Balancing engagement and neutrality in technology assessment

Should technology assessment take a stance – when, on what, and how? How to deal with its neutrality paradigm in times of anti-democratic tendencies

Value capture from low embodied emissions of buildings - A business model innovation perspective

The transition to a society with low emissions has led to several intensives for decreasing operational energy and the environmental impact of buildings. The embodied impacts from manufacturing materials have been shown to increase in relative importance as the operational energy efficiency has increased. Several case studies have shown various technical solutions which can reduce embodied carbon emissions. But is this reduction good for business? There are several building projects that have achieved low embodied emissions, but these are often in segments of premium private clients or green public procurement where additional motivation such as reputation and long-term viability is in place. However, with the transition to a low emission society, there is a need to include all types of building markets. This study aims to find business model innovation opportunities with reduced embodied emissions in building projects where the clients have low motivation beyond reducing costs. The approach is through action research with a Norwegian contractor seeking new opportunities while keeping the main competitive advantage. The research starts with a case that could reduce overall greenhouse gas emissions, and includes the potential savings from green loans to find potentials to capture value from reducing emissions. The results show that criteria exist for green loans based on reducing operational and embodied emissions. Future studies are however need to make an integrated assessment on the potential value captured from these green loans.</p

Normativität in der Technikfolgenabschätzung. Einleitung in das TATuP-Thema

Neutralität galt lange als unhinterfragte Grundlage im Selbstverständnis von Technikfolgenabschätzung (TA). Dieser Fokus verstellte allerdings den Blick darauf, dass normative Aspekte nicht außer Acht gelassen werden dürfen – sei es in den Ergebnissen von TA-Analysen oder in normativen Setzungen, die im TA-Prozess auftreten. Im TATuP-Thema dieses Heftes wird „Normativität in der TA“ auf drei Ebenen adressiert: in der Funktion von TA als Politikberatung, im Kontext des TA-Forschungsprozesses und in der Auseinandersetzung um ihren „normativen Kern“. Angesichts manch autoritärer Tendenzen auch in westlichen Demokratien ist die Debatte um die Rolle von Normativität in der TA heute besonders aktuell.Neutrality has long been considered a key prerequisite of technology assessment (TA). The need to stay neutral often obscured the importance of normative aspects of TA – be it in the findings or in normative settings in the TA process. The special topic addresses normativity in TA at three levels: (1) regarding TA’s role as policy advisor, (2) in the context of the research process, and (3) with respect to its “normative core”. The problem of normativity in TA gains significance in the light of recent authoritarian tendencies also in Western democracies

Interplay between Toxin Transport and Flotillin Localization

The flotillin proteins are localized in lipid domains at the plasma membrane as well as in intracellular compartments. In the present study, we examined the importance of flotillin-1 and flotillin-2 for the uptake and transport of the bacterial Shiga toxin (Stx) and the plant toxin ricin and we investigated whether toxin binding and uptake were associated with flotillin relocalization. We observed a toxin-induced redistribution of the flotillins, which seemed to be regulated in a p38-dependent manner. Our experiments provide no evidence for a changed endocytic uptake of Stx or ricin in cells silenced for flotillin-1 or -2. However, the Golgi-dependent sulfation of both toxins was significantly reduced in flotillin knockdown cells. Interestingly, when the transport of ricin to the ER was investigated, we obtained an increased mannosylation of ricin in flotillin-1 and flotillin-2 knockdown cells. The toxicity of both toxins was twofold increased in flotillin-depleted cells. Since BFA (Brefeldin A) inhibits the toxicity even in flotillin knockdown cells, the retrograde toxin transport is apparently still Golgi-dependent. Thus, flotillin proteins regulate and facilitate the retrograde transport of Stx and ricin

Dissolved noble gases and stable isotopes as tracers of preferential fluid flow along faults in the Lower Rhine Embayment, Germany

Groundwater in shallow unconsolidated sedimentary aquifers close to the Bornheim fault in the Lower Rhine Embayment (LRE), Germany, has relatively low δ2H and δ18O values in comparison to regional modern groundwater recharge, and 4He concentrations up to 1.7 × 10−4 cm3 (STP) g–1 ± 2.2 % which is approximately four orders of magnitude higher than expected due to solubility equilibrium with the atmosphere. Groundwater age dating based on estimated in situ production and terrigenic flux of helium provides a groundwater residence time of ∼107 years. Although fluid exchange between the deep basal aquifer system and the upper aquifer layers is generally impeded by confining clay layers and lignite, this study’s geochemical data suggest, for the first time, that deep circulating fluids penetrate shallow aquifers in the locality of fault zones, implying  that sub-vertical fluid flow occurs along faults in the LRE. However, large hydraulic-head gradients observed across many faults suggest that they act as barriers to lateral groundwater flow. Therefore, the geochemical data reported here also substantiate a conduit-barrier model of fault-zone hydrogeology in unconsolidated sedimentary deposits, as well as corroborating the concept that faults in unconsolidated aquifer systems can act as loci for hydraulic connectivity between deep and shallow aquifers. The implications of fluid flow along faults in sedimentary basins worldwide are far reaching and of particular concern for carbon capture and storage (CCS) programmes, impacts of deep shale gas recovery for shallow groundwater aquifers, and nuclear waste storage sites where fault zones could act as potential leakage pathways for hazardous fluids

The Lectin-like Receptor KLRE1 Inhibits Natural Killer Cell Cytotoxicity

We report the cloning and functional characterization in the mouse and the rat of a novel natural killer (NK) cell receptor termed KLRE1. The receptor is a type II transmembrane protein with a COOH-terminal lectin-like domain, and constitutes a novel KLR family. Rat Klre1 was mapped to the NK gene complex. By Northern blot and flow cytometry using newly generated monoclonal antibodies, KLRE1 was shown to be expressed by NK cells and a subpopulation of CD3+ cells, with pronounced interstrain variation. Western blot analysis indicated that KLRE1 can be expressed on the NK cell surface as a disulphide-linked dimer. The predicted proteins do not contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or a positively charged amino acid in the transmembrane domain. However, in a redirected lysis assay, the presence of whole IgG, but not of F(ab′)2 fragments of a monoclonal anti-KLRE1 antibody inhibited lysis of Fc-receptor bearing tumor target cells. Moreover, the tyrosine phosphatase SHP-1 was coimmunoprecipitated with KLRE1 from pervanadate-treated interleukin 2–activated NK cells. Together, our results indicate that KLRE1 may form a functional heterodimer with an as yet unidentified ITIM-bearing partner that recruits SHP-1 to generate an inhibitory receptor complex

Live imaging of cellular internalization of single colloidal particle by combined label-free and fluorescence total internal reflection microscopy

In this work we utilise the combination of label-free total internal reflection microscopy and total internal reflectance fluorescence (TIRM/TIRF) microscopy to achieve a simultaneous, live imaging of single, label-free colloidal particle endocytosis by individual cells. The TIRM arm of the microscope enables label free imaging of the colloid and cell membrane features, while the TIRF arm images the dynamics of fluorescent-labelled clathrin (protein involved in endocytosis via clathrin pathway), expressed in transfected 3T3 fibroblasts cells. Using a model polymeric colloid and cells with a fluorescently-tagged clathrin endocytosis pathway, we demonstrate that wide field TIRM/TIRF co-imaging enables live visualization of the process of colloidal particle interaction with the labelled cell structure, which is valuable for discerning the membrane events and route of colloid internalization by the cell. We further show that 500 nm model polystyrene colloid associates with clathrin, prior to and during its cellular internalisation. This association is not apparent with larger, 1 μm colloid, indicating an upper particle size limit for clathrin-mediated endocytosis

Bone marrow stroma-derived PGE2 protects BCP-ALL cells from DNA damage-induced p53 accumulation and cell death

Background B cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common paediatric cancer. BCP-ALL blasts typically retain wild type p53, and are therefore assumed to rely on indirect measures to suppress transformation-induced p53 activity. We have recently demonstrated that the second messenger cyclic adenosine monophosphate (cAMP) through activation of protein kinase A (PKA) has the ability to inhibit DNA damage-induced p53 accumulation and thereby promote survival of the leukaemic blasts. Development of BCP-ALL in the bone marrow (BM) is supported by resident BM-derived mesenchymal stromal cells (MSCs). MSCs are known to produce prostaglandin E2 (PGE2) which upon binding to its receptors is able to elicit a cAMP response in target cells. We hypothesized that PGE2 produced by stromal cells in the BM microenvironment could stimulate cAMP production and PKA activation in BCP-ALL cells, thereby suppressing p53 accumulation and promoting survival of the malignant cells. Methods Primary BCP-ALL cells isolated from BM aspirates at diagnosis were cocultivated with BM-derived MSCs, and effects on DNA damage-induced p53 accumulation and cell death were monitored by SDS-PAGE/immunoblotting and flow cytometry-based methods, respectively. Effects of intervention of signalling along the PGE2-cAMP-PKA axis were assessed by inhibition of PGE2 production or PKA activity. Statistical significance was tested by Wilcoxon signed-rank test or paired samples t test. Results We demonstrate that BM-derived MSCs produce PGE2 and protect primary BCP-ALL cells from p53 accumulation and apoptotic cell death. The MSC-mediated protection of DNA damage-mediated cell death is reversible upon inhibition of PGE2 synthesis or PKA activity. Furthermore our results indicate differences in the sensitivity to variations in p53 levels between common cytogenetic subgroups of BCP-ALL. Conclusions Our findings support our hypothesis that BM-derived PGE2, through activation of cAMP-PKA signalling in BCP-ALL blasts, can inhibit the tumour suppressive activity of wild type p53, thereby promoting leukaemogenesis and protecting against therapy-induced leukaemic cell death. These novel findings identify the PGE2-cAMP-PKA signalling pathway as a possible target for pharmacological intervention with potential relevance for treatment of BCP-ALL

Asymptotically optimal purification and dilution of mixed qubit and Gaussian states

Given an ensemble of mixed qubit states, it is possible to increase the purity of the constituent states using a procedure known as state purification. The reverse operation, which we refer to as dilution, reduces the level of purity present in the constituent states. In this paper we find asymptotically optimal procedures for purification and dilution of an ensemble of i.i.d. mixed qubit states, for some given input and output purities and an asymptotic output rate. Our solution involves using the statistical tool of local asymptotic normality, which recasts the qubit problem in terms of attenuation and amplification of a single displaced Gaussian state. Therefore, to obtain the qubit solutions, we must first solve the analogous problems in the Gaussian setup. We provide full solutions to all of the above, for the (global) trace norm figure of merit.Comment: 11 pages, 6 figure