This is version 10 of kkit. This is a minor and probably final upgrade before converting to a MOOSE/GENESIS3 based version. It includes provision for diffusive interactions in 1 dimension. It has provisions for loading multiple models for the purpose of running demos. --------------------------------------------------------------------------- This is version 9 of kkit. It is a major upgrade since version 8, involving a few new features, but also including the stochastic solver. MAJOR CHANGES 1. Stochastic solver included, with 3 new integration methods. The options dialog controls this. 2. Automatic dose-response calculation implemented. 3. Timestep calculation included. This is particularly useful for the mixed stochastic method. It is too conservative for the Exp Euler method. 4. Fixes made to database dumping. 5. Tool for setting all initial concentrations to current concentration 6. Tool for scaling all rates. CLEANUPS. 1. Minor cleanups of the main menu controls. 2. Batch-interface fixed so it now loads batch jobs without error messages about /file/module 3. Batch-interface now handles creation of the dummies for volume scaling functions. --------------------------------------------------------------------------- This is version 8 of kkit. It is a major upgrade since version 7, involving large changes to the interface, greatly expanded functionality, changes to file format, and requirements for new binaries. It requires GENESIS 2.2 or later, including the kinetics library. Major changes since version 7: 1. Modularization. Organizational structure for very complex models. 2. Stochastic models (through a very inefficient algorithm) 3. Unlimited size for notes. 4. New file format, which is incompatible. A conversion utility is provided. 5. Major interface changes, geared towards modularization. 6. Snap-to-grid display option 7. Improvements to postscript dump, especially in b/w mode 8. Database dump feature for connecting to the DOQCS database. Under the hood, the following changes have ocurred - Display coordinates are now simply the x y z coordinates of the respective pools, etc. - 'Mirrors' are now used extensively. This is a change to the pool code which effectively allows a pool to be in many places at once. Mirrors can participate in reactions etc, but it is as if the same master pool is represented in each place. The change involved in modularization is based on a conceptual development which is being prepared for publication. The key idea is that nearly all signaling interactions can be represented by a single motif, that of duplication of structurally identical reactions involved in interactions. The parameters of these interactions vary in individual cases, but the reaction structure is preserved. This generalization makes it possible to make a library of modules and their interactions (links). Because links can be represented in a stereotyped way, they can be set up at the block-diagram level rather than through the detailed hooking up of individual reactions. The modularization changes in kinetikit build on this to allow setup of modules and links, and a still evolving system for managing them. Access to the gory details of reactions and mechanisms is retained, but the fully defined model can be set up at a higher block-diagram level. Minor changes: There is a persistent 'feature' which happens when a user accidentally drags an enzyme onto its own parent, or vice-versa. The natural response is that the user now corrects the mistake by repeating the drag to delete the offending message. This sequence of actions causes a subtle but disastrous change in the messaging such that the REAC eA B message becomes a REAC sA B message. This does horrible things like eat up all the enzyme. I have implemented two things to fix this. First, the action itself no longer is permitted. There is an error message that pops up when the user tries to make an enzyme act on itself. Second, the system automatically scans loaded files for such messages and warns the user so they can take corrective measures. =========================================================================== This is version 7 of kkit. It requires Genesis version 2.1 or later, plus the kinetics library. The new transporter object requires GENESIS 2.2 for proper operation. Installation instructions are in the README of the parent directory for kinetikit. Major changes since version 6: 1 Addition of units 2 Addition of default volume settings 3 Addition of experimental parameters 4 Addition of transporter module 5 Fixes to the xtab object. 6 Pseudo-Variable timestep for integration. 7 Major update of help section. Please use it! Minor changes: 8 Easier assignment of colors to objects 9 Automatic updating of pool concentrations 10 Plots delete correctly and prevent overwriting 11 Minor updates to copyright information These changes are all backward compatible, so existing files will load correctly. There may be some surprises in the volumes and concentrations, as explained below. 1. Rates and concentrations now have a variety of time and concentration units you can use in addition to the somewhat cumbersone #/cell default that kinetikit originally used. The 'units' menu item allows you to select between these. When units are changed the actual concentration does not change but the display scales appropriately. 2. The default volume settings are in the 'units' menu item. They start out at a volume of 1e-15 m^3 which is a 10 micron cube. THIS IS DIFFERENT FROM THE PREVIOUS VERSION. The old 'volume' term in the pools and enzymes was actually a conversion factor from #/cell into concentration units. For example, for a 10 micron cube the previous 'volume' term was 6e5 to convert this into micromolar. Now the conversion is still done but it is internal and the user is presented with familiar volume and concentration terms. For reference, some simulations (such as the feedback.g example) used a 'volume' scale factor of 1 in earlier versions. This converts to an actual volume of 1.667e-21 m^3, which the reader can verify is the volume for which 1 molecule gives a concentration of 1 micromolar. So the example will still work, but the volumes look a bit odd at first sight. 3. Enzymes and reactions now have several additional dialog boxes for entering and/or viewing conventional experimental parameters for reactions. The reaction dialog incorporates a Kd and a tau which are read-only, since the tau term is not simply defined for higher-order reactions. The enzyme dialog has the Michaelis-Menten parameters Km and Vmax in conventional units, as well as a ratio term to explicitly set the ratio between k1 and k2. These values are read-write and convert immediately between the k1/k2/k3 terms. 4. There is a new module on the menu bar for doing transport. Its icon is a molecule on a filament, with an arrow indicating movement. This functions like a unidirectional reaction with a delay. The usual sort of interaction arrows and click-and-drag apply to this. the transporter is useful to model nuclear or axonal transport in which there is a significant time-delay in the arrival of the molecule. Note that the transporter itself accumulates molecules in transit, so the amount available to reactions appears to decraese. The use of this module is shown in the example model transport.g 5. Fixes to xtab object. xtab was seriously broken in version 6. It is now more functional. The file read/write now handles xy as well as y-only type ascii data files. The selection of table options is hopefully a bit cleaner. It is now again possible to create a table graphically, with many nifty options. 6. Pseudo-variable timestep. The timestep at the start of a simulation can be set to a different value than for the rest of the run. This is selected in the 'options' menu. This can greatly speed up simulations while preserving numerical accuracy. Transients at the start of simulations and at the time of addition of reactants can lead to numerical errors. These are usually fixed by reducing the timestep, but for most of the reaction a longer timestep usually suffices. So the 'variable timestep' allows the user to set a very tiny timestep (typically 10 times shorter than the regular dt) for the start of a simulation (usually a couple of seconds). Once selected in the 'options' menu, the shorter timestep comes into play whenever one presses the 'start' button. So user inputs to the simulation which result in transients can also be accomodated by this mechanism. 7. Help section. Lots of new material added to reflect changes. 8. Assignment of colors. A little rainbow-colored scale replaces the text entry for color names. 9. Pool concentration updating. The Co and n dialogs in the pool parameter window now update during the course of the simulation. 10. When objects with an attached plot are deleted, the plots are now also deleted. There is also a warning issued when the user attempts to create duplicate plots in the same graph. These fixes avoid a possible segmentation violation, in addition to making things a bit smoother to work with. 11. I have made minor changes in the wording of the copyright notice, mainly in the section about Models and Experiments. The message is the same, that you cannot do biology without biological experiments. I hope it is a bit more clearly stated.