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Open Access Publications from the University of California

Scholarly Works (277 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2011)
While studying on epigenetic regulatory mechanisms (DNA methylation at C-5 of -CpG- cytosine and demethylation of methylated DNA) of certain genes (FAS, CLU, E-cadh, CD44, and Cav-1) associated with prostate cancer development and its better management, we noticed that the used in vivo dose of 5-aza-2'-deoxycytidine (5.0 to 10.0 nM, sufficient to inhibit DNA methyltransferase activity in vitro) helped in the transcription of various genes with known (steroid receptors, AR and ER; ER variants, CD44, CDH1, BRCA1, TGFβR1, MMP3, MMP9, and UPA) and unknown (DAZ and Y-chromosome specific) proteins and the respective cells remained healthy in culture. At a moderate dose (20 to 200 nM) of the inhibitor, cells remain growth arrested. Upon subsequent challenge with increased dose (0.5 to 5.0 μM) of the inhibitor, we observed that the cellular morphology was changing and led to death of the cells with progress of time. Analyses of DNA and anti-, pro-, and apoptotic factors of the affected cells revealed that the molecular events that went on are characteristics of programmed cell death (apoptosis).
    Cover page: 5-Aza-2′-deoxycytidine stress response and apoptosis in prostate cancer
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2010)
    Cancer is a life threatening disease characterized by uncontrolled growth and spread of abnormal cells. Extensive research in the field for the last fifty years led to the discovery of diverse classes of drugs called chemotherapeutics. The mode of action of many of these drugs exploits the fact that cancer cells replicate much faster than normal cells. Different classes of drugs target different proteins in the DNA replication and repair pathways and kill cells by interfering with these indispensable life processes. Two major obstacles to successful cancer chemotherapy are the significant cytotoxicity of the chemicals to normal cells and the high probability of resistance. Combination therapies, in which two or more different drugs are used, may help avoid both these problems. In this study I investigated the effects of a hexapeptide molecule (sequence wrwycr) in cancer cells versus normal cells with particular emphasis on the cytotoxicity of the peptide, and DNA damage resulting from exposure. Peptide wrwycr was originally isolated in our laboratory in a combinatorial peptide library screen for inhibitors of phage lambda site-specific recombination. Subsequently it was discovered that the peptide stabilizes a transient DNA intermediate, the Holliday junction (HJ) generated in the process of recombination and disrupts the equilibrium of the reaction. Extensive in vitro and ex vivo characterization of the peptide has revealed that it belongs to the class of broad spectrum antibacterial that induces its bactericidal effect via DNA damage. Since HJs (and other branched DNA substrates) are produced in both prokaryotes and eukaryotes, I tested the effects of wrwycr on human cells by studying two cancer cell lines, U2OS, HeLa and a non-cancerous lung fibroblast, IMR-90 as a control. This is a preliminary step towards exploring the anticancer potential of this peptide. Our results indicate that the effect of wrwycr in cultured human cells is cell- type dependent. Like natural, cationic, hydrophobic antibacterial peptides, wrwycr can enter cancer cells more efficiently than normal cells. U2OS, an osteosarcoma cell line is more sensitive to wrwycr-induced cytotoxicity than HeLa, a cervical cancer cell line. In U2OS cells, wrwycr produces a non-linear dose-dependent cytotoxicity partly via apoptosis. Concurrent administration of a sublethal dose of etoposide with wrwycr potentiates cell death in U2OS and induces the DNA double strand break response. More specifically, wrwycr interferes with recovery from intra-S arrest in synchronized U2OS cells in a linear, dose-dependent manner with no significant killing. This suggests that the exponential increase in cell death upon linear increase in wrwycr dose could be due to the interaction of peptide wrwycr with other cellular targets generating different forms of damage like ER stress, membrane rupture or mitochondrial damage. HeLa cells show more signs of cell cycle arrest than cell death with wrwycr treatment. This becomes more evident upon simultaneous treatment with etoposide. Interestingly, IMR- 90 cells are the most resistant to wrwycr lethality and DNA damage. This can be attributed only partly to lesser uptake inside these cells. Taken together, we have starting evidence that wrwycr has potential to be used as an anticancer drug by itself or in combination therapy. Much more basic and clinical research needs to be done before this long term goal can be achieved
      Cover page: Effect of a Holliday junction binding peptide, wrwycr, in human cells
      • Article
      • Peer Reviewed
      The Proceedings of the International Plant Nutrition Colloquium XVI (2009)

