47 research outputs found
Early Helladic pottery traditions in western Greece: the case of Kephalonia and Ithaca
Pelikata on northern Ithaca was a rare known settlement dating to the Early Helladic period in the Ionian Islands, until recent rescue excavations on Kephalonia brought to light substantial architectural remains on the EKO property at the southern entrance to the modern town of Sami. The analytical results from a total of 55 samples indicate that the Early Helladic pottery production is heavily based on local resources. The raw materials are transformed into durable clay pastes by clay mixing and tempering, as these islands (notably Ithaca) are characterised by sediments which are not suitable for pottery making if unprocessed. Imports were not identified within the analysed assemblage, suggesting the existence of a very strong local tradition and possibly the rather introvert character of Early Helladic Ionian pottery production
Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores
BACKGROUND: Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection. METHODS: In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR. RESULTS: Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan(R) Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient. CONCLUSION: We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen
Classification across gene expression microarray studies
<p>Abstract</p> <p>Background</p> <p>The increasing number of gene expression microarray studies represents an important resource in biomedical research. As a result, gene expression based diagnosis has entered clinical practice for patient stratification in breast cancer. However, the integration and combined analysis of microarray studies remains still a challenge. We assessed the potential benefit of data integration on the classification accuracy and systematically evaluated the generalization performance of selected methods on four breast cancer studies comprising almost 1000 independent samples. To this end, we introduced an evaluation framework which aims to establish good statistical practice and a graphical way to monitor differences. The classification goal was to correctly predict estrogen receptor status (negative/positive) and histological grade (low/high) of each tumor sample in an independent study which was not used for the training. For the classification we chose support vector machines (SVM), predictive analysis of microarrays (PAM), random forest (RF) and k-top scoring pairs (kTSP). Guided by considerations relevant for classification across studies we developed a generalization of kTSP which we evaluated in addition. Our derived version (DV) aims to improve the robustness of the intrinsic invariance of kTSP with respect to technologies and preprocessing.</p> <p>Results</p> <p>For each individual study the generalization error was benchmarked via complete cross-validation and was found to be similar for all classification methods. The misclassification rates were substantially higher in classification across studies, when each single study was used as an independent test set while all remaining studies were combined for the training of the classifier. However, with increasing number of independent microarray studies used in the training, the overall classification performance improved. DV performed better than the average and showed slightly less variance. In particular, the better predictive results of DV in across platform classification indicate higher robustness of the classifier when trained on single channel data and applied to gene expression ratios.</p> <p>Conclusions</p> <p>We present a systematic evaluation of strategies for the integration of independent microarray studies in a classification task. Our findings in across studies classification may guide further research aiming on the construction of more robust and reliable methods for stratification and diagnosis in clinical practice.</p
c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study
INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. METHODS: In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. RESULTS: Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. CONCLUSION: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer
A novel single-cell based method for breast cancer prognosis
Breast cancer prognosis is challenging due to the heterogeneity of the disease. Various computational methods using bulk RNA-seq data have been proposed for breast cancer prognosis. However, these methods suffer from limited performances or ambiguous biological relevance, as a result of the neglect of intra-tumor heterogeneity. Recently, single cell RNA-sequencing (scRNA-seq) has emerged for studying tumor heterogeneity at cellular levels. In this paper, we propose a novel method, scPrognosis, to improve breast cancer prognosis with scRNA-seq data. scPrognosis uses the scRNA-seq data of the biological process Epithelial-to-Mesenchymal Transition (EMT). It firstly infers the EMT pseudotime and a dynamic gene co-expression network, then uses an integrative model to select genes important in EMT based on their expression variation and differentiation in different stages of EMT, and their roles in the dynamic gene co-expression network. To validate and apply the selected signatures to breast cancer prognosis, we use them as the features to build a prediction model with bulk RNA-seq data. The experimental results show that scPrognosis outperforms other benchmark breast cancer prognosis methods that use bulk RNA-seq data. Moreover, the dynamic changes in the expression of the selected signature genes in EMT may provide clues to the link between EMT and clinical outcomes of breast cancer. scPrognosis will also be useful when applied to scRNA-seq datasets of different biological processes other than EMT.Xiaomei Li, Lin Liu, Gregory J. Goodall, Andreas Schreiber, Taosheng Xu, Jiuyong Li, Thuc D. L
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
The Pottery from the Mycenaean Site of Palia Staneprospholeika, Κephalonia. A Preliminary Report
Archaeological Activity and Research in North West Greece and the Ionian Islands, Ioannina, Greece, 23-26 November 2017The site of Palia Stane-Prospholeika (P. Tsilimidos property) is located at a short distance south of the modern town of Argostoli, and occupies a commanding position on the lower slopes of the hilly zone overlooking the alluvial plain and the bay of Koutavos to the ENE. Four short excavation campaigns have taken place (2010, 2013, 2014) under the direction of Andreas Sotiriou of the 35th EΠKA. The excavation of the plot has not been completed. Preliminary results were presented at the 2014 Conference on the Archaeological Work in NW Greece and the Ionian Islands (Σωτηρίου et al. 2018).Author states that this has been published in proceedings but could not find details of this on publisher's website - will discuss with JG - ACCheck for published version during checkdate report - A
A single nucleotide polymorphism in the 3′UTR of the SNCA gene encoding alpha-synuclein is a new potential susceptibility locus for Parkinson disease
ABSTRAKSUCI AKTORIANI Pengaruh Pendidikan, Pelatihan, Pengalaman, dan Kompensasi Terhadap Kinerja Karyawan pada PT. Pelindo (Persero) di Makassar. Komisi pembimbing adalah Prof. Dr. H,.Abdul Rahman Mus, SE., MSi., sebagai ketua komisi dan Dr. Ibrahim Dani,. SE., MSi sebagai Anggota Komisi Pembimbing .Penelitian ini bertujuan untuk menganalisis Pengaruh Pendidikan, Pelatihan, Pengalaman, dan Kompensasi Terhadap Kinerja Karyawan pada PT. Pelindo (Persero) di Makassar..Popuasi sebanyak 155 orang dan ditarik sampel dengan menggunakan metode Slovin sehingga diperoleh sampel sebanyak 61 orang. Metode analisisnya yang digunakan adalah analisis regresi linear berganda versi 20.Hasil penelitian ini menunjukkan bahwa pendidikan, pelatihan, pengalaman kerja, dan kompensasi berpengaruh positif dan signifikan terhadap kinerja karyawan pada PT. Pelindo (Persero) Pengaruh Pendidikan, Pelatihan, Pengalaman, dan Kompensasi Terhadap Kinerja Karyawan pada PT. Pelindo (Persero) di Makassar. Makassar. Sedang secara parsial ditemukan bahwa variabel kompensasi kerja memiliki pengaruh yang paling dominan terhadap kinerja karyawan.. Kata Kunci: Kinerja karyawan, pendidikan, pelatihan, pengalaman dan kompensasi kerja.