Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation

Effective inhibitors of osteopontin (OPN)-mediated neoplastic transformation and metastasis are still lacking. (-)-Agelastatin A is a naturally occurring oroidin alkaloid with powerful antitumor effects that, in many cases, are superior to cisplatin in vitro. In this regard, past comparative assaying of the two agents against a range of human tumor cell lines has revealed that typically (-)-agelastatin A is 1.5 to 16 times more potent than cisplatin at inhibiting cell growth, its effects being most pronounced against human bladder, skin, colon, and breast carcinomas. In this study, we have investigated the effects of (-)-agelastatin A on OPN-mediated malignant transformation using mammary epithelial cell lines. Treatment with (-)-agelastatin A inhibited OPN protein expression and enhanced expression of the cellular OPN inhibitor, Tcf-4. (-)-Agelastatin A treatment also reduced beta-catenin protein expression and reduced anchorage-independent growth, adhesion, and invasion in R37 OPN pBK-CMV and C9 cell lines. Similar effects were observed in MDA-MB-231 and MDA-MB-435s human breast cancer cell lines exposed to (-)-agelastatin A. Suppression of Tcf-4 by RNA interference (short interfering RNA) induced malignant/invasive transformation in parental benign Rama 37 cells; significantly, these events were reversed by treatment with (-)-agelastatin A. Our study reveals, for the very first time, that (-)-agelastatin A down-regulates beta-catenin expression while simultaneously up-regulating Tcf-4 and that these combined effects cause repression of OPN and inhibition of OPN-mediated malignant cell invasion, adhesion, and colony formation in vitro. We have also shown that (-)-agelastatin A inhibits cancer cell proliferation by causing cells to accumulate in the G(2) phase of cell cycle.

A Novel Packet Marking Function for Real-Time Interactive MPEG-4 Video Applications in a Differentiated Services Network

The future convergence of voice, video and data applications on the Internet requires that next generation technology provides bandwidth and delay guarantees. Current technology trends are moving towards scalable aggregate-based systems where applications are grouped together and guarantees are provided at the aggregate level only. This solution alone is not enough for interactive video applications with sub-second delay bounds. This paper introduces a novel packet marking scheme that controls the end-to-end delay of an individual flow as it traverses a network enabled to supply aggregate- granularity Quality of Service (QoS). IPv6 Hop-by-Hop extension header fields are used to track the packet delay encountered at each network node and autonomous decisions are made on the best queuing strategy to employ. The results of network simulations are presented and it is shown that when the proposed mechanism is employed the requested delay bound is met with a 20% reduction in resource reservation and no packet loss in the network.

Design flow for efficient FPGA reconfiguration

In Run Time Reconfiguration (RTR) systems, the amount of reconfiguration is considerable when compared to the circuit changes implemented. This is because reconfiguration is not considered as part of the design flow. This paper presents a method for reconfigurable circuit design by modeling the underlying FPGA reconfigurable circuitry and taking it into consideration in the system design. This is demonstrated for an image processing example on the Xilinx Virtex FPGA.