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Abstract Herein we present non‐noble metal single‐atom catalysts (SACs) based on carbonized transition metal‐doped zeolitic imidazolate frameworks (ZIFs) as stable and efficient electrocatalysts for the hydrogen evolution reaction in acidic media. In this work, earth‐abundant metals are embedded in a porous N‐rich carbon matrix by pyrolyzing metal‐doped ZIF structures and characterized by spectroscopic, microscopic, and electrochemical methods. The complete synthesis of these high surface area SACs was carried out without any solvents and hence offers a promising route for a more sustainable catalyst production and industrial upscaling. As the best‐performing catalyst, cobalt SAC illustrated already with a low cobalt loading of

Membrane proteins play key roles in biology. Determination of their structure in a membrane environment, however, is highly challenging. To address this challenge, we developed an approach that couples hydrogen/deuterium exchange of membrane proteins to rapid unfolding and detection by solution-state NMR spectroscopy. We show that the method allows analysis of the solvent protection of single residues in liposome-embedded proteins such as the 349-residue Tom40, the major protein translocation pore in the outer mitochondrial membrane, which has resisted structural analysis for many years.

Plexiform neurofibromas are congenital peripheral nerve sheath tumors characteristic of neurofibromatosis type 1 (NF1)-a frequent neurocutaneous disorder caused by mutations of the NF1 tumor suppressor gene. Since plexiform neurofibromas are a major cause of the burden of disease and may also progress to malignancy, many efforts have been undertaken to find a cure for these tumors. However, neither surgery nor medication has so far produced a breakthrough therapeutic success. Recently, a clinical phase I study reported significant shrinkage of plexiform neurofibromas following treatment with the MEK inhibitor selumetinib. Here, we report an 11-year-old NF1 patient with a large plexiform neurofibroma of the neck that had led to a sharp-angled kinking of the cervical spine and subsequent myelopathy. Although surgical stabilization of the cervical vertebral column was urgently recommended, the vertebral column was inaccessible due to extensive tumor growth. In this situation, treatment with the MEK inhibitor trametinib was initiated which resulted in a 22% reduction in tumor volume after 6 months of therapy and finally enabled surgery. These data show that MEK inhibitors may not lead to complete disappearance of NF1-associated plexiform neurofibromas but can be an essential step in a multimodal therapeutic approach for these tumors. The course of our patient suggests that MEK inhibitors are likely to play a significant role in providing a cure for one of the most devastating manifestations of NF1., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram., Method: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002., Results: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo., Conclusion: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.

The reaction times of saccades (SRT) to a suddenly presented visual stimulus (pro-saccade) can be decreased and a separate mode of express saccades can occur when a gap paradigm is used (i.e. fixation-point offset precedes target onset by 200 ms). A valid peripheral cue, presented briefly (100 ms) before target onset, has been found to facilitate the generation of saccades to the target, thereby increasing the frequency of express saccades and decreasing the mean latency. This facilitation occurs only for cues that correctly indicate the direction of the subsequent target presentation (valid cues). The present study investigates the effects of valid cues on SRTs and error rate in the anti-saccade task (saccades in the direction opposite to the stimulus) by systematically varying the cue lead time (CLT) and using the gap and overlap conditions, i.e. fixation point remains on throughout the trial. For a CLT of 100 ms, both reaction times and error rates were significantly increased. With increasing CLT (200-500 ms), both the reaction times of the anti-saccades and the error rates returned to approximately control level, with CLT more than 200 ms in both the gap and the overlap condition. Additional experiments using non-informative cues in the overlap task showed that the reaction times of correct anti-saccades and the error rate were decreased when cue and stimulus appeared at the same side. Analysis of the erratic pro-saccades revealed that almost all of them were corrected, i.e. they were followed by a second saccade towards the required location. It is found that the correction times were usually very short, with intersaccadic intervals between 0 and 150 ms. We suggest that the orienting mechanism, elicited by a transient peripheral cue, relates to the command and the decision to make a pro- rather than an anti-saccade. The cue elicits pro-orienting towards its position when a pro-saccade is required, and anti-orienting when an anti-saccade is required. The orienting effect is transient and decays with CLTs of more than 200 ms; this result holds for both anti-saccades and pro-saccades. Since subjects reported that they could not prevent the erratic pro-saccades or were often not aware of them, we conclude that this orienting mechanism occurs automatically, beyond voluntary control.