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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 (2015)

This dissertation investigates the design of control algorithms and calibration methods for

Microscale Rate Integrating Gyroscopes (MRIGs). As its name implies, a MRIG operates

in rate integrating mode and can directly measure the rotation angle of the base where it

is mounted. However, the MRIG mechanical system does not spontaneously operate in a

rate integrating mode, but requires an active controller. Such a controller enables the MRIG to oscillate in a specific pattern that is related to the input rotation angle in a measurable way.

Conventional micro-machined gyroscopes (i.e. MEMS gyroscopes) operate in rate mode (as apposed to rate integrating mode). That is, the gyroscope directly measures the rotation rate of the base. The measured rotation rate is then numerically integrated over time to obtain the input rotation angle. The main drawback of this measuring mechanism is that, by integrating, the rate measurement error will propagate over time, causing the angle measurement to drift from the real input angle. MRIG, by its operating principle, can directly measure the input rotation angle; hence it suffers from no such error propagation.

A well-known control scheme for rate integrating gyroscopes was proposed by Lynch in 1995 [51]. This control scheme has demonstrated its efficacy on precisely fabricated rate integrating gyroscopes such as Hemispherical Resonance Gyroscopes (HRGs). However, for MRIGs fabricated by micro-fabrication technology, fabrication imperfections significantly degrade the gyro performance. In addition, the Lynch-proposed-scheme is essentially nonlinear. As a consequence, the controller performance is hard to predict and analyze prior to real tests.

In this dissertation, a novel demodulation method is developed to transform the original nonlinear control problem into a linear time invariant controller design problem. This technique is based on the averaging method proposed by Lynch [50] but enables the use of well studied linear system theory for MRIG controller design and analysis. The resulting controller design for MRIGs is much more tractable and the performance is rather predictable. This fundamental improvement also opens up new opportunities for implementing and analyzing control systems based on linear control theory.

Two schemes are proposed in this dissertation to compensate for the parameter mismatches caused by fabrication imperfections. The first one is based on electrostatic spring softening and tuning. The basic operation principle is first introduced. Then a full derivation of this method on a real MRIG configuration is conducted. Experimental results confirm that this compensation scheme can significantly attenuate the parameter mismatch.

The other compensation scheme considered in this dissertation is an adaptive compensation scheme consisting of three feedforward controllers. Each of them runs on top of the corresponding feedback control loop and estimates and compensates parameter mismatches in real time. We also present a stability and convergence analysis that shows such adaptive controllers converge to the correct values and perfectly cancel the parameter mismatch. A simulation study performed on a MRIG model also confirms the efficacy of the compensation scheme. Then a self-calibration process is proposed to automatically calibrate the gyroscope. This self-calibration method requires no human involvement or auxiliary device, hence enables the gyroscope to calibrate itself whenever necessary, even in use.

    Cover page: Control and Self-Calibration of Microscale Rate Integrating Gyroscopes (MRIGs)
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2024)
    Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.
      Cover page: Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2022)
      Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.
        Cover page: SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)
        Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8.43 months) than low baseline pEGFRmut (16.23 months; p = 0.0019). By contrast, there were no differences in tumor shrinkage or overall survival between groups. During EGFR-TKI treatment, pEGFRmut levels decreased to zero in 89.58% of patients. Twenty-five of the 27 patients who progressed had basal pEGFRmut, and 18 also had circulating T790M. All 20 patients with dramatic progression (according to a categorization system for EGFR-TKIs failure) had basal pEGFRmut, and 13 had T790M mutation at progression. These results support the use of ddPCR for analysis of plasma EGFR mutations for prediction of PFS and to monitor clinical responses to EGFR-TKIs in NSCLC patients.
          Cover page: Estimation of cell-free circulating EGFR mutation concentration predicts outcomes in NSCLC patients treated with EGFR-TKIs
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2018)
          Zika virus (ZIKV) has elicited global concern due to its unique biological features, unusual transmission routes, and unexpected clinical outcomes. Although ZIKV transmission through anal intercourse has been reported in humans, it remains unclear if ZIKV is detectable in the stool, if it can infect the host through the anal canal mucosa, and what the pathogenesis of such a route of infection might be in the mouse model. Herein, we demonstrate that ZIKV RNA can be recovered from stools in multiple mouse models, as well as from the stool of a ZIKV patient. Remarkably, intra-anal (i.a.) inoculation with ZIKV leads to efficient infection in both Ifnar1-/- and immunocompetent mice, characterized by extensive viral replication in the blood and multiple organs, including the brain, small intestine, testes, and rectum, as well as robust humoral and innate immune responses. Moreover, i.a. inoculation of ZIKV in pregnant mice resulted in transplacental infection and delayed fetal development. Overall, our results identify the anorectal mucosa as a potential site of ZIKV infection in mice, reveal the associated pathogenesis of i.a. infection, and highlight the complexity of ZIKV transmission through anal intercourse.
            Cover page: Zika virus shedding in the stool and infection through the anorectal mucosa in mice
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2022)

            Background

            Viral tracers are important tools for mapping brain connectomes. The feature of predominant anterograde transneuronal transmission offers herpes simplex virus-1 (HSV-1) strain H129 (HSV1-H129) as a promising candidate to be developed as anterograde viral tracers. In our earlier studies, we developed H129-derived anterograde polysynaptic tracers and TK deficient (H129-dTK) monosynaptic tracers. However, their broad application is limited by some intrinsic drawbacks of the H129-dTK tracers, such as low labeling intensity due to TK deficiency and potential retrograde labeling caused by axon terminal invasion. The glycoprotein K (gK) of HSV-1 plays important roles in virus entry, egress, and virus-induced cell fusion. Its deficiency severely disables virus egress and spread, while only slightly limits viral genome replication and expression of viral proteins. Therefore, we created a novel H129-derived anterograde monosynaptic tracer (H129-dgK) by targeting gK, which overcomes the limitations of H129-dTK.

            Methods

            Using our established platform and pipeline for developing viral tracers, we generated a novel tracer by deleting the gK gene from the H129-G4. The gK-deleted virus (H129-dgK-G4) was reconstituted and propagated in the Vero cell expressing wildtype H129 gK (gKwt) or the mutant gK (gKmut, A40V, C82S, M223I, L224V, V309M), respectively. Then the obtained viral tracers of gKmut pseudotyped and gKwt coated H129-dgK-G4 were tested in vitro and in vivo to characterize their tracing properties.

            Results

            H129-dgK-G4 expresses high levels of fluorescent proteins, eliminating the requirement of immunostaining for imaging detection. Compared to the TK deficient monosynaptic tracer H129-dTK-G4, H129-dgK-G4 labeled neurons with 1.76-fold stronger fluorescence intensity, and visualized 2.00-fold more postsynaptic neurons in the downstream brain regions. gKmut pseudotyping leads to a 77% decrease in retrograde labeling by reducing axon terminal invasion, and thus dramatically improves the anterograde-specific tracing of H129-dgK-G4. In addition, assisted by the AAV helper trans-complementarily expressing gKwt, H129-dgK-G4 allows for mapping monosynaptic connections and quantifying the circuit connectivity difference in the Alzheimer's disease and control mouse brains.

            Conclusions

            gKmut pseudotyped H129-dgK-G4, a novel anterograde monosynaptic tracer, overcomes the limitations of H129-dTK tracers, and demonstrates desirable features of strong labeling intensity, high tracing efficiency, and improved anterograde specificity.
              Cover page: A novel H129-based anterograde monosynaptic tracer exhibits features of strong labeling intensity, high tracing efficiency, and reduced retrograde labeling
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