Computational and spectroscopic studies of organic mixed-valence compounds: where is the charge?

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.This article discusses recent progress by a combination of spectroscopy and quantum-chemical calculations in classifying and characterizing organic mixed-valence systems in terms of their localized vs.delocalized character. A recently developed quantum-chemical protocol based on non-standard hybrid functionals and continuum solvent models is evaluated for an extended set of mixed-valence bis-triarylamine radical cations, augmented by unsymmetrical neutral triarylamine-perchlorotriphenylmethyl radicals. It turns out that the protocol is able to provide a successful assignment to class II or class III Robin-Day behavior and gives quite accurate ground- and excited-state properties for the radical cations. The limits of the protocol are probed by the anthracene-bridged system8, where it is suspected that specific solute–solvent interactions are important and not covered by the continuum solvent model. Intervalence charge-transfer excitation energies for the neutral unsymmetrical radicals are systematically overestimated, but dipole moments and a number of other properties are obtained accurately by the protocol.DFG, GRK 1221, Steuerung elektronischer Eigenschaften von Aggregaten pi-konjugierter Molekül

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

<p>Abstract</p> <p>Background</p> <p><it>Helicobacter pylori </it>is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the <it>Cox-2 </it>gene is up-regulated in the gastric mucosa during <it>H. pylori </it>infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an <it>in vivo </it>model, thereby identifying potential targets for the study of the role of Cox- 2 in <it>H. pylori </it>pathogenesis and the initiation of pre- cancerous changes.</p> <p>Results</p> <p>Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after <it>H. pylori </it>infection. <it>H. pylori </it>infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of <it>H. pylori </it>infection. The Cox-2 dependent subset included those influencing gastric physiology (<it>Gastrin, Galr1</it>), epithelial barrier function (<it>Tjp1, connexin45, Aqp5</it>), inflammation (<it>Icam1</it>), apoptosis (<it>Clu</it>) and proliferation (<it>Gdf3, Igf2</it>). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression.</p> <p>Conclusion</p> <p>This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by <it>H. pylori </it>infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity.</p

Informal Caregiving in Amyotrophic Lateral Sclerosis (ALS): A High Caregiver Burden and Drastic Consequences on Caregivers’ Lives

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required

Measuring, modelling and managing gully erosion at large scales: A state of the art

Soil erosion is generally recognized as the dominant process of land degradation. The formation and expansion of gullies is often a highly significant process of soil erosion. However, our ability to assess and simulate gully erosion and its impacts remains very limited. This is especially so at regional to continental scales. As a result, gullying is often overlooked in policies and land and catchment management strategies. Nevertheless, significant progress has been made over the past decades. Based on a review of >590 scientific articles and policy documents, we provide a state-of-the-art on our ability to monitor, model and manage gully erosion at regional to continental scales. In this review we discuss the relevance and need of assessing gully erosion at regional to continental scales (Section 1); current methods to monitor gully erosion as well as pitfalls and opportunities to apply them at larger scales (section 2); field-based gully erosion research conducted in Europe and European Russia (section 3); model approaches to simulate gully erosion and its contribution to catchment sediment yields at large scales (section 4); data products that can be used for such simulations (section 5); and currently existing policy tools and needs to address the problem of gully erosion (section 6). Section 7 formulates a series of recommendations for further research and policy development, based on this review. While several of these sections have a strong focus on Europe, most of our findings and recommendations are of global significance.info:eu-repo/semantics/publishedVersio

Association of TLR7 Variants with AIDS-Like Disease and AIDS Vaccine Efficacy in Rhesus Macaques

In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP) as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV)-infected male rhesus macaques, including an ‘MHC adjusted’ subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i) that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii) the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T), located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype

UNICARagil - Disruptive Modular Architectures for Agile, Automated Vehicle Concepts

This paper introduces UNICARagil, a collaborative project carried out by a consortium of seven German universities and six industrial partners, with funding provided by the Federal Ministry of Education and Research of Germany. In the scope of this project, disruptive modular structures for agile, automated vehicle concepts are researched and developed. Four prototype vehicles of different characteristics based on the same modular platform are going to be build up over a period of four years. The four fully automated and driverless vehicles demonstrate disruptive architectures in hardware and software, as well as disruptive concepts in safety, security, verification and validation. This paper outlines the most important research questions underlying the project

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements