54 research outputs found

    Revisiting past cyber operations in light of new cyber norms and interpretations of international law:: inching towards lines in the sand?

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    This article traces the evolution of interpretations of international law and international cyber norms on responsible state behaviour in cyberspace by reassessing five major – and allegedly state-led – cyber operations: Stuxnet 2010; Belgacom 2013-2014, the Ukrainian power grid 2015, the US presidential election 2016, and NotPetya 2017. Taking recent normative developments and emerging state practices as primary points of refence, it investigates how the current normative landscape can shed light on the nature, (il)legitimacy, and (un)lawfulness of these past operations. For each case, the analysis engages with: i) the elements triggering the violation of norms, principles and international law; ii) the legal and normative significance of recent sources of norms and interpretations of international law; and iii) the legal and political obstacles still lying beyond their application. Taken together, the reassessment of these cyber operations reveals how, in hindsight, the international community has come a long way in calibrating its normative language and practices in calling out irresponsible behaviour in cyberspace. With states taking small, but unprecedented, steps through public attributions and statements on international law in cyberspace, most of the past cyber operations analysed here would arguably feature an attribution in the current climate. At the same time, substantial differences in national interpretations of international law continue to stand in the way of clarity on the terms of its application. In light of this, this article ultimately suggests that cyber norms and the interpretations of international law require further granularity to become ‘lines in the sand’

    Evolution of the HIV-1 envelope glycoproteins with a disulfide bond between gp120 and gp41

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    BACKGROUND: We previously described the construction of an HIV-1 envelope glycoprotein complex (Env) that is stabilized by an engineered intermolecular disulfide bond (SOS) between gp120 and gp41. The modified Env protein antigenically mimics the functional wild-type Env complex. Here, we explore the effects of the covalent gp120 – gp41 interaction on virus replication and evolution. RESULTS: An HIV-1 molecular clone containing the SOS Env gene was only minimally replication competent, suggesting that the engineered disulfide bond substantially impaired Env function. However, virus evolution occurred in cell culture infections, and it eventually always led to elimination of the intermolecular disulfide bond. In the course of these evolution studies, we identified additional and unusual second-site reversions within gp41. CONCLUSIONS: These evolution paths highlight residues that play an important role in the interaction between gp120 and gp41. Furthermore, our results suggest that a covalent gp120 – gp41 interaction is incompatible with HIV-1 Env function, probably because this impedes conformational changes that are necessary for fusion to occur, which may involve the complete dissociation of gp120 from gp41

    The carbohydrate at asparagine 386 on HIV-1 gp120 is not essential for protein folding and function but is involved in immune evasion

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    <p>Abstract</p> <p>Background</p> <p>The HIV-1 envelope glycoprotein gp120, which mediates viral attachment to target cells, consists for ~50% of sugar, but the role of the individual sugar chains in various aspects of gp120 folding and function is poorly understood. Here we studied the role of the carbohydrate at position 386. We identified a virus variant that had lost the 386 glycan in an evolution study of a mutant virus lacking the disulfide bond at the base of the V4 domain.</p> <p>Results</p> <p>The 386 carbohydrate was not essential for folding of <it>wt </it>gp120. However, its removal improved folding of a gp120 variant lacking the 385–418 disulfide bond, suggesting that it plays an auxiliary role in protein folding in the presence of this disulfide bond. The 386 carbohydrate was not critical for gp120 binding to dendritic cells (DC) and DC-mediated HIV-1 transmission to T cells. In accordance with previous reports, we found that N386 was involved in binding of the mannose-dependent neutralizing antibody 2G12. Interestingly, in the presence of specific substitutions elsewhere in gp120, removal of N386 did not result in abrogation of 2G12 binding, implying that the contribution of N386 is context dependent. Neutralization by soluble CD4 and the neutralizing CD4 binding site (CD4BS) antibody b12 was significantly enhanced in the absence of the 386 sugar, indicating that this glycan protects the CD4BS against antibodies.</p> <p>Conclusion</p> <p>The carbohydrate at position 386 is not essential for protein folding and function, but is involved in the protection of the CD4BS from antibodies. Removal of this sugar in the context of trimeric Env immunogens may therefore improve the elicitation of neutralizing CD4BS antibodies.</p

    Vademecum politie Euregio Maas-Rijn

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    EU data protection in transatlantic cooperation in criminal matters<br> Will the EU be serving its citizens an American meal?

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    The still to be adopted Stockholm Programme, setting out the policy for justice and home affairs for the next five years, includes a chapter on data protection that calls for a comprehensive legal framework on data protection covering all areas of EU competence. With Directive 95/46 and a newly enacted Framework Decision on data protection in criminal matters there is still a need for such a comprehensive EU protection scheme. Both existing instruments are not consistent with each other and cannot thus form a comprehensive framework of data protection. The inconsistencies have equally penetrated the transatlantic cooperation in criminal matters. When assessing the agreements concluded between Europol, Eurojust and the EU, on the one hand, and the US, on the other (including the PNR Agreements), the same issues can be detected. Still, the communication on the Stockholm Programme refers to the data protection provisions in these agreements as an example for future bilateral and multilateral agreements

    A European criminal records database: an integrated model

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