Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, it (...) is associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. (shrink)

For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient (...) nature of transgene expression invivomust be overcome before their use in human gene therapy becomes clinically applicable. (shrink)

This paper resists the virality of contemporary paranoia by turning to “French epistemology”, a philosophical ethos that embraces uncertainty and complexity by registering the transformative impact of scientific knowledge on thought. Despite its popular uses describing phenomena of communication today, the idea of virality comes from biomedicine. This paper, therefore, investigates the extent to which an epidemiological concept of viral transmission—the disease vector—can comprehend and encourage new possibilities of thought beyond paranoia. Briefly, I attempt to analyze thought as (...) a vector. I pursue this by examining Delaporte’s important, but neglected, study of the 1832 Parisian cholera epidemic. First elucidating his reconstruction of the ways tentative epistemological progress intertwined with and supported projects of working-class and colonial control. My vectorial analysis then considers how his argument infects contemporary readers with doubts that undo the bases of paranoia. I pursue this analysis further via a methodological examination of Delaporte’s study as both carrier of predecessors’ methods and host in which they alter, becoming newly infectious. I conclude by reflecting on this formulation of thought as disease vector and what Delaporte’s singular treatment of the problem of error reveals about an ethos committed to registering the impact of knowledge on thought. (shrink)

The cloning of eukaryotic genes by standard recombinant DNA techniques permits their structural characterization. However, analysis of the expression properties of these genes often requires their introduction into and replication within eukaryotic cells in culture. Certain viral vectors based on the papilloma viruses may prove to be especially important in such investigations. These ‘shuttle vectors’, capable of replication in both bacterial and eukaryotic cells, have already provided several findings of interest about the relationship between eukaryotic gene structure and function. (...) Further analysis of these vectors and their properties promises to enhance their use as investigative tools. (shrink)

Baculovirus vectors have proven useful in producing high levels of biologically active eukaryotic proteins and providing cellular fractions which are enriched in the protein of interest. Expression occurs in infected insect cells which also provide a suitable environment for posttranslational modification and folding of the protein product. Stable baculovirus vectors can be constructed rapidly with a minimum of viral manipulation.

Site‐specific or target‐specific mutagenesis of viral DNA genomes, using a selectable marker system is a powerful tool for the analysis of the function of specific regions of large DNA genomes. Through these techniques the construction of vectors capable of delivering vaccines for the prevention of infectious disease in humans and animals is possible.

ABSTRACT Why did the popping of the housing bubble bring the financial system—rather than just the housing sector of the economy—to its knees? The answer lies in two methods by which banks had evaded regulatory capital requirements. First, they had temporarily placed assets—such as securitized mortgages—in off‐balance‐sheet entities, so that they did not have to hold significant capital buffers against them. Second, the capital regulations also allowed banks to reduce the amount of capital they held against assets that remained on (...) their balance sheets—if those assets took the form of AAA‐rated tranches of securitized mortgages. Thus, by repackaging mortgages into mortgage‐backed securities, whether held on or off their balance sheets, banks reduced the amount of capital required against their loans, increasing their ability to make loans many‐fold. The principal effect of this regulatory arbitrage, however, was to concentrate the risk of mortgage defaults in the banks and render them insolvent when the housing bubble popped. (shrink)

Recombinant adeno‐associated viruses (rAAVs) are promising vectors for the delivery of various genetic constructs into eukaryotic cells. rAAVs have a number of properties that make it possible to successfully use them both in vitro and in vivo. Purification and concentration of rAAV vectors are critical for achieving high viral titer, stability, efficiency, and purity. This review systematically analyses all available purification approaches. The purification methods described in this work differ substantially from each other in mechanisms, efficiency, labor time, and (...) cost. Researchers have to choose a purification algorithm depending on the purpose of their work. We strive to simplify the choice of the necessary and sufficient technique based on the experimental needs and available resources of the laboratory. (shrink)

