Regulating a Benzodifuran Single Molecule Redox Switch via Electrochemical Gating and Optimization of Molecule/Electrode Coupling

We report a novel strategy for the regulation of charge transport through single molecule junctions via the combination of external stimuli of electrode potential, internal modulation of molecular structures, and optimization of anchoring groups. We have designed redox-active benzodifuran (BDF) compounds as functional electronic units to fabricate metal–molecule–metal (m–M–m) junction devices by scanning tunneling microscopy (STM) and mechanically controllable break junctions (MCBJ). The conductance of thiol-terminated BDF can be tuned by changing the electrode potentials showing clearly an off/on/off single molecule redox switching effect. To optimize the response, a BDF molecule tailored with carbodithioate (−CS2–) anchoring groups was synthesized. Our studies show that replacement of thiol by carbodithioate not only enhances the junction conductance but also substantially improves the switching effect by enhancing the on/off ratio from 2.5 to 8.

Highly-effective gating of single-molecule junctions: an electrochemical approach

We report an electrochemical gating approach with [similar]100% efficiency to tune the conductance of single-molecule 4,4′-bipyridine junctions using scanning-tunnelling-microscopy break junction technique. Density functional theory calculation suggests that electrochemical gating aligns molecular frontier orbitals relative to the electrode Fermi-level, switching the molecule from an off resonance state to “partial” resonance.

Promising anchoring groups for single-molecule conductance measurements

The understanding of the charge transport through single molecule junctions is a prerequisite for the design and building of electronic circuits based on single molecule junctions. However, reliable and robust formation of such junctions is a challenging task to achieve. In this topical review, we present a systematic investigation of the anchoring group effect on single molecule junction conductance by employing two complementary techniques, namely scanning tunneling microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques, based on the studies published in the literature and important results from our own work. We compared conductance studies for conventional anchoring groups described earlier with the molecular junctions formed through π-interactions with the electrode surface (Au, Pt, Ag) and we also summarized recent developments in the formation of highly conducting covalent Au–C σ-bonds using oligophenyleneethynylene (OPE) and an alkane molecular backbone. Specifically, we focus on the electron transport properties of diaryloligoyne, oligophenyleneethynylene (OPE) and/or alkane molecular junctions composed of several traditional anchoring groups, (dihydrobenzo[b]thiophene (BT), 5-benzothienyl analogue (BTh), thiol (SH), pyridyl (PY), amine (NH2), cyano (CN), methyl sulphide (SMe), nitro (NO2)) and other anchoring groups at the solid/liquid interface. The qualitative and quantitative comparison of the results obtained with different anchoring groups reveals structural and mechanistic details of the different types of single molecular junctions. The results reported in this prospective may serve as a guideline for the design and synthesis of molecular systems to be used in molecule-based electronic devices.

The Synthesis of Functionalised Diaryltetraynes and Their Transport Properties in Single-Molecule Junctions

The synthesis and characterisation is described of six diaryltetrayne derivatives [Ar-(C[TRIPLE BOND]C)4-Ar] with Ar=4-NO2-C6H4- (NO24), 4-NH(Me)C6H4- (NHMe4), 4-NMe2C6H4- (NMe24), 4-NH2-(2,6-dimethyl)C6H4- (DMeNH24), 5-indolyl (IN4) and 5-benzothienyl (BTh4). X-ray molecular structures are reported for NO24, NHMe4, DMeNH24, IN4 and BTh4. The stability of the tetraynes has been assessed under ambient laboratory conditions (20 °C, daylight and in air): NO24 and BTh4 are stable for at least six months without observable decomposition, whereas NHMe4, NMe24, DMeNH24 and IN4 decompose within a few hours or days. The derivative DMeNH24, with ortho-methyl groups partially shielding the tetrayne backbone, is considerably more stable than the parent compound with Ar=4-NH2C6H4 (NH24). The ability of the stable tetraynes to anchor in Au|molecule|Au junctions is reported. Scanning-tunnelling-microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques are employed to investigate single-molecule conductance characteristics.

EPA guidance on the early intervention in clinical high risk states of psychoses

This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional provements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk Status.

EPA guidance on the early detection of clinical high risk states of psychoses

The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.

Deletion of Fibrinogen-like Protein 2 (FGL-2), a Novel CD4+ CD25+ Treg Effector Molecule, Leads to Improved Control of Echinococcus multilocularis Infection in Mice.

BACKGROUND The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection. METHODS/FINDINGS Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation. CONCLUSIONS FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.

International Frameworks for Disaster Risk Reduction: Useful Guidance for Sustainable Mountain Development?

In recent decades, a number of global frameworks have been developed for disaster risk reduction (DRR). The Hyogo Framework for Action 2005–2015 and its successor document, the Sendai Framework for Disaster Risk Reduction, adopted in Japan in March 2015, provide general guidance for reducing risks from natural hazards. This is particularly important for mountainous areas, but DRR for mountain areas and sustainable mountain development received little attention in the recent policy debate. The question remains whether the Hyogo and Sendai frameworks can provide guidance for sustainable mountain development. This article evaluates the 2 frameworks in light of the special challenges of DRR in mountain areas and argues that, while the frameworks offer valuable guidance, they need to be further adapted for local contexts—particularly for mountain areas, which require special attention because of changing risk patterns like the effects of climate change and high land-use pressure.