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Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin
No full textAbstractThe skin is an ideal target tissue for vaccine delivery for a number of reasons. It is highly accessible, and most importantly, enriched in professional antigen presenting cells. Possessing strong similarities to human skin physiology and displaying a defined epidermis, the guinea pig is an appropriate model to study epidermal delivery of vaccine. However, whilst we have characterized the humoral responses in the guinea pig associated with skin vaccine protocols we have yet to investigate the T cell responses. In response to this inadequacy, we developed an IFN-γ ELISpot assay to characterize the cellular immune response in the peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA vaccination regimen, we characterized host T cell responses. After delivery of the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell responses. The levels of IFN-γ spot-forming units averaged approximately 5000 per million cells after two immunizations. These responses were broad in that multiple regions across the NP antigen elicited a T cell response. Interestingly, we identified a number of NP immunodominant T cell epitopes to be conserved across an outbred guinea pig population, a phenomenon which was also observed after immunization with a RSV DNA vaccine. We believe this data enhances our understanding of the cellular immune response elicited to a vaccine in guinea pigs, and globally, will advance the use of this model for vaccine development, especially those targeting skin as a delivery site
Special Issue: Targeted Woodland Removal to Recover At-Risk Grouse and Their Sagebrush-Steppe and Prairie Ecosystems
No full textOutcome of ureteral distensibility on the success of ureteroscopy: A prospective hospital-based descriptive study
No full textAbstractIntroduction“Difficult ureter” is a known problem that increases the complications during ureteroscopy.ObjectiveTo categorize ureters according to their distensibility, and to determine whether ureteric distensibility is associated with the success of ureteroscopy and its complications.Subjects and methodsBetween January 2010 and September 2012, we tested ureteral distensibility in 306 patients who had a unilateral single radiopaque ureteral stone, 6–20mm in diameter. Ureteral distensibility was classified into two categories according to the maximum size of a ureteral dilator that could be introduced before ureteroscopy: non-distensible ureters, which admitted a dilator up to 10 Fr and distensible ureters, which admitted a dilator >10 Fr. Correlations between distensibility and the success rate and complications of ureteroscopy were determined.ResultsOverall, 102 patients (33.3%) had non-distensible ureters and 204 (66.7%) had distensible ureters. Distensibility was correlated with the success of ureteroscopy because initial ureteroscopy failed in 38.2% of non-distensible ureters. Ureteroscopy was successful in all distensible ureters. The incidence of ureteric injury was higher in non-distensible ureters than in distensible ureters.ConclusionsOur results suggest that ureteric distensibility should be tested before ureteroscopy. Primary ureteroscopy is recommended in distensible ureters because of its low complication rates and favorable outcome. Pre-stenting may be necessary before ureteroscopy in non-distensible ureters; secondary ureteroscopy may be safer and more feasible in these settings
LCA of emerging technologies: addressing high uncertainty on inputs' variability when performing global sensitivity analysis
No full textAbstractIn the life cycle assessment (LCA) context, global sensitivity analysis (GSA) has been identified by several authors as a relevant practice to enhance the understanding of the model's structure and ensure reliability and credibility of the LCA results. GSA allows establishing a ranking among the input parameters, according to their influence on the variability of the output. Such feature is of high interest in particular when aiming at defining parameterized LCA models.When performing a GSA, the description of the variability of each input parameter may affect the results. This aspect is critical when studying new products or emerging technologies, where data regarding the model inputs are very uncertain and may cause misleading GSA outcomes, such as inappropriate input rankings. A systematic assessment of this sensitivity issue is now proposed.We develop a methodology to analyze the sensitivity of the GSA results (i.e. the stability of the ranking of the inputs) with respect to the description of such inputs of the model (i.e. the definition of their inherent variability). With this research, we aim at enriching the debate on the application of GSA to LCAs affected by high uncertainties.We illustrate its application with a case study, aiming at the elaboration of a simple model expressing the life cycle greenhouse gas emissions of enhanced geothermal systems (EGS) as a function of few key parameters. Our methodology allows identifying the key inputs of the LCA model, taking into account the uncertainty related to their description
Excessive trading, a gambling disorder in its own right? A case study on a French disordered gamblers cohort
