Social Media and the Digital Structural Transformation of the Public Sphere

This article explores the question of how to understand social media following the Habermasian theory of the structural transformation of the public sphere. We argue for a return to political-economic fundamentals as the basis for analysing the public sphere and seek to establish a characteristic connection between digital-behavioural control and singularised audiences in the context of proprietary markets. In the digital constellation, it is less a matter of immobilising the citizen as a consumer but rather of their political activation – albeit in conditions under which commercial interests have primacy: privatisation without privatism.Peer Reviewe

Computational Methods for the Modulation of Protein-Protein Interactions

During the last decades, drug discovery development has made considerable progress. However, annual numbers of released drugs for novel targets have been decreasing concomitantly. Limited success rates of combinatorial chemistry and high-throughput screening, as well as availability of feasible targets are some reasons for this problem. A strategy to overcome it is exploration of novel target classes in order to expand the druggable space. An example are protein-protein interactions (PPIs) that can be inhibited or stabilized. Inhibition aims at developing binders for one protein to prevent complex formation. However, known PPI inhibitors differ significantly from conventional drugs and current active site-biased compound libraries are probably inappropriate to discover them. The design of novel screening libraries is thus very important. PPI stabilization aims at developing molecules that bind to a protein complex to increase its stability like a molecular glue. In contrast to inhibition, it is rather unexplored but ground-breaking examples from nature inspire research efforts. This work presents novel theoretical and experimental drug discovery approaches for these challenges. In the first part, we introduce novel chemoinformatics approaches for clustering of large chemical libraries. The development of a fast algorithm for pairwise similarity calculations forms the basis for an exact and deterministic clustering method, which is able to process the available chemical space in a short time. We complement our chemoinformatics work by a novel approach for fast classification of small molecules according to the similarity of their frameworks, the so-called scaffolds. The method generates families of molecules that share geometry conserving scaffolds and we show that family members possess similar activity on identical targets. The second part introduces computational methods for PPI modulation. First, we present structure-based analysis of known stabilized PPIs, which enables the development of novel in silico approaches to screen for small molecule PPI stabilizers. We demonstrate their applicability by an experimentally tested virtual screening for 14-3-3 protein interaction stabilizers. Finally, we present a virtual screening approach dedicated to identify small molecule inhibitors of 14-3-3 protein interactions. Predicted inhibitors are experimentally verified and characterized by in vitro assays and X-ray crystallography. Structure-activity relationship studies yielded PPI inhibitors in the low micromolar range, which are also active in cell-based experiments

An ancient FMRFamide-related peptide-receptor pair induces defense behavior in a brachiopod larva

Animals show different behaviors that can consist of various spatially or temporally separated sub-reactions. Even less complex organisms, like ciliated larvae that display important behaviors (e.g. metamorphosis, defense, feeding), need to coordinate coherent sub-reactions with their simple nervous system. These behaviors can be triggered by neuropeptides, which are short signaling peptides. Despite the high diversity of neuropeptides in animals, and although their immunoreactivity is widely used in morphological studies of animal nervous systems (e.g. FMRFamide), their function and role in trochozoan larval behavior has so far only been tested in a few cases. When mechanically disturbed, the planktonic larvae of the brachiopod Terebratalia transversa protrude their stiff and pointy chaetae in a defensive manner and sink down slowly: a startle reaction that is known from different chaetous trochozoan larvae. We found that both of these reactions can be induced simultaneously by the FMRFamide-related neuropeptide FLRFamide. We deorphanized the Terebratalia FLRFamide receptor and found its expression spatially separated in the apical lobe at the prototroch of the larvae and in the trunk musculature, which correlates with the tissues that are responsible to perform the two sub-reactions. A behavioral assay showed a decreasing efficiency of modified peptides in triggering this behavior, which correlates with the decreasing efficiency of activating the FLRFamide receptor in transfected CHO-K1 cells. Immunohistochemistry and in situ hybridization show FLRFamidergic neurons in the apical lobe as well as next to the trunk musculature. Our results show that the single neuropeptide FLRFamide can specifically induce the two coherent sub-reactions of the T. transversa startle behavior.draf

Toll-like receptor stimulation induces higher TNF-alpha secretion in peripheral blood mononuclear cells from patients with hyper IgE syndrome

Hyper IgE syndromes (HIES) are primary immunodeficiency disorders of unknown pathogenesis. Patients are typically affected with `cold' abscesses of the skin, recurrent cyst-forming pneumonia, chronic mucocutaneous candidiasis and other less frequent features such as progressive skeletal abnormalities. Defective signaling in the Toll-like receptor (TLR) pathways has been suggested as a responsible pathologic mechanism, however, in previous reports, 10 patients revealed no defect in inflammatory cytokine responses to different TLR ligands. Here, we report the increase in pro-inflammatory cytokines TNF-alpha and IL-8, following TLR2 and TLR4 stimulation in a larger cohort of 25 additional patients with HIES, and provide a meta-analysis of the TLR data in HIES. Copyright (C) 2008 S. Karger AG, Basel

