Essays on location patterns of creative industries

Aquesta tesi analitza i identifica quins són els factors que faciliten la localització i aglomeració de les indústries creatives a nivell local i les compara amb les de la resta d’activitats econòmiques. Aquesta tesi contribueix a la literatura de les indústries creatives a través de l'anàlisi de les pautes de localització d'aquestes indústries tant des d'una perspectiva d’anàlisi tradicional a nivell municipal com introduint algunes innovacions quant a l'ús de la econometria espacial, els mètodes basats en la distància i els Sistemes d’Informació Geogràfica (SIG) gràcies a l’accés a dades micro-geogràfiques. L'aplicació empírica se centra en els municipis catalans per al període 2002-2007, en l'Àrea Metropolitana de Barcelona i, finalment, en la ciutat de Barcelona per al període 2006-2015. Tot i que els determinants de localització de les indústries creatives no són tan diferents dels de les no creatives, els principals resultats d'aquesta tesi confirmen la naturalesa específica d'aquestes indústries i la seva major necessitat d'aglomeració, especialment per a les indústries creatives basades en un coneixement més simbòlic. A més, aquesta tesi corrobora l'associació positiva entre les indústries creatives i el creixement econòmic, en termes de creació d’empreses i de productivitat. Tanmateix, els resultats suggereixen que la capacitat d'atraure activitats creatives i ocupació a una àrea estan estretament vinculats a l’entorn creatiu existent i les dinàmiques culturals històriques que defineixen la personalitat de l’àrea. Tenint en compte el gran potencial de les indústries creatives en termes de, per exemple, el dinamisme econòmic, la regeneració urbana o el màrqueting urbà, els resultats d'aquesta tesi permeten extreure una sèrie de recomanacions per a les autoritats públiques disposades a fomentar la diversificació de l'activitat econòmica per tal d’augmentar la seva competitivitat en un context econòmic i social cada vegada més global.Esta tesis analiza e identifica cuáles son los factores que facilitan la localización y aglomeración de las industrias creativas a nivel local y las compara con las del resto de actividades económicas. Esta tesis contribuye a la literatura de las industrias creativas a través del análisis de las pautas de localización de estas industrias tanto desde una perspectiva de análisis tradicional a nivel municipal como introduciendo algunas innovaciones en cuanto al uso de la econometría espacial, los métodos basados en la distancia y los Sistemas de Información Geográfica (SIG) gracias al acceso a datos micro-geográficos. La aplicación empírica se centra en los municipios catalanes para el periodo 2002-2007, en el Área Metropolitana de Barcelona y, finalmente, en la ciudad de Barcelona entre 2006-2015. A pesar de que los determinantes de localización de las industrias creativas no son tan diferentes de los de las no creativas, los principales resultados confirman la naturaleza específica de estas industrias y su mayor necesidad de aglomeración, especialmente para a las industrias creativas basadas en un conocimiento más simbólico. Además, esta tesis corrobora la asociación positiva entre industrias creativas y crecimiento económico, en términos de creación de empresas y de productividad. Sin embargo, los resultados también sugieren que la capacidad de atraer actividades creativas y empleo en un área está claramente asociada al entorno creativo existente y las dinámicas culturales históricas que definen la personalidad del área. Teniendo en cuenta el gran potencial de las industrias creativas en términos de, por ejemplo, el dinamismo económico, la regeneración urbana o el marketing urbano, los resultados de esta tesis permiten extraer una serie de recomendaciones para las autoridades públicas dispuestas a apoyar la diversificación de la actividad económica a efectos de aumentar su competitividad en un contexto económico y social cada vez más global.This thesis analyses and identifies which factors facilitate the location and agglomeration of creative industries at the local level and compare them to those of the other economic activities. This thesis contributes to the literature on creative industries by analysing the location behaviour of these industries both from a traditional analysis at municipality level and by introducing some innovations regarding the use of spatial econometrics, distance-based methods and Geographical Information Systems (GIS) thanks to the access to micro-geographic data. The empirical application focuses on Catalan municipalities for the period 2002-2007, on the Metropolitan Area of Barcelona and on the city of Barcelona for the period 2006-2015. Main findings of this thesis show that, despite the fact that creative industries location determinants are not so different from those of non-creative industries, the specific nature of these industries and their greater need for agglomeration is confirmed, especially for symbolic-based creative industries. Moreover, this thesis confirms the positive association between creative industries and economic growth – in terms of firm creation or productivity. Finally, it also suggests that the ability to attract creative activities and employment to an area strongly depends on the existing creative milieu and the cultural path dependence of the area. Based on the assumption that creative industries have great potential in terms of, for example, economic dynamism, urban regeneration or city marketing, results of this thesis allows having a series of recommendations for public authorities willing to support the diversification of economic activity for the purpose of enhancing their competitiveness in an economic and social context increasingly global

Chiral recognition by dissolution dynamic nuclear polarization NMR spectroscopy

The recognition of enantiomeric molecules by chemical analytical techniques is still a challenge. A method based on d-DNP (dissolution dynamic nuclear polarization) NMR spectroscopy to study chiral recognition was described for the first time [1]. DNP allows NMR sensitivity to be boosted by several orders of magnitude, overcoming one of the main limitations of NMR spectroscopy [2]. A method integrating d-DNP and 13C-NMR-aided enantiodifferentiation using chiral solvating agents (CSA) was developed, in which only the chiral analyte was hyperpolarized and selectively observed by NMR. The described method enhances the sensitivity of the conventional NMR-based procedure [3] and lightens the common problem of signal overlapping between analyte and CSA. As proof of concept, racemic metabolite 13C-labeled DL-methionine was enantiodifferentiated by a single-scan 13C-NMR experiment. This method entails a step forward in the chiral recognition of small molecules by NMR spectroscopy; it opens new possibilities in situations where the sensitivity is limited, for example, when low analyte concentration is available or when measurement of an insensitive nucleus is required. The advantages and current limitations of the method, as well as future perspectives, are discussed

Refinement of computational identification of somatic copy number alterations using DNA methylation microarrays illustrated in cancers of unknown primary

High-throughput genomic technologies are increasingly used in personalized cancer medicine. However, computational tools to maximize the use of scarce tissues combining distinct molecular layers are needed. Here we present a refined strategy, based on the R-package 'conumee', to better predict somatic copy number alterations (SCNA) from deoxyribonucleic acid (DNA) methylation arrays. Our approach, termed hereafter as 'conumee-KCN', improves SCNA prediction by incorporating tumor purity and dynamic thresholding. We trained our algorithm using paired DNA methylation and SNP Array 6.0 data from The Cancer Genome Atlas samples and confirmed its performance in cancer cell lines. Most importantly, the application of our approach in cancers of unknown primary identified amplified potentially actionable targets that were experimentally validated by Fluorescence in situ hybridization and immunostaining, reaching 100% specificity and 93.3% sensitivity

Se_nos gener@ mujeres. La construcción discursiva del pecho femenino en el ámbito médico

El objetivo de este artículo es reflexionar sobre el impacto de los mandatos de género en los cuerpos de las mujeres en el contexto biomédico. Exploramos cómo se construye discursivamente la mamoplastia en tres grupos de mujeres: que han padecido cáncer de pecho, trans y que se intervienen por motivos estéticos. Mediante el análisis del discurso estudiamos cómo profesionales de la salud especialistas en los tres casos elaboran la distinción entre ellos, cómo otorgan diferentes grados de legitimidad a la demanda y cómo justifican si su coste se debe cubrir públicamente. Resultado de este análisis detectamos que se establecen dos fronteras entre los cuerpos susceptibles de recibir esta intervención: una relativa a la necesidad y otra a la legitimidad de la demanda.The aim of the article is to reflect on the impact of gender norms in women's bodies in the medical context. We explore the discursive construction of breast implant in three groups of women: those who suffered breast cancer, trans, and women that submit to surgery for aesthetic reasons. Through discourse analysis, we study how do health professionals elaborate distinctions between the three cases, how do they give different levels of legitimacy to women's demand, and how do they argue if the cost of the intervention has to be covered with public funds. In the end, we see how health professionals interviewed draw two boundaries to distinguish the bodies of the women demanding the intervention: the first one is related to the perception of the need and the second one, to the legitimacy attributed to the demand

Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis

Cervical sample; Endometrial cancer; ProteinMostra cervical; Càncer d'endometri; ProteïnaMuestra cervical; Cáncer de endometrio; ProteínaBackground: Abnormal uterine bleeding is the main symptom of endometrial cancer (EC), but it is highly nonspecific. This represents a huge burden for women’s health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90–95% of those women who do not have EC. Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC. We evaluated the protein quantity and the proteome composition of five cervical sampling methods. Results: Samples collected with a Rovers Cervex Brush® and the HC2 DNA collection device, Digene, were the most suitable samples for EC proteomic studies. Most proteins found in uterine fluids were also detected in both cervical samples. We then conducted a clinical retrospective study to assess the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), using targeted proteomics. We identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential protein biomarkers to discriminate between EC and symptomatic non-EC women with abnormal uterine bleeding in cervical fluids (AUC > 0.8). Conclusions: This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) grant number PI17/02155, PI20/00644 to E.C. and S.C., and the IFI19/00029 to E.C.-d.l.-R.; from Fundación Científica Asociación Española Contra el Cáncer (AECC) grant number GCTRA1804MATI; and the INVES20051COLA to E.C.; the CIBERONC network grant number CB16/12/00328; and the ERA PerMed ERA-NET grant (PERME212443COLA funded by AECC and AEC21_2/00030 funded by ISCIII); and 2021 SGR 1157 by AGAUR. The present work has been also supported by a Televie grant 5/20/5—TLV/DD to G.D

In silico Approach for Validating and Unveiling New Applications for Prognostic Biomarkers of Endometrial Cancer

Bioinformática; Cáncer de endometrio; Biomarcador pronósticoBioinformàtica; Càncer d'endometri; Biomarcador pronòsticBioinformatics; Endometrial cancer; Prognostic biomarkerEndometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified in multiple studies and explore their prognostic application by analyzing them in TCGA and CPTAC datasets. We analyzed the mRNA and proteomic expression data to assess the statistical prognostic performance of the 255 proteins. Significant biomarkers related to overall survival (OS) and recurrence-free survival (RFS) were combined and signatures generated. A total of 30 biomarkers were associated either to one or more of the following prognostic factors: histological type (n = 15), histological grade (n = 6), FIGO stage (n = 1), molecular classification (n = 16), or they were associated to OS (n = 11), and RFS (n = 5). A prognostic signature composed of 11 proteins increased the accuracy to predict OS (AUC = 0.827). The study validates and identifies new potential applications of 30 proteins as prognostic biomarkers and suggests to further study under-studied biomarkers such as TPX2, and confirms already used biomarkers such as MSH6, MSH2, or L1CAM. These results are expected to advance the quest for biomarkers to accurately assess the risk of EC patients.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) grant number PI17/02155, PI20/00644, and the IFI19/00029 to E.C.-d.l.R., the Ministerio de ciencia, Innovación y Universidades through a RETOS Colaboración (RTC-2017-6261-1), both co-financed by the European Regional Development Fund (FEDER); from Fundación Científica Asociación Española Contra el Cáncer (AECC) grant number GCTRA1804MATI and CIBERONC network grant number CB16/12/00328; and Grups Consolidats de la Generalitat de Catalunya (2017SGR1661). E.C. is supported by an Investigator Grant from AECC (INVES20051COLA). E.M.-G. was supported by Televie grant F5/20/5-TLV/DD

rPinecone : Define sub-lineages of a clonal expansion via a phylogenetic tree

The ability to distinguish different circulating pathogen clones from each other is a fundamental requirement to understand the epidemiology of infectious diseases. Phylogenetic analysis of genomic data can provide a powerful platform to identify lineages within bacterial populations, and thus inform outbreak investigation and transmission dynamics. However, resolving differences between pathogens associated with low-variant (LV) populations carrying low median pairwise single nucleotide variant (SNV) distances remains a major challenge. Here we present rPinecone, an R package designed to define sub-lineages within closely related LV populations. rPinecone uses a root-to-tip directional approach to define sub-lineages within a phylogenetic tree according to SNV distance from the ancestral node. The utility of this software was demonstrated using both simulated outbreaks and real genomic data of two LV populations: a hospital outbreak of methicillin-resistant Staphylococcus aureus and endemic Salmonella Typhi from rural Cambodia. rPinecone identified the transmission branches of the hospital outbreak and geographically confined lineages in Cambodia. Sub-lineages identified by rPinecone in both analyses were phylogenetically robust. It is anticipated that rPinecone can be used to discriminate between lineages of bacteria from LV populations where other methods fail, enabling a deeper understanding of infectious disease epidemiology for public health purposes.Peer reviewe

Estimating digital product trade through corporate revenue data

Despite global efforts to harmonize international trade statistics, our understanding of digital trade and its implications remains limited. Here, we introduce amethod to estimate bilateral exports and imports for dozens of sectors starting from the corporate revenue data of large digital firms. This method allows us to provide estimates for digitally ordered and delivered trade involving digital goods (e.g. video games), productized services (e.g. digital advertising), and digital intermediation fees (e.g. hotel rental), which together we call digital products. We use these estimates to study five key aspects of digital trade. We find that, compared to trade in physical goods, digital product exports are more spatially concentrated, have been growing faster, and can offset trade balance estimates, like the United States trade deficit on physical goods. We also find that countries that have decoupled economic growth from greenhouse gas emissions tend to have larger digital exports and that digital exports contribute positively to the complexity of economies. This method, dataset, and findings provide a new lens to understand the impact of international trade in digital products

Genomic Validation of Endometrial Cancer Patient-Derived Xenograft Models as a Preclinical Tool

Bioinformatics; Endometrial cancer; Molecular markerBioinformática; Cáncer endometrial; Marcador molecularBioinformàtica; Càncer d'endometri; Marcador molecularEndometrial cancer (EC) is the second most frequent gynecological cancer worldwide. Although improvements in EC classification have enabled an accurate establishment of disease prognosis, women with a high-risk or recurrent EC face a dramatic situation due to limited further treatment options. Therefore, new strategies that closely mimic the disease are required to maximize drug development success. Patient-derived xenografts (PDXs) are widely recognized as a physiologically relevant preclinical model. Hence, we propose to molecularly and histologically validate EC PDX models. To reveal the molecular landscape of PDXs generated from 13 EC patients, we performed histological characterization and whole-exome sequencing analysis of tumor samples. We assessed the similarity between PDXs and their corresponding patient’s tumor and, additionally, to an extended cohort of EC patients obtained from The Cancer Genome Atlas (TCGA). Finally, we performed functional enrichment analysis to reveal differences in molecular pathway activation in PDX models. We demonstrated that the PDX models had a well-defined and differentiated molecular profile that matched the genomic profile described by the TCGA for each EC subtype. Thus, we validated EC PDX’s potential to reliably recapitulate the majority of histologic and molecular EC features. This work highlights the importance of a thorough characterization of preclinical models for the improvement of the success rate of drug-screening assays for personalized medicine.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) grant number PI17/02071, PI20/01566, and from the Ministerio de ciencia, Innovación y Universidades through a RETOS Colaboración (RTC-2017-6261-1), both co-financed by the European Regional Development Fund (FEDER); from Fundación Científica Asociación Española Contra el Cáncer (AECC) grant number GCTRA1804MATI, Biomedical Research Center Network (CIBERONC) grant number CB16/12/00328 and Generalitat de Catalunya, grant number 2017SGR1661. B.V.-M. is supported by a predoctoral fellowship (PERIS-SLT017/20/000183) from Generalitat de Catalunya. E.C. is supported by an Investigator Grant from AECC (INVES20051COLA)

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies