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Open Access Publications from the University of California

Scholarly Works (11 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2021)

Internet of things (IoT) has greatly improved our understanding and control of the world. By deploying sensors to the environment, different types of environmental parameters can be sensed and with proper processing of the data, such as artificial intelligence, we can observe and control at both the top-level and detail. However, various IoT applications also pose lots of challenges for the integrated circuit design, especially for the power efficiency, speed and size. Solving these problems are the keys to turn the ideas into real and practical design and improve the user experience.

In this dissertation, the circuits and systems design of the IoT sensor is presented and discussed. The power management unit (PMU) is an important block in an IoT sensing system, which determines the maximum performance of the circuit. For lots of applications where it is hard to replace the battery and has limited energy source, the efficiency of the PMU also significantly affects the system lifetime. A fast-response-time, high-power-efficiency and dynamic-range change-pump-based LDO is proposed to solve the trade-off between speed, power consumption and stability. The event-driven mechanism and AC-coupled high-Z feedback loop enable fast detection and response speed with low power. The charge-pump with single power transistor architecture helps the LDO achieve a high dynamic range and low ripple over the entire load range. In addition to the power management unit, the clock generation circuit also significantly affects the system performance and power efficiency. Several techniques are proposed to achieve an energy-efficient fast start-up. With the multi-path feedforward negative resistance boosting and dynamic pulse-width injection technique, the start-up time of different frequency XOs can be greatly reduced without a precise injection oscillator. Last, a battery-powered ion-sensing platform is presented and discussed.

