XMM-Newton Archival Study of the ULX Population in Nearby Galaxies

We present the results of an archival XMM-Newton study of the bright X-ray point sources (L_X > 10^38 erg/s) in 32 nearby galaxies. From our list of approximately 100 point sources, we attempt to determine if there is a low-state counterpart to the Ultraluminous X-ray (ULX) population, searching for a soft-hard state dichotomy similar to that known for Galactic X-ray binaries and testing the specific predictions of the IMBH hypothesis. To this end, we searched for "low-state" objects, which we defined as objects within our sample which had a spectrum well fit by a simple absorbed power law, and "high-state" objects, which we defined as objects better fit by a combined blackbody and a power law. Assuming that ``low-state'' objects accrete at approximately 10% of the Eddington luminosity (Done & Gierlinski 2003) and that "high-state" objects accrete near the Eddington luminosity we further divided our sample of sources into low and high state ULX sources. We classify 16 sources as low-state ULXs and 26 objects as high-state ULXs. As in Galactic black hole systems, the spectral indices, Gamma, of the low-state objects, as well as the luminosities, tend to be lower than those of the high-state objects. The observed range of blackbody temperatures for the high state is 0.1-1 keV, with the most luminous systems tending toward the lowest temperatures. We therefore divide our high-state ULXs into candidate IMBHs (with blackbody temperatures of approximately 0.1 keV) and candidate stellar mass BHs (with blackbody temperatures of approximately 1.0 keV). A subset of the candidate stellar mass BHs have spectra that are well-fit by a Comptonization model, a property similar of Galactic BHs radiating in the "very-high" state near the Eddington limit.Comment: 54 pages, submitted to ApJ (March 2005), accepted (May 2006); changes to organization of pape

Researching the Research: Applying Machine Learning Techniques to Dissertation Classification

This research examines industry-based dissertation research in a doctoral computing program through the lens of machine learning algorithms to determine if natural language processing-based categorization on abstracts alone is adequate for classification. This research categorizes dissertation by both their abstracts and by their full-text using the GraphLab Create library from Apple’s Turi to identify if abstract analysis is an adequate measure of content categorization, which we found was not. We also compare the dissertation categorizations using IBM’s Watson Discovery deep machine learning tool. Our research provides perspectives on the practicality of the manual classification of technical documents; and, it provides insights into the: (1) categories of academic work created by experienced fulltime working professionals in a Computing doctoral program, (2) viability and performance of automated categorization of the abstract analysis against the fulltext dissertation analysis, and (3) natual language processing versus human manual text classification abstraction

4-Aminopyridine Decreases Progesterone Production by Porcine Granulosa Cells

BACKGROUND: Ion channels occur as large families of related genes with cell-specific expression patterns. Granulosa cells have been shown to express voltage-gated potassium channels from more than one family. The purpose of this study was to determine the effects of 4-aminopyridine (4-AP), an antagonist of KCNA but not KCNQ channels. METHODS: Granulosa cells were isolated from pig follicles and cultured with 4-AP, alone or in combination with FSH, 8-CPT-cAMP, estradiol 17β, and DIDS. Complimentary experiments determined the effects of 4-AP on the spontaneously established pig granulosa cell line PGC-2. Granulosa cell or PGC-2 function was assessed by radio-immunoassay of media progesterone accumulation. Cell viability was assessed by trypan blue exclusion. Drug-induced changes in cell membrane potential and intracellular potassium concentration were documented by spectrophotometric determination of DiBAC(4)(3) and PBFI fluorescence, respectively. Expression of proliferating cell nuclear antigen (PCNA) and steroidogenic acute regulatory protein (StAR) was assessed by immunoblotting. Flow cytometry was also used to examine granulosa cell viability and size. RESULTS: 4-AP (2 mM) decreased progesterone accumulation in the media of serum-supplemented and serum-free granulosa cultures, but inhibited cell proliferation only under serum-free conditions. 4-AP decreased the expression of StAR, the production of cAMP and the synthesis of estradiol by PGC-2. Addition of either 8-CPT-cAMP or estradiol 17β to serum-supplemented primary cultures reduced the inhibitory effects of 4-AP. 4-AP treatment was also associated with increased cell size, increased intracellular potassium concentration, and hyperpolarization of resting membrane potential. The drug-induced hyperpolarization of resting membrane potential was prevented either by decreasing extracellular chloride or by adding DIDS to the media. DIDS also prevented 4-AP inhibition of progesterone production. CONCLUSION: 4-AP inhibits basal and FSH-stimulated progesterone production by pig granulosa cells via drug action at multiple interacting steps in the steroidogenic pathway. These inhibitory effects of 4-AP on steroidogenesis may reflect drug-induced changes in intracellular concentrations of K(+)and Cl(- )as well as granulosa cell resting membrane potential

Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

Abstract Background Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. Methods We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants. Results Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased. Conclusions The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute. Trial registration NCT00281216 , ClinicalTrials.gov.http://deepblue.lib.umich.edu/bitstream/2027.42/112169/1/12931_2015_Article_251.pd

Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

Abstract Background Although T cells, especially CD8+, have been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, their role during acute exacerbations (AE-COPD) is uncertain. Methods We recruited subjects with COPD and a history of previous AE-COPD and studied them quarterly to collect blood and spontaneously expectorated sputum while stable. During exacerbations (defined by a change in symptoms plus physician diagnosis and altered medications), we collected blood and sputum before administering antibiotics or steroids. We used flow cytometry to identify leukocytes in peripheral blood, plus Luminex® analysis or ELISA to determine levels of inflammatory biomarkers in serum and sputum supernatants. Results Of 33 enrolled subjects, 13 participated in multiple stable visits and had ≥1 AE-COPD visit, yielding 18 events with paired data. Flow cytometric analyses of peripheral blood demonstrated decreased CD4+ and CD8+ T cells during AE-COPD (both absolute and as a percentage of all leukocytes) and significantly increased granulocytes, all of which correlated significantly with serum C-reactive protein (CRP) concentrations. No change was observed in other leukocyte populations during AE-COPD, although the percentage of BDCA-1+ dendritic cells expressing the activation markers CD40 and CD86 increased. During AE-COPD, sICAM-1, sVCAM-1, IL-10, IL-15 and GDF-15 increased in serum, while in sputum supernatants, CRP and TIMP-2 increased and TIMP-1 decreased. Conclusions The decrease in CD4+ and CD8+ T cells (but not other lymphocyte subsets) in peripheral blood during AE-COPD may indicate T cell extravasation into inflammatory sites or organized lymphoid tissues. GDF-15, a sensitive marker of cardiopulmonary stress that in other settings independently predicts reduced long-term survival, is acutely increased in AE-COPD. These results extend the concept that AE-COPD are systemic inflammatory events to which adaptive immune mechanisms contribute. Trial registration NCT00281216 , ClinicalTrials.gov.http://deepblue.lib.umich.edu/bitstream/2027.42/134660/1/12931_2015_Article_251.pd

NC-1059: A Channel-Forming Peptide That Modulates Drug Delivery across In Vitro Corneal Epithelium

PURPOSE. The goal of this study was to determine whether a synthetic peptide, NC-1059, can modulate the corneal epithelium to increase the permeation of therapeutic agents across this barrier. METHODS. An in vitro system employing transformed human corneal epithelial (THCE) cells was optimized for this study. Culture conditions were identified to promote formation of a confluent monolayer that rapidly develops a substantial transepithelial electrical resistance. Electrical parameters were measured with a modified Ussing flux chamber, and solute flux was quantified with fluorescently labeled compounds. RESULTS. NC-1059 causes a concentration-dependent increase in short-circuit current and an increase in transepithelial electrical conductance when assessed in modified Ussing chambers. The effect of NC-1059 on transepithelial electrical resistance was reversible. To test for paracellular permeability and size exclusion, FITC-labeled dextran ranging in size from 10 to 70 kDa was used. Dextran permeated the corneal cell monolayer in the presence, but not the absence, of NC-1059. Fluorescein sodium and carboxyfluorescein were then used as low molecular weight markers with similar NC-1059 -modulated kinetics being observed. Maximum permeation for the fluorescein derivatives occurred 30 to 90 minutes after a 5-minute NC-1059 exposure. A prototypical drug, methotrexate, also exhibited increased permeation in the presence of NC-1059. CONCLUSIONS. NC-1059 enhances drug permeation across cultured corneal epithelial cell monolayers by transiently affecting the paracellular pathway. Thus, NC-1059 is a lead compound for development of cotherapeutic agents to enhance access and effectiveness of ophthalmic compounds. (Invest Ophthalmol Vis Sci. 2009;50:3337-3345) DOI:10.1167/iovs.08-3053 D rug delivery of ocular therapeutics presents several challenges. There are many difficulties in attaining and sustaining adequate therapeutic levels in the eye while avoiding systemic toxicity. Although there are several routes of administration available for the eye (e.g., topical, subconjunctival, retrobulbar, intracameral, and systemic), topical application of therapeutic agents to the eye offers several advantages including localized drug effects with limited entry into systemic circulation, better accessibility than can be achieved by systemic delivery, avoidance of first-pass hepatic metabolism, convenience, and simplicity. Despite the benefits of topical application, many factors limit the bioavailability of therapeutic agents. For instance, the maximum volume that can be contained within the conjunctival cul-de-sac and precorneal tear film is approximately 30 L, and the solutes are eliminated rapidly from the precorneal area by lacrimal secretions. The cornea is the outermost transparent portion of the eye and provides the primary barrier through which ocular absorption must occur

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays

Background: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. Findings: In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. Conclusions: Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred

Photometric and Spectroscopic Observations of SN 1990E in NGC 1035: Observational Constraints for Models of Type II Supernovae

We present 126 photometric and 30 spectral observation of SN 1990E spanning from 12 days before B maximum to 600 days past discovery. These observations show that SN 1990E was of type II-P, displaying hydrogen in its spectrum, and the characteristic plateau in its light curve. SN 1990E is one of the few SNe II which has been well observed before maximum light, and we present evidence that this SN was discovered very soon after its explosion. In the earliest spectra we identify, for the first time, several N II lines. We present a new technique for measuring extinction to SNe II based on the evolution of absorption lines, and use this method to estimate the extinction to SN 1990E, Av=1.5+/-0.3 mag. From our photometric data we have constructed a bolometric light curve for SN 1990E and show that, even at the earliest times, the bolometric luminosity was falling rapidly. We use the late-time bolometric light curve to show that SN 1990E trapped a majority of the gamma rays produced by the radioactive decay of 56Co, and estimate that SN 1990E ejected 0.073 Mo of 56Ni, an amount virtually identical to that of SN 1987A. [excerpt