612 research outputs found

    Relationships between geographic and inertial coordinates of position

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    Relationships between geographic and inertial coordinates of positio

    Unnormalized associated Legendre functions: A compendium of graphs, expansions, properties, and integrals

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    Compendium of graphs, expansions, propertites, and integrals for unnormalized associated Legendre function

    Incorporation of membrane-bound, mammalian-derived immunomodulatory proteins into influenza whole virus vaccines boosts immunogenicity and protection against lethal challenge

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    <p>Abstract</p> <p>Background</p> <p>Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.</p> <p>Results</p> <p>We have evaluated the immunogenicity of inactivated cytokine-bearing influenza vaccines using a mouse model of lethal influenza virus challenge. CYT-IVACs were produced by stably transfecting MDCK cell lines with mouse-derived cytokines (GM-CSF, IL-2 and IL-4) fused to the membrane-anchoring domain of the viral hemagglutinin. Influenza virus replication in these cell lines resulted in the uptake of the bioactive membrane-bound cytokines during virus budding and release. <it>In vivo </it>efficacy studies revealed that a single low dose of IL-2 or IL-4-bearing CYT-IVAC is superior at providing protection against lethal influenza challenge in a mouse model and provides a more balanced Th<sub>1</sub>/Th<sub>2 </sub>humoral immune response, similar to live virus infections.</p> <p>Conclusion</p> <p>We have validated the protective efficacy of CYT-IVACs in a mammalian model of influenza virus infection. This technology has broad applications in current influenza virus vaccine development and may prove particularly useful in boosting immune responses in the elderly, where current vaccines are minimally effective.</p

    Ariel - Volume 6 Number 2

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    Editors Mark Dembert J.D. Kanofsky Frank Chervenak John Lammie Curt Cummings Entertainment Robert Breckenridge Joe Conti Gary Kaskey Photographer Larry Glazerman Overseas Editor Mike Sinason Humorist Jim McCann Staff Ken Jaffe Bob Skarloff Halley Faust Jim Burk

    Skin cancer excision is more efficient and cost effective in a specialist secondary care service

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    Aim: To compare the relative efficiencies of skin excisions in primary and secondary care. Methods: We compared the benign: malignant ratio for specimens referred by General Practice, General Surgery and the Skin Cancer Service to the regional pathology laboratory over one month. We used cost minimization analysis to compare the relative efficiencies of the services. Results: 620 excisions were received: 139 from General Practice, 118 from General Surgery and 363 from the Skin Cancer Service. The number (%) of malignant lesions was 13 (9.4%) from General Practice, 18 (15.2%) from General Surgery and 137 (37.7%) from the Skin Cancer Service. Excision was cheaper in General Practice at €84.58 as compared to €97.49 in the hospital day surgical unit. However, the cost per malignant lesion excised was €1779.80 in general practice versus €381.78 in the Skin Cancer Service. Conclusion: Our results indicate that moving skin cancer treatment to General Practice may result in an excess of benign excisions and therefore be both less efficient and less cost effective

    Justice in solar energy development.

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    To achieve national energy and climate targets across the world, there is a key focus on solar energy development. It is clear from literature that many countries have enormous, under-utilised potentials for solar energy, which can significantly change their energy mix and contribute to the low-carbon ambitions they signed up to under the 2015 Paris Agreement. Our research highlights that there are benefits to solar energy development from a law and economic perspective that are still underexplored. These benefits centre on justice and on how solar energy increases justice within the energy system. From a legal perspective, we review 72 countries and their introduction of energy law with respect to solar energy development. Our analysis illustrates that in some developing countries (new) legislation was not associated with a significant increase in the share of solar energy in the energy mix. We then highlight how to achieve solar energy development through law that can provide certainty for investment. Furthermore, we stress the importance of flexibility that allows the full potential of solar energy to be realised within the energy system. The corresponding form of flexibility justice, combining law and economics, can contribute to increased economic welfare based on market reforms that centre on new market design and market access, while ensuring that it keeps pace with ongoing developments in technology, cost, and ownership

    Low-density lipoprotein aggregation predicts adverse cardiovascular events in peripheral artery disease

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    Background and aims: Peripheral artery disease (PAD) is a systemic manifestation of atherosclerosis that is associated with a high risk of major adverse cardiovascular events (MACE). LDL aggregation contributes to atherosclerotic plaque progression and may contribute to plaque instability. We aimed to determine if LDL aggregation is associated with MACE in patients with PAD undergoing lower extremity revascularization (LER). Methods: Two hundred thirty-nine patients with PAD undergoing LER had blood collected at baseline and were followed prospectively for MACE (myocardial infarction, stroke, cardiovascular death) for one year. Nineteen age, sex and LDL-C-matched control subjects without cardiovascular disease also had blood drawn. Subject LDL was exposed to sphingomyelinase and LDL aggregate size measured via dynamic light scattering. Results: Mean age was 72.3 10.9 years, 32.6% were female, and LDL-cholesterol was 68 +/- 25 mg/dL. LDL aggregation was inversely associated with triglycerides, but not associated with demographics, LDL-cholesterol or other risk factors. Maximal LDL aggregation occurred significantly earlier in subjects with PAD than in control subjects. 15.9% of subjects experienced MACE over one year. The 1st tertile (shortest time to maximal aggregation) exhibited significantly higher MACE (25% vs. 12.5% in tertile 2 and 10.1% in tertile 3, p = 0.012). After multivariable adjustment for demographics and CVD risk factors, the hazard ratio for MACE in the 1st tertile was 4.57 (95% CI 1.60-13.01; p = 0.004) compared to tertile 3. Inclusion of LDL aggregation in the Framingham Heart Study risk calculator for recurrent coronary heart disease events improved the c-index from 0.57 to 0.63 (p = 0.01). Conclusions: We show that in the setting of very well controlled LDL-cholesterol, patients with PAD with the most rapid LDL aggregation had a significantly elevated MACE risk following LER even after multivariable adjustment. This measure further improved the classification specificity of an established risk prediction tool. Our findings support broader investigation of this assay for risk stratification in patients with atherosclerotic CVD.Peer reviewe

    Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella

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    Salmonella is a primary cause of enteric diseases in a variety of animals. During its evolution into a pathogenic bacterium, Salmonella acquired an elaborate regulatory network that responds to multiple environmental stimuli within host animals and integrates them resulting in fine regulation of the virulence program. The coordinated action by this regulatory network involves numerous virulence regulators, necessitating genome-wide profiling analysis to assess and combine efforts from multiple regulons. In this review we discuss recent high-throughput analytic approaches used to understand the regulatory network of Salmonella that controls virulence processes. Application of high-throughput analyses have generated large amounts of data and necessitated the development of computational approaches for data integration. Therefore, we also cover computer-aided network analyses to infer regulatory networks, and demonstrate how genome-scale data can be used to construct regulatory and metabolic systems models of Salmonella pathogenesis. Genes that are coordinately controlled by multiple virulence regulators under infectious conditions are more likely to be important for pathogenesis. Thus, reconstructing the global regulatory network during infection or, at the very least, under conditions that mimic the host cellular environment not only provides a bird's eye view of Salmonella survival strategy in response to hostile host environments but also serves as an efficient means to identify novel virulence factors that are essential for Salmonella to accomplish systemic infection in the host
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