The Plasminogen Activation System and the Regulation of Catecholaminergic Function

The local environment of neurosecretory cells contains the major components of the plasminogen activation system, including the plasminogen activators, tissue plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), as well as binding sites for t-PA, the receptor for u-PA (uPAR), and also the plasminogen activator inhibitor, PAI-1. Furthermore, these cells express specific binding sites for plasminogen, which is available in the circulation and in interstitial fluid. Colocalization of plasminogen and its activators on cell surfaces provides a mechanism for promoting local plasminogen activation. Plasmin is retained on the cell surface where it is protected from its inhibitor, α2-antiplasmin. In neurosecretory cells, localized plasmin activity provides a mechanism for extracellular processing of secreted hormones. Neurotransmitter release from catecholaminergic cells is negatively regulated by cleavage products formed by plasmin-mediated proteolysis. Recently, we have identified a major plasminogen receptor, Plg-RKT. We have found that Plg-RKT is highly expressed in chromaffin cells of the adrenal medulla as well as in other catecholaminergic cells and tissues. Plg-RKT-dependent plasminogen activation plays a key role in regulating catecholaminergic neurosecretory cell function

Poxvirus-Encoded Gamma Interferon Binding Protein Dampens the Host Immune Response to Infection

Ectromelia virus (ECTV), a natural mouse pathogen and the causative agent of mousepox, is closely related to variola virus (VARV), which causes smallpox in humans. Mousepox is an excellent surrogate small-animal model for smallpox. Both ECTV and VARV encode a multitude of host response modifiers that target components of the immune system and that are thought to contribute to the high mortality rates associated with infection. Like VARV, ECTV encodes a protein homologous to the ectodomain of the host gamma interferon (IFN-γ) receptor 1. We generated an IFN-γ binding protein (IFN-γbp) deletion mutant of ECTV to study the role of viral IFN-γbp (vIFN-γbp) in host-virus interaction and also to elucidate the contribution of this molecule to the outcome of infection. Our data show that the absence of vIFN-γbp does not affect virus replication per se but does have a profound effect on virus replication and pathogenesis in mice. BALB/c mice, which are normally susceptible to infection with ECTV, were able to control replication of the mutant virus and survive infection. Absence of vIFN-γbp from ECTV allowed the generation of an elective host immune response that was otherwise diminished by this viral protein. Mice infected with a vIFN-γbp deletion mutant virus, designated ECTV-IFN-γbpΔ, produced increased levels of IFN-γ and generated robust cell-mediated and antibody responses. Using several strains of mice that exhibit differential degrees of resistance to mousepox, we show that recovery or death from ECTV infection is determined by a balance between the host's ability to produce IFN-γ and the virus' ability to dampen its effects

Analysis of Gga Null Mice Demonstrates a Non-Redundant Role for Mammalian GGA2 during Development

Numerous studies using cultured mammalian cells have shown that the three GGAs (Golgi-localized, gamma-ear containing, ADP-ribosylation factor- binding proteins) function in the transport of cargo proteins between the trans- Golgi network and endosomes. However, the in vivo role(s) of these adaptor proteins and their possible functional redundancy has not been analyzed. In this study, the genes encoding GGAs1-3 were disrupted in mice by insertional mutagenesis. Loss of GGA1 or GGA3 alone was well tolerated whereas the absence of GGA2 resulted in embryonic or neonatal lethality, depending on the genetic background of the mice. Thus, GGA2 mediates a vital function that cannot be compensated for by GGA1and/or GGA3. The combined loss of GGA1 and GGA3 also resulted in a high incidence of neonatal mortality but in this case the expression level of GGA2 may be inadequate to compensate for the loss of the other two GGAs. We conclude that the three mammalian GGAs are essential proteins that are not fully redundant

Non-linear Static Analysis of Offshore Steep Wave Riser

A new solution combining finite difference method and shooting method is developed to analyze the behavior of steep wave riser suffering from current loading. Based on the large deformation beam theory and mechanics equilibrium principle, a set of non-linear ordinary differential equations describing the motion of the steep wave riser are obtained. Then, finite difference method and shooting method are adopted and combined to solve the ordinary differential equations with zero moment boundary conditions at both the seabed end and surface end of the steep wave riser. The resulting non-linear finite difference formulations can be solved effectively by Newton-Raphson method. To improve iterative efficiency, shooting method is also employed to obtain the initial value for Newton-Raphson method. Results are compared with that of FEM by OrcaFlex, to verify the accuracy and reliability of the numerical method

Non-linear Static Analysis of Offshore Steep Wave Riser

A new solution combining finite difference method and shooting method is developed to analyze the behavior of steep wave riser suffering from current loading. Based on the large deformation beam theory and mechanics equilibrium principle, a set of non-linear ordinary differential equations describing the motion of the steep wave riser are obtained. Then, finite difference method and shooting method are adopted and combined to solve the ordinary differential equations with zero moment boundary conditions at both the seabed end and surface end of the steep wave riser. The resulting non-linear finite difference formulations can be solved effectively by Newton-Raphson method. To improve iterative efficiency, shooting method is also employed to obtain the initial value for Newton-Raphson method. Results are compared with that of FEM by OrcaFlex, to verify the accuracy and reliability of the numerical method

Non-linear Static Analysis of Offshore Steep Wave Riser

A new solution combining finite difference method and shooting method is developed to analyze the behavior of steep wave riser suffering from current loading. Based on the large deformation beam theory and mechanics equilibrium principle, a set of non-linear ordinary differential equations describing the motion of the steep wave riser are obtained. Then, finite difference method and shooting method are adopted and combined to solve the ordinary differential equations with zero moment boundary conditions at both the seabed end and surface end of the steep wave riser. The resulting non-linear finite difference formulations can be solved effectively by Newton-Raphson method. To improve iterative efficiency, shooting method is also employed to obtain the initial value for Newton-Raphson method. Results are compared with that of FEM by OrcaFlex, to verify the accuracy and reliability of the numerical method

Exploiting Relationship for Complex-scene Image Generation

The significant progress on Generative Adversarial Networks (GANs) has facilitated realistic single-object image generation based on language input. However, complex-scene generation (with various interactions among multiple objects) still suffers from messy layouts and object distortions, due to diverse configurations in layouts and appearances. Prior methods are mostly object-driven and ignore their inter-relations that play a significant role in complex-scene images. This work explores relationship-aware complex-scene image generation, where multiple objects are inter-related as a scene graph. With the help of relationships, we propose three major updates in the generation framework. First, reasonable spatial layouts are inferred by jointly considering the semantics and relationships among objects. Compared to standard location regression, we show relative scales and distances serve a more reliable target. Second, since the relations between objects have significantly influenced an object's appearance, we design a relation-guided generator to generate objects reflecting their relationships. Third, a novel scene graph discriminator is proposed to guarantee the consistency between the generated image and the input scene graph. Our method tends to synthesize plausible layouts and objects, respecting the interplay of multiple objects in an image. Experimental results on Visual Genome and HICO-DET datasets show that our proposed method significantly outperforms prior arts in terms of IS and FID metrics. Based on our user study and visual inspection, our method is more effective in generating logical layout and appearance for complex-scenes