1,819 research outputs found

    Chariots of Salvation: The Biblical Drama of Armageddon [review] / Hans K. LaRondelle.

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    Emissivity of Frozen Regions Retrieved from Aquarius Measurements

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    The land emissivity model used in the Aquarius data processing has been updated for the latest data release (V5.0). In order to improve the estimates of the brightness temperatures of frozen regions, the new model uses values of surface emissivity that have been estimated from the Aquarius measurements averaged over the entire duration of the mission. The retrieved emissivities depend on the geographic location, but they depend only marginally on time, temperature and snow cover

    Different radiolabelling methods alter the pharmacokinetic and biodistribution properties of Plasminogen Activator Inhibitor Type 2 (PAI-2) forms

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    Introduction: Tumour-associated urokinase plasminogen activator (uPA) is a critical marker of invasion and metastasis, and it is recognised as having strong prognostic relevance as well as being a therapeutic target. The specific uPA inhibitor plasminogen activator inhibitor type-2 (PAI-2, SerpinB2) specifically targets cell bound uPA and is internalised. Furthermore, preclinical studies have established the “proof-of-principle” of uPA-targeting by PAI-2-cytotoxin conjugates in human carcinoma models. However, these studies also suggest that PAI-2 is rapidly cleared via the renal system with low total dose reaching the tumour. In this study, a comparative single photon emission computed tomography (SPECT) and biodistribution (BD) analysis of different forms of PAI-2 labelled with the radioisotopes iodine-123 (123I) and technetium-99m (99mTc) was undertaken. Methods: The pharmacokinetic (PK) properties and BD of wild-type, ΔCD-loop and PEGylated ΔCD-loop PAI-2 labelled with the commonly used diagnostic SPECT radioisotopes 99mTc or 123I were compared in mouse models of human prostate carcinoma. Whole body SPECT imaging was also performed. Results: Both wild-type or the shorter but active ΔCD-loop form of PAI-2 123I-labelled indirectly via conjugation to free amine groups (termed 123I-Bn-PAI-2) exhibited low tumour uptake, rapid excretion and similar PK profiles. Preliminary studies with a short branched-chain PEGylated 123I-Bn-PAI-2 ΔCD-loop indicated an increase in blood retention time and tumour uptake. All 123I-Bn-labelled radiotracers were largely excreted through the kidneys. By comparison, both wild-type 123I-PAI-2 (labelled directly via tyrosine residues) and 99mTc-PAI-2 displayed different PK/BD patterns compared to 123IBn- PAI-2, suggesting greater liver based catabolism and thus slower elimination. SPECT imaging mimicked the BD results of all radiotracers. Conclusion: The different labelling methods gave distinct PAI-2 BD and tumour uptake profiles, with radioiodination resulting in the best non-tumour organ clearance profiles. Preliminary analyses with short branched-chain PEGylated 123I-Bn-PAI-2 ΔCD-loop suggest that further investigations with other PEGylation reagents are required to optimise this approach for tumour imaging. These findings impact on the use of PAI-2 for drug delivery and/or diagnostic development

    Effects on the immune system associated with living near a pesticide dump site.

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    In this paper, we report results of the second phase of a larger study designed to evaluate the effects on the immune system of living near a Superfund site containing organochlorine pesticides, volatile organic compounds, and metals. Phase II was conducted to determine whether living near the site, consisting of six locations in Aberdeen, North Carolina, is associated with higher plasma organochlorine levels, immune suppression, or DNA damage. Each of 302 residents of Aberdeen and neighboring communities provided a blood specimen, underwent a skin test, and answered a questionnaire. Blood specimens were analyzed for organochlorine pesticides, immune markers, and micronuclei. Of 20 organochlorines tested, only DDE was detected in the blood of participants (except for one individual). Age-adjusted mean plasma DDE levels were 4.05 ppb for Aberdeen residents and 2.95 ppb (p = 0.01) for residents of neighboring communities. Residents of 40-59 years of age who lived within a mile of any site, but particularly the Farm Chemicals site, had higher plasma DDE levels than residents who lived farther away. Residents who lived near the Farm Chemicals site before versus after 1985 also had higher plasma DDE levels. Overall, there were few differences in immune markers between residents of Aberdeen and the neighboring communities. However, residents who lived closer to the dump sites had statistically significantly lower mitogen-induced lymphoproliferative activity than residents who lived farther away (p < 0.05). Residential location was not consistently associated with frequency of micronuclei or skin test responses. Although some statistically significant differences in immune markers were noted in association with residential location, the magnitude of effects are of uncertain clinical importance

    The CD-loop of PAI-2 (SERPINB2) is redundant in the targeting, inhibition and clearance of cell surface uPA activity

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    <p>Abstract</p> <p>Background</p> <p>Plasminogen activator inhibitor type-2 (PAI-2, SERPINB2) is an irreversible, specific inhibitor of the urokinase plasminogen activator (uPA). Since overexpression of uPA at the surface of cancer cells is linked to malignancy, targeting of uPA by exogenous recombinant PAI-2 has been proposed as the basis of potential cancer therapies. To this end, reproducible yields of high purity protein that maintains this targeting ability is required. Herein we validate the use <it>in vitro </it>of recombinant 6 × His-tagged-PAI-2 lacking the intrahelical loop between C and D alpha-helices (PAI-2 ΔCD-loop) for these purposes.</p> <p>Results</p> <p>We show that PAI-2 ΔCD-loop expressed and purified from the pQE9 vector system presents an easier purification target than the previously used pET15b system. Additionally, PAI-2 ΔCD-loop gave both higher yield and purity than wild-type PAI-2 expressed and purified under identical conditions. Importantly, absence of the CD-loop had no impact on the inhibition of both solution phase and cell surface uPA or on the clearance of receptor bound uPA from the cell surface. Furthermore, uPA:PAI-2 ΔCD-loop complexes had similar binding kinetics (K<sub>D </sub>~5 nM) with the endocytosis receptor Very Low Density Lipoprotein Receptor (VLDLR) to that previously published for uPA:PAI-2 complexes.</p> <p>Conclusion</p> <p>We demonstrate that the CD-loop is redundant for the purposes of cellular uPA inhibition and cell surface clearance (endocytosis) and is thus suitable for the development of anti-uPA targeted cancer therapeutics.</p

    Aggregating energy supply and demand

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    Energy usage in general, and electricity usage in particular, are major concerns internationally due to the increased cost of providing energy supplies and the environmental impacts of electricity generation using carbon-based fuels. If a "systems" approach is taken to understanding energy issues then both supply and demand need to be considered holistically. This paper examines two research projects in the energy area with IT tools as key deliverables, one examining supply issues and the other studying demand side issues. The supply side project used hard engineering methods to build the models and software, while the demand side project used a social science approach. While the projects are distinct, there was an overlap in personnel. Comparing the knowledge extraction, model building, implementation and interface issues of these two deliverables identifies both interesting contrasts and commonalities

    Natural emotion vocabularies as windows on distress and well-being

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    To date we know little about natural emotion word repertoires, and whether or how they are associated with emotional functioning. Principles from linguistics suggest that the richness or diversity of individuals’ actively used emotion vocabularies may correspond with their typical emotion experiences. The current investigation measures active emotion vocabularies in participant-generated natural speech and examined their relationships to individual differences in mood, personality, and physical and emotional well-being. Study 1 analyzes stream-of-consciousness essays by 1,567 college students. Study 2 analyzes public blogs written by over 35,000 individuals. The studies yield consistent findings that emotion vocabulary richness corresponds broadly with experience. Larger negative emotion vocabularies correlate with more psychological distress and poorer physical health. Larger positive emotion vocabularies correlate with higher well-being and better physical health. Findings support theories linking language use and development with lived experience and may have future clinical implications pending further research
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