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Open Access Publications from the University of California

Scholarly Works (26 results)

  • Thesis
  • Peer Reviewed
UC San Francisco Electronic Theses and Dissertations (1978)

    Cover page: The hormonal control of subcellular calcium and the possible effects on contractility in the rabbit uterus
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2010)
    Management of lung tumor motion is a challenging and important problem for modern, highly conformal radiotherapy. Poorly managed tumor motion can lead to imaging artifacts, poor target coverage, and unnecessarily high dose to normal tissues. The goals of this dissertation are to develop a real-time localization algorithm that is applicable to rotational cone-beam projections acquired during regular (6̃0 seconds) cone-beam computed tomography (CBCT) scans, and to use these tracking results to reconstruct a tumor's trajectory, shape and size immediately prior to treatment. Direct tumor tracking is performed via a multiple template matching algorithm where templates are derived from digitally reconstructed radiographs (DRRs) generated from four-dimensional computed tomography (4DCT). Three- dimensional (3D) tumor trajectories are reconstructed by binning two-dimensional (2D) tracking results according to their corresponding respiratory phases. Within each phase bin a point is calculated approximating the 3D tumor position, resulting in a 3D phase-binned trajectory. These 3D trajectories are used to construct motion blurring functions which are in turn used to remove motion blurring artifacts from reconstructed CBCT volumes with a deconvolution algorithm. Finally, the initial direct tracking algorithm is combined with diaphragm-based tracking to develop a more robust "combined" tracking algorithm. Respiratory motion phantoms (digital and physical), and example patient cases were used to test each technique. Direct tumor tracking performed well for both phantom cases, with sub-millimeter root mean square error (erms) in the axial and tangential imager dimensions. In patient studies the algorithm performed well for many angles, but exhibited large errors for some projections. Accurate 3D trajectories were successfully reconstructed for patients and phantoms. Errors in reconstructed trajectories were smaller than the errors in the direct tracking results in all cases. The deblurring algorithm performed excellently in phantom studies. Deblurring was also effective on an example patient case, though the benefits were less stark. Finally, the combined tracking algorithm performed equally to or better than direct tumor tracking in the phantom and patient cases examined. While the preliminary results for each technique are promising, the algorithms must be tested on a larger data set with well defined ground truth to investigate potential clinical applications
      Cover page: Lung tumor tracking, trajectory reconstruction, and motion artifact removal using rotational cone-beam projections
      • Thesis
      • Peer Reviewed
      UC San Diego Electronic Theses and Dissertations (2008)
      Across species, increases in white matter volume outpace increases in gray-matter volume, but increases in gray- matter volume outpace increases in the size of the corpus callosum. This dissertation explores the hypothesis that this hyposcaling of the callosum stems from the impact of the conduction delays and cellular costs of the long- distance connections on normal developmental mechanisms. Neuroanatomy research to date has only indirectly examined this relation, using measures such as brain volume. The research in this dissertation uses diffusion tensor imaging to more directly measure the relation between the length of the interhemispheric connections and the degree of connectivity -- the ratio of between-area connections to total projection neurons in the areas connected. Using tractography to detail the patterns of interhemispheric connectivity and to determine the length of the connections, and formulae based on histological results to estimate degree of connectivity, we show that, across normal young adult males, connection length is significantly negatively correlated with degree of connectivity in the anterior, posterior, and body of the callosum. Using the same methodology, in typically developing boys a significant relation between connection length and degree of connectivity was found only in the posterior of the callosum. The combined results indicate that the relation between connection length and degree of connectivity develops during childhood and adolescence. Children with autism are known to have enlarged brains during the first years of life. This is predicted to lead to decreased long-distance connectivity. To explore this prediction, neural networks which modeled inter- hemispheric interaction were grown at the rate of either typically developing children or children with autism. By 2 years of simulated age, the networks that modeled autistic growth showed a reduced reliance on long-distance connections, performance reductions, and reductions in structural connectivity. Using the same methodology as with the adults and children, the relation between connection length and degree of connectivity in adults with autism was examined. Connection length and degree of connectivity showed the typical negative relation, but with a reduced degree of connectivity in anterior regions -- the locus of development during the period of maximal brain overgrowth, and where axon diameters are smallest
        Cover page: Size always matters : an investigation of the influence of connection length on the organization of white-matter in typical development and in autism
        • Article
        • Peer Reviewed
        Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 21 (1999)
          Cover page: The Syntax-Semantics Interface and the Innateness of Scope
          • Article
          • Peer Reviewed
          Proceedings of the Annual Meeting of the Cognitive Science Society, Volume 23 (2001)
            Cover page: A Connectionist Investigtion of Linguistic Arguments from the Poverty of the Stimulus: Learning the Unlearnable
            • Thesis
            • Peer Reviewed
            UCLA Electronic Theses and Dissertations (2021)

            Magnetic resonance-guided radiation therapy (MRgRT) has drawn enormous clinical and research interests. The superior soft-tissue contrast of magnetic resonance imaging (MRI) compared with computed tomography (CT) allows more accurate tumor and organ-at-risk (OAR) segmentation for brain, prostate, and abdominal cancer. Additionally, real-time target tracking ability and high-quality daily MR images offered by the online MRgRT system could further minimize treatment delivery uncertainties. However, the current MRgRT workflow has several limitations including the need to acquire an additional CT for treatment planning, slow tumor and OAR recontouring in the adaptive workflow, and underdeveloped tools for predicting treatment response and survival outcome. In this dissertation, we developed and investigated several deep learning (DL) methods to address these three limitations.

            First, 2D and 3D convolutional neural networks (CNNs) were proposed to generate pelvic synthetic CT (sCT) images from 1.5T MR images. Second, conditional generative adversarial network (cGAN) and cycle-consistent generative adversarial network (cycleGAN) were investigated for abdominal sCT generation based on 0.35T MR images. Third, a novel multi-path 3D DenseNet was proposed for automatic glioblastoma multiforme (GBM) segmentation based on multi-modal MR images and compared with the corresponding single-path DenseNet. For predicting neoadjuvant chemoradiation treatment (nCRT) response in patients with locally advanced rectal cancer (LARC), two logistic regression models were built using handcrafted radiomic features and DL-based radiomic features, respectively. These radiomic features were extracted from pre-treatment diffusion-weighted MR images based on manually delineated gross tumor volume. Additionally, an automatic radiomic workflow was proposed for GBM survival prediction based on multi-modal MR images. This workflow consisted of an automatic tumor segmentation CNN and a Cox regression model.

            The proposed 3D CNN generated more accurate pelvic sCT images compared with the 2D CNN. Abdominal sCT images generated by both GANs achieved accurate dose calculation for liver radiotherapy plans. The multi-path DenseNet achieved more accurate GBM segmentation compared with the single-path DenseNet. The logistic regression model constructed using DL-based features achieved significantly better classification performance in predicting nCRT response compared with the model constructed using handcrafted features. The proposed automatic workflow demonstrated the potential of improving patient stratification and survival prediction in GBM patients.

            The proposed DL methods could potentially address three limitations of the MRgRT workflow but were investigated across different cancer types due to limited data availability. Future work could be adapting these methods for one cancer type and conducting further investigation to translate them into clinics.

              Cover page: Deep Learning Approaches for Assisting MR-guided Radiation Therapy
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (1977)
              Various methods were employed to induce antibodies in rabbits that were capable of neutralizing different families of lymphotoxins (LT). Both stable (alpha-LT) and unstable (beta-LT) molecules, released by activated human lymphocytes in vitro, were neutralized. The different LT families were first separated into their respective groups by physical-chemical methods. Immunization with small quantities of antigen yielded a high percentage of responder animals. Techniques were developed for eliciting alpha-LT antibodies using as little as 2--3 ml of a cell-free supernatant. The situation was more difficult, however, when the unstable beta-LT molecules were employed as antigens. We found that because of the low concentration and lability of beta-LT in supernatants, the immunizing dose had to be: a) handled rapidly, b) larger than that used with the alpha-LT, and c) injected at closer intervals and over a longer immunization protocol. Physical-chemical studies supperted the concept that the LT-neutralizing activity in the immune serum was immunoglobulin.
                Cover page: Antibodies against human lymphokines: I. Methods for induction of antibodies capable of neutralizing stable (α) and unstable (β) lymphotoxins released in vitro by activated human lymphocytesCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2010)

                Naturalistic observations of infant/caregiver social attention have yielded rich information about human social develop- ment. However, observational data are expensive, laborious, and reliant on fallible human coders. We model interactions between caregivers and infants using a three dimensional sim- ulation environment in order to gain greater insight into the development of infant attention sharing, specifically gaze fol- lowing. Most models of infant cognition have been only ab- stractly linked to the detail of a real life environment and to the perception-and-action physicality of human infants. Our simulation uses human data from videotaped infant/caregiver interactions and a rich 3D environment to model the develop- ment of gaze following. Initial tests suggest that infant gaze following can be learned in our simulation using parameters derived from behavioral data.

                  Cover page: Building a model of infant social interaction
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (1976)
                  An in vitro method has been developed utilizing phytohemagglutinin (PHA) activated lymphocytes obtained from human tonsils and adenoids which permit the accumulation of multi-liter quantities of cell-free supernatants containing lymphotoxin and other lymphocyte effector molecules (LEM). An enriched media is employed which contains a large molecular weight, heat stable bovine serum fraction which supports lymphoid cell activation and levels of LEM secretion equal to that of cultures maintained in medium supplemented with whole serum. Elimination of whole serum from the media greatly reduces overall protein concentrations and facilitates concentration and purification studies. Various technical aspects of these cultures have been examined, i.e.: 1) cell concentration, 2) kinetics of LT production over a ten-day period, 3) mitogen dosage, and 4) types of media. Supernatants can be harvested repeatedly from a single culture over the ten day period, thus doubling the yield of LEM collected from a single culture.
                    Cover page: Lymphocyte effector molecules: An in vitro production method for obtaining liter volumes of supernatants from mitogen-stimulated human lymphocytesCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2015)

                    Background

                    Exposure to dichlorvos (DDVP), an organophosphorus pesticide, is known to result in neurotoxicity as well as other metabolic perturbations. However, the molecular causes of DDVP toxicity are poorly understood, especially in cells other than neurons and muscle cells. To obtain a better understanding of the process of non-neuronal DDVP toxicity, we exposed zebrafish to different concentrations of DDVP, and investigated the resulting changes in liver histology and gene transcription.

                    Results

                    Functional enrichment analysis of genes affected by DDVP exposure identified a number of processes involved in energy utilization and stress response in the liver. The abundance of transcripts for proteins involved in glucose metabolism was profoundly affected, suggesting that carbon flux might be diverted toward the pentose phosphate pathway to compensate for an elevated demand for energy and reducing equivalents for detoxification. Strikingly, many transcripts for molecules involved in β-oxidation and fatty acid synthesis were down-regulated. We found increases in message levels for molecules involved in reactive oxygen species responses as well as ubiquitination, proteasomal degradation, and autophagy. To ensure that the effects of DDVP on energy metabolism were not simply a consequence of poor feeding because of neuromuscular impairment, we fasted fish for 29 or 50 h and analyzed liver gene expression in them. The patterns of gene expression for energy metabolism in fasted and DDVP-exposed fish were markedly different.

                    Conclusion

                    We observed coordinated changes in the expression of a large number of genes involved in energy metabolism and responses to oxidative stress. These results argue that an appreciable part of the effect of DDVP is on energy metabolism and is regulated at the message level. Although we observed some evidence of neuromuscular impairment in exposed fish that may have resulted in reduced feeding, the alterations in gene expression in exposed fish cannot readily be explained by nutrient deprivation.
                      Cover page: Dichlorvos exposure results in large scale disruption of energy metabolism in the liver of the zebrafish, Danio rerio
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