Charles Eisenmann, dans un compte-rendu critique de la Pensée juridique, publié dans la Revue de droit public en 1961, écrivait : " On voudrait proclamer d'abord sans réserves, les rares qualités de l'ouvrage, qui en rendent la lecture très recommandable, en particulier pour ceux qui, jeunes ou juristes déjà formés, n'ont pas encore ou n'ont plus commerce très assidu avec la théorie ou la philosophie du droit. Ils prendront contact avec une pensée vivante et chaude, qui cherche avec ardeur, souplesse (...) et agilité." Les qualités qui ont conduit la Pensée juridique à être un des ouvrages de base de la formation théorique de toute une génération de juristes, celle des décennies 60-70, demeurent encore aujourd'hui intactes. C'est pourquoi il nous a paru souhaitable d'ouvrir la nouvelle collection des introuvables des éditions Panthéon- Assas par une réédition de l'ouvrage de Michel Virally. (shrink)

Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is (...) subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. (shrink)

Neuwelt et al. have proposed gene-transfer experiments utilizing an animal model that offers many important advantages for investigating the feasibility of gene therapy in the human brain. A variety of tissues concerning the viral vector and mode of delivery of the corrective genes need to be resolved, however, before such therapy is scientifically supportable.

For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the transient (...) nature of transgene expression invivomust be overcome before their use in human gene therapy becomes clinically applicable. (shrink)

Gender and public markets have long been intertwined in Peru. The vast majority of market-sellers are women, and significantly this kind of work has been intimately related to women’s empowerment and agency within a deeply patriarchal society. However, with the arrival of COVID-19 the woman-centred space of the marketplace became compromised. While once a place of female empowerment, during the pandemic the market became seen as a dangerous ‘viral vector’, with 79% of Lima market sellers testing positive for (...) Coronavirus during the first lockdown of 2020. Further still, a gender-segregated quarantine policy drove women to the markets en-masse; a policy that was withdrawn early due to its spectacular, although unsurprising, failure, causing a total inability to social distance on ‘women’s days’. As such, this paper investigates the extent to which the pandemic increased the ‘feminised burden of care’ to include deadly viral infection during the gender segregated quarantine. Applying an intersectional, post-colonial framework, the ‘feminised burden of care’ is approached as stratified along racial and class lines since markets are not spaces for all women. Furthermore, this paper will show how these intersecting structures of power that have persisted through time may become more visible and observable in times of crisis, such as through Peru’s short-lived gender segregated quarantine. With this in mind, it will be possible to suggest that the events of 2020 were more than just policymaker missteps, but a persistence and exacerbation of long-existing entangled structures of colonial and patriarchal powers. As such, it can be inferred that in an emergency, it is these power structures that were automatically adopted as the first port of call, and thereby perpetuate and strengthen them into the future. (shrink)

Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll‐like (...) receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T‐ and B‐lymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS‐CoV‐2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID‐19 vaccinations could launch a new era of personalized healthcare. (shrink)

The Sleeping Beauty transposon system is a nonviral DNA transfer tool capable of efficiently mediating transposition‐based, stable integration of DNA sequences of choice into eukaryotic genomes. Continuous refinements of the system, including the emergence of hyperactive transposase mutants and novel approaches in vectorology, greatly improve upon transposition efficiency rivaling viral‐vector‐based methods for stable gene insertion. Current developments, such as reversible transgenesis and proof‐of‐concept RNA‐guided transposition, further expand on possible applications in the future. In addition, innate advantages such as (...) lack of preferential integration into genes reduce insertional mutagenesis‐related safety concerns while comparably low manufacturing costs enable widespread implementation. Accordingly, the system is recognized as a powerful and versatile tool for genetic engineering and is playing a central role in an ever‐expanding number of gene and cell therapy clinical trials with the potential to become a key technology to meet the growing demand for advanced therapy medicinal products. (shrink)

The prelude to successful human somatic gene therapy, i.e. the efficient transfer and expression of a variety of human genes into target cells, has already been accomplished in several systems. Safe methods have been devised to do this using non‐viral and viral vectors. Potentially therapeutic genes have been transferred into many accessible cell types, including hematopoietic cells, hepatocytes and cancer cells, in several different approaches to ex vivo gene therapy. Successful in vivo gene therapy requires improvements in tissuetargeting (...) and new vector design, which are already being sought. Gene‐transfer protocols have been approved for human use in inherited diseases, cancer and acquired disorders. Althouth the results of these trials to date have been somewhat disappointing, human somatic cell gene therapy promises to be an effective addition to the arsenal of approaches to the therapy of many human diseases in the 21st century if not sooner. (shrink)

Recent results confirm that long‐term expression of therapeutic transgenes can be achieved by using a transposon‐based system in primary stem cells and in vivo. Transposable elements are natural DNA transfer vehicles that are capable of efficient genomic insertion. The latest generation, Sleeping Beauty transposon‐based hyperactive vector (SB100X), is able to address the basic problem of non‐viral approaches – that is, low efficiency of stable gene transfer. The combination of transposon‐based non‐viral gene transfer with the latest improvements of (...) non‐viral delivery techniques could provide a long‐term therapeutic effect without compromising biosafety. The new challenges of pre‐clinical research will focus on further refinement of the technology in large animal models and improving the safety profile of SB vectors by target‐selected transgene integration into genomic “safe harbors.” The first clinical application of the SB system will help to validate the safety of this approach. (shrink)

The concept of human gene therapy came on the heels of fundamental discoveries on the nature and working of the gene. However, realistic prospects to correct the underlying cause of recessive genetic disorders through the transfer of wild‐type alleles of defective genes had to wait for the arrival of recombinant DNA technology. These techniques permitted the isolation and insertion of genes into the first recombinant delivery systems. The realization that viruses are natural gene carriers provided inspiration for gene therapy and, (...) as engineered vectors, viruses became prominent gene delivery vehicles. Nonetheless, when put in the context of human and non‐human primate studies, all vectors fell short of success regardless of their viral or non‐viral origin. Recognition of issues such as inefficient gene transfer and short‐lived or scant expression in the relevant cell type(s) prompted researchers to refine and develop several gene delivery systems, in particular those based on retroviruses, adeno‐associated viruses and adenoviruses. Concomitantly, available technology was deployed to tackle disorders that require few genetically corrected cells to attain therapy. BioEssays 27: 506–517, 2005. © 2005 Wiley periodicals, Inc. (shrink)

Two groups of plant viruses have DNA in their genomes. One group, the caulimoviruses, are non‐integrating retroviruses that package dsDNA in virions. The other group, the geminiviruses, package small circular ssDNA and include the only DNA viruses known with bipartite genomes. The regulation of transcription of these viruses is not well characterized, but recent work is beginning to yield interesting results. Regulatory sequences from these viruses function in cells of species that are not hosts of the virus and are finding (...) use in constitutive expression of chimeric genes in transformed plants. Development of vectors based on plant viruses requires further characterization at the molecular level of viral life cycles. (shrink)

Doping can be both of chemical and protein nature or may involve prohibited methods, such as illegal blood transfusions. The rapidly increasing number of genetic therapies as a promising new branch of regular medicine, has raised the issue whether these techniques might be abused in the field of sports. The risks involved in gene doping are several, and are related both to the vector protein used (DNA, chemical, viral) and to the encoded transgene. A concern in the athletic (...) community is that no one knows how easily gene doping can be detected. The DNA used for gene transfer is of human origin, and not different from that of the person applying gene doping. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping. (shrink)

Complementation and correction of a genetic defect with CNS manifestations lags behind gene therapy for inherited disorders affecting other organ systems because of shortcomings in delivery vehicles and access to the CNS. The effects of improvements in viral and nonviral vectors, coupled with the development of delivery strategies designed to transfer genetic material thoughout the CNS are being investigated by a number of laboratories in efforts to overcome these problems.

New possibilities to modify function and direct repair in the central nervous system (CNS) have been established by the merger of gene transfer technology with neural transplantation. Rapid advances in viral‐mediated DNA‐delivery procedures permit the study of novel gene expression in neurons and glial cells. Foreign genes, transferred by a virus vector, can be used to generate new cell lines, identify transplanted cells, and express growth factors or enzymes for neurotransmitter synthesis. In addition to CNS cell types, non‐neural (...) cells are also being studied with transgene technology in the nervous system. Functional effects have been obtained with grafts of genetically modified cells in animal models of several nervous system disorders, and the recent results set the stage for potential application of these techniques to human CNS gene therapy. (shrink)

Although 80–90% of adults are seropositive for antibodies against the human parvovirus adeno‐associated virus (AAV), infection has not been associated with either symptoms or disease. In cell culture, AAV infection is not productive unless there is a coinfection with a helper virus, either adenovirus or any type of herpes virus; in the absence of a helper virus coinfection the viral genome is integrated into the genome, usually at a specific site on chromosome 19q13.3‐qter. The integrated genome can be activated (...) and rescued by subsequent super infection by a helper virus. The high frequency of site‐specific integration by AAV and the lack of associated disease have encouraged the use of AAV as a vector for gene therapy. This review will focus on the molecular mechanisms involved in the establishment of, and rescue from, the latent state and their relevance to use of AAV as a vector. (shrink)

Livestock are important assets in Africa, helping improve the nutritional status of their owners, and contributing to economic growth. Can these roles continue and can livestock production systems be further developed so that they will be sustainable? A key feature of livestock in Africa is that they fulfill multiple roles, ranging from draught power, to providing manure, milk, and meat. Constraints to increasing productivity include both physical and institutional. In the former category, constraints to adopting draught power include insufficient numbers (...) at the individual household level. Lack of adequate pasture is probably the most important constraint. Diseases are also notable constraints to improving productivity, particularly those categorized as Group I (highly contagious — e.g., rinderpest) or Group II (vector-borne parasitic and viral—e.g., trypanosomiasis). Institutional constraints include lack of research and market distortions. To improve productivity, at the macroeconomic level, governments must continue or start policies aimed at liberalizing markets and revaluing exchange rates. Also, research institutions need an increase in funding for periods of ten or more years. Research and other livestock institutions may be able to leverage limited resources by forming more collaborative relationships at the regional level. Research priorities include breeding on specific aspects, such as increased milk production. However, it must be realized that breeding programs have an inherent problem in disseminating improved breeds in a rapid and equitable manner. Quality of pasture may be improved by further research on more accurately calculating stocking rates and on developing mechanisms to control numbers on pastures (e.g., community controlled grazing schemes). Other research priorities include new technologies to improve animal health, funding of micro-enterprises to add value to livestock products, and market information systems for small-scale farmers. Schemes to increase livestock production in Africa will only occur if innovations closely match the local sets of circumstances. Given the multiple roles of livestock, research into innovations that local communities will readily adopt must take a systems approach. (shrink)

Viral modernity is a concept based upon the nature of viruses, the ancient and critical role they play in evolution and culture, and the basic application to understanding the role of information and forms of bioinformation in the social world. The concept draws a close association between viral biology on the one hand, and information science on the other – it is an illustration and prime example of bioinformationalism that brings together two of the most powerful forces that (...) now drive cultural evolution. The concept of viral modernity applies to viral technologies, codes and ecosystems in information, publishing, education and emerging knowledge systems. This paper traces the relationship between epidemics, quarantine, and public health management and outlines elements of viral-digital philosophy based on the fusion of living and technological systems. We discuss Covid-19 as a ‘bioinformationalist’ response that represents historically unprecedented level of sharing information from the sequencing of the genome to testing for a vaccination. Finally, we look at the US response to Covid-19 through the lens of infodemics and post-truth. The paper is followed by three open reviews, which further refine its conclusions as they relate to philosophy and the notion of the virus as Pharmakon. (shrink)

In this thought-provoking work, Tony D. Sampson presents a contagion theory fit for the age of networks. Unlike memes and microbial contagions, _Virality_ does not restrict itself to biological analogies and medical metaphors. It instead points toward a theory of contagious assemblages, events, and affects. For Sampson, contagion is not necessarily a positive or negative force of encounter; it is how society comes together and relates. Sampson argues that a biological knowledge of contagion has been universally distributed by way of (...) the rhetoric of fear used in the antivirus industry and other popular discourses surrounding network culture. This awareness is also detectable in concerns over _too much connectivity_, such as problems of global financial crisis and terrorism. Sampson’s “virality” is as established as that of the biological meme and microbe but is not understood through representational thinking expressed in metaphors and analogies. Rather, Sampson interprets contagion theory through the social relationalities first established in Gabriel Tarde’s microsociology and subsequently recognized in Gilles Deleuze’s ontological worldview. According to Sampson, the reliance on representational thinking to explain the social behavior of networking—including that engaged in by nonhumans such as computers—allows language to overcategorize and limit analysis by imposing identities, oppositions, and resemblances on contagious phenomena. It is the power of these categories that impinges on social and cultural domains. Assemblage theory, on the other hand, is all about relationality and encounter, helping us to understand the viral as a positively sociological event, building from the molecular outward, long before it becomes biological. (shrink)

In late March of 2020, a new hashtag, #FilmYourHospital, made its first appearance on social media. The hashtag encouraged people to visit local hospitals to take pictures and videos of empty hospitals to help “prove” that the COVID-19 pandemic is an elaborate hoax. Using techniques from Social Network Analysis, this case study examines how this conspiracy theory propagated on Twitter and whether the hashtag virality was aided by the use of automation or coordination among Twitter users. We found that while (...) much of the content came from users with limited reach, the oxygen that fueled this conspiracy in its early days came from a handful of prominent conservative politicians and far right political activists on Twitter. These power users used this hashtag to build awareness about the campaign and to encourage their followers to break quarantine and film what is happening at their local hospitals. After the initial boost by a few prominent accounts, the campaign was mostly sustained by pro-Trump accounts, followed by a secondary wave of propagation outside the U.S. The rise of the #FilmYourHospital conspiracy from a single tweet demonstrates the ongoing challenge of addressing false, viral information during the COVID-19 pandemic. While the spread of misinformation can be potentially mitigated by fact-checking and directing people to credible sources of information from public health agencies, false and misleading claims that are driven by politics and supported by strong convictions and not science are much harder to root out. (shrink)

This paper addresses global bioethical challenges entailed in emerging viral diseases, focussing on their socio-cultural dimension and seeing them as symptomatic of the current era of globalisation. Emerging viral threats exemplify the extent to which humans evolved into a global species, with a pervasive and irreversible impact on the planetary ecosystem. To effectively address these disruptive threats, an attitude of preparedness seems called for, not only on the viroscientific, but also on bioethical, regulatory and governance levels. This paper (...) analyses the global bioethical challenges of emerging viral threats from a dialectical materialist (Marxist) perspective, focussing on three collisions: (1) the collision of expanding networks of globalisation with local husbandry practices; (2) the collision of global networks of mobility with disrupted ecosystems; and (3) the collision of viroscience as a globalised research field with existing regulatory frameworks. These collisions emerge in a force field defined by the simultaneity of the non-simultaneous. Evidence-based health policies invoke discontent as they reflect the normative logic of a globalised knowledge regime. The development of a global bioethics or macro-ethics requires us to envision these collisions not primarily as issues of benefits and risks, but first and foremost as normative tensions closely entangled with broader socio-economic and socio-cultural developments. (shrink)

Critics of reliability theories of epistemic justificationoften claim that the `generality problem' is an insurmountabledifficulty for such theories. The generality problem is theproblem of specifying the level of generality at which abelief-forming process is to be described for the purposeof assessing its reliability. This problem is not asintractable as it seems. There are illuminating solutionsto analogous problems in the ethics literature. Reliabilistsought to attend to utilitarian approaches to choices betweeninfinite utility streams; they also ought to attend towelfarist approaches to social (...) choice situations that donot demand full aggregation of individual welfares.These analogies suggest that the traditional `single number'approach to reliability is misguided. I argue that a newapproach – the `vector reliability' approach – is preferable.Vector reliability theories associate target beliefs withreliability vectors – that is, structured collections ofreliability numbers – and construct criteria of epistemicjustification that appeal to these vectors. The bulk of thetheoretical labor involved in a reliability account of epistemicjustification is thus transferred from picking a uniquereliability number to constructing a plausible criterionof epistemic justification. (shrink)

We are experiencing a historical moment characterized by unprecedented conditions of virality: a viral pandemic, the viral diffusion of misinformation and conspiracy theories, the viral momentum of ongoing Hong Kong protests, and the viral spread of #BlackLivesMatter demonstrations and related efforts to defund policing. These co-articulations of crises, traumas, and virality both implicate and are implicated by big data practices occurring in a present that is pervasively mediated by data materialities, deeply rooted dataist ideologies that entrench (...) processes of datafication as granting objective access to truth and attendant practices of tracking, data analytics, algorithmic prediction, and data-driven targeting of individuals and communities. This collection of papers explores how data is figuring in the making of the discourses, lived realities, and systemic inequalities of the uneven impacts of the coronavirus pandemic. (shrink)

Viruses are major drivers of global biogeochemistry and the etiological agents of many diseases. They are also the winners in the game of life: there are more viruses on the planet than cellular organisms and they encode most of the genetic diversity on the planet. In fact, it is reasonable to view life as a viral incubator. Nevertheless, most ecological and evolutionary theories were developed, and continue to be developed, without considering the virosphere. This means these theories need to (...) be to reinterpreted in light of viral knowledge or we need to develop new theory from the viral point-of-view. Here we briefly introduce our viral planet and then address a major outstanding question in biology: why is most of life viral? A key insight is that during an infection cycle the original virus is completely broken down and only the associated information is passed on to the next generation. This is different for cellular organisms, which must pass on some physical part of themselves from generation to generation. Based on this premise, it is proposed that the thermodynamic consequences of physical information (e.g., Landauer’s principle) are observed in natural viral populations. This link between physical and genetic information is then used to develop the Viral Information Hypothesis, which states that genetic information replicates itself to the detriment of system energy efficiency (i.e., is viral in nature). Finally, we show how viral information can be tested, and illustrate how this novel view can explain existing ecological and evolutionary theories from more fundamental principles. (shrink)

Controversial taboo appeals as an executional cue in viral advertising have commonly been used by advertisers. In this context, the study investigates the role of medium context on the effectiveness of controversial taboo ads. By implementing a tightly controlled experiment which deals with controversial taboo ads embedded in a press article and in a viral context, the study finds that the viral medium context does not lead to a more positive attitude toward the embedded brand or to (...) more positive purchase intentions. In addition, a viral medium context triggers ‘unintended consequences’ that lead consumers to undermine the level of tabooness of the viral advertising and subjective norms. To increase the external validity of the research, the results were replicated for two kinds of controversial taboo appeals; one related to sexuality, and the other to death. The results provide useful implications for theory and practice. Extending viral advertising research, a different angle on controversial viral advertising has been taken, shifting from an advertiser and brand focus, to a societal and social one. The work leads to a better understanding of the ethics of controversial viral advertising, and demonstrates its role in the trivialization of taboo behaviors and imagery. The results confirm the need for more regulation of online buzz communication and encourage regulatory bodies to extend policies of viral advertising regulation. (shrink)

This chapter argues that the human, all too human vulnerability to mimesis (imitation) is a central and so far underdiagnosed element internal to the Covid-19 pandemic crisis. Supplementing medical accounts of viral contagion, the chapter develops a genealogy of the concept of mimesis – from antiquity to modernity to the present – that is attentive to both its pathological and therapeutic properties. If an awareness of the pathological side of mimetic contagion is constitutive of the origins of philosophy, in (...) Plato’s Republic, and crowd psychology called attention to the mirroring dynamic of affective contagion among crowds and publics in the modern period, the Covid-19 pandemic crisis highlights the pathological implications of hypermimetic conspiracies reloaded by new media, while also revealing the human ability to develop therapeutic patho-logies – that is, critical discourses (or logoi), on the contagious dynamic of mimetic pathos. Like a Janus-faced mirror, then, this genealogy of homo mimeticus calls attention to both the contemporary dangers of affective contagion and to the urgency of transformations or metamorphosis to counter future pandemic and environmental threats that loom large in the Anthropocene. (shrink)

There is an ecology of bad ideas, just as there is an ecology of weeds, and it is characteristic of the system that basic error propagates itself.–Gregory Bateson, Steps Towards an Ecology of Mind...

The global response to managing the spread of HIV has recently undergone a significant shift with the advent of ‘treatment as prevention’, a strategy which presumes that scaling-up testing and treatment for people living with HIV will produce a broader preventative benefit. Treatment as prevention includes an array of diagnostic, technological and policy developments that are creating new understandings of how HIV circulates in bodies and spaces. Drawing on the work of Michel Foucault, we contextualize these developments by linking them (...) to systems of governance and discursive subjectivation. The goal of this article is to problematize the growing importance of viral suppression in the management of HIV and the use of related surveillance technologies. For people living with HIV, we demonstrate how treatment-as-prevention’s emphasis on individual and collective viral load is transforming the performative dimensions of embodied risk, affect, subjectivity and sex. (shrink)

As companies increasingly communicate CSR initiatives through social media, viral message propagation has become a crucial prerequisite for CSR success. Evidence from two experimental studies, one based on a national representative online sample, shows that social media peers’ endorsement of a CSR message in terms of number of shares, likes and positive replies contributes to an individual’s intention to share it on the social network and thereby participate in message propagation, and that this process can be explained by normative (...) influences exerted by the social media community through the activation of injunctive and descriptive norms, as well as social identity motives. Findings further confirmed that the norm-activating effects of social media endorsement are moderated by the empowering qualities of the CSR message, the sharing source of the message by affecting CSR credibility, and the recipient’s interdependent self-construal. Corporate communication managers are advised to achieve a high degree of initial social media endorsement of their CSR message, for recipients of the message to perceive social pressure motivating message sharing with their social media peers. (shrink)

Excerpt from Vector Analysis and the Theory of Relativity One of the most striking effects of the publication of Einstein's papers on generalized relativity and of the discussions which arose in connection with the subsequent astronomical observations was to make students of physics renew their study of mathematics. At first they attempted to learn simply the technique, but soon there was a demand to understand more; real mathematical insight was sought. Unfortunately there were no books available, not even papers. (...) Dr. Murnaghan's little book is a most successful attempt to supply what is a definite need. Every physicist can read it with profit. He will learn the meaning of a vector for the first time. He will learn methods which are available for every field of mathematical physics. He will see which of the processes used by Einstein and others are strictly mathematical and which are physical. Every chapter is illuminating, and the treatment of the subject is that of a student of mathematics and is not developed ad hoc. The extension of surface and line integrals is most interesting for physicists and the discussion of the space relations in a four-dimensional geometry is one most needed. This is specially true concerning the case of point-symmetry which forms the basis of Einstein's formulae for gravitation as applied to the solar system. I feel personally that I owe to this book a great debt. I have read it with care and shall read it again. It has given me a definiteness of understanding which I never had before, and a vision of a field of knowledge which before was remote. About the Publisher Forgotten Books publishes hundreds of thousands of rare and classic books. Find more at www.forgottenbooks.com This book is a reproduction of an important historical work. Forgotten Books uses state-of-the-art technology to digitally reconstruct the work, preserving the original format whilst repairing imperfections present in the aged copy. In rare cases, an imperfection in the original, such as a blemish or missing page, may be replicated in our edition. We do, however, repair the vast majority of imperfections successfully; any imperfections that remain are intentionally left to preserve the state of such historical works. (shrink)

Stereotypes about exotic peoples and animals of the Orient shaped popular origin stories about COVID-19 in media reports. Outbreak narratives centred on the seafood market in Wuhan began to fall apart as new evidence was published by medical doctors, virologists, and epidemiologists. No viruses in bats or pangolins have been found that are direct ancestors of SARS-CoV2, the virus responsible for COVID-19 symptoms. Viruses are also being transformed as they interact with the human institutions, infrastructures and behaviours that facilitate their (...) spread. Epidemiological growth curves are shaped by national and foreign capital, cosmopolitanism, aspirations for independence and ongoing interdependence, the discourse of power and the discourse of resistance, as well as coexistence and violence. In reckoning with SARS-CoV2, we need to anticipate disruptive surprise of viral emergence rather recursively search for origins. Departing from Foucault’s foundational insights, this article gestures towards genealogies of possible viral futures. (shrink)

Retroviral vectors utilize the biochemical processes unique to retroviruses, to transfer genes with high efficiency into a wide variety of cell types in tissue culture and in living animals. With such vectors, the effect of newly introduced genes and the mechanism of gene expression can be studied in cell types so far refractory to other methods of transfer.

Whereas telomeres protect terminal ends of linear chromosomes, telomerases identify natural chromosome ends, which differ from broken DNA and replicate telomeres. Although telomeres play a crucial role in the linear chromosome organization of eukaryotic cells, their molecular syntax most probably descended from an ancient retroviral competence. This indicates an early retroviral colonization of large double-stranded DNA viruses, which are putative ancestors of the eukaryotic nucleus. This contribution demonstrates an advantage of the biosemiotic approach towards our evolutionary understanding of telomeres, telomerases, (...) other reverse transcriptases and mobile elements. Their role in genetic/genomic content organization and maintenance is no longer viewed as an object of randomly derived alterations (mutations) but as a highly sophisticated hierarchy of regulatory networks organized and coordinated by natural genome-editing competences of viruses. (shrink)

In this paper I provide an ontology for the co‐variant vectors, contra‐variant vectors and tensors that are familiar from General Relativity. This ontology is developed in response to a problem that Timothy Maudlin uses to argue against universals in the interpretation of physics. The problem is that if vector quantities are universals then there should be a way of identifying the same vector quantity at two different places, but there is no absolute identification of vector quantities, merely (...) a path‐relative one.My solution to the problem is to use the mathematical characterization of vectors as differential operators on scalar fields. On the proposed hypothesis a scalar field is a conjunctive state of affairs, and vector and tensor fields are relations instantiated by scalar fields. (shrink)

From Editors' Introduction: "With our invitation to turn over (re-turn) hospitality in these times Marietta Radomska’s response combines her own research within the emerging field of Queer Death Studies6 with a detailed reading of the coronavirus disease pandemic. In her essay, “Viral queerings, amplified vulnerabilities”, Marietta seeks to subvert normative and simplified understandings of our present. Following the thread that the pandemic affects some bodies more than others, Marietta highlights how “the exploitation and degradation of nature mixed with intensifying (...) socio-economic inequalities directly contribute to the emergence of zoonoses”. Untangling the myth of the containable body and human-exceptionalism, Marietta challenges which lives are considered grievable drawing our attention to “more-than-human necropolitics”. In queering the pandemic she asks us to “reimagine the ways we relate to human and nonhuman others, perhaps in a more hospitable register”." Edited by Yvonne Billimore and Jussi Koitela. (shrink)

Throughout the COVID-19 pandemic the use of the term “hero” has been widespread. This is especially common in the context of healthcare workers and it is now unremarkable to see large banners on hospital exteriors that say “heroes work here”. There is more to be gleaned from the rhetoric of heroism than just awareness of public appreciation, however. Calling physicians and nurses heroes for treating sick people indicates something about the concept of medicine and medical professionals. In this essay, I (...) will examine three aspects of the social role of medicine exposed by the language of heroism. One, if a hero is someone who goes above and the call of duty, then does that mean exposing oneself to risk of infection is no longer a duty of physicians? If so, does that mean the “profession” of medicine is much like any other business? Two, physicians and nurses are not the only “heroes” this go-around. Anyone deemed essential to the US “infrastructure” is designated by the US government as having “special responsibilities” to remain at their posts for the public good, which explicitly puts physicians in the same category as sewage workers and grocery store cashiers. Three, what does it mean to belong to a profession that does have self-sacrifice and risk-taking as part of its mission—especially a profession that rarely gets called upon to practice these obligations? (shrink)

Polioviruses of reduced neurovirulence contain point mutations in the viral RNA that are responsible for the attenuated phenotype. Two such point mutations have been identified in the genomes of the Sabin live oral vaccine strains, one in the 5′‐noncoding region of the viral RNA, and one in capsid polypeptide VP3.

In plants, virus‐derived double‐stranded RNA is processed into small interfering (si)RNAs by RNAse III‐type enzymes. siRNAs are believed to guide an RNA‐induced silencing complex (RISC) to promote sequence‐specific degradation (or ‘slicing’) of homologous viral transcripts. This process, called RNA silencing, likely involves Argonaute (AGO) proteins that are known components of plant and animal RISCs. Plant viruses commonly counteract the silencing immune response by producing suppressor proteins, but the molecular basis of their action has remained largely unclear. A recent study (...) by Zhang and colleagues1 now shows that the 2b suppressor of Cucumber mosaic virus directly interacts with Arabidopsis AGO1 and inhibits its slicing activity, suggesting that AGO1 might be a component of the elusive plant antiviral RISC. BioEssays 29:319–323, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

We show that vector space semantics and functional semantics in two-sorted first order logic are equivalent for pregroup grammars. We present an algorithm that translates functional expressions to vector expressions and vice-versa. The semantics is compositional, variable free and invariant under change of order or multiplicity. It includes the semantic vector models of Information Retrieval Systems and has an interior logic admitting a comprehension schema. A sentence is true in the interior logic if and only if the (...) ‘usual’ first order formula translating the sentence holds. The examples include negation, universal quantifiers and relative pronouns. (shrink)