      Agriculture in the Indian sub-continent aims at competitive production of higher level of food, vegetables and fruits and industrial raw materials from the existing cultivable land through innovative research and development applications. The land holdings with the farmers are small, not amendable to the mechanized agricultural practices responsible for high crop yields, such as obtained in the developed part of the globe. Production of agriculture per unit area and time is largely dependent on provision of fertilizers and irrigation in ample measure for the adequate expression of genetic potential of improved varieties of food grain, vegetable crops and industrial crops. Urea is the widely used nitrogenous fertilizer. However, it appears that benefits from large level of urea fertilizer can be expanded by increasing the effectiveness of fertilization. Recovery of applied fertilizer urea-N seldom exceeds 50% in many crops; it is yet low in waterlogged paddies. The products of hydrolysis and nitrification are prone to losses through volatilization, and denitrification and leaching. Arrest of N-loss in the crop fields can help increase N utilization. This, if achieved, will provide several advantages: decrease the cost of agricultural production and increase profits to farmers, expand the use of urea in optimal amount over larger cultivated area and contain N- pollution that results from inefficient use of urea-N. Regulation of urea transformation reactions that occur in soil for better utilization of its N by crops has been an active R& D area. Several classes of compounds viz. phosphorodiamidates and triamidates, sulphahydryl reagents, dihydric phenols, aminocresols, catechol, p-benzoquinones, dihydric phenols etc, have been found to restrict hydrolysis of urea in soil. Ammonium polyphosphate and phosphoric, boric and nitric acid have been found to reduce volatilization of ammonia generated from urea. Rapid nitrification or oxidation of ammonium to nitrate in soil catalysed by microbes has been founds to be inhibited by nitrapyrin (2-chloro -6- tricholoro methyl pyridine), BHC, sodium azide, sodium chlorate, dicyandiamide (DCD), ATC (4-amino-1-2-4 triazole), N-serve and certain other compounds. The use of many of these chemicals has been restricted to academic experimental levels because of high cost, lack of availability and adverse side effects. Nitrification inhibitory properties of several plants materials like Karanj (Pongamia glabra), Neem (Azaddirachta indica), and tea (Camellia sinensis) waste have been evaluated by many researchers and their advantages and disadvantages have been reported. Commercial use of these materials has not been possible due to lack of their availability, cumbersome coating process with urea, inefficient promotional activities etc. The recent inclusion of botanicals in the list of plant based materials is the natural essential oils and their by- products. The advantages of these materials are that they are easily available, cheap, eco-friendly and can be cultivated as per their requirement. This paper deals with the different aspects of plants based materials as nitrification inhibitors.

        Cover page: Natural Nitrification Inhibitors for Augmenting Nitrogen Use Efficiency in Soil-Plant System
        • Article
        • Peer Reviewed
        Multicampus Research Programs and Initiatives (MRPI) Funded Publications (2017)
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2018)
          Landauer's Principle states that the energy cost of information processing must exceed the product of the temperature and the change in Shannon entropy of the information-bearing degrees of freedom. However, this lower bound is achievable only for quasistatic, near-equilibrium computations -- that is, only over infinite time. In practice, information processing takes place in finite time, resulting in dissipation and potentially unreliable logical outcomes. For overdamped Langevin dynamics, we show that counterdiabatic potentials can be crafted to guide systems rapidly and accurately along desired computational paths, providing shortcuts that allows for the precise design of finite-time computations. Such shortcuts require additional work, beyond Landauer's bound, that is irretrievably dissipated into the environment. We show that this dissipated work is proportional to the computation rate as well as the square of the information-storing system's length scale. As a paradigmatic example, we design shortcuts to erase a bit of information metastably stored in a double-well potential. Though dissipated work generally increases with erasure fidelity, we show that it is possible perform perfect erasure in finite time with finite work. We also show that the robustness of information storage affects the energetic cost of erasure---specifically, the dissipated work scales as the information lifetime of the bistable system. Our analysis exposes a rich and nuanced relationship between work, speed, size of the information-bearing degrees of freedom, storage robustness, and the difference between initial and final informational statistics.
            Cover page: Shortcuts to Thermodynamic Computing: The Cost of Fast and Faithful Erasure
            • Thesis
            • Peer Reviewed
            UC Berkeley Electronic Theses and Dissertations (2024)

            Astrophysical transient events, particularly Type Ia supernovae (SNe Ia) and tidal disruption events (TDEs), provide critical insights into stellar systems and black hole activity. This thesis studies polarimetry of SNe Ia and TDEs in an attempt to better understand the geometry and physical processes behind these explosive events.

            For SN 2019ein, spectropolarimetric data from approximately 11 days before to 10 days after peak brightness revealed a continuum polarization of 0.0--0.3\%. The constant polarization angle indicates axial symmetry in the explosion, consistent across inner and outer ejecta regions. Notably, polarization at the Si II and Ca II lines reached about 1\%, suggesting a largely spherical explosion with localized clumping of intermediate-mass elements. These observations largely disfavor merger-induced models for SN 2019ein. A larger sample of SNe Ia spectropolarimetry observed at Lick Observatory is presented and described.

            In the study of the TDE AT\,2019qiz, spectropolarimetry showed negligible continuum polarization at peak brightness, suggesting a nearly spherical, optically thick electron scattering photosphere around the black hole. By day 29, polarization increased to around 1\%, indicating a more aspherical interior as the fallback rate decreased and the photosphere receded. This marks the first detailed spectropolarimetric evolution observed in a TDE, and supports the reprocessing model for the source of optical emission in TDEs. The study of AT\,2019qiz is followed by imaging polarimetry of several TDEs from Keck Observatory in an attempt to build a more comprehensive picture of gas geometry in TDEs.

