Harnessing Soluble NK Cell Killer Receptors for the Generation of Novel Cancer Immune Therapy

The natural cytotoxic receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The NCRs, which include three members; NKp46, NKp44 and NKp30, are critically involved in NK cytotoxicity against different targets, including a wide range of tumor cells derived from various origins. Even though the tumor ligands of the NCRs have not been identified yet, the selective manner by which these receptors target tumor cells may provide an excellent basis for the development of novel anti-tumor therapies. To test the potential use of the NCRs as anti-tumor agents, we generated soluble NCR-Ig fusion proteins in which the constant region of human IgG1 was fused to the extracellular portion of the receptor. We demonstrate, using two different human prostate cancer cell lines, that treatment with NKp30-Ig, dramatically inhibits tumor growth in vivo. Activated macrophages were shown to mediate an ADCC response against the NKp30-Ig coated prostate cell lines. Finally, the Ig fusion proteins were also demonstrated to discriminate between benign prostate hyperplasia and prostate cancer. This may provide a novel diagnostic modality in the difficult task of differentiating between these highly common pathological conditions

REACTIVITY OF CHLOROPHYLL a/b-PROTEINS AND MICELLAR TRITON X-100 COMPLEXES OF CHLOROPHYLLS a OR b WITH BOROHYDRIDE

The reaction of several plant chlorophyll-protein complexes with NaBH4 has been studied by absorption spectroscopy. In all the complexes studied, chlorophyll b is more reactive than Chi a, due to preferential reaction of its formyl substituent at C-7. The complexes also show large variations in reactivity towards NaBH4 and the order of reactivity is: LHCI > PSII complex > LHCII > PSI > P700 (investigated as a component of PSI). Differential pools of the same type of chlorophyll have been observed in several complexes. Parallel work was undertaken on the reactivity of micellar complexes of chlorophyll a and of chlorophyll b with NaBH4 to study the effect of aggregation state on this reactivity. In these complexes, both chlorophyll a and b show large variations in reactivity in the order monomer > oligomer > polymer with chlorophyll b generally being more reactive than chlorophyll a. It is concluded that aggregation decreases the reactivity of chlorophylls towards NaBH4 in vitro, and may similarly decrease reactivity in naturally-occurring chlorophyll-protein complexes

On the asymptotic and practical complexity of solving bivariate systems over the reals

This paper is concerned with exact real solving of well-constrained, bivariate polynomial systems. The main problem is to isolate all common real roots in rational rectangles, and to determine their intersection multiplicities. We present three algorithms and analyze their asymptotic bit complexity, obtaining a bound of \sOB(N^{14}) for the purely projection-based method, and \sOB(N^{12}) for two subresultant-based methods: this notation ignores polylogarithmic factors, where $N$ bounds the degree and the bitsize of the polynomials. The previous record bound was \sOB(N^{14}). Our main tool is signed subresultant sequences. We exploit recent advances on the complexity of univariate root isolation, and extend them to sign evaluation of bivariate polynomials over two algebraic numbers, and real root counting for polynomials over an extension field. Our algorithms apply to the problem of simultaneous inequalities; they also compute the topology of real plane algebraic curves in \sOB(N^{12}), whereas the previous bound was \sOB(N^{14}). All algorithms have been implemented in MAPLE, in conjunction with numeric filtering. We compare them against FGB/RS, system solvers from SYNAPS, and MAPLE libraries INSULATE and TOP, which compute curve topology. Our software is among the most robust, and its runtimes are comparable, or within a small constant factor, with respect to the C/C++ libraries. Key words: real solving, polynomial systems, complexity, MAPLE softwareComment: 17 pages, 4 algorithms, 1 table, and 1 figure with 2 sub-figure