Instrumentalizing Failure: Edison's Invention of the Carbon Microphone

For Thomas Edison, experiencing a failure did not mean that he had failed. Through an examination of the process that led to his invention of the carbon microphone, I argue that his positive approach to failure contributed both to his success as an inventor and to the functional success of his inventions. Edison's laboratory notebooks and legal testimony reveal that his seemingly erratic approach and reliance on trial and error methods in fact had a consistent direction and a rational basis, well suited to the under-determined problems he faced. The outcome of this process, the carbon microphone, contributed significantly to the commercial success of the telephone and remains in use today. Thomas Hughes has observed that nineteenth century inventors made use of the unexpected behaviour of their inventions as sources of novel phenomena to exploit in new inventions. This paper identifies other ways in which Edison made use of failure and proposes that, paradoxically, the success of technological artefacts can be determined by the thoroughness with which failure is pursued in their creation. It also notes a parallel between Edison's instrumentalizing of failure and the way in which recent philosophers of science have proposed that scientists should make use of error.     

Purification and unique properties of mammary epithelial stem cells

Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.     

Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations

The molecular mechanisms by which different mutations in the same gene can result in distinct disease phenotypes remain largely unknown. Truncating mutations of SOX10 cause either a complex neurocristopathy designated PCWH or a more restricted phenotype known as Waardenburg-Shah syndrome (WS4; OMIM 277580). Here we report that although all nonsense and frameshift mutations that cause premature termination of translation generate truncated SOX10 proteins with potent dominant-negative activity, the more severe disease phenotype, PCWH, is realized only when the mutant mRNAs escape the nonsense-mediated decay (NMD) pathway. We observe similar results for truncating mutations of MPZ that convey distinct myelinopathies. Our experiments show that triggering NMD and escaping NMD may cause distinct neurological phenotypes.     

The plant response： stress in the daily environment

Like animals, plants have evolved to survive in almost every climatic and environmental niche available. They have, however, evolved more sophisticated and varied methods to enable them to survive environmental changes in light, temperature, atmosphere composition, water and nutrients and