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Abstract In the recent years, primordial black holes (PBHs) have emerged as one of the most interesting and hotly debated topics in cosmology. Among other possibilities, PBHs could explain both some of the signals from binary black hole mergers observed in gravitational-wave detectors and an important component of the dark matter in the Universe. Significant progress has been achieved both on the theory side and from the point of view of observations, including new models and more accurate calculations of PBH formation, evolution, clustering, merger rates, as well as new astrophysical and cosmological probes. In this work, we review, analyze and combine the latest developments in order to perform end-to-end calculations of the various gravitational-wave signatures of PBHs. Different ways to distinguish PBHs from stellar black holes are emphasized. Finally, we discuss their detectability with LISA, the first planned gravitational-wave observatory in space.

In recent years, Design has assumed an increasingly significant role in the field of food systems, contributing through the formulation of strategies and approaches as well as the creation of innovative artefacts and solutions. This integration is evident in the most advanced iterations of food culture, such as Molecular Cuisine, nutraceuticals, and Sci-Fi Food, which apply scientific tools and principles of Design to food production and consumption processes. From this perspective, the paper explores the emerging scientific field of Gastrophysics, interpreting it not only as an analytical tool but also as a design methodology to foster sustainable innovations in Food Design. The contribution also provides an overview of the state of the art of sustainable food systems, with a focus on recent experiments and projects that, through the synergies between Gastrophysics and Communication Design, Service Design, Technological Innovation, and Medical Design, can open up new holistic and systemic perspectives for research fields that can develop synergies between the different Sustainable Development Goals. Article info Received: 03/07/2024; Revised: 10/12/2024; Accepted: 11/12/2024

AGATHÓN issue number 16 is a collection of essays, studies, research and projects on ‘Dealing with Complexity | Knowledge, design, and management of the built environment’. Complexity (from the Latin verb ‘plectere’ = to weave, ‘cum’ = together) is a condition in which many elements intertwine together to form a unit. The ‘complexity’ of the Planet’s condition is evident: climate change, according to Amitav Ghosh (2017), is not a danger in itself but rather represents a ‘threat multiplier’ that stresses and amplifies the instability and insecurity already present in some areas of the world, even more so because many industrialised countries have already greatly exceeded their relative ‘biocapacity’, effectively becoming ‘ecological debtors’. In this view, ‘complex’ should be brought back to its etymological meaning of ‘woven’ or ‘held together’, connecting different forms of knowledge in the virtuous circle of a body of knowledge articulated in a systemic view of the real world based on the principle of ‘co-evolution’ of social and ecological systems (of culture and nature) and the awareness that it determines; on the one hand, the interweaving of multiple causal chains (e.g., although the pandemic crisis is a health crisis it has also become a biological, ecological, economic, social, cultural and spiritual crisis) with interdependent effects, and on the other hand, effects that also retroact on causes since causality is circular. According to Ceruti and Bardi (2021), unfortunately, it isn’t easy to translate this vision into the workings of everyday life and to guide both the observation of the world and the project, which is an expression of our being in the world. How we live, regardless of where this happens, has an impact on the biosphere and determines chain reactions in different areas that affect both nature and human beings on a global scale: climate change, health risks, loss of biodiversity, indiscriminate use of non-renewable resources, inequalities, and accessibility contribute to a condition of ‘polycrysis’ that amplifies the state of uncertainty about our future and the vulnerability of the entire ecosystem, especially since the actions put in place do not address the cogent environmental issue in a systemic and holistic key. Therefore, the question is, how do we transform complexity from challenge to opportunity? How do we deal with the complex issues that concern the knowledge, the design, and the management of the built compared to the now essential pragmatic indicators of environmental, social, and economic sustainability? Which strategies, measures, actions, and tools can Architecture disciplines implement in a holistic view and with a systems approach to meet the terms of the Paris Agreement? How do we identify those with the best cost/benefit ratio capable of producing synergies to achieve the largest possible number of the Sustainable Development Goals promoted by the United Nations? How do we rethink extractive (production-based) economic systems and direct them toward regenerative ones (based on the enhancement of that which already exists and of services)? How to put into practice new systemic design approaches capable of addressing today’s complexities from their roots, developing solutions through which entire societies can intentionally transition to a more sustainable, equitable, and desirable long-term future, including through co-created visions capable of informing the solutions of the present and paving the way to a desirable future? How do we place knowledge and learning into a system to better understand the current era’s multidimensional, fundamental, and global issues in their irreducible complexity? The articles published in issue 16 of AGATHÓN offer valuable insights into addressing the complex issues surrounding the knowledge, design, and management of the built environment in light of the increasingly urgent pragmatic indicators of environmental, social, and economic sustainability, demonstrating that the complexity of the built environment, rather than being a challenge, can become an opportunity to advance the achievement of the 17 Sustainable Development Goals. The published contributions certainly do not fully encompass the fields of inquiry, strategies, measures, and actions that the scientific community and the construction sector can implement to contain human activity within planetary boundaries and make both the built environment and biophysical systems more resilient. However, they provide an initial theoretical-practical framework on the topic, which will hopefully contribute to stimulating the scientific debate and inspire new research initiatives based on multiscalar approaches, capable of leveraging the potential of digital technologies to address the pressing challenges of contemporary times, including the global goals of climate and carbon neutrality.

Abstract We argue that the Starobinsky model of inflation, realised via an R 2 term in the Lagrangian, can originate from quantum effects due to a tower of light species. By means of two separate arguments, we show how this implies that the scale of the R 2 term must be of order of the species scale Λs, namely the energy at which gravity becomes strongly coupled. We discuss the implications and challenges of this scenario for inflation, inflationary reheating, and string theory embeddings. In this context, we collect strong evidence to conclude that Starobinsky inflation lies in the Swampland.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system1. Astrocytes are heterogeneous glial cells that are resident in the central nervous system and participate in the pathogenesis of multiple sclerosis and its model experimental autoimmune encephalomyelitis2,3. However, few unique surface markers are available for the isolation of astrocyte subsets, preventing their analysis and the identification of candidate therapeutic targets; these limitations are further amplified by the rarity of pathogenic astrocytes. Here, to address these challenges, we developed focused interrogation of cells by nucleic acid detection and sequencing (FIND-seq), a high-throughput microfluidic cytometry method that combines encapsulation of cells in droplets, PCR-based detection of target nucleic acids and droplet sorting to enable in-depth transcriptomic analyses of cells of interest at single-cell resolution. We applied FIND-seq to study the regulation of astrocytes characterized by the splicing-driven activation of the transcription factor XBP1, which promotes disease pathology in multiple sclerosis and experimental autoimmune encephalomyelitis4. Using FIND-seq in combination with conditional-knockout mice, in vivo CRISPR-Cas9-driven genetic perturbation studies and bulk and single-cell RNA sequencing analyses of samples from mouse experimental autoimmune encephalomyelitis and humans with multiple sclerosis, we identified a new role for the nuclear receptor NR3C2 and its corepressor NCOR2 in limiting XBP1-driven pathogenic astrocyte responses. In summary, we used FIND-seq to identify a therapeutically targetable mechanism that limits XBP1-driven pathogenic astrocyte responses. FIND-seq enables the investigation of previously inaccessible cells, including rare cell subsets defined by unique gene expression signatures or other nucleic acid markers.

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan–Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.

