66 research outputs found
Temporal Regulation of Light-Induced Extracellular Signal-Regulated Kinase Activation in the Suprachiasmatic Nucleus
No full textNonlinear Optimization Approach to Construction of General Linear Methods of High Order
No full text. We describe the construction of diagonally implicit multistage integration methods of order and stage order p = q = 7 and p = q = 8 for ordinary differential equations. These methods were obtained using state-ofthe -art optimization methods, particularly variable-model trust-region leastsquares algorithms. Key Words. General linear method, ordinary differential equation, Astability, L-stability, least-squares minimization. AMS Subject Classification. 65L05, 65L20. Department of Mathematics and Statistics, The University of Auckland, Private Bag 92019, Auckland, New Zealand. The work of this author was assisted by the Marsden Fund of New Zealand. y Department of Mathematics, Arizona State University, Tempe, Arizona 85287. The work of this author was partially supported by the National Science Foundation under grant NSF DMS--9208048. z Department of Mathematics, Arizona State University, Tempe, Arizona 85287. The work of this author was partially supported by the National Scien..
Characterization of water and wildlife strains as a subgroup of Campylobacter jejuni using DNA microarrays.
No full textCampylobacter jejuni is the leading cause of human bacterial gastroenteritis worldwide, but source attribution of the organism is difficult. Previously, DNA microarrays were used to investigate isolate source, which suggested a non-livestock source of infection. In this study we analysed the genome content of 162 clinical, livestock and water and wildlife (WW) associated isolates combined with the previous study. Isolates were grouped by genotypes into nine clusters (C1 to C9). Multilocus sequence typing (MLST) data demonstrated that livestock associated clonal complexes dominated clusters C1-C6. The majority of WW isolates were present in the C9 cluster. Analysis of previously reported genomic variable regions demonstrated that these regions were linked to specific clusters. Two novel variable regions were identified. A six gene multiplex PCR (mPCR) assay, designed to effectively differentiated strains into clusters, was validated with 30 isolates. A further five WW isolates were tested by mPCR and were assigned to the C7-C9 group of clusters. The predictive mPCR test could be used to indicate if a clinical case has come from domesticated or WW sources. Our findings provide further evidence that WW C. jejuni subtypes show niche adaptation and may be important in causing human infection
An introduction to biological modeling using coin flips to predict the outcome of a diffusion activity
No full textIn order to increase students’ awareness for and comfort with mathematical modeling of biological processes, and increase their understanding of diffusion, the following lab was developed for use in 100-level, majors/non-majors biology and neuroscience courses. The activity begins with generation of a data set that uses coin-flips to replicate movement of dye molecules at an interface of a permeable gel. The class results are then collapsed into a single data set that is used to predict the movement of real dye molecules over time, which are then measured by students in a “wet-lab” activity
Mitogen‐ and stress‐activated protein kinase 1 modulates photic entrainment of the suprachiasmatic circadian clock
No full textThe master circadian clock in mammals, the suprachiasmatic nucleus (SCN), is under the entraining influence of the external light cycle. At a mechanistic level, intracellular signaling via the p42/44 mitogen-activated protein kinase pathway appears to play a central role in light-evoked clock entrainment; however, the precise downstream mechanisms by which this pathway influences clock timing are not known. Within this context, we have previously reported that light stimulates activation of the mitogen-activated protein kinase effector mitogen-stress-activated kinase 1 (MSK1) in the SCN. In this study, we utilised MSK1-/- mice to further investigate the potential role of MSK1 in circadian clock timing and entrainment. Locomotor activity analysis revealed that MSK1 null mice entrained to a 12 h light/dark cycle and exhibited circadian free-running rhythms in constant darkness. Interestingly, the free-running period in MSK1 null mice was significantly longer than in wild-type control animals, and MSK1 null mice exhibited a significantly greater variance in activity onset. Further, MSK1 null mice exhibited a significant reduction in the phase-delaying response to an early night light pulse (100 lux, 15 min), and, using an 8 h phase-advancing 'jet-lag' experimental paradigm, MSK1 knockout animals exhibited a significantly delayed rate of re-entrainment. At the molecular level, early night light-evoked cAMP response element-binding protein (CREB) phosphorylation, histone phosphorylation and Period1 gene expression were markedly attenuated in MSK1-/- animals relative to wild-type mice. Together, these data provide key new insights into the molecular mechanisms by which MSK1 affects the SCN clock.</p
