719 research outputs found
Furious Angels
No full textReunited by tragedy, Andrew and Will are unlikely pawns in a high-stakes game of A.I. and religious fanaticism. Answering a call from beyond the grave they are unwittingly thrown into a vast technological world both deadly and fascinating. This is the breathtaking first book in the series by Irish author Dr Damien Mac Namara
How Is Damien Hirst a Cultural Entrepreneur?
No full textabstract: An on-going academic debate occupying Entrepreneurship researchers for the past several decades is concerned with defining what an entrepreneur is and what an entrepreneur does. The debate also extends to exploring the influence different types of entrepreneurs have on their environment. In the new creative economy, entrepreneurship has become a central issue for the regeneration of urban space. This essay first differentiates between economic and cultural entrepreneurs and second explores what influence cultural entrepreneurs, especially, have on urban developments. By using Damien Hirst as exemplar for the discussion of the entrepreneurial character and spheres of action, the analysis of his career demonstrates how difficult it is in practice to draw a line between artistic, cultural and commercial activities in the creative economy. Hirst’s approach to contemporary conceptual art and his factory-like art production are both controversial and successful as defined by the author. Nevertheless, there seems to be agreement that his entrepreneurial artistic work has had a profound impact on the revitalization of East London and thus can be used as model for urban planners. The author posits that Hirst is a cultural entrepreneur based on this model for creating/regenerating viable economic urban spaces who embraces the blending of the artistic and market spheres
Dissecting patient macrophage responses to Mycobacterium tuberculosis Complex strains from Tanzania and assessing T cell biomarkers for TB diagnosis and treatment monitoring
No full textTuberculosis (TB) has existed throughout human history, traced back to 9000 years ago to date. TB is transmitted through inhalation of infective air droplets from an infected person to the next susceptible host. This devastating disease has been a major cause of death from a single infectious agent more than HIV/AIDS and malaria combined before the COVID-19 pandemic. Caused by several genetically distinct Mycobacterium tuberculosis complex (MTBC) species, TB causes the death of a person every 22 seconds making MTBC one of the most successful human pathogen. TB is mostly curable with a specific combination of anti-TB drugs. Yet the increase of strains carrying drug-resistance mutations and the gap between people who are not diagnosed contributes to the reported TB related deaths. Ending this ongoing epidemic will require investment in biomedical, public health and socioeconomic interventions to sustain the necessary research and development of the necessary tools. Improvement of current diagnostic tests and development of new diagnostic approaches is necessary to increase case detection rates and close in the 4.2 million gap of people who are currently missed every year. In addition, genetically distinct MTBC lineages are differentially distributed globally; further understanding of the link between this diversity and MTBC pathogenesis is likely to improve management of TB patients in different epidemiological settings.
In the first part of this thesis, we hypothesized that TB disease epidemiology in Tanzania is driven by the human-MTBC genetic interactions resulting in an increased susceptibility of specific hosts to a specific circulating MTBC strain. This hypothesis was investigated in Chapter 3, where I will first give detailed introduction of the human adapted MTBC lineages, their distribution and factors contributing to their global distribution. I will then introduce current concepts of strain adaptation to local host populations driven by genetic interaction between human hosts and the circulating strains in various epidemiological settings. To test our hypothesis, we selected representative MTBC strain endemic to the Temeke District of Dar es Salaam where patients were recruited, and peripheral blood mononuclear cells cryopreserved. Patient-derived macrophages from monocytes isolated from their collected blood were infected either with a genetically related strain that had originally infected the patient (“matched infection”) or with other endemic lineages (“mismatched infection”). MTBC replication within patients’ macrophages as well as cytokine and chemokine production in response to infection were assessed. We observed that lineage-matched ex-vivo infection of macrophages derived from TB patients could not deliver sympatric associations signals. In turn, our results suggest that TB epidemiology in Tanzania is mainly driven by different MTBC strain-specific pathogenesis strategies rather than host-specific genetic traits.
In the second part of this thesis, we explored the hypothesis that bacterial load perception by the host adaptive immune system results in a measurable activation status that can be used to: i) diagnose TB infection and; ii) monitor disease resolution. This work is presented in Chapter 4 in which we investigated the diagnostic potential of two T-cell activation markers (TAM) for TB diagnosis (TAM-TB assay). The TAM-TB assay was assessed using a simplified protocol starting from 1ml of blood to comply with childhood TB diagnosis. In this chapter, I will introduce the current TB diagnostic tools, their limitations and provide reasons supporting the implementation of the TAM-TB assay in the field. I will then detail how we assessed the diagnostic performance of the TAM-TB assay for TB diagnosis starting from 1ml of blood from 479 active TB patients and 108 symptomatic controls. I will present how sample processing was done to measure expression of CD38 or CD27 by CD4 T cells producing IFN-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences MTBC ESAT-6, CFP-10 and TB10.4 antigens using a 4-color FACSCalibur apparatus. The CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). I will demonstrate how TAM-TB routine testing with a 24h turnaround time at district level in a resource-limited setting was successfully implemented. Starting from 1ml of blood and being not affected by HIV status, I will conclude that CD38-based TAM-TB assay performance appears closely compatible with the optimal target product profile accuracy criteria defined by WHO for a non-sputum confirmatory TB test.
In Chapter 5, we explored the use of the TAM-TB assay as proxy of host bacterial load and consequently, a treatment-monitoring tool. In this chapter, I will introduce why treatment monitoring is important not only for patient management but also for clinical trials evaluating new treatment regimens. I will also develop the shortcomings of current tools used to measure bacterial load and disease resolution and the need for alternative measures. In this work, we hypothesized that the phenotype of MTBC-specific T cells may be quantitatively impacted by the load of bacteria present in a given patient. To test this hypothesis, we obtained 1 ml blood from 105 active TB patients, before and after 5 months of antibiotic treatment. We evaluated the relationships between patients’ clinical characteristics of disease severity and microbiological as well as molecular proxies of bacterial load in sputum at the time of diagnosis. Reflecting the difficulty to extrapolate bacterial burden from a single end-point read-out, we observed statistically significant but weak correlations between Xpert MTB/RIF, MBLA and time to culture positivity. We demonstrated that resolution of CD38 expression by antigen-specific T cells was observed readily following 5 months of antibiotic therapy. However, the intensity of CD38-TAM signals measured at diagnosis did not significantly correlate with MTBC 16S rRNA or rpoB DNA detected in patients’ sputa. Altogether, our data support CD38-TAM as an accurate marker of infection resolution independently of sputum bacterial load. The CD38-based TAM-TB assay constitutes a promising assay to monitor treatment response.
In summary, in this thesis I dissected the influence of both human and MTBC genetic variability in the epidemiology of TB in Tanzania to an unprecedented extent matching endemic strains to infect patient’s host cells. Secondly, we addressed key aspects in the END-TB strategy to circumvent the limitations of current TB diagnostic tools showing the potential of CD38-based TAM-TB assay as a promising non-sputum diagnostic test that can be implemented in the field and routinely deliver accurate results with a 24h turnaround time
Transforming the Reading Experience of Scientific Documents with Polymorphism
No full textDespite the opportunities created by digital reading, documents remain mostly static and mimic paper. Any improvement in the shape or form of documents has to come from authors who contend with current digital formats, workflows, and software and who impose a presentation to readers. Instead, I propose the concept of polymorphic documents which are documents that can change in form to offer better representations of the information they contain. I believe that multiple representations of the same information can help readers, and that any document can be made polymorphic, with no intervention from the original author. This thesis presents four projects investigating what information can be obtained from existing documents, how this information can be better represented, and how these representations can be generated using only the source document. To do so, I draw upon theories showing the benefit of presenting information using multiple representations; the design of interactive systems to support morphing representations; and user studies to evaluate system usability and the benefits of the new representations on reader comprehension
Etude du rôle des polykétides mycobactériens dans la biogénèse de l'enveloppe et la virulence des mycobactéries : caractérisation de l'étape de condensation des acides mycoliques
No full textCertaines mycobactéries sont responsables à l'heure actuelle et depuis l'antiquité de pathologies infectieuses graves comme la tuberculose, résultante d'une infection par Mycobacterium tuberculosis. En dépit d'une médecine efficace liée à l'avènement des antibiotiques, cette infection bactérienne est à l'échelle mondiale, la première cause de mortalité due à un agent infectieux. Deux millions de décès seraient annuellement liés à cette pathologie selon les données de l'organisation mondiale de la santé (OMS, 2002). La tuberculose est un véritable fléau dans la majorité des pays en voie de développement où son endémie corrèle celle liée à l'épidémie du VIH, et le nombre de tuberculeux recensé en Europe comme dans d'autres pays développés reste non négligeable. La pathogénie du bacille tuberculeux laisse apparaître un équilibre quasi-parasitique avec un tiers de la population mondiale infectée. L'apparition de souches multi-résistantes aux chimiothérapies actuelles inquiète le milieu médical en réduisant le nombre de médicaments disponibles. Une stratégie de prise en charge mondiale par l'OMS a récemment été adoptée pour tenter d'endiguer l'épidémie de tuberculose. En parallèle, des efforts en recherche fondamentale et clinique sont entrepris afin de décortiquer la pathogénie du bacille tuberculeux pour mieux le combattre. Dans cet objectif, le séquençage récent de son génome a représenté une avancée majeure. Il dévoile notamment 250 gènes relatifs à la biosynthèse lipidique, soit cinq fois plus que chez E.coli, dont 24 coderaient des polykétides synthases (Pks). Ces enzymes sont sources de molécules complexes souvent biologiquement actives, dont la toxine de Mycobacterium ulcerans, la mycolactone, est particulièrement représentative chez les mycobactéries. Récemment, nombre de produits de polykétides synthases se sont révélés être des composantes de l'enveloppe de Mycobacterium tuberculosis. Cette enveloppe représente une arme remarquable pour le bacille tuberculeux tant par la barrière d'imperméabilité qu'elle constitue que par ses propriétés immunologiques vraisemblablement impliquées dans sa résistance à l'immunité de l'hôte. L'approche génétique abordée dans ce travail a permis d'évaluer la contribution des différents polykétides mycobactériens dans la virulence de M.bovis BCG et M.tuberculosis en modèle murin. De plus, nous avons pu caractériser la fonction d'un locus comprenant la polykétide synthase 13 ainsi qu'une acyl-AMP synthase et une acyl-coA carboxylase dans la dernière étape de la biosynthèse des acides mycoliques, lipides majeurs de l'enveloppe mycobactérienne et essentiels pour la survie des mycobactéries. Ainsi, les enzymes caractérisées dans ce travail constituent des cibles de choix pour le développement de nouveaux antituberculeux.Since the antiquity, mycobacteria have been involved in lethal pathology such as leprosy or tuberculosis, the latter caused by Mycobacterium tuberculosis and the former by Mycobacterium leprae. Despite modern medicine including antibiotics, tuberculosis keep on being the first cause of mortality due to a single infectious agent with an average of two millions deaths per year, according to the world health organisation (WHO, 2002). Tuberculosis is a real plague in the majority of developping countries where its endemy correlates those of the HIV epidemy. Furthermore the number of tuberculosis patient number in Europe as well as in other developping countries is still not negligible. Moreover, the emergence of strains resistant to the currently used antibiotics is worrying the medical profession by reducing avalaible active molecules. Without the huge mortality associated with tuberculosis, this disease would be considered as a parasitic infection regarding the estimated number of infected but asymptomatic people (around 33% of the world population). Recently, the WHO has initiated a global approach to control the epidemy. In parallel, efforts in fondamental and clinical investigation are ongoing to understand tuberculosis pathogeny and to developp new clinical tools. Recently, the entire genome of M.tuberculosis was sequenced. It revealed 250 genes related to lipid biosynthesis, which represents a considerable involvment regarding the approximativly 50 genes found in E.coli genome. Remarkably 24 of this 250 genes encode polyketide synthase (Pks). In other bacteria, these enzymes are known to produce complex molecules with pharmaceutical interest. In mycobacteria, the mycolactone, is a potent toxin produced by Mycobacterium ulcerans. Recently, numerous polyketides has been shown to be components of the M.tuberculosis envelop. This envelop represents a powerfull weapon for the tuberculous bacillus constituting a permeability barrier and delivering immunological advantages. The genetic approach used in this work allowed us to evaluate the contribution of the various polyketides in the virulence of M.bovis BCG and M.tuberculosis in a mouse model. Furthermore, we caracterised the fonction of the locus including the polyketide synthase 13, an acyl-AMP synthase and an acyl-coA carboxylase in the last step of mycolic acid biosynthesis. Mycolic acids are major constituent of the mycobacterial cell envelop and are essential for mycobacterial viability, therefore the enzymes caracterised in the second part of this work constitutes promising targets for developping new antituberculous drugs
L’« Incroyable » trésor de Damien Hirst présenté à Venise en 2017
No full textCet article se propose de revenir sur l’exposition Treasures from the Wreck of the Unbelievable de l’artiste britannique Damien Hirst. Présentée à Venise en 2017, elle mettait en lumière le prétendu trésor de l’épave « l’Incroyable », découvert au large des côtes d’Afrique en 2008. Il s’agit d’une lecture personnelle de l’auteur à la suite de sa visite en septembre 2017.This paper aims to analyse the exhibition “Treasures from the Wreck of the Unbelievable” by the British artist Damien Hirst. Presented at Venice in 2017, the exhibition showed the treasure of the so-called “Unbelievable”, discovered off the African West coast in 2008. This paper is a personal analyze of the author after her visit in September 2017
The 'auto cannibal'
No full textThe relentless triumph of technology is increasingly dismissive of the human desire for interaction; we are deprived of experiences with the ordinary and become less aware of the potential such objects contain. The author primarily considers art as a means of understanding the world and his practice is based on personal observations and autonomous processes. This can often lead to an over-analysis of the mundane, which is directly confronted in each of my projects through an enthusiasm for the objects we not only take for granted, but do so to the extent that we barely notice their existence. Drawing inspiration from literature, philosophy and ideas which surround permanence in a society which is frequently considered throwaway, the author is influenced by personal insecurities and have developed a creative style that not only explores construction - in the obsessive means by which a work is made; but also one that celebrates the process of destruction - in that the materials the author uses have the potential to instigate their own demise in a process I generally refer to as autocannibalism
Dress, law and naked truth : a cultural study of fashion and form
No full textWhy are civil authorities in so-called liberal democracies affronted by public nudity and the Islamic full-face 'veil'? Why is law and civil order so closely associated with robes, gowns, suits, wigs and uniforms? Why is law so concerned with the 'evident' and the need for justice to be 'seen' to be done? Why do we dress and obey dress codes at all? In this, the first ever study devoted to the many deep cultural connections between dress and law, the author addresses these questions and more. His responses flow from the radical thesis that 'law is dress and dress is law'. Engaging with sources from The Epic of Gilgamesh to Shakespeare, Carlyle, Dickens and Damien Hirst, Professor Watt draws a revealing history of dress and civil order and offers challenging conclusions about the nature of truth and the potential for individuals to fit within the forms of civil life
Natural killer cell cytokine response to M. bovis BCG is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+)CD56(bright) cells
No full textMycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK) cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright) NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright) population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright) NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright) cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent
Law, Politics and the Limits of Prosecuting Mass Atrocity
No full textDamien Rogers is Senior Lecturer at the Centre for Defence and Security Studies at Massey University, New Zealand. This book offers a unique and powerful critique of the quest for international criminal justice. It explores the efforts of three successive generations of international prosecutors, recognising the vital roles they play in the enforcement of international criminal law. By critically examining prosecutorial performance during the pre-trial and trial phases, the volume argues that these prosecutors are simultaneously political actors serving in the interests of economic liberalisation. It also posits that international prosecutors help wage a mostly silent and largely unacknowledged politico-cultural war fought for control over the institutions governing modernist international affairs. As the author contends, international prosecutors are thus best understood as agents not only of the law and politics, but also of a war fought by proponents of various utopian projects
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