| 1. |
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| 2. |
- Bernal, Ximena E., et al.
(author)
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Empowering Latina scientists
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
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Journal article (other academic/artistic)
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| 3. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 4. |
- Bentham, James, et al.
(author)
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A century of trends in adult human height
- 2016
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In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
-
Journal article (peer-reviewed)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 5. |
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| 6. |
- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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| 7. |
- Kassebaum, Nicholas J., et al.
(author)
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Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
-
Journal article (peer-reviewed)abstract
- Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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| 8. |
- Kehoe, Laura, et al.
(author)
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Make EU trade with Brazil sustainable
- 2019
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Journal article (other academic/artistic)
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| 9. |
- Manzoni, Claudia, et al.
(author)
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Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
- 2024
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In: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
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Journal article (peer-reviewed)abstract
- Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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| 10. |
- Torruella, Pau, et al.
(author)
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3D Visualization of the Iron Oxidation State in FeO/Fe3O4 Core-Shell Nanocubes from Electron Energy Loss Tomography
- 2016
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 16:8, s. 5068-5073
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Journal article (peer-reviewed)abstract
- The physicochemical properties used in numerous advanced nanostructured devices are directly controlled by the oxidation states of their constituents. In this work we combine electron energy-loss spectroscopy, blind source separation, and computed tomography to reconstruct in three dimensions the distribution of Fe2+ and Fe3+ ions in a FeO/Fe3O4 core/shell cube-shaped nanoparticle with nanometric resolution. The results highlight the sharpness of the interface between both oxides and provide an average shell thickness, core volume, and average cube edge length measurements in agreement with the magnetic characterization of the sample.
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| 11. |
- Abercrombie, Daniel, et al.
(author)
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Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
- 2020
-
In: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
-
Journal article (peer-reviewed)abstract
- This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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| 12. |
- Alberto Diaz-Sanchez, Adrian, et al.
(author)
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First molecular evidence of bovine hemoplasma species (Mycoplasma spp.) in water buffalo and dairy cattle herds in Cuba
- 2019
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In: Parasites & Vectors. - : BioMed Central. - 1756-3305. ; 12
-
Journal article (peer-reviewed)abstract
- Background: Hemotropic mycoplasmas (aka hemoplasmas) are small bacteria which cause infectious anemia in several mammalian species including humans. Information on hemoplasma infections in Cuban bovines remains scarce and no studies applying molecular methods have been performed so far. The aim of the present study was to utilize real-time PCR and sequence analysis to investigate dairy cattle and buffalo from Cuba for the presence of bovine hemoplasma species.Results: A total of 80 blood samples from 39 buffalo and 41 dairy cattle were investigated for the presence of Mycoplasma wenyonii and Candidatus Mycoplasma haemobos using two species-specific real-time TaqMan PCR assays. PCR results revealed overall 53 (66.2%; 95% CI: 55.3-75.7%) positive animals for M. wenyonii and 33 (41.2%; 95% CI: 31.1-52.2%) for Ca. M. haemobos; the latter were all co-infections with M. wenyonii. The sample prevalences were similar in cattle and buffalo. Based on the sequence analysis of the nearly full-length 16S rRNA gene from two cattle and two buffalo, the presence of M. wenyonii and Ca. M. haemobos was confirmed. Statistical analysis revealed that buffalo and cattle one year of age or older were more frequently infected with M. wenyonii or Ca. M. haemobos than younger animals. PCR-positivity was not associated with anemia; however, the infection stage was unknown (acute infection versus chronic carriers).Conclusions: The high occurrence of bovine hemoplasma infections in buffalo and dairy cattle may have a significant impact on Cuban livestock production. To the best of our knowledge, this is the first molecular evidence of bovine hemoplasma species infection in dairy cattle and buffalo from Cuba and the Caribbean.
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| 13. |
- Alberto Morales, Oscar, et al.
(author)
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Estructura léxico-gramatical de títulos de artculos de investigación de odontología en español
- 2020
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In: RLA. Revista de Lingüística Teórica y Aplicada. - : UNIV CONCEPCION, FAC HUMANIDADES ARTE. - 0033-698X .- 0718-4883. ; 58:2, s. 69-92
-
Journal article (peer-reviewed)abstract
- This paper aims to analyze the syntactic structure and rhetorical function of 250 dentistry research articles titles in Spanish. Length, punctuation, lexical-grammatical structure, and styles of titles were examined qualitatively and quantitatively. It was found an average of 15.5 words per title; three types of titles: nominal (78%), compound (21.2%) and full-sentence titles (0.8%). Titles without punctuation predominated. 21.2% used colon and period to form compound titles predominated. It was observed that compound titles combine two rhetorical components: topic-method and topic-description. Uni-head nominal constructions (using mainly non-discipline-specific nouns) using prepositional phrases (100%), adjectives (29%), non-personal verbal phrases (28%) and relative clauses (4.4%) as postmodifiers predominated.
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| 14. |
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| 15. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Assessing Aesthetic Criteria in the Evolutionary dungeon Designer
- 2018
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In: Proceedings of the 13th International Conference on the Foundations of Digital Games. - New York, NY, USA : ACM Digital Library.
-
Conference paper (peer-reviewed)abstract
- The Evolutionary Dungeon Designer (EDD) [1] is as a mixed-initiative tool for creating dungeons for adventure games. Results from a user study with game developers positively evaluated EDD as a suitable framework for collaboration between human designers and PCG suggestions, highlighting these as time-saving and inspiring for creating dungeons [2]. Previous work on EDD identified the need of assessing aesthetic criteria as a key area for improvement in its PCG Engine. By upgrading the individual encoding system and the fitness evaluation in EDD's evolutionary algorithm, we present three techniques to preserve and account the designer's aesthetic criteria during the dungeon generation process: the capability of locking sections for preserving custom aesthetic structures, as well as the measurement of symmetry and similarity in the provided suggestions.
