Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (16 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2013)

In this thesis, an oscillator-based touch sensor detection circuit with adaptive resolution has been proposed. Current popular touch screen detection technologies include resistive, capacitance, infrared based imaging sensor; however, some are designed with a fixed resolution and it is not optimal for nowadays low power requirement.

In order to solve this problem, an oscillator-based touch sensor detection circuit with adaptive resolution has been presented. The circuit detects the touching finger by using a 6 stage ring oscillator to sense the change of the input capacitance. To make the resolution tunable, an 8 bit R-2R DAC has been implemented to change the bias voltage of the ring oscillator which will change the oscillator's resonant frequency as well as system resolution. Finally, a digital processing unit has been designed which is used to analyzes the change of the frequency and transfer information to PC to do post-signal processing

The design is achieved by using TSMC 65nm technology, occupying an area of 0.9mm x 1.1mm, power consumption of 10mW when oscillating at 120MHz, and runs on a digital clock frequency of 100KHz. Test result shows that the system can be very sensitive to detect if a finger touch it or not and the resolution can be adaptive by changing the frequency of the oscillator through DAC's output

    Cover page: Oscillator-Based Touch Sensor with Adaptive Resolution
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2016)

    Touch sensing has been widely implemented as a main methodology to bridge human and machine interactions. The traditional touch sensing range is two dimensional and therefore limits the user experience. The required physical contact inherent of the technology creates several disadvantages, including unresponsiveness due to wet fingers, and unavoidable fingerprint residue on the screen surface.

    To overcome these limitations, we propose a novel 3D contactless touch sensing system called Airtouch System, which improves user experience by remotely detecting single/multi-finger position. A single layer touch panel with triangular electrodes is used to achieve 3D multi-touch detection capability as well as manufacturing cost reduction. A lumped model of the touch panel is proposed to model the touch panel property and define the system specification. The hardware part of the proposed 3D touch sensor uses correlated double sampling (CDS) to achieve a high sensing resolution in Z direction and employs bootstrapping circuitry to reduce the mobile screen’s inter-channel-coupling effects. Additionally, to reduce chip area and assembly, the sensing oscillator is implemented with inverter-based active resonators instead of using either on or off chip inductors. The prototyped 3D touch sensor is fabricated using 65-nm CMOS process technology and consumes an area of 2mm2.

    To detect the finger position in space, a new algorithm for finger position estimation is created with grouping filter invented to reduce system background noise. The algorithm is proposed to eliminate the fringing capacitance effect and achieve accurate finger position estimation. EM simulation proved that by taking account of fringing capacitance effect, the proposed algorithm reduced the systematic error by 11dB in the horizontal position detection. Accurate Z direction detection is achieved through using 2nd order polynomial curve to fit the EM model and compensate the non-linear fringing capacitance effect. The proposed system’s hardware circuit consumes 2.3mW and is fully compatible with existing mobile device environments. A prototype is built to demonstrate that the system can successfully detect finger movement in a vertical direction up to 6cm and achieve a horizontal resolution up to 0.6cm at 1cm finger-height. As a new interface for human and machine interactions, this system offers great potential in 3D gesture recognition for small-sized electronics and advanced human interactive games for mobile devices.

      Cover page: AIRTOUCH: A NOVEL SINGLE LAYER 3D TOUCH SENSING SYSTEM FOR HUMAN/MOBILE DEVICE INTERACTIONS
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2022)
      SARS-CoV-2 remains a global health crisis even with effective vaccines and the availability of FDA approved therapies. Efforts to understand the complex disease pathology and develop effective strategies to limit mortality and morbidity are needed. Recent studies reveal circulating Galectin-9 (gal-9), a soluble beta-galactoside binding lectin with immunoregulatory properties, are elevated in SARS-CoV-2 infected individuals with moderate to severe disease. Moreover, in silico studies demonstrate gal-9 can potentially competitively bind the ACE2 receptor on susceptible host cells. Here, we determined whether early introduction of exogenous gal-9 following SARS-CoV-2 infection in humanized ACE2 transgenic mice (K18-hACE2) may reduce disease severity. Mice were infected and treated with a single dose of a human recombinant form of gal-9 (rh-gal-9) and monitored for morbidity. Subgroups of mice were humanely euthanized at 2- and 5- days post infection (dpi) for viral levels by plaque assay, immune changes measures by flow cytometry, and soluble mediators by protein analysis from lung tissue and bronchoalveolar Lavage fluid (BALF). Mice treated with rh-gal-9 during acute infection had improved survival compared to PBS treated controls. At 5 dpi, rh-gal-9 treated mice had enhanced viral clearance in the BALF, but not in the lung parenchyma. Increased T and dendritic cells and decreased neutrophil frequencies in the lung at 5 dpi were observed, whereas BALF had elevated levels of type-I interferons and proinflammatory cytokines. These results suggest a role for rh-gal-9 in limiting acute COVID-19. Further studies are required to determine the optimal design of gal-9 treatment to effectively ameliorate COVID-19 disease.
        Cover page: Galectin-9 protects humanized-ACE2 immunocompetent mice from SARS-CoV-2 infection.
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2023)
          Cover page: CSQ: Growing Mixed-Precision Quantization Scheme with Bi-level Continuous SparsificationCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2023)
            Cover page: NoisyQuant: Noisy Bias-Enhanced Post-Training Activation Quantization for Vision TransformersCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2022)

            Background and aims

            Immunotherapy with programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade has shown low response rates in liver cancer patients, with the underlying mechanisms unclear. To decipher a specific impact of the liver microenvironment, we compared the effects of anti-PD-L1 antibody (αPD-L1) blockade on the same tumor grown s.c. or in the liver.

            Approach and results

            We generated s.c. tumors in mice by inoculating MC38 colorectal cancer (CRC) cells under the skin and metastatic liver tumors by portal vein or splenic injection of CRC cells. Tumor-bearing mice were treated by i.p. injection of αPD-L1, polyinosinic:polycytidylic acid (poly[I:C]), or both. αPD-L1 monotherapy significantly suppressed s.c. tumor growth, but showed no effect on metastatic liver tumors. However, the combination of αPD-L1 with poly(I:C), an innate immunity-stimulating reagent, robustly inhibited tumor progression in liver. The combination therapy effectively down-regulated myeloid-derived suppressor cells (MDSCs), but up-regulated ratios of M1/M2 macrophages, CD8/CD4, and CD8/regulatory T (Treg) cells infiltrated into liver tumors and whole liver. A group of long-lasting T-bet+ Eomes- PD-1- cytotoxic T cells was maintained in the combo-treated liver, leading to resistance to tumor recurrence. Depleting macrophages or blocking type Ⅰ interferon signaling abrogated the synergistic antitumor effect of αPD-L1 and poly(I:C), indicating a requirement of boosting innate immunity for optimized activation of cytotoxic T cells by PD-1/PD-L1 blockade.

            Conclusions

            The poor response of liver cancers to αPD-L1 therapy is largely attributable to a unique hepatic immunotolerant microenvironment, independent of tumor origins or types. The success of a combinatorial immunotherapy relies on coordinated inhibition or activation of various innate and adaptive immune cell activities.
              Cover page: Enhancing the therapeutic efficacy of programmed death ligand 1 antibody for metastasized liver cancer by overcoming hepatic immunotolerance in mice
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2023)

              Background and aims

              SH2 domain-containing protein tyrosine phosphatase 2 (Shp2) is the first identified pro-oncogenic tyrosine phosphatase that acts downstream of receptor tyrosine kinases (RTKs) to promote Ras-extracellular signal-regulated kinase signaling. However, this phosphatase was also shown to be antitumorigenic in HCC. This study is aimed at deciphering paradoxical Shp2 functions and mechanisms in hepatocarcinogenesis and at exploring its value as a pharmaceutical target in HCC therapy.

              Approaches and results

              We took both genetic and pharmaceutical approaches to examine the effects of Shp2 inhibition on primary liver cancers driven by various oncogenes and on metastasized liver tumors. We show here that the catalytic activity of Shp2 was essential for relay of oncogenic signals from RTKs in HCC and that chemical inhibition of Shp2 robustly suppressed HCC driven by RTKs. However, in contrast to a tumor-promoting hepatic niche generated by genetically deleting Shp2 in hepatocytes, treatment with a specific Shp2 inhibitor had a tumor-suppressing effect on metastasized liver tumor progression. Mechanistically, the Shp2 inhibitor enhanced antitumor innate immunity by down-regulating inflammatory cytokines, suppressing the chemokine (C-C motif) receptor 5 signaling axis, but up-regulating interferon-β secretion.

