Immunologic privilege in the central nervous system and the blood-brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.

Democratic Transition and Political Patronage

Mr. Korosenyi begins by analysing the particular relationship holding between politics and administration in different countries. Within Europe three major patterns have emerged in the 20th century. Firstly there is the politically neutral British Civil Service, secondly the German and French state bureaucracies, which traditionally are supposed to embody the "common good", and thirdly there is the patronage system of the so-called consociate democracies, e.g. Austria. In general Mr. Korosenyi believes that, though politics do not penetrate into the Hungarian administration to the extent they do in Belgium and Austria, nevertheless, there is a stronger fusion than there is in the traditional British pattern. He is particularly interested in this relationship with regard to its effect on democratic institution building and the stabilisation of the new regime in Hungary, now the old "nomenklatura" system has been abolished. The structure of the Hungarian government was a result of the constitutional amendments of 1989 and 1990. Analysing this period, it becomes clear that for all the political actors who initiated and supported the democratic transition to democracy, the underlying assumption was a radical depoliticisation of the administration in order to maintain its stability. The political leadership of the executive is a cabinet government. The government is structured along ministries, each headed by a politician, i.e. the minister, who is a member of the cabinet. The minister's political secretary is not a cabinet member, but he or she is a politician, usually a member of the parliament. The head of the administration of the ministry is the administrative state secretary, who is a civil servant. He or she usually has four deputies, also civil servants. Naturally it is assumed that there should be a clear separation between politicians and civil servants. However in practice, the borders can be blurred, giving rise to a hybrid known as the "political civil servant". Mr. Korosenyi analyses the different faces of these hybrids. They are civil servants for the following reasons. They need special educational qualifications, working experience, a civil service exam etc., they are not allowed to do anything which is incompatible with their impartial role, and they cannot occupy political office nor may they appear in the name of any political party. On the other hand, the accepted political dimension to their function is revealed by the following facts. The state secretary (a civil servant) may participate in cabinet meetings instead of the minister. The state secretary is employed by the minister. A state secretary or any of their deputies can be dismissed at any time by the minister or the prime minister. In practice then, ministers appoint to these senior administrative positions civil servants whose personal and political loyaties are strong. To the second level of political patronage in ministries belong the ministerial cabinet, press office and public relation office. The ministerial cabinet includes the private advisors and members of the personal staff of the minister. The press office and the PR office, if they exist, are not adjusted to the administrative hierarchy of the ministry, but under the direct control of the minister. In the beginning of the 1990s, such offices were exceptions; in the second half of the 90s they are accepted and to be found in most ministries. Mr. Korosenyi's work, a 92-page manuscript of a book in Hungarian, marks the first piece of literature within the field of political science which analyses the structure of the Hungarian government in the 1990s and the relationship between the political leadership and the public administration.

Central Europeans towards Integration with the European Union: A Study of Public Opinion, Social Attitudes and National Identities

Since the turbulence of 1989, the countries of Central and Eastern Europe have striven to "return to Europe". Agreements have been signed with ten post-communist countries, beginning in 1991 with Czechoslovakia (before its division), Hungary and Poland. Since that time several countries have expressed a desire to become members of the EU. In 1997 the European Commission announced its opinion on the applications for EU membership of the Czech Republic, Hungary, Poland, Slovakia, and seven other applicant countries. The Commission recommended the commencement of negotiations on accession with the Czech Republic, Estonia, Hungary, Poland, and Slovenia. Mr. Kucia's report, presented in the form of a series of manuscripts totalling 91 pages, written in English and Polish and including many pages of tables and graphs, presents the results of a study of public opinion on European integration in four countries of Central Europe (CE): the Czech Republic (CZ), Hungary (H), Poland (PL), and Slovakia (SK). The research results are primarily based on a public-opinion survey known as the Central and Eastern Eurobarometer (CEEB). CEEB has been conducted on behalf of the European Commission in the Central and Eastern European countries each year in autumn since 1990. Below is a very small selection of Mr. Kucia's research findings. Throughout the 90s people in the four countries increasingly saw their countries' future tied up with the EU, since economic and political connections to the EU were growing and prospects for EU membership were increasing. Regional co-operation within CE did not gain much popular recognition. However, initially high levels of enthusiasm for the EU were gradually superseded by a more realistic approach or even scepticism. Poland was the exception in this respect; its population was more positive about the EU in 1996 than ever before. Mr. Kucia concludes that, since the political "elites" in CE are more positive about the EU than the people they serve, they should do their best to bring people round to their beliefs, lest the project of European integration become purely the business of the elites, as Mr. Kucia claims it has been in the EU up till now. He accuses the governments of the region, the EU authorities and the media of failing to provide appropriate information, especially about the two subjects which most affect them, association with the EU and the PHARE assistance programme. Respondents were asked to rank in order the countries or regions they saw their country's future most closely tied up with. In the period 92-96 the EU received the highest ratings in all of CE. The ratings were highest in CZ in 92 and 93 (46%) and in Poland in 96 (46%). They were the lowest in Hungary (22% in 94). After the EU came "Other Western European countries (non EU)", that is Austria, Sweden and Finland (before they joined the EU in 1995), Switzerland and Norway. Mr. Kucia puts the high ratings of these countries down to historical connections and geographical proximity, particularly in the case of Austria. The USA always came second in Poland, and in Hungary too its standing has always been higher than in CZ or SK. Indeed Mr. Kucia suggests that the USA's standing is disproportionately low in especially the CZ. Germany was nominated frequently by Hungarians, though in the CZ and SK, figures have been consistently low (1-2%). "Other CE/EE countries" increased their ratings in all of CE except Poland between 92 and 96. With regard to these last figures, Mr. Kucia makes an interesting note. Assuming that for the respondents in the four countries this category covered the Visegrad 4, least support was found in Poland, whose government was the most in favour of close political co-operation within the V4, while most support was in evidence in CZ and SK, for whose governments V4 was simply not a priority. Again, there is evidence of a divide between the political elites and the people. Russia has occupied a consistently modest rank. It was the highest in PL, fairly low in H and SK and the lowest in CZ. The Slovak government's policy of closer ties with Russia is reflected in a growth in the figures from 2% in 93 to 6% in 95. Every year the spontaneous answer "we should depend on ourselves" appeared, which Mr. Kucia interprets as either a sign of isolationism and disillusionment or as a call for self-reliance. Unfortunately he regards both these tendencies as unfeasible in the uniting Europe. Moving to more general conclusions, Mr. Kucia finds that the concept "Central Europe" does not have much meaning for Central Europeans. He believes that this is probably due to the failure to establish a viable regional co-operation network. Group discussions also revealed that people thought themselves European as a consequence of being Czech or Polish etc. Thus European identity is based on national identities. Generally within the surveyed period, the numbers of those who said they often think themselves European decreased, while the numbers of those who said they never think themselves European increased from 41% in PL, 36% in CZ, and 30% in H in 1990, to 67% in CZ, 58% in PL, and 51% in H in 1995.

Racism, Youth Violence and the New Right: A Comparative Study of the Political Transformation of Extremism in Hungary and Romania

This research focused on the re-emerging of national and minority identities and the concomitant hostilities emerging from them in Hungary and in Romania. In particular the findings indicate that extremist incidents against members of minority groups on the local level seem to follow patterns in publicised media events. Violent attacks by skinheads against Gypsies in Hungary are often isolated incidents but are also inadvertently supported by biased media coverage, hostile majority attitudes and stereotyped behaviour reproduced in the media. The research also indicates that extremism both in Hungary against Gypsies and in Romania against Hungarians is of three kinds: organised within the framework of extremist groups, state-supported violence (both real and symbolic), and isolated, local instances with a few perpetrators committing atrocities. However, and this is a positive development, with rising interethnic tensions and extremist attacks prevalent in Hungary and Romania, there is also a parallel emergence of a more sophisticated human and minority rights campaign to combat them.

Compensation, Incentives and Risk: Economic Theory and Russian Practise

Mr. Pechersky set out to examine a specific feature of the employer-employee relationship in Russian business organisations. He wanted to study to what extent the so-called "moral hazard" is being solved (if it is being solved at all), whether there is a relationship between pay and performance, and whether there is a correlation between economic theory and Russian reality. Finally, he set out to construct a model of the Russian economy that better reflects the way it actually functions than do certain other well-known models (for example models of incentive compensation, the Shapiro-Stiglitz model etc.). His report was presented to the RSS in the form of a series of manuscripts in English and Russian, and on disc, with many tables and graphs. He begins by pointing out the different examples of randomness that exist in the relationship between employee and employer. Firstly, results are frequently affected by circumstances outside the employee's control that have nothing to do with how intelligently, honestly, and diligently the employee has worked. When rewards are based on results, uncontrollable randomness in the employee's output induces randomness in their incomes. A second source of randomness involves the outside events that are beyond the control of the employee that may affect his or her ability to perform as contracted. A third source of randomness arises when the performance itself (rather than the result) is measured, and the performance evaluation procedures include random or subjective elements. Mr. Pechersky's study shows that in Russia the third source of randomness plays an important role. Moreover, he points out that employer-employee relationships in Russia are sometimes opposite to those in the West. Drawing on game theory, he characterises the Western system as follows. The two players are the principal and the agent, who are usually representative individuals. The principal hires an agent to perform a task, and the agent acquires an information advantage concerning his actions or the outside world at some point in the game, i.e. it is assumed that the employee is better informed. In Russia, on the other hand, incentive contracts are typically negotiated in situations in which the employer has the information advantage concerning outcome. Mr. Pechersky schematises it thus. Compensation (the wage) is W and consists of a base amount, plus a portion that varies with the outcome, x. So W = a + bx, where b is used to measure the intensity of the incentives provided to the employee. This means that one contract will be said to provide stronger incentives than another if it specifies a higher value for b. This is the incentive contract as it operates in the West. The key feature distinguishing the Russian example is that x is observed by the employer but is not observed by the employee. So the employer promises to pay in accordance with an incentive scheme, but since the outcome is not observable by the employee the contract cannot be enforced, and the question arises: is there any incentive for the employer to fulfil his or her promises? Mr. Pechersky considers two simple models of employer-employee relationships displaying the above type of information symmetry. In a static framework the obtained result is somewhat surprising: at the Nash equilibrium the employer pays nothing, even though his objective function contains a quadratic term reflecting negative consequences for the employer if the actual level of compensation deviates from the expectations of the employee. This can lead, for example, to labour turnover, or the expenses resulting from a bad reputation. In a dynamic framework, the conclusion can be formulated as follows: the higher the discount factor, the higher the incentive for the employer to be honest in his/her relationships with the employee. If the discount factor is taken to be a parameter reflecting the degree of (un)certainty (the higher the degree of uncertainty is, the lower is the discount factor), we can conclude that the answer to the formulated question depends on the stability of the political, social and economic situation in a country. Mr. Pechersky believes that the strength of a market system with private property lies not just in its providing the information needed to compute an efficient allocation of resources in an efficient manner. At least equally important is the manner in which it accepts individually self-interested behaviour, but then channels this behaviour in desired directions. People do not have to be cajoled, artificially induced, or forced to do their parts in a well-functioning market system. Instead, they are simply left to pursue their own objectives as they see fit. Under the right circumstances, people are led by Adam Smith's "invisible hand" of impersonal market forces to take the actions needed to achieve an efficient, co-ordinated pattern of choices. The problem is that, as Mr. Pechersky sees it, there is no reason to believe that the circumstances in Russia are right, and the invisible hand is doing its work properly. Political instability, social tension and other circumstances prevent it from doing so. Mr. Pechersky believes that the discount factor plays a crucial role in employer-employee relationships. Such relationships can be considered satisfactory from a normative point of view, only in those cases where the discount factor is sufficiently large. Unfortunately, in modern Russia the evidence points to the typical discount factor being relatively small. This fact can be explained as a manifestation of aversion to risk of economic agents. Mr. Pechersky hopes that when political stabilisation occurs, the discount factors of economic agents will increase, and the agent's behaviour will be explicable in terms of more traditional models.

Connectionism as metaphor: Towards an integrated, unified conception of self-system and individual difference

Comments on an article by Kashima et al. (see record 2007-10111-001). In their target article Kashima and colleagues try to show how a connectionist model conceptualization of the self is best suited to capture the self's temporal and socio-culturally contextualized nature. They propose a new model and to support this model, the authors conduct computer simulations of psychological phenomena whose importance for the self has long been clear, even if not formally modeled, such as imitation, and learning of sequence and narrative. As explicated when we advocated connectionist models as a metaphor for self in Mischel and Morf (2003), we fully endorse the utility of such a metaphor, as these models have some of the processing characteristics necessary for capturing key aspects and functions of a dynamic cognitive-affective self-system. As elaborated in that chapter, we see as their principal strength that connectionist models can take account of multiple simultaneous processes without invoking a single central control. All outputs reflect a distributed pattern of activation across a large number of simple processing units, the nature of which depends on (and changes with) the connection weights between the links and the satisfaction of mutual constraints across these links (Rummelhart & McClelland, 1986). This allows a simple account for why certain input features will at times predominate, while others take over on other occasions. (PsycINFO Database Record (c) 2008 APA, all rights reserved)

Expression and hypoxic regulation of the endothelin system in endocrine cells of human and rat pancreatic islets

CONTEXT: The success of pancreatic islet transplantation depends largely on the capacity of the islet graft to survive the initial phase immediately after transplantation until revascularization is completed. Endothelin-1 (ET-1) is a strong vasoconstrictor which has been involved in solid organ graft failure but is also known to be a potent mitogenic/anti-apoptotic factor which could also potentially enhance the survival of the transplanted islets. OBJECTIVE: Characterization of the endothelin system with regard to a potential endothelin agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin system in human and rat pancreatic islets and beta-cell lines was assessed by means of immunohistochemistry, competition binding studies, western blot, RT-PCR, real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor immunoreactivity was identified in the endocrine cells of human and rat pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines and isolated rat and human pancreatic islets. Competition binding studies on rat islets revealed binding sites for both receptor types. ET-1 stimulated the phosphorylation of mitogen-activated protein kinase, which was prevented by ETA- and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets were robustly induced whereas ETA-receptor mRNA did not show significant changes. Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia and after transplantation. Our results provide the biological basis for the study of the potential use of endothelin agonists/antagonists to improve islet transplantation outcome.

Groundwater Under the Butte Hill - The East Camp Mining System and the Berkeley Pit

This lecture discusses monitoring activities of the Berkeley Pit for the past 31 years at the Montana Bureau of Mines and Geology in Butte, Montana.

A Discussion of the Geology and an Isopach Map of the Pennsylvanian System in Wyoming and Adjacent Areas

Pennsylvanian strata in Wyoming and adjacent areas have been the subject of much work and discussion. Most of the work has been due to the economic importance of the system as an oil producer in this region. Oil production from strata of Pennsylvanian age is rather recent history; and therefore, much of the available information is local­ized and incomplete.