Neutron stars are the most compact astronomical objects in the universe which are accessible by direct observation. Studying neutron stars means studying physics in regimes unattainable in any terrestrial laboratory.

Understanding their observed complex phenomena requires a wide range of scientific disciplines, including the nuclear and condensed matter physics of very dense matter in neutron star interiors, plasma physics and quantum electrodynamics of magnetospheres, and the relativistic magneto-hydrodynamics of electron-positron pulsar winds interacting with some ambient medium. Not to mention the test bed neutron stars provide for general relativity theories, and their importance as potential sources of gravitational waves. It is this variety of disciplines which, among others, makes neutron star research so fascinating, not only for those who have been working in the field for many years but also for students and young scientists.

The aim of this book is to serve as a reference work which not only reviews the progress made since the early days of pulsar astronomy, but especially focuses on questions such as: "What have we learned about the subject and how did we learn it?," "What are the most important open questions in this area?" and "What new tools, telescopes, observations, and calculations are needed to answer these questions?."

All authors who have contributed to this book have devoted a significant part of their scientific careers to exploring the nature of neutron stars and understanding pulsars. Everyone has paid special attention to writing educational comprehensive review articles with the needs of beginners, students and young scientists as potential readers in mind. This book will be a valuable source of information for these groups.

Combiningtwodifferentscienti?cdisciplines-morphologyandimmunochemistry- immunohistochemistryhasdevelopedasanimportantinstrumentinresearchand clinicalpathology. A basicunderstandingofunderlying principlesandpotential problemsisunavoidableifyouwanttobesuccessfulinyouruseofimmunohis- chemistry,aswellasingettingyourpaperspublishedandyourresearchgrants funded. Whilemanyexcellenttextsandmonographsexistwhichcovervariousaspects ofimmunohistochemistry,thelackofaconcisecomprehensiveguidetousing thesemethodswasamajormotivationforwritingthisbook. Ourintentionwasto createaneasy-to-readandfocusedresourcebasedonstate-of-the-artinformation forabroadaudiencerangingfromstudentsandtechnicalassistantstoexperienced researchers. Thishandbookhasaconciseformat,withprotocolsandinstructionsfor methodsimmediatelyfollowingtheshortintroductorytheoreticalmaterialineach chapter. BeingconsciousofthegrowingroleofInternetasaninformationsource, wehavefounditreasonableinmanycasestosubstitutecitingbooksandjournal publications with corresponding Internet websites. Where possible, commercial sourcesofreagents,kits,andequipmentarelistedthroughoutthetextinsteadof inaseparateindex. Thougheachchapterissmallandintroductory,thishandbook itself is self-suf?cient and provides a comprehensive look at the principles of immunohistochemistry. For readers wanting further depth of knowledge, each chapterisbackedupbyashortlistofcarefullyselectedoriginalarticles. Duringthelastdecade,pioneeringeffortsofhistochemistshaveledtoan- menseimprovementinthereagentsandprotocols. Theresearcherisurgedalwaysto determinethereasonforeverymethodandstepbeforedoingit. Thishandbookis intendedtohelpreaderstoavoidtroublesinthechoiceofanadequatemethod,which happenswhenusingstandardtextbooks. Forthishandbook,wecarefullyselected establishedmethodsandeasy-to-adoptprotocols,payingattentiontomoderndev- opmentsinimmunohistochemistry,suchasantigenretrieval,signalampli?cation, the use of epitope tags in immunohistochemistry, multiple immunolabeling or diagnosticimmunohistochemistry. Eachofthemethodsdescribedinthishandbook v vi Preface was provedby the authors; many of these methods are routinely used in daily practiceintheirinstitute. Allthepracticalmethodsadvocatedareclearlydescribed, withaccompanyingtables,andtheresultsobtainableareillustratedwithcolour micrographs. Acknowledgements We thank Vera Samoilova forthe perfect technical assistance and other colleaguesfromtheMunsterUniversityClinicforsharingprobesandreagents. IgorB. BuchwalowandWernerBocker Munster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen-nster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen- immunohistochemistryhasdevelopedasanimportantinstrumentinresearchand clinicalpathology. A basicunderstandingofunderlying principlesandpotential problemsisunavoidableifyouwanttobesuccessfulinyouruseofimmunohis- chemistry,aswellasingettingyourpaperspublishedandyourresearchgrants funded. Whilemanyexcellenttextsandmonographsexistwhichcovervariousaspects ofimmunohistochemistry,thelackofaconcisecomprehensiveguidetousing thesemethodswasamajormotivationforwritingthisbook. Ourintentionwasto createaneasy-to-readandfocusedresourcebasedonstate-of-the-artinformation forabroadaudiencerangingfromstudentsandtechnicalassistantstoexperienced researchers. Thishandbookhasaconciseformat,withprotocolsandinstructionsfor methodsimmediatelyfollowingtheshortintroductorytheoreticalmaterialineach chapter. BeingconsciousofthegrowingroleofInternetasaninformationsource, wehavefounditreasonableinmanycasestosubstitutecitingbooksandjournal publications with corresponding Internet websites. Where possible, commercial sourcesofreagents,kits,andequipmentarelistedthroughoutthetextinsteadof inaseparateindex. Thougheachchapterissmallandintroductory,thishandbook itself is self-suf?cient and provides a comprehensive look at the principles of immunohistochemistry. For readers wanting further depth of knowledge, each chapterisbackedupbyashortlistofcarefullyselectedoriginalarticles. Duringthelastdecade,pioneeringeffortsofhistochemistshaveledtoan- menseimprovementinthereagentsandprotocols. Theresearcherisurgedalwaysto determinethereasonforeverymethodandstepbeforedoingit. Thishandbookis intendedtohelpreaderstoavoidtroublesinthechoiceofanadequatemethod,which happenswhenusingstandardtextbooks. Forthishandbook,wecarefullyselected establishedmethodsandeasy-to-adoptprotocols,payingattentiontomoderndev- opmentsinimmunohistochemistry,suchasantigenretrieval,signalampli?cation, the use of epitope tags in immunohistochemistry, multiple immunolabeling or diagnosticimmunohistochemistry. Eachofthemethodsdescribedinthishandbook v vi Preface was provedby the authors; many of these methods are routinely used in daily practiceintheirinstitute. Allthepracticalmethodsadvocatedareclearlydescribed, withaccompanyingtables,andtheresultsobtainableareillustratedwithcolour micrographs. Acknowledgements We thank Vera Samoilova forthe perfect technical assistance and other colleaguesfromtheMunsterUniversityClinicforsharingprobesandreagents. IgorB. BuchwalowandWernerBocker Munster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen-AntibodyBinding ...21 3. 2 Paraf?nSectionsforImmunohistochemicalAnalysis ...22 3. 2. 1 EmbeddingandCutting ...22 3. 2. 2 MountingParaf?nSectionsontoSlides ...23 3. 3 CryosectionsforImmunohistochemicalAnalysis ...24 3. 4 BuffersforWashingandAntibodyDilution ...25 3. 5 MountingFollowingImmunohistochemicalStaining ...27 3. 6 StorageFollowingImmunohistochemicalStaining ...28 References ...28 vii viii Contents 4 WorkingwithAntibodies ...31 4. 1 DirectImmunostainingMethod ...31 4. 2 IndirectImmunostainingMethod ...33 4. 3 TheChoiceofAntibodies ...35 4. 3. 1 TheChoiceofPrimaryAntibodies ...35 4. 3. 2 TheChoiceofSecondaryAntibodies ...

Combiningtwodifferentscienti?cdisciplines-morphologyandimmunochemistry- immunohistochemistryhasdevelopedasanimportantinstrumentinresearchand clinicalpathology. A basicunderstandingofunderlying principlesandpotential problemsisunavoidableifyouwanttobesuccessfulinyouruseofimmunohis- chemistry,aswellasingettingyourpaperspublishedandyourresearchgrants funded. Whilemanyexcellenttextsandmonographsexistwhichcovervariousaspects ofimmunohistochemistry,thelackofaconcisecomprehensiveguidetousing thesemethodswasamajormotivationforwritingthisbook. Ourintentionwasto createaneasy-to-readandfocusedresourcebasedonstate-of-the-artinformation forabroadaudiencerangingfromstudentsandtechnicalassistantstoexperienced researchers. Thishandbookhasaconciseformat,withprotocolsandinstructionsfor methodsimmediatelyfollowingtheshortintroductorytheoreticalmaterialineach chapter. BeingconsciousofthegrowingroleofInternetasaninformationsource, wehavefounditreasonableinmanycasestosubstitutecitingbooksandjournal publications with corresponding Internet websites. Where possible, commercial sourcesofreagents,kits,andequipmentarelistedthroughoutthetextinsteadof inaseparateindex. Thougheachchapterissmallandintroductory,thishandbook itself is self-suf?cient and provides a comprehensive look at the principles of immunohistochemistry. For readers wanting further depth of knowledge, each chapterisbackedupbyashortlistofcarefullyselectedoriginalarticles. Duringthelastdecade,pioneeringeffortsofhistochemistshaveledtoan- menseimprovementinthereagentsandprotocols. Theresearcherisurgedalwaysto determinethereasonforeverymethodandstepbeforedoingit. Thishandbookis intendedtohelpreaderstoavoidtroublesinthechoiceofanadequatemethod,which happenswhenusingstandardtextbooks. Forthishandbook,wecarefullyselected establishedmethodsandeasy-to-adoptprotocols,payingattentiontomoderndev- opmentsinimmunohistochemistry,suchasantigenretrieval,signalampli?cation, the use of epitope tags in immunohistochemistry, multiple immunolabeling or diagnosticimmunohistochemistry. Eachofthemethodsdescribedinthishandbook v vi Preface was provedby the authors; many of these methods are routinely used in daily practiceintheirinstitute. Allthepracticalmethodsadvocatedareclearlydescribed, withaccompanyingtables,andtheresultsobtainableareillustratedwithcolour micrographs. Acknowledgements We thank Vera Samoilova forthe perfect technical assistance and other colleaguesfromtheMunsterUniversityClinicforsharingprobesandreagents. IgorB. BuchwalowandWernerBocker Munster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen-nster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen- immunohistochemistryhasdevelopedasanimportantinstrumentinresearchand clinicalpathology. A basicunderstandingofunderlying principlesandpotential problemsisunavoidableifyouwanttobesuccessfulinyouruseofimmunohis- chemistry,aswellasingettingyourpaperspublishedandyourresearchgrants funded. Whilemanyexcellenttextsandmonographsexistwhichcovervariousaspects ofimmunohistochemistry,thelackofaconcisecomprehensiveguidetousing thesemethodswasamajormotivationforwritingthisbook. Ourintentionwasto createaneasy-to-readandfocusedresourcebasedonstate-of-the-artinformation forabroadaudiencerangingfromstudentsandtechnicalassistantstoexperienced researchers. Thishandbookhasaconciseformat,withprotocolsandinstructionsfor methodsimmediatelyfollowingtheshortintroductorytheoreticalmaterialineach chapter. BeingconsciousofthegrowingroleofInternetasaninformationsource, wehavefounditreasonableinmanycasestosubstitutecitingbooksandjournal publications with corresponding Internet websites. Where possible, commercial sourcesofreagents,kits,andequipmentarelistedthroughoutthetextinsteadof inaseparateindex. Thougheachchapterissmallandintroductory,thishandbook itself is self-suf?cient and provides a comprehensive look at the principles of immunohistochemistry. For readers wanting further depth of knowledge, each chapterisbackedupbyashortlistofcarefullyselectedoriginalarticles. Duringthelastdecade,pioneeringeffortsofhistochemistshaveledtoan- menseimprovementinthereagentsandprotocols. Theresearcherisurgedalwaysto determinethereasonforeverymethodandstepbeforedoingit. Thishandbookis intendedtohelpreaderstoavoidtroublesinthechoiceofanadequatemethod,which happenswhenusingstandardtextbooks. Forthishandbook,wecarefullyselected establishedmethodsandeasy-to-adoptprotocols,payingattentiontomoderndev- opmentsinimmunohistochemistry,suchasantigenretrieval,signalampli?cation, the use of epitope tags in immunohistochemistry, multiple immunolabeling or diagnosticimmunohistochemistry. Eachofthemethodsdescribedinthishandbook v vi Preface was provedby the authors; many of these methods are routinely used in daily practiceintheirinstitute. Allthepracticalmethodsadvocatedareclearlydescribed, withaccompanyingtables,andtheresultsobtainableareillustratedwithcolour micrographs. Acknowledgements We thank Vera Samoilova forthe perfect technical assistance and other colleaguesfromtheMunsterUniversityClinicforsharingprobesandreagents. IgorB. BuchwalowandWernerBocker Munster Contents 1 AntibodiesforImmunohistochemistry ...1 1. 1 StructureofAntibodies ...2 1. 2 PolyclonalAntibodies ...4 1. 3 MouseMonoclonalAntibodies ...4 1. 4 RabbitMonoclonalAntibodies ...5 1. 5 ProteinAandProteinGinImmunohistochemistry ...7 References ...8 2 AntibodyLabelingandtheChoiceoftheLabel ...9 2. 1 CovalentLabelingofAntibodies ...9 2. 2 Non-CovalentLabelingofPrimaryAntibodieswith LabeledFabFragments ...10 2. 3 EnzymeLabelsforLightMicroscopy ...13 2. 4 FluorophoreLabelsforFluorescenceMicroscopy ...15 2. 5 ColloidalGoldLabelsforElectronMicroscopy ...16 References ...17 3 ProbesProcessinginImmunohistochemistry ...19 3. 1 FixationinImmunohistochemistry ...19 3. 1. 1 FixationinAlcoholsandAcetone ...20 3. 1. 2 FixationinFormaldehyde ...20 3. 1. 3 EffectofFormaldehydeFixationon Antigen-AntibodyBinding ...21 3. 2 Paraf?nSectionsforImmunohistochemicalAnalysis ...22 3. 2. 1 EmbeddingandCutting ...22 3. 2. 2 MountingParaf?nSectionsontoSlides ...23 3. 3 CryosectionsforImmunohistochemicalAnalysis ...24 3. 4 BuffersforWashingandAntibodyDilution ...25 3. 5 MountingFollowingImmunohistochemicalStaining ...27 3. 6 StorageFollowingImmunohistochemicalStaining ...28 References ...28 vii viii Contents 4 WorkingwithAntibodies ...31 4. 1 DirectImmunostainingMethod ...31 4. 2 IndirectImmunostainingMethod ...33 4. 3 TheChoiceofAntibodies ...35 4. 3. 1 TheChoiceofPrimaryAntibodies ...35 4. 3. 2 TheChoiceofSecondaryAntibodies ...

In recent years, a series of excellent textbooks have been published dealing with pathology of the thyroid gland. The present volume of CURRENT TOPICS IN PATHOLOGY provides further information for both pathologists and clinicians interested in the thyroid gland. The contributions deal with surgical pathology of the thyroid as well as with basic aspects of thyroid metabolism, hormone transport, and growth factors in thyroid cells. The topics covered in this book should mainly be considered as adjuncts to common textbooks on thyroid pathology. The contributions should help pathologists in their routine diagnosis and should stimulate further thyroid research.

Neutron stars are the most compact astronomical objects in the universe which are accessible by direct observation. Studying neutron stars means studying physics in regimes unattainable in any terrestrial laboratory. Understanding their observed complex phenomena requires a wide range of scientific disciplines, including the nuclear and condensed matter physics of very dense matter in neutron star interiors, plasma physics and quantum electrodynamics of magnetospheres, and the relativistic magneto-hydrodynamics of electron-positron pulsar winds interacting with some ambient medium. Not to mention the test bed neutron stars provide for general relativity theories, and their importance as potential sources of gravitational waves. It is this variety of disciplines which, among others, makes neutron star research so fascinating, not only for those who have been working in the field for many years but also for students and young scientists. The aim of this book is to serve as a reference work which not only reviews the progress made since the early days of pulsar astronomy, but especially focuses on questions such as: "What have we learned about the subject and how did we learn it?", "What are the most important open questions in this area?" and "What new tools, telescopes, observations, and calculations are needed to answer these questions?". All authors who have contributed to this book have devoted a significant part of their scientific careers to exploring the nature of neutron stars and understanding pulsars. Everyone has paid special attention to writing educational comprehensive review articles with the needs of beginners, students and young scientists as potential readers in mind. This book will be a valuable source of information for these groups.

Herausgeber und Autoren stellen die gesamte Wertschopfungskette auf den Prufstand. Mit Konzepten u. a. zu Life Science Informatics, Supply Chain Transformation und integriertem Customer Relationship Management bieten sie nutzliche Handlungsansatze und konkrete Entscheidungshilfen fur die Praxis.

Werner Becker analysiert die Dynamik des Kommunikationswettbewerbs pharmazeutischer Unternehmen und entwickelt ein neues Konzept fur die Ausgestaltung eines normativ verankerten und strategisch orientierten Kommunikationsmanagement.
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