    Cover page: Energy-Efficient Circuits for IoT Systems
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2021)
    High temperatures are a major threat to plant growth and development, leading to yield losses in crops. Calcium-dependent protein kinases (CPKs) act as critical components of Ca2+ sensing in plants that transduce rapid stress-induced responses to multiple environmental stimuli. However, the role of CPKs in plant thermotolerance and their mechanisms of action remain poorly understood. To address this issue, tomato (Solanum lycopersicum) cpk28 mutants were generated using a CRISPR-Cas9 gene-editing approach. The responses of mutant and wild-type plants to normal (25°C) and high temperatures (45°C) were documented. Thermotolerance was significantly decreased in the cpk28 mutants, which showed increased heat stress-induced accumulation of reactive oxygen species (ROS) and levels of protein oxidation, together with decreased activities of ascorbate peroxidase (APX) and other antioxidant enzymes. The redox status of ascorbate and glutathione were also modified. Using a yeast two-hybrid library screen and protein interaction assays, we provide evidence that CPK28 directly interacts with cytosolic APX2. Mutations in APX2 rendered plants more sensitive to high temperatures, whereas the addition of exogenous reduced ascorbate (AsA) rescued the thermotolerance phenotype of the cpk28 mutants. Moreover, protein phosphorylation analysis demonstrated that CPK28 phosphorylates the APX2 protein at Thr-59 and Thr-164. This process is suggested to be responsive to Ca2+ stimuli and may be required for CPK28-mediated thermotolerance. Taken together, these results demonstrate that CPK28 targets APX2, thus improving thermotolerance. This study suggests that CPK28 is an attractive target for the development of improved crop cultivars that are better adapted to heat stress in a changing climate.
      Cover page: Inflorescence abscission protein SlIDL6 promotes low light intensity-induced tomato flower abscission
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2021)
      In many fruiting plant species, flower abscission is induced by low light stress. Here, we elucidated how signaling mediated by the peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) controls low light-induced flower drop in tomato (Solanum lycopersicum). We analyzed the expression patterns of an IDA-Like gene (SlIDL6) during low light-induced flower abscission, and used tandem mass spectrometry to identify and characterize the mature SlIDL6 peptide. Tomato knockout lines were created to investigate the in vivo function of SlIDL6. In addition, yeast one-hybrid assays were used to investigate the binding of the SlWRKY17 transcription factor to the SlIDL6 promoter, and silencing of SlWRKY17 expression delayed low light-induced flower abscission. SlIDL6 was specifically expressed in the abscission zone and at high levels during low light-induced abscission and ethylene treatment. SlIDL6 knockout lines showed delayed low light-induced flower drop, and the application of SlIDL6 peptide accelerated abscission. Overexpression of SlIDL6 rescued the ida mutant phenotype in Arabidopsis (Arabidopsis thaliana), suggesting functional conservation between species. SlIDL6-mediated abscission was via an ethylene-independent pathway. We report a SlWRKY17-SlIDL6 regulatory module that functions in low light promoted abscission by increasing the expression of enzymes involved in cell wall remodeling and disassembly.
        Cover page: Inflorescence abscission protein SlIDL6 promotes low light intensityinduced tomato flower abscission
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2021)
        Abscission of plant organs is induced by developmental signals and diverse environmental stimuli and involves multiple regulatory networks, including biotic or abiotic stress-impaired auxin flux in the abscission zone (AZ). Depletion of auxin activates AZ ethylene (ETH) production and triggers acceleration of abscission, a process that requires hydrogen peroxide (H2O2). However, the interaction between these networks and the underlying mechanisms that control abscission are poorly understood. Here, we found that expression of tonoplast intrinsic proteins, which belong to the aquaporin (AQP) family in the AZ was important for tomato (Solanum lycopersicum) pedicel abscission. Liquid chromatography-tandem mass spectrometry and in situ hybridization revealed that SlTIP1;1 was most abundant and specifically present in the tomato pedicel AZ. SlTIP1;1 localized in the plasma membrane and tonoplast. Knockout of SlTIP1;1 resulted in delayed abscission, whereas overexpression of SlTIP1;1 accelerated abscission. Further analysis indicated that SlTIP1;1 mediated abscission via gating of cytoplasmic H2O2 concentrations and osmotic water permeability (Pf). Elevated cytoplasmic levels of H2O2 caused a suppressed auxin signal in the early abscission stage and enhanced ETH production during abscission. Furthermore, we found that increasing Pf was required to enhance the turgor pressure to supply the break force for AZ cell separation. Moreover, we observed that SlERF52 bound directly to the SlTIP1;1 promoter to regulate its expression, demonstrating a positive loop in which cytoplasmic H2O2 activates ETH production, which activates SlERF52. This, in turn, induces SlTIP1;1, which leads to elevated cytoplasmic H2O2 and water influx.
          Cover page: SlERF52 Regulates SlTIP1;1 Expression to Accelerate Tomato Pedicel Abscission
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2022)
          Plant organ abscission, a process that is important for development and reproductive success, is inhibited by the phytohormone auxin and promoted by another phytohormone, jasmonic acid (JA). However, the molecular mechanisms underlying the antagonistic effects of auxin and JA in organ abscission are unknown. We identified a tomato (Solanum lycopersicum) class III homeodomain-leucine zipper transcription factor, HOMEOBOX15A (SlHB15A), which was highly expressed in the flower pedicel abscission zone and induced by auxin. Knocking out SlHB15A using clustered regularly interspaced short palindromic repeats-associated protein 9 technology significantly accelerated abscission. In contrast, overexpression of microRNA166-resistant SlHB15A (mSlHB15A) delayed abscission. RNA sequencing and reverse transcription-quantitative PCR analyses showed that knocking out SlHB15A altered the expression of genes related to JA biosynthesis and signaling. Furthermore, functional analysis indicated that SlHB15A regulates abscission by depressing JA-isoleucine (JA-Ile) levels through inhabiting the expression of JASMONATE-RESISTANT1 (SlJAR1), a gene involved in JA-Ile biosynthesis, which could induce abscission-dependent and abscission-independent ethylene signaling. SlHB15A bound directly to the SlJAR1 promoter to silence SlJAR1, thus delaying abscission. We also found that flower removal enhanced JA-Ile content and that application of JA-Ile severely impaired the inhibitory effects of auxin on abscission. These results indicated that SlHB15A mediates the antagonistic effect of auxin and JA-Ile during tomato pedicel abscission, while auxin inhibits abscission through the SlHB15A-SlJAR1 module.
            Cover page: The HD-Zip transcription factor SlHB15A regulates abscission by modulating jasmonoyl-isoleucine biosynthesis.
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2022)
            Premature abscission of flowers and fruits triggered by low light stress can severely reduce crop yields. However, the underlying molecular mechanism of this organ abscission is not fully understood. Here, we show that a gene (SlCLV3) encoding CLAVATA3 (CLV3), a peptide hormone that regulates stem cell fate in meristems, is highly expressed in the pedicel abscission zone (AZ) in response to low light in tomato (Solanum lycopersicum). SlCLV3 knockdown and knockout lines exhibit delayed low light-induced flower drop. The receptor kinases SlCLV1 and BARELY ANY MERISTEM1 function in the SlCLV3 peptide-induced low light response in the AZ to decrease expression of the transcription factor gene WUSCHEL (SlWUS). DNA affinity purification sequencing identified the transcription factor genes KNOX-LIKE HOMEDOMAIN PROTEIN1 (SlKD1) and FRUITFULL2 (SlFUL2) as SlWUS target genes. Our data reveal that low light reduces SlWUS expression, resulting in higher SlKD1 and SlFUL2 expression in the AZ, thereby perturbing the auxin response gradient and causing increased ethylene production, eventually leading to the initiation of abscission. These results demonstrate that the SlCLV3-SlWUS signaling pathway plays a central role in low light-induced abscission by affecting auxin and ethylene homeostasis.
              Cover page: A SlCLV3-SlWUS module regulates auxin and ethylene homeostasis in low light-induced tomato flower abscission.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)

              Background

              In 2015, herpes simplex virus 1 (HSV-1)-derived talimogene laherparepvec (T-VEC) was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment. However, its antitumor application is limited to local treatment of melanoma, and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity. We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.

              Methods

              We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1. Then, we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1. Furthermore, we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.

              Results

              We identified eight IFN-stimulated genes (ISGs) controlling HSV-1 replication, among which BTB and CNC homology 1 (BACH1) suppressed HSV-1 replication by inhibiting the transcription of ICP4, ICP27, and UL39. Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis, HMGB1 secretion, and calreticulin exposure in tumor cells. More importantly, hemin, an FDA-approved drug known to downregulate BACH1, significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.

              Conclusions

              Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.
                Cover page: Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2017)
                The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.
                  Cover page: A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2023)
                  Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.
                    Cover page: Signalling by senescent melanocytes hyperactivates hair growth
                    • Article
                    • Peer Reviewed
                    UC Santa Cruz Previously Published Works (2024)
                    Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.
                      Cover page: Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA.
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