Civil society and democracy in nineteenth century Europe: Entanglements, variations, conflicts

It is ironic that the travelogue of a French aristocrat became one of the canonical texts of American democracy. Even today, American liberals and conservatives rely on De la Démocratie en Amérique to support their arguments and assume that Tocqueville’s insights, including his conviction that voluntary associations are the bedrock of American democracy, are still relevant today. However, in a historical and transnational perspective, Tocqueville’s famous passages in Democracy in America are as unexceptional as the American society of his time, given the enthusiasm for associative sociability by eighteenth and nineteenth-century practitioners of civil society in France, Germany, the Habsburg Empire and Russia. Revisiting the history of these “sociable societies” provides an answer to the question whether voluntary associations can be considered schools for democracy or not.Es entbehrt nicht der Ironie, dass der Reisebericht eines französischen Aristokraten zu einem kanonischen Text der amerikanischen Demokratie aufstieg. Noch heute berufen sich Liberale wie Konservative in den Vereinigten Staaten auf De la Démocratie en Amérique, um ihren politischen Argumenten Gewicht zu geben. Dabei gehen sie davon aus, dass Tocquevilles Analysen, insbesondere seine Überzeugung, die Grundlage der amerikanischen Demokratie beruhe auf ihren freien Vereinigungen, noch heute von Bedeutung sind. Aus historischer und transnational vergleichender Perspektive lässt sich aber feststellen, dass Tocquevilles Einsichten in Die Demokratie in Amerika ebenso wenig einen Sonderstatus einnehmen wie die amerikanische Gesellschaft seiner Zeit. Das zeigt die Leidenschaft der Praktiker der Bürgergesellschaft für gesellige Vereine in Frankreich, den deutschen Staaten, dem Habsburgerreich und Rußland im 18. und 19. Jahrhundert. Ein neuer Blick auf die Geschichte dieser ‚geselligen Gesellschaften’ gibt Antwort auf die Frage, ob freie Vereinigungen Schulen der Demokratie sind oder nicht

Civil society and democracy in nineteenth century Europe: entanglements, variations, conflicts

"It is ironic that the travelogue of a French aristocrat became one of the canonical texts of American democracy. Even today, American liberals and conservatives rely on De la Démocratie en Amérique to support their arguments and assume that Tocqueville's insights, including his conviction that voluntary associations are the bedrock of American democracy, are still relevant today. However, in a historical and transnational perspective, Tocqueville's famous passages in Democracy in America are as unexceptional as the American society of his time, given the enthusiasm for associative sociability by eighteenth and nineteenth-century practitioners of civil society in France, Germany, the Habsburg Empire and Russia. Revisiting the history of these 'sociable societies' provides an answer to the question whether voluntary associations can be considered schools for democracy or not." (author's abstract)"Es entbehrt nicht der Ironie, dass der Reisebericht eines französischen Aristokraten zu einem kanonischen Text der amerikanischen Demokratie aufstieg. Noch heute berufen sich Liberale wie Konservative in den Vereinigten Staaten auf De la Démocratie en Amérique, um ihren politischen Argumenten Gewicht zu geben. Dabei gehen sie davon aus, dass Tocquevilles Analysen, insbesondere seine Überzeugung, die Grundlage der amerikanischen Demokratie beruhe auf ihren freien Vereinigungen, noch heute von Bedeutung sind. Aus historischer und transnational vergleichender Perspektive lässt sich aber feststellen, dass Tocquevilles Einsichten in Die Demokratie in Amerika ebenso wenig einen Sonderstatus einnehmen wie die amerikanische Gesellschaft seiner Zeit. Das zeigt die Leidenschaft der Praktiker der Bürgergesellschaft für gesellige Vereine in Frankreich, den deutschen Staaten, dem Habsburgerreich und Russland im 18. und 19. Jahrhundert. Ein neuer Blick auf die Geschichte dieser 'geselligen Gesellschaften' gibt Antwort auf die Frage, ob freie Vereinigungen Schulen der Demokratie sind oder nicht." (Autorenreferat

Os Direitos Humanos e a História

Tradução do texto “Human Rights and History”, de Stefan-Ludwig Hoffmann, publicado na revista Past & Present, Volume 232, Issue 1, August 2016, Pages 237–278, https://doi.org/10.1093/pastj/gtw01

Large nuclear spin polarization in gate-defined quantum dots using a single-domain nanomagnet

The electron-nuclei (hyperfine) interaction is central to spin qubits in solid state systems. It can be a severe decoherence source but also allows dynamic access to the nuclear spin states. We study a double quantum dot exposed to an on-chip single-domain nanomagnet and show that its inhomogeneous magnetic field crucially modifies the complex nuclear spin dynamics such that the Overhauser field tends to compensate external magnetic fields. This turns out to be beneficial for polarizing the nuclear spin ensemble. We reach a nuclear spin polarization of ~50%, unrivaled in lateral dots, and explain our manipulation technique using a comprehensive rate equation model

Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

Multivalent interactions at biological interfaces occur frequently in nature and mediate recognition and interactions in essential physiological processes such as cell-to-cell adhesion. Multivalency is also a key principle that allows tight binding between pathogens and host cells during the initial stages of infection. One promising approach to prevent infection is the design of synthetic or semisynthetic multivalent binders that interfere with pathogen adhesion1,2,3,4. Here, we present a multivalent binder that is based on a spatially defined arrangement of ligands for the viral spike protein haemagglutinin of the influenza A virus. Complementary experimental and theoretical approaches demonstrate that bacteriophage capsids, which carry host cell haemagglutinin ligands in an arrangement matching the geometry of binding sites of the spike protein, can bind to viruses in a defined multivalent mode. These capsids cover the entire virus envelope, thus preventing its binding to the host cell as visualized by cryo-electron tomography. As a consequence, virus infection can be inhibited in vitro, ex vivo and in vivo. Such highly functionalized capsids present an alternative to strategies that target virus entry by spike-inhibiting antibodies5 and peptides6 or that address late steps of the viral replication cycle

Copy number variations in 375 patients with oesophageal atresia and/or tracheoesophageal fistula

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444-143839360)-(159119486-159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition

Human Rights and German Intellectual History in Transnational Perspective

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156446/1/gequ12147.pd

Methylation matters: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells

The forkhead-box protein P3 (Foxp3) is a key transcription factor for the development and suppressive activity of regulatory T cells (Tregs), a T cell subset critically involved in the maintenance of self-tolerance and prevention of over-shooting immune responses. However, the transcriptional regulation of Foxp3 expression remains incompletely understood. We have previously shown that epigenetic modifications in the CpG-rich Treg-specific demethylated region (TSDR) in the Foxp3 locus are associated with stable Foxp3 expression. We now demonstrate that the methylation state of the CpG motifs within the TSDR controls its transcriptional activity rather than a Treg-specific transcription factor network. By systematically mutating every CpG motif within the TSDR, we could identify four CpG motifs, which are critically determining the transcriptional activity of the TSDR and which serve as binding sites for essential transcription factors, such as CREB/ATF and NF-κB, which have previously been shown to bind to this element. The transcription factor Ets-1 was here identified as an additional molecular player that specifically binds to the TSDR in a demethylation-dependent manner in vitro. Disruption of the Ets-1 binding sites within the TSDR drastically reduced its transcriptional enhancer activity. In addition, we found Ets-1 bound to the demethylated TSDR in ex vivo isolated Tregs, but not to the methylated TSDR in conventional CD4+ T cells. We therefore propose that Ets-1 is part of a larger protein complex, which binds to the TSDR only in its demethylated state, thereby restricting stable Foxp3 expression to the Treg lineage

Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity.

BACKGROUND: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. METHODS: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. FINDINGS: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. INTERPRETATION: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA. FUNDING: NIH, Damon Runyon Foundation, ACS, NYCT, DFG, EU, Berlin Mathematics center MATH+, BMBF, Lower Saxony, Lundbeck Foundation, Novo Nordisk Foundation