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High-altitude remote sites are unique places to study aerosol–cloud interactions, since they are located at the altitude where clouds may form. At these remote sites, organic aerosols (OAs) are the main constituents of the overall aerosol population, playing a crucial role in defining aerosol hygroscopicity (κ). To estimate the cloud condensation nuclei (CCN) budget at OA-dominated sites, it is crucial to accurately characterize OA hygroscopicity (κOA) and how its temporal variability affects the CCN activity of the aerosol population, since κOA is not well established due to the complex nature of ambient OA. In this study, we performed CCN closures at a high-altitude remote site during summer to investigate the role of κOA in predicting CCN concentrations under different atmospheric conditions. In addition, we performed an OA source apportionment using positive matrix factorization (PMF). Three OA factors were identified from the PMF analysis: hydrocarbon-like OA (HOA), less-oxidized oxygenated OA (LO-OOA), and more-oxidized oxygenated OA (MO-OOA), with average contributions of 5 %, 36 %, and 59 % of the total OA, respectively. This result highlights the predominance of secondary organic aerosol (SOA) with a high degree of oxidation at this high-altitude site. To understand the impact of each OA factor on the overall OA hygroscopicity, we defined three κOA schemes that assume different hygroscopicity values for each OA factor. Our results show that the different κOA schemes lead to similar CCN closure results between observations and predictions (slope and correlation ranging between 1.08–1.40 and 0.89–0.94, respectively). However, the predictions were not equally accurate across the day. During the night, CCN predictions underestimated observations by 6 %–16 %, while, during morning and midday hours, when the aerosol was influenced by vertical transport of particles and/or new particle formation events, CCN concentrations were overestimated by 0 %–20 %. To further evaluate the role of κOA in CCN predictions, we established a new OA scheme that uses the OA oxidation level (parameterized by the f44 factor) to calculate κOA and predict CCN. This method also shows a large bias, especially during midday hours (up to 40 %), indicating that diurnal information about the oxygenation degree does not improve CCN predictions. Finally, we used a neural network model with four inputs to predict CCN: N80 (number concentration of particles with diameter > 80 nm), OA fraction, f44, and solar global irradiance. This model matched the observations better than the previous approaches, with a bias within ± 10 % and with no daily variation, reproducing the CCN variability throughout the day. Therefore, neural network models seem to be an appropriate tool to estimate CCN concentrations using ancillary parameters accordingly.

Abstract Introduction KRASG12C and KRASG12D inhibitors represent a major translational breakthrough for non-small cell lung cancer (NSCLC) and cancer in general by directly targeting its most mutated oncoprotein. However, resistance to these small molecules has highlighted the need for rational combination partners necessitating a critical understanding of signaling downstream of KRAS mutant isoforms. Methods We contrasted tumor development between Kras G12C and Kras G12D genetically engineered mouse models (GEMMs). To corroborate findings and determine mutant subtype-specific dependencies, isogenic models of Kras G12C and Kras G12D initiation and adaptation were profiled by RNA sequencing. We also employed cell line models of established KRAS mutant NSCLC and determined therapeutic vulnerabilities through pharmacological inhibition. We analysed differences in survival outcomes for patients affected by advanced KRAS G12C or KRAS G12D -mutant NSCLC. Results KRASG12D exhibited higher potency in vivo, manifesting as more rapid lung tumor formation and reduced survival of KRASG12D GEMMs compared to KRASG12C. This increased potency, recapitulated in an isogenic initiation model, was associated with enhanced PI3K-AKT-mTOR signaling. However, KRASG12C oncogenicity and downstream pathway activation were comparable with KRASG12D at later stages of tumorigenesis in vitro and in vivo, consistent with similar clinical outcomes in patients. Despite this, established KRASG12D NSCLC models depended more on the PI3K-AKT-mTOR pathway, while KRASG12C models on the MAPK pathway. Specifically, KRASG12D inhibition was enhanced by AKT inhibition in vitro and in vivo. Conclusions Our data highlight a unique combination treatment vulnerability and suggest that patient selection strategies for combination approaches using direct KRAS inhibitors should be i) contextualised to individual RAS mutants, and ii) tailored to their downstream signaling.

Using numerical simulations, we explore the static and dynamic response of hopfions to an external magnetic field in cylindrical and toroidal nanorings. Results evidence that the nucleation and stability of hopfions are intricately linked to geometry. When including an external field, due to the Dzyaloshinskii–Moriya interaction and the field direction-dependent annihilation mechanism, the hopfion displays distinct behavior under magnetic fields pointing along opposite directions. We have also obtained the spin wave resonance modes of the magnetization patterns nucleated in both nanorings and show the impact of geometry on the suppression of some of them. The interplay between curvature, topology, and magnetization dynamics opens new possibilities toward hopfion-based spin torque oscillator fabrication.

Abstract Currently, technological tools have positioned themselves in the first places of human development, and higher education has not been the exception. This research aims to improve academic performance with the application of mathematical simulators (Wólfram Alpha, GeoGebra, Derive, and Matlab) as a didactic strategy for the study of integral calculus in engineering students. This research has a quantitative approach, which allows for the investigation of the data from academic activities; likewise, it includes an explanatory study with the purpose of verifying the relationship that exists between the dependent and independent variables. In addition, the method of the questionnaire technique with raised exercises was used, and then the qualification averages of the groups were taken. Similarly, the perspective provided a solid base to analyze the data objectively and establish statistical relationships between the variables involved. The methodology used in this study was to obtain precise and measurable information on the impact of mathematical simulators on learning integral calculus. The questionnaire technique with posed exercises made it possible to collect data directly from the participants, providing detailed information on their understanding and performance in relation to integral calculus. The exercises posed in the questionnaire served as a structured way to assess the knowledge and skills acquired by students. The design applied in the study is made up of two control and experimental groups, applying the pretest and posttest methods. For the analysis and interpretation of data, the parametric statistical student's T-test was used for related samples, where the simulators significantly influenced the learning of integral calculus, at a significance level of 5%. The results of the analysis indicated that the mathematical simulators significantly influenced the learning of integral calculus. That is, statistically significant improvements were observed in the academic performance of the students after the intervention with the simulators. Briefly, the study used a two-group (control and experimental) design, applied pretest and posttest methods to assess academic performance, and used the Student's T-test for related samples in data analysis. Therefore, the importance of the role of the teacher in the learning process of higher mathematics is exemplified.

To fight against the first wave of coronavirus disease 2019 (COVID-19) in 2020, lockdown measures were implemented in most European countries. These lockdowns had well-documented effects on human mobility. We assessed the impact of the lockdown implementation and relaxation on air pollution by comparing daily particulate matter (PM), nitrogen dioxide (NO2) and ozone (O3) concentrations, as well as particle number size distributions (PNSDs) and particle light absorption coefficient in situ measurement data, with values that would have been expected if no COVID-19 epidemic had occurred at 28 sites across Europe for the period 17 February–31 May 2020. Expected PM, NO2 and O3 concentrations were calculated from the 2020 Copernicus Atmosphere Monitoring Service (CAMS) ensemble forecasts, combined with 2019 CAMS ensemble forecasts and measurement data. On average, lockdown implementations did not lead to a decrease in PM2.5 mass concentrations at urban sites, while relaxations resulted in a +26 ± 21 % rebound. The impacts of lockdown implementation and relaxation on NO2 concentrations were more consistent (−29 ± 17 and +31 ± 30 %, respectively). The implementation of the lockdown measures also induced statistically significant increases in O3 concentrations at half of all sites (+13 % on average). An enhanced oxidising capacity of the atmosphere could have boosted the production of secondary aerosol at those places. By comparison with 2017–2019 measurement data, a significant change in the relative contributions of wood and fossil fuel burning to the concentration of black carbon during the lockdown was detected at 7 out of 14 sites. The contribution of particles smaller than 70 nm to the total number of particles significantly also changed at most of the urban sites, with a mean decrease of −7 ± 5 % coinciding with the lockdown implementation. Our study shows that the response of PM2.5 and PM10 mass concentrations to lockdown measures was not systematic at various sites across Europe for multiple reasons, the relationship between road traffic intensity and particulate air pollution being more complex than expected.

Thanks to the rapidly increasing time-domain facilities, we are entering a golden era of research on gamma-ray bursts (GRBs). In this Letter, we report our observations of GRB 240529A with the Burst Optical Observer and Transient Exploring System, the 1.5 m telescope at Observatorio de Sierra Nevada, the 2.5 m Wide Field Survey Telescope of China, the Large Binocular Telescope, and the Telescopio Nazionale Galileo. The prompt emission of GRB 240529A shows two comparable energetic episodes separated by a quiescence time of roughly 400 s. Combining all available data on the GRB Coordinates Network, we reveal the simultaneous apparent X-ray plateau and optical rebrightening around 10 ^3 –10 ^4 s after the burst. Rather than the energy injection from the magnetar as widely invoked for similar GRBs, the multiwavelength emissions could be better explained as two shocks launched from the central engine separately. The optical peak time and our numerical modeling suggest that the initial bulk Lorentz factor of the later shock is roughly 50, which indicates that the later jet should be accretion driven and have a higher mass loading than a typical one. The quiescence time between the two prompt emission episodes may be caused by the transition between different accretion states of a central magnetar or black hole, or the fallback accretion process. A sample of similar bursts with multiple emission episodes in the prompt phase and sufficient follow-up could help to probe the underlying physics of GRB central engines.

An off-center shift of the magnetic hysteresis loop, usually known as exchange bias, develops in an asymmetric nanodisk due to the Dzyaloshinskii-Moriya (DM) interaction. Results exhibit the onset of bias in a system without material interfaces, originating from the relation between the chirality defined by the DM interaction and the geometry. In addition, programmable magnetization bias by the variation of an external field emerges as a possibility. Our simulations, carried out using Mumax3 code, also yield double hysteresis loops, evidencing a magnetization reversal driven by vortex nucleation and annihilation. Bias in a homogeneous nanodisk and its control seem promising for applications.

Measuring complexity statistical indicators is a key method to analyze and characterize dynamical systems. In this work, we perform a comparative analysis among the López-Ruiz, Mancini & Calbet complexity indicator and the largest Lyapunov exponent for the convection problem of a viscoelastic fluid in a porous medium with feedback control based in an Oldroyd carrier liquid through a four-dimensional generalized Lorenz system. With both indicators can be distinguished from chaotic to periodic states. We perform intensive numerical simulations with 4×106 in the space parameters, finding good agreement between them, such that difference is close to 2%. We have also detected that the computing time is much faster in the case of complexity indicator than for Lyapunov exponents. Finally, we have also studied the effect of the initial conditions in the coexistence states, encountering multistability.

Natural diversity and composition patterns of ferns depend highly on environmental conditions such as moisture, temperature, and light imposed by altitudinal gradients. Currently, the main factor that causes changes in the diversity patterns of plants at different altitudes is the increased intensity of human activities. This research analyzed the response in the composition and diversity of terrestrial fern species in an Abies religiosa forest to the altitude and magnitude of anthropogenic disturbance. The effect of human disturbance and altitude on the composition and abundance of ferns was evaluated through Generalized Linear Models, a Structural Equations Model (SEM), and a Canonical Correspondence Analysis. The community of terrestrial ferns was found to be composed of ten species belonging to five families. The SEM showed that anthropogenic factors affect the richness and abundance patterns of ferns in the studied area. We suggest that Dryopteris wallichiana could be an indicator of open and most anthropogenically disturbed sites in temperate forest.

Abstract As the south-westernmost region of Europe, the Iberian Peninsula stands as a key area for understanding the process of modern human dispersal into Eurasia. However, the precise timing, ecological setting and cultural context of this process remains controversial concerning its spatiotemporal distribution within the different regions of the peninsula. While traditional models assumed that the whole Iberian hinterland was avoided by modern humans due to ecological factors until the retreat of the Last Glacial Maximum, recent research has demonstrated that hunter-gatherers entered the Iberian interior at least during Solutrean times. We provide a multi-proxy geoarchaeological, chronometric and paleoecological study on human–environment interactions based on the key site of Peña Capón (Guadalajara, Spain). Results show (1) that this site hosts the oldest modern human presence recorded to date in central Iberia, associated to pre-Solutrean cultural traditions around 26,000 years ago, and (2) that this presence occurred during Heinrich Stadial 2 within harsh environmental conditions. These findings demonstrate that this area of the Iberian hinterland was recurrently occupied regardless of climate and environmental variability, thus challenging the widely accepted hypothesis that ecological risk hampered the human settlement of the Iberian interior highlands since the first arrival of modern humans to Southwest Europe.

This article describes a fuzzy logic-based method optimized for the dome control of a robotic astronomical observatory. A Mamdani inference has been developed in order to make the decision to open or close the dome. The input variables are obtained from data received from a weather station besides the percentage of cloudy sky as derived by two allsky cameras. The software has been tested at the BOOTES-1 observatory as part of the BOOTES Global Network of Robotic Telescopes led by IAA-CSIC.

Genetic Algorithms (GAs) are introduced to tackle the packing problem. The scheduling in Additive Manufacturing (AM) is also dealt with to set up a managed market, called “Lonja3D”. This will enable to determine an alternative tool through the combinatorial auctions, wherein the customers will be able to purchase the products at the best prices from the manufacturers. Moreover, the manufacturers will be able to optimize the production capacity and to decrease the operating costs in each case.

In this work we analyze the influence of curvature on the dynamic properties of the magnetization in bent nanotubes. Our results show that both the resonance frequencies and the number of resonant peaks have a strong dependence on the ground state of the magnetization created by the curvature. Our results can be understood from the analysis of the effective anisotropy and the Dzyaloshinskii–Moriya interaction (DMI) induced by curvature. The ability to control the dynamic properties of these curved ferromagnets makes them excellent candidates for developing applications based on resonant modes of spin waves.

In this paper, we analyze the existence and uniqueness of remotely almost periodic solutions for systems of ordinary differential equations. The existence and uniqueness of remotely almost periodic solutions are achieved by using the results about the exponential dichotomy and the Bi-almost remotely almost periodicity of the homogeneous part of the corresponding systems of ordinary differential equations under our consideration.

It is a matter of current study to determine potential climate changes in different parts of the world, especially in regions like a basin which has the potential to affect socioeconomic and environmental issues in a defined area. This study provides a comparison between several climate change indices trends of two very different basins in Mexico, one located in the northern arid region (the Conchos River basin) and the other in the southern humid area (the Usumacinta River basin). First, quality control, homogenization, and completion of the missing data were applied before calculating the climate change indices and their respective trends for the combined period 1961–1994. A clear warming signal was found for the two basins in addition to an increment in the DTR, in agreement with other studies in Mexico. Also, the Conchos River basin was found to be more humid and the Usumacinta River basin drier, in accordance to a supposed seesaw behavior indicated in previous analysis.

This is the case of a 58 year-old man with a painful tumour in his right ankle, resulting from a long development. An osteolytic injury was found in an X-ray, formed by bone or osteoid trabeculae surrounded by epithelioid osteoblasts and amongst these cells there were osteoclast-type multinucleated cells. The histogenesis of the tumour, the differential diagnosis and the treatment modalities are reported. Resumen: Se presenta el caso de un hombre de 58 años de edad con un tumor doloroso en el tobillo derecho, de larga evolución. Radiológicamente se encontró una lesión osteolítica, con un anillo de esclerosis en el astrágalo. Histológicamente el tumor, está formado por trabéculas de hueso u osteoide rodeadas de osteoblastos epitelioides y entre estas células hay células multinucleadas tipo osteoclasto. Se comenta la histogénesis del tumor, el diagnóstico diferencial y las modalidades de tratamiento. Keywords: Osteoblastoma, Aggressive osteoblastoma, Epithelioid osteoblastoma, Palabras clave: Osteoblastoma, Osteoblastoma agresivo, Osteoblastoma epitelioides

In this study, the chemical composition, antimicrobial, and antioxidant activities of orange essential oil (AN), its folded orange oils (5×, 10×, 20×) and d-limonene (LN) were investigated. The results observed in the chemical composition showed a decrease in the major component LN, in contrast to other minor components, which increased their concentration, such as decanal, linalool, and α-terpineol. The antimicrobial activity was determined for foodborne pathogens using the disk diffusion method followed by the minimum inhibitory concentration and minimum bactericidal concentration. Results showed that folded orange oils (5×, 10×, 20×) had better antimicrobial activity than AN and LN. The antioxidant activity was carried out by 2,2ʹ-azinobis-3-ethylbenzthiazoline-6-sulphonate and 1,1-diphenyl-2-picrylhydrazyl methods; folded orange oil 20× presented significantly better results (p ≤ 0.05) than other oils studied. Using folded oils from AN could be a natural alternative in food processing as ingredients with antimicrobial and antioxidant effect.

ABSTRACT USA500 isolates are clonal complex 8 (CC8) Staphylococcus aureus strains closely related to the prominent community- and hospital-associated USA300 group. Despite being relatively understudied, USA500 strains cause a significant burden of disease and are the third most common methicillin-resistant S. aureus (MRSA) strains identified in the U.S. Emerging Infections Program (EIP) invasive S. aureus surveillance. To better understand the genetic relationships of the strains, we sequenced the genomes of 539 USA500 MRSA isolates from sterile site infections collected through the EIP between 2005 and 2013 in the United States. USA500 isolates fell into three major clades principally separated by their distribution across different U.S. regions. Clade C1 strains, found principally in the Northeast, were associated with multiple IS256 insertion elements in their genomes and higher levels of antibiotic resistance. C2 was associated with Southern states, and E1 was associated with Western states. C1 and C2 strains all shared a frameshift in the gene encoding AdsA surface-attached surface protein. We propose that the term “USA500” should be used for CC8 strains sharing a recent common ancestor with the C1, C2, and E1 strains but not in the USA300 group. IMPORTANCE In this work, we have removed some of the confusion surrounding the use of the name “USA500,” placed USA500 strains in the context of the CC8 group, and developed a strategy for assignment to subclades based on genome sequence. Our new phylogeny of USA300/USA500 will be a reference point for understanding the genetic adaptations that have allowed multiple highly virulent clonal strains to emerge from within CC8 over the past 50 years.

José María García de Paredes, construyó entre 1964 y 1967 tres escuelas en Granada, una arquitectura comprometida, que sigue sorprendiendo cincuenta años después por la vigencia y rotundidad de los principios que las originaron. Estos son los únicos edificios escolares que García de Paredes construyó en su carrera, en ellos sintetizo un discurso completo sobre los nuevos espacios docentes que se demandaban por la sociedad de la época. Y lo hizo en unas circunstancias especialmente complicadas en las que el proyecto surge como solución a un problema casi imposible de tiempos, economía y construcción. Aunque nunca fueron pensadas para estar en servicio tanto tiempo y construidas con materiales humildes, han cumplido de una manera ejemplar los cincuenta años, y lo hacen en pleno funcionamiento, sin haber sufrido importantes modificaciones en las formas y principios que las generaron.

 Se logró el aislamiento de Toxoplasma gondii en una muestra de diafragma de un bovino clínicamente sano, sacrificado para ser destinado al consumo de la población en el Matadero Industrial Centro Occidental de Barquisimeto, estado Lara. La muestra fue inoculada en ratones blancos los cuales se dejaron en observación durante 30 días. al final de este período se inoculó otro lote de ratones. lográndose el aislamiento 7 días después del pasaje. Con esto se confirma la infección inaparente por T. gondii en la especie bovina en Venezuela.