Levels: Descriptive, Explanatory, and Ontological

Scientists and philosophers frequently speak about levels of description, levels of explanation, and ontological levels. In this paper, I propose a unified framework for modelling levels. I give a general definition of a system of levels and show that it can accommodate descriptive, explanatory, and ontological notions of levels. I further illustrate the usefulness of this framework by applying it to some salient philosophical questions: (1) Is there a linear hierarchy of levels, with a fundamental level at the bottom? And what does the answer to this question imply for physicalism, the thesis that everything supervenes on the physical? (2) Are there emergent properties? (3) Are higher-level descriptions reducible to lower-level ones? (4) Can the relationship between normative and non-normative domains be viewed as one involving levels? Although I use the terminology of “levels”, the proposed framework can also represent “scales”, “domains”, or “subject matters”, where these are not linearly but only partially ordered by relations of supervenience or inclusion

Bro1 binding to Snf7 regulates ESCRT-III membrane scission activity in yeast

The ubiquitin hydrolase activating factor Bro1 enhances ESCRT-III stability by inhibiting Vps4-mediated disassembly

Kovesi and the Formal and Material Elements of Concepts

Published in Philosophia, December 2011, Volume 39, Issue 4, pp 699-720. doi: 10.1007/s11406-011-9305-x</p

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers