From innovation to diversification: a simple competitive model

Few attempts have been proposed in order to describe the statistical features and historical evolution of the export bipartite matrix countries/products. An important standpoint is the introduction of a products network, namely a hierarchical forest of products that models the formation and the evolution of commodities. In the present article, we propose a simple dynamical model where countries compete with each other to acquire the ability to produce and export new products. Countries will have two possibilities to expand their export: innovating, i.e. introducing new goods, namely new nodes in the product networks, or copying the productive process of others, i.e. occupying a node already present in the same network. In this way, the topology of the products network and the country-product matrix evolve simultaneously, driven by the countries push toward innovation.Comment: 8 figures, 8 table

Detecting early signs of the 2007-2008 crisis in the world trade

Since 2007, several contributions have tried to identify early-warning signals of the financial crisis. However, the vast majority of analyses has focused on financial systems and little theoretical work has been done on the economic counterpart. In the present paper we fill this gap and employ the theoretical tools of network theory to shed light on the response of world trade to the financial crisis of 2007 and the economic recession of 2008-2009. We have explored the evolution of the bipartite World Trade Web (WTW) across the years 1995-2010, monitoring the behavior of the system both before and after 2007. Our analysis shows early structural changes in the WTW topology: since 2003, the WTW becomes increasingly compatible with the picture of a network where correlations between countries and products are progressively lost. Moreover, the WTW structural modification can be considered as concluded in 2010, after a seemingly stationary phase of three years. We have also refined our analysis by considering specific subsets of countries and products: the most statistically significant early-warning signals are provided by the most volatile macrosectors, especially when measured on developing countries, suggesting the emerging economies as being the most sensitive ones to the global economic cycles.Comment: 18 pages, 9 figure

Randomizing bipartite networks: the case of the World Trade Web

Within the last fifteen years, network theory has been successfully applied both to natural sciences and to socioeconomic disciplines. In particular, bipartite networks have been recognized to provide a particularly insightful representation of many systems, ranging from mutualistic networks in ecology to trade networks in economy, whence the need of a pattern detection-oriented analysis in order to identify statistically-significant structural properties. Such an analysis rests upon the definition of suitable null models, i.e. upon the choice of the portion of network structure to be preserved while randomizing everything else. However, quite surprisingly, little work has been done so far to define null models for real bipartite networks. The aim of the present work is to fill this gap, extending a recently-proposed method to randomize monopartite networks to bipartite networks. While the proposed formalism is perfectly general, we apply our method to the binary, undirected, bipartite representation of the World Trade Web, comparing the observed values of a number of structural quantities of interest with the expected ones, calculated via our randomization procedure. Interestingly, the behavior of the World Trade Web in this new representation is strongly different from the monopartite analogue, showing highly non-trivial patterns of self-organization.Comment: 22 pages, 13 figure

Inferring monopartite projections of bipartite networks: an entropy-based approach

Bipartite networks are currently regarded as providing a major insight into the organization of many real-world systems, unveiling the mechanisms driving the interactions occurring between distinct groups of nodes. One of the most important issues encountered when modeling bipartite networks is devising a way to obtain a (monopartite) projection on the layer of interest, which preserves as much as possible the information encoded into the original bipartite structure. In the present paper we propose an algorithm to obtain statistically-validated projections of bipartite networks, according to which any two nodes sharing a statistically-significant number of neighbors are linked. Since assessing the statistical significance of nodes similarity requires a proper statistical benchmark, here we consider a set of four null models, defined within the exponential random graph framework. Our algorithm outputs a matrix of link-specific p-values, from which a validated projection is straightforwardly obtainable, upon running a multiple hypothesis testing procedure. Finally, we test our method on an economic network (i.e. the countries-products World Trade Web representation) and a social network (i.e. MovieLens, collecting the users' ratings of a list of movies). In both cases non-trivial communities are detected: while projecting the World Trade Web on the countries layer reveals modules of similarly-industrialized nations, projecting it on the products layer allows communities characterized by an increasing level of complexity to be detected; in the second case, projecting MovieLens on the films layer allows clusters of movies whose affinity cannot be fully accounted for by genre similarity to be individuated.Comment: 16 pages, 9 figure

Phenotypic characterization of human prostatic stromal cells in primary cultures derived from human tissue samples

Emerging evidence has shown that the tumor microenvironment plays a crucial role in prostate cancer (PCa) development and progression. However, the mechanism(s) through which stromal cells regulate epithelial cells and the differences among prostatic stromal cells of different histological/pathological origin in PCa progression remain unclear. Therefore, it is necessary to characterize the stromal cell populations present in benign prostatic hyperplasia (BPH) and PCa. To this end, we used cultures from stromal cells obtained from BPH-derived (15 cases) and PCa-derived (30 cases) primary cultures. In culture, stromal cells are a mixture of fibroblasts, myofibroblasts (MFs) and muscle cells. Fibroblasts are characterized for the expression of vimentin, MFs for the co-expression of α-smooth muscle actin (α-SMA) and vimentin, whereas muscle cells for the expression of α-SMA and desmin. Fibroblasts were present in large amounts in the BPH-compared to the PCa-derived cultures, whereas MFs were more representative of PCa-as opposed to BPH-derived cultures. Some α-SMA-positive cells retained the expression of basal cytokeratin K14. This population was defined as myoepithelial cells and was associated with senescent cultures. The percentage of MFs was higher in high-grade compared to moderate-and low-grade PCa-derived cultures, whereas the number of myoepithelial cells was lower in high-grade compared to moderate-and low-grade PCa-derived cultures. In addition, we analyzed the expression of p75NTR, as well as the expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors of MMPs (TIMPs). p75NTR expression was elevated in the stromal cultures derived from PCa compared to those derived from BPH and in cultures derived from cases with Gleason scores.7 compared to those derived from cases with Gleason scores <7, as well as in cultures with a high concentration of MFs compared to those with a high concentration of fibroblasts. MMP-2 was secreted by all primary cultures, whereas MMP-9 secretion was observed only in some PCa-derived stromal cells, when the percentage of MFs was significantly higher compared to BPH-derived cultures. TIMP1, TIMP2 and TIMP3 were secreted in elevated amounts in the BPH-compared to the PCa-derived stromal cultures, suggesting the differential regulation of extracellular matrix (ECM) degradation. When we used 22rv1 and PC3 PCa xenograft models for the isolation and characterization of murine cancer-associated fibroblasts (CAFs) we noted that the angiogenic wave was concurrent with the appearance of a reactive stroma phenotype, as determined by staining for α-SMA, vimentin, tenascin, calponin, desmin and Masson's trichrome. In conclusion, MF stromal cells from PCa participate in the progression and metastasis of PCa, modualting inflammation, angiogenesis and epithelial cancer cell proliferation

Remediación de un suelo crónicamente contaminado con hidrocarburos policíclicos aromáticos (PAH) combinando la oxidación química y la inoculación de un hongo ligninolítico

La actividad petrolera en nuestro país genera grandes volúmenes de residuos que impactan negativamente en suelos, agua y aire. Estos residuos se depositan como barros oleosos en los fondos de tanques de almacenamiento de crudo y se generan en grandes cantidades en la etapa final de su refinación, en separadores gravitacionales API (American Petroleum Institute). Los barros oleosos son considerados residuos peligrosos según la normativa vigente en Argentina, la cual exige tratamiento previo a su disposición final. En este contexto, la presente tesis tuvo como objetivo general remediar matrices sólidas complejas contaminadas con un barro petroquímico proviene del fondo de pileta API (FP), utilizando procesos combinados de oxidación química y bioaumento con un hongo ligninolítico. Para el desarrollo de la presente tesis se utilizó persulfato de amonio (PSA) como oxidante y al hongo ligninolítico Coriolopsis rigida LPSC 232. Es conocida la habilidad de este hongo para degradar hidrocarburos alifáticos y aromáticos provenientes del petróleo o suelos contaminados, involucrando complejos sistemas oxidativos que incluyen a enzimas extracelulares, siendo necesario que los contaminantes están biodisponibles. El pretratamiento con PSA tuvo la finalidad de oxidar los compuestos orgánicos presentes en los barros, a especies químicas eventualmente menos tóxicas con mayor solubilidad y biodisponibilidad. Por lo que la aplicación de estrategias combinadas potenciaría las ventajas de las técnicas individuales a fin de minimizar sus limitaciones. Inicialmente el barro FP fue caracterizado en función de sus propiedades físicas, químicas, microbiológicas y toxicológicas, revelando un efecto fitotóxico con una alta concentración de hidrocarburos totales (HT), representada principalmente por resinas. La abundancia relativa de representantes del phylum Proteobacteria, con miembros reconocidos degradadores de hidrocarburos sugiere la existencia de una microbiota bacteriana con un potencial metabólico para la degradación. La aplicación del PSA sobre el barro FP redujo un 31±5% el contenido de HT, actuando principalmente sobre la fracción de resinas, acompañado de la disminución de la concentración bacteriana. El análisis taxonómico (secuenciación masiva del gen 16S rARN) reveló la selección de representantes del orden Pseudomonadales, con miembros potencialmente degradadores de hidrocarburos, y representantes de Lactobacillales, reconocidos como generalistas. El impacto negativo también fue evidenciado sobre la comunidad fúngica nativa, con la consecuente dominancia de representantes del género Penicillium (Eurotiales). Dicho efecto indicaría que el pretratamiento con PSA reduce las posibilidades de competencia de la biota nativa con el inoculante fúngico. Paralelamente se evaluó la habilidad del hongo candidato para tolerar y/o transformar hidrocarburos modelos y del barro FP antes y después de la oxidación. Los resultados demuestran que C. rigida LPSC 232 posiblemente a través de procesos cometabólicos, tiene capacidad de tolerar bajo ciertas condiciones determinados PAH, incluyendo los más complejos disponibles en el barro FP. Bajo ciertas condiciones, se comprobó que hidrocarburos específicos alteran los procesos de glucólisis y la síntesis de ácidos grasos por el hongo, así como su habilidad para remover y/o mineralizar compuestos tóxicos. Bajo condiciones de fermentación en estado sólido se evidenció la capacidad fúngica de mineralizar componentes del barro FP, sin alterar la actividad de los microorganismos autóctonos del residuo. Sobre un suelo contaminado con barro FP al 10%, LPSC 232 removió eficientemente HT en presencia de la microbiota nativa luego de 90 días, disminuyendo su fitotoxicidad respecto del tratamiento control. En sistemas con barro FP al 25%, la estrategia de inoculación de LPSC 232 condicionó el alcance del proceso, siendo prometedor la aplicación de una suspensión miceliar en adición a un sustrato lignocelulósico en comparación a la utilización de este último como un simple vehículo de inoculación. Se sugiere que esto puede tener relación con los niveles de actividad lacasa detectados en los sistemas de estudio. Se comprobó que el tratamiento combinado de oxidación del barro FP seguido de bioaumento con C. rigida LPSC 232 promueve la recuperación de las comunidades bacterianas y fúngicas nativas del sistema. Además de generar cambios sobre los hidrocarburos del barro FP luego de 60 días, asociados a la formación de quinonas y a la desorganización de los núcleos aromáticos. Dichos cambios fueron evidenciados tempranamente en presencia de la microbiota nativa. De esta manera se demuestra que C. rigida LPSC 232 genera cambios en la microbiota asociada a matrices contaminadas con un barro FP API y promueve una activa degradación de hidrocarburos. No obstante, el proceso de remediación de una matriz contaminada como un barro FP es complejo, siendo aún necesarios estudios adicionales para confirmar la eficiencia del bioaumento a posteriori del tratamiento con un oxidante químico.Facultad de Ciencias Exacta

Increased levels of DNA methyltransferases are associated with the tumorigenic capacity of prostate cancer cells

DNA methylation might be the earliest somatic genome changes in prostate cancer that also play an important role in the process of tumor invasion, growth and metastasis. In recent years, several inhibitors of DNA methyltransferases (DNMTis) have been developed and evaluated in pre-clinical models and in clinical trials. While these compounds are effective in the treatment of hematological conditions, clinical trials in solid tumors and in prostate cancer have shown limited or no efficacy. This may be attributed to inappropriate dose regimens leading to toxicity-related adverse events. As with other anti-target compounds, one of the obstacles encountered with DNMTis in prostate cancer could be the inability to select patients for the clinical studies as well as the inability to monitor the efficacy of the drug if not the conclusion of the study. Primary cultures derived from human prostatic tissues harvested from patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa) as well as neoplastic and non-neoplastic prostate cell lines were tested for DNMT expression/activity and to monitor azacitidine molecular efficacy. We observed that in primary cultures the levels of DNMT activity as well as the protein levels of DNMT1, DNMT3a and DNMT3b were higher in cultures derived from PCa compared to BPH tissue samples and significantly higher in cultures derived from PCa with Gleason scores ≥7 compared to those observed in cultures derived from Gleason scores <7. In addition, DNMT activity as well as DNMT1, DNMT3a and DNMT3b levels were higher in PCa cell lines compared to their non-neoplastic counterparts. Although DNMT activity was higher in high tumorigenic/aggressive PCa cell lines compared to low tumorigenic/aggressive cell lines, only the levels of DNMT3a and DNMT3b were significantly higher in the first group of cells, suggesting that DNMT1 activity is related to the transition to non-neoplastic versus neoplastic phenotype whereas the de novo methylation enzymes were mainly related to progression. Nevertheless, the comparison in the more aggressive PC3 cell derivatives (PC3-LN4 cells) also possessed higher levels of DNMT1 compared to PC3 and PC3M from which these cells were derived. Collectively, our results confirm previous data on the increased methylation in more aggressive tumors supporting the use of DNMTis in advanced prostate cancer. In addition, since glutathione S-transferase-π (GSTP1) was re-expressed or its protein levels were increased after treatment with non-toxic azacitidine doses and since GSTP1 can easily be measured in patient sera, the monitoring of this protein may aide in the evaluation of therapy in future clinical trials

Diversification versus specialization in complex ecosystems

By analyzing the distribution of revenues across the production sectors of quoted firms we suggest a novel dimension that drives the firms diversification process at country level. Data show a non trivial macro regional clustering of the diversification process, which underlines the relevance of geopolitical environments in determining the microscopic dynamics of economic entities. These findings demonstrate the possibility of singling out in complex ecosystems those micro-features that emerge at macro-levels, which could be of particular relevance for decision-makers in selecting the appropriate parameters to be acted upon in order to achieve desirable results. The understanding of this micro-macro information exchange is further deepened through the introduction of a simplified dynamic model

CFTR Modulation Reduces SARS-CoV-2 Infection in Human Bronchial Epithelial Cells

People with cystic fibrosis should be considered at increased risk of developing severe symptoms of COVID-19. Strikingly, a broad array of evidence shows reduced spread of SARS-CoV-2 in these subjects, suggesting a potential role for CFTR in the regulation of SARS-CoV-2 infection/replication. Here, we analyzed SARS-CoV-2 replication in wild-type and CFTR-modified human bronchial epithelial cell lines and primary cells to investigate SARS-CoV-2 infection in people with cystic fibrosis. Both immortalized and primary human bronchial epithelial cells expressing wt or F508del-CFTR along with CRISPR/Cas9 CFTR-ablated clones were infected with SARS-CoV-2 and samples were harvested before and from 24 to 72 h post-infection. CFTR function was also inhibited in wt-CFTR cells with the CFTR-specific inhibitor IOWH-032 and partially restored in F508del-CFTR cells with a combination of CFTR modulators (VX-661+VX-445). Viral load was evaluated by real-time RT-PCR in both supernatant and cell extracts, and ACE-2 expression was analyzed by both western blotting and flow cytometry. SARS-CoV-2 replication was reduced in CFTR-modified bronchial cells compared with wild-type cell lines. No major difference in ACE-2 expression was detected before infection between wild-type and CFTR-modified cells, while a higher expression in wild-type compared to CFTR-modified cells was detectable at 72 h post-infection. Furthermore, inhibition of CFTR channel function elicited significant inhibition of viral replication in cells with wt-CFTR, and correction of CFTR function in F508del-CFTR cells increased the release of SARS-CoV-2 viral particles. Our study provides evidence that CFTR expression/function is involved in the regulation of SARS-CoV-2 replication, thus providing novel insights into the role of CFTR in SARS-CoV-2 infection and the development of therapeutic strategies for COVID-19

Vaginal Intraepithelial Neoplasia: Histopathological Upgrading of Lesions and Evidence of Occult Vaginal Cancer

Objective The aim of this study was to analyze women treated with excisional procedures for vaginal high-grade squamous intraepithelial lesions (HSILs). The histopathological upgrading of the lesions previously detected on vaginal biopsy and the presence of occult invasive vaginal cancer in the specimens excised were investigated, to identify a higher risk subset of women.Materials and Methods A retrospective analysis of the medical records of 86 women with a biopsy histopathologic diagnosis of vaginal HSIL (vaginal intraepithelial neoplasias [VaINs]: VaIN2 and VaIN3) and subsequent excisional therapy, consecutively referred to the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014, was performed.Results Of the 86 patients, 4 cases (4.6%) of occult vaginal cancer were detected, all of them in women previously diagnosed with VaIN3 on biopsy (4/39 cases, 10.3%). Women with diagnosis of VaIN2 on biopsy showed an upgrading of lesions, with diagnosis of VaIN3 on the final specimen in 5 (10.6%) of 47 cases, with no cases of VAIN2 upgraded to invasive cancer. In 33.3% of the women initially diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related disease, a final histopathological upgrading of lesions emerged. Furthermore, tobacco use was significantly related to the histopathological upgrading of lesions previously detected on vaginal biopsy.Conclusions Women diagnosed with VaIN3 should be treated with excisional procedures as first-line surgical approach, given the risk of occult invasive disease in 10% of the cases. Women diagnosed with VaIN2 and with previous hysterectomy for human papillomavirus-related cervical diseases should always be carefully evaluated and possibly excised, given the higher risk of histopathological upgrading of lesions and thus the potential risk of occult vaginal cancer. Tobacco users should be considered as high-risk group