Several mechanisms can extend the equilibrium domain of a liquid phase into the solid region of the normal phase diagram. The causes of premelting, which include surface melting, interface curvature and substrate disorder, occur in all types of substances, including HzO. In the case of H20, premelting can have important environmental consequences, among which are the heaving of frozen ground, breakdown of rock and concrete, sintering of snow, flow of glaciers, scavenging of atmospheric traw gases by snow and ice, and the electrification of thunderclouds. This article reviews the basic mechanisms of premelting and discusses their roles in the environmental phenomena. The principal results of numerous studies are reviewed, and trends in current research are outlined.

Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/ β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.glypican | neuroblastoma | single-domain antibody | chimeric antigen receptor T-cell therapy | immunotoxin