Modelling process knowledge in architectural design: A case-based approach

The paper presents on-going research aimed at the understanding and support of process knowledge in architectural design, from early and not sufficiently defined, to satisfactorily-defined phases. Today, technical, planning, management and environmental issues have created a scenario of such complexity that traditionally efficient control tools (e.g. technical manuals) are inadequate and there is a demand for new, integrated instruments to handle the decision process underlying architectural design. We assume design as a recursive and incrementally specified intentional planning activity, involving goals, constraints and their relationships. The essence of architectural design is thus encapsulated in the continual recursive transformation of the initial model, in order to map the desired state onto the enacted one. On the basis of this concept of design we describe the model of an environment aimed at progressively representing the enlarging space of acquired knowledge, and at supporting the designer's central role in the management of complexity

Partikelforureningen set i et EU-perspektiv

EU-kommissionen skal i slutningen af 2003 rapportere om muligheder for at opfylde de krav til luftkvaliteten, der er træder i kraft i 2005, og som er foreslået for 2010. Der er nedsat en arbejdsgruppe, der skal se specielt på situationen vedrørende partikler, herunder den nuværende luftkvalitet i EU, niveauer og tendenser, karakterisering af kilder til partikelforureningen i forskellige EU-lande og mulige reduktions tiltag. Indlægget vil give et overblik over luftforureningen med partikler i Europa, og diskutere nogle af de konklusioner, det kan forventes, arbejdsgruppen kommer frem til

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests the involvement of autophagic as well as lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be the major lysosomal protease involved in SNCA degradation, its deficiency has been linked to the presence of insoluble SNCA conformers in the brain of mice and humans as well as to the transcellular transmission of SNCA aggregates. We here postulate that SNCA degradation can be enhanced by the application of the recombinant human proform of CTSD (rHsCTSD). Our results reveal that rHsCTSD is efficiently endocytosed by neuronal cells, correctly targeted to lysosomes and matured to an enzymatically active protease. In dopaminergic neurons derived from induced pluripotent stem cells (iPSC) of PD patients harboring the A53T mutation within the SNCA gene, we confirm the reduction of insoluble SNCA after treatment with rHsCTSD. Moreover, we demonstrate a decrease of pathological SNCA conformers in the brain and within primary neurons of a CTSD-deficient mouse model after dosing with rHsCTSD. Boosting lysosomal CTSD activity not only enhanced SNCA clearance, but also restored endo-lysosome and autophagy function in human and murine neurons as well as tissue. Our findings indicate that CTSD is critical for SNCA clearance and function. Thus, enzyme replacement strategies utilizing CTSD may also be of therapeutic interest for the treatment of PD and other synucleinopathies aiming to decrease the SNCA burden.authorsversionepub_ahead_of_prin

Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections

SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron