Scope of tetrazolo[1,5-a] quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

The conversion of tetrazolo[1,5-a]quinoxalines to 1,2,3-triazoloquinoxalines and triazoloimidazoquinoxalines under typical conditions of a CuAAC reaction has been investigated. Derivatives of the novel compound class of triazoloimidazoquinoxalines (TIQ) and rhenium(I) triazoloquinoxaline complexes as well as a new TIQ rhenium complex were synthesized. As a result, a small 1,2,3-triazoloquinoxaline library was obtained and the method could be expanded towards 4-substituted tetrazoloquinoxalines. The compatibility of various aliphatic and aromatic alkynes towards the reaction was investigated and the denitrogenative annulation towards imidazoloquinoxalines could be observed as a competing reaction depending on the alkyne concentration and the substitutions at the quinoxaline

Factors associated with the presence and prevalence of contagious ovine digital dermatitis: a 2013 study of 1136 random English sheep flocks

In 2013, a questionnaire was used to gather data on risks for introduction, and factors associated with prevalence, of contagious ovine digital dermatitis (CODD). There were 1136 (28.4%) usable responses from 4000 randomly selected sheep farmers in England. CODD was present in 58% (662) of flocks, with a reported prevalence of CODD lesions of 2.3%. The geometric mean period prevalence of all lameness was 4.2% and 2.8% in CODD positive and negative flocks respectively. Factors associated with a greater risk of presence of CODD were purchasing replacement ewes, not always checking the feet of sheep before purchase, not isolating purchased sheep, foot bathing returning ewes, foot trimming the flock more than twice in the year all compared with not doing these activities and increasing log10 flock size. Farmers who vaccinated sheep with Footvax™ were less likely to report presence of CODD. Factors associated with increasing prevalence of CODD lesions were not always checking the feet of purchased sheep, flocks that mixed with other flocks and sheep that left the farm for summer grazing and later returned. In addition, flocks where farmers followed the current recommended managements for control of footrot, had a lower prevalence of CODD whilst those who used foot bathing and where feet bled during routine foot trimming had a higher prevalence of CODD. The prevalence of CODD decreased with each log10 increase in flock size. We conclude that CODD is an infectious cause of lameness in sheep of increasing importance in GB. Introduction is linked to poor biosecurity with one likely source of the pathogen being introduction of or mixing with infected sheep. As with footrot, prevalence of CODD was lower in flocks where farmers focused on individual treatment to manage lameness and avoided foot bathing and trimming feet. We conclude that most of the currently recommended biosecurity and treatment approaches to control footrot in GB are also effective for control of CODD

Synthesis of Substituted Triazole-Pyrazole Hybrids using Triazenopyrazoles Precursors

A synthesis route to access triazole-pyrazole hybrids via pyrazolotriazenes was developed. Contrary to existing methods, this route allows the facile N-functionalization of the pyrazole before the attachment of the triazole unit via a copper-catalyzed azide-alkyne cycloaddition. The developed methodology was used to synthesize a library of over fifty novel multi-substituted pyrazole-triazole hybrids. We could also demonstrate a one-pot strategy that renders the isolation of potentially hazardous azides obsolete. In addition, the compatibility of the method with solid-phase synthesis was shown exemplarily

ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans

Allele-specific distinctions in the human apolipoprotein E (APOE) locus represent the best-characterized genetic predictor of Alzheimer's disease (AD) risk. Expression of isoform APOEε2 is associated with reduced risk, while APOEε3 is neutral and APOEε4 carriers exhibit increased susceptibility. Using Caenorhabditis elegans, we generated a novel suite of humanized transgenic nematodes to facilitate neuronal modeling of amyloid-beta peptide (Aβ) co-expression in the context of distinct human APOE alleles. We found that co-expression of human APOEε2 with Aβ attenuated Aβ-induced neurodegeneration, whereas expression of the APOEε4 allele had no effect on neurodegeneration, indicating a loss of neuroprotective capacity. Notably, the APOEε3 allele displayed an intermediate phenotype; it was not neuroprotective in young adults but attenuated neurodegeneration in older animals. There was no functional impact from the three APOE isoforms in the absence of Aβ co-expression. Pharmacological treatment that examined neuroprotective effects of APOE alleles on calcium homeostasis showed allele-specific responses to changes in ER-associated calcium dynamics in the Aβ background. Additionally, Aβ suppressed survival, an effect that was rescued by APOEε2 and APOEε3, but not APOEε4. Expression of the APOE alleles in neurons, independent of Aβ, exerted no impact on survival. Taken together, these results illustrate that C. elegans provides a powerful in vivo platform with which to explore how AD-associated neuronal pathways are modulated by distinct APOE gene products in the context of Aβ-associated neurotoxicity. The significance of both ApoE and Aβ to AD highlights the utility of this new pre-clinical model as a means to dissect their functional inter-relationship. This article has an associated First Person interview with the first author of the paper

Ecologische effecten van kustsuppleties : Systeembeschrijving (deel A), onderzoeksprioriteiten (deel B) en ontwerp uitvoeringsplan (deel C)

Rijkswaterstaat moet een suppletiestrategie ontwikkelen en uitvoeren welke voldoet aan de veiligheidsopgave en in samenhang is met natuurbehoud en –ontwikkeling van de Nederlandse kust. Dit document beschrijft de vraagstukken voor de komende vijf jaar voor mogelijke effecten van zandsuppleties op de ecologie van de Nederlandse kust. Het doel is om te onderzoeken hoe suppletiestrategieën in de nabije toekomst kunnen bijdragen aan het kustbeheer in samenhang met het kustecosysteem. De resultaten hiervan zullen ingebed moeten worden in de suppletiepraktijk via aanpassing en/of aanvulling van de richtlijnen voor suppleren

Reduction of air pollution through an alternative system of waste collection: The introduction of an underground waste container system

Gläser S, Stücken M. Reduction of air pollution through an alternative system of waste collection: The introduction of an underground waste container system. In: Ban M, Duic N, Schneider DR, et al., eds. Proceedings of the 15th Conference on Sustainable Development of Energy, Water and Environment Systems . Zagreb: Faculty of Mechanical Engineering and Naval Architecture, Zagreb ; 2020.Air pollution is a substantial environmental health risk in Europe. The municipal activity of waste collection contributes to air pollution. When collecting household waste via a door-to-door collection system the collection vehicles drive down all streets to empty the bins on the curb. In this paper we therefore deal with the question of whether the introduction of an underground waste container system, in which waste would be collected at central locations in so-called underground waste containers with a much larger capacity, is a sensible alternative that leads to less traffic and therefore less air pollution. We compare the costs of the two systems using two different optimization problems. On the basis of extended, artificial instances from the literature, we show the great potential for cost reduction of an underground waste collection system in comparison to a door-to-door collection system. The distances to be covered by the refuse collection vehicles can be significantly reduced, which is particularly important in times of air pollution

Enhancing FAIRdata by providing digital workflows from data generation to the publication of data: an open source approach described for cyclic voltammetry

Analytical data in chemistry and other disciplines is usually generated in different formats and lacks common data and metadata standards that are necessary for a FAIR handling of research data. In the work presented herein, we describe a workflow that uses non-standardized, in some cases proprietary data formats from cyclic voltammetry measurements coming from individual devices as an instructive example, to yield open, standardized data that are annotated with rich metadata. The presented workflow includes concepts, software and infrastructure that can be used to support the whole data life cycle from the measurement of data to the publication of data and metadata in repositories. Components used for this workflow were made available as open source, allowing the re-use of this approach in other laboratories. The methods described for cyclic voltammetry can be adapted and used for other measurements and experimental data collections, allowing for an easy way to integrate new methods for digitalized research and FAIR data management