Mol. Cell. Proteomics

Chemical cross-linking in combination with mass spectrometric analysis offers the potential to obtain low-resolution structural information from proteins and protein complexes. Identification of peptides connected by a cross-link provides direct evidence for the physical interaction of amino acid side chains, information that can be used for computational modeling purposes. Despite impressive advances that were made in recent years, the number of experimentally observed cross-links still falls below the number of possible contacts of cross-linkable side chains within the span of the cross-linker. Here, we propose two complementary experimental strategies to expand cross-linking data sets. First, enrichment of cross-linked peptides by size exclusion chromatography selects cross-linked peptides based on their higher molecular mass, thereby depleting the majority of unmodified peptides present in proteolytic digests of cross-linked samples. Second, we demonstrate that the use of proteases in addition to trypsin, such as Asp-N, can additionally boost the number of observable cross-linking sites. The benefits of both SEC enrichment and multiprotease digests are demonstrated on a set of model proteins and the improved workflow is applied to the characterization of the 20S proteasome from rabbit and Schizosaccharomyces pombe

Proving or Improving: On Health Care Research as a Form of Self-Reflection

As it is, clinical trials are the gold standard of health care research, employed to prove that the care practices they study are good. Here, the author suggests that we would do better to develop research methods that work toward another goal: to improve care practices. This requires that we no longer foreground the effectiveness but, instead, investigate the various effects of interventions. If undesirable, they might then be tinkered with. As a part of this, the effects on bodily parameters and on the intricacies of daily lives should not be separated out but studied in connection. With examples drawn from studies into care practices for patients with diabetes or atherosclerosis, the author argues that instead of trying to turn the clinic into a laboratory, we should strive to support and strengthen clinical ways of working

Revisiting the Schwarzschild and the Hilbert-Droste Solutions of Einstein Equation and the Maximal Extension of the Latter

In this pedagogical note, the differences between the Schwarzschild and the Hilbert-Droste solutions of Einstein equation are scrutinized through a rigorous mathematical approach, based on the idea of warped product of manifolds. It will be shown that those solutions are indeed different because the topologies of the manifolds corresponding to them are different. After establishing this fact beyond any doubt, the maximal extension of the Hilbert-Droste solution (the Kruskal-Szekeres spacetime) is derived with details and its topology compared with the ones of the Schwazschild and the Hilbert-Droste solution. We also study the problem of the imbedding of the Hilbert-Droste solution in a vector manifold, hopefully clarifying the work of Kasner and Fronsdal on the subject. In an Appendix, we present a rigorous discussion of the Einstein-Rosen Bridge. A comprehensive bibliography of the historical papers involved in our work is given at the end.Comment: 59 pages, no figure

Environmental Authority: Transformations and Relocations in Global Modernity = Autoridade ambiental: transformações e relocações na modernidade global

As a public good, the environment has traditionally been handled by public authorities. However, with globalization conventional state environmental authority is transformed, relocated and deterritorialized. New non-state environmental authorities emerge. This paper conceptualizes the shifts in and relocation of environmental authority structures and illustrates this with examples from the fields of certification and labeling and environmental partnerships. While relocation does take place, new environmental authority structures are often mixes of state and non-state authorities. The paper finally assesses these developments, reflecting on the conventional criticism of the poor environmental and democratic potentials of such new non-state environmental authoritie

Does being R&D intensive still discourage outsourcing? : evidence from Dutch manufacturing

Being R&D intensive has traditionally been seen as an impediment to outsourcing. This study confirms that empirically this was the case for a set of manufacturing industries in the Netherlands in the early 1990s but also shows that R&D intensity became a positive predictor for changes in outsourcing levels over the 1990s, suggesting firms in R&D intensive industries have increasingly started to rely on partnership relations with outside suppliers. This confirms the need to move the analysis from scale, opportunism and appropriation concerns to a relational perspective when studying outsourcing in R&D intensive industries

Accurate ab initio anharmonic force field and heat of formation for silane, SiH_4

From large basis set coupled cluster calculations and a minor empirical adjustment, an anharmonic force field for silane has been derived that is consistently of spectroscopic quality ($\pm 1 cm^{-1}$ on vibrational fundamentals) for all isotopomers of silane studied. Inner-shell polarization functions have an appreciable effect on computed properties and even on anharmonic corrections. From large basis set coupled cluster calculations and extrapolations to the infinite-basis set limit, we obtain TAE_0=303.80 \pm 0.18 kcal/mol, which includes an anharmonic zero-point energy (19.59 kcal/mol), inner-shell correlation (-0.36 kcal/mol), scalar relativistic corrections (-0.70 kcal/mol), and atomic spin-orbit corrections (-0.43 kcal/mol). In combination with the recently revised \HVSI{0}, we obtain $\Delta H^{\circ}_{f,0}[SiH_4(g)]=9.9 \pm 0.4 kcal/mol$, in between the two established experimental values.Comment: Mol. Phys., in pres