Intrinsic differences between backward and forward vehicle simulation models

Two common methods for predicting the energy usage in vehicles through mathematical\ua0simulation, the `backward\u27 and the `forward\u27 schemes, are discussed and compared in terms\ua0of what longitudinal vehicle behaviour they predict. In the backward scheme, the input driving\ua0cycle is initially assumed to be followed perfectly and therefore the vehicle speed is not a dynamic\ua0state. In the forward scheme, a driver model controls the vehicle in an attempt to follow the\ua0input driving cycle, and the vehicle speed is intrinsically a dynamic state. A theoretical study is\ua0made with a simple mathematical vehicle model, where it is shown that the two methods neither\ua0predict the same expected energy use nor energy variation. Next, the simulation model that isused for the CO2 rating of heavy-duty trucks in Europe, VECTO, is used as an example of the\ua0backward method, and an equivalent implementation in a forward scheme is attempted. Two\ua0numerical experiments are made with these models: a detailed study of the longitudinal vehicle\ua0behaviour on a reference mission; and a study of the predicted CO2 emissions on a family of\ua0stochastically generated missions. The conclusion is that the backward method is easier to use\ua0but the forward method has a greater potential to predict realistic behaviour

Alkali-wall interactions in a laboratory-scale reactor for chemical looping combustion studies

Alkali metal-containing compounds are readily released during thermal conversion of solid fuels, and may have both detrimental and beneficial effects on chemical looping combustion. Here, we characterize alkali interactions with the inner walls of a laboratory-scale reactor under oxidizing, reducing and inert conditions at temperatures up to 900 \ub0C. KCl aerosol particles are continuously introduced to the stainless steel reactor and the alkali concentration is measured on-line with a surface ionization detector. Aerosol particles evaporate at temperatures above 500 \ub0C and KCl molecules rapidly diffuse to the reactor wall. Up to 92% of the alkali reaching the wall below 700 \ub0C remains adsorbed, while re-evaporation is important at higher temperatures, where up to 74% remains adsorbed. Transient changes in alkali concentration are observed during repeated redox cycles, which are associated with changes in chemical composition of the wall material. Metal oxides on the reactor wall are partially depleted under reducing conditions, which allow for the formation of a new potassium-rich phase that is stable in a reducing atmosphere, but not under inert conditions. The observed wall effects are concluded to be extensive and include major transient effects depending on gas composition, and the implications for laboratory studies and improved experimental methodology are discussed

Variability of gene expression profiles in human blood and lymphoblastoid cell lines

BACKGROUND: Readily accessible samples such as peripheral blood or cell lines are increasingly being used in large cohorts to characterise gene expression differences between a patient group and healthy controls. However, cell and RNA isolation procedures and the variety of cell types that make up whole blood can affect gene expression measurements. We therefore systematically investigated global gene expression profiles in peripheral blood from six individuals collected during two visits by comparing five of the following cell and RNA isolation methods: whole blood (PAXgene), peripheral blood mononuclear cells (PBMCs), lymphoblastoid cell lines (LCLs), CD19 and CD20 specific B-cell subsets. RESULTS: Gene expression measurements were clearly discriminated by isolation method although the reproducibility was high for all methods (range rho = 0.90-1.00). The PAXgene samples showed a decrease in the number of expressed genes (P < 1*10(-16)) with higher variability (P < 1*10(-16)) compared to the other methods. Differentially expressed probes between PAXgene and PBMCs were correlated with the number of monocytes, lymphocytes, neutrophils or erythrocytes. The correlations (rho = 0.83; rho = 0.79) of the expression levels of detected probes between LCLs and B-cell subsets were much lower compared to the two B-cell isolation methods (rho = 0.98). Gene ontology analysis of detected genes showed that genes involved in inflammatory responses are enriched in B-cells CD19 and CD20 whereas genes involved in alcohol metabolic process and the cell cycle were enriched in LCLs. CONCLUSION: Gene expression profiles in blood-based samples are strongly dependent on the predominant constituent cell type(s) and RNA isolation method. It is crucial to understand the differences and variability of gene expression measurements between cell and RNA isolation procedures, and their relevance to disease processes, before application in large clinical studies

Coexpression Network Analysis in Abdominal and Gluteal Adipose Tissue Reveals Regulatory Genetic Loci for Metabolic Syndrome and Related Phenotypes

Metabolic Syndrome (MetS) is highly prevalent and has considerable public health impact, but its underlying genetic factors remain elusive. To identify gene networks involved in MetS, we conducted whole-genome expression and genotype profiling on abdominal (ABD) and gluteal (GLU) adipose tissue, and whole blood (WB), from 29 MetS cases and 44 controls. Co-expression network analysis for each tissue independently identified nine, six, and zero MetS–associated modules of coexpressed genes in ABD, GLU, and WB, respectively. Of 8,992 probesets expressed in ABD or GLU, 685 (7.6%) were expressed in ABD and 51 (0.6%) in GLU only. Differential eigengene network analysis of 8,256 shared probesets detected 22 shared modules with high preservation across adipose depots (DABD-GLU = 0.89), seven of which were associated with MetS (FDR P<0.01). The strongest associated module, significantly enriched for immune response–related processes, contained 94/620 (15%) genes with inter-depot differences. In an independent cohort of 145/141 twins with ABD and WB longitudinal expression data, median variability in ABD due to familiality was greater for MetS–associated versus un-associated modules (ABD: 0.48 versus 0.18, P = 0.08; GLU: 0.54 versus 0.20, P = 7.8×10−4). Cis-eQTL analysis of probesets associated with MetS (FDR P<0.01) and/or inter-depot differences (FDR P<0.01) provided evidence for 32 eQTLs. Corresponding eSNPs were tested for association with MetS–related phenotypes in two GWAS of >100,000 individuals; rs10282458, affecting expression of RARRES2 (encoding chemerin), was associated with body mass index (BMI) (P = 6.0×10−4); and rs2395185, affecting inter-depot differences of HLA-DRB1 expression, was associated with high-density lipoprotein (P = 8.7×10−4) and BMI–adjusted waist-to-hip ratio (P = 2.4×10−4). Since many genes and their interactions influence complex traits such as MetS, integrated analysis of genotypes and coexpression networks across multiple tissues relevant to clinical traits is an efficient strategy to identify novel associations

The Use of Genome-Wide eQTL Associations in Lymphoblastoid Cell Lines to Identify Novel Genetic Pathways Involved in Complex Traits

Peer reviewe

Run-Off Replication of Host-Adaptability Genes Is Associated with Gene Transfer Agents in the Genome of Mouse-Infecting Bartonella grahamii

The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms