Analysis of signalling pathways using continuous time Markov chains

We describe a quantitative modelling and analysis approach for signal transduction networks. We illustrate the approach with an example, the RKIP inhibited ERK pathway [CSK+03]. Our models are high level descriptions of continuous time Markov chains: proteins are modelled by synchronous processes and reactions by transitions. Concentrations are modelled by discrete, abstract quantities. The main advantage of our approach is that using a (continuous time) stochastic logic and the PRISM model checker, we can perform quantitative analysis such as what is the probability that if a concentration reaches a certain level, it will remain at that level thereafter? or how does varying a given reaction rate affect that probability? We also perform standard simulations and compare our results with a traditional ordinary differential equation model. An interesting result is that for the example pathway, only a small number of discrete data values is required to render the simulations practically indistinguishable

Geometric Path Integrals. A Language for Multiscale Biology and Systems Robustness

In this paper we suggest that, under suitable conditions, supervised learning can provide the basis to formulate at the microscopic level quantitative questions on the phenotype structure of multicellular organisms. The problem of explaining the robustness of the phenotype structure is rephrased as a real geometrical problem on a fixed domain. We further suggest a generalization of path integrals that reduces the problem of deciding whether a given molecular network can generate specific phenotypes to a numerical property of a robustness function with complex output, for which we give heuristic justification. Finally, we use our formalism to interpret a pointedly quantitative developmental biology problem on the allowed number of pairs of legs in centipedes

On the Interplay between the Evolvability and Network Robustness in an Evolutionary Biological Network: A Systems Biology Approach

In the evolutionary process, the random transmission and mutation of genes provide biological diversities for natural selection. In order to preserve functional phenotypes between generations, gene networks need to evolve robustly under the influence of random perturbations. Therefore, the robustness of the phenotype, in the evolutionary process, exerts a selection force on gene networks to keep network functions. However, gene networks need to adjust, by variations in genetic content, to generate phenotypes for new challenges in the network’s evolution, ie, the evolvability. Hence, there should be some interplay between the evolvability and network robustness in evolutionary gene networks. In this study, the interplay between the evolvability and network robustness of a gene network and a biochemical network is discussed from a nonlinear stochastic system point of view. It was found that if the genetic robustness plus environmental robustness is less than the network robustness, the phenotype of the biological network is robust in evolution. The tradeoff between the genetic robustness and environmental robustness in evolution is discussed from the stochastic stability robustness and sensitivity of the nonlinear stochastic biological network, which may be relevant to the statistical tradeoff between bias and variance, the so-called bias/variance dilemma. Further, the tradeoff could be considered as an antagonistic pleiotropic action of a gene network and discussed from the systems biology perspective

Strategi kepala sekolah madrasah dalam membangun budaya kerja produktif guru di Madrasah Aliyah Swasta : Studi multisitus di Madrasah Aliyah An-Nusyur dan Madrasah Aliyah Darul Ihsan Pragaan Sumenep

