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

Representing Dependencies in Event Structures

Event structures where the causality may explicitly change during a computation have recently gained the stage. In this kind of event structures the changes in the set of the causes of an event are triggered by modifiers that may add or remove dependencies, thus making the happening of an event contextual. Still the focus is always on the dependencies of the event. In this paper we promote the idea that the context determined by the modifiers plays a major role, and the context itself determines not only the causes but also what causality should be. Modifiers are then used to understand when an event (or a set of events) can be added to a configuration, together with a set of events modeling dependencies, which will play a less important role. We show that most of the notions of Event Structure presented in literature can be translated into this new kind of event structure, preserving the main notion, namely the one of configuration

A Stakeholder Analysis to Assess Preferences and Willingness-to-Pay for Management of Rice Wild Relatives in Sri Lanka

Proper management of rice wild relative populations scattered in Sri Lanka in smallquantities are highly warranted as they constitute an increasingly important genetic resourcethat can be used with further research to increase yield of existing hybrid rice varieties. Inlight of this, this paper presents the outcome of a multi-phased research study carried out toassess the preferences of key stakeholders for conservation and utilisation of thosepopulations. The information contained in databases from a series of empirical analysescarried out with key stakeholders, including the: (a) Breeders (n=30); (b) Environmentmanagers (n=65); (c) Government officials (n=40); (d) Rural communities (n=50), and (e)Urban communities (n=300) were used to select the most relevant attributes pertaining tomanagement of rice wild relatives, including: (1) responsibility for conservation; (2)utilisation of WRR sites; (3) the best conservation method, and (4) Marginal Willingness-to-Pay (MWTP). The outcome of analysis, which employed both Choice Experiment andContingent Ranking methods highlights that the willingness-to-pay of rural adjacentcommunity was significantly higher (Rs. 82.73) than that of urban households (Rs. 1.34),breeders (Rs. 10.00), policy planners (Rs. 20.46) and environmental managers (Rs. 7.34). Theoverall MWTP for all stakeholders was estimated to be Rs. 4.83. It also shows that themajority of stakeholders prefer government takes the sole responsibility of conservation ofWRR and the adjacent communities should be allowed to utilise WRR sites under thesupervision of government. All the stakeholders preferred in-situ conservation. The resultsdraw attention on progressive policy measures which encompass participation of all groups ofstakeholders at equal levels; mainstreaming of conservation activities into livelihooddevelopment strategies to address the local needs, and setting up of alternative institutionalarrangements towards proper execution of policies and research programs aimingconservation of rice wild relatives for the future

DEVELOPMENT OF AN ECO~BUSINESS DIRECTORY: APPROACHES AND CHALLENGES

Eco-business is the provision of products and services that are environmentally friendly.When the preferences of the society are heading towards environmental safety, ,manufacturers need to adjust their production and marketing strategies to respond to thischange in consumer preferences. Eco-business aims at exploiting the market mechanismto provide the market with more environmentally responsible products. This studypresents the approaches used and challenges faced in the development of an eeo businessdirectory for Sri LankaThe building of the preliminary model for an eco business directory was done with thehelp of five types of surveys. Firstly, an island-wide industrial survey has been carried outwhich included major industries, hotel industry and minor industries. Secondly, an expertopinion survey was carried out to review the existing situation on a sectoral basisregarding eco-friendly products/services and to explore the possibilities and recentdevelopments of new products and services. Thirdly, a survey of existing literature wasdone in order to understand experiences regarding eco-friendly products in differentcontexts. In addition, NGO activities related environment has been collected in order toidentify gaps in public participation. In addition, available financial mechanisms for ecoindustries have also been listed.The main challenges faced in the preparation was the limited response from the relevantparties for the surveys. The lack of awareness on the 'eco friendly' products and serviceswas another issue which need further theoretical and practical definitionsIf eco ousinesses are to be establisued as a complete business s.rategy, environmentalclaims had to be accurate and independently substantiated. It is not likely that marketplace would resolve these problems on its own. The paper elaborates on the need ofguidelines and specifications on eco friendly products and services.

Structuring Collaboration Scripts: Optimizing online group work on classroom dilemmas in teacher education

The optimal structure in collaboration scripts for serious games has appeared to be a key success factor. In this study we compare a ‘high- structured’ and ‘low-structured’ version of a mastership game where teachers-in-training discuss solutions on classroom dilemmas. We collected data on the differences in learning effects and student appreciation. The most interesting result shows that reports delivered by students that played the low-structured version received significantly higher teacher grades when compared to the high-structured version

Characterization of Neuronal Tau Protein as a Target of Extracellular Signal-regulated Kinase

Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its dysregulation in pathological conditions. Molecular mechanisms leading to hyperphosphorylation of Tau in pathological conditions are unknown. Here, we characterize phosphorylation of Tau by extracellular-regulated kinase (ERK2), a mitogen-activated kinase (MAPK) that responds to extracellular signals. Analysis of in vitro phosphorylated Tau by activated recombinant ERK2 with nuclear magnetic resonance spectroscopy (NMR) reveals phosphorylation of 15 Ser/Thr sites. In vitro phosphorylation of Tau using rat brain extract and subsequent NMR analysis identifies the same sites. Phosphorylation with rat brain extract is known to transform Tau into an Alzheimer disease-like state. Our results indicate that phosphorylation of Tau by ERK2 alone is sufficient to produce the same characteristics. We further investigate the mechanism of ERK2 phosphorylation of Tau. Kinases are known to recognize their protein substrates not only by their specificity for a targeted Ser or Thr phosphorylation site but also by binding to linear-peptide motifs called docking sites. We identify two main ERK2 docking sites in Tau sequence using NMR. Our results suggest that ERK2 dysregulation in Alzheimer disease could lead to abnormal phosphorylation of Tau resulting in the pathology of the disease.This work was supported by TGE RMN THC (FR-3050, France) and FRABio (Lille University, CNRS, FR 3688) and also by a grant from the LabEx (Laboratory of Excellence), DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to Alzheimer's disease), and in part by the French government funding agency Agence Nationale de la Recherche TAF. This work was supported by National Institutes of Health Grant R01 GM081578 (to S. P. and J. G.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

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

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

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338