In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni

The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154(-/-) mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154(-/-) mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154(-/-) mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154(-/-) mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154(-/-) mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c(+) cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154(-/-) mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs

Sit Up and Take Notice

Discusses, with reference to UKI (Kingsway) Ltd v Westminster City Council (SC), the issues which notice provisions in a lease should include. Examines the importance of specifying that the notice be in writing, the address for service, the permitted methods of giving notices, such as via post, email or fax, and the role of deeming provisions. Includes an example form of notice clause

NON-MALIGNANT OESOPHAGO-BRONCHIAL FISTULA IN THE ADULT

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The Violent Art: Caricatures of Conflict in Germany

War furnishes a – perhaps the – classic case of ‘black humour’, which is understood here in the broad sense, not merely as the humour of the gallows or the cheating of death, but humour deriving from a confrontation with suffering or death, either as a victim or a perpetrator. War cartoons relied on the manipulation of images for comic effect, which – at least until the absurdist experiments of the Dada and Surrealist movements during and after the First World War – appeared impossible in photography, painting and cinematography. Caricature permitted artists simultaneously to conjure up, simplify and undermine reality. The selection and exaggeration of character traits and circumstantial detail, which was fundamental to caricature, revealed graphically how cartoonists perceived the social and political world in which they lived. This chapter examines how such selection and exaggeration worked in extreme conditions during wartime

GEO600: building a gravitational wave observatory

An international network of laser-interferometric gravitational wave detectors is nearing the end of the main commissioning phase and will soon enter into an extended observational period, collecting data for a duration of order one year. This article outlines the construction, design and commissioning of the GEO 600 gravitational wave observatory. GEO 600 is a laser-interferometric gravitational wave detector which has 600 m long arms and uses advanced optical and suspension techniques to achieve a sensitivity comparable to the longer base-line detectors currently operating in the U.S.A and Europe

Introduction: Visualizing Violence

The Introduction explores the relationship between visual and literary representations of modern warfare. What impact have paintings, cartoons, films and television had on the reporting of conflicts? How has the visual imagery of military violence – as the most extensive and damaging form of violence – changed? Here, Susan Sontag's 2003 essay Regarding the Pain of Others is used as a starting point for a wider discussion of what it means to portray, and to witness portrayals of, wartime violence. Few events have been represented with such frequency, exhaustiveness, unevenness and distortion as have wars. In the modern and contemporary eras, which are the focus of this volume, such representation has become largely mediatic and increasingly visual, with the images of photographic journalism, newsreels and television supplementing and contradicting the longer-established genres of military art, monuments, cartoons, treatises, war poems, plays and novels. ‘Being a spectator of calamities taking place in another country is a quintessential modern experience’, the cumulative offering ‘by more than a century and a half's worth of those professional, specialized tourists known as journalists,’ writes Susan Sontag in Regarding the Pain of Others (2003): Wars are now also living room sights and sounds. Information about what is happening elsewhere, called ‘news’, features conflict and violence – ‘If it bleeds, it leads’ runs the venerable guideline of tabloids and twenty-four-hour headline news shows – to which the response is compassion, or indignation, or titillation, or approval, as each misery heaves into view.1 This impression of knowing ‘what happens every day throughout the whole world’, with the reports of journalists placing, ‘as it were, those in agony on fields of battle under the eyes of readers’ and allowing the cries of the wounded to ‘resonate in their ears’, as the first president of the Red Cross, Gustav Moynier, expressed it in 1899, has been juxtaposed with and opposed to other means of remembering, commemorating and glorifying military conflict, which usually demand separate spaces of reflection, away from the bustle and fragmentation of everyday life.2 Here, we ask how wars were visualized in different media, as artists, photographers, film directors and TV producers sought to evoke military conflicts which many had experienced and virtually everyone had ‘seen’ and ‘heard of’. The relationship between soldiers' and civilians' experiences of warfare and their conceptions of it has been complicated by the clashing imperatives and changing conditions of military conflict. On the one hand, the mediatization of war – with the rise of war correspondents and the use of war photography from the Crimean War onwards, for example – combined with mass participation in politics to make governments highly sensitive to press revelations and sensationalism, which they sought to censor, and receptive to the use and abuse of propaganda, which they attempted to instigate and foster. The idea that propaganda was the preserve of the state and involved the presentation and misrepresentation of information in ways favourable to one's own country and damaging to enemies owed most to the newly formed agencies of the First World War, such as the British Department (and later Ministry) of Information, before it was taken up by the post-war dictatorships of the 1920s and 1930s and condemned by critics of the Great War like Arthur Ponsonby, whose Falsehood in War-Time: Propaganda Lies of the First World War was published in 1928.3 On the other hand, citizens' direct exposure to warfare had increased as a consequence of conscription and mass mobilization, which had resulted in the military service of more than 80 per cent of men between the ages of twenty and forty-five in Germany and France between 1914 and 1918, and as a result of a widening theatre of operations, with motorized armies and aerial bombardment ensuring that about two-thirds of the casualties in the Second World War were civilians, compared to less than a third of the deaths caused by the First World War.4 Given the stakes, the conflicting claims of different kinds of combatants, victims, journalists, artists, propagandists and officials were bound to create confusion and controversy about the nature of wars, both as they were being waged and as they were later recollected, studied and memorialized.5 The proximity and disjunction of individuals' experiences, the re-presentation of events, private and public memories, and historical investigation make the interpretation of visual and literary portrayals of wartime violence difficult, but essential, to interpret and explain

Data Analysis Methods for Testing Alternative Theories of Gravity with LISA Pathfinder

In this paper we present a data analysis approach applicable to the potential saddle-point fly-by mission extension of LISA Pathfinder (LPF). At the peak of its sensitivity, LPF will sample the gravitational field in our Solar System with a precision of several $\text{fm/s}^2/\sqrt{\text{Hz}}$ at frequencies around $1\,\text{mHz}$. Such an accurate accelerometer will allow us to test alternative theories of gravity that predict deviations from Newtonian dynamics in the non-relativistic limit. As an example, we consider the case of the Tensor-Vector-Scalar theory of gravity and calculate, within the non-relativistic limit of this theory, the signals that anomalous tidal stresses generate in LPF. We study the parameter space of these signals and divide it into two subgroups, one related to the mission parameters and the other to the theory parameters that are determined by the gravity model. We investigate how the mission parameters affect the signal detectability concluding that these parameters can be determined with the sufficient precision from the navigation of the spacecraft and fixed during our analysis. Further, we apply Bayesian parameter estimation and determine the accuracy to which the gravity theory parameters may be inferred. We evaluate the portion of parameter space that may be eliminated in case of no signal detection and estimate the detectability of signals as a function of parameter space location. We also perform a first investigation of non-Gaussian "noise-glitches" that may occur in the data. The analysis we develop is universal and may be applied to anomalous tidal stress induced signals predicted by any theory of gravity

A New Approach to Understanding, Achieving, and Demonstrating IMAS Compliance

Mine action organizations routinely state that they are “IMAS compliant,” but it isn’t clear exactly what that means, how anyone knows with confidence whether they are compliant or not, or who is authorized to make such statements. This article draws on recent work by Fenix Insight Ltd. to database the requirements and recommendations found in IMAS, setting out a rigorous, evidence-based approach to answering key questions about the compliance status of mine action organizations. It suggests methods for determining which requirements are relevant to which organizations, what different levels of compliance there might be and how to integrate compliance checking into established approaches to tendering, accreditation, and organizational monitoring processes. The article describes the freely available Fenix IMAS compliance database tool