INDONESIA: Munculnya konsep budaya kerja bisa jadi berangkat dari ketidakpuasan terhadap hasil, ataupun pencapaian tujuan yang kurang memuaskan. Hal itu dipicu oleh cara bekerja para karyawan dalam organisasi, yang biasanya identik dengan birokrasi yang berbelit-belit, kurang terbuka dengan orang lain, lamban bekerja, kaku, serta kurang percaya pada kemampuan orang. Perubahan dalam budaya kerja termasuk potensi, penerapan, dan pengembangan ilmu pengetahuan serta teknologi agar dapat meningkatkan kualitas hidup. Oleh karena itu, agar lembaga pendidikan dalam upaya berdaya saing, berkualitas dan mampu menjawab persoalan dari masyarakat, perlu adanya strategi kiat-kiat khusus yang dilakukan oleh kepala sekolah dalam membangun budaya kerja yang produktif demi memajukan lembaga pendidikan. Adapun tujuan penelitian ini menfokuskan pada 3 hal yaitu; Pertama, Bagaimana konsep budaya kerja guru produktif di sekolah menurut kepala sekolah madrasah aliyah swasta di pragaan sumenep. Kedua, bagaimana langkah-langkah strategis kepala sekolah dalam membangun budaya kerja guru produktif dan Ketiga, Bagaimana kesulitan yang dihadapi kepala sekolah dalam membangun budaya kerja guru produktif. Penelitian ini menggunakan pendekatan kualitatif dengan studi multisitus yang dilakukan di Madrasah Aliyah An Nusyur dan Madrasah Aliyah Darul Ihsan Pragaan Sumenep. Tehnik pengumpulan data menggunakan 1) wawancara, 2) observasi dan 3) dokumentasi. Adapun tahapan analisis data dilakukan dengan 1) cheeking (pengecekan), 2) organizing (pengelompokan), dan 3) coding. Hasil penelitian menunjukkan bahwa; Pertama, konsep budaya kerja produktif guru di Madrasah Aliyah An Nusyur meliputi a) guru yang mampu menyusun program pembelajaran, b) guru yang mampu mengembangkan kompetensi yang dimiliki, c) guru yang memahami terhadap pekerjaannya, d) guru yang mampu mengevaluasi hasil kinerjanya, dan e) guru yang kompetitif. Sedangkan Madrasah Aliyah Darul Ihsan adalah a) guru yang mampu merencanakan program pembelajaran, b) guru yang memahami profesinya; guru sebagai mentor siswa, menekankan pada pengembangan bakat dan guru yang visioner. Kedua, Langkah strategis yang dilakukan oleh kepala sekolah Madrasah Aliyah An Nusyur yaitu; a) membangun kebersamaan diantaranya dengan; forum silaturrahim, istighasah pagi, dan sholat berjamaah, b) Pengembangan SDM yaitu: MGMP (Musyawarah Guru Mata Pelajaran), workshop kurikulum dan diklat dan seminar, c) studi banding dan d) membudayakan disiplin dan tanggung jawab.Sedangkan Langkah strategis yang dilakukan oleh kepala sekolah Madrasah Aliyah Darul ihsan yaitu; a) menerapkan budaya disiplin dan tanggung jawab, b) mengadakan diskusi rutin, c) pertemuan bulanan, d) MGMP (Musyawarah Guru Mata Pelajaran), e) mengadakan workshop, f) pelatihan dibidang tehnologi dan g) kursus bahasa. Ketiga, Kesulitan yang dihadapi kepala sekolah Madrasah Aliyah An Nusyur antara lain; a) penunjang pembelajaran, b) akses internet yang terbatas, dan c) kesibukan lain guru Sedangkan Kesulitan yang dihadapi kepala sekolah Madrasah Aliyah Darul ihsan antara lain; a) sarana dan prasarana yang terbatas, b) kesiapan mental, dan c) guru mengajar tidak pada bidangnya. ENGLISH: The appearance of concept Productive work culture may be departing from dissatisfaction with the outcome, or reaches aim less satisfactory. It’s triggered by from employees organisation, usually identical with convoluted birocration, less opened with other, work slow, rigid, and not beleived to other ability. change in work culture including potential, application and development of science, technology in order to improve the quality of life. Because of it, so that educational institution in an effort to compete, quality and can answer from society problem. need to be specific strategies wich doing by head master of build Productive work culture in order to advance educational institutions. The purpose of this study focuses on three things: First, how the concept of productive teacher work culture in school according to the head of private madrasah aliyah school in sumenep pragaan. Second, how are the principal's strategic steps in building a productive teacher work culture and Third, how is the difficulties faced by the principal in building a productive teacher work culture. This reseach used a qualitative approach with a multisite study conducted in Madrasah Aliyah An Nusyur and Madrasah Aliyah Darul Ihsan Pragaan Sumenep. Data collection techniques used 1) interview, 2) observation and 3) documentation. The stages of data analysis is done by 1) cheeking (checking), 2) organizing (grouping), and 3) coding. The results showed that; First, the concept of productive work culture of teachers in Madrasah Aliyah An Nusyur includes a) teachers who are able to develop learning programs, b) teachers who are able to develop their competencies, c) teachers who understand their work, d) teachers who are able to evaluate the results of their performance, and e) competitive teachers. While Madrasah Aliyah Darul Ihsan is a) a teacher who is able to plan a learning program, b) a teacher who understands his profession; teacher as a student mentor, emphasizes the development of gifted and visionary teachers. Second, the strategic steps taken by the principal of Madrasah Aliyah An Nusyur namely; a) build togetherness among others with; (b) Human Resource Development, ie: MGMP (Subject Teachers' Conference), curriculum workshops and training and seminars, c) comparative study and d) cultivate discipline and responsibility. While strategic steps undertaken by principal of Madrasah Aliyah Darul ihsan namely; a) apply a culture of discipline and responsibility, b) hold regular discussions, c) monthly meetings, d) MGMP (Subject Teacher Consultative), e) conduct workshops, f) technological training and g) language courses. Third, faced by the principal of Madrasah Aliyah An Nusyur, among others; a) the support of learning, b) limited internet access, and c) other busyness of the teachers. The difficulties faced by the principal of Madrasah Aliyah Darul ihsan, among others; a) limited facilities and infrastructure, b) mental readiness, and c) teachers are not teaching in their field

Reconstructing metabolic networks using interval analysis

Recently, there has been growing interest in the modelling and simulation of biological systems. Such systems are often modelled in terms of coupled ordinary differential equations that involve parameters whose (often unknown) values correspond to certain fundamental properties of the system. For example, in metabolic modelling, concentrations of metabolites can be described by such equations, where parameters correspond to the kinetic rates of the underlying chemical reactions. Within this framework, the increasing availability of time series data opens up the attractive possibility of reconstructing approximate parameter values, thus enabling the in silico exploration of the behaviour of complex dynamical systems. The parameter reconstruction problem, however, is very challenging – a fact that has resulted in a plethora of heuristics methods designed to fit parameters to the given data. In this paper we propose a completely deterministic method for parameter reconstruction that is based on interval analysis. We illustrate its utility by applying it to reconstruct metabolic networks using S-systems. Our method not only estimates the parameters very precisely, it also determines the appropriate network topologies. A major strength of the proposed method is that it proves that large portions of parameter space can be disregarded, thereby avoiding spurious solutions