La displasia cleidocraneal (OMIM #119600) es una osteocondrodisplasia de herencia autosómica dominante debida a una mutación en heterocigosis en el gen RUNX2. Su prevalencia es 1 en 1.000.000 individuos. Puede detectarse en pacientes de estatura baja asociada a alteraciones dentales, malformaciones craneofaciales y ausencia o hipoplasia de clavículas; el diagnóstico se corrobora con estudios imagenológicos y moleculares; el tratamiento es sintomático, ortopédico y dental. Objetivo: describir una enfermedad genética de baja prevalencia, sus características clínicas y la importancia de la aproximación diagnóstica. Se presenta caso de adolescente masculino con talla baja, presencia prolongada de dientes primarios y supernumerarios, macrocefalia, prominencia frontal, hipertelorismo ocular, asimetría de tórax y extremidades; antecedentes familiares positivos; estudio radiológico revela ausencia de clavículas y estudio molecular confirma la displasia cleidocraneal. El paciente asistió tardíamente a consulta de nutrición y desarrollo. La historia clínica exhaustiva, estudios complementarios adecuados y seguimiento oportuno por equipo multidisciplinario son aspectos claves para un diagnóstico precoz y pronóstico favorable.

Nowadays, developing countries have seen a reduction in male reproductive parameters, and it has been linked to the exposure of endocrine disrupting chemicals (EDCs), which are able to mimic or disrupt steroid hormone actions. Also, nanoparticles have shown effects on the male reproductive system, in particular the use of TiO2-NPs in drugs, cosmetics, and food as pigment additives, and, thanks to their small size (1–100 nm), provide themselves the opportunity to be internalized by the body and pass the blood–testis barrier (BTB). Therefore, TiO2-NPs can act on spermatogenesis and spermatozoa. In this study, we carried out an in vitro assay on human spermatozoa to evaluate the effects of TiO2-NPs at the concentrations of 500, 250, 100, and 50 ppm. Exposure did not statistically alter sperm parameters (e.g., motility and viability) but induced damage to sperm DNA and the expression of biomarkers by spermatozoa. This immunofluorescence investigation showed a positivity for biomarkers of stress (HSP70 and MTs) on the connecting piece of spermatozoa and also for sex hormone binding globulin (SHBG) biomarkers. The SHBG protein acts as a carrier of androgens and estrogens, regulating their bioavailability; therefore, its expression in the in vitro assay did not rule out the ability of TiO2-NPs to act as endocrine disruptors.

Reseñas iberoamericanas

Abstract Dendritic cells (DCs) are essential orchestrators of immune responses and represent potential targets for immunomodulation in autoimmune diseases. Human amniotic fluid secretome is abundant in immunoregulatory factors, with extracellular vesicles (EVs) being a significant component. However, the impact of these EVs on dendritic cells subsets remain unexplored. In this study, we investigated the interaction between highly purified dendritic cell subsets and EVs derived from amniotic fluid stem cell lines (HAFSC‐EVs). Our results suggest that HAFSC‐EVs are preferentially taken up by conventional dendritic cell type 2 (cDC2) through CD29 receptor‐mediated internalization, resulting in a tolerogenic DC phenotype characterized by reduced expression and production of pro‐inflammatory mediators. Furthermore, treatment of cDC2 cells with HAFSC‐EVs in coculture systems resulted in a higher proportion of T cells expressing the regulatory T cell marker Foxp3 compared to vehicle‐treated control cells. Moreover, transfer of HAFSC‐EV‐treated cDC2s into an EAE mouse model resulted in the suppression of autoimmune responses and clinical improvement. These results suggest that HAFSC‐EVs may serve as a promising tool for reprogramming inflammatory cDC2s towards a tolerogenic phenotype and for controlling autoimmune responses in the central nervous system, representing a potential platform for the study of the effects of EVs in DC subsets.

Volume 15 of AGATHÓN follows on from its predecessors on Innovability©® | Digital Transition and Innovability©® | Ecological Transition, aware of its pressing topicality but also of the scope that the proposal of a threefold key of interpretation suggests. We have clarified the meaning of the term ‘innovability’©®, formerly in use in the economic and social sciences, which is attributed to a renewed driving force for a new paradigm of development that expresses one of the most crucial challenges of our time and the need for a ‘solidary’ convergence between the two inescapable instances of ‘innovation’ and ‘sustainability’, as if they were opposites and contrasts: beyond the term used, in a historical moment characterised by environmental, social and economic emergencies, Humanity promotes one of its prerogatives, the use of the ‘things’ that nature makes available to us to do something other than their primary function (innovation), aware that those resources are not inexhaustible (sustainability). In this context, which must always look forward, we must design our best political and systemic actions to promote the need to innovate by using the Planet’s resources well and consciously. The goals of climate neutrality by 2050 and the reduction of CO2 emissions by 55% (compared to the 1990 level) by 2030 (European Commission, 2019, 2021) pose the European Union, and even more so the rest of the world, with several complex issues, including a significant increase in ‘clean’ energy production from alternative and renewable sources, the reduction of energy poverty, greater security of energy supply and a drastic decrease in dependence on energy imports; at the same time, the aim is to foster modern economic growth decoupled from the use of non-renewable resources, the creation of new jobs, and to generate environmental and health benefits, objectives with inevitable cultural, political, economic, production, technological and social implications to be addressed both within one’s borders and in foreign policy. The energy transition is, therefore, complex and challenging to implement because it involves ‘everything’ and is needed ‘everywhere’ but also because globally, primary energy consumption has been steadily increasing for at least half a century. The theoretical and experimental framework presented in Volume 15 of AGATHÓN demonstrates how energy, ecological and digital transitions can contribute synergistically to achieving the goals of decarbonisation and climate neutrality. The contributions published in the form of essays and research papers appear consistent with the 2022 Strategic Foresight Report (European Commission, 2022) based on the JRC report entitled Towards a Green and Digital Future – Key Requirements for Successful Twin Transitions in the European Union (Muench et alii, 2022) and founded on the fundamental concepts of (a) ‘twin’ transitions, as the key to a sustainable, fair and competitive future; (b) ‘just’ transition, for widespread acceptance of green and digital solutions to mitigate consumption and improve efficiency; (c) ‘integrated approach’ to challenges, to maximise the benefits of synergies and better manage risks. From the published contributions, it emerges the need for a paradigm shift that, on the one hand, is characterised by a ‘sufficiency’ approach (regarding new land occupation and new constructions) and a circular economy (to limit the use of non-renewable resources) capable of exploiting the potential of technologies for the new services made possible by digitisation, and on the other hand, relies on new user awareness of the limits of the Planet, pursuable through ‘soft’ urgent actions that are robust, flexible and easy to implement as they require a lower financial commitment. We assume that community energy renewable energy production from hydrogen and production chains can help mitigate greenhouse gas emissions. In that case, the vast existing real estate heritage is an area in which it is possible to intervene effectively, even where it has a historical and cultural value, using tools such as digital twins or analysis methodologies capable of assessing ex-ante the impacts on the ecosystem and prefigure scenarios for cities, buildings and production processes aimed at sustainable development and compatible with the urgent objectives set for 2030 and 2050. These are some of the strategies, pathways, measures and actions that can take place by exploiting the availability of the substantial financial resources allocated by governments for transitions, stimulating the sensitivity of local administrators and enhancing the skills and transversal competencies of technicians and operators in the sector, but also and above all by raising users’ awareness of the risks posed by climate change, to activate their ‘behavioural’ response to the consumption of energy and non-renewable natural resources.

Design, understood as a modern discipline in its broadest sense, has always been inextricably linked to energy production, availability and accessibility. Every project resulting from human creativity and ingenuity, whether material or immaterial, analogue or digital, depends on it; it is necessary to break free from this atavistic dependence by finding alternative paths that lead us to the energy transition. An increase in human awareness is required to accomplish this and achieve social and environmental equity. In this perspective, this paper, starting with the concepts of ‘mitigation’, ‘sufficiency’, ‘circular economy’ and ‘innovability’, illustrates a number of highly replicable experiments carried out by the multidisciplinary Dotdotdot Studio by employing storytelling, emotive technology and the value of data to generate awareness in users on the issue of energy conservation. Article info Received: 15/05/2024; Revised: 17/05/2024; Accepted: 20/05/2024

The Gulf of Maine in the northwestern Atlantic Ocean is one of the world’s fastest warming marine regions. Changes in ocean conditions are affecting growth, survival, and distribution of American lobster (Homarus americanus), which supports iconic fisheries along the coast of Maine, USA. In this study, we analyzed 15 years of oral records from the Maine Fishermen’s Climate Roundtables to explore fishermen’s observations of and responses to social–ecological changes. Fishermen reported an overall shift in lobster biomass further east and offshore, resulting in strategic expansion of fishing seasons and areas. Biomass shifts were thought to be connected to increases in temperature, decreases in salinity, a shift in ocean currents, and a loss of predator species. Fishing strategies were categorized according to five domains of adaptive capacity, but the majority of fishers’ responses fell into two domains: “access to assets” and “diversity and flexibility”. Strategies within these domains included increased expansion into federal lobster fisheries and extension of fishing seasons. Fishermen highlighted data gaps that need to be addressed to meet the challenges of climate change. Fisheries learning exchanges, such as the Climate Roundtables, create social networks that foster knowledge sharing to support the continued viability of local livelihoods.

This study aimed to characterize the physiological and structural responses of potted one-year-old olive trees belonging to two olive cultivars—‘Nocellara del Belice’ and ‘Cerasuola’—exposed to prolonged drought under greenhouse conditions. Two irrigation treatments based on evapotranspiration (ET) were imposed for 69 days, i.e., well-watered (WW, 100% ET) and drought-stressed (DS, 10−30% ET). Leaf stomatal conductance (gs), stem water potential (Ψstem), transpiration (E), photosynthetic capacity (Amax), water use efficiency (WUE), stem (Kstem) and root (Kroot) hydraulic conductance, trunk diameter variations (TDV), and leaf patch attenuated pressure fluctuations (pp, a proxy of the inverse of leaf turgor pressure) were measured in WW and DS trees at different stages of the experiment. Leaf gs did not significantly differ between cultivars under DS, whereas differences in Ψstem only became significant at the end of prolonged drought, when ‘Nocellara del Belice’ experienced Ψstem < −4 MPa. ‘Cerasuola’ trees expressed the best WUE under drought, although they were more susceptible to photoinhibition under optimal plant water status. Both cultivars tended to increase their Kstem at the end of the drought period. A marked reduction in Kroot occurred in ‘Cerasuola’ plants after prolonged drought; however, a similar mechanism was not observed in ‘Nocellara del Belice’. The ratio between Kstem and Kroot exponentially increased towards the end of the prolonged drought period in both cultivars, but more markedly in ‘Cerasuola’. TDV and pp trends suggested that ‘Cerasuola’ plants keep better plant water status under severe drought compared to ‘Nocellara del Belice’ by maintaining high leaf turgor and reduced trunk diameter fluctuations. These responses may be related to reduced cell wall elasticity and xylem vessel size and/or wall thickness—drought avoidance mechanisms. The Kstem/Kroot ratio can serve as an indicator of drought stress avoidance mechanisms to compare genotype-specific responses to drought stress.

Abstract Early Dark Energy (EDE) is a prominent model to resolve the Hubble tension, which employs a dynamical axion with a periodic potential. In this work, we take first steps towards the embedding of this model into stable compactifications of string theory. First, we provide a pedagogical review of the EDE scenario and its main challenges. Second, we construct a simple supergravity toy model using only minimal ingredients. Already at this level, we can understand the origin of the harmonics of the EDE scalar potential in terms of a delicate balance of the leading terms from separate non-perturbative effects. Third and final, we embed the model into a KKLT-type compactification, with the EDE scalar field realized by a two-form axion. We find that a successful embedding, with all moduli stabilized, requires restrictive assumptions, which are lacking at present a known string theory implementation mechanism, both on the Pfaffians and on the exponents of the non-perturbative terms responsible for the EDE dynamics. We point out that such non-generic conditions reflect well known challenges of the EDE model and further investigation might guide us towards a conclusive resolution. An alternative viewpoint suggests that rather than serving as the foundation for a string theory embedding, these conditions might instead indicate that EDE is, in fact, incompatible with string theory, at least in the realizations we study here. Further investigation will be needed to ascertain the status of EDE in string theory.

