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A commonly used routine in seismic signal processing is deconvolution, which comprises two operations: reflectivity detection and magnitude estimation. Existing statistical detectors are computationally expensive. In the paper, a Hopfield neural network is constructed to perform the reflectivity detection operation. The basic idea is to represent the reflectivity detection problem by an equivalent optimization problem and then construct a Hopfield neural network to solve this optimization problem. The neural detector is applied to a synthetic seismic trace and 30 real seismic traces. The processing results show that the accuracy of the neural detector is about the same as that of the existing detectors, but the speed of the neural detector is much faster. >

Fifty-three patients with facial spasm were treated by acupuncture therapy. Taichong (LR 3), Fengchi (GB 20), Yifeng (TE 17), and Sanyinjiao (SP 6) were selected as main points, and others points were selected based on symptom. Of the 53 cases, 9 cases were cured, 13 cases were markedly effective, 27 cases were effective, and 4 cases were ineffective, with an effective rate of 92.5%.

Cross-presentation of exogenous antigens by host professional antigen-presenting cells (APCs) plays a pivotal role in the initiation and development of T-cell immune responses to tumor-associated antigens, including self or mutated self-antigens derived from tumor cells, and foreign antigens derived from infectious agents. Cross-presentation requires multiple steps that involve the antigens' synthesis and compartmentalization in donor cells, packaging and delivery, and processing and presentation by MHC class I molecules on professional APCs. The intricate pathways that lead to protein degradation and the formation of MHC I-peptide complexes inside the APC are well documented for both soluble and particulate antigens. However, much less is known about how cross-presentation is regulated by the protein degradation pathways in antigen-donor cells (ADCs), including autophagy-mediated lysosomal proteolysis and proteasomal degradation. The exact nature or form of the antigens derived from donor cells at the time of delivery to the APC for cross-presentation is very controversial.

A highly efficient asymmetric hydrogenation of racemic acyclic alpha-amino aliphatic ketones via dynamic kinetic resolution has been realized, providing chiral amino alcohols in excellent enantioselectivities and diastereoselectivities. A hydrogen-bonding transition state mode was proposed for explaining the high diastereoselectivity and enantioselectivity of the reaction.

A highly efficient copper-catalyzed asymmetric carbenoid insertion into O−H bonds of phenols has been realized by using chiral spiro bisoxazoline ligands, affording α-aryloxypropionates and the related propionic acids in high yields with excellent enantiomeric excesses.

A highly efficient nickel-catalyzed asymmetric reductive coupling of dienes and aldehydes has been realized by using bulky spirobiindane phosphoramidite ligands, affording bishomoallylic alcohols in high yields with excellent diastereoselectivities and enantioselectivities.

We propose an identification scheme for nonlinear discrete-time systems using fuzzy systems that takes the specific internal structure of the fuzzy system explicitly into consideration. We first design a fuzzy system and give the upper bound of its approximation error to a general nonlinear function. Then we propose a projection algorithm to turn the parameters in the fuzzy identification model and prove that the parameter error is nonincreasing and the identification error converges to an error band which can be made arbitrarily small by properly designing the fuzzy system. We also determine conditions under which the parameters converge.

Relapsed, refractory Hodgkin’s or non-Hodgkin’s lymphoma remains to be a challenge and lacks efficient treatment. A small number of tumor cells that escape from treatment become resistant or unresponsive to chemotherapeutic agents. These cells grow rapidly and soon regenerate into large tumors. Immune vaccination with dendritic cells (DCs) efficiently inhibits growth of small size tumor only. The progression of tumors induces accumulation of Gr-1+CD11b+ myeloid derived suppressor cells (MDSCs) in the lymphatic organs and vicinity of tumor cells. MDSCs enable tumor cells to escape from host or exogenous immune cells mediated surveillance and attack. Gemcitabine is the chemotherapeutic agent used for lymphoma treatment. Gemcitabine has been reported to selectively eliminate MDSCs in tumor bearing animals. Thus, gemcitabine not only eliminates the majority of tumor to leave fewer resistant cells, it also reduces MDSCs to improve the immune environment favorable for the subsequent tumor vaccination. In this presentation, we used A20 cells to establish a large size, murine B-cell lymphoma model. We confirmed the accumulation of MDSCs in the spleen of lymphoma-bearing mice. Gemcitabine induced increased apoptosis in isolated, cultured MDSCs. In vivo injection of gemcitabine eliminated the majority of MDSCs in the spleen of lymphoma-bearing mice. Gemcitabine treatment combined with intratumoral injection of DCs markedly reduced the size of tumor, and significantly improved the survival of the lymphoma-bearing mice. We demonstrated that intra-large-size-lymphoma injection with inactivated DCs in combination with gemcitabine chemotherapy enhanced the therapeutic efficacy of either DC-based vaccination or chemotherapeutic reagent alone. Together with other studies, our report supports the hypothesis that gemcitabine-mediated reduction in MDSCs significantly reduces the immune suppression in tumor-bearing animal environment. This study established novel experimental foundation for the combination of immune-chemotherapy to treat relapsed or refractory lymphoma in large size with enhanced efficacy. Disclosures: No relevant conflicts of interest to declare.

There is considerable interest in developing approaches to specifically target tumor progenitor cells. Our previous results demonstrated that adoptive transfer of CD4+ and CD8+ T cells primed with a breast cancer progenitor vaccine inhibited the progression of spontaneous primary tumors in neuN mice. Interestingly, post-treatment serum but not pre-treatment serum was reactive with surface molecules on the vaccine cells. This indicates that the transferred T cells resulted in uptake of tumor antigens and stimulation of host B cells. To characterize the antigenic targets, we generated hybridomas from spleen cells derived from treated mice. Three candidate clones which were strongly reactive with a neu-negative variant tumor line were subjected to two rounds of limiting dilution cloning. The mAb prepared from hybridoma #1 (IgG1) and hybridoma #2 (IgG2b) were each reactive against two independent tumor lines derived from spontaneous breast tumors in neuN mice (C2D1 and MMC5) when these cells were maintained in serum-free culture medium as tumorspheres. There was no reactivity against the same tumor cell lines when cultured as adherent monolayers in serum-containing medium nor was there reactivity against 3T3 adherent or tumorsphere cultures. Our previous analysis of tumorsphere cultures of C2D1 and MMC5 indicated that they express a panel of markers associated with tumor progenitor cells and have markedly enhanced per-cell tumorigenicity. Two of these antibodies have been purified by protein G or Protein A columns and retain binding to C2D1-tumorsphere cells, but not to C2D1 adherent cells. Importantly, these two antibodies can also bind to cultured 4T1-tumorsphere cells, an additional breast cancer cell line arising initially in BALB/c mice. These studies will allow us to identity corresponding antigens and determine expression on a broader array of spontaneous breast carcinomas in neuN mice. The epitopes recognized by these mAbs, which are expressed on progenitor cells from multiple tumor lines, might have importance as an immunotherapy target. Citation Format: Li-Xin Wang, Mona Patel, Michael Berk, Gregory E. Plautz. Monoclonal antibodies derived in neuN mice following successful T cell therapy of spontaneous breast tumors are specific for tumor progenitor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2853. doi:10.1158/1538-7445.AM2013-2853

Highly enantioselective direct vinylogous Michael reactions of γ-aryl-substituted deconjugated butenolides with maleimides, catalyzed by only 1 mol% bifunctional squaramides derived from cinchona alkaloids, were achieved with excellent yields (up to 96%) and enantioselectivities (up to 97% ee). This protocol features a very low catalyst loading, mild reaction conditions and provides a potential and effective method for the construction of optically active chiral butenolides with adjacent quaternary and tertiary stereocenters.

The first organocatalytic asymmetric sequential allylic alkylation–cyclization of Morita–Baylis–Hillman carbonates and 3-hydroxyoxindoles has been developed to afford spirooxindoles bearing α-methylene-γ-butyrolactone motifs in 25–85% yield, 60–94% ee and up to >20 : 1 diastereoselectivity.

A stereoselective [3+2] cycloaddition of isocyanoesters to methyleneindolinones catalyzed by a quinine-based thiourea-tertiary amine has been successfully developed. Just by tuning the protecting groups on substrates, a variety of optically enriched 3,3'-pyrrolidinyl spirooxindole diastereomers could be obtained in excellent enantioselectivities (up to 99% ee).

Diamond films with high preferential orientation (111) on silicon (100) crystalline orientation substrates had been obtained by hot-filament chemical vapor deposition (HFCVD) method. X-ray diffraction (XRD), scanning electron microscopy (SEM), Raman spectroscopy, and high-resolution cross-sectional transmission electron microscopy (HREM) are used to characterizate the structure and morphology of the synthesised diamond films. Diamond (111) plans had been local grown epitaxially on the Si(100) substrate observed by HREM. SEM photographes show that plane diamond crystals have been obtained.

