Spatial development policy in the European Constitutional Treaty: position paper from the ARL, Hanover

As the implementation of the European single market has continued, it has become increasingly clear that a more closely integrated Europe cannot simply have an exclusively economic dimension. For a harmonious overall development, a large number of other policy areas clearly have to be included. One of these is spatial policy (spatial development policy), which aims to contribute to a more balanced spatial development. In the view of the ARL, the time has now come to initiate the institutional steps which have thus far emerged from the Europe-wide debate. The "territorial cohesion" of the Union cannot be achieved until we have clear legal foundations and definitions, which must also apply to spatial development policy in Europe. For that reason, the constitutional aspects of a European spatial development policy must form part of the agenda of the European Constitutional Convention.Mit der fortschreitenden Verwirklichung des Europäischen Binnenmarktes ist im Laufe der Zeit immer deutlicher geworden, dass das zusammenwachsende Europa nicht lediglich eine ökonomische Dimension haben kann, sondern dass für eine harmonische Gesamtentwicklung zahlreiche weitere Politikfelder einbezogen werden müssen. Dazu gehört auch die Raumpolitik (Raumentwicklungspolitik) mit dem Ziel einer ausgewogenen räumlichen Entwicklung. Nach Auffassung der Akademie ist es an der Zeit, aus dem bisherigen europaweiten Diskussionsstand endlich institutionelle Konsequenzen zu ziehen. Der "territoriale Zusammenhalt" der Union kann nicht gesichert werden, solange es keine klaren rechtlichen Grundlagen und Abgrenzungen auch für die Raumentwicklungspolitik in Europa gibt. Deshalb gehören die konstitutionellen Fragen einer europäischen Raumentwicklungspolitik auf die Agenda des Europäischen Verfassungskonvents.L'achèvement progressif du Grand marché intérieur de l'Union européenne a fait ressortir de plus en plus clairement au fil du temps que l'Europe, en s'intégrant, ne doit pas se limiter à la seule dimension économique. Son évolution harmonieuse globale requiert plutôt une approche qui englobe de nombreux autres champs politiques comme par exemple la politique spatiale (politique de développement de l'espace) envisageant un développement spatial équilibré. De l'avis de l'ARL, il est temps de tirer enfin des conclusions d'ordre institutionnel de l'état d'avancement des discussions en Europe. Il ne sera pas possible d'assurer la "cohésion territoriale" de l'Union européenne sans avoir créé des bases et des délimitations juridiques claires pour la politique du développement de l'espace européen. C'est pourquoi il appartient à la Convention européenne de traiter les questions constitutionnelles relatives à la politique européenne de développement de l'espace

Patterns-based Evaluation of Open Source BPM Systems: The Cases of jBPM, OpenWFE, and Enhydra Shark

In keeping with the proliferation of free software development initiatives and the increased interest in the business process management domain, many open source workflow and business process management systems have appeared during the last few years and are now under active development. This upsurge gives rise to two important questions: what are the capabilities of these systems? and how do they compare to each other and to their closed source counterparts? i.e. in other words what is the state-of-the-art in the area?. To gain an insight into the area, we have conducted an in-depth analysis of three of the major open source workflow management systems - jBPM, OpenWFE and Enhydra Shark, the results of which are reported here. This analysis is based on the workflow patterns framework and provides a continuation of the series of evaluations performed using the same framework on closed source systems, business process modeling languages and web-service composition standards. The results from evaluations of the three open source systems are compared with each other and also with the results from evaluations of three representative closed source systems - Staffware, WebSphere MQ and Oracle BPEL PM, documented in earlier works. The overall conclusion is that open source systems are targeted more toward developers rather than business analysts. They generally provide less support for the patterns than closed source systems, particularly with respect to the resource perspective which describes the various ways in which work is distributed amongst business users and managed through to completion

Breaking Up the C Complex Spliceosome Shows Stable Association of Proteins with the Lariat Intron Intermediate

Spliceosome assembly requires several structural rearrangements to position the components of the catalytic core. Many of these rearrangements involve successive strengthening and weakening of different RNA∶RNA and RNA∶proteins interactions within the complex. To gain insight into the organization of the catalytic core of the spliceosome arrested between the two steps of splicing chemistry (C complex), we investigated the effects of exposing C complex to low concentrations of urea. We find that in the presence of 3M urea C complex separates into at least three sub-complexes. One sub-complex contains the 5′exon, another contains the intron-lariat intermediate, and U2/U5/U6 snRNAs likely comprise a third sub-complex. We purified the intron-lariat intermediate sub-complex and identified several proteins, including U2 snRNP and PRP19 complex (NTC) components. The data from our study indicate that U2 snRNP proteins in C complex are more stably associated with the lariat-intron intermediate than the U2 snRNA. The results also suggest a set of candidate proteins that hold the lariat-intron intermediate together in C complex. This information is critical for further interpreting the complex architecture of the mammalian spliceosome

Biotic interactions as drivers of algal origin and evolution

Biotic interactions underlie life's diversity and are the lynchpin to understanding its complexity and resilience within an ecological niche. Algal biologists have embraced this paradigm, and studies building on the explosive growth in omics and cell biology methods have facilitated the in-depth analysis of nonmodel organisms and communities from a variety of ecosystems. In turn, these advances have enabled a major revision of our understanding of the origin and evolution of photosynthesis in eukaryotes, bacterial–algal interactions, control of massive algal blooms in the ocean, and the maintenance and degradation of coral reefs. Here, we review some of the most exciting developments in the field of algal biotic interactions and identify challenges for scientists in the coming years. We foresee the development of an algal knowledgebase that integrates ecosystem-wide omics data and the development of molecular tools/resources to perform functional analyses of individuals in isolation and in populations. These assets will allow us to move beyond mechanistic studies of a single species towards understanding the interactions amongst algae and other organisms in both the laboratory and the field

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570