Influence of particle size on electrical transport properties of La0.67Sr0.33MnO3La_{0.67}Sr_{0.33}MnO_3 manganite system

A systematic investigation of lanthanum-based manganite, $La_{0.67}Sr_{0.33}MnO_3$, has been undertaken with a view to understand the influence of varying particle sizes on electrical transport properties. With a view to obtain materials with varying particle size, they were prepared by sol-gel route, sintering at four different temperatures. The samples were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The XRD data has been analyzed by Rietveld refinement technique and it has been confirmed that the materials have rhombohedral crystal structure with R (3) over barc space group. Metal-insulator transition temperatures $(T_p)$ were found to decrease continuously with decreasing particle size where as ferro to paramagnetic transition temperatures $(T_c)$ are found to remain constant. The magnetoresistance (MR) values are found to increase with decreasing particle size. With a view to understand the conduction mechanism, the electrical resistivity data have been analyzed both in the ferromagnetic metallic $(T < T_p)$ as well as high temperature paramagnetic insulating $(T > T_p)$ regions

Personalized oncology through integrative high-throughput sequencing: a pilot study

methods will be needed for tumors of lower purity. And perhaps most important, we need a broader array of clinical and small RNA variants will allow more informative characterization. Sequencing at higher depth or enrichment $3600, well within the cost of routine clinical tests. But aspects need improvement: Additional testing for epigenetic The good news resulting from these studies was that the patients&apos; tumors were analyzed with in 24 days for suitable for this patient. melanoma, the Sequencing Tumor Board suggested that combined treatment with PI3K and MEK inhibitors would be a structural rearrangement in CDKN2C and HRas. Although the HRAS mutation has not been described before in trials, although none were available at the time. Similar analysis of another patient with metastatic melanoma revealed Sequencing Tumor Board concluded that the NRAS and CDK8 aberrations could potentially be matched to clinical TP53, aurora kinase A, a myosin heavy chain and the FAS death receptor, plus amplification of CDK8. Of these, the treated. Characterization of his metastatic tumor showed mutations in the oncogene NRAS, the tumor suppressor The authors then turned to an actual patient, a 46 year old with colorectal cancer, who had been unsuccessfully receptor signaling pathways. concluded that this pattern of mutations could in theory be treated by combined block of the PI3K and androgen fusion. Also, the androgen receptor gene was amplified and two tumor suppressors were inactivated. The Board specific gene fusion of TMPRSS2 and ERG and another, previously undescribed, gene − common prostate cancer xenografts established from patients with metastatic prostate cancer. They found that one of these carried the To verify that their sequencing strategy would work before testing it on actual patients, they assessed two enough time to be useful clinically. sequencing of transcribed RNA, the authors were able to find informative mutations within 3 to 4 weeks, a short experts to determine the appropriate treatment. With a combination of whole genome and exome sequencing plus approach by extensively characterizing cancers in several patients and then convening a Sequencing Tumor Board of particular tumor. This sounds appealing, but is it even possible? Roychowdhury and his colleagues tested this In an optimistic vision of personalized medicine, each cancer patient is treated with drugs tailored for their Stephen B. Gruber, 2,10 Kenneth J. Pienta, 1,2,10,13 Moshe Talpaz, 2,10 Arul M. Chinnaiyan 1,3,4,5,13 † Individual cancers harbor a set of genetic aberrations that can be informative for identifying rational therapies currently available or in clinical trials. We implemented a pilot study to explore the practical challenges of applying high-throughput sequencing in clinical oncology. We enrolled patients with advanced or refractory cancer who were eligible for clinical trials. For each patient, we performed whole-genome sequencing of the tumor, targeted whole-exome sequencing of tumor and normal DNA, and transcriptome sequencing (RNA-Seq) of the tumor to identify potentially informative mutations in a clinically relevant time frame of 3 to 4 weeks. With this approach, we detected several classes of cancer mutations including structural rearrangements, copy number alterations, point mutations, and gene expression alterations. A multidisciplinary Sequencing Tumor Board (STB) deliberated on the clinical interpretation of the sequencing results obtained. We tested our sequencing strategy on human prostate cancer xenografts. Next, we enrolled two patients into the clinical protocol and were able to review the results at our STB within 24 days of biopsy. The first patient had metastatic colorectal cancer in which we identified somatic point mutations in NRAS, TP53, AURKA, FAS, and MYH11, plus amplification and overexpression of cyclin-dependent kinase 8 (CDK8). The second patient had malignant melanoma, in which we identified a somatic point mutation in HRAS and a structural rearrangement affecting CDKN2C. The STB identified the CDK8 amplification and Ras mutation as providing a rationale for clinical trials with CDK inhibitors or MEK (mitogenactivated or extracellular signal-regulated protein kinase kinase) and PI3K (phosphatidylinositol 3-kinase) inhibitors, respectively. Integrative high-throughput sequencing of patients with advanced cancer generates a comprehensive, individual mutational landscape to facilitate biomarker-driven clinical trials in oncology