On the transitional dynamics and policy analysis of the Romer (1990) model

In this paper we prove the existence, uniqueness and saddle-point stability of the steady state (or balanced growth path) of the Romer (1990) model by utilizing the reduction of dimensionality. Furthermore, we found out a set of policy instruments to improve the monopolistic competitive equilibrium allocation up to social optimum

Uniqueness and determinacy of the Romer model

In this paper we prove the existence, uniqueness and saddle-point stability of the steady state (or balanced growth path) of the Romer (1990) model by utilizing the reduction of dimensionality. Furthermore, we found out a set of policy instruments to improve the monopolistic competitive equilibrium allocation up to social optimum

Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins.

Botulinum neurotoxin (BoNT) is one of the most acutely lethal toxins known to humans, and effective treatment for BoNT intoxication is urgently needed. Single-domain antibodies (VHH) have been examined as a countermeasure for BoNT because of their high stability and ease of production. Here, we investigate the structures and the neutralization mechanisms for six unique VHHs targeting BoNT/A1 or BoNT/B1. These studies reveal diverse neutralizing mechanisms by which VHHs prevent host receptor binding or block transmembrane delivery of the BoNT protease domain. Guided by this knowledge, we design heterodimeric VHHs by connecting two neutralizing VHHs via a flexible spacer so they can bind simultaneously to the toxin. These bifunctional VHHs display much greater potency in a mouse co-intoxication model than similar heterodimers unable to bind simultaneously. Taken together, our studies offer insight into antibody neutralization of BoNTs and advance our ability to design multivalent anti-pathogen VHHs with improved therapeutic properties

Construction and validation of safe Clostridium botulinum Group II surrogate strain producing inactive botulinum neurotoxin type E toxoid

Botulinum neurotoxins (BoNTs), produced by the spore-forming bacterium Clostridium botulinum, cause botulism, a rare but fatal illness affecting humans and animals. Despite causing a life-threatening disease, BoNT is a multipurpose therapeutic. Nevertheless, as the most potent natural toxin, BoNT is classified as a Select Agent in the US, placing C. botulinum research under stringent governmental regulations. The extreme toxicity of BoNT, its impact on public safety, and its diverse therapeutic applications urge to devise safe solutions to expand C. botulinum research. Accordingly, we exploited CRISPR/Cas9-mediated genome editing to introduce inactivating point mutations into chromosomal bont/e gene of C. botulinum Beluga E. The resulting Beluga Ei strain displays unchanged physiology and produces inactive BoNT (BoNT/Ei) recognized in serological assays, but lacking biological activity detectable ex- and in vivo. Neither native single-chain, nor trypsinized di-chain form of BoNT/Ei show in vivo toxicity, even if isolated from Beluga Ei sub-cultured for 25 generations. Beluga Ei strain constitutes a safe alternative for the BoNT research necessary for public health risk management, the development of food preservation strategies, understanding toxinogenesis, and for structural BoNT studies. The example of Beluga Ei generation serves as template for future development of C. botulinum producing different inactive BoNT serotypes.Peer reviewe

Global hybrid simulations of soft X-ray emissions in the Earth’s magnetosheath

Earth’s magnetopause is a thin boundary separating the shocked solar wind plasma from the magnetospheric plasmas, and it is also the boundary of the solar wind energy transport to the magnetosphere. Soft X-ray imaging allows investigation of the large-scale magnetopause by providing a two-dimensional (2-D) global view from a satellite. By performing 3-D global hybrid-particle-in-cell (hybrid-PIC) simulations, we obtain soft X-ray images of Earth’s magnetopause under different solar wind conditions, such as different plasma densities and directions of the southward interplanetary magnetic field. In all cases, magnetic reconnection occurs at low latitude magnetopause. The soft X-ray images observed by a hypothetical satellite are shown, with all of the following identified: the boundary of the magnetopause, the cusps, and the magnetosheath. Local X-ray emissivity in the magnetosheath is characterized by large amplitude fluctuations (up to 160%); however, the maximum line-of-sight-integrated X-ray intensity matches the tangent directions of the magnetopause well, indicating that these fluctuations have limited impact on identifying the magnetopause boundary in the X-ray images. Moreover, the magnetopause boundary can be identified using multiple viewing geometries. We also find that solar wind conditions have little effect on the magnetopause identification. The Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission will provide X-ray images of the magnetopause for the first time, and our global hybrid-PIC simulation results can help better understand the 2-D X-ray images of the magnetopause from a 3-D perspective, with particle kinetic effects considered

Crystal structures of OrfX1, OrfX2, and the OrfX1–OrfX3 complex from the orfX gene cluster of botulinum neurotoxin E1

Botulinum neurotoxins (BoNTs) are among the most lethal toxins known to humans, comprising seven established serotypes termed BoNT/A–G encoded in two types of gene clusters (ha and orfX) in BoNT-producing clostridia. The ha cluster encodes four non-toxic neurotoxin-associated proteins (NAPs) that assemble with BoNTs to protect and enhance their oral toxicity. However, the structure and function of the orfX-type NAPs remain largely unknown. Here, we report the crystal structures for OrfX1, OrfX2, and an OrfX1–OrfX3 complex, which are encoded in the orfX cluster of a BoNT/E1-producing Clostridium botulinum strain associated with human foodborne botulism. These structures lay the foundation for future studies on the potential roles of OrfX proteins in oral intoxication and pathogenesis of BoNTs.Peer reviewe