Substrate-free miniaturized thin-film filters for single-element coarse wavelength division multiplexing fibers

We have created high-precision, miniaturized, substrate-free filters, based on ion beam sputtering on a sacrificial substrate. The sacrificial layer is cost efficient and environmentally friendly and can be dissolved using only water. We demonstrate an improved performance compared to filters on thin polymer layers from the same coating run. With these filters, a single-element coarse wavelength division multiplexing transmitting device for telecommunication applications can be realized by inserting the filter between fiber ends

Distribution of preoperative angle alpha and angle kappa values in patients undergoing multifocal refractive lens surgery based on a positive contact lens test

Purpose: To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods: Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results: Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (<0.5mm). In the 1-year follow-up, UCVA improved by 0.68 logMAR (SD 0.51; p<0.001) from baseline. Eyes with both small angle alpha and kappa sizes improved by 0.78 logMAR (SD 0.56), as did eyes with high (≥0.5mm) angle sizes (0.82 logMAR (SD 0.53). UCVA of eyes (n=24) with high alpha but low kappa sizes improved less (-0.31 logMAR (SD 0.13; p=0.019)). Conclusion: Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes. Keywords: Angle alpha; Angle kappa; Decision-making; Multifocal intraocular lens; Refractive lens surgery

Flattening the curve in 52 days: characterisation of the COVID-19 pandemic in the Principality of Liechtenstein - an observational study.

BACKGROUND The principality of Liechtenstein had its first COVID-19 case at the beginning of March 2020. After exponential growth, the pandemic&rsquo;s first wave was contained, with the last case being diagnosed 52 days after the initial occurrence. AIM To characterise the COVID-19 pandemic in Liechtenstein. METHODS All patients diagnosed in Liechtenstein were followed up until recovery and again 6&ndash;8 weeks after symptom onset. They were contacted every 2 days to record their clinical status until the resolution of their symptoms. The diagnosis of COVID-19 was based on clinical symptoms and molecular testing. Household and close workplace contacts were included in the follow-up, which also comprised antibody testing. In addition, public health measures installed during the pandemic in Liechtenstein are summarised. RESULTS During the first wave, 5% of the population obtained a reverse transcriptase polymerase chain reaction test. A total of 95 patients (median age 39 years) were diagnosed with COVID-19 (82 who resided in Liechtenstein), resulting in an incidence in Liechtenstein of 0.211%. One patient, aged 94, died (mortality rate 1%). Only 62% of patients could retrospectively identify a potential source of infection. Testing the patients&rsquo; household and close workplace contacts (n = 170) with antibody tests revealed that 25% of those tested were additional COVID-19 cases, a quarter of whom were asymptomatic. Those households which adhered to strict isolation measures had a significantly lower rate of affected household members than those who didn&rsquo;t follow such measures. The national public health measures never restricted free movement of residents. Masks were only mandatory in healthcare settings. The use of home working for the general workforce was promoted. Gatherings were prohibited. Schools, universities, certain public spaces (like sports facilities and playgrounds), childcare facilities, nonessential shops, restaurants and bars were closed. Social distancing, hygienic measures, solidarity and supporting individuals who were at risk were the main pillars of the public health campaigns. CONCLUSION The close collaboration of all relevant stakeholders allowed for the complete workup of all COVID-19 patients nationwide. A multitude of factors (e.g., young age of the patients, low-threshold access to testing, close monitoring of cases, high alertness and adherence to public health measures by the population) led to the early containment of the first wave of the pandemic, with a very low rate of serious outcomes. Antibody testing for SARS-CoV-2 revealed a substantial proportion of undiagnosed COVID-19 cases among close contacts of the patients

Multi-Chip Integration by Photonic Wire Bonding: Connecting Surface and Edge Emitting Lasers to Silicon Chips

We demonstrate coupling of surface and edge emitting InP lasers to silicon photonic chips using photonic wire bonding. We confirm that back-reflections from the silicon chip do not deteriorate the linewidth of the lasers

EpiToolKit—a web server for computational immunomics

Predicting the T-cell-mediated immune response is an important task in vaccine design and thus one of the key problems in computational immunomics. Various methods have been developed during the last decade and are available online. We present EpiToolKit, a web server that has been specifically designed to offer a problem-solving environment for computational immunomics. EpiToolKit offers a variety of different prediction methods for major histocompatibility complex class I and II ligands as well as minor histocompatibility antigens. These predictions are embedded in a user-friendly interface allowing refining, editing and constraining the searches conveniently. We illustrate the value of the approach with a set of novel tumor-associated peptides. EpiToolKit is available online at www.epitoolkit.org