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Abstract Background 2,4-Dimethoxyphenyl-E-4-arylidene-3-isochromanone (IK11) was previously described to induce apoptotic death of A431 tumor cells. In this report, we investigated the molecular action of IK11 in the HepG2 human hepatocellular carcinoma cell line to increase our knowledge of the role of poly (ADP-ribose)-polymerase (PARP), protein kinase B/Akt and mitogen activated protein kinase (MAPK) activation in the survival and death of tumor cells and to highlight the possible role of PARP-inhibitors in co-treatments with different cytotoxic agents in cancer therapy. Results We found that sublethal concentrations of IK11 prevented proliferation, migration and entry of the cells into their G2 phase. At higher concentrations, IK11 induced reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activation of c-Jun N-terminal kinase 2 (JNK2), and substantial loss of HepG2 cells. ROS production appeared marginal in mediating the cytotoxicity of IK11 since N-acetyl cysteine was unable to prevent it. However, the PARP inhibitor PJ34, although not a ROS scavenger, strongly inhibited both IK11-induced ROS production and cell death. JNK2 activation seemed to be a major mediator of the effect of IK11 since inhibition of JNK resulted in a substantial cytoprotection while inhibitors of the other kinases failed to do so. Inhibition of Akt slightly diminished the effect of IK11, while the JNK and Akt inhibitor and ROS scavenger trans-resveratrol completely protected against it. Conclusions These results indicate significant involvement of PARP, a marginal role of ROS and a pro-apoptotic role of Akt in this system, and raise attention to a novel mechanism that should be considered when cancer therapy is augmented with PARP-inhibition, namely the cytoprotection by inhibition of JNK2.

This paper investigates, by simulation study, the potential of five different ventilation and cooling strategies with regard to energy efficiency and thermal comfort in different climates. A 5-zones building simulation model is set-up considering a typical office building. The results demonstrate a high potential for night ventilation strategies in cool climates with low ambient air temperatures. In temperate climates, water based low-energy cooling technologies based on radiant cooling make use of the cool ground in summer. Active cooling provides good thermal comfort in warm and hot climates with high and fluctuating cooling loads. The results also point out that the use of different comfort models has a significant influence on the comfort rating. [ABSTRACT FROM AUTHOR]

Little is known about the potential threats of silver nanoparticles (AgNPs) to ecosystem health, with no detailed report existing on the stress and immune responses of soil invertebrates. Here we use earthworm primary cells, cross-referencing to human cell cultures with a particular emphasis on the conserved biological processes, and provide the first in vitro analysis of molecular and cellular toxicity mechanisms in the earthworm Eisenia fetida exposed to AgNP5 (83 ± 22 run). While we observed a clear difference in cytotoxicity of dissolved silver salt on earthworm coelomocytes and human cells (THP-1 cells, differentiated THP-1 cells and peripheral blood mononuclear cells), the coelomocytes and differentiated (macrophage-like) THP-I cells showed a similar response to AgNP's. Intracellular accumulation of AgNPs in the coelomocytes, predominantly in a phagocytic population, was evident by several methods including transmission electron microscopy. Molecular signatures of oxidative stress and selected biomarker genes probed in a time-resolved manner suggest early regulation of oxidative stress genes and subsequent alteration of immune signaling processes following the onset of AgNP exposure in the coelomocytes and THP-I cells. Our findings provide mechanistic dues on cellular innate immunity toward AgNPs that is likely to be evolutionarily conserved across the animal kingdom [ABSTRACT FROM AUTHOR]

In some advanced countries, when the time is right, civil engineers can reduce failures and other disappointments in urban and infrastructure developments by taking the lead in establishing a formative, multi-sector design process I call “development engineering.” Based on a wide range of experience in thirty countries and with engineering firms and the World Bank, I advocate establishing “Regional and National Design Centers” within three countries (Chile, Mexico, and Turkey) to provide stable settings for design teams, which can be responsive and responsible to the country and people they serve. I describe a proposed comprehensive process for doing pre-investment work that should produce efficient, sustainable development by applying basic engineering design principles. [ABSTRACT FROM AUTHOR]

The article discusses the author's coming to grips with the difficulties of the semiotics theory of knowledge, which was pioneered in France by Ferdinand Saussure and is elucidated by the work of Claude Levi-Strauss, Roman Jacobson, Roland Barthes, and in particular Algirdas Greimas. The anti-positivist and linguistic basis of semiotics is noted.

The increasing global energy demand, the foreseen reduction of available fossil fuels and the increasing evidence off global warming during the last decades have generated a high interest in renewable energy sources. However, renewable energy sources, such as wind and solar power, have an intrinsic variability that can seriously affect the stability of the energy system if they account for a high percentage of the total generation. The Energy Flexibility of buildings is commonly suggested as part of the solution to alleviate some of the upcoming challenges in the future demand-respond energy systems (electrical, district heating and gas grids). Buildings can supply flexibility services in different ways, e.g. utilization of thermal mass, adjustability of HVAC system use (e.g. heating/cooling/ventilation), charging of electric vehicles, and shifting of plug-loads. However, there is currently no overview or insight into how much Energy Flexibility different building may be able to offer to the future energy systems in the sense of avoiding excess energy production, increase the stability of the energy networks, minimize congestion problems, enhance the efficiency and cost effectiveness of the future energy networks. Therefore, there is a need for increasing knowledge on and demonstration of the Energy Flexibility buildings can provide to energy networks. At the same time, there is a need for identifying critical aspects and possible solutions to manage this Energy Flexibility, while maintaining the comfort of the occupants and minimizing the use of non-renewable energy. In this context, the IEA (International Energy Agency) EBC (Energy in Buildings and Communities program) Annex 67: “Energy Flexible Buildings” was started in 2015. The article presents the background and the work plan of IEA EBC Annex 67 as well as already obtained results. Annex 67 is a corporation between participants from 16 countries: Austria, Belgium, Canada, China, Denmark, Finland, France, Germany, Ireland, Italy, The Netherlands, Norway, Portugal, Spain, Switzerland and UK. [ABSTRACT FROM AUTHOR]