Translating the concept of sustainability into architectural design practices: London’s City Hall as an exemplar

This thesis is a Science and Technology Studies (STS) inspired exploration of the design practices that brought London’s City Hall (1997-2002) into being. The minister responsible for finding a suitable building for the Greater London Authority (GLA) ambitiously declared it to be an exemplar project of “environmentally progressive objectives, the principles of sustainability”. Since there is much contestation about how to enact such an ambitious agenda, I as a form of theory in practice retrospectively follow architects, engineers, clients and others through the complexities of design process to investigate how the concept of sustainability and environmental problems were interpreted from the outset and then transformed into environmental (and other) design challenges and targets in order to guide and align the diverse practitioners who worked towards materialising City Hall. In order to develop a better understanding of how environmental challenges were addressed during City Hall’s contingent and unpredictable practices, I draw on the concept of translation to analyse how design problems were defined in the joint action plan to house the GLA, how design practices expanded through the concurrent production of design knowledge and association of additional heterogeneous elements, and how City Hall increasingly took shape through negotiations, choices, conflicts, transformations and adaptations. Through many translations the design briefing, building forms, landmark building requests, technological devices, specific interests, environmental performance targets, facade specifications and many other issues became reciprocally modified, reordered and stabilised. I then use post-occupancy data to explore City Hall in operation (2002 to 2011) to develop an understanding of how its facility management produced knowledge about the headquarters’ environmental operations. Thus I develop an account to what extent environmental performance targets were translated from the world of the design studio to the world of actual building operations

Die Beeinflussung zentraler Signalkaskaden von Inflammation und kolorektaler Karzinogenese durch die Lipidphosphatase Myotubularin-Related Protein-7

Hintergrund Die molekulare Pathologie der weit verbreiteten kolorektalen Karzinome beruht auf Treibermutationen in den WNT-β-Catenin- und EGF-assoziierten Signalwegen. Im Besonderen stellen KRAS-Mutationen in der Tumortherapie eine große Herausforderung dar. Die Lipidphosphatase MTMR7 gehört zu den Myotubularinen, eine Gruppe von PtIns-Phosphatasen, deren Funktion im Vesikeltransport beschrieben ist. Unsere Arbeitsgruppe zeigte, dass MTMR7 in gastro-intestinalen Tumormodellen eine Verringerung der K-RAS nachgeschalteten MEK1/2-ERK1/2 und AKT-Phosphorylierungen bewirkt. Zudem wurde eine agonistische Aktivität zu dem Peroxisomen-Proliferator-aktivierten Rezeptor γ (PPARγ) gezeigt. Dadurch entfaltet PPARγ seine genomische, antiproliferative Wirkung. In der aktuellen Arbeit wurden neben der EGFR-RAS-Signalkaskade weitere Signalwege auf den Einfluss durch MTMR7 untersucht. Material und Methoden Es wurden Luziferase-Reportergen-Tests durchgeführt, bei denen Modell- und kolorektale Tumorzellen mit Vektoren wichtiger Signalwege transfiziert wurden (PPARγ Response Element (PPRE), Serum Response Element (SRE), Topflash-TCF4/β-Catenin, NFκB-responsive Reporter, PDL1 Promotor). Zudem wurden die Zellen mit MTMR7-Expressionsplasmid kotransfiziert, oder mit MTMR7-CC-Peptid behandelt. Des Weiteren wurden Western Blots und immun-histochemische Färbungen eines gastrointestinalen Maus-Tumormodells durchgeführt. Ergebnisse MTMR7 hemmte die Serum response element-abhängige Promotoraktivität, sowie die Topflash-TCF4/β-Catenin-Reporter-Aktivität und verringerte den zellulären Gehalt von nukleärem aktiven β-Catenin. Die Aktivität des PDL1 Promotors und des PPRE wurden dagegen durch die Behandlung mit dem MTMR7-CC-Peptid verstärkt. Die Aktivität von NFκB wurde nicht beeinflusst. Immunhistochemische Auswertungen des Maus-Modells zeigen eine relative Verringerung von nukleärem β-Catenin, ERK1/2 und einen verminderten Ki67-Index. Schlussfolgerung und Ausblick MTMR7 bewirkt eine Hemmung der EGFR-RAS-Signalkaskade auf der genomischen Ebene. Diese Hemmung könnte wiederum eine verminderte Inhibition von PPARγ bewirken. Dadurch und durch die bereits bekannte agonistische Interaktion von MTMR7 und PPARγ könnte die PPARγ-abhängige Aktivierung des PDL1-Promotors verstärkt werden. Die Hemmung des WNT-β-Catenin-Signalweges könnte durch eine Interaktion oder Beeinflussung von PPARγ und β-Catenin vermittelt sein, wodurch die Aktivität des Letzteren vermindert wird. Eine PPARγ-unabhängige WNT-Inhibition erscheint auch möglich und könnte mit der subzellulären Lokalisation von MTMR7 zusammenhängen. Zusammenfassend weisen die erhobenen Daten daraufhin, dass MTMR7 als Tumorsuppressor wirken kann. Die molekularen Mechanismen sollten in zukünftigen Experimenten auf eine mögliche therapeutische Relevanz im KRK geprüft werden

Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells

Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming inflammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhesion molecules on tumor necrosis factor-α (TNF-α) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under flow in vitro. TNF-α stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-di-chloro-phenyl)-3-pyrazolidone. We tested the inhibition of adhesion molecule expression at different inhibitor concentrations before, during, and after the stimulation of HUVECs. The inhibition of endothelial cell expression on HUVECs was measured by flow cytometry. Rolling and firm adhesion of leukocytes to pretreated endothelium was examined in a parallel plate flow chamber. Phenidone inhibited the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVECs when added prior to HUVEC stimulation. The inhibitory effect of phenidone was still observed when added simultaneously, but not when added after HUVEC stimulation. 4-4-dimethyl-phenidone and 5-phenyl-phenidone inhibited the expression of adhesion molecules more effectively than phenidone. The attenuation of leukocyte rolling under flow conditions was also significantly more effective with 4-4-dimethyl-phenidone than with phenidone. Lipoxygenase inhibitors might be of therapeutically interest for the treatment of overwhelming systemic inflammation during shock, trauma, and sepsis

Self-organized critical neural networks

A mechanism for self-organization of the degree of connectivity in model neural networks is studied. Network connectivity is regulated locally on the basis of an order parameter of the global dynamics which is estimated from an observable at the single synapse level. This principle is studied in a two-dimensional neural network with randomly wired asymmetric weights. In this class of networks, network connectivity is closely related to a phase transition between ordered and disordered dynamics. A slow topology change is imposed on the network through a local rewiring rule motivated by activity-dependent synaptic development: Neighbor neurons whose activity is correlated, on average develop a new connection while uncorrelated neighbors tend to disconnect. As a result, robust self-organization of the network towards the order disorder transition occurs. Convergence is independent of initial conditions, robust against thermal noise, and does not require fine tuning of parameters.Comment: 5 pages RevTeX, 7 figures PostScrip

Kritische Entgegnung auf die Studie «Zur Relevanz informatischer Bildung in der Schule für den Erwerb computer- bzw. informationsbezogener Kompetenzen»

Dieser Beitrag nimmt Bezug auf den Artikel «Zur Relevanz informatischer Bildung in der Schule für den Erwerb computer- und informationsbezogener Kompetenzen als Teilaspekt von Medienbildung», der an gleicher Stelle in einem früheren Heft erschien. Basierend auf Sekundäranalysen der ICILS 2013-Daten wird darin geschlussfolgert, es gebe einen Zusammenhang zwischen der Belegung von Informatikunterricht in der Schule und geringeren computer- bzw. informationsbezogenen Kompetenzen. Der vorliegende Beitrag legt dar, warum diese und andere Schlussfolgerungen basierend auf dem zur Verfügung stehenden Datenmaterial und der von den Autorinnen gewählten Auswertungsmethodik wissenschaftlich nicht haltbar sind

NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272

BACKGROUND: The most important receptor for nitic oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase. RESULTS: We developed a photoaffinity label ((3)H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of (3)H-meta-PAL together with the highly purified sGC leads to a covalent binding to the α(1)-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the (3)H-meta-PAL labeled sGC was fragmented by CNBr digest. The (3)H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236–290 of the α(1)-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the (3)H-meta-PAL. CONCLUSIONS: Our data demonstrate that the region surrounding the cysteines 238 and 243 in the α(1)-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators

From pole to pole : 33 years of physical oceanography onboard R/V Polarstern

Measuring temperature and salinity profiles in the world's oceans is crucial to understanding ocean dynamics and its influence on the heat budget, the water cycle, the marine environment and on our climate. Since 1983 the German research vessel and icebreaker Polarstern has been the platform of numerous CTD (conductivity, temperature, depth instrument) deployments in the Arctic and the Antarctic. We report on a unique data collection spanning 33 years of polar CTD data. In total 131 data sets (1 data set per cruise leg) containing data from 10 063 CTD casts are now freely available at doi: 10.1594/PANGAEA.860066. During this long period five CTD types with different characteristics and accuracies have been used. Therefore the instruments and processing procedures (sensor calibration, data validation, etc.) are described in detail. This compilation is special not only with regard to the quantity but also the quality of the data -the latter indicated for each data set using defined quality codes. The complete data collection includes a number of repeated sections for which the quality code can be used to investigate and evaluate long-term changes. Beginning with 2010, the salinity measurements presented here are of the highest quality possible in this field owing to the introduction of the OPTIMARE Precision Salinometer.Peer reviewe