Based on these findings, the FISH assays were highly accurate, with immunohistochemical assays performed with R60 and 10H8 nearly as accurate. The DAKO HercepTest and the Ventana CB11 immunohistochemical assay were statistically significantly different from the Vysis FISH assay in evaluating these previously molecularly characterized breast cancer specimens.

Purpose: To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 (HER-2) testing in outside/local community-based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab (Herceptin)b ased clinical trials. Experimental Design: Breast cancer specimens from 2,600 women were prospectively evaluated by fluorescence in situ hybridization (FISH) for entry into Breast Cancer International Research Group (BCIRG) clinical trials for HER-2-directed therapies. Results: HER-2 gene amplification by FISH was observed in 657 of the 2,502 (26%) breast cancers successfully analyzed. Among 2,243 breast cancers with central laboratory immunohistochemistry (10H8-IHC) analysis, 504 (22.54%) showed overexpression (2+ or 3+). Outside/ local laboratories assessed HER-2 status by immunohistochemistry in 1,536 of these cases and by FISH in 131cases. Overall, the HER-2 alteration status determined by outside/local immunohistochemistry showed a 79% agreement rate [j statistic, 0.56; 95% confidence interval (95% CI), 0.52-0.60], with FISH done by the central laboratories. The agreement rate comparing BCIRG central laboratory 10H8-IHC and outside/local laboratory immunohistochemistry was 77.5% (j statistic, 0.51; 95% CI, 0.46-0.55). Finally, HER-2 status, determined by unspecified FISH assay methods at outside/local laboratories, showed a 92% agreement rate (j statistic, 0.83; 95% CI, 0.73-0.93), with FISH done at the BCIRG central laboratories. Conclusions: Compared with the HER-2 status determined at centralized BCIRG reference laboratories, these results indicate superiority of FISH to accurately and reproducibly assess tumors for the HER-2 alteration at outside/local laboratories for entry to clinical trials.

This paper investigates the issue of accurate reactive, harmonic and imbalance power sharing in a microgrid. Harmonic and imbalance droop controllers are developed to proportionally share the harmonic power and the imbalance power among distributed generation (DG) units and improve the voltage quality at the point of common coupling (PCC). Further, a distributed consensus protocol is developed to adaptively regulate the virtual impedance at fundamental frequency and selected harmonic frequencies. Additionally, a dynamic consensus based method is adopted to restore the voltage to their average voltage. With the proposed methods, the microgrid system reliability and flexibility can be enhanced and the knowledge of the line impedance is not required. And the reactive, harmonic and imbalance power can be proportionally shared among the DG units. Moreover, the quality of the voltage at PCC can be greatly improved. Simulation and experimental results are presented to demonstrate the proposed method.Index Terms-microgrid, adaptive virtual impedance, reactive power sharing, harmonic power sharing, imbalance power sharing, distributed control, consensus protocol. NOMENCLATURE ω DGReference angular frequency of the DG unit ω *The nominal angular frequency of the DG unit E DG The reference voltage magnitude of the DG unit E * The nominal voltage magnitude of the DG unit m n Droop coefficients P Q Measured active and reactive power after low-pass filtering X DGf,i The reactance of DG equivalent positive sequence impedances Q Rated,i The rated reactive powers of DG units E DGh,i Reference harmonic voltage magnitudes of the DG units E DGI,i Reference imbalance voltage magnitudes of the DG units Q Har,i Harmonic power of the i th DG unit Q Imb,i Imbalance power of the i th DG unit n h,i Coefficient of the harmonic droop controller m I,i Coefficient of the imbalance droop controller

Cytogenetic analysis was performed on 16 primary tumors, 2 effusions, and 3 cell lines from 21 patients with non-small cell lung cancer (NSCLC). In 20 patients specimens were obtained prior to initiating cytotoxic therapy. Extensive clonal chromosome alterations were found in all cases. The most frequent numerical changes were polysomy 7 and polysomy 20 (each seen in 12 specimens). In addition, tumor cells from another six cases exhibited partial trisomy 7, with the shortest region of overlap (SRO) at 7p11-p13. Rearrangements of chromosomes 1, 3, 6, 8, 11, 15, 17, and 19 were each observed in nine or more tumors. Breakpoints were clustered at several chromosomal sites, including 1p13, 3p13, 15p11-q11, 17p11, and 19q13. Recurrent loss involving 1p, 3p, 6q, 11p, 15p, 17p, and 19q were each seen in at least eight cases. The SRO of 3p losses was at band 3p21. Double minute chromosomes were found in three tumors. Overall, our findings indicate that even though karyotypes in newly diagnosed NSCLC are very complex, recurrent cytogenetic changes can be identified. The high incidence of loss of 17p (14 of 21 specimens) appears to be compatible with reports implicating the TP53 gene (at band 17p13) as a frequent site for genetic alteration in lung cancer. Moreover, the recurrence of loss of 3p (12 cases) and 11p (10 cases) is also consistent with recent molecular evidence. The existence of other "hot spots" for cytogenetic change, particularly those involving specific regions on chromosomes 7, 15, and 19, warrants further molecular investigation of these sites in NSCLC.

The 1,25-dihydroxy-16-ene-23-yne-vitamin D3 [1,25(OH)2-16-ene-23-yne-D3] is a vitamin D analog that is very potent in inhibiting proliferation and inducing differentiation of myeloid leukemic cells in vitro. Also, 1,25(0H)2-16-ene-23-yne-D3 is 300 times less active in mediating intestinal calcium absorption and bone calcium mobilization as compared to 1,25-dihydroxyvitamin D3 [1,25(OH)2D31, the physiologically active metabolite. Furthermore, 1,25(OH)2-16-ene-23-yne-D3 is 10-25 times less potent than 1,25(OH)2D3 in causing hypercalcemia in BALB/c mice injected intraperitoneally (i.p.) every other day (q.o.d.) for 6 weeks. We explored the therapeutic potential of 1,25(OH)2-16-ene-23-yne-D3 by developing and using the following three leukemia models. Chemotherapy has improved survival of some cancer patients, but alternative approaches are still needed for many malignancies. Phenotypically, most cancer cells have a block in their ability to undergo terminal differentiation; the cells remain in the proliferative pool providing them a growth advantage over their normal counterparts. Induction of terminal differentiation of these cancer cells may be a therapeutic approach. We have used acute myelogenous leukemia as a prototype to study induction of differentiation and inhibition of proliferation of cancer (1). These results prompted us to develop several in vivo models of acute myelogenous leukemia. We found that WEHI 3BD+, a murine myeloid leukemia line (8), can be induced by either 1,25(OH)2D3 or 1,25(OH)2-16-ene-23-yne-D3 to lose clonal proliferative capacity as the cell terminally differentiates. We injected these cells into syngeneic BALB/ c mice; these mice developed and died of leukemia. Treatment of these mice with 1,25(OH)2-16-ene-23-yne-D3 considerably prolonged their survival and possibly even cured some mice. MATERIALS AND METHODS Cells

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Objectives To determine the utility of the amide proton transfer-weighted (APTw) MR imaging in distinguishing solitary brain metastases (SBMs) from glioblastomas (GBMs). Methods Forty-five patients with SBMs and forty-three patients with GBMs underwent conventional and APT-weighted sequences before clinical intervention. The APTw parameters and relative APTw (rAPTw) parameters in the tumor core and the peritumoral brain zone (PBZ) were obtained and compared between SBMs and GBMs. The receiver operating characteristic (ROC) curve was used to assess the best parameter for distinguishing between the two groups. Results The APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the tumor core were not significantly different between the SBM and GBM groups (P=0.141, 0.361, 0.221, 0.305, 0.578 and 0.448, respectively). However, the APTwmax, APTwmin, APTwmean, rAPTwmax, rAPTwmin or rAPTwmean values in the PBZ were significantly lower in the SBM group than in the GBM group (P<0.001). The APTwmin values had the highest area under the ROC curve 0.905 and accuracy 85.2% in discriminating between the two neoplasms. Conclusion As a noninvasive imaging method, APT-weighted MR imaging can be used to distinguish SBMs from GBMs.

A detailed cytogenetic analysis of 63 non-small cell lung carcinomas (NSCLCs) was carried out for identification of recurrent chromosomal alterations. Most specimens displayed very complex karyotypes with multiple numerical and structural changes (median number, 31). Losses of chromosomes 9 (65% of cases) and 13 (71%) were the most frequent numerical changes. Loss of the Y was often observed in tumors from males. Gain of chromosome 7 was also frequent (41%). Chromosome arms 1p, 1q, 3p, 3q, 6q, 7q, 8q, 9p, 11q, 17p, and 19q were particularly prone to rearrangement. The chromosome arm most often contributing to losses was 9p (79%). Other arms that were frequently lost included 3p, 6q, 8p, 9q, 13q, 17p, 18q, 19p, 21q, 22q, and the short arm of each acrocentric chromosome. The percentage of cases with loss of 3p was significantly higher in squamous cell carcinomas (94%) than in adenocarcinomas (60%). There was also a statistically significant increase in the proportion of cases with gains of 1q, 7p, and 11q in adenocarcinomas compared to squamous cell carcinomas. Several recurrent isochromosomes and unbalanced exchanges were found. Among these was i(5p), which was observed in nine tumors, eight of which displayed adenomatous features. An i(8q) was identified in six cases, including five adenocarcinomas. Double minutes and/or homogeneously staining regions were seen in seven specimens. These data indicate that numerous chromosome alterations contribute to the pathogenesis of NSCLC and that, amid this widespread genomic disarray, recurrent abnormalities exist that could have biological and clinical implications.