A Novel Theoretical Probabilistic Model for Opportunistic Routing with Applications in Energy Consumption for WSNs

This paper proposes a new theoretical stochastic model based on an abstraction of the opportunistic model for opportunistic networks. The model is capable of systematically computing the network parameters, such as the number of possible routes, the probability of successful transmission, the expected number of broadcast transmissions, and the expected number of receptions. The usual theoretical stochastic model explored in the methodologies available in the literature is based on Markov chains, and the main novelty of this paper is the employment of a percolation stochastic model, whose main benefit is to obtain the network parameters directly. Additionally, the proposed approach is capable to deal with values of probability specified by bounded intervals or by a density function. The model is validated via Monte Carlo simulations, and a computational toolbox (R-packet) is provided to make the reproduction of the results presented in the paper easier. The technique is illustrated through a numerical example where the proposed model is applied to compute the energy consumption when transmitting a packet via an opportunistic network

Protective Antibody and CD8+ T-Cell Responses to the Plasmodium falciparum Circumsporozoite Protein Induced by a Nanoparticle Vaccine

Background The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8+ and CD4+ T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects. Methodology/Principal Findings To establish the basis for a SAPN-based vaccine, B- and CD8+ T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ+, IL-2+) long-lived central memory CD8+ T-cells. Furthermore, we demonstrated that these Ab or CD8+ T–cells can independently provide sterile protection against a lethal challenge of the transgenic parasites. Conclusion The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Phenotypic Characterization of Peripheral Osteoclast Precursors their Lineage Relation to Macrophages and Dendritic Cells and their Population Dynamics Influenced by Parathyroid Hormone and Inflammatory Signals.

Osteoclasts are unique multinuclear cells that are highly specialized for resorbing bone tissue and therefore play crucial roles in bone remodeling. The identification of bona fide populations of osteoclast precursors (OCPs) is crucial to understand their biology in homeostatic and pathological conditions. We identified a bone marrow precursor with high osteoclastogenic activity (Jacquin et al., 2006) and extended these findings to test their clonogenic potential and bone resorptive capacity at the single cell level. We also identified the phenotype of peripheral blood and spleen OCPs. In chapter III, we showed that bone marrow and peripheral OCPs gave rise to macrophages and dendritic cells (in addition to osteoclasts) when stimulated with differential cytokines, suggesting a common developmental pathway among these cells. We developed a fluorescent reporter mouse model to study osteoclast migration and differentiation in vivo. Transplant studies showed that bone marrow OCPs home back to the bone marrow and migrated to the spleen while circulating in peripheral blood. Interestingly, spleen precursors were able to migrate to bone marrow and also engrafted in the spleen. In addition, transferred OCPs differentiated to fluorescent osteoclasts associated to bone surfaces. These experiments suggest that the bone marrow and spleen precursors are developmentally related. Osteoclasts are critically involved in skeletal function such as bone remodeling, fracture repair, and in pathological bone resorption associated with inflammatory conditions. We challenged mice with LPS and found that peripheral OCPs increased their number and resorptive capacity. In addition, we studied how chronic inflammation modulated OCPs in arthritic (hTNF) mice, and found that peripheral precursors were increased in number. OCPs derived from CathepsinK-Cre-tdTomatoFP recipient mice and transferred to hTNF, engrafted to localize sites of inflammation and differentiated to RFP+ osteoclasts associated to bone surfaces in diarthrodial joints. These experiments suggest that inflammatory signals modulate osteoclast precursor migration, distribution, resorptive capacity and differentiation. Finally, we studied the effect of parathyroid hormone (PTH) on osteoclast precursor populations in the bone marrow. We found that intermittent administration of PTH to mice increased the frequency of these populations in the bone marrow and increased their ability to form osteoclast in vitro