No full textAbstractIntroductionTrading and gambling appear to share some similarities. Indeed, traders can get professionally involved in high-risk types of trading as if it were gambling. This research explores whether excessive trading can be conceptualized as a subset of gambling disorders.ObjectiveTo better acknowledge the existence of an addictive-like trading behavior and to discuss its phenomenological similarities with gambling disorders.MethodsThe data of 8 excessive traders out of a cohort of 221 outpatients seeking treatment in our Problem Gambling unit were analyzed.ResultsOur case series revealed important similarities with gambling disorders in terms of diagnosis, trajectory and comorbidities. Like many disordered gamblers, excessive traders of this study experienced a number of small early wins, chased their losses, and ended up losing control over the money they invested. All of them invested in very risky stocks associated with short-term trading leading to potential large gains, but also with very significant losses. The structure itself of the two activities (gambling and trading) is very close.ConclusionOur results tended to support the idea of an addictive-like trading behavior as a subset of gambling disorders. Investing is not a form of gambling, but some people gamble with investments. Several observations and recommendations can be made: (i) conduct researches; (ii) build and validate specific assessment tools; (iii) develop strategies for prevention and treatment; and (iv) conduct more rigorous studies to clarify what we named an addictive-like trading behavior
Hydrogen network retrofit via flexibility analysis: The steady-state flexibility index
No full textAbstractA systematic approach is presented to retrofit design of a hydrogen distribution network. A methodology is based on the steady-state flexibility index (FIs) for optimizing network and enhancing the efficiency of purifiers. The main object of this technique is to investigate hydrogen network flexibility under severe operation uncertainty and to reduce streams to purifiers by consideration inlet feed purity of purifiers. The presented approach is applied to the hydrogen network of a real installation
Potential of nano crystalline calcium hydroxyapatite for Tin(II) removal from aqueous solutions: Equilibria and kinetic processes
No full textAbstractThe potential of the synthesized nano hydroxyapatite to remove Sn2+ from aqueous solutions was investigated in a batch reactor under different experimental conditions. The study also investigates the effects of process parameters such as initial concentration of Sn2+ ions, temperature, and adsorbent mass. Various thermodynamic parameters, such as ΔGo, ΔHo and ΔSo have been calculated. The thermodynamics of an Sn2+ ion onto nano HAp system indicates a spontaneous and endothermic nature of the process. Tin uptake was quantitatively evaluated using the Langmuir, Freundlich and Dubinin–Kaganer–Radushkevich models. The adsorption data follow the adsorption equilibrium described well by the Langmuir isotherm model with maximum adsorption capacity of 2500mg/g of Sn2+ ions on nano HAp. Using the second-order kinetic constants, the activation energy of adsorption (Ea) was determined as 4.125kJmol−1 according to the Arrhenius equation
Metastable dark energy
No full textAbstractWe build a model of metastable dark energy, in which the observed vacuum energy is the value of the scalar potential at the false vacuum. The scalar potential is given by a sum of even self-interactions up to order six. The deviation from the Minkowski vacuum is due to a term suppressed by the Planck scale. The decay time of the metastable vacuum can easily accommodate a mean life time compatible with the age of the universe. The metastable dark energy is also embedded into a model with SU(2)R symmetry. The dark energy doublet and the dark matter doublet naturally interact with each other. A three-body decay of the dark energy particle into (cold and warm) dark matter can be as long as large fraction of the age of the universe, if the mediator is massive enough, the lower bound being at intermediate energy level some orders below the grand unification scale. Such a decay shows a different form of interaction between dark matter and dark energy, and the model opens a new window to investigate the dark sector from the point-of-view of particle physics
Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann Pick type C disease
No full textAbstractNiemann Pick type C (NPC) disease is a progressive lysosomal storage disorder caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by neurological defects, hepatosplenomegaly and premature death. While the primary biochemical feature of NPC disease is the intracellular accumulation of cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial cholesterol accumulation has also been reported. As accumulation of cholesterol in mitochondria is known to impair the transport of GSH into mitochondria, resulting in mitochondrial GSH (mGSH) depletion, we investigated the impact of mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE), but not N-acetylcysteine (NAC), restored the mGSH pool in liver and brain of Npc1-/- mice and in fibroblasts from NPC patients, while both GSH-EE and NAC increased total GSH levels. GSH-EE but not NAC increased the median survival and maximal life span of Npc1-/- mice. Moreover, intraperitoneal therapy with GSH-EE protected against oxidative stress and oxidant-induced cell death, restored calbindin levels in cerebellar Purkinje cells and reversed locomotor impairment in Npc1-/- mice. High-resolution respirometry analyses revealed that GSH-EE improved oxidative phosphorylation, coupled respiration and maximal electron transfer in cerebellum of Npc1-/- mice. Lipidomic analyses showed that GSH-EE treatment had not effect in the profile of most sphingolipids in liver and brain, except for some particular species in brain of Npc1-/- mice. These findings indicate that the specific replenishment of mGSH may be a potential promising therapy for NPC disease, worth exploring alone or in combination with other options