533 research outputs found
Complexity of Strong Implementability
We consider the question of implementability of a social choice function in a
classical setting where the preferences of finitely many selfish individuals
with private information have to be aggregated towards a social choice. This is
one of the central questions in mechanism design. If the concept of weak
implementation is considered, the Revelation Principle states that one can
restrict attention to truthful implementations and direct revelation
mechanisms, which implies that implementability of a social choice function is
easy to check. For the concept of strong implementation, however, the
Revelation Principle becomes invalid, and the complexity of deciding whether a
given social choice function is strongly implementable has been open so far. In
this paper, we show by using methods from polyhedral theory that strong
implementability of a social choice function can be decided in polynomial space
and that each of the payments needed for strong implementation can always be
chosen to be of polynomial encoding length. Moreover, we show that strong
implementability of a social choice function involving only a single selfish
individual can be decided in polynomial time via linear programming
Historicising the Birangona: Interrogating the Politics of Commemorating the Wartime Rape of 1971 in the context of the 50th Anniversary of Bangladesh
Two decades ago, ‘1971’ was deemed to not have a market within Indian publishing houses and media outlets. Yet, one is struck by the contemporary Indian focus on the iconic figure of the Birangona – brave women, a title given by the State of Bangladesh to women raped by the Pakistani army and their Bengali and non-Bengali collaborators during the Bangladesh war of 1971. It is important to engage with the public memory of wartime sexual violence of 1971 beyond the horrific constructions of the Birangona and the potential for propaganda and geopolitical calculations that the narrative engenders for India
Graphic Ethnography and Generative Resilience of Sexual Violence in Conflict of the Birangonas (War-heroines) in Bangladesh
The use of rape was common during the 1971 war in Bangladesh. Six days after the war ended, the new government publicly declared that any woman raped in the war was a birangona or ‘war heroine’. There exists a public memory of wartime rape through various literary, visual and testimonial forms, ensuring that the raped woman endures as an iconic figure. However, women’s experiences of wartime sexual violence are often explained through the limited lenses of silence, voice, shame, honour, gender, patriarchy, stigma, trauma and ostracisation, which help to create the figure of the horrific raped woman – meaning that birangonas are often assumed to have a horrific life trajectory. This can undermine the very resilience that characterises many of the women who were raped. In contrast, this chapter focuses on generative resilience, as offering a different narrative of sexual violence that emphasises women’s abilities to continue to live with and pass on the experiences of sexual violence in ways that are uniquely relational. It is this contextualised and social ecological understanding of resilience that needs to inform adaptive peacebuilding, in order to foster a nuanced understanding of the effects of rape as a weapon of war
Side Chain Hydrophobicity Modulates Therapeutic Activity and Membrane Selectivity of Antimicrobial Peptide Mastoparan-X
The discovery of new anti-infective compounds is stagnating and multi-resistant bacteria continue to emerge, threatening to end the "antibiotic era". Antimicrobial peptides (AMPs) and lipo-peptides such as daptomycin offer themselves as a new potential class of antibiotics; however, further optimization is needed if AMPs are to find broad use as antibiotics. In the present work, eight analogues of mastoparan-X (MPX) were investigated, having side chain modifications in position 1, 8 and 14 to modulate peptide hydrophobicity. The self-association properties of the peptides were characterized, and the peptide-membrane interactions in model membranes were compared with the bactericidal and haemolytic properties. Alanine substitution at position 1 and 14 resulted in higher target selectivity (red blood cells versus bacteria), but also decreased bactericidal potency. For these analogues, the gain in target selectivity correlated to biophysical parameters showing an increased effective charge and reduction in the partitioning coefficient for membrane insertion. Introduction of an unnatural amino acid, with an octyl side chain by amino acid substitution, at positions 1, 8 and 14 resulted in increased bactericidal potency at the expense of radically reduced membrane target selectivity. Overall, optimized membrane selectivity or bactericidal potency was achieved by changes in side chain hydrophobicity of MPX. However, enhanced potency was achieved at the expense of selectivity and vice versa in all cases
The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production
Abstract Innate defense mechanisms are aimed at quickly containing and removing infectious microorganisms and involve local stromal and immune cell activation, neutrophil recruitment and activation and the induction of host defense peptides (defensins and cathelicidins), acute phase proteins and complement activation. As an alternative to antibiotics, innate immune mechanisms are highly relevant as they offer rapid general ways to, at least partially, protect against infections and enable the build-up of a sufficient adaptive immune response. This review describes two classes of promising alternatives to antibiotics based on components of the innate host defense. First we describe immunoglobulins applied to mimic the way in which they work in the newborn as locally acting broadly active defense molecules enforcing innate immunity barriers. Secondly, the potential of host defense peptides with different modes of action, used directly, induced in situ or used as vaccine adjuvants is described
Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation
Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
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