Preparation of northern mid-continent petroleum atlas

Project will develop a prototype for a digital and hard-copy atlas of petroleum fields and reservoirs in the northern Mid-continent region. A limited number of reservoirs in Kansas are to be included in the prototype project, but the goal is to expand beyond the prototype atlas to include significant reservoirs representing the major plays in Kansas, Nebraska, South Dakota, North Dakota, the Williston basin portion of Montana, the Denver-Julesburg basin of eastern Colorado and southeastern Colorado. Primary products of the prototype atlas will be on-line accessible digital data bases covering two selected petroleum plays in Kansas. `Pages` and data schema for the first field studies of the atlas have been developed and are accessible through the World-Wide-Web. The atlas structure includes access to geologic, geophysical and production information at levels from the regional, to the field to the individual well. Several approaches have been developed that provide efficient and flexible screening and search procedures. The prototype of the digital atlas is accessible through the Kansas Geological Survey Petroleum Research Section (PRS) HomePage (The Universal Resource Locator [URL] is http://www.kgs. ukans.edu/PRS/PRS.html). The DPA HomePage is available directly at http://www.kg.ukans.edu/DPA/dpaHome.html. Technology transfer is underway through the use of monthly electronic updates and the on- line availability of DPA products. Quarterly Progress Reports are posted on the digital Petroleum Atlas HomePage

The Planetary Nebula Luminosity Function at the Dawn of Gaia

The [O III] 5007 Planetary Nebula Luminosity Function (PNLF) is an excellent extragalactic standard candle. In theory, the PNLF method should not work at all, since the luminosities of the brightest planetary nebulae (PNe) should be highly sensitive to the age of their host stellar population. Yet the method appears robust, as it consistently produces < 10% distances to galaxies of all Hubble types, from the earliest ellipticals to the latest-type spirals and irregulars. It is therefore uniquely suited for cross-checking the results of other techniques and finding small offsets between the Population I and Population II distance ladders. We review the calibration of the method and show that the zero points provided by Cepheids and the Tip of the Red Giant Branch are in excellent agreement. We then compare the results of the PNLF with those from Surface Brightness Fluctuation measurements, and show that, although both techniques agree in a relative sense, the latter method yields distances that are ~15% larger than those from the PNLF. We trace this discrepancy back to the calibration galaxies and argue that, due to a small systematic error associated with internal reddening, the true distance scale likely falls between the extremes of the two methods. We also demonstrate how PNLF measurements in the early-type galaxies that have hosted Type Ia supernovae can help calibrate the SN Ia maximum magnitude-rate of decline relation. Finally, we discuss how the results from space missions such as Kepler and Gaia can help our understanding of the PNLF phenomenon and improve our knowledge of the physics of local planetary nebulae.Comment: 12 pages, invited review at the conference "The Fundamental Cosmic Distance Scale: State of the Art and Gaia Perspective", to appear in Astrophysics and Space Scienc

Neuronal pentraxin 2 : a synapse-derived CSF biomarker in genetic frontotemporal dementia

Introduction: Synapse dysfunction is emerging as an early pathological event in frontotemporal dementia (FTD), however biomarkers are lacking. We aimed to investigate the value of cerebrospinal fluid (CSF) neuronal pentraxins (NPTXs), a family of proteins involved in homeostatic synapse plasticity, as novel biomarkers in genetic FTD. Methods: We included 106 presymptomatic and 54 symptomatic carriers of a pathogenic mutation in GRN, C9orf72 or MAPT, and 70 healthy non-carriers participating in the Genetic Frontotemporal dementia Initiative (GENFI), all of whom had at least one CSF sample. We measured CSF concentrations of NPTX2 using an in-house ELISA, and NPTX1 and NPTX receptor (NPTXR) by Western blot. We correlated NPTX2 with corresponding clinical and neuroimaging datasets as well as with CSF neurofilament light chain (NfL) using linear regression analyses. Results: Symptomatic mutation carriers had lower NPTX2 concentrations (median 643 pg/mL, IQR (301-872)) than presymptomatic carriers (1003 pg/mL (624-1358), p&lt;0.001) and non-carriers (990 pg/mL (597-1373), p&lt;0.001) (corrected for age). Similar results were found for NPTX1 and NPTXR. Among mutation carriers, NPTX2 concentration correlated with several clinical disease severity measures, NfL and grey matter volume of the frontal, temporal and parietal lobes, insula and whole brain. NPTX2 predicted subsequent decline in phonemic verbal fluency and Clinical Dementia Rating scale plus FTD modules. In longitudinal CSF samples, available in 13 subjects, NPTX2 decreased around symptom onset and in the symptomatic stage. Discussion: We conclude that NPTX2 is a promising synapse-derived disease progression biomarker in genetic FTD

Automated workflow-based exploitation of pathway databases provides new insights into genetic associations of metabolite profiles

Background: Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) that associate with clinical phenotypes, but these SNPs usually explain just a small part of the heritability and have relatively modest effect sizes. In contrast, SNPs that associate with metabolite levels generally explain a higher percentage of the genetic variation and demonstrate larger effect sizes. Still, the discovery of SNPs associated with metabolite levels is challenging since testing all metabolites measured in typical metabolomics studies with all SNPs comes with a severe multiple testing penalty. We have developed an automated workflow approach that utilizes prior knowledge of biochemical pathways present in databases like KEGG and BioCyc to generate a smaller SNP set relevant to the metabolite. This paper explores the opportunities and challenges in the analysis of GWAS of metabolomic phenotypes and provides novel insights into the genetic basis of metabolic variation through the re-analysis of published GWAS datasets. Results: Re-analysis of the published GWAS dataset from Illig et al. (Nature Genetics, 2010) using a pathway-based workflow (http://www.myexperiment.org/packs/319.html), confirmed previously identified hits and identified a new locus of human metabolic individuality, associating Aldehyde dehydrogenase family1 L1 (ALDH1L1) with serine/glycine ratios in blood. Replication in an independent GWAS dataset of phospholipids (Demirkan et al., PLoS Genetics, 2012) identified two novel loci supported by additional literature evidence: GPAM (Glycerol-3 phosphate acyltransferase) and CBS (Cystathionine beta-synthase). In addition, the workflow approach provided novel insight into the affected pathways and relevance of some of these gene-metabolite pairs in disease development and progression. Conclusions: We demonstrate the utility of automated exploitation of background knowledge present in pathway databases for the analysis of GWAS datasets of metabolomic phenotypes. We report novel loci and potential biochemical mechanisms that contribute to our understanding of the genetic basis of metabolic variation and its relationship to disease development and progression

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Social cognition impairment in genetic frontotemporal dementia within the GENFI cohort

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split into early and late groups) and symptomatic mutation carriers. Groups were compared using a linear regression model with bootstrapping, adjusting for age, sex, education, and for the FP recognition test, language. Neural correlates of social cognition deficits were explored using a voxel-based morphometry (VBM) study. All three of the symptomatic genetic groups were impaired on both tasks with no significant difference between them. However, prior to onset, only the late presymptomatic C9orf72 mutation carriers on the FER test were impaired compared to the control group, with a subanalysis showing differences particularly in fear and sadness. The VBM analysis revealed that impaired social cognition was mainly associated with a left hemisphere predominant network of regions involving particularly the striatum, orbitofrontal cortex and insula, and to a lesser extent the inferomedial temporal lobe and other areas of the frontal lobe. In conclusion, theory of mind and emotion processing abilities are impaired in familial FTD, with early changes occurring prior to symptom onset in C9orf72 presymptomatic mutation carriers. Future work should investigate how performance changes over time, in order to gain a clearer insight into social cognitive impairment over the course of the disease

Preparation of Northern Mid-Contient Petroleum Atlas.

As proposed, the second year program will continue and expand upon the Kansas elements of the original program, and provide improved on-line access to the prototype atlas. The second year of the program will result in a prototype digital atlas sufficient to demonstrate the approach and provide a permanent improvement in data access to Kansas operators. The ultimate goal of providing an interactive history-matching interface with a regional data base remains for future development as the program covers more geographic territory and the data base expands. The long-term goal is to expand beyond the prototype atlas to include significant reservoirs representing the major plays in Kansas, Nebraska, South Dakota, North Dakota, the Williston basin portion of Montana, the Denver-Julesberg basin of eastern Colorado and southeastern Colorado

Preparation of northern mid-continent petroleum. Quarterly report, July 1--September 20, 1996

Project will develop a prototype for a digital and hard-copy atlas of petroleum fields and reservoirs in the northern Mid-continent region. A limited number of reservoirs in Kansas are to be included in the prototype project,but the goal is to expand beyond the prototype atlas to include significant reservoirs representing the major plays in Kansas, Nebraska, south dakota, North Dakota, the Williston basin portion of Montana, the Denver-Julesburg basin of eastern Colorado and southeastern Colorado. Primary products of the prototype atlas will be on-line accessible digital data bases covering two selected petroleum plays in Kansas. ``Pages`` and data schema for the atlas overview and field studies have been developed and are accessible through the world-wide-web. The atlas structure includes access to geologic, geophysical and production information at levels from the national, to the regional, to the field to the individual well. Several approaches have been developed that provide efficient and flexible screening and search procedures. The prototype of the digital atlas is accessible through the Kansas Geological Survey Petroleum Research Section (PRS) HomePage (the Universal Resource Locator [URL] is http://www.kgs.ukans.edu/PRS/PRS.html). The Digital Petroleum Atlas (DPA) HomePage is available directly at http://www.kgs. ukans.edu/DPA/dpaHome.html. Technology transfer is underway through presentations at national and regional meetings and through the use of monthly electronic updates and the on-line availability of the DPA products. Project information and Quarterly Progress Reports are linked to the Digital Petroleum Atlas HomePage

Preparation of northern mid-continent petroleum atlas. Quarterly report, October 1, 1996--December 31, 1996

As proposed, the second year program will continue and expand upon the Kansas elements of the original program, and provide improved on-line access to the prototype atlas. The second year of the program will result in a prototype digital atlas sufficient to demonstrate the approach and to provide a permanent improvement in data access to Kansas operators. The ultimate goal of providing an interactive history-matching interface with a regional data base remains for future development as the program covers more geographic territory and the data base expands. As part of the first year project ``Pages`` and data schema for the atlas overview and field studies were developed and made accessible through the world-wide-web. The atlas structure includes access to geologic, geophysical and production information at levels from the natural, to the regional, to the field to the individual well. Several approaches have been developed that provide efficient and flexible screening and search procedures. The prototype of the digital atlas is accessible through the Kansas Geological Survey Petroleum Research Section (PRS) HomePage (the Universal Resource locator [URL] is http://www.kgs.ukans. edu/PRS/PRS.html). The Digital Petroleum Atlas (DPA) HomePage is available directly at http://www.kgs.ukans.edu/DPA/dpaHome.html