Processible nanostructured materials with electrical conductivity and magnetic susceptibility: Preparation and properties of maghemite polyaniline nanocomposite films

We here present a versatile process for the preparation of maghemite/polyaniline (gamma-Fe2O3/ PAn) nanocomposite films with macroscopic processibility, electrical conductivity, and magnetic susceptibility. The gamma-Fe2O3 nanoparticles are coated and the PAn chains are doped by anionic surfactants of omega-methoxypoly(ethylene glycol) phosphate (PEOPA), 4-dodecylbenzenesulfonic acid (DBSA), and 10-camphorsulfonic acid (CSA). Both the coated gamma-Fe2O3 and the doped PAn are soluble in common organic solvents, and casting of the homogeneous solutions gives free-standing nanocomposite films with gamma-Fe2O3 contents up to similar to 50 wt %. The morphology of the gamma-Fe2O3 nanoparticles are characterized by transmission electron microscopy, UV-vis spectroscopy, and X-ray diffractometry. The gamma-Fe2O3/PAn films prepared from chloroform/m-cresol solutions of DBSA-coated gamma-Fe2O3 and CSA-doped PAn are conductive (sigma = 82-237 S/cm) and superpapamagnetic, exhibiting no hysteresis at room temperature. The zero-field-cooled magnetization experiment reveals that the nanocomposite containing 20.8 wt % gamma-Fe2O3 has a blocking temperature (T-b) in the temperature region of 63-83 K.

Study on the bond covalency and bond susceptibility in NdCr1-xMxO3 (M=Mn, Fe, Co)

Bond covalency, bond susceptibility and macroscopic linear susceptibility in NdCr1-xMxO3 (M=Mn, Fe, Co, 0.0 less than or equal to x less than or equal to 1.0) are investigated by complex chemical bond theory. The results indicate the bond covalencies are insensitive to the doping level. With the increasing doping level, the macroscopic linear susceptibilities increase for M=Mn, Fe, decrease for M=Co. The valence state of Cr can be strongly influenced by the properties of the doping ions.

The polymorphism of lysozyme gene in Zhikong scallop (Chlamys farreri) and its association with susceptibility/resistance to Listonella anguillarum

Lysozyme functions as a crucial biodefence effector against the infection of bacterial pathogens in innate immunity. The nucleotide sequence polymorphisms in promoter region of a nuclear goose type lysozyme gene from Zhikong scallop Chlamys farreri (designated as CFLysG) were investigated to explore their association with susceptibility/resistance to Listonella anguillarum infection. Eight sites of single nucleotide polymorphisms (SNPs) and two sites of insert-deletion (ins-del) polymorphisms were identified in the promoter region of CFLysG. Two of them, -753 TATCTCGATCAGG ins-del polymorphism and -391 A-G SNP were selected to analyze their distribution in the susceptible and resistant stocks, which were identified according to the survival time after L. anguillarum challenge. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), two genotypes were found at each site, which were ins/del and ins/ins at locus -753, and A/A and A/G at locus -391, respectively. The -753 ins/del genotype was more prevalent in the resistant stock than that in the susceptible stock, 30% vs 16.67% in frequency, but there was no significant difference in the frequency distribution between these two stocks (P=0.15). In contrast, the frequency of -391A/G genotype in the resistant stock was significantly higher (30%) than that in the susceptible stock (7.14%) (P=0.007), indicating a significant association with the resistance of Zhikong scallop to L anguillarum. To confirm the presumption, another independent challenge experiment was performed, in which the cumulative mortality of scallops with -391 A/A genotype (96.8%) was significantly higher than those with -391 A/G genotype (64.5%) (P=0.001), which further validate the association between -391 A/G genotype and the resistance of Zhikong scallop to L anguillarum. These results suggested that the -391 A/G could be a potential marker applied in future selection of Zhikong scallop with enhanced resistance to L anguillarum. (C) 2008 Elsevier Ltd. All rights reserved.

滑坡泥石流信息遥感获取与空间预测

On the issue of geological hazard evaluation（GHE）, taking remote sensing and GIS systems as experimental environment, assisting with some programming development, this thesis combines multi-knowledges of geo-hazard mechanism, statistic learning, remote sensing (RS), high-spectral recognition, spatial analysis, digital photogrammetry as well as mineralogy, and selects geo-hazard samples from Hong Kong and Three Parallel River region as experimental data, to study two kinds of core questions of GHE, geo-hazard information acquiring and evaluation model. In the aspect of landslide information acquiring by RS, three detailed topics are presented, image enhance for visual interpretation, automatic recognition of landslide as well as quantitative mineral mapping. As to the evaluation model, the latest and powerful data mining method, support vector machine (SVM), is introduced to GHE field, and a serious of comparing experiments are carried out to verify its feasibility and efficiency. Furthermore, this paper proposes a method to forecast the distribution of landslides if rainfall in future is known baseing on historical rainfall and corresponding landslide susceptibility map. The details are as following: (a) Remote sensing image enhancing methods for geo-hazard visual interpretation. The effect of visual interpretation is determined by RS data and image enhancing method, for which the most effective and regular technique is image merge between high-spatial image and multi-spectral image, but there are few researches concerning the merging methods of geo-hazard recognition. By the comparing experimental of six mainstream merging methods and combination of different remote sensing data source, this thesis presents merits of each method ,and qualitatively analyzes the effect of spatial resolution, spectral resolution and time phase on merging image. (b) Automatic recognition of shallow landslide by RS image. The inventory of landslide is the base of landslide forecast and landslide study. If persistent collecting of landslide events, updating the geo-hazard inventory in time, and promoting prediction model incessantly, the accuracy of forecast would be boosted step by step. RS technique is a feasible method to obtain landslide information, which is determined by the feature of geo-hazard distribution. An automatic hierarchical approach is proposed to identify shallow landslides in vegetable region by the combination of multi-spectral RS imagery and DEM derivatives, and the experiment is also drilled to inspect its efficiency. (c) Hazard-causing factors obtaining. Accurate environmental factors are the key to analyze and predict the risk of regional geological hazard. As to predict huge debris flow, the main challenge is still to determine the startup material and its volume in debris flow source region. Exerting the merits of various RS technique, this thesis presents the methods to obtain two important hazard-causing factors, DEM and alteration mineral, and through spatial analysis, finds the relationship between hydrothermal clay alteration minerals and geo-hazards in the arid-hot valleys of Three Parallel Rivers region. (d) Applying support vector machine (SVM) to landslide susceptibility mapping. Introduce the latest and powerful statistical learning theory, SVM, to RGHE. SVM that proved an efficient statistic learning method can deal with two-class and one-class samples, with feature avoiding produce ‘pseudo’ samples. 55 years historical samples in a natural terrain of Hong Kong are used to assess this method, whose susceptibility maps obtained by one-class SVM and two-class SVM are compared to that obtained by logistic regression method. It can conclude that two-class SVM possesses better prediction efficiency than logistic regression and one-class SVM. However, one-class SVM, only requires failed cases, has an advantage over the other two methods as only "failed" case information is usually available in landslide susceptibility mapping. (e) Predicting the distribution of rainfall-induced landslides by time-series analysis. Rainfall is the most dominating factor to bring in landslides. More than 90% losing and casualty by landslides is introduced by rainfall, so predicting landslide sites under certain rainfall is an important geological evaluating issue. With full considering the contribution of stable factors (landslide susceptibility map) and dynamic factors (rainfall), the time-series linear regression analysis between rainfall and landslide risk mapis presented, and experiments based on true samples prove that this method is perfect in natural region of Hong Kong. The following 4 practicable or original findings are obtained: 1) The RS ways to enhance geo-hazards image, automatic recognize shallow landslides, obtain DEM and mineral are studied, and the detailed operating steps are given through examples. The conclusion is practical strongly. 2) The explorative researching about relationship between geo-hazards and alteration mineral in arid-hot valley of Jinshajiang river is presented. Based on standard USGS mineral spectrum, the distribution of hydrothermal alteration mineral is mapped by SAM method. Through statistic analysis between debris flows and hazard-causing factors, the strong correlation between debris flows and clay minerals is found and validated. 3) Applying SVM theory (especially one-class SVM theory) to the landslide susceptibility mapping and system evaluation for its performance is also carried out, which proves that advantages of SVM in this field. 4) Establishing time-serial prediction method for rainfall induced landslide distribution. In a natural study area, the distribution of landslides induced by a storm is predicted successfully under a real maximum 24h rainfall based on the regression between 4 historical storms and corresponding landslides.

