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Open Access Publications from the University of California

Scholarly Works (12 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2019)

Software is becoming increasingly pervasive and complex. During software development and maintenance, developers often make ad hoc decisions based on local program contexts and their own experience only, which may increase technical debt and raise unknown consequences as software evolves. This dissertation explores several opportunities to guide software development and maintenance by exploiting and visualizing the commonalities and variations among similar programs. Our hypothesis is that unveiling what has and has not been done in other similar program contexts can help developers make more systematic decisions, explore implementation alternatives, and reduce the risk of unknown consequences.

The inherent repetitiveness in software systems provides a solid foundation for identifying and exploiting similar code. This dissertation first presents two approaches that leverage the syntactic similarity and repetitiveness in local codebases to improve code reviews and

software testing. First, in contrast to inspecting local program edits line by line, Critics enables developers to reason about related edits scattered across multiple files by summarizing similar edits and detecting inconsistencies in similar locations. Second, Grafter boosts test coverage by transplanting test cases between similar programs and helps developers discern the behavioral similarity and differences between these programs via differential testing.

This dissertation further extends the idea of systematic software development from local codebases to the open world, by exploiting the large and growing body of successful open-source projects on the Internet. In particular, we present three approaches that analyze a massive number of open-source projects and provide systematic guidance based on software reuse and adaptation patterns in the open-source community. First, ExampleCheck mines common API usage patterns from 380K GitHub projects and contrasts online code examples with these patterns to alert developers about potential API misuse during opportunistic code reuse. Second, to help developers comprehensively understand the variety of API usage at scale, Examplore aligns and super-imposes hundreds of code examples into a single code skeleton with statistical distributions of distinct API usage features among these examples.

Finally, ExampleStack guides developers to adapt a code example to a target project by detecting similar code fragments in GitHub and by illuminating possible variations of this example with respect to its GitHub counterparts.

The viability and usability of these techniques are evaluated by their application to large-scale projects as well as within-subjects user studies. First, in a user study with twelve Java developers, Critics helps developers identify 47% more edit mistakes with 32% less time

than a line-level program diff tool. Second, Grafter transplants test cases in three open-source projects with 94% success rate and improves the statement and branch coverage by 22% and 16% respectively. Third, ExampleCheck reduces the risk of bug propagation by detecting API usage violations in almost one third of code examples in a popular Q&A forum, Stack Overflow. These API usage violations can potentially lead to software anomalies such as program crashes and resource leaks in target programs. Fourth, in a study with sixteen Java developers, Examplore helps developers understand the distribution of API usage patterns and answer common API usage questions accurately with concrete details. Finally, in another study with sixteen Java developers, ExampleStack helps developers identify more adaptation opportunities about code safety and logic customization, rather than shallow adaptations such as variable renaming. These key findings demonstrate that discovering and representing the commonalities and variations in similar contexts helps a developer achieve better program comprehension, discover more design alternatives, and capture more errors in different software development and maintenance tasks.

    Cover page: Leveraging Program Commonalities and Variations for Systematic Software Development and Maintenance
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2024)
    Centromeric localization of evolutionarily conserved CENP-A (Cse4 in Saccharomyces cerevisiae) is essential for chromosomal stability. Mislocalization of overexpressed CENP-A to noncentromeric regions contributes to chromosomal instability in yeasts, flies, and humans. Overexpression and mislocalization of CENP-A observed in many cancers are associated with poor prognosis. Previous studies have shown that F-box proteins, Cdc4 and Met30 of the Skp, Cullin, F-box ubiquitin ligase cooperatively regulate proteolysis of Cse4 to prevent Cse4 mislocalization and chromosomal instability under normal physiological conditions. Mck1-mediated phosphorylation of Skp, Cullin, F-box-Cdc4 substrates such as Cdc6 and Rcn1 enhances the interaction of the substrates with Cdc4. Here, we report that Mck1 interacts with Cse4, and Mck1-mediated proteolysis of Cse4 prevents Cse4 mislocalization for chromosomal stability. Our results showed that mck1Δ strain overexpressing CSE4 (GAL-CSE4) exhibits lethality, defects in ubiquitin-mediated proteolysis of Cse4, mislocalization of Cse4, and reduced Cse4-Cdc4 interaction. Strain expressing GAL-cse4-3A with mutations in three potential Mck1 phosphorylation consensus sites (S10, S16, and T166) also exhibits growth defects, increased stability with mislocalization of Cse4-3A, chromosomal instability, and reduced interaction with Cdc4. Constitutive expression of histone H3 (Δ16H3) suppresses the chromosomal instability phenotype of GAL-cse4-3A strain, suggesting that the chromosomal instability phenotype is linked to Cse4-3A mislocalization. We conclude that Mck1 and its three potential phosphorylation sites on Cse4 promote Cse4-Cdc4 interaction and this contributes to ubiquitin-mediated proteolysis of Cse4 preventing its mislocalization and chromosomal instability. These studies advance our understanding of pathways that regulate cellular levels of CENP-A to prevent mislocalization of CENP-A in human cancers.
      Cover page: Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2020)

