Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 x 10(-10)), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 x 10(-26)) and 18q21 (rs4939827; OR = 1.2; P = 7.8 x 10(-28)). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75-3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.     

The earliest dromaeosaurid theropod from South America

The evolutionary history of Maniraptora, the clade of carnivorous dinosaurs that includes birds and the sickle-clawed Dromaeosauridae, has hitherto been largely restricted to Late Jurassic and Cretaceous deposits on northern continents. The stunning Early Cretaceous diversity of maniraptorans from Liaoning, China, coupled with a longevity implied by derived Late Jurassic forms such as Archaeopteryx, pushes the origins of maniraptoran lineages back to Pangaean times and engenders the possibility that such lineages existed in Gondwana. A few intriguing, but incomplete, maniraptoran specimens have been reported from South America, Africa and Madagascar. Their affinities remain contested, however, and they have been interpreted as biogeographic anomalies relative to other faunal components of these land-masses. Here we describe a near-complete, small dromaeosaurid that is both the most complete and the earliest member of the Maniraptora from South America, and which provides new evidence for a unique Gondwanan lineage of Dromaeosauridae with an origin predating the separation between northern and southern landmasses.     

ERAAP customizes peptides for MHC class I molecules in the endoplasmic reticulum

The ability of killer T cells carrying the CD8 antigen to detect tumours or intracellular pathogens requires an extensive display of antigenic peptides by major histocompatibility complex (MHC) class I molecules on the surface of potential target cells. These peptides are derived from almost all intracellular proteins and reveal the presence of foreign pathogens and mutations. How cells produce thousands of distinct peptides cleaved to the precise lengths required for binding different MHC class I molecules remains unknown. The peptides are cleaved from endogenously synthesized proteins by the proteasome in the cytoplasm and then trimmed by an unknown aminopeptidase in the endoplasmic reticulum (ER). Here we identify ERAAP, the aminopeptidase associated with antigen processing in the ER. ERAAP has a broad substrate specificity, and its expression is strongly upregulated by interferon-gamma. Reducing the expression of ERAAP through RNA interference prevents the trimming of peptides for MHC class I molecules in the ER and greatly reduces the expression of MHC class I molecules on the cell surface. Thus, ERAAP is the missing link between the products of cytosolic processing and the final peptides presented by MHC class I molecules on the cell surface.     

Raman injection laser

Stimulated Raman scattering is a nonlinear optical process that, in a broad variety of materials, enables the generation of optical gain at a frequency that is shifted from that of the incident radiation by an amount corresponding to the frequency of an internal oscillation of the material. This effect is the basis for a broad class of tunable sources known as Raman lasers. In general, these sources have only small gain (approximately 10(-9) cm W(-1)) and therefore require external pumping with powerful lasers, which limits their applications. Here we report the realization of a semiconductor injection Raman laser designed to circumvent these limitations. The physics underlying our device differs in a fundamental way from existing Raman lasers: it is based on triply resonant stimulated Raman scattering between quantum-confined states within the active region of a quantum cascade laser that serves as an internal optical pump--the device is driven electrically and no external laser pump is required. This leads to an enhancement of orders of magnitude in the Raman gain, high conversion efficiency and low threshold. Our lasers combine the advantages of nonlinear optical devices and of semiconductor injection lasers, and could lead to a new class of compact and wavelength-agile mid-and far-infrared light sources.     

A Proposal for a Coherent Ontology of Fundamental Entities

We argue that the distinction between framework and interaction theories should be taken carefully into consideration when dealing with the philosophical implications of fundamental theories in physics. In particular, conclusions concerning the nature of reality can only be consistently derived from assessing the ontological and epistemic purport of both types of theories. We put forward an epistemic form of realism regarding framework theories, such as Quantum Field Theory. The latter, indeed, informs us about the general properties of quantum fields, laying the groundwork for interaction theories. Yet, concerning interaction theories, we recommend a robust form of ontological realism regarding the entities whose existence is assumed by these theories. As an application, we refer to the case of the Standard Model, so long as it has proved to successfully inform us about the nature of various sorts of fundamental particles making up reality. In short, although we acknowledge that both framework and interaction theories partake in shaping our science-based view of reality, and that neither would do by itself the work we expect them to accomplish together, our proposal for a coherent ontology of fundamental entities advances a compromise between two forms of realism about theories in each case.