Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics.

When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders.

Gerhard Gross, Ludwigshafen, Germany

Mark A. Geyer, La Jolla, CA

This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively."

This volume tries to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. The volume concentrates on reviewing the ongoing research attempting to identify novel treatments for the cognitive deficits and negative symptoms of schizophrenia, which are not treated adequately by current antipsychotic medications.

Component-based software development regards software construction in terms of conventional engineering disciplines where the assembly of systems from readily-available prefabricated parts is the norm. Because both component-based systems themselves and the stakeholders in component-based development projects are different from traditional software systems, component-based testing also needs to deviate from traditional software testing approaches.

Gross first describes the specific challenges related to component-based testing like the lack of internal knowledge of a component or the usage of a component in diverse contexts. He argues that only built-in contract testing, a test organization for component-based applications founded on building test artifacts directly into components, can prevent catastrophic failures like the one that caused the now famous ARIANE 5 crash in 1996. Since building testing into components has implications for component development, built-in contract testing is integrated with and made to complement a model-driven development method. Here UML models are used to derive the testing architecture for an application, the testing interfaces and the component testers. The method also provides a process and guidelines for modeling and developing these artifacts.

This book is the first comprehensive treatment of the intricacies of testing component-based software systems. With its strong modeling background, it appeals to researchers and graduate students specializing in component-based software engineering. Professionals architecting and developing component-based systems will profit from the UML-based methodology and the implementation hints based on the XUnit and JUnit frameworks.

Multipotent mesenchymal stem cells (MSCs) are a heterogeneous population of cells which reside in a variety of tissues. They differentiate into several mesodermal lineages, secrete a multitude of trophic factors and contribute to tissue homeostasis. MSCs are able to exert immunosuppressive activities by interfering with inflammatory cytokine production and with T- and B-cell proliferation. These immunomodulating properties make MSCs promising candidates for the treatment of chronic inflammatory and autoimmune disorders. There are, however, certain caveats involved including inappropriate migration of cells in the body, immune rejection, tumor formation, or graft versus host disease (GvHD). This book investigates the current state of the MSC-dependent therapy of chronic inflammatory disorders and autoimmune diseases. Among the covered topics are GvHD, chronic kidney, liver and lung disease, ischemic heart and inflammatory bowel disease, diabetes, osteoarthritis, various rheumatic and neurological disorders and, lastly, tumors and solid organ transplantations. This book also questions the immunoprivileged status of MSCs, discusses the therapeutic role of MSCs in experimental animal disease models and their translation to the corresponding human disorders, envisions a role for MSCs in tumor interventions and, lastly, describes a systems biology approach for stem cells and inflammation.

Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics. When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders. Gerhard Gross, Ludwigshafen, Germany Mark A. Geyer, La Jolla, CA This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively.

This volume tries to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. The volume concentrates on reviewing the ongoing research attempting to identify novel treatments for the cognitive deficits and negative symptoms of schizophrenia, which are not treated adequately by current antipsychotic medications.

Component-based software development regards software construction in terms of conventional engineering disciplines where the assembly of systems from readily-available prefabricated parts is the norm. Because both component-based systems themselves and the stakeholders in component-based development projects are different from traditional software systems, component-based testing also needs to deviate from traditional software testing approaches.

Gross first describes the specific challenges related to component-based testing like the lack of internal knowledge of a component or the usage of a component in diverse contexts. He argues that only built-in contract testing, a test organization for component-based applications founded on building test artifacts directly into components, can prevent catastrophic failures like the one that caused the now famous ARIANE 5 crash in 1996. Since building testing into components has implications for component development, built-in contract testing is integrated with and made to complement a model-driven development method. Here UML models are used to derive the testing architecture for an application, the testing interfaces and the component testers. The method also provides a process and guidelines for modeling and developing these artifacts.

This book is the first comprehensive treatment of the intricacies of testing component-based software systems. With its strong modeling background, it appeals to researchers and graduate students specializing in component-based software engineering. Professionals architecting and developing component-based systems will profit from the UML-based methodology and the implementation hints based on the XUnit and JUnit frameworks.

Embedded systems are ubiquitous. They appear in cell phones, microwave ovens, refrigerators, consumer electronics, cars, and jets. Some of these embedded s- tems are safety- or security-critical such as in medical equipment, nuclear plants, and X-by-wire control systems in naval, ground and aerospace transportation - hicles. With the continuing shift from hardware to software, embedded systems are increasingly dominated by embedded software. Embedded software is complex. Its engineering inherently involves a mul- disciplinary interplay with the physics of the embedding system or environment. Embedded software also comes in ever larger quantity and diversity. The next generation of premium automobiles will carry around one gigabyte of binary code. The proposed US DDX submarine is e?ectively a ?oating embedded so- ware system, comprising 30 billion lines of code written in over 100 programming languages. Embedded software is expensive. Cost estimates are quoted at around US$15- 30 per line (from commencement to shipping). In the defense realm, costs can range up to $100, while for highly critical applications, such as the Space Shuttle, the cost per line approximates $1,000. In view of the exponential increase in complexity, the projected costs of future embedded software are staggering.