A Note on K-modes Clustering

Recently, Chaturvedi, Green and Carroll (2001) presented a nonparametric approach to deriving clusters from categorical data using a new clustering procedure called K-modes. Huang (1998) proposed the K-modes clustering algorithm. In this note, we demonstrate the equivalence of the two K-modes procedures.     

Positional cloning of the combined hyperlipidemia gene Hyplip1.

Familial combined hyperlipidemia (FCHL, MIM-144250) is a common, multifactorial and heterogeneous dyslipidemia predisposing to premature coronary artery disease and characterized by elevated plasma triglycerides, cholesterol, or both. We identified a mutant mouse strain, HcB-19/Dem (HcB-19), that shares features with FCHL, including hypertriglyceridemia, hypercholesterolemia, elevated plasma apolipoprotein B and increased secretion of triglyceride-rich lipoproteins. The hyperlipidemia results from spontaneous mutation at a locus, Hyplip1, on distal mouse chromosome 3 in a region syntenic with a 1q21-q23 FCHL locus identified in Finnish, German, Chinese and US families. We fine-mapped Hyplip1 to roughly 160 kb, constructed a BAC contig and sequenced overlapping BACs to identify 13 candidate genes. We found substantially decreased mRNA expression for thioredoxin interacting protein (Txnip). Sequencing of the critical region revealed a Txnip nonsense mutation in HcB-19 that is absent in its normolipidemic parental strains. Txnip encodes a cytoplasmic protein that binds and inhibits thioredoxin, a major regulator of cellular redox state. The mutant mice have decreased CO2 production but increased ketone body synthesis, suggesting that altered redox status down-regulates the citric-acid cycle, sparing fatty acids for triglyceride and ketone body production. These results reveal a new pathway of potential clinical significance that contributes to plasma lipid metabolism.     

Locke’s construction of the idea of power

I explain Locke’s account of the origin of our idea of power, showing that it concerns the idea of the disposition to act or change, and that this idea is constructed out of the ideas of action or change. I also show how Locke could have modified his account to avoid Hume’s criticism and argue that his neglect to do so reflects a studied neglect of taxonomy, an ambiguity in the notion of capacity, and complications in Locke’s conception of simple ideas. A comparison of the two empiricists reveals that not only do they disagree about the role of reason in the origin of our idea of power, but they are also talking about different ideas. Within the framework of Locke’s account of the origin of the idea of power, I explain why he believes that bodies only provide us with an obscure idea of active power. I conclude by defending his insight that there is a deep connection between the ability to predict and the idea of power.     

Identification of Trypanosoma theileri as a contaminant in primary cultures of bovine retina

T. theileri has been isolated from primary cultures of bovine retina and subcultered successfully for 2 passages in sub-confluent cultures. When cultures reached confluency no trypomastigotes or epimastigotes could be detected and attempts to recover trypanosomes from these cultures were unsuccessful. The presence of intracellular forms could not formally be excluded.     

Automated real-time immunoassay of biomolecules.

ImmunoDetection is a novel technique combining perfusion chromatography technology with antibodies to perform the steps of an immunoassay in a flow-through column format. Sensitive and precise measurements are performed in seconds to minutes using automated liquid chromatography instrumentation.     

Proof-analysis and Continuity

During the first phase of Greek mathematics a proof consisted in showing or making visible the truth of a statement. This was the epagogic method. This first phase was followed by an apagogic or deductive phase. During this phase visual evidence was rejected and Greek mathematics became a deductive system. Now epagoge and apagoge, apart from being distinguished, roughly according to the modern distinction between inductive and deductive procedures, were also identified on account of the conception of generality as continuity. Epistemology of mathematics today only remembers the distinction, forgetting where they agreed, in this manner not only destroying the unity of the perceptual and conceptual but also forgetting what could be gained from Aristotelian demonstrative science.     

The theory theory thrice over: the child as scientist, Superscientist or social institution?

Alison Gopnik and Andrew Meltzoff have argued for a view they call the ‘theory theory’: theory change in science and children are similar. While their version of the theory theory has been criticized for depending on a number of disputed claims, we argue that there is a fundamental problem which is much more basic: the theory theory is multiply ambiguous. We show that it might be claiming that a similarity holds between theory change in children and (i) individual scientists, (ii) a rational reconstruction of a Superscientist, or (iii) the scientific community. We argue that (i) is false, (ii) is non-empirical (which is problematic since the theory theory is supposed to be a bold empirical hypothesis), and (iii) is either false or doesn't make enough sense to have a truth-value. We conclude that the theory theory is an interesting failure. Its failure points the way to a full, empirical picture of scientific development, one that marries a concern with the social dynamics of science to a psychological theory of scientific cognition.     

Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.