229 research outputs found

    Waterkwaliteit binnen de normen; Haalbaarheid en betaalbaarheid van ambities in 2e Nota Duurzame Gewasbescherming

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    In 2012 hebben LEI Wageningen UR, CLM en RIVM al een aantal maatregelen van de 2e Nota Duurzame Gewasbescherming doorgerekend. De aanleiding van deze aanvullende studie is dat het kabinet Rutte-Asscher de kwaliteit van het oppervlaktewater verder wil verbeteren. Die aanscherping van het beleid is haalbaar en betaalbaar op zes van de zeven onderzochte bedrijfstypen. De voorgestelde maatregelen leveren de benodigde emissiereducties op en kosten de ondernemers gemiddeld minder dan één procent van het bedrijfssaldo. Een uitzondering vormen de glastuinbouwbedrijven die nog geen waterzuivering hebben: bij deze bedrijven wordt de grens voor betaalbaarheid overschreden

    Супутні зміни рівнів в плазмі стероїдних гормонів за різних варіантів впливу бальнеотерапії на курорті Трускавець на рівень тестостерону у жінок

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    В клинико-физиологическом наблюдении за 100 женщинами 20-40 лет с сочетанной хронической патологией пищеварительной и репродуктивной систем изучено влияние курса стандартной бальнеотерапии на курорте Трускавец на сопутствующие изменения содержания в плазме стероидных гормонов эстрадиола, прогестерона, кортизола и альдостерона при различных начальных уровнях тестостерона. Выявлены тесные прямые корреляционные связи между тестостеронемией и содержанием в плазме эстрадиола и кортизола и умеренные - с прогестеронемией (прямую) и альдостероном (обратную). Динамика тестостеронемии под влиянием бальнеотерапии тесно прямо коррелирует с изменениями уровней кортизола и эстрадиола и умеренно инверсно - с динамикой альдостерона, тогда как с динамикой прогестерона связь имеет нелинейный характер.In the clinical physiological looking after 100 women 20-40 years with combinative chronic pathology of the digestive and genesial systems is studied influence of course of standard balneotherapy on spa Truskavets on the concomitant changes of maintenance in plasma of steroide hormones estradiol, progesterone, cortisol and aldosterone at the different initial levels of testosterone. Close lines are exposed cross-correlation connections between testosterone and maintenance in plasma of estradiol and cortisol and moderate - with progesterone (line) and aldosterone (reverse). Dynamics of testosterone under influence of balneotherapy closely straight correlates with the changes of levels of cortisol and estradiol and mildly inversely - with the dynamics of aldosterone, while with the dynamics of progesterone connection has nonlinear character

    The problem of racemization in drug discovery and tools to predict it

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    Introduction: Racemization has long been an ignored risk in drug development, probably because of a lack of convenient access to good tools for its detection and an absence of methods to predict racemization risk. As a result, the potential effects of racemization have been systematically underestimated. Areas covered: Herein, the potential effects of racemization are discussed through a review of drugs for which activity and side effects for both enantiomers are known. Subsequently, drugs known to racemize are discussed and the authors review methods to predict racemization risk. Application of a method quantitatively predicting racemization risk to databases of compounds from the medicinal chemistry literature shows that success in clinical trials is negatively correlated with racemization risk. Expert opinion: It is envisioned that a quantitative method of predicting racemization risk will remove a blind spot from the drug development pipeline. Removal of the blind spot will make drug development more efficient and result in less late-stage attrition of the drug pipeline

    Elkaar een toekomst gunnen : naar een modern en duurzaam teeltareaal glastuinbouw

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    Voorjaar 2012 heeft een aantal partijen de handen ineengeslagen in de Initiatiefgroep ' Duurzame modernisering teeltareaal '. Zij hebben zich tot doel gesteld 'het aanjagen van de modernisering en verduurzaming van het teeltareaal door het maken van een gereedschapskist met nieuwe instrumenten en stimulering van de (creatieve) aanwending daarvan' . Dit alles met als uiteindelijke doel: het verhogen van de toegevoegde waarde van de glastuinbouwbedrijven per m2 en de concurrentiekracht van de sector als geheel

    Influence of Individual Surgeon Volume on Oncological Outcome of Colorectal Cancer Surgery

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    Background. Surgery performed by a high-volume surgeon improves short-term outcomes. However, not much is known about long-term effects. Therefore we performed the current study to evaluate the impact of high-volume colorectal surgeons on survival. Methods. We conducted a retrospective analysis of our prospectively collected colorectal cancer database between 2004 and 2011. Patients were divided into two groups: operated on by a high-volume surgeon (>25 cases/year) or by a low-volume surgeon (<25 cases/year). Perioperative data were collected as well as follow-up, recurrence rates, and survival data. Results. 774 patients underwent resection for colorectal malignancies. Thirteen low-volume surgeons operated on 453 patients and 4 high-volume surgeons operated on 321 patients. Groups showed an equal distribution for preoperative characteristics, except a higher ASAclassification in the low-volume group. A high-volume surgeon proved to be an independent prognostic factor for disease-free survival in the multivariate analysis ( = 0.04). Although overall survival did show a significant difference in the univariate analysis ( < 0.001) it failed to reach statistical significance in the multivariate analysis ( = 0.09). Conclusions. In our study, a higher number of colorectal cases performed per surgeon were associated with longer disease-free survival. Implementing high-volume surgery results in improved long-term outcome following colorectal cancer

    Site-selective Csp3–Csp/Csp3–Csp2 cross-coupling reactions using frustrated Lewis pairs

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    The donor–acceptor ability of frustrated Lewis pairs (FLPs) has led to widespread applications in organic synthesis. Single electron transfer from a donor Lewis base to an acceptor Lewis acid can generate a frustrated radical pair (FRP) depending on the substrate and energy required (thermal or photochemical) to promote an FLP into an FRP system. Herein, we report the Csp3–Csp cross-coupling reaction of aryl esters with terminal alkynes using the B(C6F5)3/Mes3P FLP. Significantly, when the 1-ethynyl-4-vinylbenzene substrate was employed, the exclusive formation of Csp3–Csp cross-coupled products was observed. However, when 1-ethynyl-2-vinylbenzene was employed, solvent-dependent site-selective Csp3–Csp or Csp3–Csp2 cross-coupling resulted. The nature of these reaction pathways and their selectivity has been investigated by extensive electron paramagnetic resonance (EPR) studies, kinetic studies, and density functional theory (DFT) calculations both to elucidate the mechanism of these coupling reactions and to explain the solvent-dependent site selectivity

    Targeted cell imaging properties of a deep red luminescent iridium(III) complex conjugated with a c-Myc signal peptide

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    A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (λex = 550 nm; λem = 677 nm) cyclometalated organometallic iridium(III) complex to give the conjugate Ir-CMYC. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18–24 h incubation show that Ir-CMYC concentrations of 80–100 μM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(III) complex lacking the peptide sequence, Ir-PYR, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 μM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that Ir-PYR and Ir-CMYC display similarly low affinities for DNA (ca. 103 M−1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of Ir-CMYC are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex
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