            Additionally, the thesis explores the newly discovered X-ray quasi-periodic eruptions (QPEs), analyzing archival {\it Hubble Space Telescope} images of the QPE source GSN 069. The data revealed a compact [O III] emission region within a 35 pc radius of the nucleus, along with extended emission up to 2 kpc away. Simulations with the photoionization code \textsc{Cloudy} suggest this emission comes from dense gas, likely ionized by X-rays from a young accretion disk, offering a unique glimpse into the dynamic processes at play in the host galaxies of QPEs.

              • Article
              • Peer Reviewed
              UC Santa Cruz Previously Published Works (2016)
              Three rationally designed glucose-platinum conjugates (Glc-Pts) were synthesized and their biological activities evaluated. The Glc-Pts, 1-3, exhibit high levels of cytotoxicity toward a panel of cancer cells. The subcellular target and cellular uptake mechanism of the Glc-Pts were elucidated. For uptake into cells, Glc-Pt 1 exploits both glucose and organic cation transporters, both widely overexpressed in cancer. Compound 1 preferentially accumulates in and annihilates cancer, compared to normal epithelial, cells in vitro.
                Cover page: A Potent Glucose–Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2022)
                Landauer's Principle states that the energy cost of information processing must exceed the product of the temperature, Boltzmann's constant, and the change in Shannon entropy of the information-bearing degrees of freedom. However, this lower bound is achievable only for quasistatic, near-equilibrium computations-that is, only over infinite time. In practice, information processing takes place in finite time, resulting in dissipation and potentially unreliable logical outcomes. For overdamped Langevin dynamics, we show that counterdiabatic potentials can be crafted to guide systems rapidly and accurately along desired computational paths, providing shortcuts that allow for the precise design of finite-time computations. Such shortcuts require additional work, beyond Landauer's bound, that is irretrievably dissipated into the environment. We show that this dissipated work is proportional to the computation rate as well as the square of the information-storing system's length scale. As a paradigmatic example, we design shortcuts to create, erase, and transfer a bit of information metastably stored in a double-well potential. Though dissipated work generally increases with operation fidelity, we show that it is possible to compute with perfect fidelity in finite time with finite work. We also show that the robustness of information storage affects an operation's energetic cost-specifically, the dissipated work scales as the information lifetime of the bistable system. Our analysis exposes a rich and nuanced relationship between work, speed, size of the information-bearing degrees of freedom, storage robustness, and the difference between initial and final informational statistics.
                  Cover page: Shortcuts to Thermodynamic Computing: The Cost of Fast and Faithful Information Processing
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2005)

                  We consider the problem of routing in a delay tolerant network (DTN) in the presence of path failures. Previous work on DTN routing has focused on using precisely known network dynamics, which does not account for message losses due to link failures, buffer overruns, path selection errors, unscheduled delays, or other problems. We show how to split, replicate, and erasure code message fragments over multiple delivery paths to optimize the probability of successful message delivery. We provide a formulation of this problem and solve it for two cases: a 0/1 (Bernoulli) path delivery model where messages are either fully lost or delivered, and a Gaussian path delivery model where only a fraction of a message may be delivered. Ideas from the modern portfolio theory literature are borrowed to solve the underlying optimization problem. Our approach is directly relevant to solving similar problems that arise in replica placement in distributed file systems and virtual node placement in DHTs. In three different simulated DTN scenarios covering a wide range of applications, we show the effectiveness of our approach in handling failures.

                    Cover page: Using Redundancy to Cope with Failures in a Delay Tolerant Network
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2018)
                    24S-hydroxycholesterol (24OHC) and Tau are produced in neuronal cells and neurodegeneration leads to increased flux of both of them into cerebrospinal fluid (CSF). In the present study, CSF levels of 24OHC and 27S-hydroxycholesterol (27OHC) along with those of Tau, P-Thr181-Tau and Aβ42 were measured in patients with early Parkinson's disease (PD), Corticobasal syndrome (CBS), Corticobasal Degeneration (CBD), and controls. Using mouse models with increased or no formation of Tau protein and increased production of 24OHC, we have also tested the hypothesis that there is a direct association between neuronal turnover of 24OHC and Tau. The levels of 24OHC are increased, at a group level, in patients with PD or CBS. We found significant correlations between levels of 24OHC and Tau or P-Thr181-Tau in CSF from patients with PD, CBS or CBD. There were no similar correlations between 24OHC and Aβ42 in CSF from these patients. The neuronal levels of 24OHC were not altered in Tau knockout or Tau overexpressing mice. Vice versa, Tau species levels were not changed in Cyp46 overexpressing mice with increased neuronal levels of 24OHC. We conclude that the strongly correlative fluxes of 24OHC and Tau from neuronal cells to CSF are likely to be secondary to neurodegeneration and not due to direct interaction between the two factors. We suggest that this high correlation reflects a rapid neurodegeneration of specific neuronal subtypes with simultaneous release of 24OHC and Tau into the CSF.
                      Cover page: 24S-Hydroxycholesterol Correlates With Tau and Is Increased in Cerebrospinal Fluid in Parkinson's Disease and Corticobasal SyndromeCreative Commons 'BY' version 4.0 license
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