14 results on '"Nassa, Giovanni"'
Search Results
2. Combinatorial targeting of a chromatin complex comprising Dot1L, menin and the tyrosine kinase BAZ1B reveals a new therapeutic vulnerability of endocrine therapy-resistant breast cancer
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Salvati, Annamaria, Melone, Viola, Sellitto, Assunta, Rizzo, Francesca, Tarallo, Roberta, Nyman, Tuula A., Giurato, Giorgio, Nassa, Giovanni, and Weisz, Alessandro
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- 2022
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3. Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells
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Dago, Dougba Noel, Scafoglio, Claudio, Rinaldi, Antonio, Memoli, Domenico, Giurato, Giorgio, Nassa, Giovanni, Ravo, Maria, Rizzo, Francesca, Tarallo, Roberta, and Weisz, Alessandro
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Human Genome ,Genetics ,Cancer ,Estrogen ,Biotechnology ,Breast Cancer ,Aetiology ,Underpinning research ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Alternative Splicing ,Breast Neoplasms ,Estradiol ,Estrogen Receptor alpha ,Estrogen Receptor beta ,Estrogens ,High-Throughput Nucleotide Sequencing ,Humans ,MCF-7 Cells ,Promoter Regions ,Genetic ,RNA ,Messenger ,Sequence Analysis ,RNA ,Breast cancer ,Estrogen receptor beta ,Alternative splicing ,Alternative promoters ,RNAseq ,Information and Computing Sciences ,Medical and Health Sciences ,Bioinformatics ,Biological sciences ,Biomedical and clinical sciences - Abstract
BackgroundEstrogens play an important role in breast cancer (BC) development and progression; when the two isoforms of the estrogen receptor (ERα and ERβ) are co-expressed each of them mediate specific effects of these hormones in BC cells. ERβ has been suggested to exert an antagonist role toward the oncogenic activities of ERα, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERβ in cancer cells. We have previously described the ERβ and ERα interactomes from BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERα and ERβ pathways. Guided by these findings, here we performed RNA sequencing to investigate in depth the differences in the early transcriptional events and RNA splicing patterns induced by estradiol in cells expressing ERα alone or ERα and ERβ.ResultsExon skipping was the most abundant splicing event in the post-transcriptional regulation by estradiol. We identified several splicing events induced by ERα alone and by ERα+ERβ, demonstrating for the first time that ERβ significantly affects estrogen-induced splicing in BC cells, as revealed by modification of a subset of ERα-dependent splicing by ERβ, as well as by the presence of splicing isoforms only in ERβ+cells. In particular, we observed that ERβ+BC cell lines exhibited around 2-fold more splicing events than the ERβ- cells. Interestingly, we identified putative direct targets of ERβ-mediated alternative splicing by correlating the genomic locations of ERβ and ERα binding sites with estradiol-induced differential splicing in the corresponding genes.ConclusionsTaken together, these results demonstrate that ERβ significantly affects estrogen-induced early transcription and mRNA splicing in hormone-responsive BC cells, providing novel information on the biological role of ERβ in these tumors.
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- 2015
4. Genome-wide DNA methylation changes upon DOT1L inhibition in hormone-responsive breast cancer cells.
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Giurato, Giorgio, Terenzi, Ilaria, Chiuso, Francesco, Salvati, Annamaria, Rizzo, Francesca, Tarallo, Roberta, Weisz, Alessandro, and Nassa, Giovanni
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DNA methylation ,CANCER cell growth ,ESTROGEN ,DNA methyltransferases ,BREAST cancer ,CANCER cells ,DEVELOPMENTAL biology - Abstract
This article discusses a study on DNA methylation changes in hormone-responsive breast cancer cells. The researchers inhibited two proteins, ERα and DOT1L, and analyzed the resulting DNA methylation patterns using bioinformatics and functional annotation analyses. They found that the differentially methylated CpGs were mainly located in gene promoters and enhancers, and these changes were associated with estrogen response gene pathways. The study provides valuable data for future research on the role of DNA methylation in breast cancer. The article also includes information about funding sources, conflicts of interest, and references to other relevant articles. [Extracted from the article]
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- 2023
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5. New Insights on Estrogen Receptor Actions in Hormone-Responsive Breast Cancer Cells by Interaction Proteomics
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Ambrosino, Concetta, Tarallo, Roberta, Nassa, Giovanni, Cirillo, Francesca, Weisz, Alessandro, and Schatten, Heide, editor
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- 2013
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6. Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management.