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| 16. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Assessing the Effects of Interacting with MAP-Elites
- 2021
-
In: Proceedings of the seventeenth {AAAI} Conference on Artificial Intelligence and Interactive Digital Entertainment. - : Association for the Advancement of Artificial Intelligence. - 9781577358718 ; , s. 124-131
-
Conference paper (peer-reviewed)abstract
- MAP-Elites has been successfully applied to the generation of game content and robot behaviors. However, its behavior and performance when interacted with in co-creative systems is underexplored. This paper analyzes the implications of synthetic interaction for the stability and adaptability of MAP-Elites in such scenarios. We use pre-recorded human-made level design sessions with the Interactive Constrained MAP-Elites (IC MAP-Elites). To analyze the effect of each edition step in the search space over time using different feature dimensions, we introduce Temporal Expressive Range Analysis (TERA). With TERAs, MAP-Elites is assessed in terms of its adaptability and stability to generate diverse and high-performing individuals. Our results show that interactivity, in the form of design edits and MAP-Elites adapting towards them, directs the search process to previously unexplored areas of the fitness landscape and points towards how this could improve and enrich the co-creative process with quality-diverse individuals.
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| 17. |
- Alvarez, Alberto, et al.
(author)
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Cdc42 is required in mural cells for proper patterning of the retinal vasculature
-
Other publication (other academic/artistic)abstract
- Mural cells constitute the outer lining of blood vessels. They are known as pericytes in the capillary network and referred to as smooth muscle cells (SMC) around arteries and veins. Despite their ubiquity, their contribution to vascular morphogenesis remains obscure. In this work, we investigated the role of Cdc42 in mural cells in vivo, using the developing mouse retina as a model. We find that, during postnatal development, Cdc42 is required in both, pericytes and smooth muscle cells to maintain proper cell morphology, coverage and distribution. During retinal angiogenesis, Cdc42-depleted pericytes lag behind the sprouting front, at least in part due to decreased proliferation. Consequently, capillaries at the sprouting front remain pericyte deprived and are prone to increased vascular leakage. In addition, arteries and arterioles deviate from their normal growth directions and trajectory. While in the adult retina, mural cell coverage normalizes and pericytes adopt a normal morphology, smooth muscle cell morphologies remain abnormal and arteriolar branching angles are markedly reduced. Our findings demonstrate that Cdc42 is required for mural cell proliferation, morphology and distribution and suggest that mural cells are essential for normal vascular morphogenesis of the developing retinal vasculature.
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| 18. |
- Alvarez, Alberto, 1992-
(author)
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ChatGPT as a Narrative Structure Interpreter
- 2023
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In: Interactive Storytelling. - : Springer. - 9783031476570 - 9783031476587 ; , s. 113-121
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Conference paper (peer-reviewed)abstract
- Narrative structures define the skeleton of narratives and help at identifying common structures in stories, that then can be used to compare structures, define variations, and understand prototypical [structural] components. However, narrative structures are just one piece of the puzzle, their interpretation is what gives room to the stories seen in transmedia storytelling. In principle, a structure can be interpreted and developed with a myriad of stories, but requires some type of corpus to develop it further. Large language models such as ChatGPT could be employed for this task, if we are able to define a good narrative structure and give the tools to the algorithm to develop them further. For this paper, we use a narrative structure system called TropeTwist, which employs interconnected tropes as narrative structures, defining characters, conflicts, and plot devices in a relational graph, which gives raise to a set of trope micro- and meso-patterns. Using ChatGPT and through the web interface, we communicate all the possible elements to be used from TropeTwist and tasked ChatGPT to interpret them and generate stories. We describe our process and methodology to reach these interpretations, and present some of the generated stories based on a constructed narrative structure. Our results show the possibilities and limitations of using these systems and elaborate on future work to combine large language models for other tasks within narrative interpretation and generation.
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| 19. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Empowering Quality Diversity in Dungeon Design with Interactive Constrained MAP-Elites
- 2019
-
Conference paper (peer-reviewed)abstract
- We propose the use of quality-diversity algorithms for mixed-initiative game content generation. This idea is implemented as a new feature of the Evolutionary Dungeon Designer, a system for mixed-initiative design of the type of levels you typically find in computer role playing games. The feature uses the MAP-Elites algorithm, an illumination algorithm which divides the population into a number of cells depending on their values along several behavioral dimensions. Users can flexibly and dynamically choose relevant dimensions of variation, and incorporate suggestions produced by the algorithm in their map designs. At the same time, any modifications performed by the human feed back into MAP-Elites, and are used to generate further suggestions.
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| 20. |
- Alvarez, Alberto, 1992-
(author)
-
Exploring Game Design through Human-AI Collaboration
- 2022
-
Doctoral thesis (other academic/artistic)abstract
- Game design is a hard and multi-faceted task that intertwines different gameplay mechanics, audio, level, graphic, and narrative facets. Games' facets are developed in conjunction with others with a common goal that makes games coherent and interesting. These combinations result in plenty of games in diverse genres, which usually require a collaboration of a diverse group of designers. Collaborators can take different roles and support each other with their strengths resulting in games with unique characteristics. The multi-faceted nature of games and their collaborative properties and requirements make it an exciting task to use Artificial Intelligence (AI). The generation of these facets together requires a holistic approach, which is one of the most challenging tasks within computational creativity. Given the collaborative aspect of games, this thesis approaches their generation through Human-AI collaboration, specifically using a mixed-initiative co-creative (MI-CC) paradigm. This paradigm creates an interactive and collaborative scenario that leverages AI and human strengths with an alternating and proactive initiative to approach a task. However, this paradigm introduces several challenges, such as Human and AI goal alignment or competing properties.In this thesis, game design and the generation of game facets by themselves and intertwined are explored through Human-AI collaboration. The AI takes a colleague's role with the designer, arising multiple dynamics, challenges, and opportunities. The main hypothesis is that AI can be incorporated into systems as a collaborator, enhancing design tools, fostering human creativity, and reducing workload. The challenges and opportunities that arise from this are explored, discussed, and approached throughout the thesis. As a result, multiple approaches and methods such as quality-diversity algorithms and designer modeling are proposed to generate game facets in tandem with humans, create a better workflow, enhance the interaction, and establish adaptive experiences.
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| 21. |
- Alvarez, Alberto, 1992-
(author)
-
Exploring the Dynamic Properties of Interaction in Mixed-Initiative Procedural Content Generation
- 2020
-
Licentiate thesis (other academic/artistic)abstract
- As AI develops, grows, and expands, the more benefits we can have from it. AI is used in multiple fields to assist humans, such as object recognition, self-driving cars, or design tools. However, AI could be used for more than assisting humans in their tasks. It could be employed to collaborate with humans as colleagues in shared tasks, which is usually described as Mixed-Initiative (MI) paradigm. This paradigm creates an interactive scenario that leverage on AI and human strengths with an alternating and proactive initiative to approach a task. However, this paradigm introduces several challenges. For instance, there must be an understanding between humans and AI, where autonomy and initiative become negotiation tokens. In addition, control and expressiveness need to be taken into account to reach some goals. Moreover, although this paradigm has a broader application, it is especially interesting for creative tasks such as games, which are mainly created in collaboration. Creating games and their content is a hard and complex task, since games are content-intensive, multi-faceted, and interacted by external users. Therefore, this thesis explores MI collaboration between human game designers and AI for the co-creation of games, where the AI's role is that of a colleague with the designer. The main hypothesis is that AI can be incorporated in systems as a collaborator, enhancing design tools, fostering human creativity, reducing their workload, and creating adaptive experiences. Furthermore, This collaboration arises several dynamic properties such as control, expressiveness, and initiative, which are all central to this thesis. Quality-Diversity algorithms combined with control mechanisms and interactions for the designer are proposed to investigate this collaboration and properties. Designer and Player modeling is also explored, and several approaches are proposed to create a better workflow, establish adaptive experiences, and enhance the interaction. Through this, it is demonstrated the potential and benefits of these algorithms and models in the MI paradigm.
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| 22. |
- Alvarez, Alberto, 1992-, et al.
(author)
-
Fostering Creativity in the Mixed-Initiative Evolutionary Dungeon Designer
- 2018
-
In: Proceedings of the 13th International Conference on the Foundations of Digital Games. - New York, NY, USA : ACM Digital Library.
-
Conference paper (peer-reviewed)abstract
- Mixed-initiative systems highlight the collaboration between humans and computers in fostering the generation of more interesting content in game design. In light of the ever-increasing cost of game development, providing mixed-initiative tools can not only significantly reduce the cost but also encourage more creativity amongst game designers. The Evolutionary Dungeon Designer (EDD) [3] is a mixed-initiative tool with a focus on using evolutionary computation to procedurally generate content that adhere to game design patterns. As part of an ongoing project, feedback from a user study on EDD's capabilities as a mixed-initiative design tool pointed out the need for improvement on the tool's functionalities [4]. In this paper we present a review of the principles of the mixed-initiative model, as well as the existing approaches that implement it. The outcome of this analysis allows us to address the appointed needs for improvement by shaping a new version of EDD that we describe here. Finally, we also present the results from a user study carried out with professional game developers, in order to assess EDD's new functionalities. Results show an overall positive evaluation of the tool's intuitiveness and capabilities for empowering game developers' creative skills during the design process of dungeons for adventure games. They also allow us to identify upcoming challenges pattern-based mixed-initiative tools could benefit from.
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| 23. |
- Alvarez, Alberto, 1992-, et al.
(author)
-
Interactive Constrained MAP-Elites : Analysis and Evaluation of the Expressiveness of the Feature Dimensions
- 2022
-
In: IEEE Transactions on Games. - : IEEE. - 2475-1502 .- 2475-1510. ; 14:2, s. 202-211
-
Journal article (peer-reviewed)abstract
- We propose the Interactive Constrained MAP-Elites, a quality-diversity solution for game content generation, implemented as a new feature of the Evolutionary Dungeon Designer (EDD): a mixed-initiative co-creativity tool for designing dungeons. The feature uses the MAP-Elites algorithm, an illumination algorithm that segregates the population among several cells depending on their scores with respect to different behavioral dimensions. Users can flexibly and dynamically alternate between these dimensions anytime, thus guiding the evolutionary process in an intuitive way, and then incorporate suggestions produced by the algorithm in their room designs. At the same time, any modifications performed by the human user will feed back into MAP-Elites, closing a circular workflow of constant mutual inspiration. This paper presents the algorithm followed by an in-depth evaluation of the expressive range of all possible dimension combinations in several scenarios, and discusses their influence in the fitness landscape and in the overall performance of the procedural content generation in EDD.
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| 24. |
- Alvarez, Alberto, 1992-, et al.
(author)
-
Learning the Designer’s Preferences to Drive Evolution
- 2020
-
In: EvoApplications 2020. - Cham : Springer. - 9783030437220 - 9783030437213 ; , s. 431-445
-
Conference paper (peer-reviewed)abstract
- This paper presents the Designer Preference Model, a data-driven solution that pursues to learn from user generated data in a Quality-Diversity Mixed-Initiative Co-Creativity (QD MI-CC) tool, with the aims of modelling the user’s design style to better assess the tool’s procedurally generated content with respect to that user’s preferences. Through this approach, we aim for increasing the user’s agency over the generated content in a way that neither stalls the user-tool reciprocal stimuli loop nor fatigues the user with periodical suggestion handpicking. We describe the details of this novel solution, as well as its implementation in the MI-CC tool the Evolutionary Dungeon Designer. We present and discuss our findings out of the initial tests carried out, spotting the open challenges for this combined line of research that integrates MI-CC with Procedural Content Generation through Machine Learning.
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| 25. |
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| 26. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Questgram [Qg] : Toward a Mixed-Initiative Quest Generation Tool
- 2021
-
In: Proceedings of the 16th International Conference on the Foundations of Digital Games. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 1-10
-
Conference paper (peer-reviewed)abstract
- Quests are a core element in many games, especially role-playing and adventure games, where quests drive the gameplay and story, engage the player in the game’s narrative, and in most cases, act as a bridge between different game elements. The automatic generation of quests and objectives is an interesting challenge since this can extend the lifetime of games such as in Skyrim, or can help create unique experiences such as in AI Dungeon. This work presents Questgram [Qg], a mixed-initiative prototype tool for creating quests using grammars combined in a mixed-initiative level design tool. We evaluated our tool quantitatively by assessing the generated quests and qualitatively through a small user study. Human designers evaluated the system by creating quests manually, automatically, and through mixed-initiative. Our results show the Questgram’s potential, which creates diverse, valid, and interesting quests using quest patterns. Likewise, it helps engage designers in the quest design process, fosters their creativity by inspiring them, and enhance the level generation facet of the Evolutionary Dungeon Designer with steps towards intertwining both level and quest design.
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| 27. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Story Designer: Towards a Mixed-Initiative Tool to Create Narrative Structures
- 2022
-
In: FDG '22: Proceedings of the 17th International Conference on the Foundations of Digital Games. - New York, NY, USA : ACM Digital Library. - 9781450397957
-
Conference paper (peer-reviewed)abstract
- Narratives are a predominant part of games, and their design poses challenges when identifying, encoding, interpreting, evaluating, and generating them. One way to address this would be to approach narrative design in a more abstract layer, such as narrative structures. This paper presents Story Designer, a mixed-initiative co-creative narrative structure tool built on top of the Evolutionary Dungeon Designer (EDD) that uses tropes, narrative conventions found across many media types, to design these structures. Story Designer uses tropes as building blocks for narrative designers to compose complete narrative structures by interconnecting them in graph structures called narrative graphs. Our mixed-initiative approach lets designers manually create their narrative graphs and feeds an underlying evolutionary algorithm with those, creating quality-diverse suggestions using MAP-Elites. Suggestions are visually represented for designers to compare and evaluate and can then be incorporated into the design for further manual editions. At the same time, we use the levels designed within EDD as constraints for the narrative structure, intertwining both level design and narrative. We evaluate the impact of these constraints and the system’s adaptability and expressiveness, resulting in a potential tool to create narrative structures combining level design aspects with narrative.
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| 28. |
- Alvarez, Alberto, et al.
(author)
-
Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreER(T2) lines
- 2020
-
In: Transgenic research. - : Springer Nature. - 0962-8819 .- 1573-9368. ; 29:1, s. 53-68
-
Journal article (peer-reviewed)abstract
- The CreER(T2)/loxP system is widely used to induce conditional gene deletion in mice. One of the main advantages of the system is that Cre-mediated recombination can be controlled in time through Tamoxifen administration. This has allowed researchers to study the function of embryonic lethal genes at later developmental timepoints. In addition, CreER(T2) mouse lines are commonly used in combination with reporter genes for lineage tracing and mosaic analysis. In order for these experiments to be reliable, it is crucial that the cell labeling approach only marks the desired cell population and their progeny, as unfaithful expression of reporter genes in other cell types or even unintended labeling of the correct cell population at an undesired time point could lead to wrong conclusions. Here we report that all CreER(T2) mouse lines that we have studied exhibit a certain degree of Tamoxifen-independent, basal, Cre activity. Using Ai14 and Ai3, two commonly used fluorescent reporter genes, we show that those basal Cre activity levels are sufficient to label a significant amount of cells in a variety of tissues during embryogenesis, postnatal development and adulthood. This unintended labelling of cells imposes a serious problem for lineage tracing and mosaic analysis experiments. Importantly, however, we find that reporter constructs differ greatly in their susceptibility to basal CreER(T2) activity. While Ai14 and Ai3 easily recombine under basal CreER(T2) activity levels, mTmG and R26R-EYFP rarely become activated under these conditions and are therefore better suited for cell tracking experiments.
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| 29. |
- Alvarez, Alberto, 1992-, et al.
(author)
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Toward Designer Modeling Through Design Style Clustering
- 2022
-
In: IEEE Transactions on Games. - : IEEE. - 2475-1502 .- 2475-1510. ; 14:4, s. 676-686
-
Journal article (peer-reviewed)abstract
- We propose modeling designer style in mixed-initiative game content creation tools as archetypical design traces. These design traces are formulated as transitions between design styles; these design styles are in turn found through clustering all intermediate designs along the way to making a complete design. This method is implemented in the Evolutionary Dungeon Designer, a research platform for mixed-initiative systems to create adventure and dungeon crawler games. We present results both in the form of design styles for rooms, which can be analyzed to better understand the kind of rooms designed by users, and in the form of archetypical sequences between these rooms, i.e., Designer Personas.
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| 30. |
- Alvarez, Alberto, 1992-, et al.
(author)
-
TropeTwist:Trope-based Narrative Structure Generation
- 2022
-
In: Proceedings of the 13th Workshop on Procedural Content Generation, FDG. - New York, NY, USA : Association for Computing Machinery (ACM).
-
Conference paper (other academic/artistic)abstract
- Games are complex, multi-faceted systems that share common elements and underlying narratives, such as the conflict between a hero and a big bad enemy or pursuing a goal that requires overcoming challenges. However, identifying and describing these elements together is non-trivial as they might differ in certain properties and how players might encounter the narratives. Likewise, generating narratives also pose difficulties when encoding, interpreting, and evaluating them. To address this, we present TropeTwist, a trope-based system that can describe narrative structures in games in a more abstract and generic level, allowing the definition of games' narrative structures and their generation using interconnected tropes, called narrative graphs. To demonstrate the system, we represent the narrative structure of three different games. We use MAP-Elites to generate and evaluate novel quality-diverse narrative graphs encoded as graph grammars, using these three hand-made narrative structures as targets. Both hand-made and generated narrative graphs are evaluated based on their coherence and interestingness, which are improved through evolution.
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| 31. |
- Alvarez, Alberto, et al.
(author)
-
VEGF Receptor Tyrosine Kinases : Key Regulators of Vascular Function
- 2017
-
In: Protein Kinases In Development And Disease. - : Elsevier. - 9780128015131 ; 123, s. 433-
-
Book chapter (peer-reviewed)abstract
- Vascular endothelial growth factor receptor (VEGFR) tyrosine kinases are key regulators of vascular development in vertebrates. Their activation is regulated through a family of secreted glycoproteins, the vascular endothelial growth factors (VEGFs). Expression, proteolytic processing, and diffusion range of VEGF proteins need to be tightly regulated, due to their crucial roles in development. While some VEGFs form concentration gradients across developing tissues and act as morphogenes, others function as inhibitors of receptor activation and downstream signaling. Ligand-induced receptor dimerization leads to activation of the intrinsic tyrosine kinase activity, which results in autophosphorylation of the receptors and in turn triggers the recruitment of interacting proteins as well as the initiation of downstream signaling. Although many biochemical details of VEGFR signaling have been revealed, the in vivo relevance of certain signaling aspects still remains to be demonstrated. Here, we highlight basic principles of VEGFR signaling and discuss its crucial role during development of the vascular system in mammals.
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| 32. |
- Álvarez-Aznar, Alberto
(author)
-
Cdc42, orchestrator of vascular morphogenesis in the retina
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Cdc42 is a small GTPase that controls many cellular functions related to cytoskeletal dynamics, such as migration, polarity, and proliferation. Despite what we know of Cdc42 in other cell types, not much research has been done on the vasculature. This thesis describes the consequences of Cdc42 deletion in two vascular cell types—endothelial and mural cells—during developmental angiogenesis.In paper I, we demonstrate through a combination of in vitro, in silico, and in vivo assays, that Cdc42-deficient endothelial cells migrate less and fail to distribute normally in areas of naturally occurring high proliferation during angiogenesis, causing vascular malformations with enlarged lumens. In addition, these cells present impaired filopodia formation, a disadvantage for the tip cell position, disturbed axial polarity and altered junctions.With an in vivo approach, in paper III we demonstrate that the deletion of Cdc42 in mural cells has consequences on the morphogenesis of the retinal vasculature. Cdc42-deficient mural cells proliferate less and cannot keep up with the nascent angiogenic vasculature, which results in a complete pericyte loss at the sprouting front. Furthermore, we describe that mural cells contribute to the remodeling of the vasculature, also after the initial phases of angiogenesis.The CreERT2 system is frequently used for conditional gene deletion and lineage tracing. Tamoxifen administration allows spatiotemporally controlled recombination of fluorescent reporters, and tracing of the labeled cells. However, in the course of our studies, we observed tamoxifen-independent recombination. In paper II, we describe this phenomenon in detail, using different combinations of CreERT2 and fluorescent reporter lines. We conclude that tamoxifen-independent recombination is a widespread occurrence, and that fluorescent reporter lines present varying levels of susceptibility to it.In summary, the work presented here sheds new light on the role of Cdc42 in the vasculature. Additionally, this thesis describes in detail an important feature of CreERT2 and reporter lines that should be taken into account when performing lineage-tracing experiments.
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| 33. |
- Alvarez, Lluc, et al.
(author)
-
eProcessor: European, Extendable, Energy-Efficient, Extreme-Scale, Extensible, Processor Ecosystem
- 2023
-
In: Proceedings of the 20th ACM International Conference on Computing Frontiers 2023, CF 2023. ; , s. 309-314
-
Conference paper (peer-reviewed)abstract
- The eProcessor project aims at creating a RISC-V full stack ecosystem. The eProcessor architecture combines a high-performance out-of-order core with energy-efficient accelerators for vector processing and artificial intelligence with reduced-precision functional units. The design of this architecture follows a hardware/software co-design approach with relevant application use cases from the high-performance computing, bioinformatics and artificial intelligence domains. Two eProcessor prototypes will be developed based on two fabricated eProcessor ASICs integrated into a computer-on-module.
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| 34. |
- Alvarez-Larran, Alberto, et al.
(author)
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Unmet clinical needs in the management of CALR-mutated essential thrombocythaemia : a consensus-based proposal from the European LeukemiaNet
- 2021
-
In: The Lancet Haematology. - : Elsevier. - 2352-3026. ; 8:9, s. E658-E665
-
Research review (peer-reviewed)abstract
- Recommendations regarding management of essential thrombocythaemia rely on studies done before the discovery of the CALR mutation. On May 20, 2020, the European LeukemiaNet annual meeting was held with the goal to identify unmet clinical needs in myeloproliferative neoplasms. Because patients with a CALR mutation have specific clinical characteristics, treatment of CALR-mutated essential thrombocythaemia was considered an unmet clinical need by the European LeukemiaNet. The elaboration of a consensus document with recommendations according to current evidence was proposed as a solution for resolving uncertainties in the treatment of CALR-mutated essential thrombocythaemia. A steering committee comprising four European LeukemiaNet members was then formed and a panel of ten experts in the field was recruited. The experts proposed 51 potential unmet clinical needs in the management of CALR-mutated essential thrombocythaemia and were asked to score the relevance of each topic. Those topics that obtained the highest scores as relevant unmet clinical needs were identified, including antiplatelet therapy in patients at low risk, definition of extreme thrombocytosis and its management in patients at low risk, indications of cytoreduction and targets of therapy, first-line treatment of choice in young patients (<60 years), and management of pregnancy. After the steering committee revised the available evidence for each topic, a consensus on management and proposal for improving knowledge was achieved by use of an email-based, two round, Delphi approach. Consensus was achieved when 90% of the panellists agreed with a statement and included 14 recommendations and six solution proposals. Key recommendations included careful observation for asymptomatic patients with classical, low-risk, CALR-mutated essential thrombocythaemia without cardiovascular risk factors; caution in the use of antiplatelet therapy for symptomatic patients at low risk with platelet counts of 1000-1500 × 109 platelets per L, in such cases cytoreduction is an adequate option, especially if adquired Von Willebrand disease is present; cytoreduction is recommended for extreme thrombocytosis (platelet count >1500 × 109 platelets per L) with pegylated interferon alfa being the preferred option for younger patients; both hydroxycarbamide and anagrelide might be given to patients ineligible for pegylated interferon alfa; and treatment algorithms for patients with high-risk pregnancies should not be changed according to genotype. The European LeukemiaNet proposes to use these recommendations in the routine management of patients with CALR-mutated essential thrombocythaemia, and designing new clinical studies in this field might be useful.
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| 35. |
- Alvarez, Maria Teresa, et al.
(author)
-
Lab-scale production of biogenic sulphide for metal precipitation in remote areas
- 2012
-
In: International Journal of Environment and Waste Management. - 1478-9876. ; 9:3-4, s. 313-329
-
Journal article (peer-reviewed)abstract
- Batch cultures with wheat straw, biomass of Paja Brava (Festuca orthophylla), filter paper, newspaper and beech leaves (Fagus sylvatica) were established to produce sulphide. Sulphide production, sulphate reduction, concentration of Volatile Fatty Acids (VFAs), enzyme activities and Fluorescence in situ hybridisation were determined. Approximately 5 mM of sulphide was produced during anaerobic digestion of wheat straw, while the production with newspaper as carbon source was the lowest (ca.1 mM). The sulphide production (2-5 mM) in the semi-continuous culture of the consortium A10, using wheat straw supported Cu(II), Pb (II) and Zn (II) removal up to 90%.
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| 36. |
- Andersson, Johan, et al.
(author)
-
Are You Lucky or Skilled? An Analysis of Elements of Randomness in Slay the Spire
- 2023
-
In: 2023 IEEE Conference on Games (CoG). - : IEEE. - 9798350322774 - 9798350322781
-
Conference paper (peer-reviewed)abstract
- Elements of randomness are a very common factor in modern digital games, from simple rolls of a die to complex AI systems. These elements have an impact on how the player experiences a game. We believe that exploring the field of luck analysis can benefit designers through a developed understanding of how such elements affect players. In this study, we explore how elements of randomness affect players in the roguelike deckbuilding game, Slay the Spire using data clustering. Three player skill groups were identified with the use of clustering: Winners, Low skill losers and High skill losers. Our results indicate that people who succeeded in beating the game, had an increased amount of randomness in the form of cards by a factor of 1.82. Showing that more skilled players do not shy away from randomness but instead embrace it more than lower skilled players.
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| 37. |
- Barbaud, Annick, et al.
(author)
-
Allergies and COVID-19 vaccines : An ENDA/EAACI Position paper
- 2022
-
In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 77:8, s. 2292-2312
-
Journal article (peer-reviewed)abstract
- Background Anaphylaxis, which is rare, has been reported after COVID-19 vaccination, but its management is not standardized.Method Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed.Results No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine are excipients. The authors propose allergy evaluation of persons with the following histories: 1-anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2-anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine; and 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left-over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable.Conclusions These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.
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| 38. |
- Barranco, Isabel, et al.
(author)
-
Extracellular vesicles isolated from porcine seminal plasma exhibit different tetraspanin expression profiles
- 2019
-
In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
-
Journal article (peer-reviewed)abstract
- Seminal extracellular vesicles (EVs) include exosomes (phi 40-120 nm) and microvesicles (MVs, phi 120-1000 nm), which would be involved in multiple functional reproductive roles. The study aimed to establish which EV subtypes are present in pig semen, using a high-resolution flow cytometer to explore differences in their tetraspanin expression profile. The EVs were isolated from 12 pig ejaculates using serial ultracentrifugation and characterized by dynamic light scattering and electron microscopy for size and morphology as well as for tetraspanin expression using flow cytometry with Carboxyfluorescein succinimidyl ester (CFSE) and antibodies against CD9, CD63 and CD81. Pig semen contained a heterogeneous EV-population regarding size and morphology. Flow cytometric analysis demonstrated that the proportion of EVs expressing CD63 and CD9 was higher in MVs (P amp;lt; 0.001 and P amp;lt; 0.05, respectively) than in exosomes, while the opposite was true for CD81; higher (P amp;lt; 0.001) in exosomes than in MVs. In conclusion, (1) the new generation of flow cytometers are able to accurately identify EVs and to gate them in two size-different populations named exosomes and MVs. (2) Tetraspanins CD9, CD63 and CD81 are present in both seminal EVs, albeit with exosomes and MVs differing in expression profiles, suggesting dissimilar cargo and binding affinity.
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| 39. |
- Barranco, Isabel, et al.
(author)
-
The Proteome of Large or Small Extracellular Vesicles in Pig Seminal Plasma Differs, Defining Sources and Biological Functions
- 2023
-
In: Molecular & Cellular Proteomics. - : ELSEVIER. - 1535-9476 .- 1535-9484. ; 22:4
-
Journal article (peer-reviewed)abstract
- Seminal plasma contains many morphologically hetero-geneous extracellular vesicles (sEVs). These are sequentially released by cells of the testis, epididymis, and accessory sex glands and involved in male and fe-male reproductive processes. This study aimed to define in depth sEV subsets isolated by ultrafiltration and size exclusion chromatography, decode their proteomic profiles using liquid chromatography-tandem mass spectrometry, and quantify identified proteins using sequential window acquisition of all theoretical mass spectra. The sEV subsets were defined as large (L-EVs) or small (S-EVs) by their protein concentration, morphology, size distribution, and EV-specific protein markers and purity. Liquid chromatography-tandem mass spectrometry identified a total of 1034 proteins, 737 of them quantified by SWATH in S-EVs, L-EVs, and non-EVs-enriched samples (18-20 size exclusion chromatography-eluted fractions). The differential expression analysis revealed 197 differentially abundant proteins between both EV subsets, S-EVs and L-EVs, and 37 and 199 between S-EVs and L-EVs versus non-EVs-enriched samples, respectively. The gene ontology enrichment analysis of differentially abundant proteins suggested, based on the type of protein detected, that S-EVs could be mainly released through an apocrine blebbing pathway and be involved in modulating the im-mune environment of the female reproductive tract as well as during sperm-oocyte interaction. In contrast, L-EVs could be released by fusion of multivesicular bodies with the plasma membrane becoming involved in sperm physiological processes, such as capacitation and avoidance of oxidative stress. In conclusion, this study provides a procedure capable of isolating subsets of EVs from pig seminal plasma with a high degree of purity and shows differences in the proteomic profile between EV subsets, indicating different sources and biological functions for the sEVs.
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| 40. |
- Bemmerer, D., et al.
(author)
-
Feasibility of low-energy radiative-capture experiments at the LUNA underground accelerator facility
- 2005
-
In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 24:2, s. 313-319
-
Journal article (peer-reviewed)abstract
- The LUNA (Laboratory Underground for Nuclear Astrophysics) facility has been designed to study nuclear reactions of astrophysical interest. It is located deep underground in the Gran Sasso National Laboratory, Italy. Two electrostatic accelerators, with 50 and 400 kV maximum voltage, in combination with solid and gas target setups allowed to measure the total cross-sections of the radiative-capture reactions 2H2H(p, γ) 3He3Heand 14N14N(p, γ) 15O15Owithin their relevant Gamow peaks. We report on the gamma background in the Gran Sasso laboratory measured by germanium and bismuth germanate detectors, with and without an incident proton beam. A method to localize the sources of beam-induced background using the Doppler shift of emitted gamma rays is presented. The feasibility of radiative-capture studies at energies of astrophysical interest is discussed for several experimental scenarios. © Società Italiana di Fisica/Springer-Verlag 2005.
