The phase shift of line solitons for the KP-II equation

The KP-II equation was derived by [B. B. Kadomtsev and V. I. Petviashvili,Sov. Phys. Dokl. vol.15 (1970), 539-541] to explain stability of line solitary waves of shallow water. Stability of line solitons has been proved by [T. Mizumachi, Mem. of vol. 238 (2015), no.1125] and [T. Mizumachi, Proc. Roy. Soc. Edinburgh Sect. A. vol.148 (2018), 149--198]. It turns out the local phase shift of modulating line solitons are not uniform in the transverse direction. In this paper, we obtain the $L^\infty$-bound for the local phase shift of modulating line solitons for polynomially localized perturbations

Measles virus causes immunogenic cell death in human melanoma

Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response

Energy dispersed large data wave maps in 2+1 dimensions

In this article we consider large data Wave-Maps from $\mathbb{R}^{2+1}$ into a compact Riemannian manifold $(\mathcal{M},g)$, and we prove that regularity and dispersive bounds persist as long as a certain type of bulk (non-dispersive) concentration is absent. In a companion article we use these results in order to establish a full regularity theory for large data Wave-Maps.Comment: 89 page

Roles of cholecystokinin receptor phosphorylation in agonist-stimulated desensitization of pancreatic acinar cells and receptorbearing Chinese hamster ovary cholecystokinin receptor cells

SUMMARY Receptor phosphorylation has been implicated in desensitization responses to some agonist ligands, in which receptors may become uncoupled from G proteins and move into cellular compartments inaccessible to hydrophilic ligands. Understanding of the linkage between these processes, however, has come largely from recombinant receptor-bearing cell systems with consensus sites of kinase action mutagenized. We recently established methodology permitting direct assessment of sites of phosphorylation of the cholecystokinin receptor (CCKR) in its native milieu in the pancreatic acinar cell and in a Chinese hamster ovary (CHO)-CCKR cell line (1, 2). Although CCK binding leads to phosphorylation of serine residues within the third intracellular loop of the receptor in both cell types, there are clear differences in the time course of phosphorylation, in the balance of action of kinases and a receptor phosphatase, and in a few of the distinct sites phosphorylated. In this work, we have directly assessed the inositol 1,4,5-triphosphate responses to CCK and desensitization of these responses in both cells. CHO cell lines expressing receptor mutants with protein kinase C consensus sites modified were also studied. CCK-stimulated inositol 1,4,5-triphosphate responses in both cells expressing wild-type receptors were rapidly and completely desensitized, associated with the onset of receptor phosphorylation. However, despite maintenance of the phosphorylated state of the receptor in the CHO-CCKR cell and its dephosphorylation returning the receptor to its basal state in the acinar cell, desensitization continued to be present in both. Mutagenesis of Ser260 and Ser264 to alanines individually reduced receptor phosphorylation by approximately 50%, whereas the dual mutant completely eliminated agonist-stimulated phosphorylation. Because other sites of phosphorylation were still intact in this construct, this raises the possibility of hierarchical phosphorylation with these two sites key in making other sites accessible to kinases. Constructs modifying Ser264 delayed the onset of desensitization, whereas all constructs proceeded to achieve complete desensitization by 10 min. Receptor internalization occurred independent of its phosphorylation state in the CHO cell lines, explaining the desensitization observed. In the acinar cell in which the receptor remains on the cell surface after agonist occupation, we postulate that receptor insulation achieves similar uncoupling from G protein association as is achieved by receptor phosphorylation early after agonist occupation. Eukaryotic cells use a variety of mechanisms to dampen their responses to sustained hormonal agonist stimulation. Among these mechanisms for desensitization are processes involving the receptor itself, including uncoupling from G protein signal transducers and movement into cellular compartments inaccessible to hydrophilic ligands (3-7). A key regulatable and reversible biochemical modification of the receptor that has been implicated in these events in selected systems is phosphorylation (8). However, it has been difficult to correlate specific receptor phosphorylation events with specific desensitization or resensitization events because a detailed understanding of this covalent modification is only available for a few receptors in this superfamily. Also, most of our insights come from recombinant receptor-bearing cells in which consensus sites of action of kinases have been mutagenized. We have extensive information about the phosphorylation of the CCKR as it resides in its natural setting in pancreatic acinar cells, as well as in recombinant receptor-bearing cell