Power Allocation for Adaptive OFDM Index Modulation in Cooperative Networks

In this paper, we propose a power allocation strategy for the adaptive orthogonal frequency-division multiplexing (OFDM) index modulation (IM) in cooperative networks. The allocation strategy is based on the Karush-Kuhn-Tucker (KKT) conditions, and aims at maximizing the average network capacity according to the instantaneous channel state information (CSI). As the transmit power at source and relay is constrained separately, we can thus formulate an optimization problem by allocating power to active subcarriers. Compared to the conventional uniform power allocation strategy, the proposed dynamic strategy can lead to a higher average network capacity, especially in the low signal-to-noise ratio (SNR) region. The analysis is also verified by numerical results produced by Monte Carlo simulations. By applying the proposed power allocation strategy, the efficiency of adaptive OFDM IM can be enhanced in practice, which paves the way for its implementation in the future, especially for cell-edge communications

Severe malaria: what's new on the pathogenesis front?

Plasmodium falciparum causes the most severe and fatal form of malaria in humans with over half a million deaths each year. Cerebral malaria, a complex neurological syndrome of severe falciparum malaria, is often fatal and represents a major public health burden. Despite vigorous efforts, the pathophysiology of cerebral malaria remains to be elucidated, thereby hindering the development of adjunctive therapies. In recent years, multidisciplinary and collaborative approaches have led to groundbreaking progress both in the laboratory and in the field. Here we review the latest breakthroughs in severe malaria pathogenesis, with a specific focus on new pathogenetic mechanisms leading to cerebral malaria. The most recent findings point towards specific parasite phenotypes targeting brain microvasculature, endothelial dysfunction and subsequent oedema-induced brain swelling

Les Cluses – Fort romain de la Cluse Haute

Date de l'opération : 1991 (SU) ; 1960 - 1970 (SD) Inventeur(s) : Castellvi Georges ; Grau Roger Localisation Le fort de la rive droite, situé au village actuel de la Cluse Haute, affecte une forme polygonale, allongée d'est en ouest sur une longueur de 105 m, pour une largeur de 28 m à l'ouest et de seulement 6 m à l'est (Fig. n°1 : Face est du fort romain (Cluses (Les), la Cluse Haute)). De ses accès vers l'extérieur, pour le moment, seule une poterne a été mise au jour sur la courtine sud..

Inhibition of endothelial activation: a new way to treat cerebral malaria?

BACKGROUND: Malaria is still a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria (CM), remains incompletely understood. However tumor necrosis factor (TNF) is thought to play a key role in the development of this neurological syndrome, as well as lymphotoxin alpha (LT). METHODS AND FINDINGS: Using an in vitro model of CM based on human brain-derived endothelial cells (HBEC-5i), we demonstrate the anti-inflammatory effect of LMP-420, a 2-NH2-6-Cl-9-[(5-dihydroxyboryl)-pentyl] purine that is a transcriptional inhibitor of TNF. When added before or concomitantly to TNF, LMP-420 inhibits endothelial cell (EC) activation, i.e., the up-regulation of both ICAM-1 and VCAM-1 on HBEC-5i surfaces. Subsequently, LMP-420 abolishes the cytoadherence of ICAM-1-specific Plasmodium falciparum-parasitized red blood cells on these EC. Identical but weaker effects are observed when LMP-420 is added with LT. LMP-420 also causes a dramatic reduction of HBEC-5i vesiculation induced by TNF or LT stimulation, as assessed by microparticle release. CONCLUSION: These data provide evidence for a strong in vitro anti-inflammatory effect of LMP-420 and suggest that targeting host cell pathogenic mechanisms might provide a new therapeutic approach to improving the outcome of CM patients

Microparticles as Immune Regulators in Infectious Disease – An Opinion

Despite their clear relationship to immunology, few existing studies have examined the potential role of microparticles (MP) in infectious disease. MP have a different size range from exosomes and apoptotic bodies, with which they are often grouped and arise by different mechanisms in association with inflammatory cytokine action or stress on the source cell. Infection with pathogens usually leads to the expression of a range of inflammatory cytokines and chemokines, as well as significant stress in both infected and uninfected cells. It is thus reasonable to infer that infection-associated inflammation also leads to MP production. MP are produced by most of the major cell types in the immune system, and appear to be involved at both innate and adaptive levels, potentially serving different functions in each. Thus, they do not appear to have a universal function; instead their functions are source- or stimulus-dependent, although likely to be primarily either pro- or anti-inflammatory. We argue that in infectious diseases, MP may be able to deliver antigen, derived from the biological cargo acquired from their cells of origin, to antigen-presenting cells. Another potential benefit of MP would be to transfer and/or disseminate phenotype and function to target cells. However, MP may also potentially be manipulated, particularly by intracellular pathogens, for survival advantage

TNF inhibits malaria hepatic stages in vitro via synthesis of IL-6

We examined the capacity of murine recombinant tumor necrosis factor (rmTNF) to induce an inhibitory effect at the hepatic stage on malaria induced by Plasmodium yoelll sporozoitea. When injected three times, 1.0 μg of rmTNF was found to protect 78% of mice against a sporozoite challenge. In contrast, whatever the dose and the schedule of administration, no inhibition was observed when purified hepatocyte cultures were infected with P. yoelii. The addition of non-parenchymal hepatic cells to hepatocyte cultures restored the capacity of TNF to modulate hepatic stage development, leading to up to 44% inhibition. Antibodies to interleukin 6 reversed the anti-parasite activity in the co-culture syste

Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF.

Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC(CM) ) or UM (EC(UM) ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, EC(CM) displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with EC(UM) . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in EC(CM) than in EC(UM) . These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria

The Ins and Outs of Cerebral Malaria Pathogenesis: Immunopathology, Extracellular Vesicles, Immunometabolism, and Trained Immunity

Complications from malaria parasite infections still cost the lives of close to half a million people every year. The most severe is cerebral malaria (CM). Employing murine models of CM, autopsy results, in vitro experiments, neuroimaging and microscopic techniques, decades of research activity have investigated the development of CM immunopathology in the hope of identifying steps that could be therapeutically targeted. Yet important questions remain. This review summarizes recent findings, primarily mechanistic insights on the essential cellular and molecular players involved gained within the murine experimental cerebral malaria model. It also highlights recent developments in (a) cell-cell communication events mediated through extracellular vesicles (EVs), (b) mounting evidence for innate immune memory, leading to “trained“ increased or tolerised responses, and (c) modulation of immune cell function through metabolism, that could shed light on why some patients develop this life-threatening condition whilst many do not

Contribution of Tumor Necrosis Factor to Host Defense against Staphylococci in a Guinea Pig Model of Foreign Body Infections

The contribution of the cytokine tumor necrosis factor (cachectin; TNF) to host defenses against staphylococcal foreign body infections was studied in vivo. In tissue cages subcutaneously implanted into guinea pigs, progressive infection was initiated by a very low inoculum (100 cfu) of Staphylococcus aureus with a success rate of 100%, as is frequently encountered in related clinical situations. Locally injected autologous bacterial components derived from the cell wall of S. aureus, in particular peptidoglycan, were very active in raising TNF levels in tissue cage fluid and in preventing the development of infection by the 100% infective dose of the test strain. Furthermore, injection of murine recombinant TNF into tissue cages could substitute for the bacterial components in preventing experimental infection by S. aureus. The protective effect of TNF-eliciting bacterial components could be neutralized by anti-TNF antibodies. A local increase in TNF levels might improve host defenses against staphylococcal foreign body infection