ASU Scholarship Showcase

Explosive extrusion of cold material from the interior of icy bodies, or cryovolcanism, has been observed on Enceladus and, perhaps, Europa, Triton, and Ceres. It may explain the observed evidence for a young surface on Charon (Pluto’s surface is masked by frosts). Here, we evaluate prerequisites for cryovolcanism on dwarf planet-class Kuiper belt objects (KBOs). We first review the likely spatial and temporal extent of subsurface liquid, proposed mechanisms to overcome the negative buoyancy of liquid water in ice, and the volatile inventory of KBOs. We then present a new geochemical equilibrium model for volatile exsolution and its ability to drive upward crack propagation. This novel approach bridges geophysics and geochemistry, and extends geochemical modeling to the seldom-explored realm of liquid water at subzero temperatures. We show that carbon monoxide (CO) is a key volatile for gas-driven fluid ascent; whereas CO₂ and sulfur gases only play a minor role. N₂, CH₄, and H₂ exsolution may also drive explosive cryovolcanism if hydrothermal activity produces these species in large amounts (a few percent with respect to water). Another important control on crack propagation is the internal structure: a hydrated core makes explosive cryovolcanism easier, but an undifferentiated crust does not. We briefly discuss other controls on ascent such as fluid freezing on crack walls, and outline theoretical advances necessary to better understand cryovolcanic processes. Finally, we make testable predictions for the 2015 New Horizons flyby of the Pluto-Charon system.

Carbon can be a major constituent of crustal and mantle fluids, occurring both as dissolved ionic species (e.g., carbonate ions or organic acids) and molecular species (e.g., CO₂, CO, CH₄, and more complex organic compounds). The chemistry of dissolved carbon changes dramatically with pressure (P) and temperature (T). In aqueous fluids at low P and T, molecular carbon gas species such as CO₂ and CH₄ saturate at low concentration to form a separate phase. With modest increases in P and T, these molecular species become fully miscible with H₂O, enabling deep crustal and mantle fluids to become highly concentrated in carbon. At such high concentrations, carbon species play an integral role as solvent components and, with H₂O, control the mobility of rock-forming elements in a wide range of geologic settings. The migration of carbon-bearing crustal and mantle fluids contributes to Earth’s carbon cycle; however, the mechanisms, magnitudes, and time variations of carbon transfer from depth to the surface remain least understood parts of the global carbon budget (Berner 1991, 1994; Berner and Kothavala 2001).

Contemporary vaccine development relies less on empirical methods of vaccine construction, and now employs a powerful array of precise engineering strategies to construct immunogenic live vaccines. In this review, we will survey various engineering techniques used to create attenuated vaccines, with an emphasis on recent advances and insights. We will further explore the adaptation of attenuated strains to create multivalent vaccine platforms for immunization against multiple unrelated pathogens. These carrier vaccines are engineered to deliver sufficient levels of protective antigens to appropriate lymphoid inductive sites to elicit both carrier-specific and foreign antigen-specific immunity. Although many of these technologies were originally developed for use in Salmonella vaccines, application of the essential logic of these approaches will be extended to development of other enteric vaccines where possible. A central theme driving our discussion will stress that the ultimate success of an engineered vaccine rests on achieving the proper balance between attenuation and immunogenicity. Achieving this balance will avoid over-activation of inflammatory responses, which results in unacceptable reactogenicity, but will retain sufficient metabolic fitness to enable the live vaccine to reach deep tissue inductive sites and trigger protective immunity. The breadth of examples presented herein will clearly demonstrate that genetic engineering offers the potential for rapidly propelling vaccine development forward into novel applications and therapies which will significantly expand the role of vaccines in public health.

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse Poll-driven plasmid for efficient production of influenza virus. Results: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)-10(6) 50 % tissue culture infective dose (TCID50)/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin-Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. Conclusions: An all-in-one plasmid and a 3-plasmid murine Poll-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust "1 + 2" approach to generate influenza vaccine seed virus.