The NCBI dbGaP database of genotypes and phenotypes

The National Center for Biotechnology Information has created the dbGaP public repository for individual-level phenotype, exposure, genotype and sequence data and the associations between them. dbGaP assigns stable, unique identifiers to studies and subsets of information from those studies, including documents, individual phenotypic variables, tables of trait data, sets of genotype data, computed phenotype-genotype associations, and groups of study subjects who have given similar consents for use of their data.     

Einstein's Revolution: A Case Study in Communicative Rationality

The aim of the paper is to demonstratethat Special Relativity and the Early Quantum Theory were created within the same programme of statisticalmechanics, thermodynamics and maxwellianelectrodynamics reconciliation. I shall try to explainwhy classical mechanics and classicalelectrodynamics were ``refuted' almost simultaneouslyor, in more suitable terms for the present congress,why did the quantum revolution and the relativisticone both took place at the beginning of the 20-thcentury. I shall argue that the quantum andrelativistic revolutions were simultaneous since theyhad a common origin -- the clash between thefundamental theories of the second half of the 19-thcentury that constituted the ``body' of ClassicalPhysics. The revolution's most dramatic pointwas Einstein's 1905 photon paper that laid thefoundations of both Special Relativity and OldQuantum Theory. Hence the dialectic of the oldtheories is crucial for theory change. Modern physicsbegan with Einstein's reconciliation ofelectrodynamics, mechanics and thermodynamics in 1905and his unification of Special Relativity andNewtonian Theory of Gravity. Or, in a more generalsocial context: progressive scientific change can bedescribed not in Weberian terms of zweckrationalaction forcing out all the other forms of action onlybut in terms of Habermas's communicative rationalityencouraging the establishment of mutual understandingbetween the various scientific communities also.Einstein's programme constituted a progressive stepwith respect to its rivals not because it couldexplain more ``facts' or was more ``mathematical'. Itwas better than its rivals because it constituted abasis of communication and interpenetration betweenthree main paradigms of 19-th century physics. Ofcourse in the long run it resulted in empiricalsuccesses.     

NF-kappaB functions as a tumour promoter in inflammation-associated cancer

The causes of sporadic human cancer are seldom recognized, but it is estimated that carcinogen exposure and chronic inflammation are two important underlying conditions for tumour development, the latter accounting for approximately 20% of human cancer. Whereas the causal relationship between carcinogen exposure and cancer has been intensely investigated, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. We proposed that activation of the nuclear factor kappaB (NF-kappaB), a hallmark of inflammatory responses that is frequently detected in tumours, may constitute a missing link between inflammation and cancer. To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a prototype of inflammation-associated cancer. We monitored hepatitis and cancer progression in Mdr2-knockout mice, and here we show that the inflammatory process triggers hepatocyte NF-kappaB through upregulation of tumour-necrosis factor-alpha (TNFalpha) in adjacent endothelial and inflammatory cells. Switching off NF-kappaB in mice from birth to seven months of age, using a hepatocyte-specific inducible IkappaB-super-repressor transgene, had no effect on the course of hepatitis, nor did it affect early phases of hepatocyte transformation. By contrast, suppressing NF-kappaB inhibition through anti-TNFalpha treatment or induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma. Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases.