FDE-vdW: A van der Waals Inclusive Subsystem Density-Functional Theory

We present a formally exact van der Waals inclusive electronic structure theory, called FDE-vdW, based on the Frozen Density Embedding formulation of subsystem Density-Functional Theory. In subsystem DFT, the energy functional is composed of subsystem additive and non-additive terms. We show that an appropriate definition of the long-range correlation energy is given by the value of the non-additive correlation functional. This functional is evaluated using the Fluctuation-Dissipation Theorem aided by a formally exact decomposition of the response functions into subsystem contributions. FDE-vdW is derived in detail and several approximate schemes are proposed, which lead to practical implementations of the method. We show that FDE-vdW is Casimir-Polder consistent, i.e. it reduces to the generalized Casimir-Polder formula for asymptotic inter-subsystems separations. Pilot calculations of binding energies of 13 weakly bound complexes singled out from the S22 set show a dramatic improvement upon semilocal subsystem DFT, provided that an appropriate exchange functional is employed. The convergence of FDE-vdW with basis set size is discussed, as well as its dependence on the choice of associated density functional approximant

The State of Small Business in the Netherlands 1997/1998

Negende uitgave van 'The State of Small Business in the Netherlands', met een beschrijving van Nederlandse MKB-bedrijven in internationaal perspectief. Aan bod komen de algemene kenmerken van het MKB, zoals aantallen bedrijven, werkgelegenheid, omzet, toegevoegde waarde en gemiddelde bedrijfsomvang. Voorts wordt aandacht besteed aan transnationale samenwerking tussen MKB-bedrijven en het door het MKB gebruikte externe advies. Ook wordt aandacht besteed aan milieu-aspecten van het MKB, vanuit het perspectief van risico’s en mogelijkheden. Waar mogelijk, zijn de gegevens van Nederland vergeleken met de andere landen van de 19 West-Europese landen die deel uitmaken van de European Economic Area.

The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: Understanding the determinants of binding affinity by comparison with Abl-SH3

BACKGROUND: SH3 domains are small protein modules of 60–85 amino acids that bind to short proline-rich sequences with moderate-to-low affinity and specificity. Interactions with SH3 domains play a crucial role in regulation of many cellular processes (some are related to cancer and AIDS) and have thus been interesting targets in drug design. The decapeptide APSYSPPPPP (p41) binds with relatively high affinity to the SH3 domain of the Abl tyrosine kinase (Abl-SH3), while it has a 100 times lower affinity for the α-spectrin SH3 domain (Spc-SH3). RESULTS: Here we present the high-resolution structure of the complex between the R21A mutant of Spc-SH3 and p41 derived from NMR data. Thermodynamic parameters of binding of p41 to both WT and R21A Spc-SH3 were measured by a combination of isothermal titration and differential scanning calorimetry. Mutation of arginine 21 to alanine in Spc-SH3 increases 3- to 4-fold the binding affinity for p41 due to elimination at the binding-site interface of the steric clash produced by the longer arginine side chain. Amide hydrogen-deuterium experiments on the free and p41-bound R21A Spc-SH3 domain indicate that binding elicits a strong reduction in the conformational flexibility of the domain. Despite the great differences in the thermodynamic magnitudes of binding, the structure of the R21A Spc-SH3:P41 complex is remarkably similar to that of the Abl-SH3:P41 complex, with only few differences in protein-ligand contacts at the specificity pocket. Using empirical methods for the prediction of binding energetics based on solvent-accessible surface area calculations, the differences in experimental energetics of binding between the two complexes could not be properly explained only on the basis of the structural differences observed between the complexes. We suggest that the experimental differences in binding energetics can be at least partially ascribed to the absence in the R21A Spc-SH3:P41 complex of several buried water molecules, which have been proposed previously to contribute largely to the highly negative enthalpy and entropy of binding in the Abl-SH3:P41 complex. CONCLUSION: Based on a deep structural and thermodynamic analysis of a low and high affinity complex of two different SH3 domains with the same ligand p41, we underline the importance of taking into account in any effective strategy of rational design of ligands, factors different from the direct protein-ligand interactions, such as the mediation of interactions by water molecules or the existence of cooperative conformational effects induced by binding

Bestuurdersaansprakelijkheid in de praktijk

__Samenvatting__ Een van de mogelijkheden om de schade van wanbestuur te beperken, is het aansprakelijk stellen van de bestuurders die deze schade hebben veroorzaakt. Waar de mogelijkheid van een externe aansprakelijkheidsprocedure veelvuldig wordt benut, lijkt het veel minder vaak voor te komen dat een interne aansprakelijkheidsprocedure wordt gestart, door de rechtspersoon tegen de eigen (ex-)bestuurders. In deze bijdrage brengen wij daarom de redenen in kaart die meespelen in de beslissing om bestuurders al dan niet aansprakelijk te stellen. Inzicht in de beweegredenen van betrokkenen kan licht werpen op de werking van artikel 2:9 BW in de praktijk, en op eventuele belemmeringen die aan het aansprakelijk stellen in de weg staan. Daarmee kan een indruk ontstaan van de wijze waarop de beoogde functies van interne bestuurdersaansprakelijkheid in de praktijk worden vervuld

Characteristics of Positive Deviants in Western Chimpanzee Populations

With continued expansion of anthropogenically modified landscapes, the proximity between humans and wildlife is continuing to increase, frequently resulting in species decline. Occasionally however, species are able to persist and there is an increased interest in understanding such positive outliers and underlying mechanisms. Eventually, such insights can inform the design of effective conservation interventions by mimicking aspects of the social-ecological conditions found in areas of species persistence. Recently, frameworks have been developed to study the heterogeneity of species persistence across populations with a focus on positive outliers. Applications are still rare, and to our knowledge this is one of the first studies using this approach for terrestrial species conservation. We applied the positive deviance concept to the western chimpanzee, which occurs in a variety of social-ecological landscapes. It is now categorized as Critically Endangered due to hunting and habitat loss and resulting excessive decline of most of its populations. Here we are interested in understanding why some of the populations did not decline. We compiled a dataset of 17,109 chimpanzee survey transects (10,929 km) across nine countries and linked them to a range of social and ecological variables. We found that chimpanzees seemed to persist within three social-ecological configurations: first, rainforest habitats with a low degree of human impact, second, steep areas, and third, areas with high prevalence of hunting taboos and low degree of human impact. The largest chimpanzee populations are nowadays found under the third social-ecological configuration, even though most of these areas are not officially protected. Most commonly chimpanzee conservation has been based on exclusion of threats by creation of protected areas and law enforcement. Our findings suggest, however, that this approach should be complemented by an additional focus on threat reduction, i.e., interventions that directly target individual human behavior that is most threatening to chimpanzees, which is hunting. Although changing human behavior is difficult, stakeholder co-designed behavioral change approaches developed in the social sciences have been used successfully to promote pro-environmental behavior. With only a fraction of chimpanzees and primates living inside protected areas, such new approaches might be a way forward to improve primate conservation

Advancing conservation planning for western chimpanzees using IUCN SSC A.P.E.S.-the case of a taxon-specific database

Even though information on global biodiversity trends becomes increasingly available, large taxonomic and spatial data gaps persist at the scale relevant to planning conservation interventions. This is because data collectors are hesitant to share datawith global repositories due toworkload, lack of incentives, and perceived risk of losing intellectual property rights. In contrast, due to greater conceptual and methodological proximity, taxon-specific database initiatives can provide more direct benefits to data collectors through research collaborations and shared authorship.TheIUCNSSC Ape Populations, Environments and Surveys (A.P.E.S.) database was created in 2005 as a repository for data on great apes and other primate taxa. It aims to acquire field survey data and make different types of data accessible, and provide up-to-date species status information. To support the current update of the conservation action plan forwestern chimpanzees (Pan troglodytes verus) we compiled field surveys for this taxon from IUCNSSCA.P.E.S., 75%ofwhich were unpublished. We used spatial modeling to infer total population size, range-wide density distribution, population connectivity and landscape-scale metrics.Weestimated a total abundance of 52 800 (95%CI 17 577–96 564) western chimpanzees, of which only 17%occurred in national parks.We also found that 10%of chimpanzees live within 25 kmof fourmulti-national ‘development corridors’ currently planned forWestAfrica. These large infrastructure projects aim to promote economic integration and agriculture expansion, but are likely to cause further habitat loss and reduce population connectivity.We close by demonstrating the wealth of conservation-relevant information derivable from a taxon-specific database like IUCNSSC A.P.E.S. and propose that a network of many more such databases could be created to provide the essential information to conservation that can neither be supplied by one-off projects nor by global repositories, and thus are highly complementary to existing initiatives

Memorial Viewpoint for Joop van Lenthe

Contains fulltext : 283769.pdf (Publisher’s version ) (Closed access

Persistent anthrax as a major driver of wildlife mortality in a tropical rainforest

Anthrax is a globally important animal disease and zoonosis. Despite this, our current knowledge of anthrax ecology is largely limited to arid ecosystems, where outbreaks are most commonly reported. Here we show that the dynamics of an anthrax-causing agent, Bacillus cereus biovar anthracis, in a tropical rainforest have severe consequences for local wildlife communities. Using data and samples collected over three decades, we show that rainforest anthrax is a persistent and widespread cause of death for a broad range of mammalian hosts. We predict that this pathogen will accelerate the decline and possibly result in the extirpation of local chimpanzee (Pan troglodytes verus) populations. We present the epidemiology of a cryptic pathogen and show that its presence has important implications for conservation