滑坡和泥石流致灾条件叠合技术及风险分析-以川藏公路然乌至鲁朗段为例

As one part of national road No. 318, Sichuan-Tibet (Chengdu-Lasha) Highway is one of traffic life lines connecting Tibet municipality to the inland, which is very important to the economic development of Tibet. In addition, it is still an important national defence routeway, with extremely important strategic position on maintaining the stability and solidarity of Tibet municipality and consolidating national defence. Particular geological condition, terrain and landform condition and hydrometeorological condition induce large-scale debris flows and landslides (including landslips) and the like geological hazards frequently occur along the highway. High frequency geological hazards not only result in high casualties and a great property loss, but also block traffic at every turn, obstructing the Sichuan-Tibet highway seriously. On the basis of considerable engineering geological investigation and analysis to the relative studying achievements of predecessors, it is found that one of the dominating reason incurring landslides or debris flows again and again in a place is that abundant loose materials are accumulated in valleys and slopes along the highway. Taking landslides' and debris flows along Ranwu-Lulang section of Sichuan-Tibet highway as studying objects, the sources and cause of formation of loose accumulation materials in the studying area are analyzed in detail, the major hazard-inducing conditions, hazard, dynamic risk, prediction of susceptibility degree of landslides and debris flows, and the relations between landslides and debris flows and various hazard-inducing conditions are systematically researched in this paper. All of these will provide scientific foundation for the future highway renovating and reducing and preventing geological hazards. For the purpose of quantitatively analyzing landslide and debris flow hazards, the conception of entropy and information entropy are extended, the conception of geological hazard entropy is brought forward, and relevant mathematics model is built. Additionally, a new approach for the dynamic risk analysis of landslide and debris flow is put forward based on the dynamic characteristics of the hazard of hazard-inducings and the vulnerability of hazard-bearings. The formation of landslide and debris flow is a non-linear process, which is synthetically affected by various factors, and whose formation mechanics is extremely complex. Aiming at this question, a muli-factors classifying and overlapping technique is brought forward on the basis of engineering geomechanics meta-synthesis (EGMS) thought and approach, and relevant mathematics model is also built to predict the susceptibility degree of landslide or debris flow. The example analysis result proves the validity of this thought and approach. To studying the problem that whether the formation and space distribution of landslides and debris flows are controlled by one or several hazard-inducing conditions, the theme graphics of landslides and debris flows hazard and various hazard-inducing conditions are overlapped to determine the relationship between hazard and hazard-inducing conditions. On this basis, the semi-quantitative engineering zonation of the studying area is carried out. In addition, the overlapping analysis method of the hazard-indue ing conditions of landslides and debris flows based on "digital graphics system" is advanced to orderly organize and effectively manage the spatial and attributive data of hazard and hazard-inducing conditions theme graphics, and to realize the effectively combination of graphics, images and figures.

