Implication of climate changes on design of structures

The climatic data on which the current generation of the Eurocodes are based are mostly about 20 years old, with some exceptions of recent updates at a national level. The second generation of the Eurocodes for structural design is expected to be nationally implemented within next few years and operational National Annexes should be subsequently developed and the climatic maps revised. Some models for extreme climate actions are still missing within Eurocodes including wind action effects due to non-synoptic storms, which are common in most of the world and are of increasing importance in Europe.The aim of this contribution is to analyse how the impact of anticipated changes in European climate could affect the assessment of design weather parameters, including the partial factor design approach for structures according to Eurocodes, based on current knowledge concerning projectionmodels of future climate in Europe

A cyclometallated IrIII complex conjugated to a coumarin derivative is a potent photodynamic agent against prostate differentiated and tumorigenic cancer stem cells

A cyclometalated IrIII complex conjugated to a far-red-emitting coumarin, IrIII-COUPY (3), was recently shown as a very promising photosensitizer suitable for photodynamic therapy of cancer. Therefore, the primary goal of this work was to deepen knowledge on the mechanism of its photoactivated antitumor action so that this information could be used to propose a new class of compounds as drug candidates for curing very hardly treatable human tumors, such as androgen resistant prostatic tumors of metastatic origin. Conventional anticancer chemotherapies exhibit several disadvantages, such as limited efficiency to target cancer stem cells (CSCs), which are considered the main reason for chemotherapy resistance, relapse, and metastasis. Herein, we show, using DU145 tumor cells, taken as the model of hormone-refractory and aggressive prostate cancer cells resistant to conventional antineoplastic drugs, that the photoactivated conjugate 3 very efficiently eliminates both prostate bulk, differentiated and prostate, hardly treatable CSCs simultaneously and with a similar efficiency. Notably, the very low toxicity of IrIII-COUPY conjugate in the prostate DU145 cells in the dark and its pronounced selectivity for tumor cells compared with noncancerous cells could result in low side effects and reduced damage of healthy cells during the photoactivated therapy by this agent. Moreover, the experiments performed with the 3D spheroids formed from DU145 CSCs showed that conjugate 3 can penetrate the inner layers of tumorspheres, which might markedly increase its therapeutic effect. Also interestingly, this conjugate induces apoptotic cell death in prostate cancer DU145 cells associated with calcium signaling flux in these cells and autophagy. To the best of our knowledge, this is the first study demonstrating that a photoactivatable metal-based compound is an efficient agent capable of killing even hardly treatable CSC

Ruthenium(II)-Tris-pyrazolylmethane Complexes Inhibit Cancer Cell Growth by Disrupting Mitochondrial Calcium Homeostasis

While ruthenium arene complexes have been widely investigated for their medicinal potential, studies on homologous compounds containing a tridentate tris(1-pyrazolyl)methane ligand are almost absent in the literature. Ruthenium(II) complex 1 was obtained by a modified reported procedure; then, the reactions with a series of organic molecules (L) in boiling alcohol afforded novel complexes 2-9 in 77-99% yields. Products 2-9 were fully structurally characterized. They are appreciably soluble in water, where they undergo partial chloride/water exchange. The antiproliferative activity was determined using a panel of human cancer cell lines and a noncancerous one, evidencing promising potency of 1, 7, and 8 and significant selectivity toward cancer cells. The tested compounds effectively accumulate in cancer cells, and mitochondria represent a significant target of biological action. Most notably, data provide convincing evidence that the mechanism of biological action is mediated by the inhibiting of mitochondrial calcium intake

New European Technical Rules for the Assessment and Retrofitting of Existing Structures.

