Une interdisciplinarit� sans m�taphysique

Schmid, Anne-Françoise

doi:10.1016/s1240-1307(00)80009-6

Cited by 4 publications

(12 citation statements)

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“…Globally open or globally closed conformations may differ in local structural arrangements. Although not all four conformations are directly distinguishable in terms of FRET efficiency, the observed kinetic behavior implies a 4-state model: [22] in excellent agreement, this is shown by the dwell-time distributions and the Bayesian information criterion ( Supplementary Figures S4 and S5). We generally observe the fastest transition rates between the short-lived states 1 and 2, whereas states 0 and 3 represent longer-lived but less frequently accessed states.…”

Section: Resultsmentioning

confidence: 66%

“…Therefore, we analyzed the observed kinetics more thoroughly using the software SMACKS. [22] As shown in Figure 3A, a 4-state model with 3 links was found for Hsp90 in the presence of each of the four inhibitors, no matter from which class they were. The states 0/1 represent open conformations; states 2/3 denote closed conformations.…”

Section: Resultsmentioning

confidence: 94%

“…smFRET was measured as previously detailed using a home built TIRF setup. [22] Hetero-dimers (acceptor + donor) were obtained by 20 min incubation of 1 mM donor and 0.1 mM biotinylated acceptor homodimers in measurement buffer (40 mM HEPES, 150 mM KCl, and 10 mM MgCl 2 , pH 7.5) at 47 8C. In this way, predominantly biotinylated heterodimers bind to the polyethylene glycol (PEG, Rapp Polymere, Tuebingen, Germany) passivated and neutravidin (Thermo Fisher Scientific, Waltham, MA) coated fluid chamber.…”

Section: Single-molecule Fret Measurementsmentioning

confidence: 99%

“…We provide a quantitative description of these kinetics, which became available by our recently developed single molecule analysis of complex kinetic sequences (SMACKS). [22] Altogether, this single molecule approach is very sensitive to drug induced changes in the relative population of open and closed conformations, and also to changes in transition kinetics between those.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Inhibitors on Hsp90′s Conformational Dynamics, Cochaperone and Client Interactions

2018

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The molecular chaperone and heat-shock protein Hsp90 has become a central target in anti-cancer therapy. Nevertheless, the effect of Hsp90 inhibition is still not understood at the molecular level, preventing a truly rational drug design. Here we report on the effect of the most prominent drug candidates, namely, radicicol, geldanamycin, derivatives of purine, and novobiocin, on Hsp90's characteristic conformational dynamics and the binding of three interaction partners. Unexpectedly, the global opening and closing transitions are hardly affected by Hsp90 inhibitors. Moreover, we find no significant changes in the binding of the cochaperones Aha1 and p23 nor of the model substrate Δ131Δ. This holds true for competitive and allosteric inhibitors. Therefore, direct inhibition mechanisms affecting only one molecular interaction are unlikely. We suggest that the inhibitory action observed in vivo is caused by a combination of subtle effects, which can be used in the search for novel Hsp90 inhibition mechanisms.

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Section: Resultsmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 94%

Section: Single-molecule Fret Measurementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of Inhibitors on Hsp90′s Conformational Dynamics, Cochaperone and Client Interactions

2018

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“…So far, the main focus of this research area has been: (i) to identify different material systems that exhibit this effect (whether metallic [6], insulating [7], semiconducting [8], or oxides [9]); (ii) to try to understand the impact of substrate induced phonon drag [10]; or (iii) to rule out erroneous contributions such as proximity induced magnetism in the Pt layer [11], or the anomalous Nernst effect (ANE, an electric field generated in a conductive magnetised material subjected to a temperature gradient).…”

mentioning

confidence: 99%

Demonstration of polycrystalline thin film coatings on glass for spin Seebeck energy harvesting

Caruana

Cropper

Zipfel

et al. 2016

Physica Rapid Research Ltrs

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The spin Seebeck effect, a newly discovered phenomena, has been suggested as a potential ‘game changer’ for thermoelectric technology due to the possibility of separating the electric and thermal conductivities. This is due to a completely different device architecture where, instead of an arrangement of p‐ and n‐type pillars between two ceramic blocks, a thermopile could be deposited directly onto a magnetic film of interest. Here we report on the spin Seebeck effect in polycrystalline Fe3O4:Pt bilayers deposited onto amorphous glass substrates with a view for economically viable energy harvesting. Crucially, these films exhibit large coercive fields (197 Oe) and retain 75% of saturation magnetisation, in conjunction with energy conversion comparable to epitaxially grown films. This demonstrates the potential of this technology for widespread application in harvesting waste heat for electricity.

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Regionalised heat demand and power-to-heat capacities in Germany – An open dataset for assessing renewable energy integration

Heitkoetter¹,

Medjroubi²,

Vogt³

et al. 2020

Applied Energy

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Higher shares of fluctuating generation from renewable energy sources (RES) in the power system lead to an increase of grid balancing demand. One approach for avoiding RES curtailment, is to use excess electricity feed-in for heating applications. To assess in which regions power-to-heat (PtH) technologies can contribute to RES integration, detailed data on the spatial distribution of the heat demand are needed. In this contribution, we determine the overall heat load in the residential building sector and the share covered by electric heating technologies for each administrative district (NUTS-3) in Germany, with a temporal resolution of 15 minutes. For the detailed regionalisation of the residential building stock, we ordered a special evaluation of the German census data at the Research Data Centre with a combination of six building features. Using these data, 729 building categories were defined and heat demand values were assigned to each category. Furthermore, heating types and different classes of installed heating capacity were defined. Our analysis showed that the share of small scale single-storey heatings and large scale central heatings is higher in cities, whereas there are more medium scale central heatings in rural areas. Both is caused by the different shares of single and multi-family houses in the respective regions. To determine the electrically covered heat demand, we took into account heat pumps and resistive heating technologies. All results, as well as the developed code are published along with this contribution under open source licenses and can thus also be used by other researchers for the assessment of power-to-heat for RES integration.

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Une interdisciplinarit� sans m�taphysique

Cited by 4 publications

References 0 publications

Effects of Inhibitors on Hsp90′s Conformational Dynamics, Cochaperone and Client Interactions

Effects of Inhibitors on Hsp90′s Conformational Dynamics, Cochaperone and Client Interactions

Demonstration of polycrystalline thin film coatings on glass for spin Seebeck energy harvesting

Regionalised heat demand and power-to-heat capacities in Germany – An open dataset for assessing renewable energy integration

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