Modeling the influence of MgSO4 invariant points on multiphase reactive transport process during saline soil evaporation

In the present work, we modeled a laboratory experiment where a sand column saturated with a MgSO4 solution is subject to evaporation. We used a compositional formulation capable of representing the effect of geochemistry on flow and transport for concentrated solutions under extreme dry conditions. The model accounts for the water sink/sources terms due to hydrated mineral dissolution/precipitation and the occurrence of invariant points, which prescribe the water activity. Results show that the occurrence of the invariant points at the top of the domain could affect the vapor flux at the column top and salt precipitation along the column. In fact, the invariant points occurrence could explain the spatial fluctuation on the salt precipitates formation. Results also suggest that the complex hydrochemical interactions occurring during soil salinization, including osmotic effects, are crucial not only to understand the salt precipitation, but also the evaporation rate.Fil: Gamazo, P.. Universidad de la Republica; Uruguay. Universidad Politecnica de Catalunya; EspañaFil: Saaltink, M. W.. Universidad Politecnica de Catalunya; EspañaFil: Carrera, J.. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Slooten, L. J.. Instituto de Diagnóstico Ambiental y Estudios del Agua; EspañaFil: Bea, Sergio Andrés. Universidad Nacional del Centro de la Provincia de Buenos Aires. Rectorado. Instituto de Hidrología de Llanuras - Sede Azul; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tandil; ArgentinaFil: Gran, M.. Universidad Politecnica de Catalunya; Españ

Polymeric carriers for amphotericin B: in vitro activity, toxicity and therapeutic efficacy against systemic candidiasis in neutropenic mice

Objective: To study the toxicity and activity of two new amphotericin B formulations: poly(ε-caprolactone) nanospheres coated with poloxamer 188 (AmB-NP) and mixed micelles with the same surfactant (AmB-MM). Materials and methods: The toxicity of these formulations was evaluated in erythrocytes, J774.2 macrophages and LLCPK1 renal cells, as well as in mice. Activity was determined in clinical isolates and in neutropenic mice. Mice were made neutropenic with 5-fluorouracil, infected with Candida albicans and treated with the antifungal formulations for three consecutive days. AmB association in cells and accumulation in kidneys and liver of animals was quantified by HPLC. Results: Both formulations decreased between 8- and 10-fold the MIC of the polyene against clinical isolates of C. albicans. However, their activity was lower than or equal to that of AmB-deoxycholate when it was assessed against C. albicans-infected macrophages. When given as a single intravenous dose in mice, AmB-MM and AmB-NP had an LD50 of 9.8 and 18.6 mg/kg, respectively, compared with 4 mg/kg for AmBdeoxycholate. Comparison of residual infection burdens in the liver and kidneys showed that AmB-deoxycholate (0.5 mg/kg) was more effective and faster in eradicating yeast cells than polymeric formulations. This fact can be related to a lower AmB accumulation inside macrophages and in liver and kidneys (about 1.5 mg drug/g tissue) of mice, compared with those detected for AmB-deoxycholate (4 mg drug/g). Overall, the efficacy of these formulations at 2 mg/kg was equal to that of AmB-deoxycholate at 0.5 mg/kg. Conclusions: AmB-MM and AmB-NP decreased the in vivo antifungal activity of AmB, and higher concentrations were therefore necessary to obtain a similar therapeutic effect. However, these higher concentrations were achievable owing to the reduced toxicity of these formulations

Evaluation of bioadhesive capacity and immunoadjuvant properties of vitamin B(12)-Gantrez nanoparticles.

PURPOSE: To design bioadhesive Gantrez AN (poly[methyl vinyl ether-co-maleic anhydride], PVM/MA) nanoparticles (NP) coated with Vitamin B12 (Vit B12), and investigate their application in oral antigen delivery. METHODS: The association of Vit B12 to Gantrez AN nanoparticles was performed by the direct attachment of reactive Vit B12 to the surface of the nanoparticles (NPB), or linking to the copolymer chains in dimethylformamide prior to NP formation (NPBDMF). Nanoparticles were characterized by measuring the size, zeta potential, Vit B12 association efficacy, and stability of Vit B12 on the surface of the nanoparticles. In vivo bioadhesion study was performed by the oral administration of fluorescently-labeled nanoparticle formulations to rats. Both systemic and mucosal immune responses were evaluated after oral and subcutaneous immunization with ovalbumin (OVA) containing Vit B12-coated nanoparticles. RESULTS: The Vit B12 nanoparticles displayed homogenous size distribution with a mean diameter of about 200 nm and a negative surface charge. The association efficiency of Vit B12 to NPB-DMF formulation was about two times higher than to the NPB, showing also a higher surface stability of Vit B12. The bioadhesion study demonstrated that NPB-DMF had an important tropism to the distal portions of the gut, which was about 2 and 3.5 times higher than the tropism observed for NPB and control NP, respectively (P< 0.05). Oral administration of OVA-NPB-DMF induced also stronger and more balanced serum anti-OVA titers of IgG2a (Th1) and IgG1 (Th2) compared to control OVA-NP. In addition, oral immunization with OVA-NPB-DMF induced a higher mucosal IgA response than subcutaneous administration. CONCLUSIONS: These results indicate the benefits of bioadhesive Vit B12-coated nanoparticles in oral antigen delivery eliciting systemic and mucosal immune response

Brucella abortus Choloylglycine Hydrolase Affects Cell Envelope Composition and Host Cell Internalization

Choloylglycine hydrolase (CGH, E.C. 3.5.1.24) is a conjugated bile salt hydrolase that catalyses the hydrolysis of the amide bond in conjugated bile acids. Bile salt hydrolases are expressed by gastrointestinal bacteria, and they presumably decrease the toxicity of host's conjugated bile salts. Brucella species are the causative agents of brucellosis, a disease affecting livestock and humans. CGH confers Brucella the ability to deconjugate and resist the antimicrobial action of bile salts, contributing to the establishment of a successful infection through the oral route in mice. Additionally, cgh-deletion mutant was also attenuated in intraperitoneally inoculated mice, which suggests that CGH may play a role during systemic infection other than hydrolyzing conjugated bile acids. To understand the role CGH plays in B. abortus virulence, we infected phagocytic and epithelial cells with a cgh-deletion mutant (Δcgh) and found that it is defective in the internalization process. This defect along with the increased resistance of Δcgh to the antimicrobial action of polymyxin B, prompted an analysis of the cell envelope of this mutant. Two-dimensional electrophoretic profiles of Δcgh cell envelope-associated proteins showed an altered expression of Omp2b and different members of the Omp25/31 family. These results were confirmed by Western blot analysis with monoclonal antibodies. Altogether, the results indicate that Brucella CGH not only participates in deconjugation of bile salts but also affects overall membrane composition and host cell internalization

Computational approaches to explainable artificial intelligence: Advances in theory, applications and trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9th International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications.MCIU - Nvidia(UMA18-FEDERJA-084

Computational Approaches to Explainable Artificial Intelligence:Advances in Theory, Applications and Trends

Deep Learning (DL), a groundbreaking branch of Machine Learning (ML), has emerged as a driving force in both theoretical and applied Artificial Intelligence (AI). DL algorithms, rooted in complex and non-linear artificial neural systems, excel at extracting high-level features from data. DL has demonstrated human-level performance in real-world tasks, including clinical diagnostics, and has unlocked solutions to previously intractable problems in virtual agent design, robotics, genomics, neuroimaging, computer vision, and industrial automation. In this paper, the most relevant advances from the last few years in Artificial Intelligence (AI) and several applications to neuroscience, neuroimaging, computer vision, and robotics are presented, reviewed and discussed. In this way, we summarize the state-of-the-art in AI methods, models and applications within a collection of works presented at the 9 International Conference on the Interplay between Natural and Artificial Computation (IWINAC). The works presented in this paper are excellent examples of new scientific discoveries made in laboratories that have successfully transitioned to real-life applications

Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections

Research and Development for Near Detector Systems Towards Long Term Evolution of Ultra-precise Long-baseline Neutrino Experiments

Document submitted to the European Strategy For European Particle PhysicsDocument submitted to the European Strategy For European Particle PhysicsDocument submitted to the European Strategy For European Particle PhysicsWith the discovery of non-zero value of $\theta_{13}$ mixing angle, the next generation of long-baseline neutrino (LBN) experiments offers the possibility of obtaining statistically significant samples of muon and electron neutrinos and anti-neutrinos with large oscillation effects. In this document we intend to highlight the importance of Near Detector facilities in LBN experiments to both constrain the systematic uncertainties affecting oscillation analyses but also to perform, thanks to their close location, measurements of broad benefit for LBN physics goals. A strong European contribution to these efforts is possible