Instructions and Tutorial

Because the simulation is written in Java1.1, either Netscape 4.08 or better, or Internet Explorer 5 or better should be used to view the simulation. (Mac users may need to download Sun's Hotjava Browser.) Results are best displayed on a monitor with 32-bit color.

The Simulation Region

Shown here is a typical display at some instant of the simulation.

The simulation box consists of a region which contains the animation (shown in color), surrounded by panels which allow actions to be taken, or which select a variety of options for how to view the results or how to obtain information about the system at a given instant.

During the course of the simulation, the movement of the cells (microglia in green and astrocytes in blue) and the spread of amyloid and cytokines will be shown in animation. If a panel such as the one shown here does not appear, this may indicate that your browser is incompatible with Java.

Instructions for viewing the simulation and selecting options are given in detail below. We also describe the features currently available.


Just above the simulation screen, there is a row of checkboxes as shown below:

These act as toggles and allow you to choose which cell representation you would like to view.

When astrocytes are viewed as large cells, the darker colors indicate a more advanced state. The states of an astrocyte are inactive, receptive, motile and blocking. (See the formulation to find out more.) When the astrocytes toggle is turned off, the astrocytes are represented by blue discs. The darker colors in this case indicate a greater density of astrocytes.

With the microglia toggle turned on, microglia are viewed as red cells. When the toggle is turned off, microglia are depicted by green discs. Darker shades of green indicate a greater density of microglia.

When the neurons toggle is turned on, an electron micrograph of nerves is shown. We find that it is much easier to view the simulation with the neurons toggle turned off. In the case that you are zooming in on a region, keeping the neurons toggle off, greatly speeds up the simulation.


To start the simulation, press the start button. To stop the simulation, press the stop button. The Reset button returns the screen to a new random initial configuration. You must stop the simulation before you can change to a new set of parameters, or reset to new initial state.

Also while the simulation is in progress, you can select the desired view (Soluble Amyloid-B, IL-1B, IL-6, etc) via the BACKGROUND DISPLAY pull-down menu (found just beneath the action buttons) to the right of the screen. (See figure below.) This can be done continuously, while the concentrations of various substances are changing. Soluble amyloid is shown in magenta, IL-1Beta in turquoise, IL-6 in yellow, TNFAlpha in red, Neuron Health in grey shades and Astrocytic Effect in grey shades as well.

In order to change the GENETIC TYPE the simulation must be stopped. You can then choose the genetic type to simulate by selecting the appropriate type from the pull-down menu as shown below. In order to incorporate the changes into the simulation, you should reset the simulation after you have chosen a genetic type. WARNING: Because the simulation reads in a file with all the parameter values for that type, all previously changed parameters will be set to the default values for the genetic type chosen.

Information about the chemical concentration and number of cells at any site inside the simulation window is available by clicking on that site. We call this a probe. When you click on a site, the following window appears with the desired information:

At the bottom of the simulation window, you will see panels that display current information about the time, numbers of cells, etc. This is updated as the simulation proceeds.


The user may zoom in on a region (a 2 times magnification factor) and then zoom back out by selecting the desired zoom buttons.

To "Zoom In", the simulation must be in a stopped state. After pressing the "Zoom In" button, an instruction box will appear:

The user may cancel the act of zooming by selecting the "Cancel" button. To zoom in, though, the user simply has to click on a point within the simulation region. The simulation will attempt to center the zoom on the point that was clicked. In the case, that the selected point is too close to the boundary to center on it, the zoomed region will automatically center on the point that gives the largest area for zooming.

While in a zoomed state, the simulation runs significantly faster if the image for the neurons is turned off.

To zoom back out, the user simply has to press the "Zoom Out" button, regardless of the state of the simulation.

Graph of Neuron Health

When the simulation is first initiated, a separate window titled Neuron Health Graph is displayed along with the simulation. You can close this window at any time and redisplay it by clicking on the Redisplay Graph button. The graph shows the overall neuron health as a function of time. Overall neuron health is defined in the simulation formulation.

Each time you Reset the simulation a new curve will appear. The plot can show up to four curves at a time. After the fourth run, the oldest curve will be removed to make room for a new one. The colors of the curves will cycle through: blue, green, red, and orange. Clicking on the Clear button, clears all curves from the display.

The plot window can be minimized, maximized, or closed by clicking on the appropriate buttons provided by your operating system. (The figure to the right shows these buttons on the upper right of the window.)

By clicking on the Show Data button underneath the graph, you can see the exact (x,y) values used for the graph. You can then cut these values from the window (shown below) with your browser's default cut command (usually control-x or control-c) and paste them in to any program or file that you like (usually with control-v). In this manner, you can take the data and display/manipulate it with the program (such as Excel) with which you are most comfortable.

Manipulating Parameter Values

The remaining options deal with manipulating the parameter values. These buttons appear to the bottom right of the simulation window as

Changing Parameter Values

You can change almost any parameter in the simulation by clicking on the Change Parameter Values button. When you click on this button, a window will appear (shown below) that gives you the option to select what type of parameter you want to change.

By clicking on the desired parameter type, another window will appear (if the simulation is in a stopped state), showing all the possible parameter values that you can change. (Shown below are the astrocyte parameters.) To change the parameter value, make sure the simulation is in a stopped state and then move the slider until the desired value is shown. To begin a new run with the changed parameter values, we suggest that you first change the parameter values and then hit the "Reset" button so that parameters such as the initial number of microglia and astrocytes get updated. You can find an explanation of the parameters used in the simulation by going to the status of parameters page.

WARNING: The program must be STOPPED before an adjustment can be made. However, as soon as the program is started again, the simulation will continue with the changes that have been made.

When changing the parameters for Amyloid-B, the user has the option of removing an amyloid source, by clicking on the button labeled Remove Amyloid Source at the bottom. Once this is done, the following instruction window will appear that explains what needs to be done.

To continue removing an amyloid source, put the pointer over the source in the simulation window that you would like to remove and then click the mouse button. If you have changed your mind and do not want to remove a source, click on the "Cancel" button in the Instructions window. (In the event that you click on a neuron that is not a source, then the simulation will continue with that neuron never becoming a source.)

Listing Current Parameter Values

By pressing the Show Parameter Values button, you can open a window that lists all of the parameter values currently used in the simulation. You can cut and paste these values into a file that can then be loaded into the simulation (or batch runs) at a later time (see below). This also is a handy tool for specifying the parameters used to obtain results that you got for others to verify/use.

Saving/Loading Parameters

The set of parameters that produces an interesting simulation can be saved by using the windows shown below. By clicking on the Save/Load Parameters option button when the simulation is STOPPED, the slots available for your use appear. Click on the slot that you wish to use and then the Save/Load window will appear. To save the current parameter values into the slot that you selected, press the Save button. To load the parameter values that are in the slot that you selected, press the Load button.


Another feature is the ability to load parameters from a file. In the course of studying a simulation, one can easily see the current parameter values by pressing the Show Parameter Values button. To save these values, simply highlight everything in the window and copy (Window users simply need to press CTRL-C) them into a text editor with the paste command (for Windows this is CTRL-V). (Note: The file must be saved as a standard text/ASCII file.) To then load these files into the simulation, select the Load From File button from the Save/Load Parameters panel. Because this requires the program to read from your computer, security restrictions in your browser's preferences need to be relaxed in order for this feature to be enabled.

To relax security in IE5, select the "Tools" menu and select "Internet Options". Click on the "Security" tab and select "Custom Level". On the next screen scroll down to "Microsoft VM". Under "Java Permissions", click on "Custom". Now the "Java Custom Settings..." button will become active at the bottom left of the window. Click on it. Select the "Edit Permissions" tab of the new window. Simply change the first choice under "Unsigned Content" and "Run Unsigned Content" to "Enable" rather than "Run in sandbox". Because this removes all security for Java applets, once you are done, go back to the "Security" screen and under "Microsoft VM" change the "Java Permissions" to Medium or High Safety.

Grabbing/Saving Images

Unfortunately, this simulation has no means for saving images. However, saving images and graphs is easy to do when using image capturing software. We highly recommend the freeware program, WinGrab, for windows based platforms. Using this program, you can capture specific windows and edit them before saving them as jpeg's or other image formats. For UNIX based platforms, we highly recommend xv. Simply use the Grab command to capture windows. You can then use other xv commands to crop the images and save them in your favorite graphics format. (Note: This instruction page was created using WinGrab and xv.)

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