三峡库区滑坡的时空分布、成因及其预报模式

Landslides are widely distributed along the main stream banks of the Three Gorges Reservoir area. Especially with the acceleration of the human economic activities in the recent 30 years, the occurrence of landslide hazards in the local area trends to be more serious. Because of the special geological, topographic and climatic conditions of the Three Gorges areas, many Paleo-landslides are found along the gentle slope terrain of the population relocation sites. Under the natural condition, the Paleo-landslides usually keep stable. The Paleo-landslides might revive while they are influenced under the strong rainfall, water storage and migration engineering disturbance. Therefore, the prediction and prevention of landslide hazards have become the important problem involving with the safety of migration engineering of the Three Gorges Reservoir area.The past research on the landslides of the Three Gorges area is mainly concentrated on the stability analysis of individual landslide, and importance was little attached to the knowledge on the geological environment background of the formation of regional landslides. So, the relationship between distribution and evolution of landslides and globe dynamic processes was very scarce in the past research. With further study, it becomes difficult to explain the reasons for the magnitude and frequency of major geological hazards in terms of single endogenic or exogenic processes. It is possible to resolve the causes of major landslides in the Three Gorges area through the systematic research of regional tectonics and river evolution history.In present paper, based on the view of coupling of earth's endogenic and exogenic processes, the author researches the temporal and spacial distribution and formation evolution of major landslides(Volume^lOOX 104m3) in the Three Gorges Reservoir area through integration of first-hand sources statistics, .geological evolution history, isotope dating and numerical simulation method etc. And considering the main formation factors of landslides (topography, geology and rainfall condition), the author discusses the occurrence probability and prediction model of rainfall induced landslides.The distribution and magnitude of Paleo-landslides in the Three Gorges area is mainly controlled by lithology, geological structure, bank slope shape and geostress field etc. The major Paleo-landslides are concentrated on the periods 2.7-15.0 X 104aB.R, which conrresponds to the warm and wettest Paleoclimate stages. In the same time, the Three Gorges area experiences with the quickest crust uplift phase since 15.0X 104aB.P. It is indicated that the dynamic factor of polyphase major Paleo-landslides is the coupling processes of neotectonic movement and Quaternary climate changes. Based on the numerical simulation results of the formation evolution of Baota landslide, the quick crust uplift makes the deep river incision and the geostress relief causes the rock body of banks flexible. Under the strong rainfall condition, the pore-water pressure resulted from rain penetration and high flood level can have the shear strength of weak structural plane decrease to a great degree. Therefore, the bank slope is easy to slide at the slope bottom where shear stress concentrates. Finally, it forms the composite draught-traction type landslide of dip stratified rocks.The susceptibility idea for the rainfall induced landslide is put forward in this paper and the degree of susceptibility is graded in terms of the topography and geological conditions of landslides. Base on the integration with geological environment factors and rainfall condition, the author gives a new probabilistic prediction model for rainfall induced landslides. As an example from Chongqing City of the Three Gorges area, selecting the 5 factors of topography, lithology combination, slope shape, rock structure and hydrogeology and 21 kinds of status as prediction variables, the susceptibility zonation is carried out by information methods. The prediction criterion of landslides is established by two factors: the maximum 24 hour rainfall and the antecedent effective precipitation of 15 days. The new prediction model is possible to actualize the real-time regional landslide prediction and improve accuracy of landslide forecast.

Victimisation of street children in Addis Ababa: factors of resilience and susceptibility

Cross-cultural variations in conceptions of childhood are discussed, particularly with regard to child abuse and child labour. Regardless of cultural background, a universal minimum standard of child rearing is required. The street child literature is reviewed, culminating in an analysis of Ethiopian street children. Theoretically this work is informed by victimology. Concepts shared by victimology and rational choice perspective are discussed, after Fattah (1993a). Victim surveys are described, highlighting their accuracy of crime estimates. Juvenile prostitution, runaways and rape are examined, particularly with regard to their relevance in Addis Ababa. Fifty five male and 135 female street children were interviewed. Interviews with boys focused on delinquency. An age-related pattern emerged, with younger boys less likely to drink, chew khat, steal or be sexually active. Interviews with street girls focused on the differences between girls living on the streets (girls of the street), girls working on the streets (girls on the street) and a sample of homebased girls. Girls of the street come to the street come to the streets for many reasons. Conflicts with a parent or guardian account for almost 50%. They are highly vulnerable to sexual assaults, particularly those 43% who have worked as prostitutes. Girls on the street experience considerably less victimisation. Urban poor girls live in socio-economic circumstances akin to girls on the street but enjoy almost universal protection from victimisation because they do not spend time on the streets. Unprotected by the stability which a family provides, girls of the street experience high victimisation levels. Such victimisation is often the result of reliance on types of work, such as prostitution, which brings the girls into contact with exploitative adults. Resistance to such victimisation is provided by a secure place to sleep, companions, and relatively safe types of work. Such protective factors are more readily available to family based children as compared to those living independently.

Investigation of the genetic susceptibility to osteoporosis in the Irish population

Osteoporosis is a complex skeletal disorder characterized by compromised bone strength. Variation in bone mineral density (BMD) is a contributing factor. The aim of this research as to select informative single nucleotide polymorphisms (SNPs) in potential candidate genes from loci suggestively linked to BMD variation for fine mapping. The gene regulated by oestrogen in breast cancer 1 (GREB1), located at 2p25.1, was selected. GREB1 transcription is initiated early in the oestrogen receptor alpha regulated pathway. There was significant association between GREB1_03 and BMD variation at the lumbar spine and femoral neck (FN) in the discovery cohort. Significant association was observed between GREB1_04 and FN BMD in the replication cohort. The development and differentiation enhancing factor 2, the integrin cytoplasmic domain associated protein 1 and A-disintegrin and metalloprotease 17 were selected due to their respective roles in cell mobility and adhesion. There was no linkage or association observed between the Chr2 cluster SNPs and BMD. Two factors in bone remodelling are the attraction of bone cell precursors and endocrine regulation of the process, primarily through the action of parathyroid hormone (PTH). The C-C chemokine receptor type 3 (CCR3) encodes a CC chemokine receptor expressed in osteoclast precursors. The PTH receptor type 1 (PTHR1) encodes a G-protein coupled receptor for PTH. Association was observed between CCR3 haplotypes and BMD variation at the FN. There was no linkage or association observed between PTHR1 SNPs and BMD variation. Population genetic studies with complex phenotypes endeavour to elucidate the traits genetic architecture. This study presents evidence of association between GREB1 and BMD variation and as such, introduces GREB1 as a novel gene target for osteoporosis genetics studies. It affirms that common genomic variants in PTHR1 are not associated with BMD variation in Caucasians and supports the evidence that CCR3 may be contributing to BMD variation

Application of semi-automated strain analysis techniques and anisotropy of magnetic susceptibility in fold and thrust belts

Quantitative analysis of penetrative deformation in sedimentary rocks of fold and thrust belts has largely been carried out using clast based strain analysis techniques. These methods analyse the geometric deviations from an original state that populations of clasts, or strain markers, have undergone. The characterisation of these geometric changes, or strain, in the early stages of rock deformation is not entirely straight forward. This is in part due to the paucity of information on the original state of the strain markers, but also the uncertainty of the relative rheological properties of the strain markers and their matrix during deformation, as well as the interaction of two competing fabrics, such as bedding and cleavage. Furthermore one of the single largest setbacks for accurate strain analysis has been associated with the methods themselves, they are traditionally time consuming, labour intensive and results can vary between users. A suite of semi-automated techniques have been tested and found to work very well, but in low strain environments the problems discussed above persist. Additionally these techniques have been compared to Anisotropy of Magnetic Susceptibility (AMS) analyses, which is a particularly sensitive tool for the characterisation of low strain in sedimentary lithologies.

A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.

Although it has recently been shown that A/J mice are highly susceptible to Staphylococcus aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. Using chromosome substitution strains (CSS), we found that loci on chromosomes 8, 11, and 18 influence susceptibility to S. aureus sepsis in A/J mice. We then used two candidate gene selection strategies to identify genes on these three chromosomes associated with S. aureus susceptibility, and targeted genes identified by both gene selection strategies. First, we used whole genome transcription profiling to identify 191 (56 on chr. 8, 100 on chr. 11, and 35 on chr. 18) genes on our three chromosomes of interest that are differentially expressed between S. aureus-infected A/J and C57BL/6J. Second, we identified two significant quantitative trait loci (QTL) for survival post-infection on chr. 18 using N(2) backcross mice (F(1) [C18A]xC57BL/6J). Ten genes on chr. 18 (March3, Cep120, Chmp1b, Dcp2, Dtwd2, Isoc1, Lman1, Spire1, Tnfaip8, and Seh1l) mapped to the two significant QTL regions and were also identified by the expression array selection strategy. Using real-time PCR, 6 of these 10 genes (Chmp1b, Dtwd2, Isoc1, Lman1, Tnfaip8, and Seh1l) showed significantly different expression levels between S. aureus-infected A/J and C57BL/6J. For two (Tnfaip8 and Seh1l) of these 6 genes, siRNA-mediated knockdown of gene expression in S. aureus-challenged RAW264.7 macrophages induced significant changes in the cytokine response (IL-1 beta and GM-CSF) compared to negative controls. These cytokine response changes were consistent with those seen in S. aureus-challenged peritoneal macrophages from CSS 18 mice (which contain A/J chromosome 18 but are otherwise C57BL/6J), but not C57BL/6J mice. These findings suggest that two genes, Tnfaip8 and Seh1l, may contribute to susceptibility to S. aureus in A/J mice, and represent promising candidates for human genetic susceptibility studies.

Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury.

Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of beta(2)AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because beta(2)ARs, unlike beta(1)ARs, couple to G(i) as well as G(s), we pretreated mice with the G(i) inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either betaARK1 (TGbetaARK1) or a betaARK1 inhibitor (TGbetaARKct). Recoveries of function, ATP, and phosphocreatine were higher in TGbetaARK1 hearts than in wild-type hearts. Despite basal contractility being elevated in TGbetaARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, beta(2)AR overexpression increased ischemic injury, whereas betaARK1 overexpression was protective. Ischemic injury in the beta(2)AR overexpressors was exacerbated by PTX treatment, implying that it was G(s) not G(i) activity that enhanced injury. Unlike beta(2)AR overexpression, basal contractility was increased by betaARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.

Functional annotation signatures of disease susceptibility loci improve SNP association analysis.

BACKGROUND: Genetic association studies are conducted to discover genetic loci that contribute to an inherited trait, identify the variants behind these associations and ascertain their functional role in determining the phenotype. To date, functional annotations of the genetic variants have rarely played more than an indirect role in assessing evidence for association. Here, we demonstrate how these data can be systematically integrated into an association study's analysis plan. RESULTS: We developed a Bayesian statistical model for the prior probability of phenotype-genotype association that incorporates data from past association studies and publicly available functional annotation data regarding the susceptibility variants under study. The model takes the form of a binary regression of association status on a set of annotation variables whose coefficients were estimated through an analysis of associated SNPs in the GWAS Catalog (GC). The functional predictors examined included measures that have been demonstrated to correlate with the association status of SNPs in the GC and some whose utility in this regard is speculative: summaries of the UCSC Human Genome Browser ENCODE super-track data, dbSNP function class, sequence conservation summaries, proximity to genomic variants in the Database of Genomic Variants and known regulatory elements in the Open Regulatory Annotation database, PolyPhen-2 probabilities and RegulomeDB categories. Because we expected that only a fraction of the annotations would contribute to predicting association, we employed a penalized likelihood method to reduce the impact of non-informative predictors and evaluated the model's ability to predict GC SNPs not used to construct the model. We show that the functional data alone are predictive of a SNP's presence in the GC. Further, using data from a genome-wide study of ovarian cancer, we demonstrate that their use as prior data when testing for association is practical at the genome-wide scale and improves power to detect associations. CONCLUSIONS: We show how diverse functional annotations can be efficiently combined to create 'functional signatures' that predict the a priori odds of a variant's association to a trait and how these signatures can be integrated into a standard genome-wide-scale association analysis, resulting in improved power to detect truly associated variants.

Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify genetic determinants of susceptibility to S. aureus, and evaluate their function with regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes was found to be significantly associated with susceptibility to S. aureus infection. Of these 422 genes, whole genome transcription profiling identified five genes (Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1) that were significantly differentially expressed in a) S. aureus -infected susceptible (A/J) vs. resistant (C57BL/6J) mice and b) humans with S. aureus blood stream infection vs. healthy subjects. Three of these genes (Dcaf7, Dusp3, and Psme3) were down-regulated in susceptible vs. resistant mice at both pre- and post-infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3 induced significant increases of cytokine production in S. aureus-challenged RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) through enhancing NF-κB signaling activity. Similar increases in cytokine production and NF-κB activity were also seen in BMDMs from CSS11 (C57BL/6J background with chromosome 11 from A/J), but not C57BL/6J. These findings suggest that Dusp3 and Psme3 contribute to S. aureus infection susceptibility in A/J mice and play a role in human S. aureus infection.