Mapping genetic determinants of host susceptibility to Pseudomonas aeruginosa lung infection in mice.

Background: P. aeruginosa is one of the top three causes of opportunistic human bacterial infections. The remarkable variability in the clinical outcomes of this infection is thought to be associated with genetic predisposition. However, the genes underlying host susceptibility to P. aeruginosa infection are still largely unknown. Results: As a step towards mapping these genes, we applied a genome wide linkage analysis approach to a mouse model. A large F2 intercross population, obtained by mating P. aeruginosa-resistant C3H/HeOuJ, and susceptible A/J mice, was used for quantitative trait locus (QTL) mapping. The F2 progenies were challenged with a P. aeruginosa clinical strain and monitored for the survival time up to 7 days post-infection, as a disease phenotype associated trait. Selected phenotypic extremes of the F2 distribution were genotyped with high-density single nucleotide polymorphic (SNP) markers, and subsequently QTL analysis was performed. A significant locus was mapped on chromosome 6 and was named P. aeruginosa infection resistance locus 1 (Pairl1). The most promising candidate genes, including Dok1, Tacr1, Cd207, Clec4f, Gp9, Gata2, Foxp1, are related to pathogen sensing, neutrophils and macrophages recruitment and inflammatory processes. Conclusions: We propose a set of genes involved in the pathogenesis of P. aeruginosa infection that may be explored to complement human studie

Effect of fluorination pattern and extent on the properties of PCDTBT derivatives

Herein, we report the synthesis of a series of fluorinated dithienyl carbazole-alt-benzothiadiazoles (PCDTBT analogues) and the characterisation of their optical, electrochemical, thermal and molecular organisation in the solid state. The polymers were decorated with fluorine on either the benzothiadiazole unit, carbazole unit or both to yield PCDTffBT, PCffDTBT and PCffDTffBT, respectively. The copolymers displayed decomposition temperatures in excess of 350 1C. PCDTffBT, PCffDTBT and PCffDTffBT displayed optical band gaps of 1.86, 1.82 and 1.88 eV, respectively. It was speculated this was a consequence of the higher molecular weight of PCffDTBT relative to the other polymers. PCffDTBT and PCffDTffBT displayed shallower HOMO levels relative to PCDTffBT; a consequence of fluorinating the carbazole-donor moiety. XRD studies confirmed that fluorinating the benzothiadiazoleacceptor moiety improves molecular ordering by promoting p–p stacking of polymer backbones in solid state. Interestingly, fluorinating the carbazole-donor unit does not improve p–p stacking of polymer backbones

The use of early design tools in engineering processes : a comparative case study

Nowadays, product design is increasingly complex: not only must it answer customer needs through complex functions; it must also ensure traceability throughout the design process, keeping in mind that standards and stringent regulations must be complied with. Faced with new challenges, engineering practices have evolved to allow stakeholders to be able to manage projects in new work environments, especially during the early stages of design. After presenting a state of the art of early design tools used in product design and their integration in PLM context, we compare class diagrams for two of them : TDC software (Knowllence©) and RFLP module of CATIA V6 (Dassault Systems©). Then, our paper presents an experiment focusing on these tools, which aims to assess their usability, to evaluate and compare them. Users can raise issues, take note of which functionalities are appreciated, and provide qualitative feedback. We analyze the results obtained in this experiment and propose a comparison based on four topics: learnability, satisfaction of users, efficiency and error correction. Finally, we present some links between class diagrams and usability of the tools

Mapping liver fat female-dependent quantitative trait loci in collaborative cross mice

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the western world, with spectrum from simple steatosis to non-alcoholic steatohepatitis, which can progress to cirrhosis. NAFLD developments are known to be affected by host genetic background. Herein we emphasize the power of collaborative cross (CC) mouse for dissecting this complex trait and revealing quantitative trait loci (QTL) controlling hepatic fat accumulation in mice. 168 female and 338 male mice from 24 and 37 CC lines, respectively, of 18-20 weeks old, maintained on standard rodent diet, since weaning. Hepatic fat content was assessed, using dual DEXA scan in the liver. Using the available high-density genotype markers of the CC line, QTL mapping associated with percentage liver fat accumulation was performed. Our results revealed significant fatty liver accumulation QTL that were specifically, mapped in females. Two significant QTLs on chromosomes 17 and 18, with genomic intervals 3 and 2 Mb, respectively, were mapped. A third QTL, with a less significant P value, was mapped to chromosome 4, with genomic interval of 2 Mb. These QTLs were named Flal1-Flal3, referring to Fatty Liver Accumulation Locus 1-3, for the QTLs on chromosomes 17, 18, and 4, respectively. Unfortunately, no QTL was mapped with males. Searching the mouse genome database suggested several candidate genes involved in hepatic fat accumulation. Our results show that susceptibility to hepatic fat accumulations is a complex trait, controlled by multiple genetic factors in female mice, but not in male

