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Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2019)

Three studies within this dissertation investigated 2nd through 8th grade students’ productive use of academic language in their argumentative essays (N=741 essays). Despite the prominence of argumentative writing in the Common Core State Standards (Common Core State Standards Initiative, 2010), little research has been conducted on specific reasoning strategies and the lexical precision to signal arguments in elementary and early adolescent writing. Using quantitative and natural language processing methods, I examined argumentative reasoning and connective types (and their relations) in students’ independently written essays.

In Study 1, I analyzed 385 argumentative essays written by a sample of 385 2nd and 3rd grade students (one essay per student). All students wrote about the same topic, and essays were coded for arguments, argument sophistication, and connectives. Controlling for grade and essay length, reading comprehension had a significant positive association with argument sophistication in the essays. When connective types were added to the model, and again controlling for essay length and grade, reading comprehension and adversative connectives both had significant positive associations with argument sophistication in the essays.

In Study 2, I analyzed 198 argumentative essays written by a sample of 66 4th and 5th grade students (3 essays per student). Fourth and 5th grade students wrote about different topics, and essays were coded for arguments, argument sophistication, connectives, and connectives sophistication. Controlling for topic, essay length, and ethnicity variables, reading comprehension had a significant positive association with argument sophistication. When a measure of connectives sophistication was added to the model, reading comprehension no longer had a significant association with argument sophistication, and connectives sophistication also did not have a significant association with argument sophistication. However, adding connective types to the model explained an additional 7% of the variance, and adversative connectives had a significant positive association with argument sophistication in the essays.

In Study 3, I analyzed 158 argumentative essays written by a sample of 40 6th through 8th grade students (3 or 4 essays per student). Students in all grades wrote about the same four topics. Essays were coded for arguments and argument sophistication, and a natural language processing tool (Tool for the Automated Analysis of Cohesion, TAACO; Crossley, Kyle, & McNamara, 2016) calculated categories of connectives. Controlling for length and topic, adversative connectives had a significant positive association with argument sophistication.

Findings from this dissertation underscore that 2nd through 8th grade students marshal academic language in their argumentative writing in specific ways that are unlikely to be elucidated in holistic measures of writing quality. Findings also indicate that certain linguistic features (i.e., adversative connectives) are related to more complex arguments in these students’ essays.

References

Common Core State Standards Initiative. (2010). Common core state standards for English language arts & literacy in history/social studies, science, and technical subjects. Retrieved from http://www.corestandards.org/assets/CCSSI_ELA%20Standards.pdf

Crossley, S. A., Kyle, K., & McNamara, D. S. (2016). The tool for the automatic analysis of text cohesion (TAACO): Automatic assessment of local, global, and text cohesion. Behavior Research Methods, 48, 1227-1237. doi:10.3758/s13428-015-0651-7

    Cover page: Academic Language Features in the Argumentative Writing of Second through Eighth Grade Students
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2019)
      Cover page: Cognitive and linguistic features of adolescent argumentative writing: Do connectives signal more complex reasoning?
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2015)
      Neuronal pentraxin receptor (NPR) is a synaptic protein implicated in AMPA receptor trafficking at excitatory synapses. Since glutamate neurotransmission is disrupted in Alzheimer's disease (AD), NPR levels measured from plasma represent a potential biomarker for synaptic dysfunction associated with AD. We sought to determine the relationship between AD pathology and brain and plasma NPR levels by examining age-associated NPR levels in these compartments in a transgenic APP/PS1 rat model of AD. NPR levels in cortical homogenate were similar in wild-type (Wt) and APP/PS1 rats at 3 months of age (prior to Aβ plaque deposition), but significantly increased in APP/PS1 rats by 9 and 18-20 months of age (after the onset of plaque deposition). These age-dependent differences were driven by proportional increases in NPR in membrane-associated cortical fractions. Genotype-related differences in NPR expression were also seen in the hippocampus, which exhibits significant Aβ pathology, but not in the cerebellum, which does not. Plasma analyses revealed increased levels of a 26 kDa NPR fragment in APP/PS1 rats relative to Wt rats by 18-20 months of age, which correlated with the levels of full-length NPR in cortex. Our findings indicate that cerebral accumulation of NPR and Aβ occurs with similar temporal and regional patterns in the APP/PS1 model, and suggest that a 26 kDa plasma NPR fragment may represent a peripheral biomarker of this process.
        Cover page: Parallel age-associated changes in brain and plasma neuronal pentraxin receptor levels in a transgenic APP/PS1 rat model of Alzheimer's disease
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2019)
        Many children fail to comprehend what they read because they do not monitor their understanding, which requires making accurate judgements of what they know and then employing repair strategies when comprehension fails. Relying on research from learning science and cognitive and developmental psychology, we developed the Word Knowledge e-Book (WKe-Book) to improve children's calibration of their word knowledge, strategy use, and word knowledge overall; skills which are associated with reading comprehension. The WKe-Book, which is read on a tablet computer, is a choose-your-own adventure book where choices require choosing between two rare words (e.g., cogitate vs. procrastinate). Depending on the word chosen, the story follows a different plot. There are also embedded comprehension questions where students receive immediate feedback with consequences for incorrect answers, such as being sent back to reread a few pages. In a randomized controlled trial, we tested whether students (N = 603 in 25 third through fifth grade classrooms in Arizona in the US) reading the WKe-Book would demonstrate improved word knowledge, strategy use, and word knowledge calibration. Classrooms were randomly assigned to read the WKe-Book immediately (treatment) or later (delayed-treatment control), and within classrooms, students were randomly assigned to either participate in a 15-minute weekly book club (book club treatment) or to read the WKe-Book independently with no book club (no book club control). Results revealed a significant treatment effect of the WKe-Book on students' word knowledge, word knowledge calibration, and strategy use, which predicted student performance on standardized reading comprehension and vocabulary measures. The effects were greater for students who participated in weekly book clubs compared to students in the no book club control. These findings suggest that the affordances offered by technology, which are unavailable in paper-based books, can support students' development of metacognition, including word knowledge calibration, strategy use, and word learning skills.
          Cover page: Building word knowledge, learning strategies, and metacognition with the Word-Knowledge e-Book
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2018)
          Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein self-assembly, which act by binding selectively to lysine and arginine residues. Through this unique mechanism of action, MTs inhibit formation of toxic oligomers and aggregates. Their efficacy and safety have been demonstrated in vitro, in cell culture, and in animal models. Here, we discuss the application of MTs in diverse in vitro and in vivo systems, the experimental details, the scope of their use, and the limitations of the approach. We also consider methods for administration of MTs in animal models to measure efficacy, pharmacokinetic, and pharmacodynamic parameters in proteinopathies.
            Cover page: Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2018)
            Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein self-assembly, which act by binding selectively to lysine and arginine residues. Through this unique mechanism of action, MTs inhibit formation of toxic oligomers and aggregates. Their efficacy and safety have been demonstrated in vitro, in cell culture, and in animal models. Here, we discuss the application of MTs in diverse in vitro and in vivo systems, the experimental details, the scope of their use, and the limitations of the approach. We also consider methods for administration of MTs in animal models to measure efficacy, pharmacokinetic, and pharmacodynamic parameters in proteinopathies.
              Cover page: Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2016)

              Background

              Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge.

              Methods

              We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial.

              Results

              Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042).

              Conclusions

              This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance.

              Trial registration

              ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999.
                Cover page: Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2015)
                Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on β-amyloid (Aβ) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Aβ oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Aβ indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Aβ plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Aβ oligomer levels in the hippocampus. Further quantification of specific conformational populations of Aβ oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Aβ oligomers and decreased prefibrillar (i.e. putatively more toxic) Aβ oligomers. These results provide in vivo evidence suggesting that DHA can modulate Aβ aggregation by stabilizing soluble fibrillar Aβ oligomers and thus reduce the formation of both Aβ plaques and prefibrillar Aβ oligomers. However, since fibrillar Aβ oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Aβ oligomer levels for more effective prevention of AD in clinical settings.
                  Cover page: Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization
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