University of Cambridge

About: University of Cambridge is a education organization based out in Cambridge, United Kingdom. It is known for research contribution in the topics: Population & Galaxy. The organization has 118293 authors who have published 282289 publications receiving 14497093 citations. The organization is also known as: Cambridge University & Cambridge.

Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard

Abstract: The PHENIX AutoBuild wizard is a highly automated tool for iterative model building, structure refinement and density modification using RESOLVE model building, RESOLVE statistical density modification and phenix.refine structure refinement. Recent advances in the AutoBuild wizard and phenix.refine include automated detection and application of NCS from models as they are built, extensive model-completion algorithms and automated solvent-molecule picking. Model-completion algorithms in the AutoBuild wizard include loop building, crossovers between chains in different models of a structure and side-chain optimization. The AutoBuild wizard has been applied to a set of 48 structures at resolutions ranging from 1.1 to 3.2 A, resulting in a mean R factor of 0.24 and a mean free R factor of 0.29. The R factor of the final model is dependent on the quality of the starting electron density and is relatively independent of resolution.

Bit-Interleaved Coded Modulation

Abstract: The principle of coding in the signal space follows directly from Shannon's analysis of waveform Gaussian channels subject to an input constraint. The early design of communication systems focused separately on modulation, namely signal design and detection, and error correcting codes, which deal with errors introduced at the demodulator of the underlying waveform channel. The correct perspective of signal-space coding, although never out of sight of information theorists, was brought back into the focus of coding theorists and system designers by Imai's and Ungerbock's pioneering works on coded modulation. More recently, powerful families of binary codes with a good tradeoff between performance and decoding complexity have been (re-)discovered. Bit-Interleaved Coded Modulation (BICM) is a pragmatic approach combining the best out of both worlds: it takes advantage of the signal-space coding perspective, whilst allowing for the use of powerful families of binary codes with virtually any modulation format. BICM avoids the need for the complicated and somewhat less flexible design typical of coded modulation. As a matter of fact, most of today's systems that achieve high spectral efficiency such as DSL, Wireless LANs, WiMax and evolutions thereof, as well as systems based on low spectral efficiency orthogonal modulation, feature BICM, making BICM the de-facto general coding technique for waveform channels. The theoretical characterization of BICM is at the basis of efficient coding design techniques and also of improved BICM decoders, e.g., those based on the belief propagation iterative algorithm and approximations thereof. In this text, we review the theoretical foundations of BICM under the unified framework of error exponents for mismatched decoding. This framework allows an accurate analysis without any particular assumptions on the length of the interleaver or independence between the multiple bits in a symbol. We further consider the sensitivity of the BICM capacity with respect to the signal-to-noise ratio (SNR), and obtain a wideband regime (or low-SNR regime) characterization. We review efficient tools for the error probability analysis of BICM that go beyond the standard approach of considering infinite interleaving and take into consideration the dependency of the coded bit observations introduced by the modulation. We also present bounds that improve upon the union bound in the region beyond the cutoff rate, and are essential to characterize the performance of modern randomlike codes used in concatenation with BICM. Finally, we turn our attention to BICM with iterative decoding, we review extrinsic information transfer charts, the area theorem and code design via curve fitting. We conclude with an overview of some applications of BICM beyond the classical coherent Gaussian channel.

The GTEx Consortium atlas of genetic regulatory effects across human tissues

Abstract: The Genotype-Tissue Expression (GTEx) project was established to characterize genetic effects on the transcriptome across human tissues, and to link these regulatory mechanisms to trait and disease associations. Here, we present analyses of the v8 data, based on 17,382 RNA-sequencing samples from 54 tissues of 948 post-mortem donors. We comprehensively characterize genetic associations for gene expression and splicing in cis and trans, showing that regulatory associations are found for almost all genes, and describe the underlying molecular mechanisms and their contribution to allelic heterogeneity and pleiotropy of complex traits. Leveraging the large diversity of tissues, we provide insights into the tissue-specificity of genetic effects, and show that cell type composition is a key factor in understanding gene regulatory mechanisms in human tissues.

Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1

Abstract: To identify risk variants for lung cancer, we conducted a multistage genome-wide association study. In the discovery phase, we analyzed 315,450 tagging SNPs in 1,154 current and former (ever) smoking cases of European ancestry and 1,137 frequency-matched, ever-smoking controls from Houston, Texas. For replication, we evaluated the ten SNPs most significantly associated with lung cancer in an additional 711 cases and 632 controls from Texas and 2,013 cases and 3,062 controls from the UK. Two SNPs, rs1051730 and rs8034191, mapping to a region of strong linkage disequilibrium within 15q25.1 containing PSMA4 and the nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5, were significantly associated with risk in both replication sets. Combined analysis yielded odds ratios of 1.32 (P < 1 × 10−17) for both SNPs. Haplotype analysis was consistent with there being a single risk variant in this region. We conclude that variation in a region of 15q25.1 containing nicotinic acetylcholine receptors genes contributes to lung cancer risk.