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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2019)

This dissertation introduces a physically-informed, abstract synthesis method that applies loopback frequency modulation (FM) to real-time parametric synthesis of percussive sounds. Loopback FM is a variant of FM whereby the output ``loops back'' to modulate its frequency by an amount determined by a feedback coefficient which, when made time-varying, results in pitch glides. Here, loopback FM is used to parametrically synthesize this effect in struck percussion instruments, known to exhibit this characteristic due to nonlinearities in modal coupling. Inspired by the sonic potential of physics-based nonlinear percussion synthesis models, the loopback FM synthesis method uses an abstract synthesis approach in order to create a wide variety of percussive sounds in real-time. A linear, modal synthesis percussion model is modified to use loopback FM oscillators, which allows the model to create unique, eclectic, and experimental sounding percussive hits in real-time. Musically intuitive parameters are emphasized resulting in a usable percussion sound synthesis method.

  • 29 supplemental audio files
Cover page: Physically-informed Percussion Synthesis with Nonlinearities for Real-time Applications
  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (2009)

Many aspects of physiology and behavior are driven by circadian rhythms that oscillate with a period of roughly twenty-four hours. These circadian rhythms are evolutionarily adapted to entrain to light and to food availability. Light-entrainable circadian rhythms are driven by a master pacemaker that resides in the suprachiasmatic nucleus (SCN), while food-entrainable circadian rhythms are driven by a separate food-entrainable oscillator (FEO), the neural basis of which remains unclear. Serotonin systems have been implicated in the regulation of circadian rhythms. However, the challenge in elucidating the mechanisms by which serotonin regulates circadian rhythms lay in the fact that serotonin exerts its effects via fourteen different serotonin receptors. This thesis investigates the role of serotonin2C receptors (5-HT2CRs) in the regulation of both light- and food-entrainable circadian rhythms, using a combination of genetics, behavioral assessment, and anatomical analysis. We present data that indicates an important contribution of 5-HT2CRs to the facilitation of light entrainable circadian rhythms, and to the gating of food-entrainable circadian rhythms.

    Cover page: Contribution of serotonin 2C receptors to the regulation of circadian rhythm entrainment
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2010)
    The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin(2C) receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways.
      Cover page: Enhanced Food Anticipatory Activity Associated with Enhanced Activation of Extrahypothalamic Neural Pathways in Serotonin2C Receptor Null Mutant Mice
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)
      Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children.
        Cover page: Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda
        • Article
        • Peer Reviewed
        LBL Publications (2020)
        Although pyroptosis is critical for macrophages against pathogen infection, its role and mechanism in cancer cells remains unclear. PD-L1 has been detected in the nucleus, with unknown function. Here we show that PD-L1 switches TNFα-induced apoptosis to pyroptosis in cancer cells, resulting in tumour necrosis. Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation, enhancing the transcription of the gasdermin C (GSDMC) gene. GSDMC is specifically cleaved by caspase-8 with TNFα treatment, generating a GSDMC N-terminal domain that forms pores on the cell membrane and induces pyroptosis. Nuclear PD-L1, caspase-8 and GSDMC are required for macrophage-derived TNFα-induced tumour necrosis in vivo. Moreover, high expression of GSDMC correlates with poor survival. Antibiotic chemotherapy drugs induce pyroptosis in breast cancer. These findings identify a non-immune checkpoint function of PD-L1 and provide an unexpected concept that GSDMC/caspase-8 mediates a non-canonical pyroptosis pathway in cancer cells, causing tumour necrosis.
          Cover page: PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2016)
            Cover page: 31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part oneCreative Commons 'BY' version 4.0 license
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