Rank Difference Analysis of Microarrays (RDAM), a novel approach to statistical analysis of microarray expression profiling data

Background  

A key step in the analysis of microarray expression profiling data is the identification of genes that display statistically significant changes in expression signals between two biological conditions.     

Propagation and Purification of High-Titer Human Cytomegalovirus

High-titered yields of human cytomegalovirus (CMV), strain AD 169, were produced in WI-38 cells in large roller bottles. Maximum plaque titers were observed by the 4th day after infection at which time infectivity in the medium was 200 times greater than that associated with the cells. Virus released into the medium was recovered by sedimentation in a sucrose gradient in a continuous-flow centrifuge rotor. Maximal viral infectivity was found at a sucrose concentration of 42%, equivalent to a density of 1.18 g/cm(3). Deoxyribonucleic acid extracted from these preparations was about 80% viral and 20% cellular as judged by equilibrium centrifugation in cesium chloride density gradients.     

Is tau ready for admission to the prion club?

Aggregation-prone proteins associated with neurodegenerative disease, such as α synuclein and β amyloid, now appear to share key prion-like features with mammalian prion protein, such as the ability to recruit normal proteins to aggregates and to translocate between neurons. These features may shed light on the genesis of stereotyped lesion development patterns in conditions such as Alzheimer disease and Lewy Body dementia. We discuss the qualifications of tau protein as a possible “prionoid” mediator of lesion spread based on recent characterizations of the secretion, uptake and transneuronal transfer of human tau isoforms in a variety of tauopathy models, and in human patients. In particular, we consider (1) the possibility that prionoid behavior of misprocessed tau in neurodegenerative disease may involve other aggregation-prone proteins, including PrP itself, and (2) whether “prionlike” tau lesion propagation might include mechanisms other than protein-protein templating.     

Intensive Care Ethics in Evolution

The ethics of treating the seriously and critically ill have not been static throughout the ages. Twentieth century medicine has inherited from the nineteenth century a science which places an inappropriate weight on diagnosis over prognosis and management, combined with a seventeenth century duty to prolong life. However other earlier ethical traditions, both Hippocratic and Christian, respected both the limitations of medicine and emphasised the importance of prognosis. This paper outlines some of the historical precedents for the treatment of the critically ill, and also how the current paradigm limits clinical practice and causes ethical tensions. An understanding that other paradigms have been ethically acceptable in the past allows wider consideration and acceptance of alternatives for the future. However future alternatives will also have to address the role of technology, given its importance in this area of medicine.