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| 41. |
- Caciolli, A., et al.
(author)
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Revision of the 15N(p, γ)16O reaction rate and oxygen abundance in H-burning zones
- 2011
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 533
-
Journal article (peer-reviewed)abstract
- Context. The NO cycle takes place in the deepest layer of a H-burning core or shell, when the temperature exceeds T ≈ 30 × 106 K. The O depletion observed in some globular cluster giant stars, always associated with a Na enhancement, may be due to either a deep mixing during the red giant branch (RGB) phase of the star or to the pollution of the primordial gas by an early population of massive asymptotic giant branch (AGB) stars, whose chemical composition was modified by the hot bottom burning. In both cases, the NO cycle is responsible for the O depletion. Aims. The activation of this cycle depends on the rate of the 15N(p, γ)16O reaction. A precise evaluation of this reaction rate at temperatures as low as experienced in H-burning zones in stellar interiors is mandatory to understand the observed O abundances. Methods. We present a new measurement of the 15N(p, γ)16O reaction performed at LUNA covering for the first time the center of mass energy range 70-370 keV, which corresponds to stellar temperatures between 65 × 106 K and 780 × 106 K. This range includes the 15N(p, γ)16O Gamow-peak energy of explosive H-burning taking place in the external layer of a nova and the one of the hot bottom burning (HBB) nucleosynthesis occurring in massive AGB stars. Results. With the present data, we are also able to confirm the result of the previous R-matrix extrapolation. In particular, in the temperature range of astrophysical interest, the new rate is about a factor of 2 smaller than reported in the widely adopted compilation of reaction rates (NACRE or CF88) and the uncertainty is now reduced down to the 10% level. © 2011 ESO.
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| 42. |
- Caronna, Edoardo, et al.
(author)
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Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world
- 2024
-
In: JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY. - 0022-3050 .- 1468-330X.
-
Journal article (peer-reviewed)abstract
- Background Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. Methods European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as >= 50% and >= 75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. Results Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. Conclusions This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.
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| 43. |
- Castro, Marco, et al.
(author)
-
CDC42 deletion elicits cerebral vascular malformations via increased MEKK3-dependent KLF4 expression
- 2019
-
In: Circulation Research. - 0009-7330 .- 1524-4571. ; 124:8, s. 1240-1252
-
Journal article (peer-reviewed)abstract
- Rationale: Aberrant formation of blood vessels precedes a broad spectrum of vascular complications; however, the cellular and molecular events governing vascular malformations are not yet fully understood. Objective: Here, we investigated the role of CDC42 (cell division cycle 42) during vascular morphogenesis and its relative importance for the development of cerebrovascular malformations. Methods and Results: To avoid secondary systemic effects often associated with embryonic gene deletion, we generated an endothelial-specific and inducible knockout approach to study postnatal vascularization of the mouse brain. Postnatal endothelial-specific deletion of Cdc42 elicits cerebrovascular malformations reminiscent of cerebral cavernous malformations (CCMs). At the cellular level, loss of CDC42 function in brain endothelial cells (ECs) impairs their sprouting, branching morphogenesis, axial polarity, and normal dispersion within the brain tissue. Disruption of CDC42 does not alter EC proliferation, but malformations occur where EC proliferation is the most pronounced during brain development-the postnatal cerebellum-indicating that a high, naturally occurring EC proliferation provides a permissive state for the appearance of these malformations. Mechanistically, CDC42 depletion in ECs elicited increased MEKK3 (mitogen-activated protein kinase kinase kinase 3)-MEK5 (mitogen-activated protein kinase kinase 5)-ERK5 (extracellular signal-regulated kinase 5) signaling and consequent detrimental overexpression of KLF (Kruppel-like factor) 2 and KLF4, recapitulating the hallmark mechanism for CCM pathogenesis. Through genetic approaches, we demonstrate that the coinactivation of Klf4 reduces the severity of vascular malformations in Cdc42 mutant mice. Moreover, we show that CDC42 interacts with CCMs and that CCM3 promotes CDC42 activity in ECs. Conclusions: We show that endothelial-specific deletion of Cdc42 elicits CCM-like cerebrovascular malformations and that CDC42 is engaged in the CCM signaling network to restrain the MEKK3-MEK5-ERK5-KLF2/4 pathway.
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| 44. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 45. |
- Corona González, Belkis, et al.
(author)
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Primera evidencia molecular de especies de micoplasmas hemotrópicos (Mycoplasma spp.) en animales de importancia económica y social en Cuba : [First molecular evidence of hemotropic mycoplasma species (Mycoplasma spp.) in animals of economic and social importance in Cuba]
- 2023
-
In: Anales de la Academia de Ciencias de Cuba. - : Editorial Ciencias Medicas. - 2304-0106. ; 13:4
-
Journal article (peer-reviewed)abstract
- Introduction: Hemotropic mycoplasmas are widely distributed in several regions of the world. The aim of the present work was to determine the presence of hemotropic mycoplasma species in cattle, buffaloes, dogs and ticks in Cuba.Methods: They were analyzed thirty-nine buffalo and 41 cattle blood samples to investigate the presence of Mycoplasma wenyonii and ‘Candidatus Mycoplasma haemobos’. They were analyzed and 391 dog blood samples and 247 tick pools to detect the presence of Mycoplasma haemocanis and ‘Candidatus Mycoplasma haematoparvum’. In all cases it was used the species-specific TaqMan® real-time PCR assay.Results: For M. wenyonii 53 animals were positive and 33 for ‘Ca. Mycoplasma haemobos’; in coinfection with M. wenyonii, with similar prevalence in cattle and buffalo. 17.9% of dog samples were positive for at least one hemoplasma species, with 15.1% positive for M. haemocanis, 4.4% for ‘Ca. Mycoplasma haematoparvum’, and 1.5% co-infected. The ticks were identified as Rhipicephalus sanguineus sensu lato; none of the pools were positive for the canine mycoplasma species under study. It was demonstrated he presence of five different haplotypes for M. haemocanis and four haplotypes for ‘Ca. M. haematoparvum’; one of these haplotypes showed 100 % identity with one isolated from Grenada, which was associated with cases of zoonotic exposure.Conclusions. These results constitute the first molecular evidence of infection by hemoplasma species in cattle and buffaloes in Cuba and the Caribbean and the first molecular report of the occurrence of single infections and co-infections caused by M. haemocanis and ‘Ca. M. haematoparvum’ in dogs in Cuba. For the first time is evident the circulation of a genotype of ‘Ca. M. haematoparvum’ with zoonotic potential, common between the Greater and Lesser Antilles of the Caribbean.
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| 46. |
- Costantini, H., et al.
(author)
-
Recent results of the 14N(p,γ)15O measurement at LUNA
- 2005
-
In: Nuclear Physics A. - : Elsevier BV. - 0375-9474 .- 1873-1554. ; 758:1-4 SPEC. ISS., s. 383C-386C
-
Journal article (peer-reviewed)abstract
- The 14N(p, γ)15O reaction has been investigated by LUNA at the National Laboratory of Gran Sasso (LNGS) using two different techniques. The first study has been performed using a solid target and detecting the γ-rays coming from the single transitions with a HPGe detector in very close geometry to the target. In a second phase a windowless gas target sorrounded by a nearly 4π BGO summing crystal has been used and the total S-factor has been measured down to Eb = 80 keV. © 2005 Elsevier B.V. All rights reserved.
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| 47. |
- Díaz-Sánchez, Adrian Alberto, et al.
(author)
-
Development and application of a multiplex TaqMan® real-time qPCR assay for the simultaneous detection of anaplasma marginale and theileria annulata and molecular characterization of anaplasma marginale from cattle in Western Cuba."/>
- 2020
-
In: Ticks and Tick-borne Diseases. - : Elsevier BV. - 1877-959X .- 1877-9603. ; 11:2
-
Journal article (peer-reviewed)abstract
- Anaplasmosis and theileriosis are considered the most important tick-borne diseases for livestock production worldwide, causing significant economic losses in tropical and subtropical regions. The present study was aimed to develop a multiplex TaqMan® qPCR assay to simultaneously detect Anaplasma marginale and Theileria annulata and to applied it to investigate naturally infected cattle in Cuba. The assay was highly specific, sensible, and efficient; it was more sensitive than a well-established nested PCR and detected 1 DNA copy of each target. Consistent repeatability and reproducibility within and between multiplex qPCR runs was shown. A total of 223 blood samples collected in western Cuba were analyzed for haemoparasites infection in cattle. The multiplex qPCR assay detected A. marginale in 213 samples (95.5%; CI: 95%; 91.9%–97.5%), but all samples were negative for T. annulata. Additionally, the genetic diversity of A. marginale was assessed using 16S rRNA, MSP1a and MSP4 nucleotide and protein sequences. The MSP1a tandem repeats ranged from three to five, and twelve different MSP1a tandem repeats of A. marginale were found, which presented genotypes C, E, and G in the 5ʹUTR microsatellite region. Phylogenetic analysis using the msp4 gene showed that Cuban strains were closely related to others previously reported in Mexico, Brazil and Asian countries. The multiplex qPCR described here proved to be a rapid, specific and cost-effective mean for the simultaneous detection of A. marginale and T. annulata. Further epidemiological studies using this assay will improve the surveillance of the associated diseases in regions where they are endemic.
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| 48. |
- Embring Klang, Carl-Magnus, et al.
(author)
-
Assessing Simultaneous Action Selection and Complete Information in TAG with Sushi Go!
- 2021
-
In: Proceedings of the 3rd Conference on Games. - : IEEE. - 9781665438865 - 9781665446082
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Conference paper (peer-reviewed)abstract
- Digitalizing tabletop games for general game playing(GGP) AI research is a continuously growing field. TabletopGames Framework (TAG) is a framework developed to simplifythe process of implementing tabletop board games to digital form.Sushi Go! is a game that combines simultaneous action selectionand complete information. This creates a unique combination ofmechanics, which presents a new challenge for GGP agents. Byimplementing Sushi Go! into TAG, we can test different agent’sperformance using these mechanics and compare them to theirexisting performances in the other games of TAG. Results ofthis testing are presented, which display that the framework iscapable of implementing Sushi Go! and that the agents performwith mixed results. Further developing heuristics for the agentsshould prove to increase their performance when faced with thesetypes of games.
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| 49. |
- Estrader, Marta, et al.
(author)
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Origin of the large dispersion of magnetic properties in nanostructured oxides : FexO/Fe3O4 nanoparticles as a case study
- 2015
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:7, s. 3002-3015
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Journal article (peer-reviewed)abstract
- The intimate relationship between stoichiometry and physicochemical properties in transition-metal oxides makes them appealing as tunable materials. These features become exacerbated when dealing with nanostructures. However, due to the complexity of nanoscale materials, establishing a distinct relationship between structure-morphology and functionalities is often complicated. In this regard, in the FexO/Fe3O4 system a largely unexplained broad dispersion of magnetic properties has been observed. Here we show, thanks to a comprehensive multi-technique approach, a clear correlation between the magneto-structural properties in large (45 nm) and small (9 nm) FexO/Fe3O4 core/shell nanoparticles that can explain the spread of magnetic behaviors. The results reveal that while the FexO core in the large nanoparticles is antiferromagnetic and has bulk-like stoichiometry and unit-cell parameters, the FexO core in the small particles is highly non-stoichiometric and strained, displaying no significant antiferromagnetism. These results highlight the importance of ample characterization to fully understand the properties of nanostructured metal oxides.
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| 50. |
- Formicola, A, et al.
(author)
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Astrophysical S-factor of 14N(p,γ)15O
- 2004
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 591:1-2, s. 61-68
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Journal article (peer-reviewed)abstract
- We report on a new measurement of the 14N(p,γ) 15O capture cross section at Ep=140 to 400 keV using the 400 kV LUNA accelerator facility at the Laboratori Nazionali del Gran Sasso (LNGS). The uncertainties have been reduced with respect to previous measurements and their analysis. We have analyzed the data using the R-matrix method and we find that the ground state transition accounts for about 15% of the total S-factor. The main contribution to the S-factor is given by the transition to the 6.79 MeV state. We find a total S(0)=1.7±0.2 keVb, in agreement with recent extrapolations. The result has important consequences for the solar neutrino spectrum as well as for the age of globular clusters. © 2004 Elsevier B.V. All rights reserved.
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