21 research outputs found

    Contracts and intellectual property rights in translational R&D: furthering safeguards in the public interest

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    Intellectual property safeguards should be more widely incorporated into the bilateral contracts that underpin the translational R&D process to preserve the public interest, especially where public funds and resources have spearheaded the innovation process

    Comprehensive Assessment of the Quality of Commercial Cranberry Products. Phenolic Characterization and in Vitro Bioactivity

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    Cranberry (Vaccinium macrocarpon) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 μg/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis

    Border Security of the Schengen Area from the Perspective of the Public Goods Theory

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    Radko Hokovský Border Security of the Schengen Area from the Perspective of the Public Goods Theory Abstract In the context of increasing illegal immigration to the European Union, doubts arise whether Schengen Area is fit to face this challenge, or whether it needs to be reformed. The aim of this dissertation thesis is to clarify questions surrounding functionality of the Border Security System of the Schengen Area by applying the theory of public goods. The main inquiry of the thesis is, whether it is necessary to further strengthen the EU competences in order to improve the functioning of the Schengen Border Security System (SBSS). First, a model of an ideal- type border security system is constructed in order to identify core functions of border security in relation to protection from illegal immigration: (a) deterrence of illegal immigrants, (b) prevention of illegal border crossings, (c) interdiction of illegal immigrants, (d) apprehension of illegal immigrants, (e) apprehension of illegal residents, and (f) removal of illegal population. Second, theory of public goods is introduced as an analytical framework, which allows to identify possible solutions to collective action problems associated with production of public goods such as security in transnational contexts comparable to the EU. Third, the..

    Impact of NCT on purified Stx2 demonstrated in gel electrophoresis.

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    <p>(A) Purified Stx2 was treated with 55 mM NCT for 30 min at RT. Then, an aliquot was used for SDS-PAGE. Reducing buffer contained 4.5% v/v mercaptoethanol. A gel containing bands of aliquots containing 10 or 15 µg Stx2 is shown (one representative of three independent experiments). Bands a–f were subjected to in-gel digestion and mass spectrometry. (B) Purified Stx2 was treated with 55 mM NCT for 30 min at RT and subjected to a tricine gel for improved separation of the low molecular weight bands. Note the separation of the B subunit in bands a and b, which were subjected to in-gel digestion and mass spectrometry.</p

    N-Chlorotaurine, a Long-Lived Oxidant Produced by Human Leukocytes, Inactivates Shiga Toxin of Enterohemorrhagic <em>Escherichia coli</em>

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    <div><p><em>N</em>-chlorotaurine (NCT), the main representative of long-lived oxidants produced by granulocytes and monocytes, is known to exert broad-spectrum microbicidal activity. Here we show that NCT directly inactivates Shiga toxin 2 (Stx2), used as a model toxin secreted by enterohemorrhagic <em>Escherichia coli</em> (EHEC). Bacterial growth and Stx2 production were both inhibited by 2 mM NCT. The cytotoxic effect of Stx2 on Vero cells was removed by ≥5.5 mM NCT. Confocal microscopy and FACS analyses showed that the binding of Stx2 to human kidney glomerular endothelial cells was inhibited, and no NCT-treated Stx2 entered the cytosol. Mass spectrometry displayed oxidation of thio groups and aromatic amino acids of Stx2 by NCT. Therefore, long-lived oxidants may act as powerful tools of innate immunity against soluble virulence factors of pathogens. Moreover, inactivation of virulence factors may contribute to therapeutic success of NCT and novel analogs, which are in development as topical antiinfectives.</p> </div

    Oxidation of thio groups and aromatic groups of Stx2 detected with mass spectrometry.

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    <p>Bands a-f from the gels, as depicted for one representative in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047105#pone-0047105-g005" target="_blank">Figure 5</a>, were analyzed with mass spectrometry after in-gel digestion. Similar results gained from three independent experiments are shown. Positions and occurrence in bands are demonstrated. Amino acids 1–22 (subunit A) and 1–19 (subunit B), respectively, comprise the signal peptides. (A) Oxidation of all methionines and cysteines of subunit A occurred. Positions of oxidized amino acids in the sequence are shown and their mono- to tri-oxidation in relation to the bands excised from the gels. (B) Chlorination of phenylalanine, tyrosine, and histidine of subunit A. (C) Oxidation of methionine and chlorination of tyrosine of subunit B.</p

    Decrease of oxidation capacity of NCT and NVC-422 in EHEC Direct Medium.

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    <p>Stock solutions of NCT (A) or NVC-422 (B) were 10-fold diluted in this medium to final concentrations of 55 mM, 5.5 mM, 2.75 mM and 1.375 mM. The oxidation capacity was measured with redox potentiometry after indicated time-points. Results with NVC-612 resembled those of NCT. Mean values ± SD from three independent experiments are shown.</p

    Comparison of clinical outcomes in ibuprofen and placebo groups.

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    <p>Sixteen calves were experimentally infected with bovine respiratory syncytial virus by nebulizer on Day 0. Eight received ibuprofen and received eight placebo. (A) Shows the mean clinical score by treatment group for each day. The groups were statistically significantly different by Day 5 using a mixed effects model. (B) Shows the time taken to enter the most severe decile of illness as measured by the clinical score. Statistical significance was calculated using the log rank test. (C) Shows the percentage weight gain for each individual calf. Calves randomized to ibuprofen are in red; placebo is in blue. Statistical significance was calculated using ordinary least squares regression. (D) Shows the mean temperature by treatment group. Temperature was measured every eight hours. (E) Shows the mean respiratory rate per group. Respiratory rate was measured every eight hours. Statistical significance was calculated for both temperature and respiratory rate using a mixed effect model. (F) Shows the time taken to enter the most severe decile of tachypnea. Statistical significance for (F) was calculated using the log rank test.</p
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