The p42/44 Mitogen-activated Protein Kinase Pathway Couples Photic Input to Circadian Clock Entrainment
No full textMeasuring Personality and Values Across Cultures: Imported Versus Indigenous Measures
No full textCross-cultural studies of personality have shown cultural similarities and differences in the manifestation of personality traits. In interpreting cultural differences in personality traits, we should consider not only the experiences of people in different cultures, but also the measures adopted and the cultural orientations of researchers themselves. In this chapter, we discuss the considerations in adapting an instrument from one culture to another culture. We illustrate the alternative approach of developing an indigenous personality measure in the Chinese culture
Mismatch-based delayed thrombolysis: a meta-analysis
No full text<p><b>Background and Purpose</b>: Clinical benefit from thrombolysis is reduced as stroke onset to treatment time increases. The use of "mismatch" imaging to identify patients for delayed treatment has face validity and has been used in case series and clinical trials. We undertook a meta-analysis of relevant trials to examine whether present evidence supports delayed thrombolysis among patients selected according to mismatch criteria.</p>
<p><b>Methods</b>: We collated outcome data for patients who were enrolled after 3 hours of stroke onset in thrombolysis trials and had mismatch on pretreatment imaging. We selected the trials on the basis of a systematic search of the Web of Knowledge. We compared favorable outcome, reperfusion and/or recanalization, mortality, and symptomatic intracerebral hemorrhage between the thrombolyzed and nonthrombolyzed groups of patients and the probability of a favorable outcome among patients with successful reperfusion and clinical findings for 3 to 6 versus 6 to 9 hours from poststroke onset. Results are expressed as adjusted odds ratios (a-ORs) with 95% CIs. Heterogeneity was explored by test statistics for clinical heterogeneity, I2 (inconsistency), and L’Abbé plot.</p>
<p><b>Results</b>: We identified articles describing the DIAS, DIAS II, DEDAS, DEFUSE, and EPITHET trials, giving a total of 502 mismatch patients thrombolyzed beyond 3 hours. The combined a-ORs for favorable outcomes were greater for patients who had successful reperfusion (a-OR=5.2; 95% CI, 3 to 9; I2=0%). Favorable clinical outcome was not significantly improved by thrombolysis (a-OR=1.3; 95% CI, 0.8 to 2.0; I2=20.9%). Odds for reperfusion/recanalization were increased among patients who received thrombolytic therapy (a-OR=3.0; 95% CI, 1.6 to 5.8; I2=25.7%). The combined data showed a significant increase in mortality after thrombolysis (a-OR=2.4; 95% CI, 1.2 to 4.9; I2=0%), but this was not confirmed when we excluded data from desmoteplase doses that were abandoned in clinical development (a-OR=1.6; 95% CI, 0.7 to 3.7; I2=0%). Symptomatic intracerebral hemorrhage was significantly increased after thrombolysis (a-OR=6.5; 95% CI, 1.2 to 35.4; I2=0%) but not significant after exclusion of abandoned doses of desmoteplase (a-OR=5.4; 95% CI, 0.9 to 31.8; I2=0%).</p>
<p><b>Conclusions</b>: Delayed thrombolysis amongst patients selected according to mismatch imaging is associated with increased reperfusion/recanalization. Recanalization/reperfusion is associated with improved outcomes. However, delayed thrombolysis in mismatch patients was not confirmed to improve clinical outcome, although a useful clinical benefit remains possible. Thrombolysis carries a significant risk of symptomatic intracerebral hemorrhage and possibly increased mortality. Criteria to diagnose mismatch are still evolving. Validation of the mismatch selection paradigm is required with a phase III trial. Pending these results, delayed treatment, even according to mismatch selection, cannot be recommended as part of routine care.</p>
Simulation modelling: Educational development roles for learning technologists
No full textSimulation modelling was in the mainstream of CAL development in the 1980s when the late David Squires introduced this author to the Dynamic Modelling System. Since those early days, it seems that simulation modelling has drifted into a learning technology backwater to become a member of Laurillard's underutilized, ‘adaptive and productive’ media. Referring to her Conversational Framework, Laurillard constructs a pedagogic case for modelling as a productive student activity but provides few references to current practice and available resources. This paper seeks to complement her account by highlighting the pioneering initiatives of the Computers in the Curriculum Project and more recent developments in systems modelling within geographic and business education. The latter include improvements to system dynamics modelling programs such as STELLA®, the publication of introductory textbooks, and the emergence of online resources. The paper indicates several ways in which modelling activities may be approached and identifies some educational development roles for learning technologists. The paper concludes by advocating simulation modelling as an exemplary use of learning technologies ‐ one that realizes their creative‐transformative potential
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