Suchergebnisse

Cosmopolitans often argue that the international community has a humanitarian responsibility to intervene militarily in order to protect vulnerable individuals from violent threats and to pursue the establishment of a condition of cosmopolitan justice based on the notion of a 'global rule of law'. The purpose of this article is to argue that many of these cosmopolitan claims are incomplete and untenable on cosmopolitan grounds because they ignore the systemic and chronic structural factors that underwrite the root causes of these humanitarian threats. By way of examining cosmopolitan arguments for humanitarian military intervention and how systemic problems are further ignored in iterations of the Responsibility to Protect, this article suggests that many contemporary cosmopolitan arguments are guilty of focusing too narrowly on justifying a responsibility to respond to the symptoms of crisis versus demanding a similarly robust justification for a responsibility to alleviate persistent structural causes. Although this article recognizes that immediate principles of humanitarian intervention will, at times, be necessary, the article seeks to draw attention to what we are calling principles of Jus ante Bellum (right before war) and to stress that current cosmopolitan arguments about humanitarian intervention will remain insufficient without the incorporation of robust principles of distributive global justice that can provide secure foundations for a more thoroughgoing cosmopolitan condition of public right.

It is often argued that cosmopolitanism faces unique motivational constraints, asking more of individuals than they are able to give. This 'motivational problem' is held to pose a significant challenge to cosmopolitanism, as it appears unable to transform its moral demands into motivated political action. This article develops a novel response to the motivational problem facing cosmopolitanism, arguing that self-interest, alongside appeals to sentiment, can play a vital and neglected, transitional role in moving towards an expanded cosmopolitical condition. The article explicates the 'motivational problem', analyses the relationship between self-interest and sentimental cosmopolitanism in addressing it, and develops a series of claims that self-interest can be one important component in what we label as 'transitional cosmopolitanism'. In doing so, we argue that self-interested motivations can be compatible with sentiment-based approaches, rendering them more plausible. In addition, two expected critiques of self-interested 'transitional cosmopolitanism' are tackled: (A) That it cannot address feasibility constraints, and (B) That self-interested motivations cannot meet what an 'authentic' cosmopolitanism entails. We refute and challenge these critiques and outline three conditions in which self-interest can advance a transitional form of cosmopolitanism, while also being compatible with cosmopolitanism writ large.

G-quadruplex DNAs form four-stranded helical structures and are proposed to play key roles in different cellular processes. Targeting G-quadruplex DNAs for cancer treatment is a very promising prospect. Here, we show that CX-5461 is a G-quadruplex stabilizer, with specific toxicity against BRCA deficiencies in cancer cells and polyclonal patient-derived xenograft models, including tumours resistant to PARP inhibition. Exposure to CX-5461, and its related drug CX-3543, blocks replication forks and induces ssDNA gaps or breaks. The BRCA and NHEJ pathways are required for the repair of CX-5461 and CX-3543-induced DNA damage and failure to do so leads to lethality. These data strengthen the concept of G4 targeting as a therapeutic approach, specifically for targeting HR and NHEJ deficient cancers and other tumours deficient for DNA damage repair. CX-5461 is now in advanced phase I clinical trial for patients with BRCA1/2 deficient tumours (Canadian trial, NCT02719977, opened May 2016). ; This work was supported by the Canadian Breast Cancer Foundation BC/Yukon, BC Cancer Foundation, Stand Up to Cancer Canada (SU2C-AACR-DT-18-15), TFRI Grant 1021, CCSRI Grant 701584, CIHR Grant MOP-126119, Canada Foundation for Innovation and Cancer Research UK. Grant Brown lab is supported by CCSRI Impact Grant 702310 (to G.W.B.) and Ontario Government Scholarship (to B.H.). S.A. is supported by a Canada Research Chair in Molecular Oncology. The Balasubramanian lab is supported by a programme grant (C14303/A17197) and core funding (C14303/A17197) from Cancer Research UK.