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Register a new userA solid approach to biopharmaceutical stabilisation
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Ensilication is a technology we developed that can physically stabilise proteins in silica without use of a pre-formed particle matrix. Stabilisation is done by tailor fitting individual proteins with a silica coat using a modified sol-gel process. Biopharmaceuticals, for example, liquid-formulated vaccines with adjuvants, have poor thermal stability. Heating or freezing impairs their potency. As a result, there is an increase in the prevalence of vaccine-preventable diseases in low-income countries even when there are means to combat them. One of the root causes lies in the problematic vaccine cold-chain distribution. We believe that ensilication can improve vaccine availability by enabling transportation without refrigeration. Here, we show that ensilication stabilises tetanus toxoid C fragment (TTCF) and demonstrate that this material can be stored and transported at ambient temperature without compromising the immunogenic properties of TTCF in vivo. TTCF is a component of the diphtheria, tetanus and pertussis (DTP) vaccine. To further our understanding of the ensilication process, and its protective effect on proteins we have studied the formation of TTCF-silica nanoparticles via time-resolved Small Angle X-ray Scattering (SAXS). Our results reveal ensilication to be a staged diffusion-limited cluster aggregation (DLCA) type reaction, induced by the presence of TTCF protein at neutral pH. Analysis of scattering data indicates tailor fitting of TTCF protein. The experimental in vivo immunisation data confirms the retention of immunogenicity after release from silica. Our results suggest that we could utilise this technology for multicomponent vaccines, therapeutics or other biopharmaceuticals that are not compatible with lyophilisation.
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We give another proof, using tools from Geometric Invariant Theory, of a result due to S. Sam and A. Snowden in 2014, concerning the stability of Kro-necker coefficients. This result states that some sequences of Kronecker coefficients eventually stabilise, and our method gives a nice geometric bound from which the stabilisation occurs. We perform the explicit computation of such a bound on two examples, one being the classical case of Murnaghans stability. Moreover, we see that our techniques apply to other coefficients arising in Representation Theory: namely to some plethysm coefficients and in the case of the tensor product of representations of the hyperoctahedral group.
Motivated by the observation of non-exponential run-time distributions of bacterial swimmers, we propose a minimal phenomenological model for taxis of active particles whose motion is controlled by an internal clock. The ticking of the clock depends on an external concentration field, e.g. a chemical substance. We demonstrate that these particles can detect concentration gradients and respond to them by moving up- or down-gradient depending on the clock design, albeit measurements of these fields are purely local in space and instantaneous in time. Altogether, our results open a new route in the study of directional navigation, by showing that the use of a clock to control motility actions represents a generic and versatile toolbox to engineer behavioral responses to external cues, such as light, chemical, or temperature gradients.
Nucleation of a solid in solid is initiated by the appearance of distinct dynamical heterogeneities, consisting of `active particles whose trajectories show an abrupt transition from ballistic to diffusive, coincident with the discontinuous transition in microstructure from a {it twinned martensite} to {it ferrite}. The active particles exhibit intermittent jamming and flow. The nature of active particle trajectories decides the fate of the transforming solid -- on suppressing single particle diffusion, the transformation proceeds via rare string-like correlated excitations, giving rise to twinned martensitic nuclei. These string-like excitations flow along ridges in the potential energy topography set up by inactive particles. We characterize this transition using a thermodynamics in the space of trajectories in terms of a dynamical action for the active particles confined by the inactive particles. Our study brings together the physics of glass, jamming, plasticity and solid nucleation.
Cellular decision making allows cells to assume functionally different phenotypes in response to microenvironmental cues, without genetic change. It is an open question, how individual cell decisions influence the dynamics at the tissue level. Here, we study spatio-temporal pattern formation in a population of cells exhibiting phenotypic plasticity, which is a paradigm of cell decision making. We focus on the migration/resting and the migration/proliferation plasticity which underly the epithelial-mesenchymal transition (EMT) and the go or grow dichotomy. We assume that cells change their phenotype in order to minimize their microenvironmental entropy (LEUP: Least microEnvironmental Uncertainty Principle) and study the impact of the LEUP-driven migration/resting and migration/proliferation plasticity on the corresponding multicellular spatio-temporal dynamics with a stochastic cell-based mathematical model for the spatio-temporal dynamics of the cell phenotypes. In the case of the go or rest plasticity, a corresponding mean-field approximation allows to identify a bistable switching mechanism between a diffusive (fluid) and an epithelial (solid) tissue phase which depends on the sensitivity of the phenotypes to the environment. For the go or grow plasticity, we show the possibility of Turing pattern formation for the solid tissue phase and its relation with the parameters of the LEUP-driven cell decisions.
A fabrication method for positioning and embedding a single-walled carbon nanotube (SWNT) across the diameter of a solid state nanopore is presented. Chemical vapor deposition (CVD) is used to grow SWNTs over arrays of focused ion beam (FIB) milled pores in a thin silicon nitride membrane. This typically yields at least one pore whose diameter is centrally crossed by a SWNT. The final diameter of the FIB pore is adjusted to create a nanopore of any desired diameter by atomic layer deposition (ALD), simultaneously embedding and insulating the SWNT everywhere but in the region that crosses the diameter of the final nanopore, where it remains pristine and bare. This nanotube-articulated nanopore is an important step towards the realization of a new type of detector for biomolecule sensing and electronic characterization, including DNA sequencing.
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