Plastic additives include a wide range of pollutants, added throughout the production process of plastics aiming to improve their properties. Given that they are not chemically bound to the plastic items, they can easily migrate in the marine environment allowing their uptake by marine organisms and accumulation in their tissues. Representatives of Phthalic acid esters (PAEs) and bisphenols have been characterized for their ability to impact not only marine organisms but also humans via fish and seafood consumption. In this study, a liquid-liquid method was applied to determine the concentrations of selected PAEs and Bisphenol A (BPA) in the tissues of E.encrasicolus, S.pilchardus, B.boops, and M.barbatus from two important divisions of fisheries (North Aegean and the Western Ionian Seas, thereof NAS and IOS respectively) of the Mediterranean Sea. The level of contamination varied among the different species and geographical locations. DEHP (bis(2-ethylhexyl) phthalate) had the highest mean concentrations of the examined PAEs for all four species examined. Statistically significant differences in DEHP mean concentrations were observed between the tissues of B.boops (collected from NAS) and S.pilchardus (from IOS) (p < 0.05, Wilcoxon rank test). DIDP (di-isodecyl phthalate) was the following most common PAEs, although no statistically significant differences were presented between sites, species, and tissues. DINP (di-isononyl phthalate) was recorded only in the GIT of E.encrasicolus (from NAS), while the rest of the examined PAEs were presented in a smaller subset of the samples. Noticeably, the parent diester DBP and the metabolic monoester MNBP were concurrently detected in a part of the analyzed samples. The level of risk via fish consumption, based on the Estimated Daily Intake and the Target Hazard Quotient (THQ), showed that the PAEs and BPA had a low likelihood of a negative effect occurring for every scenario that was examined, although THQ for BPA indicated there was a higher likelihood than PAEs of an adverse effect to be presented. The results of this study highlighted the need for future efforts focusing on the factors affecting plastic additives occurrences in the marine environment, especially for marine organisms intended for consumption.

This study aimed to evaluate the effects of fruit position, light exposure and fruit surface temperature (FST) on apple fruit colour development and fruit quality at harvest, including sunburn damage severity. This was achieved by undertaking two experiments in a high-density planting of the dark-red apple ANABP 01 in Tatura, Australia. In the 2020–2021 growing season an experiment was conducted to draw relationships between fruit position and fruit quality parameters. Here, sample fruit position and level of light exposure were respectively determined using a static LiDAR system and a portable quantum photosynthetically active radiation (PAR) sensor. At harvest the sample fruit were analysed for percentage red colour coverage, objective colour parameters (L*, a*, b*, hue angle and chroma), sunburn damage, fruit diameter (FD), soluble solids concentration (SSC), flesh firmness (FF) and starch pattern index (SPI). A second experiment was conducted in the 2021–2022 growing season and focused on how fruit shading, light exposure and the removal of ultraviolet (UV) radiation affected the FST, colour development and harvest fruit quality. Five treatments were distributed among sample fruit: fully shaded with aluminium umbrellas, shaded for one month and then exposed to sunlight until harvest, exposed for one month and then shaded until harvest, covered with a longpass UV filter and a control treatment. The development of colour in this dark-red apple cultivar was highly responsive to aspects of fruit position, and the intensity and quality of light exposure. The best-coloured fruit were exposed to higher quantities of PAR, exposed to both PAR and UV radiation simultaneously and located higher in the tree canopy. Fruit that were fully exposed to PAR and achieved better colour development also displayed higher FST and sunburn damage severity.