Systems Imaging of the Immune Synapse

Three-dimensional live cell imaging of the interaction of T cells with antigen presenting cells (APC) visualizes the subcellular distributions of signaling intermediates during T cell activation at thousands of resolved positions within a cell. These information-rich maps of local protein concentrations are a valuable resource in understanding T cell signaling. Here, we describe a protocol for the efficient acquisition of such imaging data and their computational processing to create four-dimensional maps of local concentrations. This protocol allows quantitative analysis of T cell signaling as it occurs inside live cells with resolution in time and space across thousands of cells

Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems

Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility. © 2014 Hogg et al

Multi-state Modeling of Biomolecules

Multi-state modeling of biomolecules refers to a series of techniques used to represent and compute the behavior of biological molecules or complexes that can adopt a large number of possible functional states. Biological signaling systems often rely on complexes of biological macromolecules that can undergo several functionally significant modifications that are mutually compatible. Thus, they can exist in a very large number of functionally different states. Modeling such multi-state systems poses two problems: the problem of how to describe and specify a multi-state system (the “specification problem”) and the problem of how to use a computer to simulate the progress of the system over time (the “computation problem”). To address the specification problem, modelers have in recent years moved away from explicit specification of all possible states and towards rule-based formalisms that allow for implicit model specification, including the κ-calculus [1], BioNetGen [2]–[5], the Allosteric Network Compiler [6], and others [7], [8]. To tackle the computation problem, they have turned to particle-based methods that have in many cases proved more computationally efficient than population-based methods based on ordinary differential equations, partial differential equations, or the Gillespie stochastic simulation algorithm [9], [10]. Given current computing technology, particle-based methods are sometimes the only possible option. Particle-based simulators fall into two further categories: nonspatial simulators, such as StochSim [11], DYNSTOC [12], RuleMonkey [9], [13], and the Network-Free Stochastic Simulator (NFSim) [14], and spatial simulators, including Meredys [15], SRSim [16], [17], and MCell [18]–[20]. Modelers can thus choose from a variety of tools, the best choice depending on the particular problem. Development of faster and more powerful methods is ongoing, promising the ability to simulate ever more complex signaling processes in the future

Regional price levels and the agglomeration wage differential in western Germany

C15, J31, R23,

Philips Oy Healthcaren asiakaspalveluprosessin kehittäminen

Tämän insinöörityön aiheena on parantaa Philips Oy Healthcaren asiakaspalveluprosessia. Työn aiheeseen kuuluu vain pelkästään Suomessa palvelevaa Healthcaren osastoa. Työn tavoitteena oli parantaa Philips Oy Healthcaren asiakaspalveluprosessia työntekijöiden näkökulmasta, koska Philipsin johto näki siinä eniten parannettavaa. Tämän insinöörityön tutkimusmenetelmä oli laadullinen tutkimus, jolloin kaikkia Philips Oy Healthcaren asiakaspalvelijoita haastateltiin sekä myynnin että huollon puolelta. Haastateltavia oli yhteensä kuusi kappaletta ja heitä haastateltiin henkilökohtaisesti. Haastatteluista tehtyjen johtopäätöksien mukaan työtehtävät olivat erittäin epäselkeät. Tämän lisäksi puhelinrinkiin ei saatu sitovuutta ja sähköpostien hoitamisessa oli myös suuria vaikeuksia. Tutkimuksen tulokseksi saatiin uusi prosessikuvaus asiakaspalveluprosessiin, jossa on selitetty eri vaiheet ja tapahtumajärjestykset mahdollisimman selkeästi sekä ratkaisut sähköpostiin ja puhelinrinkiin. Tutkimustulosta eli prosessikuvaus annetaan työntekijöille työtehtävien selkeyttämiseksi, jolloin suurin hyöty aiheutuu työntekijöille työskennellessä