Programming agent-based demographic models with cross-state and message-exchange dependencies: A study with speculative PDES and automatic load-sharing

Agent-based modeling and simulation is a versatile and promising methodology to capture complex interactions among entities and their surrounding environment. A great advantage is its ability to model phenomena at a macro scale by exploiting simpler descriptions at a micro level. It has been proven effective in many fields, and it is rapidly becoming a de-facto standard in the study of population dynamics. In this article we study programmability and performance aspects of the last-generation ROOT-Sim speculative PDES environment for multi/many-core shared-memory architectures. ROOT-Sim transparently offers a programming model where interactions can be based on both explicit message passing and in-place state accesses. We introduce programming guidelines for systematic exploitation of these facilities in agent-based simulations, and we study the effects on performance of an innovative load-sharing policy targeting these types of dependencies. An experimental assessment with synthetic and real-world applications is provided, to assess the validity of our proposal

Uveal Melanoma, Angiogenesis and Immunotherapy, Is There Any Hope?

Uveal melanoma is considered a rare disease but it is the most common intraocular malignancy in adults. Local treatments are effective, but the systemic recurrence rate is unacceptably high. Moreover, once metastasis have developed the prognosis is poor, with a 5-year survival rate of less than 5%, and systemic therapies, including immunotherapy, have rendered poor results. The tumour biology is complex, but angiogenesis is a highly important pathway in these tumours. Vasculogenic mimicry, the ability of melanomas to generate vascular channels independently of endothelial cells, could play an important role, but no effective therapy targeting this process has been developed so far. Angiogenesis modulates the tumour microenvironment of melanomas, and a close interplay is established between them. Therefore, combining immune strategies with drugs targeting angiogenesis offers a new therapeutic paradigm. In preclinical studies, these approaches effectively target these tumours, and a phase I clinical study has shown encouraging results in cutaneous melanomas. In this review, we will discuss the importance of angiogenesis in uveal melanoma, with a special focus on vasculogenic mimicry, and describe the interplay between angiogenesis and the tumour microenvironment. In addition, we will suggest future therapeutic approaches based on these observations and mention ways in which to potentially enhance current treatments

Experiences of simulation use in industrial projects

This paper presents experiences obtained from our involvement in the development of industrial simulation projects. Some important, common questions are covered, such as the need to define model behavior using a conceptual model, the problem of choosing the appropriate tool to code the model, and the validation and verification process required. As we will see, the scope of applicability of simulation is broad and the tools are therefore diverse. A clear understanding of the objectives of the simulation, the client’s aims and the resources at our disposal are key issues that often determine the success of a simulation project.Peer ReviewedPostprint (published version

An updated biostratigraphy for the late Aragonian and the Vallesian of the Vallès-Penedès Basin (Catalonia)

The Vallès-Penedès Basin (Catalonia, Spain) is a classical area for the study of the Miocene land mammal faunas and includes one of the densest and most continuous records in Eurasia. Furthermore, it is the type area for the Vallesian European land mammal age. After decades of study a huge amount of bio- and magnetostratigraphic data have been collected, allowing an unprecedented dating accuracy. Here we provide an updated local biostratigraphy for the late Aragonian, Vallesian and Turolian of the Vallès-Penedès Basin. This new biostratigraphic scheme is almost exclusively based on fossil rodents, which are the most abundant and one of the best known mammal orders in the area. Our proposal represents a significant refinement compared to previous attempts and provides a formal diagnosis and description of each zone, as well as clear definition of boundaries and a reference locality and section. The chronology of zone boundaries and main bioevents is based on detailed magnetostratigraphic data. The defined biozones allow for the correlation of the sites without associated magnetostratigraphical data. Finally, the correlation of the Vallès-Penedès local zones with other detailed local biostratigraphies, such as those of the Calatayud-Montalbán and Teruel basins (east-central Spain) is discussed. The sequence and chronology of the main bioevents is roughly comparable, although the rodent succession and the structure of the assemblage show important differences between these areas

Análisis del riesgo en un modelo multinivel de suministro

This research proposes stress tests to evaluate a set of hypothetical crisis scenarios linked with periods of greater volatility in a sample of commercial transactions among three companies from a multilevel supply model. The solution identifies cost-related levels of impact for a set of hypothetical scenarios associated with parameters such as levels of reliability and volatility in a risky time horizon.La investigación propone las pruebas de estrés para evaluar un conjunto de escenarios hipotéticos de crisis vinculados a periodos con mayor volatilidad, dada una muestra de transacciones comerciales entre tres entidades de un modelo multinivel de suministro. La solución identifica los niveles de impacto en términos de costo para un conjunto de escenarios hipotéticos asociados a parámetros tales como niveles de confiabilidad y volatilidad en un horizonte temporal de riesgo

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

Background: Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods: We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results: TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions: We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

ErbBs inhibition by lapatinib blocks tumor growth in an orthotopic model of human testicular germ cell tumor

In this work, we have analyzed the expression of different members of the ErbB family in human samples of testicular germ cell tumors (GCTs). We observed expression of ErbB1 or ErbB2 in different tumor subtypes, but we also found high expression of ErbB3 in all GCTs tested. This pattern of expression was maintained when primary tumors were orthotopically implanted in nude mice. We have chosen a choriocarcinoma model characterized by high levels of ErbB1, but also of ErbB2 and ErbB3, to assay the in vivo effect of ErbB inhibitors on tumoral growth. Our results showed a complete lack of effect (refractoriness) to the pure ErbB1 receptor inhibitors cetuximab and gefitinib. While these inhibitors blocked ErbB1 phosphorylation, ErbB2 phosphorylation was not affected, suggesting an ErbB1-independent activation of this receptor. To confirm the importance of ErbB2 activation, animals were treated with lapatinib, a dual ErbB1 and ErbB2 inhibitor. Lapatinib treatment caused a 50% inhibition in tumor growth, an effect correlated with a blockade of both ErbB1 and ErbB2 phosphorylation levels, and of downstream signaling pathways (Akt, ERKs and Stat3). ErbB2 activation could still occur due to the formation of ErbB2/ErbB3 heterodimers, and ErbB3 activation was completely inhibited by lapatinib. Finally, combined inhibition of ErbB1 (gefitinib) and ErbB3 activities (knockdown expression by shRNA) inhibited tumoral testicular cells proliferation in a similar way to lapatinib. Our results explain why lapatinib but not anti-ErbB1 agents might be effective for treatment of testicular GCT patients

To what extent the traffic restriction policies applied in Barcelona city can improve its air quality?

Barcelona city (Spain) is applying a series of traffic restriction measures that aim at renewing and reducing the amount of circulating vehicles to improve air quality. The measures include changes in the built environment to reduce private vehicle space in specific areas through the so-called “superblocks” and tactical urban planning actions, along with the implementation of a city-wide Low Emission Zone (LEZ) that restricts the entry of the most polluting vehicles to the city. Our study quantifies the impact of these measures in the greater area of Barcelona combining a coupled macroscopic traffic and pollutant emission model with a multi-scale air quality model. Our modelling system allows estimating the effect of different traffic restrictions upon traffic and the associated emissions and air quality levels at a very high resolution (20 m). The measures were evaluated both individually and collectively to assess both their relative and overall impact upon emissions and air quality. We show that in the absence of traffic demand reductions, the application of isolated measures that reduce private vehicle space, either through superblocks or tactical urban planning, have no overall emission impacts; only localized street-level NOx positive and negative changes (±17%) are found due to traffic re-routing and the generation of new bottlenecks. It is only when these measures are combined with optimistic fleet renewal as a result of the LEZ implementation and demand reductions, that relevant global emission reductions in NOx are obtained (-13% and -30%, respectively) with estimated NO2 reductions of -36% and -23% at the two traffic air quality monitoring stations. Despite the potential improvements, our simulations suggest that current measures are insufficient to comply with EU air quality standards and that further traffic restriction policies to reduce traffic demand are needed.The authors acknowledge CARNET-The Future Mobility Research HUB to allow the usage and work on the BCN-VML network, as well as PTV VISUM for the traffic software license. The author thankfully acknowledges the computer resources at MareNostrum and the technical support pro- vided by Barcelona Supercomputing Center (PRACE, AECT-2020-1-0007, AECT-2021-1-0027). The authors also acknowledge the support from the Ministerio de Ciencia, Innovación y Universidades (MICINN) as part of the BROWNING project RTI2018-099894-B-I00 and NUTRIENT project CGL2017-88911-R and the support from the Agencia Estatal de Investigacion (AEI) as part of the VITALISE project (PID2019-108086RA- I00/AEI/10.13039/501100011033). Carlos Pérez García-Pando acknowl- edges the long-term support from the AXA Chair in Sand and Dust Storms (AXA Research Fund), as well as the support received through the Ramón y Cajal programme (grant RYC-2015-18690) of the Spanish Ministry of Economy and Competitiveness.Peer ReviewedPostprint (published version

The Miocene mammal record of the Vallès-Penedès Basin (Catalonia)

The land mammal record of the Vallès-Penedès Basin (Catalonia, NE Spain) ranges from the early Miocene (Ramblian) to the late Miocene (Turolian), that is from about 20 to 7 Ma. Here we present an updated review of the mammal succession focusing on biochronology as well as on environmental and faunal changes. Based on faunal similarities with central Europe, we interpret this basin as a transitional zone between the forested environments of northern regions and the more arid landscapes of the inner Iberian Peninsula. The quality of the Vallès-Penedès record and its chronostratigraphic control is clearly better for the late Aragonian and the Vallesian (between 12.6-9.0 Ma), especially for small mammals. Therefore, we analyze small mammal diversity dynamics during this interval. Contrary to previous analyses, which found an abrupt extinction event coinciding with the early/late Vallesian boundary (the Vallesian Crisis), our results show that this pattern is due to uneven sampling. Instead, taxonomic richness slowly decreased since the late Vallesian as a result of a series of extinctions that mostly affected forest-dwelling taxa

El Miocè inferior de la conca del Vallès-Penedès : un registre excepcional dels canvis climàtics i faunístics

Altres ajuts: CERCA Programme/Generalitat de Catalunya. Les tasques de camp es van poder dur a terme gràcies al suport del Departament de Cultura de la Generalitat de Catalunya (projecte 2014/100584) i la National Geographic Society (beca d'exploració ref. 9640-15).Les intervencions paleontològiques recents han mostrat que el registre de vertebrats continentals del Miocè inferior de la conca del Vallès-Penedès és molt més ric i continu del que es pensava. Avui dia es coneixen una vintena de jaciments que han lliurat tant microvertebrats com macrovertebrats. Els nostres estudis biostratigràfics han permès una datació precisa dels diferents jaciments i també dels principals esdeveniments faunístics i climàtics