Viral Protein Fragmentation May Broaden T-Cell Responses to HIV Vaccines

High mutation rates of human immunodeficiency virus (HIV) allows escape from T cell recognition preventing development of effective T cell vaccines. Vaccines that induce diverse T cell immune responses would help overcome this problem. Using SIV gag as a model vaccine, we investigated two approaches to increase the breadth of the CD8 T cell response. Namely, fusion of vaccine genes to ubiquitin to target the proteasome and increase levels of MHC class I peptide complexes and gene fragmentation to overcome competition between epitopes for presentation and recognition.three vaccines were compared: full-length unmodified SIV-mac239 gag, full-length gag fused at the N-terminus to ubiquitin and 7 gag fragments of equal size spanning the whole of gag with ubiquitin-fused to the N-terminus of each fragment. Genes were cloned into a replication defective adenovirus vector and immunogenicity assessed in an in vitro human priming system. The breadth of the CD8 T cell response, defined by the number of distinct epitopes, was assessed by IFN-γ-ELISPOT and memory phenotype and cytokine production evaluated by flow cytometry. We observed an increase of two- to six-fold in the number of epitopes recognised in the ubiquitin-fused fragments compared to the ubiquitin-fused full-length gag. In contrast, although proteasomal targeting was achieved, there was a marked reduction in the number of epitopes recognised in the ubiquitin-fused full-length gag compared to the full-length unmodified gene, but there were no differences in the number of epitope responses induced by non-ubiquitinated full-length gag and the ubiquitin-fused mini genes. Fragmentation and ubiquitination did not affect T cell memory differentiation and polyfunctionality, though most responses were directed against the Ad5 vector.Fragmentation but not fusion with ubiquitin increases the breadth of the CD8 T vaccine response against SIV-mac239 gag. Thus gene fragmentation of HIV vaccines may maximise responses

Modeling and simulation of the thermodynamics of lithium-ion battery intercalation materials in the open-source software Cantera

Modeling and simulation play a key role in analyzing the complex electrochemical behavior of lithium-ion batteries. We present the development of a thermodynamic and kinetic modeling framework for intercalation electrochemistry within the open-source software Cantera. Instead of using equilibrium potentials and single-step Butler-Volmer kinetics, Cantera is based on molar thermodynamic data and mass-action kinetics, providing a physically-based and flexible means for complex reaction pathways. Herein, we introduce a new thermodynamic class for intercalation materials into the open-source software. We discuss the derivation of molar thermodynamic data from experimental half-cell potentials, and provide practical guidelines. We then demonstrate the new class using a single-particle model of a lithium cobalt oxide/graphite lithium-ion cell, implemented in MATLAB. With the present extensions, Cantera provides a platform for the lithium-ion battery modeling community both for consistent thermodynamic and kinetic models and for exchanging the required thermodynamic and kinetic parameters. We provide the full MATLAB code and parameter files as supplementary material to this article

Solid Electrolyte Interphase in Li-Ion Batteries: Evolving Structures Measured In situ by Neutron Reflectometry

Li-ion batteries are made possible by the solid electrolyte interphase, SEI, a self-forming passivation layer, generated because of electrolyte instability with respect to the anode chemical potential. Ideally it offers sufficient electronic resistance to limit electrolyte decomposition to the amount needed for its formation. However, slow continued SEI growth leads to capacity fade and increased cell resistance. Despite the SEI’s critical significance, currently structural characterization is incomplete because of the reactive and delicate nature of the SEI and the electrolyte system in which it is formed. Here we present, for the first time, in situ neutron reflectometry measurements of the SEI layer as function of potential in a working lithium half-cell. The SEI layer after 10 and 20 CV cycles is 4.0 and 4.5 nm, respectively, growing to 8.9 nm after a series of potentiostatic holds that approximates a charge/discharge cycle. Specified data sets show uniform mixing of SEI components

On the Fundamental and Practical Aspects of Modeling Complex Electrochemical Kinetics and Transport

Numerous technologies, such as batteries and fuel cells, depend on electrochemical kinetics. In some cases, the responsible electrochemistry and charged-species transport is complex. However, to date, there are essentially no general-purpose modeling capabilities that facilitate the incorporation of thermodynamic, kinetic, and transport complexities into the simulation of electrochemical processes. A vast majority of the modeling literature uses only a few (often only one) global charge-transfer reactions, with the rates expressed using Butler–Volmer approximations. The objective of the present paper is to identify common aspects of electrochemistry, seeking a foundational basis for designing and implementing software with general applicability across a wide range of materials sets and applications. The development of new technologies should be accelerated and improved by enabling the incorporation of electrochemical complexity (e.g., multi-step, elementary charge-transfer reactions and as well as supporting ionic and electronic transport) into the analysis and interpretation of scientific results. The spirit of the approach is analogous to the role that Chemkin has played in homogeneous chemistry modeling, especially combustion. The Cantera software, which already has some electrochemistry capabilities, forms the foundation for future capabilities expansion

Integration of catalytic combustion and heat recovery with meso-scale solid oxide fuel cell system

To facilitate high-power density operation of a meso-scale solid oxide fuel cell (SOFC) system, fuel processing and anode exhaust catalytic combustor with waste heat recovery are critical components. An integrated modeling study of a catalytic combustor with a solid oxide fuel cell and a catalytic partial oxidation (CPOx) reactor indicates critical aspects of the butane-fueled system design in order to ensure stable operation of the SOFC as well as the combustor and CPOx reactor. The modeled system consists of: 1) a Rh-coated ceramic foam catalytic partial oxidation reactor, 2) a SOFC with a Ni/YSZ structural anode, a dense YSZ electrolyte, and a LSM/YSZ cathode layer, and 3) a Pt-coated anode exhaust combustor with waste heat recovery. Model results for a system designed to produce < 30 W electric power from n-butane show how the design of the inlet-air cooled catalytic combustor can maximize combustion efficiency of the anode exhaust and heat recovery to the system inlet air flow. The model also shows the need to minimize heat loss in the air flow passages in order to maintain stable SOFC operation at 700 °C or higher. There is a strong sensitivity of the system operation to the SOFC operating voltage as well as the overall air to fuel ratio, and these sensitivities place important bounds on the range of operating conditions

Multielement Activity Mapping and Potential Mapping in Solid Oxide Electrochemical Cells through the use of <i>operando</i> XPS

Spatially resolved ambient pressure X-ray photoelectron spectroscopy has been used to measure and visualize regions of electrochemical activity, local surface potential losses, overpotentials, and oxidation state changes on single sided ceria/yttria-stabilized zirconia (YSZ)/Pt solid oxide electrochemical cells. When hydrogen electro-oxidation (negative applied bias) or water electrolysis (positive applied bias) is promoted on the ceria electrocatalyst, the Ce³⁺/Ce⁴⁺ ratios shift away from equilibrium values and thereby demarcate electrochemically active regions on the ceria electrode. In addition to the ceria oxidation state shifts, inactive surface impurities with high photoelectron cross sections, such as Si, can provide local markers of activity through chemical and surface potential mappings under various electrochemical conditions. Localized removal of chemically active carbonaceous surface impurities also reveals regions of electrochemical oxidation activity on the ceria electrode. Finally, we show that electrochemical polarization of solid oxide electrochemical cells under different gas environments is used to control the ceria surface chemical state and oxygen vacancy density