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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2010)
We show that intermodel variations in the anthropogenically-forced evolution of September sea ice extent (SSIE) in the Arctic stem mainly from two factors: the baseline climatological sea ice thickness (SIT) distribution, and the local climate feedback parameter. The roles of these two factors evolve over the course of the twenty-first century. The SIT distribution is the most important factor in current trends and those of coming decades, accounting for roughly half the intermodel variations in SSIE trends. Then, its role progressively decreases, so that around the middle of the twenty-first century the local climate feedback parameter becomes the dominant factor. Through this analysis, we identify the investments in improved simulation of Arctic climate necessary to reduce uncertainties both in projections of sea ice loss over the coming decades and in the ultimate fate of the ice pack.
    Cover page: Sources of spread in simulations of Arctic sea ice loss over the twenty-first century: A letter
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2013)
    ADSCs are a great cell source for tissue engineering and regenerative medicine. However, the development of methods to appropriately manipulate these cells in vitro remains a challenge. Here the proliferation and differentiation of ADSCs on microfabricated surfaces with varying geometries were investigated. To create the patterned substrates, a maskless biofabrication method was developed based on dynamic optical projection stereolithography. Proliferation and early differentiation of ADSCs were compared across three distinct multicellular patterns, namely stripes (ST), symmetric fork (SF), and asymmetric fork (AF). The ST pattern was designed for uniaxial cell alignment while the SF and AF pattern were designed with altered cell directionality to different extents. The SF and AF patterns generated similar levels of regional peak stress, which were both significantly higher than those within the ST pattern. No significant difference in ADSC proliferation was observed among the three patterns. In comparison to the ST pattern, higher peak stress levels of the SF and AF patterns were associated with up-regulation of the chondrogenic and osteogenic markers SOX9 and RUNX2. Interestingly, uniaxial cell alignment in the ST pattern seemed to increase the expression of SM22α and smooth muscle α-actin, suggesting an early smooth muscle lineage progression. These results indicate that geometric cues that promote uniaxial alignment might be more potent for myogenesis than those with increased peak stress. Overall, the use of these patterned geometric cues for modulating cell alignment and form-induced stress can serve as a powerful and versatile technique towards controlling differentiation in ADSCs.
      Cover page: Relative impact of uniaxial alignment vs. form-induced stress on differentiation of human adipose derived stem cells
      • Article
      Recent Work (2012)

      Using a combination of dynamical and statistical downscaling techniques, we projected mid-21stcentury warming in the Los Angeles region at 2-km (1.2-mile) resolution. To account for uncertainty associated with the trajectory of future greenhouse gas emissions and other factors affecting the planet's energy balance, we examined projections for both "business-as-usual" (RCP8.5) and "mitigation" (RCP2.6) emissions scenarios of the Fifth Coupled Model Intercomparison Project. To account for the considerable uncertainty associated with choice of global climate model, we downscaled results for all available global models. For the business-as-usual scenario, we find that by the mid-21stcentury, the most likely warming is roughly 4.6°F averaged over the region's land areas, with a 95% confidence that the warming lies between 1.7 and 7.5°F. The high resolution of the projections reveals a pronounced spatial pattern in the warming: High elevations and inland areas separated from the coast by at least one mountain complex warm 20 to 50% more than the areas near the coast or within the Los Angeles basin. This warming pattern is especially apparent in summertime. The summertime warming contrast between the inland and coastal zones has a large effect on the most likely expected number of extremely hot days per year. Coastal locations and areas within the Los Angeles basin see roughly two to three times the number of extremely hot days, while high elevations and inland areas typically experience approximately three to five times the number of extremely hot days. Under the mitigation emissions scenario, the most likely warming and increase in heat extremes are somewhat smaller. However, the majority of the warming seen in the business-as-usual scenario still occurs at all locations in the most likely case under the mitigation scenario, and heat extremes still increase significantly. Therefore adaptation to a changing climate over the next few decades is likely to be inevitable in the Los Angeles region.

        Cover page: Mid-Century Warming in the Los Angeles Region - Part I of the “Climate Change in the Los Angeles Region” projec
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2019)
        Current methods for bioprinting functional tissue lack appropriate biofabrication techniques to build complex 3D microarchitectures essential for guiding cell growth and promoting tissue maturation1. 3D printing of central nervous system (CNS) structures has not been accomplished, possibly owing to the complexity of CNS architecture. Here, we report the use of a microscale continuous projection printing method (μCPP) to create a complex CNS structure for regenerative medicine applications in the spinal cord. μCPP can print 3D biomimetic hydrogel scaffolds tailored to the dimensions of the rodent spinal cord in 1.6 s and is scalable to human spinal cord sizes and lesion geometries. We tested the ability of µCPP 3D-printed scaffolds loaded with neural progenitor cells (NPCs) to support axon regeneration and form new 'neural relays' across sites of complete spinal cord injury in vivo in rodents1,2. We find that injured host axons regenerate into 3D biomimetic scaffolds and synapse onto NPCs implanted into the device and that implanted NPCs in turn extend axons out of the scaffold and into the host spinal cord below the injury to restore synaptic transmission and significantly improve functional outcomes. Thus, 3D biomimetic scaffolds offer a means of enhancing CNS regeneration through precision medicine.
          Cover page: Biomimetic 3D-printed scaffolds for spinal cord injury repair
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2017)
          Detection of circulating tumor DNA using droplet digital polymerase chain reaction (ddPCR) is a highly-sensitive, minimally invasive alternative to serial biopsies for assessment and management of cancer. We used ddPCR to assess the utility of measuring plasma concentrations of common epidermal growth factor receptor (EGFR) mutations (L858R, exon 19 deletion, and T790M) in 57 non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). High baseline plasma EGFR mutation (pEGFRmut) concentrations were associated with shorter progression-free survival (8.43 months) than low baseline pEGFRmut (16.23 months; p = 0.0019). By contrast, there were no differences in tumor shrinkage or overall survival between groups. During EGFR-TKI treatment, pEGFRmut levels decreased to zero in 89.58% of patients. Twenty-five of the 27 patients who progressed had basal pEGFRmut, and 18 also had circulating T790M. All 20 patients with dramatic progression (according to a categorization system for EGFR-TKIs failure) had basal pEGFRmut, and 13 had T790M mutation at progression. These results support the use of ddPCR for analysis of plasma EGFR mutations for prediction of PFS and to monitor clinical responses to EGFR-TKIs in NSCLC patients.
            Cover page: Estimation of cell-free circulating EGFR mutation concentration predicts outcomes in NSCLC patients treated with EGFR-TKIs
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2016)
            The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver-specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling.
              Cover page: Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2017)
              The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non-small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow-ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR-tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR-TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs.
                Cover page: Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC
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