Self-Potential Signals Generated by the Corrosion of Buried Metallic Objects with Application to Contaminant Plumes

Large-amplitude (\u3e100 mV) negative electric (self)-potential anomalies are often observed in the vicinity of buried metallic objects and ore bodies or over groundwater plumes associated with organic contaminants. To explain the physical and chemical mechanisms that generate such electrical signals, a controlled laboratory experiment was carried out involving two metallic cylinders buried with vertical and horizontal orientations and centered through and in the capillary fringe within a sandbox. The 2D and 3D self-potential (SP) data were collected at several time steps along with collocated pH and redox potential measurements. Large dipolar SP and redox potential anomalies developed in association with the progressive corrosion of the vertical pipe, although no anomalies were observed in the vicinity of the horizontal pipe. This discrepancy was due to the orientation of the pipes with the vertical pipe subjected to a significantly larger EH gradient. Accounting for the electrical conductivity distribution, the SP data were inverted to recover the source current density vector field using a deterministic least-squares 4D (time-lapse) finite-element modeling approach. These results were then used to retrieve the 3D distribution of the redox potential along the vertical metallic cylinder. The results of the inversion were found to be in excellent agreement with the measured distribution of the redox potential. This experiment indicated that passively recorded electrical signals can be used to nonintrusively monitor corrosion processes. In addition, vertical electrical potential profiles measured through a mature hydrocarbon contaminated site were consistent with the sandbox observations, lending support to the geobattery model over organic contaminant plumes

VKORC1 sequence variants associated with resistance to anticoagulant rodenticides in Irish populations of Rattus norvegicus and Mus musculus domesticus

While resistance to anticoagulant rodenticides is known to occur in many European populations of Norway rat and house mouse, to-date no data is available on the occurrence in Ireland of such resistance. No genetic evidence for the occurrence of resistance was found in 65 Norway rat samples analysed, indicative of an absence, or low prevalence, of resistance in rats in at least the Eastern region of the island of Ireland. The presence of two of the most commonly found amino acid substitutions Leu128Ser and Tyr139Cys associated with house mouse resistance to anticoagulant rodenticides was confirmed. The occurrence of two such mutations is indicative of the occurrence of resistance to anticoagulant rodenticides in house mice in the Eastern region of the island of Ireland

Sustained Vascular Endothelial Growth Factor Delivery Enhances Angiogenesis and Perfusion in Ischemic Hind Limb

We hypothesized that sustained delivery of vascular endothelial growth factor (VEGF) using a polymer [85:15 poly(lactide- co -glycolide) (PLG)] would enhance angiogenesis and improve perfusion of ischemic tissue.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41507/1/11095_2005_Article_5644.pd

MuSiC: Identifying mutational significance in cancer genomes

Massively parallel sequencing technology and the associated rapidly decreasing sequencing costs have enabled systemic analyses of somatic mutations in large cohorts of cancer cases. Here we introduce a comprehensive mutational analysis pipeline that uses standardized sequence-based inputs along with multiple types of clinical data to establish correlations among mutation sites, affected genes and pathways, and to ultimately separate the commonly abundant passenger mutations from the truly significant events. In other words, we aim to determine the Mutational Significance in Cancer (MuSiC) for these large data sets. The integration of analytical operations in the MuSiC framework is widely applicable to a broad set of tumor types and offers the benefits of automation as well as standardization. Herein, we describe the computational structure and statistical underpinnings of the MuSiC pipeline and demonstrate its performance using 316 ovarian cancer samples from the TCGA ovarian cancer project. MuSiC correctly confirms many expected results, and identifies several potentially novel avenues for discovery

Identification of Pharmacodynamic Transcript Biomarkers in Response to FGFR Inhibition by AZD4547

The challenge of developing effective pharmacodynamic biomarkers for preclinical and clinical testing of FGFR signaling inhibition is significant. Assays that rely on the measurement of phospho-protein epitopes can be limited by the availability of effective antibody detection reagents. Transcript profiling enables accurate quantification of many biomarkers and provides a broader representation of pathway modulation. To identify dynamic transcript biomarkers of FGFR signaling inhibition by AZD4547, a potent inhibitor of FGF receptors 1, 2, and 3, a gene expression profiling study was performed in FGFR2-amplified, drug-sensitive tumor cell lines. Consistent with known signaling pathways activated by FGFR, we identified transcript biomarkers downstream of the RAS-MAPK and PI3K/AKT pathways. Using different tumor cell lines in vitro and xenografts in vivo, we confirmed that some of these transcript biomarkers (DUSP6, ETV5, YPEL2) were modulated downstream of oncogenic FGFR1, 2, 3, whereas others showed selective modulation only by FGFR2 signaling (EGR1). These transcripts showed consistent time-dependent modulation, corresponding to the plasma exposure of AZD4547 and inhibition of phosphorylation of the downstream signaling molecules FRS2 or ERK. Combination of FGFR and AKT inhibition in an FGFR2-mutated endometrial cancer xenograft model enhanced modulation of transcript biomarkers from the PI3K/AKT pathway and tumor growth inhibition. These biomarkers were detected on the clinically validated nanoString platform. Taken together, these data identified novel dynamic transcript biomarkers of FGFR inhibition that were validated in a number of in vivo models, and which are more robustly modulated by FGFR inhibition than some conventional downstream signaling protein biomarkers

Understanding interpersonal relationships and psychopathy

Although psychopathy is widely recognised for its importance in forensic and criminal justice settings, the range of interpersonal relationships that are experienced and engaged in by individuals with psychopathy is understudied. A Rapid Evidence Assessment (Study 1) examined what is known empirically about the nature and quality of relationships for individuals with psychopathy. Affective, Cognitive and Lifestyle Assessment (ACL) interviews and genograms were then analysed in conjunction with Psychopathy Checklist: Screening Version (PCL:SV) scores to explore the extent, nature, and quality of interpersonal relationships in student and forensic psychiatric samples (Study 2). Quantitative data indicated that total psychopathy score predicted a smaller number of positive interpersonal relationships. Findings regarding Factors 1 and 2 and numbers of positive and negative interpersonal relationships varied between samples. Qualitative analyses demonstrated that psychopathic participants used less positive descriptors than non-psychopathic participants when discussing their interpersonal relationships. Findings are examined with regards to implications for future research