      Purpose

      To demonstrate that rifabutin-related corneal deposits are localized to the deep stroma using anterior segment optical coherence tomography (OCT) and confocal microscopy.

      Observations

      A 55-year-old male with a history of human immunodeficiency virus (HIV) and disseminated mycobacterium avium complex on rifabutin treatment for 3 years presented with bilateral corneal deposits. Confocal microscopy and anterior segment OCT confirm that rifabutin-related corneal deposits are located in the deep stroma, rather than in the endothelium.

      Conclusions

      And Importance: Rifabutin deposits localize to the deep corneal stroma, and can be seen with both confocal microscopy and anterior segment OCT. Anterior segment OCT is a widely available and easily used diagnostic tool, and can provide utility in the diagnosis of corneal deposits.
        Cover page: Rifabutin corneal deposits localized to the deep stroma using anterior segment optical coherence tomography
        • Article
        • Peer Reviewed
        LBL Publications (2024)
        The application of solid-state electrolytes in Li batteries is hampered by the occurrence of Li-dendrite-caused short circuits. To avoid cell failure, the electrolytes can only be stressed with rather low current densities, severely restricting their performance. As grain size and pore distributions significantly affect dendrite growth in ceramic electrolytes such as Li7La3Zr2O12 and its variants; here, a "detour and buffer" strategy to bring the superiority of both coarse and fine grains into play, is proposed. To validate the mechanism, a coarse/fine bimodal grain microstructure is obtained by seeding unpulverized large particles in the green body. The rearrangement of coarse grains and fine pores is fine-tuned by changing the ratio of pulverized and unpulverized powders. The optimized bimodal microstructure, obtained when the two powders are equally mixed, allows, without extra interface decoration, cycling for over 2000 h as the current density is increased from 1.0 mA·cm-2, and gradually, up to 2.0 mA·cm-2. The "detour and buffer" effects are confirmed from postmortem analysis. The complex grain boundaries formed by fine grains discourage the direct infiltration of Li. Simultaneously, the coarse grains further increase the tortuosity of the Li path. This study sheds light on the microstructure optimization for the polycrystalline solid-state electrolytes.
          Cover page: Solid Electrolyte Bimodal Grain Structures for Improved Cycling PerformanceCreative Commons 'BY-NC' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2020)
          Purpose: Dry eye disorders are a major health care burden. We previously reported the identification of N-methyl-N-phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR)act-K267], which activated human wild-type CFTR chloride conductance with EC50 ∼ 30 nM. Here, we report in vivo evidence for CFTRact-K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle. Methods: CFTR activation in mice in vivo was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTRact-K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining. Results: OSPD measurements demonstrated a hyperpolarization of -8.6 ± 3 mV (standard error of the mean, 5 mice) in response to CFTRact-K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2 nmol CFTRact-K267, tear fluid CFTRact-K267 concentration was >500 nM for more than 6 h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2 nmol CFTRact-K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes. Conclusion: These studies provide in vivo evidence in mice for the efficacy of a topical, human use compatible CFTRact-K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.
            Cover page: Nanomolar Potency Aminophenyltriazine CFTR Activator Reverses Corneal Epithelial Injury in a Mouse Model of Dry Eye
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2021)
            Atomic spin centers in 2D materials are a highly anticipated building block for quantum technologies. Here, we demonstrate the creation of an effective spin-1/2 system via the atomically controlled generation of magnetic carbon radical ions (CRIs) in synthetic two-dimensional transition metal dichalcogenides. Hydrogenated carbon impurities located at chalcogen sites introduced by chemical doping are activated with atomic precision by hydrogen depassivation using a scanning probe tip. In its anionic state, the carbon impurity is computed to have a magnetic moment of 1 μB resulting from an unpaired electron populating a spin-polarized in-gap orbital. We show that the CRI defect states couple to a small number of local vibrational modes. The vibronic coupling strength critically depends on the spin state and differs for monolayer and bilayer WS2. The carbon radical ion is a surface-bound atomic defect that can be selectively introduced, features a well-understood vibronic spectrum, and is charge state controlled.
              Cover page: Spin-dependent vibronic response of a carbon radical ion in two-dimensional WS2
              • Article
              • Peer Reviewed
              LBL Publications (2022)
              Individual atomic defects in 2D materials impact their macroscopic functionality. Correlating the interplay is challenging, however, intelligent hyperspectral scanning tunneling spectroscopy (STS) mapping provides a feasible solution to this technically difficult and time consuming problem. Here, dense spectroscopic volume is collected autonomously via Gaussian process regression, where convolutional neural networks are used in tandem for spectral identification. Acquired data enable defect segmentation, and a workflow is provided for machine-driven decision making during experimentation with capability for user customization. We provide a means towards autonomous experimentation for the benefit of both enhanced reproducibility and user-accessibility. Hyperspectral investigations on WS2 sulfur vacancy sites are explored, which is combined with local density of states confirmation on the Au{111} herringbone reconstruction. Chalcogen vacancies, pristine WS2, Au face-centered cubic, and Au hexagonal close-packed regions are examined and detected by machine learning methods to demonstrate the potential of artificial intelligence for hyperspectral STS mapping.
                Cover page: Autonomous scanning probe microscopy investigations over WS2 and Au{111}
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2020)
                Restricting the localization of the histone H3 variant CENP-A (Cse4 in yeast, CID in flies) to centromeres is essential for faithful chromosome segregation. Mislocalization of CENP-A leads to chromosomal instability (CIN) in yeast, fly and human cells. Overexpression and mislocalization of CENP-A has been observed in many cancers and this correlates with increased invasiveness and poor prognosis. Yet genes that regulate CENP-A levels and localization under physiological conditions have not been defined. In this study we used a genome-wide genetic screen to identify essential genes required for Cse4 homeostasis to prevent its mislocalization for chromosomal stability. We show that two Skp, Cullin, F-box (SCF) ubiquitin ligases with the evolutionarily conserved F-box proteins Met30 and Cdc4 interact and cooperatively regulate proteolysis of endogenous Cse4 and prevent its mislocalization for faithful chromosome segregation under physiological conditions. The interaction of Met30 with Cdc4 is independent of the D domain, which is essential for their homodimerization and ubiquitination of other substrates. The requirement for both Cdc4 and Met30 for ubiquitination is specifc for Cse4; and a common substrate for Cdc4 and Met30 has not previously been described. Met30 is necessary for the interaction between Cdc4 and Cse4, and defects in this interaction lead to stabilization and mislocalization of Cse4, which in turn contributes to CIN. We provide the first direct link between Cse4 mislocalization to defects in kinetochore structure and show that SCF-mediated proteolysis of Cse4 is a major mechanism that prevents stable maintenance of Cse4 at non-centromeric regions, thus ensuring faithful chromosome segregation. In summary, we have identified essential pathways that regulate cellular levels of endogenous Cse4 and shown that proteolysis of Cse4 by SCF-Met30/Cdc4 prevents mislocalization and CIN in unperturbed cells.
                  Cover page: Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2024)
                  C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation and carbon dots synthesis. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.
                    Cover page: Light-driven C–H activation mediated by 2D transition metal dichalcogenidesCreative Commons 'BY' version 4.0 license
                    • Article
                    UC Berkeley Previously Published Works (2024)
                    C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.
                      Cover page: Light-driven C-H activation mediated by 2D transition metal dichalcogenidesCreative Commons 'BY' version 4.0 license
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