              Conclusions

              These results unveil complex mechanisms for the tumor-suppressing effect of pharmaceutical Shp2 inhibition in the liver immune environment. We provide a proof of principle for clinical trials with specific Shp2 inhibitors in patients with primary and metastasized liver cancer.
                Cover page: Pharmaceutical SH2 domain–containing protein tyrosine phosphatase 2 inhibition suppresses primary and metastasized liver tumors by provoking hepatic innate immunity
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2023)

                Background & aims

                Complex communications between hepatocytes and Kupffer cells (KCs) are known to drive or suppress hepatocarcinogenesis, with controversial data in the literature. In previous experiments that aimed to decipher hepatocyte/KC interactions, we unexpectedly unveiled a tumor-suppressing effect of polyinosinic-polycytidylic acid, a widely used inducer of MX dynamin like GTPase 1 (Mx1)-cre expression, which questioned a theory of interleukin 1a/6 cytokine circuit in hepatocyte/KC communication. The goal of this study was to clarify the controversy and decipher unique functions of KCs and non-KC macrophages in liver tumorigenesis.

                Methods

                We used the C-type lectin domain family 4 member F (Clec4f)-cre system to delete Src-homology 2 domain-containing tyrosine phosphatase 2 (Shp2)/protein tyrosine phosphatase nonreceptor 11 (Ptpn11) in KCs, and a combination of Clec4f-cre and adeno-associated virus-cre to delete Shp2 in KCs and hepatocytes to investigate the effects on hepatocellular carcinoma development and immune cell compositions/activities.

                Results

                Ablating Shp2 in KCs generated a tumor-promoting niche, which was exacerbated further by concurrent removal of Shp2 in both KCs and hepatocytes. Shp2 deficiency induced KC apoptosis and decreased its numbers, which induced compensatory recruitment of bone marrow-derived monocytes into liver. These newly recruited monocytes differentiated into non-KC macrophages with tumor-associated macrophage function, leading to aggravated tumor progression through down-regulation of CD8 T cells. Tumor-associated macrophage blockade by anti-chemokine (C-C motif) ligand 2 (CCL2) antibody inhibited hepatocellular carcinoma progression, while depletion of all macrophages had a tumor-promoting effect by increasing myeloid-derived suppressor cells (M-MDSCs) and decreasing CD8 T cells.

                Conclusions

                Shp2 loss in KCs or hepatocytes generated a protumorigenic microenvironment, which was exacerbated by its removal in both cell types. These results show the complexity of intercellular signaling events in liver tumorigenesis and raises caution on the use of specific Shp2 inhibitor in liver cancer therapy. Transcript profiling: RNA sequencing data are available at Gene Expression Omnibus (GSE222594).
                  Cover page: Shp2 Deficiency in Kupffer Cells and Hepatocytes Aggravates Hepatocarcinogenesis by Recruiting Non-Kupffer Macrophages
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2018)
                  Salivary gland tumor (SGT) is a rare tumor type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models that faithfully recapitulate the naturally occurring process of human SGTs has hampered research progress on this field. In this report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) of interest in murine salivary gland upon local RU486 delivery. We have deleted two major tumor suppressors, Pten, a negative regulator of the PI3K pathway, and Smad4, the central signaling mediator of TGFβ pathway, in the murine salivary gland. Our results have shown that deletion of either Pten or Smad4 in murine salivary gland resulted in pleomorphic adenomas, the most common tumor in human SGT patients. Deletion of both Pten and Smad4 in murine salivary gland developed several malignancies, with salivary adenoid cystic carcinoma (SACC) being the most frequently seen. Molecular characterization showed that SACC exhibited mTOR activation and TGFβ1 overexpression. Examination of human SGT clinical samples revealed that loss of Pten and Smad4 is common in human SACC samples, particularly in the most aggressive solid form, and is correlated with survival of SACC patients, highlighting the human relevance of the murine models. In summary, our results offer significant insight into synergistic role of Pten and Smad4 in SGT, providing a rationale for targeting mTOR and/or TGFβ signaling to control SGT formation and progression.
                    Cover page: Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and Progression.
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2023)
                    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. In this study, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including immortalized AECs and primary AECs cultured at the air-liquid interface. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an angiotensin-converting enzyme 2 (ACE2)-dependent manner, enhancing the binding of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induced the expression of key pro-inflammatory programs in AECs, including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.
                      Cover page: Human galectin-9 potently enhances SARS-CoV-2 replication and inflammation in airway epithelial cells
                      Top