The Dynamics of Zeroth-Order Ultrasensitivity: A Critical Phenomenon in Cell Biology

It is well known since the pioneering work of Goldbeter and Koshland [Proc. Natl. Acad. Sci. USA, vol. 78, pp. 6840-6844 (1981)] that cellular phosphorylation- dephosphorylation cycle (PdPC), catalyzed by kinase and phosphatase under saturated condition with zeroth order enzyme kinetics, exhibits ultrasensitivity, sharp transition. We analyse the dynamics aspects of the zeroth order PdPC kinetics and show a critical slowdown akin to the phase transition in condensed matter physics. We demonstrate that an extremely simple, though somewhat mathematically "singular" model is a faithful representation of the ultrasentivity phenomenon. The simplified mathematical model will be valuable, as a component, in developing complex cellular signaling network theory as well as having a pedagogic value.Comment: 8 pages, 3 figure

Singularly Perturbed Monotone Systems and an Application to Double Phosphorylation Cycles

The theory of monotone dynamical systems has been found very useful in the modeling of some gene, protein, and signaling networks. In monotone systems, every net feedback loop is positive. On the other hand, negative feedback loops are important features of many systems, since they are required for adaptation and precision. This paper shows that, provided that these negative loops act at a comparatively fast time scale, the main dynamical property of (strongly) monotone systems, convergence to steady states, is still valid. An application is worked out to a double-phosphorylation ``futile cycle'' motif which plays a central role in eukaryotic cell signaling.Comment: 21 pages, 3 figures, corrected typos, references remove

Blended Learning in Health Education: Three Case Studies

Blended learning in which online education is combined with face-to-face education is especially useful for (future) health care professionals who need to keep up-to-date. Blended learning can make learning more efficient, for instance by removing barriers of time and distance. In the past distance-based learning activities have often been associated with traditional delivery-based methods, individual learning and limited contact. The central question in this paper is: can blended learning be active and collaborative? Three cases of blended, active and collaborative learning are presented. In case 1 a virtual classroom is used to realize online problem-based learning (PBL). In case 2 PBL cases are presented in Second Life, a 3D immersive virtual world. In case 3 discussion forums, blogs and wikis were used. In all cases face-to-face meetings were also organized. Evaluation results of the three cases clearly show that active, collaborative learning at a distance is possible. Blended learning enables the use of novel instructional methods and student-centred education. The three cases employ different educational methods, thus illustrating diverse possibilities and a variety of learning activities in blended learning. Interaction and communication rules, the role of the teacher, careful selection of collaboration tools and technical preparation should be considered when designing and implementing blended learning

Self-Regulation in a Web-Based Course: A Case Study

Little is known about how successful students in Web-based courses self-regulate their learning. This descriptive case study used a social cognitive model of self-regulated learning (SRL) to investigate how six graduate students used and adapted traditional SRL strategies to complete tasks and cope with challenges in a Web-based technology course; it also explored motivational and environmental influences on strategy use. Primary data sources were three transcribed interviews with each of the students over the course of the semester, a transcribed interview with the course instructor, and the students’ reflective journals. Archived course documents, including transcripts of threaded discussions and student Web pages, were secondary data sources. Content analysis of the data indicated that these students used many traditional SRL strategies, but they also adapted planning, organization, environmental structuring, help seeking, monitoring, record keeping, and self-reflection strategies in ways that were unique to the Web-based learning environment. The data also suggested that important motivational influences on SRL strategy use—self-efficacy, goal orientation, interest, and attributions—were shaped largely by student successes in managing the technical and social environment of the course. Important environmental influences on SRL strategy use included instructor support, peer support, and course design. Implications for online course instructors and designers, and suggestions for future research are offered

Designing electronic collaborative learning environments

Electronic collaborative learning environments for learning and working are in vogue. Designers design them according to their own constructivist interpretations of what collaborative learning is and what it should achieve. Educators employ them with different educational approaches and in diverse situations to achieve different ends. Students use them, sometimes very enthusiastically, but often in a perfunctory way. Finally, researchers study them and—as is usually the case when apples and oranges are compared—find no conclusive evidence as to whether or not they work, where they do or do not work, when they do or do not work and, most importantly, why, they do or do not work. This contribution presents an affordance framework for such collaborative learning environments; an interaction design procedure for designing, developing, and implementing them; and an educational affordance approach to the use of tasks in those environments. It also presents the results of three projects dealing with these three issues

Communication and proximity effects on outcomes attributable to sense of presence in distance bioinformatics education

<p>Abstract</p> <p>Background</p> <p>Online learning is increasingly popular in medical education and sense of presence has been posited as a factor contributing to its success. Communication media influences on sense of presence and learning outcomes were explored in this study. Test performance and ratings of instruction and technology, factors influenced by sense of presence, are compared under four conditions involving different media and degrees of student physical presence: 1) videoconference co-located, 2) webcast co-located, 3) videoconference dispersed, and 4) webcast dispersed.</p> <p>Methods</p> <p>Eighty one first to forth year medical students heard a lecture on telemedicine and were asked to collaboratively search a telemedicine website under conditions where the lecture was delivered by videoconference or one way streaming (webcast) and where students were either co-located or dispersed. In the videoconference conditions, co-located students could use the technology to interact with the instructor and could interact with each other face to face, while the dispersed students could use the technology to interact with both the instructor and each other. In the webcast conditions, all students could use chat to communicate with the instructor or each other, although the co-located students also could interact orally. After hearing the lecture, students collaboratively searched a telemedicine website, took a test on lecture-website content and rated the instruction and the technology they used. Test scores on lecture and website content and ratings of instruction and technology for the four conditions were compared with analysis of variance and chi-square tests.</p> <p>Results</p> <p>There were no significant differences in overall measures, although there were on selected ratings of instruction. Students in both webcast conditions indicated they were encouraged more to follow up on their own and felt instruction was more interactive than co-located videoconferencing students. Dispersed videoconferencing students indicated the highest levels of interaction and there was evidence they interacted more.</p> <p>Conclusion</p> <p>Results do not strongly support proximity as a sense of presence factor affecting performance and attitudes, but do suggest communication medium may affect interactivity.</p

Topography-derived wetness indices are associated with household-level malaria risk in two communities in the western Kenyan highlands

<p>Abstract</p> <p>Background</p> <p>Transmission of <it>Plasmodium falciparum </it>generally decreases with increasing elevation, in part because lower temperature slows the development of both parasites and mosquitoes. However, other aspects of the terrain, such as the shape of the land, may affect habitat suitability for <it>Anopheles </it>breeding and thus risk of malaria transmission. Understanding these local topographic effects may permit prediction of regions at high risk of malaria within the highlands at small spatial scales.</p> <p>Methods</p> <p>Hydrologic modelling techniques were adapted to predict the flow of water across the landscape surrounding households in two communities in the western Kenyan highlands. These surface analyses were used to generate indices describing predicted water accumulation in regions surrounding the study area. Households with and without malaria were compared for their proximity to regions of high and low predicted wetness. Predicted wetness and elevation variables were entered into bivariate and multivariate regression models to examine whether significant associations with malaria were observable at small spatial scales.</p> <p>Results</p> <p>On average, malaria case households (n = 423) were located 280 m closer to regions with very high wetness indices than non-malaria "control" households (n = 895) (t = 10.35, p < 0.0001). Distance to high wetness indices remained an independent predictor of risk after controlling for household elevation in multivariate regression (OR = 0.93 [95% confidence interval = 0.89–0.96] for a 100 m increase in distance). For every 10 m increase in household elevation, there was a 12% decrease in the odds of the house having a malaria case (OR = 0.88 [0.85–0.90]). However, after controlling for distance to regions of high predicted wetness and the community in which the house was located, this reduction in malaria risk was not statistically significant (OR = 0.98 [0.94–1.03]).</p> <p>Conclusion</p> <p>Proximity to terrain with high predicted water accumulation was significantly and consistently associated with increased household-level malaria incidence, even at small spatial scales with little variation in elevation variables. These results suggest that high wetness indices are not merely proxies for valley bottoms, and hydrologic flow models may prove valuable for predicting areas of high malaria risk in highland regions. Application in areas where malaria surveillance is limited could identify households at higher risk and help focus interventions.</p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined