bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive analysis of transcript signatures of the phosphatidylinositol‐3 kinase/protein kinase B signal‐transduction pathway in prostate cancer
Authors: Hellwinkel Olaf J.C. , Rogmann Jan‐Peer , Asong Legrehndem E. , Luebke Andreas M. , Eichelberg Christian , Ahyai Sascha , Isbarn Hendrik , Graefen Markus , Huland Hartwig , Schlomm Thorsten 
Published: March 2008

OBJECTIVETo assess the gene activities ofvarious important members of the phosphatidylinositol 3 kinase (PIK3)/protein kinase B (PKB/Akt) pathway (involved in the promotion and regulation of cellular metabolism, proliferation and apoptosis) for alterations in prostate carcinoma.PATIENTS, SUBJECTS AND METHODSUsing quantitative real‐time reverse‐transcription polymerase chain reaction, we analysed the transcript levels of 12 genes involved in the PIK3/PKB pathway in microdissected tumour tissues from 20 patients with varying stages of prostate cancer, assessing differences from adjacent normal tissues and from a pool of prostate tissues from healthy controls.RESULTSIn cancer samples with a high Gleason grade, the PIK3/PKB pathway was principally affected by marked decreases in expression over almost all the investigated stages of the pathway. These changes were in effectors of the pathway, especially PIK3 p85 α (PIK3R1) and integrin‐linked kinase, and the pathway target fork‐head box protein (FOXO)‐1A, while the transcript quantities of regulators, e.g. phosphatase/tensin homologue (PTEN), were decreased in a smaller proportion of the patients. Transcript amounts of FOXO‐1A and FOXO‐3A were significantly higher in normal tumour‐adjacent tissues than in the healthy controls.CONCLUSIONSDown‐regulation of the PIK3/PKB pathway by repression of involved effector and regulator genes at all stages of the molecular pathway could represent a marker for the formation of highly de‐differentiated prostate cancers from low‐grade tumour foci. Also, parts of the pathway are deviant in normal tumour‐adjacent tissue; this might represent a reaction to neighbouring tumours or be a sign of pre‐cancerous biological alterations.
Can the International Index of Erectile Function distinguish between organic and psychogenic erectile function?
Authors: Deveci Serkan , O’Brien Keith , Ahmed Absaar , Parker Marilyn , Guhring Patricia , Mulhall John P. 
Published: March 2008

OBJECTIVETo define the ability of the International Index of Erectile Function (IIEF) to differentiate between organic and psychogenic erectile dysfunction (ED).PATIENTS AND METHODSPatients presenting for the evaluation and treatment of ED who had penile duplex Doppler ultrasonography (DUS) completed the IIEF questionnaire. Accepted ranges of the IIEF EF domain were used to grade baseline severity (severe, moderate and mild ≤11, 11–17, 18–25, respectively). Accepted criteria were used to define normality on DUS (peak systolic velocity >30 cm/s and end‐diastolic velocity <5 cm/s). Patients with documented Peyronie’s disease, hypogonadism and a history of radical prostatectomy were excluded.RESULTSIn all, 112 patients were enrolled, with a mean (sd) age and duration of ED of 56 (16) and 2 (0.6) years, respectively. The vascular risk‐factor profile included diabetes in 15%, hypertension in 26% and hyperlipidaemia in 20%. The baseline severity of ED was mild, moderate and severe in 28%, 41% and 32% men, respectively. All patients had normal testosterone levels. Patients also with a normal DUS were diagnosed with psychogenic ED, in 50%, 13% and 17% of men with mild, moderate and severe ED by the IIEF, respectively. No patient with venous leak had mild ED, and 62% of men with venous leak had severe ED.CONCLUSIONSThese results indicate that the IIEF is not completely accurate in differentiating between organic and psychogenic ED, and that almost a fifth of men in this study population with severe ED by the IIEF had normal erectile haemodynamics. These data have potential ramifications for evaluating the baseline severity of ED in trials of erectogenic agents.
The Wrong Stuff: Chinese Rooms and the Nature of Understanding
Authors: Fisher John A. 
Published: March 2008

AbstractSearle's Chinese Room argument is a general argument that proves that machines do not have mental states in virtue of their programming. I claim that the argument expresses powerful but mistaken intuitions about understanding and the first person point of view. A distinction is drawn between a competence sense and a performance sense of ‘understanding texts’. It is argued that the Chinese Room intuition looks for a special experience (performance) of comprehension, whereas artificial intelligence is attempting to explain the knowledge (competence) required to understand texts. Moreover, a dilemma is sketched for the argument: either Searle hasn't identified the appropriate subject of understanding or he may understand after all. Finally, I question the underlying assumption that the general definition of mental states requires a projectable‐by‐us first person point of view.
INTERDEPENDENCE AND CAPABILITIES FOR EUROPEAN COOPERATION*
Authors: Russett Bruce M. 
Published: March 2008

SUMMARYIt is a commonplace that the world has grown more interdependent during the twentieth century. One can point to revolutions in transportation, communication, and weapons capabilities, or to the financial interdependencies of Eurodollars and foreign exchange sensitivities. It is not generally appreciated, however, that many of the international capabilities for dealing with problems that arise from these interdependencies have suffered a decline during the same period, at least relative to the burdens of interdependence that must be borne and often relative even to the level of capabilities that existed several decades ago. Western Europe nevertheless constitutes a substantial exception to the general trend, an island of cohesion in an increasingly disorganized world. A historical and contemporary comparative perspective may help to point out the peculiarly favorable opportunities now open to Western Europe.
Policy issues of intra‐EC direct investment: British, French and German multinationals in Greece, Portugal and Spain, with special reference to employment effects
Authors: BUCKLEY PETER J. , ARTISIEN PATRICK 
Published: March 2008

SummaryFrom this brief survey, it is apparent that Greece, Portugal and Spain are all heavily dependent on foreign investment for industrial and commercial development. In each country, critical industries such as chemicals, electrical engineering, motor vehicles and information based technologies are heavily dependent on foreign investment. Consequently, the decisions of multinationals on where to invest and how to service markets will have a profound effect on employment in these countries. These issues are discussed in detail in sections V and VI.France, Germany and the United Kingdom are major origins of firms with considerable investments in each of the countries, although British firms are under‐represented in Greece. France is the largest country of origin for multinationals investing in Portugal, and it has recently begun to invest heavily in Spain. In Greece, French firms represent a quarter of all authorized foreign direct investment (second only to the USA). West German firms are represented at a modest level in Greece but are consistently heavy investors in Spain and also contribute to investment and employment in Portuguese industry. Compared to France and West Germany, British firms have neglected these three host countries as investment targets. Their tiny representation in Greece has been mentioned, and whilst investment in Portugal matches that of West German firms, British firms' investment in Spain has recently been small relative to French and German firms.Overall, investment by multinationals from France, West Germany and the United Kingdom has played an important role in the industrial development of the three host countries, and their location and market servicing policies continue to have a major impact on employment in Greece, Portugal and Spain.The recent entry (1 January 1986) of the Iberian countries into the EC is likely to have a major impact on their prospects of attracting foreign direct investment, and, although this will have been anticipated to a certain extent by investors, its impact is worthy of further analysis. The following section begins this process by outlining the legislative measures of the three host countries.
National Governance and European Integration: Intergovernmental Relations in Germany
Authors: GOETZ KLAUS H. 
Published: March 2008

AbstractThe impact of European integration on the governance of EU Member States bas received growing attention in recent years. In analysing the Europeanization of national political systems, intergovernmental relations are of special significance, particularly in strongly decentralized or federalized polities. Focusing on Germany, it can be shown that European integration has had a major impact on Federd‐Länder and inter‐Länder relations. However, rather than challenge established features of the intergovernmental system, European integration has tended to affirm, if not reinforce, key structural principles of German federalism. Europeanization is not, therefore, necessarily equivalent to the transformation of national systems of governance.
First No, Then Yes: The Danish Referendums on the Maastricht Treaty 1992 and 1993
Authors: WORRE TORBEN 
Published: March 2008

AbstractThis article considers the behaviour of Danish voters in the two referendums on the Treaty on European Union (Maastricht Treaty). The first, in June 1992, rejected the Treaty and threatened the whole union process. The second, in May 1993, approved the Treaty. The development of opinion before and between the referendums is considered, and it is demonstrated that resistance to the Maastricht Treaty was not an effect of opposition to membership of the Community, but the result of a preference for an intergovernmental type of European Co‐operation.
Democracy and Enlarging the European Union Eastwards
Authors: ROSE RICHARD , HAERPFER CHRISTIAN 
Published: March 2008

AbstractDemocracy is a precondition for membership of the European Union (EU). What are the chances for democracy in the post‐communist states of central and eastern Europe? The first section states arguments of doubters; the second and third present fresh empirical evidence from nation‐wide surveys of public opinion in the Czech Republic, Slovakia, Hungary, Poland, Slovenia, Bulgaria and Romania. Survey data show widespread popular support for the current regime as against the old communist regime, and no substantial support for undemocratic alternatives. The critical feature of ex‐communists is that they are now ‘ex’. Given that the democratic precondition is met, this article secondly considers, what are the obstacles to enlargement within post‐communist countries? In central and eastern Europe the chief obstacle is the time required to create all the institutions of the market. Within the European Union there is also an obstacle‐ defining the post‐1996 acquits communitarian ‐ a task made more complex by the prospect of adding new Member States from central and eastern Europe.
Policy Legitimacy and the European Union
Authors: Obradovic Daniela 
Published: March 2008

AbstractAlthough numerous contributions have been made towards establishing policy legitimacy in the European Union (EU), to date no comprehensive model has been developed. The aim of this article is to explain why the search for legitimacy of the European enterprise has not ultimately been satisfied. I argue that the reason for underdeveloped policy legitimacy in the Union stems not from the lack of interest on the part of European policy‐makers caused by the comfort of ‘permissive consensus’, but from the very nature of the concept of legitimacy as such, i.e. its organic, mythical foundation. Essentially, legitimacy reflects the belief that one system is just because it embodies an accepted superior justificatory principle, the myth. The justificatory message communicated by the myth creates an effective device for legitimation. The myth is understood here in its broad sense as the symbolic values through which people share an idea of origin, continuity, historical memories, collective remembrance, common heritage and tradition, as well as a common destiny, which has often involved a binding political process by which one ethnol has become hegemonicvis‐à‐visthe rest. Myth expresses and maintains social solidarity because it refers to values of belongingness and originality and a sense of shared collective identity and fate. Such a myth of origin as the ultimate source of legitimacy is missing from the European venture. No mythologein is powerfully operative within the Union, no one can win the consent of the entire Union population. The task of firmly and indisputably establishing Union policy legitimacy therefore encounters serious theoretical difficulties.
European Integration from the 1980s: State‐Centric v. Multi‐level Governance*
Authors: Marks Gary , Hooghe Liesbet , Blank Kermit 
Published: March 2008

AbstractThis article takes initial steps in evaluating contending models of EU governance. We argue that the sovereignty of individual states is diluted in the European arena by collective decision‐making and by supranational institutions. In addition, European states are losing their grip on the mediation of domestic interest representation in international relations. We make this argument along two tracks. First, we analyse the conditions under which central state executives may lose their grip on power. Next, we divide up the policy process into stages and specify which institutional rules may induce various actors to deepen EU policy‐making.
Between Nation‐State, Regionalism and World Society: The European Integration Process*
Authors: Münch Richard 
Published: March 2008

AbstractIn this article, I aim to discuss the problems associated with European integration with particular reference to the integration processes taking place within the European Union (EU). I intend to deal with the topic in five sections: (1) how an abstract model for understanding and explaining the development of larger collective units, exemplified by the emergence of European nation‐states, can provide the tools for understanding and explaining the development of the EU as a supranational collective unit; (2) the economic problems of integration; (3) the political problems of integration; (4) the problems of integration regarding bonds of solidarity; (5) the cultural problems of integration.
Membership Matters: Limits of the Functional Approach to European Institutions*
Authors: Snvdholtz Wayne 
Published: March 2008

AbstractFunctional, transaction‐cost approaches to international institutions depict them as passive fora for bargaining among states with autonomously derived preferences. This article probes the limits of the functional, intergovernmental account of the European Union. It suggests that EU institutions can affect political behaviour and outcomes in at least three broad ways: (1) by becoming autonomous political actors; (2) by creating options for domestic actors in their choice of allies and arenas (creating ‘multi‐level politics’); and (3) by inducing changes in domestic policies and institutions. The article provides instances of each effect in the European Union. It concludes that, in order to understand how the European Union works as well as how it has evolved, analysis must move beyond the limits of the functional, intergovernmentalist approach.
An Empirical Analysis of Inward Foreign Direct Investment Flows in the EU with Emphasis on the Market Enlargement Hypothesis*
Authors: Aristotelous Kyriacos , Fountas Stilianos 
Published: March 2008

AbstractWe use a cross‐section, time‐series approach to study the determinants of foreign direct investment (FDI) in the European Union (EU) with particular emphasis on the expectations of a single market following the Single European Act of 1987. Using annual data from the 1980s and early 1990s, we investigate the determinants of US and Japanese FDI in the EU by pooling the data by the host country. We find strong evidence in favour of a single market effect where the anticipation of a larger market size due to a barriers free European market leads to an increase in the inflows of FDI. In addition, our estimation results show that FDI flows in the EU also depend on market size and the real exchange rate (as a proxy of relative labour costs).
DJ‐1‐binding compounds prevent oxidative stress‐induced cell death and movement defect in Parkinson’s disease model rats
Authors: Miyazaki Shin , Yanagida Takashi , Nunome Kana , Ishikawa Shizuma , Inden Masatoshi , Kitamura Yoshihisa , Nakagawa Shinsuke , Taira Takahiro , Hirota Kosaku , Niwa Masami , Iguchi‐Ariga Sanae M. M. , Ariga Hiroyoshi 
Published: March 2008

AbstractParkinson’s disease (PD) is caused by neuronal cell death. Although a precursor of dopamine and inhibitors of dopamine degradation have been used for PD therapy, cell death progresses during treatment. DJ‐1, a causative gene product of a familial form of PD, PARK7, plays roles in transcriptional regulation and anti‐oxidative stress, and loss of its function is thought to result in the onset of PD. Superfluous oxidation of cysteine at amino acid 106 (C106) of DJ‐1 renders DJ‐1 inactive, and such oxidized DJ‐1 has been observed in patients with the sporadic form of PD. In this study, we isolated compounds that bind to the region at C106 by a virtual screening. These compounds prevented oxidative stress‐induced death of SH‐SY5Y cells, embryonic stem cell‐derived dopaminergic cells and primary neuronal cells of the ventral mesencephalon, but not that of DJ‐1‐knockdown cells of SH‐SY5Y and NIH3T3 cells, indicating that the effect of the compounds is specific to DJ‐1. These compounds inhibited production of reactive oxygen species and restored activities of mitochondrial complex I and tyrosine hydroxylase that had been compromised by oxidative stress. These compounds prevented dopaminergic cell death in the substantia nigra and restored movement abnormality in 6‐hydroxyldopamine‐injected PD model rats. One mechanism of action of these compounds is prevention of superfluous oxidation of DJ‐1, and the compounds passed through the blood–brain barrier in vitro. Taken together, the results indicate that these compounds should become fundamental drugs for PD therapy.
The −308 TNFα Gene Polymorphism in Severe Acute Alcoholic Hepatitis: Identification of a New Susceptibility Marker
Authors: Nguyen‐Khac Eric , Houchi Hakim , Daoust Martine , Dupas Jean Louis , Naassila Mickaël 
Published: March 2008

Background:  This study investigated whether genetic polymorphisms in the tumor necrosis factor alpha (TNFα) gene’s promoter region play a role in severe acute alcoholic hepatitis (AAH).Methods:  One‐hundred and fifty patients (58 AAH patients, 45 cirrhosis group free‐AAH, 47 healthy group) were genotyped for 3 TNFα polymorphisms (−238, −308, −863) using a polymerase chain reaction‐restriction fragment length polymorphism technique. Serum TNFα levels were determined.Results  The TNFα−308 allele A frequency was significantly lower in AAH group (0.09), than cirrhosis (0.28) (p < 0.001), and healthy groups (p < 0.001). The TNFα−308 A/G, A/A genotypes were significantly lower in AAH group, than cirrhosis (p = 0.005), and healthy groups (p < 0.001). For AAH group, there were no clinical, biological, and serum TNFα differences between the −308 G/G and A/G, A/A genotype patients, apart higher transaminase in the former group (p = 0.02). AAH and cirrhosis groups did not differ for the frequency of TNFα−238, −863 polymorphisms. The specific genotype did not appear to have any influence on the therapeutic response following corticotherapy or posttreatment 6‐month survival. In the AAH group, nonsurvivors had higher TNFα levels than survivors (7.9 ± 8.8 vs. 3.3 ± 1.6 pg/ml, p = 0.01).Conclusions:  These results attest to the involvement of TNFα‐related genetic factors in susceptibility to AAH.
Acute Alcohol Intoxication Increases REDD1 in Skeletal Muscle
Authors: Lang Charles H. , Frost Robert A. , Vary Thomas C. 
Published: March 2008

Background:  The mechanism by which acute alcohol (EtOH) intoxication decreases basal muscle protein synthesis via inhibition of the Ser/Thr kinase mammalian target of rapamycin (mTOR) is poorly defined. In this regard, mTOR activity is impaired after over expression of the regulatory protein REDD1. Hence, the present study assessed the ability of REDD1 as a potential mediator of the EtOH‐induced decrease in muscle protein synthesis.Methods:  The effect of acute EtOH intoxication on REDD1 mRNA and protein was determined in striated muscle of rats and mouse myocytes using an RNase protection assay and Western blotting, respectively. Other components of the mTOR signaling pathway were also assessed by immunoblotting. For comparison, REDD1 mRNA/protein was also determined in the muscle of rats chronically fed an alcohol‐containing diet for 14 weeks.Results:  Intraperitoneal (IP) injection of EtOH increased gastrocnemius REDD1 mRNA in a dose‐ and time‐dependent manner, and these changes were associated with reciprocal decreases in the phosphorylation of 4E‐BP1, which is a surrogate marker for mTOR activity and protein synthesis. No change in REDD1 mRNA was detected in the slow‐twitch soleus muscle or heart. Acute EtOH produced comparable increases in muscle REDD1 protein. The EtOH‐induced increase in gastrocnemius REDD1 was independent of the route of EtOH administration (oral vs. IP), the nutritional state (fed vs. fasted), gender, and age of the rat. The nonmetabolizable alcohol tert‐butanol increased REDD1 and the EtOH‐induced increase in REDD1 was not prevented by pretreatment with the alcohol dehydrogenase inhibitor 4‐methylpyrazole. In contrast, REDD1 mRNA and protein were not increased in the isolated hindlimb perfused with EtOH or in C2C12 myocytes incubated with EtOH, under conditions previously reported to decrease protein synthesis. Pretreatment with the glucocorticoid receptor antagonist RU486 failed to prevent the EtOH‐induced increase in REDD1. Finally, the EtOH‐induced increase in REDD1 was not associated with altered formation of the TSC1•TSC2 complex or the phosphorylation of TSC2 which is down stream in the REDD1 stress response pathway. In contradistinction to the changes observed with acute EtOH intoxication, REDD1 mRNA/protein was not changed in gastrocnemius from chronic alcohol‐fed rats despite the reduction in 4E‐BP1 phosphorylation.Conclusions:  These data indicate that in fast‐twitch skeletal muscle (i) REDD1 mRNA/protein is increased in vivo by acute EtOH intoxication but not in response to chronic alcohol feeding, (ii) elevated REDD1 in response to acute EtOH appears due to the production of an unknown secondary mediator which is not corticosterone, and (iii) the EtOH‐induced decrease in protein synthesis can be dissociated from a change in REDD1 suggesting that the induction of this protein is not responsible for the rapid decrease in protein synthesis after acute EtOH administration or for the development of alcoholic myopathy in rats fed an alcohol‐containing diet.