Novel monodentate phosphorus ligands containing the 1,1'-spirobiindane backbone have been synthesized and applied in the asymmetric rhodium-catalyzed hydrogenation of functionalized olefins, providing excellent enantioselectivities (up to 99.3% ee).

To investigate factors which regulate T-cell mediated therapy of primary breast tumors in situ, we utilized neu-N transgenic mice. These neu-tolerant mice develop spontaneous breast tumors, several of which we have established as aggressive transplantable tumors and selected stem-like progenitor cells in vitro. We vaccinated neu-N mice with irradiated neupos breast cancer progenitor cells to prime T cells in draining LNs. We purified a minor subset (5% to 10%) of LN cells with a CD62Llow CD4+ or CD8+ phenotype representing recently activated effector cells. CD4 and CD8 subsets were separately activated in vitro with anti-CD3/IL-2/IL-7 for two stimulation cycles to induce 200-fold numerical expansion. Hosts bearing spontaneous primary breast tumors average 80 mm2 were treated with 35 × 106 of each CD4+ and CD8+ subsets. Even though the neu-tolerant hosts did not receive lymphodepletion prior to T cell transfer, the T cells significantly delayed tumor growth compared with untreated control mice (n=4 per group, p=0.037). This extends our previous work showing effective T cell therapy of inoculated lung metastases to primary in situ neu-N breast tumors. Neu is a transmembrane tumor antigen with shared expression between vaccine cells and spontaneous tumors that could contribute to the anti-tumor response. We also searched for evidence of response against other cross-reactive antigens. Interestingly, treated mice developed a humoral response and post-treatment serum IgG bound to neuneg variant tumor cells as well as neupos cell lines whereas pre-treatment serum was non-reactive. The development of an IgG serologic response following effective T cell-mediated therapy (in the absence of co-transferred B cells) indicates that transferred CD4+ T cells provided cognate helper function and immunoglobulin class switch signals to B cells and reversed tolerance to neu as well as other shared tumor antigens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 771. doi:10.1158/1538-7445.AM2011-771

A series of primary-tertiary diamine catalysts were successfully applied to promote the enantioselective aldol reaction of acetone with β,γ-unsaturated α-keto esters in excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

Compared with well-established electrophilic π-allylpalladium chemistry, the catalytic asymmetric reactions via umpolung of π-allylpalladium have received limited success. Although extensive efforts have been devoted, only modest enantioselectivities have been obtained in the palladium-catalyzed asymmetric umpolung allylation reactions. In this context, we disclose a highly enantioselective palladium-catalyzed umpolung allylation of aldehydes with allylic alcohols and their derivatives. By using sterically hindered chiral monodentate spiro phosphite ligands, we have accomplished the asymmetric allylation reaction with high yields and excellent enantioselectivities (up to 97% ee). These results represent the highest level of enantioselectivity for the umpolung allylation reactions. The present palladium-catalyzed asymmetric allylation reaction uses readily available allylic alcohols and their derivatives instead of sensitive allylic organometallic reagents, which provides a competitive alternative approach for preparation of versatile chiral homoallylic alcohols. A preliminary mechanism of palladium-catalyzed umpolung allylation reaction was discussed based on the experimental observations.

In the title compound, [Cu(NO(3))(2)(C(18)H(16)N(2)O(2))], the Cu(II) ion is six-coordinated in a Jahn-Teller-distorted octa-hedral environment defined by two O and two N atoms from the ligand and two O atoms from two monodentate nitrate anions.

There is growing evidence that a variety of tumors including breast cancer may be driven by a small subset of cancer stem/progenitor cells that exhibit chemotherapeutic resistance and cause tumor relapse. The eradication of this small subset of cells might improve therapeutic outcome. However, it is unknown whether breast cancer stem/progenitor cells are susceptible to T-cell mediated immunotherapy. We used defined serum-free conditions to establish primary neupos BCSC lines. Spontaneous breast tumors arising in neu-N transgenic mice were passaged in vivo to generate progressor lines and tumors were harvested and prepared as a single cell suspension. Paired aliquots of tumor cells were cultured in either serum-free medium supplemented with EGF and bFGF to derive BCSC sub-lines, or alternatively in standard serum-containing medium to generate mouse mammary carcinoma (MMC) sub-lines. The BCSC cells display morphologic characteristics of breast cancer stem/progenitor cells, such as non-attached growth in spheroid colonies, and high expression of CD44. We vaccinated neu-N transgenic mice with 2×107 irradiated MMC10-BCSC or its paired cell line MMC10-AD and harvested vaccine-draining lymph nodes 9 days later. Antigen-primed CD62Llow cells were isolated using MACS beads and CD62LlowCD4+ or CD62LlowCD8+ T cells were additionally purified and stimulated with anti-CD3/IL-2/IL-7 for two stimulation cycles. Adoptive transfer of 3×107 CD62Llow CD4+ cells from MMC10-BCSC-draining LNs effectively eradicated pulmonary metastases (p0.05 vs. control). In an independent experiment, adoptive transfer of 3×107 CD8+ T cells sensitized by MMC10-BCSCs mediated the regression of established MMC10 pulmonary metastasis (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1929.

