Interdisciplinarity in Translation Medicine: A Bibliometric Case Study.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

Diving Into Infographics: Research Skills for Early Undergraduates in Global Environmental Science

The common experience for many early undergraduate students is to be taught the basics of their field via a survey course. Most often, their introduction to the library and librarians might be a one-hour instructional session on how to use the library catalog and find books and articles. Students’ understanding of research and the library remains unchanged from their prior knowledge: sub- ject information comes from teachers and textbooks, and libraries are places to study and check out books. This chapter describes a course that attempts to re-envision this relationship by giving students an initial experience that is a dive into the research process in a manageable format, with a semester-long in- troduction to their field, to research, and the role of the academic librarian as a research partner

Will Washington Provide Its Own Feedstocks for Biofuels?

The study finds that Washington State’s field corn, sugar beet and canola production could satisfy only a small percentage of the State’s annual gasoline or diesel consumption. Linear programming projections for 2008 showed a relatively close match between projected and actual production. Projections for 2009-2011 showed no increase in the State’s capacity to increase biofuel crop feedstocks. In comparison to crop feedstocks, Washington’s total annual lignocellulosic biomass is abundant. However, only a fraction of the biomass could be converted to biofuel due to high costs of collection and processing, competing markets for some biomass, and limitations in current technology.biofuels, biofuel feedstocks, canola, cellulosic inventories, grain corn, linear programming, Washington State

Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells

Accurate prediction of gene feedback circuit behavior from component properties

A basic assumption underlying synthetic biology is that analysis of genetic circuit elements, such as regulatory proteins and promoters, can be used to understand and predict the behavior of circuits containing those elements. To test this assumption, we used time‐lapse fluorescence microscopy to quantitatively analyze two autoregulatory negative feedback circuits. By measuring the gene regulation functions of the corresponding repressor–promoter interactions, we accurately predicted the expression level of the autoregulatory feedback loops, in molecular units. This demonstration that quantitative characterization of regulatory elements can predict the behavior of genetic circuits supports a fundamental requirement of synthetic biology

Plxnd1 Expression in Thymocytes Regulates Their Intrathymic Migration While That in Thymic Endothelium Impacts Medullary Topology

An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO) mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1−/− genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre, or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO) lines involving thymocytes (D1ThyCKO), thymic epithelium (D1EpCKO), and thymic endothelium (D1EnCKO), respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP) thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components

Neural evidence for "intuitive prosecution": The use of mental state information for negative moral verdicts

Moral judgment depends critically on theory of mind (ToM), reasoning about mental states such as beliefs and intentions. People assign blame for failed attempts to harm and offer forgiveness in the case of accidents. Here we use fMRI to investigate the role of ToM in moral judgment of harmful vs. helpful actions. Is ToM deployed differently for judgments of blame vs. praise? Participants evaluated agents who produced a harmful, helpful, or neutral outcome, based on a harmful, helpful, or neutral intention; participants made blame and praise judgments. In the right temporo-parietal junction (right TPJ), and, to a lesser extent, the left TPJ and medial prefrontal cortex, the neural response reflected an interaction between belief and outcome factors, for both blame and praise judgments: The response in these regions was highest when participants delivered a negative moral judgment, i.e., assigned blame or withheld praise, based solely on the agent's intent (attempted harm, accidental help). These results show enhanced attention to mental states for negative moral verdicts based exclusively on mental state information.Athinoula A. Martinos Center for Biomedical ImagingSimons FoundationNational Science Foundation (U.S.)John Merck Scholars Progra

A case series of an off-the-shelf online health resource with integrated nurse coaching to support self-management in COPD

Background: COPD has significant psychosocial impact. Self-management support improves quality of life, but programs are not universally available. IT-based self-management interventions can provide home-based support, but have mixed results. We conducted a case series of an off-the-shelf Internet-based health-promotion program, The Preventive Plan (TPP), coupled with nurse-coach support, which aimed to increase patient activation and provide self-management benefits. Materials and methods: A total of 19 COPD patients were recruited, and 14 completed 3-month follow-up in two groups: groups 1 and 2 with more and less advanced COPD, respectively. Change in patient activation was determined with paired t-tests and Wilcoxon signed-rank tests. Benefits and user experience were explored in semistructured interviews, analyzed thematically. Results: Only group 1 improved significantly in activation, from a lower baseline than group 2; group 1 also improved significantly in mastery and anxiety. Both groups felt significantly more informed about COPD and reported physical functioning improvements. Group 1 reported improvements in mood and confidence. Overall, group 2 reported fewer benefits than group 1. Both groups valued nurse-coach support; for group 1, it was more important than TPP in building confidence to self-manage. The design of TPP and lack of motivation to use IT were barriers to use, but disease severity and poor IT skills were not. Discussion: Our findings demonstrate the feasibility of combining nurse-coach support aligned to an Internet-based health resource, TPP, in COPD and provide learning about the challenges of such an approach and the importance of the nurse-coach role

A protocol for a feasibility randomised controlled trial to assess the difference between functional bracing and plaster cast for the treatment of ankle fractures

Background: UK Hospital Episode Statistics 2013–2014 recorded 57,286 fractures of the lower limb including the ankle. This figure is expected to continue to increase due to a greater population of older adults. Following an ankle fracture, patients usually have their ankle immobilised with a plaster cast. This provides maximum support for the healing ankle but is associated with stiffness and muscle wasting. A Cochrane Review has concluded that functional bracing may reduce muscle wasting and speed recovery of ankle movement. The aim of this study is to determine the feasibility of conducting a full randomised controlled trial in adults with an ankle fracture followed by functional bracing and exercises versus standard plaster cast care. Methods: This is a single-centre feasibility randomised controlled trial. All patients with a fractured ankle are potentially eligible. The trial will employ 1:1 random allocation, stratified by age and non-operative/operative management. Baseline demographic and pre-injury functional data, the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) and Olerud and Molander Ankle Score (OMAS) will be collected alongside the EuroQol EQ-5D-5 L health-related quality of life questionnaire. A research associate will perform a clinical assessment and obtain X-rays in 6 weeks and 6 months post randomisation to record complications. Functional outcome and health-related quality of life will be collected in 6 weeks, 3 and 6 months post randomisation. Discussion: This feasibility trial will provide authoritative high-quality evidence to inform the design of a definitive trial in this important area