined at 1.67 for the chaotic attractor, along with a maximal Lyapunov exponent rate of about 2.94 times the fundamental optomechanical oscillation for fast adjacent trajectory divergence. Nonlinear dynamical maps demonstrate the subharmonics, bifurcations and stable regimes, along with distinct transitional routes into chaos. This provides a CMOS-compatible and scalable architecture for understanding complex dynamics on the mesoscopic scale.
            Cover page: Mesoscopic chaos mediated by Drude electron-hole plasma in silicon optomechanical oscillators
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2017)
            Clinical observations that kidney transplant recipients receiving belatacept who experienced T cell-mediated acute rejection can be successfully treated and subsequently maintained on belatacept-based immunosuppression suggest that belatacept is able to control memory T cells. We recently reported that treatment with CTLA4-Ig from day 6 posttransplantation successfully rescues allografts from acute rejection in a BALB/c to C57BL/6 heart transplant model, in part, by abolishing B cell germinal centers and reducing alloantibody titers. Here, we show that CTLA4-Ig is additionally able to inhibit established T cell responses independently of B cells. CTLA4-Ig inhibited the in vivo cytolytic activity of donor-specific CD8+ T cells, and the production of IFNγ by graft-infiltrating T cells. Delayed CTLA4-Ig treatment did not reduce the numbers of graft-infiltrating T cells nor prevented the accumulation of antigen-experienced donor-specific memory T cells in the spleen. Nevertheless, delayed CTLA4-Ig treatment successfully maintained long-term graft acceptance in the majority of recipients that had experienced a rejection crisis, and enabled the acceptance of secondary BALB/c heart grafts transplanted 30 days after the first transplantation. In summary, we conclude that delayed CTLA4-Ig treatment is able to partially halt ongoing T cell-mediated acute rejection. These findings extend the functional efficacy of CTLA4-Ig therapy to effector T cells and provide an explanation for why CTLA4-Ig-based immunosuppression in the clinic successfully maintains long-term graft survival after T cell-mediated rejection.
              Cover page: Successful Treatment of T Cell-Mediated Acute Rejection with Delayed CTLA4-Ig in Mice
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