A rule-based model of insulin signalling pathway

\u3cp\u3eBackground: The insulin signalling pathway (ISP) is an important biochemical pathway, which regulates some fundamental biological functions such as glucose and lipid metabolism, protein synthesis, cell proliferation, cell differentiation and apoptosis. In the last years, different mathematical models based on ordinary differential equations have been proposed in the literature to describe specific features of the ISP, thus providing a description of the behaviour of the system and its emerging properties. However, protein-protein interactions potentially generate a multiplicity of distinct chemical species, an issue referred to as combinatorial complexity , which results in defining a high number of state variables equal to the number of possible protein modifications. This often leads to complex, error prone and difficult to handle model definitions. Results: In this work, we present a comprehensive model of the ISP, which integrates three models previously available in the literature by using the rule-based modelling (RBM) approach. RBM allows for a simple description of a number of signalling pathway characteristics, such as the phosphorylation of signalling proteins at multiple sites with different effects, the simultaneous interaction of many molecules of the signalling pathways with several binding partners, and the information about subcellular localization where reactions take place. Thanks to its modularity, it also allows an easy integration of different pathways. After RBM specification, we simulated the dynamic behaviour of the ISP model and validated it using experimental data. We the examined the predicted profiles of all the active species and clustered them in four clusters according to their dynamic behaviour. Finally, we used parametric sensitivity analysis to show the role of negative feedback loops in controlling the robustness of the system. Conclusions: The presented ISP model is a powerful tool for data simulation and can be used in combination with experimental approaches to guide the experimental design. The model is available at http://sysbiobig.dei.unipd.it/was submitted to Biomodels Database ( https://www.ebi.ac.uk/biomodels-main/ # MODEL 1604100005).\u3c/p\u3

PENGARUH METODE ECOLA (EXTENDING CONCEPTH TRHOUGH LANGUAGE ACTIVITIES) DALAM PEMBELAJARAN MEMBACA KRITIS TAJUK RENCANA

Penelitian ini bertujuan untuk memperoleh gambaran secara objektif tentang ada tidaknya perbedaan yang signifikan antara kemampuan siswa dalam membaca kritis tajuk rencana atau teks editorial kelas eksperimen dengan menggunakan metode ECOLAdan kelas kontrol dengan metode ceramah. Populasi dalam penelitian ini adalah seluruh siswa kelas VIII SMP Negeri 16 Bandung ajaran tahun 2015/2016. Sampel dalam penelitian ini adalah dua kelas yang dipilih secara purposive sampling, yakni pertimbangan dalam mengambil sampel tersebut, disebabkan kelas VIII G dan VIII H memiliki rata-rata nilai yang hampir sama dalam pembelajaran bahasa Indonesia dilihat dari Ujian Tengah Semester. Kelas yang digunakan adalah kelas VIII H sebagai kelas eksperimen dan kelas VIII G sebagai kelas kontrol. Penelitian ini menggunakan metode eksperimen kuasi dengan desain penelitian Nonequivalent Control Group Design. Pada desain ini dilakukan tes awal dan tes akhir di kelas eksperimen dan kelas kontrol. Pengolahan data dilakukan uji realibilitas antar penimbang, uji normalitas, homogenitas, dan hipotesis. Berdasarkan hasil penelitian, didapatkan bahwa nilai rata-rata kelas eksperimen lebih tinggi daripada nilai rata-rata kelas kontrol. Rata-rata nilai tes awal kelas eksperimen yaitu 63 dan nilai rata-rata tes akhir 82. Sedangkan rata-rata nilai tes awal kontrol yaitu 54 dan rata-rata nilai tes akhir 66. Berdasarkan perolehan nilai tersebut didapatkan perbedaan nilai rata-rata kelas eksperimen 19 dan perbedaan nilai rata-rata kelas kontrol yaitu 13. Berdasarkan hasil pengujian hipotesis diperoleh nilaithitung= 5,01>ttabel = 1,99866, maka Ho ditolak dan Ha diterima. Hal ini menunjukkan bahwa metode ECOLA berpengaruh dan dapat digunakan dalam pembelajaran membaca kritis tajuk rencana. ;--- This research aims toget the objective informationwhether there is a significance differences or not between students’ abilityin editorial critical reading text in an experimental class using ECOLA methodwith a control class using lecture method. The population of the research are all students of VIII grade class of16 Junior High School of Bandung in 2015/2016 school year.The sample are two classes of students which are selected through purposive sampling, consideringG and H class have a same average scoresin Indonesia Language subject,taken from Mid-Semester Test score. The H class was the experimental classand the G class control. The research utilizes a quasi-experimental methodwithNonequivalent Control Group Designwith a pre and a post-test. Reliability test was employed between counselor, normalcy test, homogenates, andhypothesis. The result shows that the average score of experimental classis higher than the control class. The experimental class’ average pre-test score was 63 the post-test was 82 whilethe control class’ average pre-test score was 54 andpost-test score was 66. The difference between pre and post-test of experimental class was 19 and control class was 13. Hypothesis test result shows thatthitung = 5,01>ttabel= 1,99866, then Hois rejectedand Hais accepted. It concludes thatECOLAis influential and implementable in editorial critical reading

Modelling the molecular mechanisms of ageing

This document is the Accepted Manuscript version of a published work that appeared in final form in Bioscience reports. To access the final edited and published work see http://www.bioscirep.org/content/37/1/BSR20160177.The ageing process is driven at the cellular level by random molecular damage which slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the ageing process. The complexity of the ageing process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards, and discusses many specific examples of models which have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field

A Proposed Model for Evaluating the Sustainability of Continuous Change Programmes

Many studies report that it is difficult to sustain change. This article focuses on how an organization can initiate and sustain a continuous change process. A theoretical model is proposed as a fusion of two previous models for evaluating the sustainability of a change programme; the first is based on analysing stakeholder interest balance as a prerequisite for organizational sustainability, the second on analysing the design of the implementation, indicating whether long-term effects will be achieved. It is argued that the combination of these factors provides a more comprehensive perspective, since it allows us to evaluate both the 'form' and the 'direction' of the programme. To assess stakeholder interest balance, the goal for the change programme is analysed, utilizing the broad stakeholder interest balance perspective. To assess the design of the implementation, four preconditions for long-term effects should be analysed: management's ownership of the change initiative, professional steering, competent leadership and participation. Reference is given to the management concept Lean Production, which is claimed to engage the organization in continuous change. Application of the model highlights the mismatch between narrowly focused change programmes such as Lean Production and sustainable change. © 2012 Copyright Taylor and Francis Group, LLC

Proteomic profiling identifies novel inflammation-related plasma proteins associated with ischemic stroke outcome

Abstract Background The inflammatory response to cerebral ischemia is complex; however, most clinical studies of stroke outcome focus on a few selected proteins. We, therefore, aimed to profile a broad range of inflammation-related proteins to: identify proteins associated with ischemic stroke outcome that are independent of established clinical predictors; identify proteins subsets for outcome prediction; and perform sex and etiological subtype stratified analyses. Methods Acute-phase plasma levels of 65 inflammation-related proteins were measured in 534 ischemic stroke cases. Logistic regression was used to estimate associations to unfavorable 3-month functional outcome (modified Rankin Scale score > 2) and LASSO regressions to identify proteins with independent effects. Results Twenty proteins were associated with outcome in univariable models after correction for multiple testing (FDR < 0.05), and for 5 the association was independent of clinical variables, including stroke severity (TNFSF14 [LIGHT], OSM, SIRT2, STAMBP, and 4E-BP1). LASSO identified 9 proteins that could best separate favorable and unfavorable outcome with a predicted diagnostic accuracy (AUC) of 0.81; three associated with favorable (CCL25, TRAIL [TNFSF10], and Flt3L) and 6 with unfavorable outcome (CSF-1, EN-RAGE [S100A12], HGF, IL-6, OSM, and TNFSF14). Finally, we identified sex- and etiologic subtype-specific associations with the best discriminative ability achieved for cardioembolic, followed by cryptogenic stroke. Conclusions We identified candidate blood-based protein biomarkers for post-stroke functional outcome involved in, e.g., NLRP3 inflammasome regulation and signaling pathways, such as TNF, JAK/STAT, MAPK, and NF-κB. These proteins warrant further study for stroke outcome prediction as well as investigations into the putative causal role for stroke outcome