Trapping the HIV-1 V3 loop in a helical conformation enables broad neutralization

The third variable (V3) loop on the human immunodeficiency virus 1 (HIV-1) envelope glycoprotein trimer is indispensable for virus cell entry. Conformational masking of V3 within the trimer allows efficient neutralization via V3 only by rare, broadly neutralizing glycan-dependent antibodies targeting the closed prefusion trimer but not by abundant antibodies that access the V3 crown on open trimers after CD4 attachment. Here, we report on a distinct category of V3-specific inhibitors based on designed ankyrin repeat protein (DARPin) technology that reinstitute the CD4-bound state as a key neutralization target with up to >90% breadth. Broadly neutralizing DARPins (bnDs) bound V3 solely on open envelope and recognized a four-turn amphipathic α-helix in the carboxy-terminal half of V3 (amino acids 314-324), which we termed 'αV3C'. The bnD contact surface on αV3C was as conserved as the CD4 binding site. Molecular dynamics and escape mutation analyses underscored the functional relevance of αV3C, highlighting the potential of αV3C-based inhibitors and, more generally, of postattachment inhibition of HIV-1

„Hamburger Note zur Digitalisierung des kulturellen Erbes“

Das Recht, insbesondere das Urheberrecht, hat große Auswirkungen darauf, was von dem großen Reichtum unseres kulturellen Erbes im kollektiven Gedächtnis verbleibt. In der digitalen Welt, in der alles Kopie und damit – im urheberrechtlichen Sinne – Vervielfältigung ist, ist auch jede Nutzung des kulturellen Erbes urheberrechtlich relevant. Auf der anderen Seite leben wir in Zeiten einer rasanten Medienentwicklung und eines Überflusses an Informationen, Bildern, Filmen und Texten. Umso größer ist die Herausforderung, die Erinnerung an unser kulturelles Erbe wachzuhalten. Es ist also eine Frage der kulturellen Selbstbehauptung, wie die rechtlichen Rahmenbedingungen für den Umgang mit unserem kulturellen Erbe gesetzt werden. Was nicht online gefunden werden kann, wird zunehmend verschwinden. Insofern können die Auswirkungen eines unausgewogenen Urheberrechts, das das kulturelle Erbe nicht ausreichend berücksichtigt, dramatisch sein. Dieses Buch versammelt verschiedene Vorschläge und Überlegungen, wie die rechtlichen Rahmenbedingungen geändert werden können, um eine stärkere Präsenz auch des urheberrechtlich geschützten kulturellen Erbes im Netz zu ermöglichen. Verfasst sind diese Vorschläge von Experten aus den Gedächtnisinstitutionen sowie aus der Rechtswissenschaft und Politik, mithin von Autoren, die mit den internationalen Rahmenbedingungen und dem urheberrechtlichen Diskurs in Deutschland gut vertraut sind.The law, in particular copyright, has a major impact on what remains in collective memory of the great wealth of our cultural heritage. In the digital world where everything is copy and therefore - in the sense of copyright - reproduction, every use of the cultural heritage is also relevant under copyright law. On the other hand, we live in times of rapid media development and an abundance of information, images, films and texts. This is why the challenge of keeping the memory of our cultural heritage alive is all the greater. It is therefore a question of cultural self-assertion how the legal framework conditions for dealing with our cultural heritage are set. What cannot be found online will increasingly disappear. In this respect, the effects of an unbalanced copyright law that does not take sufficient account of cultural heritage can be dramatic. This book brings together various proposals and reflections on how to change the legal framework in order to increase the presence of copyrighted cultural heritage on the Internet. These proposals are written by experts from memory institutions, law and politics, and thus by authors who are well acquainted with the international framework conditions and copyright discourse in Germany

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

A Framework for Analyzing Verifiability in Traditional and Electronic Exams.

International audienceThe main concern for institutions that organize exams is to detect when students cheat. Actually more frauds are possible and even authorities can be dishonest. If institutions wish to keep exams a trustworthy business, anyone and not only the authorities should be allowed to look into an exam's records and verify the presence or the absence of frauds. In short, exams should be verifiable. However, what verifiability means for exams is unclear and no tool to analyze an exam's verifiability is available. In this paper we address both issues: we formalize several individual and universal verifiability properties for traditional and electronic exams, so proposing a set of verifiability properties and clarifying their meaning, then we implement our framework in ProVerif, so making it a tool to analyze exam verifiability. We validate our framework by analyzing the verifiability of two existing exam systems – an electronic and a paper-and-pencil system

On the verifiability of (electronic) exams

The main concern for institutions that organize exams is to detect when students cheat. Actually more frauds are possible and even authorities can be dishonest. If institutions wish to keep exams a trustworthy business, anyone and not only the authorities should be allowed to look into an exam’s records and verify the presence or the absence of frauds. In short, exams should be verifiable. However, what verifiability means for exams is unclear and no tool to analyze an exam’s verifiability is available. In this paper we address both issues: we formalize several individual and universal verifiability properties for traditional and electronic exams, so proposing a set of verifiability properties and clarifying their meaning, then we implement our framework in ProVerif, so making it a tool to analyze exam verifiability. We validate our framework by analyzing the verifiability of two existing exam systems – an electronic and a paper-and-pencil system

Formal Analysis of Electronic Exams

International audienceUniversities and other educational organizations are adopting computer-and internet-based assessment tools (herein called electronic exams, or e-exams for short) to reach widespread audiences. While this makes examination tests more accessible, it exposes them to new threats. Most current work on e-exam systems aims at mitigating the risk of cheating, but recent scandals have shown that such systems are also vulnerable to other attacks. In particular it turned out that not all exam authorities can always be trusted, and that the use of networks makes the systems vulnerable to outside attackers. Although not employed in practice, in the scientific literature there are some proposals of protocols trying to address these risks. However, there are very few strategies to check such e-exam protocols for security, and there is a lack of precise formal security definitions in this domain. This paper fills this gap: in the formal framework of the applied π-calculus, we define several fundamental authentication and privacy properties and establish the first theoretical framework for the security analysis of e-exam protocols. In particular, we consider authentication and integrity of the questions and answers , as well as privacy of marks and secrecy of the questions before the exam. Moreover, we also analyze anonymity of the examiners and candidates during the grading process to ensure fairness. As proof of concept we analyze two e-exam protocols with ProVerif, an automated protocol verification tool. The first " secure electronic exam system " proposed in the literature turns out to have several severe problems, and fails at ensuring all analyzed properties. The second protocol, called Remark!, is proved to satisfy all the security properties assuming access control on the bulletin board. We propose a simple protocol modification that removes the need of such assumption though guaranteeing all the security properties

Formal Security Analysis of Traditional and Electronic Exams

Nowadays, students can be assessed not only by means of pencil-and-paper tests but also by electronic exams which they take in examination centers or even from home. Electronic exams are appealing as they can reach larger audiences, but they are exposed to new threats that can potentially ruin the whole exam business. These threats are amplified by two issues: the lack of understanding of what security means for electronic exams (except the old concern about students cheating), and the absence of tools to verify whether an exam process is secure. This paper addresses both issues by introducing a formal description of several fundamental authentication and privacy properties, and by establishing the first theoretical framework for an automatic analysis of exam security. It uses the applied π-calculus as a framework and ProVerif as a tool. Three exam protocols are checked in depth: two Internet exam protocols of recent design, and the pencil-and-paper exam used by the University of Grenoble. The analysis highlights several weaknesses. Some invalidate authentication and privacy even when all parties are honest; others show that security depends on the honesty of parties, an often unjustified assumption in modern exams