Philosophical conceptions of information

“The original publication is available at www.springerlink.com” Copyright Springer'I love information upon all subjects that come in my way, and especially upon those that are most important.' Thus boldly declares Euphranor, one of the defenders of Christian faith in Berkley’s Alciphron (Berkeley, (1732), Dialogue 1, Section 5, Paragraph 6/10). Evidently, information has been an object of philosophical desire for some time, well before the computer revolution, Internet or the dot.com pandemonium (see for example Dunn (2001) and Adams (2003)). Yet what does Euphranor love, exactly? What is information? The question has received many answers in different fields. Unsurprisingly, several surveys do not even converge on a single, unified definition of information (see for example Braman 1989, Losee (1997), Machlup and Mansfield (1983), Debons and Cameron (1975), Larson and Debons (1983)).Peer reviewe

An isochromosome confers drug resistance in vivo by amplification of two genes, ERG11 and TAC1

Acquired azole resistance is a serious clinical problem that is often associated with the appearance of aneuploidy and, in particular, with the formation of an isochromosome [i(5L)] in the fungal opportunist Candida albicans. Here we exploited a series of isolates from an individual patient during the rapid acquisition of fluconazole resistance (FluR). Comparative genome hybridization arrays revealed that the presence of two extra copies of Chr5L, on the isochromosome, conferred increased FluR and that partial truncation of Chr5L reduced FluR. In vitro analysis of the strains by telomere-mediated truncations and by gene deletion assessed the contribution of all Chr5L genes and of four specific genes. Importantly, ERG11 (encoding the drug target) and a hyperactive allele of TAC1 (encoding a transcriptional regulator of drug efflux pumps) made independent, additive contributions to FluR in a gene copy number-dependent manner that was not different from the contributions of the entire Chr5L arm. Thus, the major mechanism by which i(5L) formation causes increased azole resistance is by amplifying two genes: ERG11 and TAC1. © 2008 The Authors

Combined tumor-directed recruitment and protection from immune suppression enable CAR T cell efficacy in solid tumors.

CAR T cell therapy remains ineffective in solid tumors, due largely to poor infiltration and T cell suppression at the tumor site. T regulatory (Treg) cells suppress the immune response via inhibitory factors such as transforming growth factor–β (TGF-β). Treg cells expressing the C-C chemokine receptor 8 (CCR8) have been associated with poor prognosis in solid tumors. We postulated that CCR8 could be exploited to redirect effector T cells to the tumor site while a dominant-negative TGF-β receptor 2 (DNR) can simultaneously shield them from TGF-β. We identified that CCL1 from activated T cells potentiates a feedback loop for CCR8+ T cell recruitment to the tumor site. This sustained and improved infiltration of engineered T cells synergized with TGF-β shielding for improved therapeutic efficacy. Our results demonstrate that addition of CCR8 and DNR into CAR T cells can render them effective in solid tumors

Learning overhypotheses with hierarchical Bayesian models

Inductive learning is impossible without overhypotheses, or constraints on the hypotheses considered by the learner. Some of these overhypotheses must be innate, but we suggest that hierarchical Bayesian models can help to explain how the rest are acquired. To illustrate this claim, we develop models that acquire two kinds of overhypotheses – overhypotheses about feature variability (e.g. the shape bias in word learning) and overhypotheses about the grouping of categories into ontological kinds like objects and substances.Charles Kemp, Amy Perfors and Joshua B. Tenenbau