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Melone, Viola, Salvati, Annamaria, Brusco, Noemi, Alexandrova, Elena, D'Agostino, Ylenia, Palumbo, Domenico, Palo, Luigi, Terenzi, Ilaria, Nassa, Giovanni, Rizzo, Francesca, Giurato, Giorgio, Weisz, Alessandro, and Tarallo, Roberta
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ESTROGEN receptors ,LINCRNA ,NON-coding RNA ,BREAST cancer ,HORMONE therapy ,HUMAN genome ,NUCLEOTIDES - Abstract
In the complex and articulated machinery of the human genome, less than 2% of the transcriptome encodes for proteins, while at least 75% is actively transcribed into non-coding RNAs (ncRNAs). Among the non-coding transcripts, those ≥200 nucleotides long (lncRNAs) are receiving growing attention for their involvement in human diseases, particularly cancer. Genomic studies have revealed the multiplicity of processes, including neoplastic transformation and tumor progression, in which lncRNAs are involved by regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels by mechanism(s) that still need to be clarified. In breast cancer, several lncRNAs were identified and demonstrated to have either oncogenic or tumor-suppressive roles. The functional understanding of the mechanisms of lncRNA action in this disease could represent a potential for translational applications, as these molecules may serve as novel biomarkers of clinical use and potential therapeutic targets. This review highlights the relationship between lncRNAs and the principal hallmark of the luminal breast cancer phenotype, estrogen receptor α (ERα), providing an overview of new potential ways to inhibit estrogenic signaling via this nuclear receptor toward escaping resistance to endocrine therapy. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Effects of Oestrogen on MicroRNA Expression in Hormone-Responsive Breast Cancer Cells
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Ferraro, Lorenzo, Ravo, Maria, Nassa, Giovanni, Tarallo, Roberta, De Filippo, Maria Rosaria, Giurato, Giorgio, Cirillo, Francesca, Stellato, Claudia, Silvestro, Silvana, Cantarella, Concita, Rizzo, Francesca, Cimino, Daniela, Friard, Olivier, Biglia, Nicoletta, De Bortoli, Michele, Cicatiello, Luigi, Nola, Ernesto, and Weisz, Alessandro
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- 2012
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8. Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells.
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Nassa, Giovanni, Salvati, Annamaria, Tarallo, Roberta, Gigantino, Valerio, Alexandrova, Elena, Memoli, Domenico, Sellitto, Assunta, Rizzo, Francesca, Malanga, Donatella, Mirante, Teresa, Morelli, Eugenio, Nees, Matthias, Åkerfelt, Malin, Kangaspeska, Sara, Nyman, Tuula A., Milanesi, Luciano, Giurato, Giorgio, and Weisz, Alessandro
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BREAST cancer , *ENDOCRINE diseases , *ESTROGEN , *METHYLTRANSFERASES , *TUMORS , *CHROMATIN - Abstract
The article discusses that breast cancer resistance to endocrine therapy results from constitutively active or aberrant estrogen receptor signaling, and ways to block pathway in these tumors are sought after. The methyltransferase is a cofactor in BC cell chromatin, in which the two proteins colocalize to regulate estrogen target gene transcription.
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- 2019
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9. Single-Cell States in the Estrogen Response of Breast Cancer Cell Lines.
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Casale, Francesco Paolo, Giurato, Giorgio, Nassa, Giovanni, Armond, Jonathan W., Oates, Chris J., Corá, Davide, Gamba, Andrea, Mukherjee, Sach, Weisz, Alessandro, and Nicodemi, Mario
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BREAST cancer ,ESTROGEN ,CANCER cells ,CELL lines ,GENETIC transcription ,GENE expression ,MICROARRAY technology - Abstract
Estrogen responsive breast cancer cell lines have been extensively studied to characterize transcriptional patterns in hormone-responsive tumors. Nevertheless, due to current technological limitations, genome-wide studies have typically been limited to population averaged data. Here we obtain, for the first time, a characterization at the single-cell level of the states and expression signatures of a hormone-starved MCF-7 cell system responding to estrogen. To do so, we employ a recently proposed model that allows for dissecting single-cell states from time-course microarray data. We show that within 32 hours following stimulation, MCF-7 cells traverse, most likely, six states, with a faster early response followed by a progressive deceleration. We also derive the genome-wide transcriptional profiles of such single-cell states and their functional characterization. Our results support a scenario where estrogen promotes cell cycle progression by controlling multiple, sequential regulatory steps, whose single-cell events are here identified. [ABSTRACT FROM AUTHOR]
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- 2014
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10. iMir: An Integrated pipeline for high-throughput analysis of small non-coding RNA data obtained by smallRNA-Seq.
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Giurato, Giorgio, De Filippo, Maria Rosaria, Rinaldi, Antonio, Hashim, Adnan, Nassa, Giovanni, Ravo, Maria, Rizzo, Francesca, Tarallo, Roberta, and Weisz, Alessandro
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NON-coding RNA ,NUCLEOTIDE sequence ,MICRORNA ,GENE expression ,BREAST cancer ,PIWI genes - Abstract
Background Qualitative and quantitative analysis of small non-coding RNAs by next generation sequencing (smallRNA-Seq) represents a novel technology increasingly used to investigate with high sensitivity and specificity RNA population comprising microRNAs and other regulatory small transcripts. Analysis of smallRNA-Seq data to gather biologically relevant information, i.e. detection and differential expression analysis of known and novel noncoding RNAs, target prediction, etc., requires implementation of multiple statistical and bioinformatics tools from different sources, each focusing on a specific step of the analysis pipeline. As a consequence, the analytical workflow is slowed down by the need for continuous interventions by the operator, a critical factor when large numbers of datasets need to be analyzed at once. Results We designed a novel modular pipeline (iMir) for comprehensive analysis of smallRNA-Seq data, comprising specific tools for adapter trimming, quality filtering, differential expression analysis, biological target prediction and other useful options by integrating multiple open source modules and resources in an automated workflow. As statistics is crucial in deepsequencing data analysis, we devised and integrated in iMir tools based on different statistical approaches to allow the operator to analyze data rigorously. The pipeline created here proved to be efficient and time-saving than currently available methods and, in addition, flexible enough to allow the user to select the preferred combination of analytical steps. We present here the results obtained by applying this pipeline to analyze simultaneously 6 smallRNASeq datasets from either exponentially growing or growth-arrested human breast cancer MCF-7 cells, that led to the rapid and accurate identification, quantitation and differential expression analysis of ~450 miRNAs, including several novel miRNAs and isomiRs, as well as identification of the putative mRNA targets of differentially expressed miRNAs. In addition, iMir allowed also the identification of ~70 piRNAs (piwi-interacting RNAs), some of which differentially expressed in proliferating vs growth arrested cells. Conclusion The integrated data analysis pipeline described here is based on a reliable, flexible and fully automated workflow, useful to rapidly and efficiently analyze high-throughput smallRNASeq data, such as those produced by the most recent high-performance next generation sequencers. iMir is available at http://www.labmedmolge.unisa.it/inglese/research/imir. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Global View of Candidate Therapeutic Target Genes in Hormone-Responsive Breast Cancer.
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Salvati, Annamaria, Gigantino, Valerio, Nassa, Giovanni, Mirici Cappa, Valeria, Ventola, Giovanna Maria, Cracas, Daniela Georgia Cristina, Mastrocinque, Raffaella, Rizzo, Francesca, Tarallo, Roberta, Weisz, Alessandro, and Giurato, Giorgio
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BRCA genes ,HORMONE therapy ,ESTROGEN ,ESTROGEN receptors ,CANCER invasiveness ,TUMOR growth - Abstract
Breast cancer (BC) is a heterogeneous disease characterized by different biopathological features, differential response to therapy and substantial variability in long-term-survival. BC heterogeneity recapitulates genetic and epigenetic alterations affecting transformed cell behavior. The estrogen receptor alpha positive (ERα+) is the most common BC subtype, generally associated with a better prognosis and improved long-term survival, when compared to ERα-tumors. This is mainly due to the efficacy of endocrine therapy, that interfering with estrogen biosynthesis and actions blocks ER-mediated cell proliferation and tumor spread. Acquired resistance to endocrine therapy, however, represents a great challenge in the clinical management of ERα+ BC, causing tumor growth and recurrence irrespective of estrogen blockade. Improving overall survival in such cases requires new and effective anticancer drugs, allowing adjuvant treatments able to overcome resistance to first-line endocrine therapy. To date, several studies focus on the application of loss-of-function genome-wide screenings to identify key (hub) "fitness" genes essential for BC progression and representing candidate drug targets to overcome lack of response, or acquired resistance, to current therapies. Here, we review the biological significance of essential genes and relative functional pathways affected in ERα+ BC, most of which are strictly interconnected with each other and represent potential effective targets for novel molecular therapies. [ABSTRACT FROM AUTHOR]
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- 2020
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12. The RNA-mediated estrogen receptor α interactome of hormone-dependent human breast cancer cell nuclei.
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Nassa, Giovanni, Giurato, Giorgio, Salvati, Annamaria, Gigantino, Valerio, Pecoraro, Giovanni, Lamberti, Jessica, Rizzo, Francesca, Nyman, Tuula A., Tarallo, Roberta, and Weisz, Alessandro
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RNA ,ESTROGEN receptors ,BREAST cancer ,CELL nuclei ,MASS spectrometry - Abstract
Estrogen Receptor alpha (ERα) is a ligand-inducible transcription factor that mediates estrogen signaling in hormone-responsive cells, where it controls key cellular functions by assembling in gene-regulatory multiprotein complexes. For this reason, interaction proteomics has been shown to represent a useful tool to investigate the molecular mechanisms underlying ERα action in target cells. RNAs have emerged as bridging molecules, involved in both assembly and activity of transcription regulatory protein complexes. By applying Tandem Affinity Purification (TAP) coupled to mass spectrometry (MS) before and after RNase digestion in vitro, we generated a dataset of nuclear ERα molecular partners whose association with the receptor involves RNAs. These data provide a useful resource to elucidate the combined role of nuclear RNAs and the proteins identified here in ERα signaling to the genome in breast cancer and other cell types. Design Type(s) parallel group design • protein and RNA interaction identification objective • cell type comparison design Measurement Type(s) RNA-Protein Interaction • protein-protein interaction detection Technology Type(s) mass spectrometry Factor Type(s) experimental condition • biological replicate Sample Characteristic(s) MCF7 cell Machine-accessible metadata file describing the reported data (ISA-Tab format) [ABSTRACT FROM AUTHOR]
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- 2019
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13. Mapping the cell-membrane proteome of the SKBR3/HER2+ cell line to the cancer hallmarks
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Iulia M. Lazar, Arba Karcini, Joshua R. S. Haueis, and Nassa, Giovanni
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2 Aetiology ,Receptor, erbB-2 ,Multidisciplinary ,Proteome ,Receptor, ErbB-2 ,Prevention ,Membrane Proteins ,3 Good Health and Well Being ,Breast Neoplasms ,Cell Line ,Cell Line, Tumor ,Breast Cancer ,2.1 Biological and endogenous factors ,Humans ,Female ,Precision Medicine ,Cancer ,Biotechnology - Abstract
The hallmarks of biological processes that underlie the development of cancer have been long recognized, yet, existing therapeutic treatments cannot prevent cancer from continuing to be one of the leading causes of death worldwide. This work was aimed at exploring the extent to which the cell-membrane proteins are implicated in triggering cancer hallmark processes, and assessing the ability to pinpoint tumor-specific therapeutic targets through a combined membrane proteome/cancer hallmark perspective. By using GO annotations, a database of human proteins associated broadly with ten cancer hallmarks was created. Cell-membrane cellular subfractions of SKBR3/HER2+ breast cancer cells, used as a model system, were analyzed by high resolution mass spectrometry, and high-quality proteins (FDR
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- 2022
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14. The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading
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Luca Ricciardi, Maria Ravo, Luciano Milanesi, Giuseppina Bruno, Giorgio Giurato, Teresa Rocco, Annamaria Salvati, Valerio Gigantino, Angela Cordella, Francesca Rizzo, Giovanna Marchese, Giovanni Cimmino, Concetta Ambrosino, Roberta Tarallo, Giovanni Nassa, Alessandro Weisz, Tuula A. Nyman, Biancamaria Pierri, Tarallo, Roberta, Giurato, Giorgio, Bruno, Giuseppina, Ravo, Maria, Rizzo, Francesca, Salvati, Annamaria, Ricciardi, Luca, Marchese, Giovanna, Cordella, Angela, Rocco, Teresa, Gigantino, Valerio, Pierri, Biancamaria, Cimmino, Giovanni, Milanesi, Luciano, Ambrosino, Concetta, Nyman, Tuula A., Nassa, Giovanni, and Weisz, Alessandro
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0301 basic medicine ,lcsh:QH426-470 ,Transcription, Genetic ,RNA splicing ,RNA-induced silencing complex ,Interaction proteomics ,Breast Neoplasms ,Biology ,Chromatin remodeling ,03 medical and health sciences ,Argonaute 2, Estrogen receptor beta, Breast cancer, Interaction proteomics, Transcriptional regulation, RNA splicing ,Breast cancer ,Transcriptional regulation ,microRNA ,Humans ,RNA-Induced Silencing Complex ,Estrogen receptor beta ,lcsh:QH301-705.5 ,Regulation of gene expression ,Argonaute 2 ,Genome, Human ,Research ,Argonaute ,Molecular biology ,Cell biology ,lcsh:Genetics ,030104 developmental biology ,Nuclear receptor ,lcsh:Biology (General) ,Gene Expression Regulation ,Interaction proteomic ,Argonaute Proteins ,MCF-7 Cells - Abstract
Background The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Results Applying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ–AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ − cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability. Conclusions These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1321-0) contains supplementary material, which is available to authorized users.
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- 2017
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