Intercellular transfer of shed tumor cell gangliosides

AbstractThree distinct steps underlie immunosuppression by tumor gangliosides: (i) their shedding by the tumor cell, (ii) binding to target leukocytes in the tumor microenvironment, and (iii) action upon the target cell. While shedding is well documented, cell to cell transfer of shed gangliosides is not. To address this, we employed a dual chamber culture system. In this system, metabolically radiolabeled lymphoma cells shed gangliosides into the conditioned medium of the contralateral chamber, which contained normal fibroblasts as the target cell. The shed lymphoma cell gangliosides bound avidly to the target fibroblasts in a trypsin-resistant manner (1−2×106 and 7×106 molecules/fibroblast in 24 and 48 h). Significantly higher than binding rates of purified lymphoma gangliosides added exogenously, these binding rates in a system which models the in vivo microenvironment suggest that cell to cell ganglioside transfer is a highly efficient process

Annotating Student Talk in Text-based Classroom Discussions

Classroom discussions in English Language Arts have a positive effect on students' reading, writing and reasoning skills. Although prior work has largely focused on teacher talk and student-teacher interactions, we focus on three theoretically-motivated aspects of high-quality student talk: argumentation, specificity, and knowledge domain. We introduce an annotation scheme, then show that the scheme can be used to produce reliable annotations and that the annotations are predictive of discussion quality. We also highlight opportunities provided by our scheme for education and natural language processing research

An Optimal Algorithm for Scheduling Reservations in a Bandwidth Market

An algorithm is presented which provides an optimal solution to the problem of scheduling non-relocatable time intervals of bandwidth in differentiated services networks. Simulations found an asymmetry between valuing an interval’s length and bandwidth requirement. Longer intervals requiring less resource are favored over shorter intervals requiring more resource. The optimal algorithm is shown to respond appropriately to price as a mechanism of control whereas the offline greedy and the online FCFS algorithms do not. The solution uses integer programming, and it is shown that, except in the general case, the problem can be solved in polynomial time

Discussion Tracker: Supporting Teacher Learning about Students' Collaborative Argumentation in High School Classrooms

Teaching collaborative argumentation is an advanced skill that many K-12 teachers struggle to develop. To address this, we have developed Discussion Tracker, a classroom discussion analytics system based on novel algorithms for classifying argument moves, specificity, and collaboration. Results from a classroom deployment indicate that teachers found the analytics useful, and that the underlying classifiers perform with moderate to substantial agreement with humans

Seasons Fall 2018 Volume 47 Number 3

Highlights : Thompson-Morris Plot Restoration Complete Botany for Beginners Preserving Our Tree Canopy Three Great Native Trees ArbNet Accreditationhttps://repository.upenn.edu/morrisarboretum_seasons/1000/thumbnail.jp

Seasons Winter/Spring 2019 Volume 48 Number 1

Winter-Flowering Shrubs A Fallen Monarch : The Bender Oak The Architect of the Swan Pond Love Temple Revealed Botany for Beginners - Part II (Conifers) A Royal Exchange (Staff Exchange Program) Nature Playhttps://repository.upenn.edu/morrisarboretum_seasons/1001/thumbnail.jp

Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells

Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight into the mechanisms involved. DC apoptosis was independent of the catabolism of gangliosides since lactosylceramide did not induce cell death. Apoptosis induced by GM3 and GD3 gangliosides was not blocked by inhibitors of de novo ceramide biosynthesis, whereas the acid sphingomyelinase inhibitor desipramine only prevented apoptosis induced by GM3. Furthermore, our results suggest that DC apoptosis was triggered via caspase activation, and it was ROS dependent with GD3 ganglioside, suggesting that GM3 and GD3 induced apoptosis through different mechanisms

Effects of the glucolipid synthase inhibitor, P4, on functional and phenotypic parameters of murine myeloma cells

This study describes the effects of the glucolipid synthase inhibitor P4, (DL-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol), on various functional and phenotypic parameters of 5T33 murine myeloma cells. Cell recovery was reduced by >85% following incubation of the cells for 3 days in the presence of 4 μM P4 (the IC50 concentration). Both cytostatic and cytotoxic inhibition was observed with tumour cell metabolic activity and clonogenic potential reduced to 42% and 14% of controls, respectively, and viability reduced to 52%. A dose-dependent increase in cells undergoing apoptosis (from 7% to 26%) was also found. P4 induced a decrease in the number of cells expressing H-2 Class I and CD44, and a large increase in cells expressing H-2 Class II and the IgG2b paraprotein. It did not affect surface expression of CD45 or CD54 (ICAM-1). Based on these alterations in tumour cell growth, adhesion molecule expression and potential immunogenicity, it is anticipated that P4 will provide a novel therapeutic approach for the treatment of multiple myeloma. In addition, given that essentially all tumours rely heavily on overexpressed or abnormal glucosphingolipids for growth, development and metastasis, glucolipid synthase inhibitors may prove to be universally effective anti-cancer agents. © 1999 Cancer Research Campaig