The p53 tumor suppressor protein binds to both cellular and viral proteins, which influence its biological activity. One such protein is the large E1b tumor antigen (E1b58kDa) from adenoviruses (Ads), which abrogates the ability of p53 to transactivate various promoters. This inactivation of p53 function is believed to be the mechanism by which E1b58kDa contributes to the cell transformation process. Although the p53-E1b58kDa complex occurs during infection and is conserved among different serotypes, there are limited data demonstrating that it has a role in virus replication. However, loss of p53 expression occurs after adenovirus infection of human cells and an E1b58kDa deletion mutant (Onyx-015, also called dl 1520) selectively replicates in p53-defective cells. These (and other) data indicate a plausible hypothesis is that loss of p53 function may be conducive to efficient adenovirus replication. However, wild-type (wt) Ad5 grows more efficiently in cells expressing a wt p53 protein. These studies indicate that the hypothesis may be an oversimplification. Here, we show that cells expressing wt p53, as well as p53-defective cells, allow adenovirus replication, but only cells expressing wt p53 show evidence of virus-induced cytopathic effect. This correlates with the ability of adenovirus to induce cell death. Our data indicate that p53 plays a necessary part in mediating cellular destruction to allow a productive adenovirus infection. In contrast, p53-deficient cells are less sensitive to the cytolytic effects of adenovirus and as such raise questions about the use of E1b58kDa-deficient adenoviruses in tumor therapy.

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Free of the prejudice of the infallibility of our senses and kept on continuous guard against the information they give, science searches for other means in the conquest of truth; it finds them in precision instruments .... These devices penetrate the intimate functions of organs where life seems to exist in ceaseless motion.'' Etienne-Jules Marey (1878, page 382)`T

This essay addresses the conditions and limits of artistic interventions in the contemporary landscape of border security. It argues that the theatrical rituals of border security — scanning, screening, verifying identity — have become domesticated and all-but-invisible in our daily scopic regimes. At the same time, the essay suggests that surprising, enchanting encounters with the techniques and technologies of security can interrupt border sequences and create invigorated possibilities for public engagement. An ethics of unanticipated worlds is proposed as an alternative to political action as always proximate to observable and visible violence. In a world where rituals of border security increasingly operate precisely by pre-deciding and pre-empting in advance, art that works in the absence of certainty and decidability offers a crucial window through which to evaluate and respond.

Anabolic-androgenic steroids are performance and image enhancing drugs (PIED) that can improve endurance and athletic performance, reduce body fat and stimulate muscle growth. The use of steroids has been studied extensively in the medical and psychological literature, as well as in the sociology of sport, health and masculinity. From the late 2000s, the worldwide trade in steroids increased significantly. However, trafficking in steroids remains a largely under-researched criminological phenomenon with a few notable exceptions. Currently in the UK there are only small and fragmented pieces of information available relating to steroids trafficking in autobiographical accounts of professional criminals. Drawing on original empirical data, the purpose of this article is to provide an account of the social organization of the steroids trafficking business in the UK. The trade in steroids is decentralized, highly flexible with no hierarchies, and open to anyone willing to either order the merchandise online or travel to producing countries and obtain steroids in bulk from legitimate manufacturers. The patterns of trafficking of this specific type of substance are patently conditioned by its embeddedness in the gym/bodybuilding scene and this greatly affects relations between actors in the business. In the steroids market, one typically encounters a multitude of individuals likely to drift between legality and illegality, online and offline, use and supply.

We have explored a role for the adenovirus (Ad5) E1b58kDa/p53 protein complex in adenovirus replication. This was done by using virus mutants containing different defects in the E1b58kDa gene and cell lines that express either a wild-type p53 protein or a mutant p53 protein. We find that infection of wild-type p53-containing cells with wild-type Ad5 causes a shutoff of p53 and alpha-actin protein synthesis by distinct mechanisms, but neither occurs in mutant p53 cells. Our data also indicate that the shutoff is dependent on formation of the p53/E1b complex and may also involve another virus protein, E4ORF6. Following from these observations we asked whether failure to form the complex resulted in impaired adenovirus replication. Our experiments showed that neither wild-type Ad5 nor the E1b mutant dl338 could replicate in cells expressing a mutant p53 protein, but that wild-type adenovirus replicated well in wild-type p53-expressing cells. Collectively, our data suggest that the interaction between p53 and the E1b58kDa protein is necessary for efficient adenovirus replication. This is the first time such a direct link between the complex and virus replication has been demonstrated. These data raise serious questions about the usefulness of E1b-defective viruses in tumor therapy.

The transformation-related protein p53 is normally very labile. The stability of p53 is significantly increased in a number of fibrosarcoma cell lines derived from mouse tumors induced by treatment with physical or chemical agents. In many instances, p53 stabilization is correlated with the ability to form a stable complex with the heat shock protein cognate hsc7O. We describe a line in which p53 is very stable yet has no detectable interaction with hsc7O. The inability to form such a complex probably resides in the primary structure of the endogenous p53, since introduction of other p53 variants into those cells resulted in the appearance of a p53-hsc7O complex. The factors affecting p53 stability were investigated by stable transfection experiments. The results indicated that the primary structure of the p53 protein is a major determinant of its turnover rate; different p53 variants were degraded at distinct and characteristic rates in a number of transformed cell types. However, at least one p53 variant was degraded differently in nontransformed BALB/c-3T3 than in transformed fibrosarcoma cells, demonstrating that the specific cellular environment can also affect the stability of p53.

Amidst a widespread turn to data analysis and automated screening in security contexts, the question of how decisions are made at the interface of embodied humans and algorithmic processes becomes pressing. This paper is concerned with the production of security decisions at the data border. It makes two contributions. First, it presents qualitative fieldwork amongst data processors at a European smart border targeting centre and, second, it traces a largely obscured cultural history of discretion as means of reflecting on the politics of contemporary data-led decision-making. Discretion is an important concept in contemporary administrative contexts, referring to a decision about the (non)application of a rule in contexts of public power and authority. Its etymon, discretio, however, referred historically to spiritual and visual discernment, as well as prudence and humility. I present the history of discretion to make two arguments: 1) decision-making at the data border is an uncertain visual practice oriented to seeing and authorising what is there and 2) discretion in contemporary data-led contexts revises the conventional ethical relationship between general and particular that has always been intrinsic to discretion. My overall point is that contemporary debates about judgement in automated security decisions are the most recent manifestation of long-standing tensions between rule and judgement, authorisation and uncertainty.