magnetic and structural investigation of growth induced magnetic anisotropies in fe50co50 thin films

In this paper, we investigate the magnetic properties of Fe50 Co50 polycrystalline thin films, grown by dc-magnetron sputtering, with thickness (t) ranging from 2.5 nm up to 100 nm. We focused on the magnetic properties of the samples to highlight the effects of possible intrinsic stress that may develop during growth, and their dependence on film thickness. Indeed, during film deposition, due to the growth technique and growth conditions, a metallic film may display an intrinsic compressive or tensile stress. In our case, due to the Fe50Co50 magnetolastic properties, this stress may in its turn promote the development of magnetic anisotropies. Samples magnetic properties were monitored with a SQUID magnetometer and a magneto–optic Kerr effect apparatus, using both an in–plane and an out–of–plane magnetic field. Magnetoresistance measurements were collected, as well, to further investigate the magnetic behavior of the samples. Indications about the presence of intrinsic stress were obtained accessing samples curvature with an optical profilometer. For t ≤ 20 nm, the shape of the in-plane magnetization loops is squared and coercivity increases with t, possibly due to fact that, for small t values, the grain size grows with t. The magnetoresistive response is anisotropic in character. For t > 20 nm, coercivity smoothly decreases, the approach to saturation gets slower and the shape of the whole loop gets less and less squared. The magnetoresistive effect becomes almost isotropic and its intensity increases of about one order of magnitude. These results suggest that the magnetization reorientation process changes for t > 20 nm, and are in agreement with the progressive development of an out-of-plane easy axis. This hypothesis is substantiated by profilometric analysis that reveals the presence of an in-plane compressive stress

The C-Band accelerating structures for SPARC photoinjector energy upgrade

n/

EpCAM (CD326) finding its role in cancer

Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future

Dark matter search in a Beam-Dump eXperiment (BDX) at Jefferson Lab

MeV-GeV dark matter (DM) is theoretically well motivated but remarkably unexplored. This Letter of Intent presents the MeV-GeV DM discovery potential for a 1 m$^3$ segmented plastic scintillator detector placed downstream of the beam-dump at one of the high intensity JLab experimental Halls, receiving up to 10$^{22}$ electrons-on-target (EOT) in a one-year period. This experiment (Beam-Dump eXperiment or BDX) is sensitive to DM-nucleon elastic scattering at the level of a thousand counts per year, with very low threshold recoil energies ($\sim$1 MeV), and limited only by reducible cosmogenic backgrounds. Sensitivity to DM-electron elastic scattering and/or inelastic DM would be below 10 counts per year after requiring all electromagnetic showers in the detector to exceed a few-hundred MeV, which dramatically reduces or altogether eliminates all backgrounds. Detailed Monte Carlo simulations are in progress to finalize the detector design and experimental set up. An existing 0.036 m$^3$ prototype based on the same technology will be used to validate simulations with background rate estimates, driving the necessary R$\&$D towards an optimized detector. The final detector design and experimental set up will be presented in a full proposal to be submitted to the next JLab PAC. A fully realized experiment would be sensitive to large regions of DM parameter space, exceeding the discovery potential of existing and planned experiments by two orders of magnitude in the MeV-GeV DM mass range.Comment: 28 pages, 17 figures, submitted to JLab PAC 4

Estudio de la calidad del agua de bebida para aves en granjas avícolas de la región centro-oeste de la provincia de Entre Ríos. Granjas de postura comercial

En Argentina existe una población de 41.000.000 de gallinas en postura, de las cuales el 20% aproximadamente están localizadas en la Provincia de Entre Ríos, representando la segunda provincia en importancia del país en producción de huevos. El agua utilizada en las granjas es de origen subterráneo. Existe información sobre sus características por los múltiples usos a que se destina. Sin embargo, el nivel de conocimientos actual no nos sirve a la hora de tomar decisiones en particular. Por este motivo y con el fin de caracterizar el agua que se destina a bebida aviar, se realizó un relevamiento de granjas de postura en los departamentos Paraná y Diamante de la provincia de Entre Ríos, donde se encuentra la mayor concentración de aves destinadas a la producción de huevos. El mismo estuvo enmarcado en el proyecto de investigación “Estudio de la calidad del agua de bebida para aves en granjas avícolas de la región centro-oeste de la provincia de Entre Ríos”, llevado a cabo por las Cátedras de Química General y Avicultura FCA-UNER. Se analizó el agua de 29 granjas de postura, realizándose análisis físico-químico y bacteriológico, los resultados muestran pH dentro de lo recomendado, elevada dureza, altos valores de sodio y sulfatos así como importantes variaciones de los componentes aun en predios cercanos y como consecuencia la necesidad realizar correcciones de los aportes minerales a fin de lograr un balance electrolítico adecuado, para el mejor rendimiento de la explotación. &nbsp

Potential Role of miRNAs in Developmental Haemostasis

MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs that are negative regulators in a crescent number of physiological and pathological processes. However, their role in haemostasis, a complex physiological process involving multitude of effectors, is just beginning to be characterized. We evaluated the changes of expression of miRNAs in livers of neonates (day one after birth) and adult mice by microarray and qRT-PCR trying to identify miRNAs that potentially may also be involved in the control of the dramatic change of hepatic haemostatic protein levels associated with this transition. Twenty one out of 41 miRNAs overexpressed in neonate mice have hepatic haemostatic mRNA as potential targets. Six of them identified by two in silico algorithms potentially bind the 3′UTR regions of F7, F9, F12, FXIIIB, PLG and SERPINC1 mRNA. Interestingly, miR-18a and miR-19b, overexpressed 5.4 and 8.2-fold respectively in neonates, have antithrombin, a key anti-coagulant with strong anti-angiogenic and anti-inflammatory roles, as a potential target. The levels of these two miRNAs inversely correlated with antithrombin mRNA levels during development (miR-19b: R = 0.81; p = 0.03; miR-18a: R = 0.91; p<0.001). These data suggest that miRNAs could be potential modulators of the haemostatic system involved in developmental haemostasis

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk

CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer

Although only 1.5% of the human genome appears to code for proteins, much effort in cancer research has been devoted to this minimal fraction of our DNA. However, the last few years have witnessed the realization that a large class of non-coding RNAs (ncRNAs), named microRNAs, contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also shown that epigenetic silencing of microRNAs with tumor suppressor features by CpG island hypermethylation is a common hallmark of human tumors. Thus, we wondered whether there were other ncRNAs undergoing aberrant DNA methylation-associated silencing in transformed cells. We focused on the transcribed-ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely conserved between orthologous regions of the human, rat and mouse genomes and that are located in both intra- and intergenic regions. We used a pharmacological and genomic approach to reveal the possible existence of an aberrant epigenetic silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating agent followed by hybridization to an expression microarray containing these sequences. We observed that DNA hypomethylation induces release of T-UCR silencing in cancer cells. Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues. The analysis of a large set of primary human tumors (n=283) demonstrated that hypermethylation of the described T-UCR CpG islands was a common event among the various tumor types. Our finding that, in addition to microRNAs, another class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in transformed cells supports a model in which epigenetic and genetic alterations in coding and non-coding sequences cooperate in human tumorigenesis

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Conceived and designed the experiments: XFL GAC RCB. Performed the experiments: XFL MIA WM RS MSN SZ. Analyzed the data: XFL SR. Contributed reagents/materials/analysis tools: YW GAC. Wrote the paper: XFL RCB.Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 39-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.This work was supported by the Anne and Henry Zarrow Foundation, kind gifts from Stuart and Gaye Lynn Zarrow and from Mrs. Delores Wilkenfeld, the Laura and John Arnold Foundation, the RGK Foundation, and the MD Anderson NCI CCSG P30 CA16672. G.A.C. is supported as a Fellow at the University of Texas MD Anderson Research Trust, as a University of Texas System Regents Research Scholar and by the CLL Global Research Foundation

Transcription factors and molecular epigenetic marks underlying EpCAM overexpression in ovarian cancer

BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is overexpressed on carcinomas, and its downregulation inhibits the oncogenic potential of multiple tumour types. Here, we investigated underlying mechanisms of epcam overexpression in ovarian carcinoma. METHODS: Expression of EpCAM and DNA methylation (bisulphite sequencing) was determined for ovarian cancer cell lines. The association of histone modifications and 16 transcription factors with the epcam promoter was analysed by chromatin immunoprecipitation. Treatment with 5-Aza-2'-deoxycytidine (5-AZAC) was used to induce EpCAM expression. RESULTS: Expression of EpCAM was correlated with DNA methylation and histone modifications. Treatment with 5-AZAC induced EpCAM expression in negative cells. Ten transcription factors were associated with the epcam gene in EpCAM expressing cells, but not in EpCAM-negative cells. Methylation of an Sp1 probe inhibited the binding of nuclear extract proteins in electromobility shift assays; such DNA methylation sensitivity was not observed for an NF-kappa B probe. CONCLUSION: This study provides insights in transcriptional regulation of epcam in ovarian cancer. Epigenetic parameters associated with EpCAM overexpression are potentially reversible, allowing novel strategies for sustained silencing of EpCAM expression. British Journal of Cancer (2011) 105, 312-319. doi: 10.1038/bjc.2011.231 www.bjcancer.com Published online 21 June 2011 (C) 2011 Cancer Research U