Life cycle-based environmental impacts of energy system transformation strategies for Germany: Are climate and environmental protection conflicting goals?

In the development of climate-friendly energy system transformation strategies it is often ignored that environmental protection encompasses more than climate protection alone. There is therefore a risk of developing transformation strategies whose climate friendliness comes at the expense of higher other environmental impacts. Consequently, an assessment of environmental impacts of energy system transformation strategies is required if undesired environmental side effects of the energy system transformation are to be avoided and transformation strategies are to be developed that are both climate and environmentally friendly. In this paper, ten structurally different transformation strategies for the German energy system were re-modeled (in a harmonized manner). Five of these scenarios describe pathways for a reduction of direct, energy related CO$_2$ emissions by 80%, the other five by 95%. Life cycle-based environmental impacts of the scenarios were assessed by coupling the scenario results with data from a life cycle inventory database focusing on energy and transport technologies. The results show that the transformation to a climate-friendly energy system reduces environmental impacts in many impact categories. However, exceptions occur with respect to the consumption of mineral resources, land use and certain human health indicators, which could increase with decreasing CO$_2$ emissions. The comparison of environmental impacts of moderately ambitious strategies (80% CO$_2$ reduction) with very ambitious strategies (95% CO$_2$ reduction) shows that there is a risk of increasing environmental impacts with increasing climate protection, although very ambitious strategies do not necessarily come along with higher environmental impacts than moderately ambitious strategies. A reduction of environmental impacts could be achieved by a moderate and – as far as possible – direct electrification of heat and transport, a balanced technology mix for electricity generation, by reducing the number and size of passenger cars and by reducing the environmental impacts from the construction of these vehicles

Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo

We dissect the transcriptional regulatory relationships coordinating the dynamic expression patterns of two signaling genes, wnt8 and delta, which are central to specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis shows that transcription of the gene encoding the Notch ligand Delta is activated by the widely expressed Runx transcription factor, but spatially restricted by HesC-mediated repression through a site in the delta 5′UTR. Spatial transcription of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus represses the repressor of delta, thereby permitting its transcription. The blimp1 gene is itself linked into a feedback circuit that includes the wnt8 signaling ligand gene, and we showed earlier that this circuit generates an expanding torus of blimp1 and wnt8 expression. The finding that delta expression is also controlled at the cis-regulatory level by the blimp1-wnt8 torus-generating subcircuit now explains the progression of Notch signaling from the mesoderm to the endoderm of the developing embryo. Thus the specific cis-regulatory linkages of the gene regulatory network encode the coordinated spatial expression of Wnt and Notch signaling as they sweep outward across the vegetal plate of the embryo

Building professional discourse in emerging markets: Language, context and the challenge of sensemaking

Using ethnographic evidence from the former Soviet republics, this article examines a relatively new and mainly unobserved in the International Business (IB) literature phenomenon of communication disengagement that manifests itself in many emerging markets. We link it to the deficiencies of the local professional business discourse rooted in language limitations reflecting lack of experience with the market economy. This hampers cognitive coherence between foreign and local business entities, adding to the liability of foreignness as certain instances of professional experience fail to find adequate linguistic expression, and complicates cross-cultural adjustments causing multi-national companies (MNCs) financial losses. We contribute to the IB literature by examining cross-border semantic sensemaking through a retrospectively constructed observational study. We argue that a relative inadequacy of the national professional idiom is likely to remain a feature of business environment in post-communist economies for some time and therefore should be factored into business strategies of MNCs. Consequently, we recommend including discursive hazards in the risk evaluation of international projects

Preparation of amino-substituted indenes and 1,4-dihydronaphthalenes using a one-pot multireaction approach: total synthesis of oxybenzo[c]phenanthridine alkaloids

Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann–Beller palladacycle was used to effect the key step during the synthesis of the natural products

Integrated multidimensional sustainability assessment of energy system transformation pathways

Sustainable development embraces a broad spectrum of social, economic and ecological aspects. Thus, a sustainable transformation process of energy systems is inevitably multidimensional and needs to go beyond climate impact and cost considerations. An approach for an integrated and interdisciplinary sustainability assessment of energy system transformation pathways is presented here. It first integrates energy system modeling with a multidimensional impact assessment that focuses on life cycle-based environmental and macroeconomic impacts. Then, stakeholders’ preferences with respect to defined sustainability indicators are inquired, which are finally integrated into a comparative scenario evaluation through a multi-criteria decision analysis (MCDA), all in one consistent assessment framework. As an illustrative example, this holistic approach is applied to the sustainability assessment of ten different transformation strategies for Germany. Applying multi-criteria decision analysis reveals that both ambitious (80%) and highly ambitious (95%) carbon reduction scenarios can achieve top sustainability ranks, depending on the underlying energy transformation pathways and respective scores in other sustainability dimensions. Furthermore, this research highlights an increasingly dominant contribution of energy systems’ upstream chains on total environmental impacts, reveals rather small differences in macroeconomic effects between different scenarios and identifies the transition among societal segments and climate impact minimization as the most important stakeholder preferences

A Versatile cascade of intramolecular vilsmeier-haack and azomethine ylide 1,3-dipolar cycloaddition toward tricyclic cores of alkaloids

Abstract: In the pursuit of synthetic efficiency, we developed an innovative one-pot transformation of linear substrates into bi- and tricyclic adducts using a cascade of amide activation, nucleophilic cyclization, azomethine ylide generation, and subsequent inter- or intramolecular 1,3-dipolar cycloaddition. Despite the high density and variety of functional groups on the substrates, the sequence occurred with perfect chemoselectivity with good to excellent yields

Magnetic Proximity Effect in YBa₂Cu₃O₇/La_2/3Ca_1/3MnO₃ and YBa₂Cu₃O₇/LaMnO₃₊ Superlattices

Using neutron reflectometry and resonant x-ray techniques we studied the magnetic proximity effect (MPE) in superlattices composed of superconducting YBa₂Cu₃O₇ and ferromagnetic-metallic La0.67Ca0.33MnO₃ or ferromagnetic-insulating LaMnO₃₊. We find that the MPE strongly depends on the electronic state of the manganite layers, being pronounced for the ferromagnetic-metallic La0.67Ca0.33MnO₃ and almost absent for ferromagnetic-insulating LaMnO₃₊. We also detail the change of the magnetic depth profile due to the MPE and provide evidence for its intrinsic nature

Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

© 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.Peer reviewe

Effects of cigarette smoke condensate on proliferation and wound closure of bronchial epithelial cells in vitro: role of glutathione

BACKGROUND: Increased airway epithelial proliferation is frequently observed in smokers. To elucidate the molecular mechanisms leading to these epithelial changes, we studied the effect of cigarette smoke condensate (CSC) on cell proliferation, wound closure and mitogen activated protein kinase (MAPK) activation. We also studied whether modulation of intracellular glutathione/thiol levels could attenuate CSC-induced cell proliferation. METHODS: Cells of the bronchial epithelial cell line NCI-H292 and subcultures of primary bronchial epithelial cells were used for the present study. The effect of CSC on epithelial proliferation was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. Modulation of epithelial wound repair was studied by analysis of closure of 3 mm circular scrape wounds during 72 hours of culture. Wound closure was calculated from digital images obtained at 24 h intervals. Activation of mitogen-activated protein kinases was assessed by Western blotting using phospho-specific antibodies. RESULTS: At low concentrations CSC increased proliferation of NCI-H292 cells, whereas high concentrations were inhibitory as a result of cytotoxicity. Low concentrations of CSC also increased epithelial wound closure of both NCI-H292 and PBEC, whereas at high concentrations closure was inhibited. At low, mitogenic concentrations, CSC caused persistent activation of ERK1/2, a MAPK involved in cell proliferation. Inhibition of cell proliferation by high concentrations of CSC was associated with activation of the pro-apoptotic MAP kinases p38 and JNK. Modulation of intracellular glutathione (GSH)/thiol levels using N-acetyl-L-cysteine, GSH or buthionine sulphoximine (BSO), demonstrated that both the stimulatory and the inhibitory effects of CSC were regulated in part by intracellular GSH levels. CONCLUSION: These results indicate that CSC may increase cell proliferation and wound closure dependent on the local concentration of cigarette smoke and the anti-oxidant status. These findings are consistent with increased epithelial proliferation in smokers, and may provide further insight in the development of lung cancer