Pyrene–benzothiadiazole-based copolymers for application in photovoltaic devices

The preparation and characterisation of four narrow band gap pyrene-benzothiadiazole based alternating copolymers is presented. An investigation of the impact of attaching different solubilising groups to the pyrene repeat units on the optical, electrochemical and thermal properties of the resulting materials was undertaken along with studies on the aggregation of polymer chains in the solid state. Unsurprisingly, polymers which had the smaller 2-ethylhexyl chains attached to the pyrene units (PPEH-DTBT and PPEH-DTffBT) displayed lower molecular weights relative to polymers with larger 2-hexyldecyl substituents (PPHD-DTBT and PPHD-DTffBT). Despite this, the 2-ethylhexyl substituted polymers displayed narrower optical band gaps relative to their analogous 2-hexyldecyl substituted polymers. Of all polymers synthesised, PPEH-DTBT displayed the lowest optical band gap (1.76 eV) in the series. All polymers display degradation temperatures in excess of 300°C. Polymers with smaller alkyl chains on the pyrene units display shallower HOMO levels which could be due to increased intramolecular charge transfer between the donor and acceptor units. Preliminary investigations on bulk heterojunction solar cells with a device structure ITO/PEDOT:PSS/Polymer:PC70BM/Ca/Al were undertaken. Polymer/PC70BM blend ratios of 1/3 were used in these studies and have indicated that PPEH-DTBT displayed the highest efficiency with a PCE of 1.86 %

From Functional Analysis to CAD Modelling Based on Knowledge Transformation Driven by the Design Process

Part 5: Modelling for PLMInternational audienceMost of industries currently spend too much time to find information on past product design process. This considerably reduces the time it can devote to innovation. The authors assume that the design process meta-model seems very interesting for modelling the design rational and then for accelerating information retrieval. Indeed, the model of the design process partly supports every resources involved in decision making activities (i.e. who, what, when, why, where, how). The authors therefore propose the use of a MBE architecture for driving the product modelling based on the design process model. The UML activity diagrams and the IDEFØ meta-model are linked for supporting automatic generation ofproduct models using specific transformation knowledge. The CAD model is partly generated from the product functional analysis

Improved efficiency in organic solar cells via conjugated polyelectrolyte additive in the hole transporting layer

An anionic conjugated polyelectrolyte poly[(9,9-bis(4-sulfonatobutyl sodium) fluorene-alt-phenylene)- ran-(4,7-di-2-thienyl-2,1,3-benzothiadiazole-alt-phenylene)] which exhibits good solubility in water was synthesised via Suzuki-cross coupling. This conjugated polyelectrolyte was used as an additive in the hole transporting layer within organic photovoltaic devices. There is an efficiency gain as a result of an improved carrier generation and charge transport across the interface into the hole transport layer when the work function of the hole transport later is well matched to the active layer of the solar cell. The best performances were achieved using 5 mg ml1 of the polyelectrolyte additive added to the hole transport layer solution in which case the average power conversion efficiency increased from 4.63% for reference devices without any additive to 5.26% when the additive is present which is a 13% improvement. The reproducibility of device performance was also significantly improved with the variation in fill factor, short circuit current and open circuit voltage all improving when the additive is present

Chasing the genes that control resistance to gastrointestinal nematodes

The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite’s antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have beenproposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes

Polymer-based solar cells having an active area of 1.6 cm2 fabricated via spray coating

We demonstrate the fabrication of polymersolar cells in which both a PEDOT:PSS hole transport and a PCDTBT:PC71BM photoactive layer are deposited by spray-casting. Two device geometries are explored, with devices having a pixel area of 165 mm2 attaining a power conversion efficiency of 3.7%. Surface metrology indicates that the PEDOT:PSS and PCDTBT:PC71BM layers have a roughness of 2.57 nm and 1.18 nm over an area of 100 μm2. Light beam induced current mapping reveals fluctuations in current generation efficiency over length-scales of ∼2 mm, with the average photocurrent being 75% of its maximum value

Thermally stable solution processed vanadium oxide as a hole extraction layer in organic solar cells

Low-temperature solution-processable vanadium oxide (V2Ox) thin films have been employed as hole extraction layers (HELs) in polymer bulk heterojunction solar cells. V2Ox films were fabricated in air by spin-coating vanadium(V) oxytriisopropoxide (s-V2Ox) at room temperature without the need for further thermal annealing. The deposited vanadium(V) oxytriisopropoxide film undergoes hydrolysis in air, converting to V2Ox with optical and electronic properties comparable to vacuum-deposited V2O5. When s-V2Ox thin films were annealed in air at temperatures of 100 °C and 200 °C, OPV devices showed similar results with good thermal stability and better light transparency. Annealing at 300 °C and 400 °C resulted in a power conversion efficiency (PCE) of 5% with a decrement approximately 15% lower than that of unannealed films; this is due to the relative decrease in the shunt resistance (Rsh) and an increase in the series resistance (Rs) related to changes in the oxidation state of vanadium