Using a task-based approach in evaluating the usability of BoBIs in an e-book environment

This paper reports on a usability evaluation of BoBIs (Back-of-the-book Indexes) as searching and browsing tools in an e-book environment. This study employed a task-based approach and within-subject design. The retrieval performance of a BoBI was compared with a ToC and Full-Text Search tool in terms of their respective effectiveness and efficiency for finding information in e-books. The results demonstrated that a BoBI was significantly more efficient (faster) and useful compared to a ToC or Full-Text Search tool for finding information in an e-book environment

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Development of inorganic membranes for gas separation

Hydrogen for commercial coal liquefaction processes may be provided by a coal gasification plant operated to maximize hydrogen production. Hydrogen is a major chemical requirement for coal liquefaction, and the use of liquefaction by-products such as mineral ash residue as feed to the gasifier can improve the overall process efficiency and economics. Also, recovery of hydrogen from gaseous streams in the coal liquefaction plant can have a significant impact on coal liquefaction process economics. In these hydrogen production scenarios, there is a need to improve the quality of the hydrogen produced by separating the other impurity gases from it. The DOE-Fossil Energy AR TD Materials Program is presently developing inorganic membranes for gas separation, including the recovery of valuable resources such as hydrogen from hot-gas streams. A summary of efforts to produce alumina membranes with mean pore radii <5 {angstrom} is presented as well as a status report on declassification of this important technology. 2 refs., 7 figs

Separating hydrogen from coal gasification gases with alumina membranes

Synthesis gas produced in coal gasification processes contains hydrogen, along with carbon monoxide, carbon dioxide, hydrogen sulfide, water, nitrogen, and other gases, depending on the particular gasification process. Development of membrane technology to separate the hydrogen from the raw gas at the high operating temperatures and pressures near exit gas conditions would improve the efficiency of the process. Tubular porous alumina membranes with mean pore radii ranging from about 9 to 22 {Angstrom} have been fabricated and characterized. Based on hydrostatic tests, the burst strength of the membranes ranged from 800 to 1600 psig, with a mean value of about 1300 psig. These membranes were evaluated for separating hydrogen and other gases. Tests of membrane permeabilities were made with helium, nitrogen, and carbon dioxide. Measurements were made at room temperature in the pressure range of 15 to 589 psi. Selected membranes were tested further with mixed gases simulating a coal gasification product gas. 5 refs., 7 figs