Aktuelle Entwicklungen im Kontext von Online-Wahlen und digitalen Abstimmungen

Seit Beginn der Pandemie stehen viele Institutionen (inkl. Vereinen, Unternehmen und Behörden) vor der Frage, wie sie ihre Wahlen und geheimen Abstimmungen organisieren sollen – ohne die Gesundheit der Wähler*innen und Wahlhelfer*innen zu gefährden. Einige Wahlverantwortliche haben sich für die Durchführung von Online-Wahlen bzw. digitalen Abstimmungen entschieden. Erfahrungen anderer Wahlverantwortlicher, die bereits vor der Pandemie online gewählt haben, ab es in Deutschland kaum. Vor der Pandemie wurde das Thema Online-Wahlen in Deutschland – bedingt durch das sogenannte Wahlgeräte-Urteil des Bundesverfassungsgerichts (2009) – kaum diskutiert. Nach über einem Jahr Pandemie sieht die Lage anders aus: Inzwischen fanden einige Wahlen und Abstimmungen online statt. Allerdings entsprechen die dazu eingesetzten Systeme häufig nicht dem Stand der Forschung. Für zukünftige Nutzungen von Online-Wahlen und digitalen Abstimmungen (insbesondere auch nach der Pandemie) ist es daher wichtig, dass Wahlverantwortliche, Kandidat*innen und Wähler*innen verstehen, welches Risiko die bisher eingesetzten Systeme mit sich bringen und wie einzelne Entwicklungen im Kontext von Online-Wahlen und digitalen Abstimmungen einzuordnen sind. Nur so können informierte Entscheidungen im Hinblick auf die einzusetzenden Ansätze getroffen und die Demokratie auch in Zukunft geschützt werden

Using ecological and field survey data to establish a national list of the wild bee pollinators of crops

The importance of wild bees for crop pollination is well established, but less is known about which species contribute to service delivery to inform agricultural management, monitoring and conservation. Using sites in Great Britain as a case study, we use a novel qualitative approach combining ecological information and field survey data to establish a national list of crop pollinating bees for four economically important crops (apple, field bean, oilseed rape and strawberry). A traits data base was used to establish potential pollinators, and combined with field data to identify both dominant crop flower visiting bee species and other species that could be important crop pollinators, but which are not presently sampled in large numbers on crops flowers. Whilst we found evidence that a small number of common, generalist species make a disproportionate contribution to flower visits, many more species were identified as potential pollinators, including rare and specialist species. Furthermore, we found evidence of substantial variation in the bee communities of different crops. Establishing a national list of crop pollinators is important for practitioners and policy makers, allowing targeted management approaches for improved ecosystem services, conservation and species monitoring. Data can be used to make recommendations about how pollinator diversity could be promoted in agricultural landscapes. Our results suggest agri-environment schemes need to support a higher diversity of species than at present, notably of solitary bees. Management would also benefit from targeting specific species to enhance crop pollination services to particular crops. Whilst our study is focused upon Great Britain, our methodology can easily be applied to other countries, crops and groups of pollinating insects.LH was funded by NERC QMEE CDT. EJB was funded by a BBSRC Ph.D. studentship under grant BB/F016581/1. LB was was supported by the Scholarship Program of the German Federal Environmental Foundation (Deutsche Bundesstiftung Umwelt, DBU, AZ 20014/302). AJC was funded by the BBSRC and Syngenta UK as part of a case award Ph.D. (grant no. 1518739). AE was funded by the Swiss National Science Foundation (grant number 405940-115642). DG and A-MK were funded by grant PCIN2014-145-C02-02 (MinECo; EcoFruit project BiodivERsA-FACCE2014-74). MG was supported by Establishing a UK Pollinator Monitoring and Research Partnership (PMRP) a collaborative project funded by Defra, the Welsh and Scottish Governments, JNCC and project partners’. GAdG was funded via research projects BO-11-011.01-051 and BO-43-011.06-007, commissioned by the Dutch Ministry of Agriculture, Nature and Food Quality. DK was funded by the Dutch Ministry of Economic Affairs (BO-11-011.01-011). AK-H was funded by the NKFIH project (FK123813), the Bolyai János Fellowship of the MTA, the ÚNKP-19-4-SZIE-3 New National Excellence Program of the Ministry for Innovation and Technology, and together with RF by the Hungarian Scientific Research Fund OTKA 101940. MM was funded by Waitrose & Partners, Fruition PO, and the University of Worcester. MM was funded by grant INIA-RTA2013-00139-C03-01 (MinECo and FEDER). BBP and RFS were funded by the UK Natural Environment Research Council as part of Wessex BESS (ref. NE/J014680/1). NJV was funded by the Walloon Region (Belgium) Direction générale opérationnelle de l’Agriculture, des Ressources naturelles et de l’Environnement (DGO3) for the "Modèle permaculturel" project on biodiversity in micro-farms, FNRS/FWO joint programme EOS — Excellence Of Science CliPS: Climate change and its impact on Pollination Services (project 30947854)". CW was funded by the Deutsche Forschungsgemeinschaft (DFG) (Project number 405945293). BW was funded by the Natural Environment Research Council (NERC) under research programme NE/N018125/1 ASSIST – Achieving Sustainable Agricultural Systems www.assist.ceh.ac.uk. TB and TO are supported by BBSRC, NERC, ESRC and the Scottish Government under the Global Food Security Programme (Grant BB/R00580X/1)

Diagnostic Mirror Concept Development for Use in the Complex Environment of a Fusion Reactor

Light-based diagnostic systems of fusion reactors require optical mirrors to channel light through the structures surrounding the plasma. With increasing plasma volume, power and plasma burn time, the environmental conditions grow more demanding and new requirements arise. In this dissertation, the design of optical mirrors inside the vacuum chamber of the prototype reactor ITER (Latin "the way") and future fusion power plants are investigated. Comparing the state of the art with the boundary conditions close to the fusion plasma, existing mirror designs and choices for the re ective surface are evaluated. For the design, it is not the individual boundary conditions that are critical, but rather, their combination and the resulting interactions. Drawing from the existing designs, possible realizations for central functionality are discussed. Included in the discussion are substrate choice, mounting, adjustment and thermal contacting as well as positioning of the mirror assembly compatible with hot cell maintenance. Building on the general discussion, mirror concepts for the charge exchange recombination spectroscopy (CXRS) diagnostic system for the ITER plasma core are proposed and simulated. In addition, prototypes are manufactured and tested to assess critical aspects of the proposed design. Testing includes positioning by pins, manufacturing of a stainless steel substrate with uid channels adapted to the mirror shape, and tests with an SiO$_{2}$/TiO$_{2}$ dielectric coating under selected ITER conditions. As a result of the work, the fusion reactor mirror design considerations given in the principal design discussion can be used as a basis for other diagnostic systems as well. In the case of the core CXRS mirror concept for ITER, the basic suitability was shown and critical topics were identified where additional work is necessary

Paying the Price of Desolvation in Solvent-Exposed Protein Pockets: Impact of Distal Solubilizing Groups on Affinity and Binding Thermodynamics in a Series of Thermolysin Inhibitors

In lead optimization, open, solvent-exposed protein pockets are often disregarded as prospective binding sites. Because of bulk-solvent proximity, researchers are instead enticed to attach charged polar groups at inhibitor scaffolds to improve solubility and pharmacokinetic properties. It is rarely considered that solvent effects from water reorganization in the first hydration shell of protein-ligand complexes can have a significant impact on binding. We investigate the thermodynamic fingerprint of thermolysin inhibitors featuring terminal charged ammonium groups that are gradually pulled from a distal, solvent-exposed position into the flat, bowl-shaped S; 2; ' pocket. Even for the most remote attachment, costs for partial desolvation of the polar group next to the protein-solvent interface are difficult to compensate by interactions with the protein or surrounding water molecules. Through direct comparison with hydrophobic analogues, a significant 180-fold affinity loss was recorded, which questions popular strategies to attach polar ligand-solubilizing groups at the exposed terminus of substituents accommodated in flat open pockets

Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin

Kinetic parameters of protein-ligand interactions are progressively acknowledged as valuable information for rational drug discovery. However, a targeted optimization of binding kinetics is not easy to achieve, and further systematic studies are necessary to increase the understanding about molecular mechanisms involved. We determined association and dissociation rate constants for 17 inhibitors of the metalloprotease thermolysin by surface plasmon resonance spectroscopy and correlated kinetic data with high-resolution crystal structures in complex with the protein. From the structure-kinetics relationship, we conclude that the strength of interaction with Asn112 correlates with the rate-limiting step of dissociation. This residue is located at the beginning of a β-strand motif that lines the binding cleft and is commonly believed to align a substrate for catalysis. A reduced mobility of the Asn112 side chain owing to an enhanced engagement in charge-assisted hydrogen bonds prevents the conformational adjustment associated with ligand release and transformation of the enzyme to its open state. This hypothesis is supported by kinetic data of ZF; P; LA, a known pseudopeptidic inhibitor of thermolysin, which blocks the conformational transition of Asn112. Interference with this retrograde induced-fit mechanism results in variation of the residence time of thermolysin inhibitors by a factor of 74 000. The high conservation of this structural motif within the M4 and M13 metalloprotease families underpins the importance of this feature and has significant implications for drug discovery

How Nothing Boosts Affinity: Hydrophobic Ligand Binding to the Virtually Vacated S₁′ Pocket of Thermolysin

We investigated the hydration state of the deep, well-accessible hydrophobic S₁′ specificity pocket of the metalloprotease thermolysin with purposefully designed ligands using high-resolution crystallography and isothermal titration calorimetry. The S₁′ pocket is known to recognize selectively a very stringent set of aliphatic side chains such as valine, leucine, and isoleucine of putative substrates. We engineered a weak-binding ligand covering the active site of the protease without addressing the S₁′ pocket, thus transforming it into an enclosed cavity. Its sustained accessibility could be proved by accommodating noble gas atoms into the pocket in the crystalline state. The topology and electron content of the enclosed pocket with a volume of 141 ų were analyzed using an experimental MAD-phased electron density map that was calibrated to an absolute electron number scale, enabling access to the total electron content within the cavity. Our analysis indicates that the S₁′ pocket is virtually vacated, thus free of any water molecules. The thermodynamic signature of the reduction of the void within the pocket by growing aliphatic P₁′ substituents (H, Me, <i>i</i>Pr, <i>i</i>Bu) reveals a dramatic, enthalpy-dominated gain in free energy of binding resulting in a factor of 41 000 in <i>K</i>_d for the H-to-<i>i</i>Bu transformation. Substituents placing polar decoy groups into the pocket to capture putatively present water molecules could not collect any evidence for a bound solvent molecule