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Open Access Publications from the University of California

Scholarly Works (35 results)

  • Article
LBL Publications (1962)
    Cover page: DIFFUSION OF XENON IN URANIUM MONOCARBIDE
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2020)

    Short DNA sequences play an important role in the immune response to pathogens. As part of the non-coding regions of the genome, short DNA sequence motifs regulate cell activation and maturation by binding chromatin modifiers and transcription factors. They also determine the ability of each cell in the adaptive immune system to respond to a specific pathogen by forming the antigen-recognizing region of their receptors. This dissertation outlines computational tools I developed for utilizing and integrating high-throughput sequencing data to study the functions of short DNA sequences in the human immune system. I focus on two main aspects of short DNA sequences: (1) As components of the regulatory landscape that control the activation of dendritic cells (DCs) in response to lipopolysaccharide (LPS), and (2) as the determinants of the specificity of T cells and B cells.

    The first part of my dissertation investigates the regulatory landscape of DC activation following LPS stimulation. In chapter two I present a model which predicts gene induction based on sequence motif occurrences in the regulatory regions of each gene and show that this regulatory logic is conserved between human and mouse. Chapter three describes a supervised learning pipeline I devised to study the contribution of short sequence motifs to temporal epigenetic changes in human DCs. The second part of my dissertation describes my work on determining the specificity of T and B cells from single-cell RNA-sequencing data. Chapter four presents software I developed to reconstruct the full sequence of T cell receptors from short read single-cell RNA-sequencing. An application of the software links the length of the antigen-recognizing region of the receptor to the state of the cell, demonstrating the importance of such combined analysis in studying the immune response to viral infections. Chapter five describes an extension of the software to reconstruct B cells receptor sequences.

      Cover page: Short-Sequence Approach to Uncovering Regulatory Mechanisms in the Human Immune System
      • Article
      LBL Publications (1966)
        Cover page: DIFFUSION OF XENON IN URANIUM MONOCARBIDE
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2019)
        RNA sequencing of single B cells provides simultaneous measurements of the cell state and its antigen specificity as determined by the B-cell receptor (BCR). However, to uncover the latter, further reconstruction of the BCR sequence is needed. We present BRAPeS ("BCR Reconstruction Algorithm for Paired-end Single cells" ), an algorithm for reconstructing BCRs from short-read paired-end single-cell RNA sequencing. BRAPeS is accurate and achieves a high success rate even at very short (25 bp) read length, which can decrease the cost and increase the number of cells that can be analyzed compared with long reads. BRAPeS is publicly available at the following link: https://github.com/YosefLab/BRAPeS.
          Cover page: Reconstructing B-cell receptor sequences from short-read single-cell RNA sequencing with BRAPeS
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2022)

          Background

          Deceased donor and recipient predictors of posttransplant steatosis/steatohepatitis and fibrosis are not well known. Our aim was to evaluate the prevalence and assess donor and recipient predictors of steatosis, steatohepatitis, and fibrosis in liver transplantation recipients.

          Methods

          Using the immune tolerance network A-WISH multicenter study (NCT00135694), donor and recipient demographic and clinical features were collected. Liver biopsies were taken from the donor liver at transplant, and from recipients per protocol and for-cause (ie, abnormal transaminases and to rule out rejection) and were interpreted by a central pathologist.

          Results

          One hundred eighty-three paired donor/recipients liver biopsies at the time of transplant and posttransplant follow-up (median time 582 d; average time to last biopsies was 704 d [SD ± 402 d]) were analyzed. Donor steatosis did not influence recipient steatosis or fibrosis. Ten of 183 recipients had steatohepatitis on the last biopsy. Recipient body mass index at the time of liver biopsy was the most influential factor associated with posttransplant steatosis. Both donor and recipient metabolic syndrome features were not associated with graft steatosis. Untreated hepatitis C viral (HCV) infection was the most influential factor associated with the development of allograft fibrosis.

          Conclusions

          In a large experience evaluating paired donor and recipient characteristics, recipient body mass index at the time of liver biopsy was most significantly associated with posttransplant steatosis. Untreated HCV etiology influenced graft fibrosis. Thus relative to untreated HCV, hepatic fibrosis in those with steatosis/steatohepatitis is less common though long-term follow-up is needed to determine the course of posttransplant fibrosis. Emphasis on recipient weight control is essential.
            Cover page: Impact of Donor and Recipient Clinical Characteristics and Hepatic Histology on Steatosis/Fibrosis Following Liver Transplantation
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2016)
            We suggest a new implementation for rapid reconstruction of three-dimensional (3-D) refractive index (RI) maps of biological cells acquired by tomographic phase microscopy (TPM). The TPM computational reconstruction process is extremely time consuming, making the analysis of large data sets unreasonably slow and the real-time 3-D visualization of the results impossible. Our implementation uses new phase extraction, phase unwrapping and Fourier slice algorithms, suitable for efficient CPU or GPU implementations. The experimental setup includes an external off-axis interferometric module connected to an inverted microscope illuminated coherently. We used single cell rotation by micro-manipulation to obtain interferometric projections from 73 viewing angles over a 180° angular range. Our parallel algorithms were implemented using Nvidia's CUDA C platform, running on Nvidia's Tesla K20c GPU. This implementation yields, for the first time to our knowledge, a 3-D reconstruction rate higher than video rate of 25 frames per second for 256 × 256-pixel interferograms with 73 different projection angles (64 × 64 × 64 output). This allows us to calculate additional cellular parameters, while still processing faster than video rate. This technique is expected to find uses for real-time 3-D cell visualization and processing, while yielding fast feedback for medical diagnosis and cell sorting.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2013)
                Cover page: Special Section Guest Editorial: Optical Imaging, Sensing, and Light Interactions in Cells and TissuesCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2014)

                Background

                Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients.

                Methods

                Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients' sera samples by a direct fluorescence method developed in our laboratory.

                Results

                Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading.

                Conclusions

                CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment.
                  Cover page: The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuriesCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2014)
                  BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. In this study a new method to measure cell free DNA (CFD) for the management of TBI is tested. Our hypothesis was that CFD concentrations correlate to the magnitude of brain damage, and may predict the outcome of injured patients. METHODS: Twenty eight patients with isolated head injury were enrolled. Their demographic and clinical data were recorded. CFD levels were determined in patients sera samples by a direct fluorescence method developed in our laboratory. RESULTS: Mean admission CFD values were lower in patients with mild TBI compared to severe injury (760 ± 340 ng/ml vs. 1600 ± 2100 ng/ml, p = 0.03), and in patients with complete recovery upon discharge compared to patients with disabilities (680 ± 260 ng/ml vs. 2000 ± 2300 ng/ml, p = 0.003). Patients with high CFD values had a relative risk to require surgery of 1.5 (95% CI 0.83 to 2.9) a relative risk to have impaired outcome on discharge of 2.8 (95% CI 0.75 - 10), and a longer length of stay (12 ± 13 days vs. 3.4 ± 4.8 days, p = 0.02). CFD values did not correlate with CT scan based grading. CONCLUSIONS: CFD levels may be used as a marker to assess the severity of TBI and to predict the prognosis. Its use should be considered as an additional tool along with currently used methods or as a surrogate for them in limited resources environment.
                    Cover page: The role of cell-free DNA measured by a fluorescent test in the management of isolated traumatic head injuries.
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2023)
                    Learning assistant (LA) programs train undergraduate students to foster peer discussion and facilitate active-learning activities in undergraduate science, technology, engineering, and mathematics (STEM) classes. Students who take courses that are supported by LAs demonstrate better conceptual understanding, lower failure rates, and higher satisfaction with the course. There is less work, however, on the impact that participating in LA programs has on the LAs themselves. The current study implements a pretest-posttest design to assess changes in LAs' metacognition and motivation to succeed in STEM across their first and second quarters as an LA. Our findings suggest that participating in this program may help LAs become more reflective learners, as was demonstrated by an increase in their scores on the Metacognitive Awareness Inventory (MAI) after the first quarter. LAs also showed increases on the Intrinsic Motivation and Self-Efficacy subscales of the Science Motivation Questionnaire. Students who participated in the program for an additional quarter continued to show increases in their MAI scores and maintained the gains that were observed in their motivation. Taken together, this work suggests that, in addition to benefiting the learner, LA programs may have positive impacts on the LAs themselves.
                      Cover page: The Benefits of Participating in a Learning Assistant Program on the Metacognitive Awareness and Motivation of Learning Assistants.Creative Commons 'BY' version 4.0 license
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