An efficient Michael–ketone aldol–dehydration domino reaction has been developed to afford spiro[cyclohex-2-enone-oxindole] motifs with high yields (up to 99%), excellent diastereoselectivities (dr >20 : 1) and enantioselectivities (up to 96% ee).

Fuzzy systems are represented as series expansions of fuzzy basis functions which are algebraic superpositions of fuzzy membership functions. Using the Stone-Weierstrass theorem, it is proved that linear combinations of the fuzzy basis functions are capable of uniformly approximating any real continuous function on a compact set to arbitrary accuracy. Based on the fuzzy basis function representations, an orthogonal least-squares (OLS) learning algorithm is developed for designing fuzzy systems based on given input-output pairs; then, the OLS algorithm is used to select significant fuzzy basis functions which are used to construct the final fuzzy system. The fuzzy basis function expansion is used to approximate a controller for the nonlinear ball and beam system, and the simulation results show that the control performance is improved by incorporating some common-sense fuzzy control rules. >

Tumor infiltrating lymphocytes (TIL) have demonstrated therapeutic effects in adoptive cell therapy of melanoma, and there is great interest in optimizing this response. However, the role of lymphocytes during tumor initiation and progression is complex and evolves over time. We have identified two distinct subsets of TIL that have divergent effector vs. regulatory function in murine tumor models. These subsets can be efficiently segregated in vitro based on differential expression of L-selectin (CD62L). Although initially present in small numbers, they can be activated in vitro with anti-CD3 mAb and expanded with a combination of IL-2 and IL-7 to provide sufficient numbers for adoptive transfer into secondary hosts with advanced tumors. Our initial studies demonstrated that the TIL CD62L-low subset is a mixture of CD4 and CD8 cells that individually or in combination mediate tumor-specific regression. By contrast, the CD62L-high subset, which is exclusively CD8+, does not have therapeutic efficacy. Moreover, when CD62Lhigh TIL are co-transferred with CD62L-low effector cells they abrogate their therapeutic efficacy, thus they have suppressor function. Because L-selectin is involved in lymphocyte homing to secondary lymphoid tissues, we hypothesized that the CD62L-high TIL cells might preferentially re-circulate into lymph nodes and inhibit primary sensitization of naïve T cells to tumor antigens. Tumor cells were inoculated subcutaneously, alone or with either CD62L-high TIL or CD62L-low TIL. The CD62L-high TIL actually enhanced the growth of subcutaneous tumors whereas the CD62L-low cells prevented tumor growth. More importantly, tumor-draining lymph nodes were harvested twelve days later and activated in vitro with anti-CD3 and IL-2/IL-7 for adoptive cell transfer to secondary tumor-bearing hosts. The presence of TIL suppressor cells during sensitization of tumor-draining lymph node cells partially inhibited the development of tumor-reactive effector cells. This inhibition was not tumor-antigen specific because TIL suppressor cells derived from the MCA205 fibrosarcoma were able to inhibit sensitization of B16/F10 draining lymph node effector cells. These data suggest that tumors acquire a population of CD8 CD62L-high T cells that can inhibit other effector T cells. The suppressor TIL cells also appear to modulate the tumor stroma to promote tumor growth and modulate antigen-presenting cells that migrate to draining lymph nodes thereby dampening the development of effector cells. Studies are ongoing to determine the mechanism of suppressor function.

Three structured networks and their corresponding training algorithms are proposed for matrix QR factorization eigenvalue and eigenvector determination, and Lyapunov equation solving. The basic procedure behind these approaches is as follows: represent a given problem by a structured network, train this structured network to match some desired patterns, and obtain the solution to the problem from the weights of the resulting structured network. A general-purpose programmable network architecture is proposed which can be programmed to solve different problems. Simulation results showed that the proposed approaches worked quite well. >