The consideration of sustainability aspects in the construction sector jointly with considerable economic interests have been the main impulse to include the work item of assessment and retrofitting of existing structures in the Mandate M/515 with a high priority. The new European technical rules will be developed using the existing organization of CEN/TC250. The present report has been worked out in the frame of CEN/TC250/WG2 activities. The report encompasses: Part I introduces the policy framework and the CEN/TC250 initiative. Part II is a collation of the different existing National regulations and standards in Europe with regard to existing structures. Part III gives a prospect for CEN guidance for the assessment and retrofitting of existing structures. Having in mind the stepwise procedure for preparation of CEN Technical Documents, the contents of Part III is broader, covers more aspects, and includes more information than the normative technical recommendations. In particular, key issues are identified that require resolution and a summary of different national perspectives is provided rather than seeking to resolve all difficult technical issues during the first work step. The report presents scientific and technical background intended to stimulate debate and serves as a basis for further work to achieve a harmonized European view on the assessment and retrofitting of existing structures.JRC.G.4-European laboratory for structural assessmen

Reliability of Structural Members Designed with the Eurocodes NDPs Selected by EU and EFTA Member States

The reliability level of structural members in buildings designed according to the Eurocodes was assessed for 20 EU and EFTA MS using the NDPs uploaded in the European Commission NDPs Database by the end of 2017 by 16 EU MS and consulting the National Annexes of four other EU and EFTA MS. The main conclusions of the study are the following: - the reliability of structural members which were designed according to the national choice of the NDPs varies in a rather broad range. The reliability levels of the structural members for most common categories of imposed loads match the reliability indices recommended in EN 1990. - in some cases the reliability levels according to the country choices of the NDPs are below the CEN target values and therefore should be further analysed and calibrated. - the reliability levels achieved using CEN recommended values should also be studied further, in order to delineate eventual needs for calibration of the recommended values. - the reliability levels of composite, steel and timber members designed according to the lower bound of imposed loads recommended in EN 1991-1-1, are commonly lower than the reliability levels recommended in EN 1990 for some fundamental combinations of actions. It should be noted, that the reliability of whole structure is normally higher than the one of a structural member. Thus, the presented results show that a generally good level of structural reliability has been achieved with the country choices of the NDPs.JRC.E.4-Safety and Security of Building

State of harmonised use of the Eurocodes

The objective of the present report is to evaluate the state of harmonised use of the Eurocodes in the EU and EFTA Member States. Besides that, the report is deemed to assess the potential for further harmonisation and the associated needs to support the on-going activities of CEN/TC250 "Structural Eurocodes" in the development of the second generation of the Eurocodes. The report analyses the national choices of the 28 EU Member States and two EFTA Member States (Norway and Switzerland). The European Commission Nationally Determined Parameters Database (NDPs Database) was used as a source of information on the countries' choices regarding the values adopted in the Eurocodes National Annexes. The data available was subject of extensive analyses, comprising (i) assessment of the representativeness of the data set to draw conclusions on the country choices, (ii) examination of harmonised patterns of the NDPs, per country, Eurocode and for specific Eurocodes parts, (iii) study of cross-border convergence of the maps for climatic and seismic actions, (iv) identification of specific NDPs that achieved a high or a low consensus in the national choices, and (v) analysis of parameters with the largest divergence from the recommended values. The analysis of the reliability levels of structural members designed with the Eurocodes using the NDPs chosen by the Member States, complemented the statistical analysis of the NDPs, providing a more global assessment of the combined impact of the national choices on the levels of safety achieved. The results demonstrate that the Eurocodes have achieved a high level of harmonisation in the EU and EFTA Member States, since most countries accepted the parameters recommended in the Standards. In fact, the analysis performed with a data availability of 71%, shows a mean acceptance rate of 73% for all NDPs with recommended values. The high rate of acceptance of the NDPs does not automatically imply that these NDPs shall be eliminated in the second generation of the Eurocodes, since many of them are directly related to the safety which is under national responsibility, or account for local geographical, geological and climatic conditions. Nevertheless, it is of primary interest for the achievement of a deeper internal market for construction products and engineering services that further harmonisation in the use of the Eurocodes is attained, as foreseen in the second generation of the Eurocodes. There are still a number of NDPs in the standards that have a good potential to be considered in the works on the second generation of the Eurocodes, as these NDPs are accounting for different design cultures and procedures for structural analysis. The cross-border convergence of the national maps for climatic and seismic actions shall be considered as an indicator for the harmonised use of data and methods for derivation of these maps. Harmonising the use of the Eurocodes in the EU and EFTA Member States, by reducing the number of Nationally Determined Parameters in the standards, will reduce the obstacles arising from different national practices and will boost the free circulation of products and services within the European Economic Area.JRC.E.4-Safety and Security of Building

Thermal design of structures and the changing climate

The report presents the work of the Joint Research Centre’s scientific network on adaptation of structural design to climate change focusing on the thermal design of buildings and infrastructure considering the changing climate. It presents scientific and technical background intended to stimulate debate and serve as a basis for further work to study the implications of climate change on the thermal design of structures. The report first outlines recent EU policies in support of sustainability and climate resilience of infrastructure and buildings. It highlights how the construction sector is encouraged to adopt more sustainable and circular economy practices, extend the lifetime of buildings and strive for better performance of buildings and infrastructure throughout their life cycle. It further emphasises the ongoing action plan to adapt the European standards to a changing climate. Following, the report explains the concept of the definition of thermal actions for the design of buildings and infrastructure using the European standards for structural design, i.e. the Eurocodes. It is showed that the adaptation of structural design to the implications of climate change is strongly linked with the assessment of changing characteristics of climatic actions (including thermal ones) in terms of the Eurocodes concept for the variable climatic actions. Variations in temperature that would directly affect the design values for thermal actions in the European standards are studied in depth for the case study of Italy. It is concluded that an increase in the maximum and minimum temperature used for structural design is expected all over Italy. It is discussed that structures, as bridges for example, are expected to be influenced by stresses from extreme temperatures and thus, should be designed for temperature amplitudes justified from climate projections for the actual region. However, the current European maps for thermal design are based on climatic data which, with some exceptions, are mostly 10 to 15 years old and ignore the potential effects of climate change. Thus, new European maps for the thermal design of structures should be developed using data that project more realistically the future climate. To this end, the authors present a methodology for developing thermal maps for structural design taking into account the influence of the changing climate and present an implementation of the methodology using the example of Italy.JRC.E.4-Safety and Security of Building

The implementation of the Eurocodes in the National Regulatory Framework

The report provides general information on the concept of the Eurocodes implementation in the regulatory system and discusses case studies of EU Member States that have successfully implemented the Eurocodes in the national regulatory system. It also highlights the experience of designers on using the Eurocodes by presenting simple application examples. Moreover, the state of the Eurocodes implementation in the non-EU Balkan countries is presented, based on the information exchanged and collected during the workshop “The way forward for the Eurocodes implementation in the Balkans” (10-11 October 2018 in Tirana, Albania), along with the activities of the Engineering Chambers in support of the Eurocodes implementation. The way towards the publication of the Second Generation of the Eurocodes, expected after 2021, is also discussed.JRC.E.4-Safety and Security of Building

Fragmentation processes of ionized 5-fluorouracil in the gas phase and within clusters

We have measured mass spectra for positive ions produced from neutral 5-fluorouracil by electron impact at energies from 0 to 100 eV. Fragment ion appearance energies of this (radio-)chemotherapy agent have been determined for the first time and we have identified several new fragment ions of low abundance. The main fragmentations are similar to uracil, involving HNCO loss and subsequent HCN loss, CO loss, or FCCO loss. The features adjacent to these prominent peaks in the mass spectra are attributed to tautomerization preceding the fragmentation and/or the loss of one or two additional hydrogen atoms. A few fragmentions are distinct for 5-fluorouracil compared to uracil, most notably the production of the reactive moiety CF+. Finally, multiphoton ionization mass spectra are compared for 5-fluorouracil from a laser thermal desorption source and from a supersonic expansion source. The detection of a new fragment ion at 114 u in the supersonic expansion experiments provides the first evidence for a clustering effect on the radiation response of 5-fluorouracil. By analogy with previous experiments and calculations on protonated uracil, this is assigned to NH3 loss from protonated 5-fluorouracil

Mitochondrial respiratory states and rate

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery