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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2010)
Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.
    Cover page: Fidelity of Target Site Duplication and Sequence Preference during Integration of Xenotropic Murine Leukemia Virus-Related Virus
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2019)
    G8 is a benchtop integrated PET/CT scanner dedicated to high-sensitivity and high-resolution imaging of mice. This work characterizes its National Electrical Manufacturers Association NU 4-2008 performance where applicable and also assesses the basic imaging performance of the CT subsystem. Methods: The PET subsystem in G8 consists of 4 flat-panel detectors arranged in a boxlike geometry. Each panel consists of 2 modules of a 26 × 26 pixelated bismuth germanate scintillator array with individual crystals measuring 1.75 × 1.75 × 7.2 mm. The crystal arrays are coupled to multichannel photomultiplier tubes via a tapered, pixelated glass lightguide. A cone-beam CT scanner consisting of a MicroFocus x-ray source and a complementary metal oxide semiconductor detector provides anatomic information. Sensitivity, spatial resolution, energy resolution, scatter fraction, count-rate performance, and the capability of performing phantom and mouse imaging were evaluated for the PET subsystem. Noise, dose level, contrast, and resolution were evaluated for the CT subsystem. Results: With an energy window of 350-650 keV, the peak sensitivity was 9.0% near the center of the field of view. The crystal energy resolution ranged from 15.0% to 69.6% in full width at half maximum (FWHM), with a mean of 19.3% ± 3.7%. The average intrinsic spatial resolution was 1.30 and 1.38 mm FWHM in the transverse and axial directions, respectively. The maximum-likelihood expectation maximization reconstructed image of a point source in air averaged 0.81 ± 0.11 mm FWHM. The peak noise-equivalent count rate for the mouse-sized phantom was 44 kcps for a total activity of 2.9 MBq (78 μCi), and the scatter fraction was 11%. For the CT subsystem, the value of the modulation transfer function at 10% was 2.05 cycles/mm. Conclusion: The overall performance demonstrates that the G8 can produce high-quality images for molecular imaging-based biomedical research.
      Cover page: Performance Evaluation of G8, a High-Sensitivity Benchtop Preclinical PET/CT Tomograph
      • Article
      • Peer Reviewed
      Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 12, Issue 4 (2011)

      Introduction: Identifying fever can influence management of the emergency department (ED) patient, including diagnostic testing, treatment, and disposition. We set out to determine how well oral and tympanic membrane (TM) temperatures compared with rectal measurements. Methods: A convenience sample of consecutively adult ED patients had oral, TM, and rectal temperatures performed within several minutes of each other. Descriptive statistics, Bland–Altman agreement matrices with 95% confidence interval (CI), and measures of test performance, including sensitivity, specificity, predictive values, and interval likelihood ratios were performed. Results: A total of 457 patients were enrolled with an average age of 64 years (standard deviation: 19 years). Mean temperatures were: oral (98.38F), TM (99.68F), and rectal (99.48F). The mean difference in rectal and oral temperatures was 1.18F, although there was considerable lack of agreement between oral and rectal temperatures, with the oral temperature as much as 2.918F lower or 0.748F higher than the rectal measurement (95% CI). Although the difference in mean temperature between right TM and rectal temperature was only 0.228F, the right TM was lower than rectal by up to 1.618F or greater by up to 2.058F (95% CI). Test performance varied as the positive predictive value of the oral temperature was 97% and for tympanic temperature was 55% (relative to a rectal temperature of 100.48F or higher). Comparative findings differed even at temperatures considered in the normal range; among patients with an oral temperature of 98.0 to 98.9, 38% (25/65) were found to have a rectal temperature of 100.4 or higher, while among patients with a TM of 98.0 to 98.9, only 7% (10/134) were found to have a rectal temperature of 100.4 or higher. Conclusion: In conclusion, the oral and tympanic temperature readings are not equivalent to rectal thermometry readings. Oral thermometry frequently underestimates the temperature relative to rectal readings, and TM values can either under- or overestimate the rectal temperature. The clinician needs to be aware of the varying relationship between oral, TM, and rectal temperatures when interpreting readings. [West J Emerg Med. 2011;12(4):505–511.]

        Cover page: Oral and Tympanic Membrane Temperatures are Inaccurate to Identify Fever in Emergency Department AdultsCreative Commons 'BY-NC' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2014)
        Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence.
          Cover page: Guidelines of care for the management of atopic dermatitis: Section 4. Prevention of disease flares and use of adjunctive therapies and approaches.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2014)
          Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.
            Cover page: Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2014)
            Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.
              Cover page: Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.
              • Article
              • Peer Reviewed
              LBL Publications (2024)
              Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 complex in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated with regulating splicing, transcriptional, and translation) and two-histidine phosphodiesterase (PDE; associated with hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss of ASCC1 function to spinal muscular atrophy with congenital bone fractures 2 (SMABF2). Herein analysis of The Cancer Genome Atlas (TCGA) suggests ASCC1 RNA overexpression in certain tumors correlates with poor survival, Signatures 29 and 3 mutations, and genetic instability markers. We determined crystal structures of Alvinella pompejana (Ap) ASCC1 and Human (Hs) PDE domain revealing high-resolution details and features conserved over 500 million years of evolution. Extending our understanding of the KH domain Gly-X-X-Gly sequence motif, we define a novel structural Helix-Clasp-Helix (HCH) nucleotide binding motif and show ASCC1 sequence-specific binding to CGCG-containing RNA. The V-shaped PDE nucleotide binding channel has two His-Φ-Ser/Thr-Φ (HXT) motifs (Φ being hydrophobic) positioned to initiate cyclic phosphate bond hydrolysis. A conserved atypical active-site histidine torsion angle implies a novel PDE substrate. Flexible active site loop and arginine-rich domain linker appear regulatory. Small-angle X-ray scattering (SAXS) revealed aligned KH-PDE RNA binding sites with limited flexibility in solution. Quantitative evolutionary bioinformatic analyses of disease and cancer-associated mutations support implied functional roles for RNA binding, phosphodiesterase activity, and regulation. Collective results inform ASCC1's roles in transactivation and alkylation damage responses, its targeting by structure-based inhibitors, and how ASCC1 mutations may impact inherited disease and cancer.
                Cover page: ASCC1 structures and bioinformatics reveal a novel helix-clasp-helix RNA-binding motif linked to a two-histidine phosphodiesteraseCreative Commons 'BY' version 4.0 license
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2014)
                Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
                  Cover page: Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents.
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