In Situ Characterization of α6B1 Integrin Protein Associations in Early Aggressive Prostate Cancer

In prostate cancer (PCa) the laminin binding integrin (LBI) α6β1 is involved in the extra capsular and muscle invasion of cohesive tumor clusters in part through dissemination via peripheral nerves expressing laminin. This invasion results in part due to the posttranslational modification (PTM) of the α6β1 integrin (α6) by the serine protease urokinase plasminogen activator (uPA, PLAU) and its cognate receptor (uPAR, PLAUR). The cleavage results in a tumor specific variant form of the α6 integrin called α6pβ1 (α6p). This leads to altered biophysical adhesive properties of the cohesive cancer clusters. This PTM occurs early in progression from indolent and confined tumors to aggressive and invasive phenotypes. Current strategies have the capability to detect aggressive cancers that have invaded, but are unreliable for identification of tumors that have an early signature of invasiveness. Therefore, an identification of a reliable diagnostic method that stratifies confined and indolent (low risk) tumors that lack migratory capability from one that will progress to early invasive phenotypes will aid informed and objective decisions for specific treatment strategies. Utilizing an emerging technique of multiplex immunohistochemistry (IHC) detection of primary antibodies specific for protein biomarkers within a single formalin fixed paraffin embedded (FFPE), LBI protein interactions and associations were detected within prostate tissue samples. The interaction of LBI biomarkers with uPAR, the essential cell-cell adhesion protein E-cadherin were detected. In addition, associations with the pathway regulating tumor suppressor protein PTEN in concert with the transcription factor ERG in human prostate tissue samples were also detected. These interactions were detected in tissues exhibiting various stages of PCa disease progression. These protein interactions and associations were also the basis for generating image analysis algorithms to quantify protein expression. Using brightfield multiplex and standard DAB IHC image analysis, two separate quantitation algorithms were created and tested utilizing multiplex chromogen and IHC DAB detections. One quantitative algorithm allowed differentiation of individual chromogenic stain intensities and co-incidence of LBIs and E-cadherin biomarkers within focal regions of interest in PCa tissues. The results also displayed increased ratio of α6 integrin and E-cadherin cell-cell co-distribution in early pre-malignant events compared to aggressive tumors. The other algorithm designed identified specific localization patterns of α6 integrin in association of PTEN and ERG status. This indicated that localization of α6β1 integrin correlating to PTEN and ERG status could be used as an indicator of PCa aggressiveness. In this study, the role of the α6β1 integrin cleavage plays in cohesive tumor invasion through muscle was characterized. A CRISPR Cas9 mouse model muscle invasion assay with DU145 prostate tumor cells injected with a transfected uncleavable α6 mutant (α6AA) exhibited significantly reduced tumor onset and extravasation (6 weeks) while mice injected with cells with a transient knockout of α3β1 integrin (α3) increased tumor burden and invasion sites in xenograft tissues. Analysis of xenograft sample tissue confirmed a significant decrease in tumor burden and reduced muscle invasion. Overall, these results suggest a loss of α3 integrin plays a role in aggressive tumor burden and muscle invasion in PCa via the cleavage of α6β1 integrin. Also, the results indicate a blockage of the α6β1 integrin cleavage demonstrate a promising mechanism to inhibit the progression of aggressive disease

The collision of pure plane gravitational and electromagnetic shock waves

Thesis (M.Sc.) -- University of Adelaide, Dept. of Mathematical Physics, 198

Hydrolytic and Photochemical Degradation of Organophosphorus Pesticides

To keep pace with demands for increasing food supplies to satisfy the expanding world population, modern agriculture has utilized the latest scientific and technological knowledge available. Increases in crop production through the use of growth regulators, fertilizers , herbicides, and insecticides have been little short of phenomenal, and drugs, feed additives, and higher-quality grain and forage have dramatically increased livestock production. But, as is usually the case, this progress has been accompanied by problems, one of the more serious being contamination of our environment by chemicals. Only in recent years have the full effects of these pollutants on the ecological balance of nature begun to be understood in all the intricacies and implications

On Monoids Related to Braid Groups and Transformation Semigroups

None

New results from H.E.S.S. observations of galaxy clusters

Clusters of galaxies are believed to contain a significant population of cosmic rays. From the radio and probably hard X-ray bands it is known that clusters are the spatially most extended emitters of non-thermal radiation in the Universe. Due to their content of cosmic rays, galaxy clusters are also potential sources of VHE (>100 GeV) gamma rays. Recently, the massive, nearby cluster Abell 85 has been observed with the H.E.S.S. experiment in VHE gamma rays with a very deep exposure as part of an ongoing campaign. No significant gamma-ray signal has been found at the position of the cluster. The non-detection of this object with H.E.S.S. constrains the total energy of cosmic rays in this system. For a hard spectral index of the cosmic rays of -2.1 and if the cosmic-ray energy density follows the large scale gas density profile, the limit on the fraction of energy in these non-thermal particles with respect to the total thermal energy of the intra-cluster medium is 8% for this particular cluster. This value is at the lower bounds of model predictions.Comment: 4 pages, one figure, invited talk at the 2nd Heidelberg workshop: "High-Energy Gamma-rays and Neutrinos from Extra-Galactic Sources", January 13 - 16, 2009, to be published in Int. J. Mod. Phys.

User Centered, Application Independent Visualization of National Airspace Data

This paper describes an application independent software tool, IV4D, built to visualize animated and still 3D National Airspace System (NAS) data specifically for aeronautics engineers who research aggregate, as well as single, flight efficiencies and behavior. IV4D was origin ally developed in a joint effort between the National Aeronautics and Space Administration (NASA) and the Air Force Research Laboratory (A FRL) to support the visualization of air traffic data from the Airspa ce Concept Evaluation System (ACES) simulation program. The three mai n challenges tackled by IV4D developers were: 1) determining how to d istill multiple NASA data formats into a few minimal dataset types; 2 ) creating an environment, consisting of a user interface, heuristic algorithms, and retained metadata, that facilitates easy setup and fa st visualization; and 3) maximizing the user?s ability to utilize the extended range of visualization available with AFRL?s existing 3D te chnologies. IV4D is currently being used by air traffic management re searchers at NASA?s Ames and Langley Research Centers to support data visualizations

Transcriptional profiling of colicin-induced cell death of Escherichia coli MG1655 identifies potential mechanisms by which bacteriocins promote bacterial diversity

We report the transcriptional response of Escherichia coli MG1655 to damage induced by colicins E3 and E9, bacteriocins that kill cells through inactivation of the ribosome and degradation of chromosomal DNA, respectively. Colicin E9 strongly induced the LexA-regulated SOS response, while colicin E3 elicited a broad response that included the induction of cold shock genes, symptomatic of translational arrest. Colicin E3 also increased the transcription of cryptic prophage genes and other laterally acquired mobile elements. The transcriptional responses to both these toxins suggest mechanisms that may promote genetic diversity in E. coli populations, pointing to a more general role for colicins in adaptive bacterial physiology than has hitherto been realized