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Open Access Publications from the University of California

Scholarly Works (6 results)

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

A multi-agent system is defined as a collection of intelligent agents which are able to interact with each other or with their environments to solve problems that are beyond the individual capacities or knowledge of each problem solver. Distributed optimization in a multi-agent system allows for acting the agents in a distributed manner (using only local information from their neighbors) to achieve global optimization objectives cooperatively so as to increase flexibility and robustness. Examples of cooperative tasks include optimization of network flows, big-data analysis, design of sensor networks, multi-robot teams, and resource allocation. In this dissertation, two distributed optimization problems are investigated, where two different methods of convex optimization and reinforcement learning are employed to solve these problems.

In our first problem, a distributed time-varying convex optimization problem is studied for continuous-time multi-agent systems. The objective is to minimize the sum of local time-varying objective functions, each of which is known to only an individual agent, through local interaction. Here, the optimal point is time varying and creates an optimal trajectory, which renders extra challenge to well-studied distributed time-invariant optimization problems. To begin with, we study distributed time-varying optimization problems with convex objective functions for undirected topologies. We propose multiple optimization algorithms for different application scenarios: 1) optimization problems that do not have explicit bounds on any information about the local objective functions, 2) optimization problems with linear equality constraints, 3) optimization problems with nonlinear inequality constraints, and 4) optimization problems with both linear equality and nonlinear inequality constraints. Furthermore, we aim to seek a design methodology for distributed time-varying optimization under possibly weight-unbalanced directed networks---the most general and thus most challenging case from the network topology perspective. Particularly, we study distributed time-varying optimization problems with quadratic objective functions, which are also called distributed average tracking problems.

In the last part of this dissertation, the packet routing (path optimization) problem is addressed for distributed communication network systems that are consist of multiple routers and multiple links. Here, the goal is that all the routers work cooperatively to get all the packets delivered to their destinations through available paths with minimum time overall. Specifically, we aim to find optimal paths for packets in the presence of link failures, which is a crucial challenge faced by communication networks. We propose to leverage deep policy optimization (reinforcement learning) algorithms for enabling distributed model-free control in communication networks and present a novel meta-learning-based framework for enabling quick adaptation to topology changes.

    Cover page: Distributed Optimization in Multi-Agent Systems: Continuous-Time Convex Optimization and Policy Optimization Based Packet Routing
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2024)
    A notable ambiguity persists concerning whether distinct forms of parent-child triangulation (unstable coercive coalition, stable coalition, detouring-attacking, detouring supportive, parentification) might mediate the association between interparental conflict and early adolescent depressive symptoms similarly within the context of Chinese Confucianism. Filling this research gap, this study aimed to examine the mediating role of the five dimensions of parent-child triangulation in the association between interparental conflict and early adolescent depressive symptoms, as well as the moderating effect of grandparent support on this mediating pathway. Data were drawn from a sample of 761 Chinese adolescents (M age = 12.82 ± 0.47, 49.1% girls). Structural equation model analyses indicated that unstable coercive coalition, stable coalition, and detouring-attacking behaviors partially mediated the association between interparental conflict and adolescent depressive symptoms, while detouring-supportive behaviors and parentification did not demonstrate such mediating effects. Unlike Western societies, a negative correlation was observed between interparental conflict and parentification in the context of China. Grandparent support mitigated the adverse effects of both interparental conflict and the unstable coercive coalition on early adolescent depressive symptoms.
      Cover page: Interparental Conflict and Early Adolescent Depressive Symptoms: Parent-Child Triangulation as the Mediator and Grandparent Support as the Moderator.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2014)

      Background

      Peptidyl-prolyl isomerase cyclophilin A (CypA) plays important roles in signaling, protein translocation, inflammation, and cancer formation. However, little is known about the mechanisms by which CypA exerts its effects. C57BL/6 Ppia (encoding CypA)-deficient embryonic fibroblasts show reduced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the p65/RelA subunit, suggesting that CypA may mediate modulation of NF-κB activity to exert its biological effects.

      Methodology

      Western blotting and qRT-PCR analyses were used to evaluate the association of CypA deficiency with reduced activation of NF-κB/p65 at the protein level. GST pull-down and co-immunoprecipitation were used to examine interactions between CypA and p65/RelA. Truncation mutants and site-directed mutagenesis were used to determine the sequences of p65/RelA required for interactions with CypA. Enhancement of p65/RelA nuclear translocation by CypA was assessed by co-transfection and immunofluorescent imaging. Treatment of cells with cycloheximide that were harvested at various time points for Western blot analyses was carried out to evaluate p65/RelA protein stability. The functional activity of NF-κB was assessed by electrophoretic mobility-shift assays (EMSA), luciferase assays, and changes in expression levels of target genes.

      Results

      GST pull-down assays in vitro and co-immunoprecipitation analyses in vivo provided evidence for protein-protein interactions. These interactions were further supported by identification of a CypA-binding consensus-like sequence within NF-κB subunit p65 at the N-terminal 170-176 amino acid residues. Significantly, CypA provided stability for NF-κB p65 and promoted NF-κB p65 nuclear translocation, resulting in increased nuclear accumulation and enhanced NF-κB activity.

      Conclusions

      Our findings revealed important mechanisms that regulate NF-κB activation, and offer new insights into the role of CypA in aberrant activation of NF-κB-mediated signaling for altered expression of its target genes, resulting in pathological effects in various diseases.
        Cover page: Cyclophilin A (CypA) Interacts with NF-κB Subunit, p65/RelA, and Contributes to NF-κB Activation Signaling
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2011)
        Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human astrocytes and normal counterparts of brain tissue. To determine the role of over-expressed CypA in glioblastoma, stable RNA interference (RNAi)-mediated knockdown of CypA (CypA KD) was performed in gliobastoma cell line U87vIII (U87MG · ΔEGFR). CypA KD stable single clones decrease proliferation, infiltration, migration, and anchorage-independent growth in vitro and with slower growth in vivo as xenografts in immunodeficient nude mice. We have also observed that knockdown of CypA inhibits expression of interleukin-8 (IL-8), a tumorigenic and proangiogenic cytokine. Conversely, enforced expression of CypA in the CypA KD cell line, Ud-12, markedly enhanced IL-8 transcripts and restored Ud-12 proliferation, suggesting that CypA-mediated IL-8 production provides a growth advantage to glioblastoma cells. CypA knockdown-mediated inhibition of IL-8 is due to reduced activity of NF-κB, which is one of the major transcription factors regulating IL-8 expression. These results not only establish the relevance of CypA to glioblastoma growth in vitro and in vivo, but also suggest that small interfering RNA-based CypA knockdown could be an effective therapeutic approach against glioblastomas.
          Cover page: Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2023)
          The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring's metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.
            Cover page: Maternal low-calorie sweeteners consumption rewires hypothalamic melanocortin circuits via a gut microbial co-metabolite pathway
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2022)
            Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region-specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.
              Cover page: Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats
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