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agents which have been used empirically for many years in the treatment of Parkinson disease and dystonia depends on their capacity to antagonize ACh at sites within the basal ganglia and in projections from the pedunculopontine nuclei. Acetylcholine appears also to act on the presynaptic membrane of striatal cells and to in uence their release of neurotransmitters, as discussed below. In addition, the basal ganglia contain other biologically active substances substance P, enkephalin, cholecystokinin, somatostatin, and neuropeptide Y which may enhance or diminish the effects of other neurotransmitters, i.e., they act as neuromodulators. The neurons utilizing these substances and the manner in which they operate are just now being identi ed. Of the catecholamines, dopamine has the most pervasive role in the function of the basal ganglia. It can be said that it is among the most important in brain disease, since disturbances of dopamine signaling are essential abnormalities of several CNS disorders including Parkinsonism, schizophrenia, attention de cit disorder, and drug abuse. Within the basal ganglia, the areas richest in dopamine are the substantia nigra, where it is synthesized in the nerve cell bodies of the pars compacta, and the termination of these bers in the striatum. In the most simpli ed models, stimulation of the dopaminergic neurons of the substantia nigra induces a speci c response in the striatum namely, an inhibitory effect on the already low ring rate of neostriatal neurons. However, the effects of dopamine have proved more dif cult to resolve, in large part because there are now ve known types of postsynaptic dopamine receptors (D1 to D5), each with its particular anatomic distribution and pharmacologic action. This heterogeneity is re ected in the excitatory effect of dopamine on the small spiny neurons of the putamen and an inhibitory effect on others. The ve types of dopamine receptors are found in differing concentration throughout various parts of the brain, each displaying differing af nities for dopamine itself and for various drugs and other agents (Table 4-2; see Jenner). The D1 and D2 receptors are highly represented in the striatum, D3 in the nucleus accumbens, D4 in the frontal cortex and certain limbic structures, and D5 in the hippocampus. In the striatum, the effects of dopamine act as a class of D1-like (D1 and D5 subtypes) and D2-like (D2, D3, and D4 subtypes) receptors. Stimulation of the D1 class stimulates adenyl cyclase, while D2 receptor binding inhibits this enzyme. Whether dopamine functions in an excitatory or inhibitory manner at a particular synapse is determined by the local receptor. As mentioned earlier, excitatory D1 receptors predominate on the small spiny putamenal neurons that are the origin of the direct striatopallidal output pathway, while D2 receptors mediate the inhibitory in uence of dopamine on the indirect striatopallidal output, as indicated in Fig. 4-4. Some of the clinical and pharmacologic effects of dopamine are made clear by considering both the anatomic sites of various receptors and their physiologic effects. For example, it appears that drug-induced parkinsonian syndromes and tardive dyskinesias (described further on) are prone to occur when drugs are administered that competitively bind to the D2 receptor, but that the newer antipsychotic drugs, which produce fewer of these effects, have a stronger af nity for the D4 receptor. However, the situation is actually far more complex, in part due to the synergistic activities of D1 and D2 receptors, each potentiating the other at some sites of convergence, and the presence on the presynaptic terminals of nigrostriatal neurons of D2 receptors, which inhibit dopamine synthesis and release. Even these intricacies do not capture the complexity of neural
We will be working our way through all of the different Web items displayed by the 0ANALYSIS_PATTERN template in later chapters, but at this point I want to introduce some of the components of the template and show you what is possible if you get into the details of the WAD. The following illustration shows just one portion of this Web template.
Using the Tell Application Pop-Up Menu
Because the OS conducts so much activity, a great number of things can go wrong. The more familiar you are with an OS s normal processes, the more easily you will be able to troubleshoot problems when they occur. For example, if you know the steps of the boot process, you will be able to identify which file is at fault when you receive a specific error, such as HIMEM.SYS not loaded or a Swapfile corrupt error. When diagnosing runtime errors, keep in mind that a number of diagnostic utilities and boot modes are available to you. There might be no way to prevent system lockups, GPFs, and illegal operations, but you can certainly help resolve them by pinpointing and reinstalling suspect applications or improving the system s resources. Some OS errors occur due to computer viruses. You can help protect a computer against viruses by using antivirus utilities to scan all incoming files. Viruses can cause unpredictable behavior, so they might be difficult to pinpoint. However, as long as you are aware of their potential and know the proper recovery steps, you can limit the amount of damage viruses do or stop their spread.
PRO Bonds are required to ensure the sucPOINTER cessful completion of a project. A payment bond assures the owner of the Bonds are required to ensure the project that all suppliers, vendors, and successful completion of a project. A subcontractors will be paid at the end payment bond assures the owner of the project that all suppliers, venof the project. A performance bond dors, and subcontractors will be paid assures the owner that the contractor at the end of the project. A perforwill perform in accordance with the mance bond assures the owner that terms and conditions of the contract. If the contractor will perform in the contractor defaults on either of accordance with the terms and conthese obligations, the bonding company ditions of the contract. If the consteps in and provides the necessary tractor defaults on either of these funds to satisfy these defaults. obligations, the bonding company When the person or firm awarding steps in and provides the necessary the contract requires a bond, they know funds to satisfy these defaults. there is a degree of safety. Bid bonds are slightly different. Bid bonds are generally required in an amount equal to 10 percent of the project s cost. They are submitted with the contractor s bid. If the contractor is notified that he is the successful bidder but declines to accept a contract, the owner will make the award to the second bidder. The proceeds from the bond will be used to make up the difference if any between the low bidder s price and the second bidder s price. The contractor who declined to accept the bid will lose his bond and forfeit the money it cost. Thus, if you are required to submit a bid bond, make sure that you are willing to accept a contract if offered or else you ll pay the penalty. It is very difficult for some new businesses to obtain a bond. If the new company doesn t have strong assets or a good track record, getting a bond is tough. But when you put up a bond, the value of the bond is at risk. If you default on your contract, you lose your bond to the person who contracted you for the job. Since many people use the equity in their home as collateral for a bond, they could lose their house. Bonds are serious business. If you can get a bond, you have an advantage in the business world.
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