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Cool- and warm-season precipitation totals have been reconstructed on a gridded basis for North America using 439 tree-ring chronologies correlated with December–April totals and 547 different chronologies correlated with May–July totals. These discrete seasonal chronologies are not significantly correlated with the alternate season; the December–April reconstructions are skillful over most of the southern and western United States and north-central Mexico, and the May–July estimates have skill over most of the United States, southwestern Canada, and northeastern Mexico. Both the strong continent-wide El Niño–Southern Oscillation (ENSO) signal embedded in the cool-season reconstructions and the Arctic Oscillation signal registered by the warm-season estimates faithfully reproduce the sign, intensity, and spatial patterns of these ocean–atmospheric influences on North American precipitation as recorded with instrumental data. The reconstructions are included in the North American Seasonal Precipitation Atlas (NASPA) and provide insight into decadal droughts and pluvials. They indicate that the sixteenth-century megadrought, the most severe and sustained North American drought of the past 500 years, was the combined result of three distinct seasonal droughts, each bearing unique spatial patterns potentially associated with seasonal forcing from ENSO, the Arctic Oscillation, and the Atlantic multidecadal oscillation. Significant 200–500-yr-long trends toward increased precipitation have been detected in the cool- and warm-season reconstructions for eastern North America. These seasonal precipitation changes appear to be part of the positive moisture trend measured in other paleoclimate proxies for the eastern area that began as a result of natural forcing before the industrial revolution and may have recently been enhanced by anthropogenic climate change.

Highly sophisticated mechanisms that modulate protein structure and function, which involve synthesis and degradation, have evolved to maintain cellular homeostasis. Perturbations in these mechanisms can lead to protein dysfunction as well as deleterious cell processes. Therefore in recent years the etiology of a great number of diseases has been attributed to failures in mechanisms that modulate protein structure. Interconnections among metabolic and cell signaling pathways are critical for homeostasis to converge on mechanisms associated with protein folding as well as for the preservation of the native structure of proteins. For instance, imbalances in secretory protein synthesis pathways lead to a condition known as endoplasmic reticulum (ER) stress which elicits the adaptive unfolded protein response (UPR). Therefore, taking this into consideration, a key part of this paper is developed around the protein folding phenomenon, and cellular mechanisms which support this pivotal condition. We provide an overview of chaperone protein function, UPR via, spatial compartmentalization of protein folding, proteasome role, autophagy, as well as the intertwining between these processes. Several diseases are known to have a molecular etiology in the malfunction of mechanisms responsible for protein folding and in the shielding of native structure, phenomena which ultimately lead to misfolded protein accumulation. This review centers on our current knowledge about pathways that modulate protein folding, and cell responses involved in protein homeostasis.

Durante los últimos años, un número importante de escritos académicos en relaciones internacionales (RRIT) ha contribuido a reflexionar críticamente sobre la narrativa tradicional de la misma. La mayor parte de esta literatura se ha concentrado en los años tempranos de RRII poniendo en tela de juicio su supuesto nacimiento en 1919, así como la existencia del idealismo liberal y del primer gran debate. El presente artículo busca contribuir a dichos esfuerzos críticos, añadiendo como variables a las mujeres internacionalistas y a algunos feminismos de la primera parte del siglo xx -particularmente relacionados con el socialismo y/o el pacifismo- para mostrar deficiencias importantes de la historia convencional. A través de un análisis textual de los escritos de diversas internacionalistas de principios del siglo Xx, así como de su trabajo en la construcción de instituciones relacionadas con asuntos internacionales, el artículo expone cinco mitos disciplinarios de RRII. Se concluye que existe una multiplicidad de contribuciones de diversos feminismos y de las mujeres a la disciplina antes de 1980, pese a que continúan siendo oscurecidas por la historia ortodoxa. Esto tiene implicaciones importantes en nuestro entendimiento historiográfico de RRII, las raíces del feminismo internacionalista, y la posibilidad de rescatar nuevos enfoques teóricos.

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the “on−off” schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases. Whether intermittent strategies of delivering drugs can improve cancer patients survival is still unclear. Here, the authors reports the results of a randomized phase II clinical trial aimed to compare the efficacy and safety of two dosing regimens (continuous and intermittent) of vemurafenib and cobimetinib combination as first-line treatment of patients with unresectable or metastatic advanced melanoma with BRAFV600 mutation

This research aimed to assess the effect of chitosan nanoparticles (ChNPs) during in vitro shoot proliferation of vanilla using temporary immersion bioreactors (TIB). TIB culture is a biotechnological process that uses semiautomated containers for the production of explants exposed in liquid culture medium. Concentrations of control, 25, 50, 100, 200, and 400 mg/L ChNPs were evaluated in Murashige and Skoog culture medium. Morphological characterization of ChNPs was performed using scanning electron microscopy. At 60 days of culture, survival (%), development variables, photosynthetic pigment content, lipid peroxidation expressed in malondialdehyde, total phenolic content (TPC), hydrogen peroxide (H2O2) content, and total antioxidant capacity (TAC) expressed in trolox equivalents were evaluated. The data were analyzed with analysis of variance, with a Tukey test (p ≤ 0.05) using SPSS statistics software, version 29. The results revealed that the greatest survival (%) was obtained at concentrations of control, 25, and 50 mg/L ChNPs, while the lowest survival (%) was observed at concentrations of 400 mg/L ChNPs. Growth stimulation was found, as well as an increase in chlorophyll and β-carotene at concentrations of 25 and 50 mg/L ChNPs. The level of H2O2 increased at 25 and 50 mg/L ChNPs. Lipid peroxidation showed no differences among treatments. TPC increased at 100 and 200 mg/L ChNPs, while TAC increased at 200 and 400 mg/L ChNPs. In conclusion, the administration of ChNPs at low concentrations can stimulate growth, while at high concentrations they can inhibit it, a response known as hormesis or hormetic effect.

Estimating wildfire greenhouse gas (GHG) emissions in Mediterranean landscapes is challenging due to heterogeneous fuel mosaics and limited scalability of field-based approaches. This study presents a Geographic Information System (GIS) based framework that integrates land-cover data, pre-fire biomass estimates, fire severity mapping, and established emission factors to produce spatially explicit estimates of biomass consumption and GHG emissions. Fire severity was derived from multitemporal Sentinel-2 imagery using the differenced Normalized Burn Ratio (ΔNBR) and combined with land-cover information to define vegetation–severity classes for emission estimation. A key innovation is the identification of co-occurring vegetation types within the same spatial units, allowing emissions to be quantified across vegetation mixtures rather than single classes, providing a more realistic representation of Mediterranean forests. Applied to the 2022 Bejis wildfire, pre-fire biomass within the burned area was 673,601 tons. Coniferous forests dominated, but co-occurrence with shrubland and herbaceous layers produced the highest emission contributions, highlighting the role of vegetation interactions. Total emissions were estimated at 625,938 tons of equivalent CO2, and comparison with large-scale datasets (CAMS Global Fire Assimilation System, Global Fire Emissions Database) shows general coherence. This severity-driven, vegetation-explicit framework demonstrates robust potential for quantifying wildfire emissions across heterogeneous Mediterranean landscapes, though uncertainties remain due to pre-defined biomass, burning efficiency, emission factors, assumptions in fire severity mapping, and limited field validation. The approach can support improved regional GHG inventories and wildfire management strategies.

Due to pathologies or age-related problems, in some disabled people, motor impairment is associated with cognitive and/or visual impairments. This combination of limitations unfortunately leads to an inability to move around independently. Indeed, their situation does not allow them to use a conventional electric wheelchair, for safety reasons, and for the moment there is no other technological solution providing safe movement capacity. This lack of access to an autonomous travel solution has the consequence of weakening the intellectual, personal, social, cultural and moral development, as well as the life expectancy, of the people concerned. In this context, our team is working on the development of an optoelectronic system that secures the displacement of electric wheelchairs. This is a large project that requires the development of several functionalities such as: the anti-collision of the wheelchair with its environment, the prevention of falls from the wheelchair on uneven levels, and the adaptation of the system mechanically and electronically to the majority of commercially available electric wheelchair models, among others. In this article, we introduce our solution for detecting dangerous height differences, also called “negative obstacles”, through the creation of a dedicated sensor. This sensor works by optical triangulation and can embed several laser beams in order to extend its detection zone. It has the particularity of being robust in direct sunlight and rain and has a sufficiently high measurement rate to be suitable for the displacement of electric wheelchairs. We develop an adapted algorithm, and point out compromises, in particular between the orientation of the laser beams and the maximal speed of the wheelchair.

This study analyses the environmental sustainability of using wooden boxes (WBs) compared to corrugated cardboard boxes (CCBs) for the transport of fruit and vegetable products, where the same box size between WB and CCB is assessed and compared. The Life Cycle Assessment (LCA) followed ISO 14040:2006 and ISO 14044:2006 standards, using the ReCiPe 2016 MidPoint methodology. The following impact categories analysed for sustainability impact, evaluation and monitoring are included: global warming potential, acidification, eutrophication, human toxicity and abiotic resource depletion. The study covered all the stages of packaging life through cradle-to-grave analysis. The study results show that CCBs have a higher environmental impact across most categories despite being single-use packaging systems. The comparison between both packaging systems shows that WBs are a more sustainable alternative, with lower overall environmental impacts in fruit and vegetable packaging and transport. As a general conclusion, WBs have a lower overall environmental impact than CCBs, especially in the key impact criteria of global warming potential, acidification, eutrophication, human non-carcinogenic toxicity, fossil resource depletion and water consumption. Due to that, the wooden box is a more sustainable material for fruit and vegetable packaging, logistics and transport than the corrugated cardboard box, considering the scope and destination analysed.

Due to their rarity and heterogeneity and despite the introduction of molecular features in the current WHO classification, clinical criteria such as those from the European Organization for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG) are still being used to make treatment decisions in low-grade gliomas (LGG). Patients with diffuse low-grade glioma treated at our institution between 2002 and 2018 were analyzed, retrieving and assessing the degree of consistency between the EORTC and RTOG criteria, as well as the isocitrate dehydrogenase 1 and 2 (IDH) gene mutational status. Likewise, multivariate analyses were performed to ascertain the superiority of any of the factors over the others. One hundred and two patients were included. The degree of consistency between the RTOG and EORTC criteria was 71.6% (K = 0.426; p = 0.0001). Notably, 51.7% of those assigned to low risk by the EORTC were classified as high risk according to the RTOG classification. In multivariate analysis, only complete resection, age > 40 years, size and IDH mutation status were independently correlated with OS. When the RTOG and EORTC scores were entered into the model, only the EORTC model was independently associated with mortality. The degree of consistency between the EORT and RTOG criteria is low. Therefore, there is a need to integrate clinical-molecular scores to improve treatment decisions in LGG.

The objective of the present study was to analyze the psychometric properties of a life satisfaction scale in older Peruvian adults using an exploratory graph analysis (EGA) approach. A total of 407 older adults aged between 60 and 95 years (M = 69.5; SD = 6.7) from three comprehensive elderly care centers (CIAMs) in Lima, Peru, were recruited. A non-probabilistic convenience sampling was used. The Satisfaction with Life Scale (SWLS) was analyzed using EGA with the Gaussian GLASSO model to assess its dimensionality and structural consistency. The relationship with other variables was analyzed using scales such as the GAD-7 and PHQ-9. The network structure of the SWLS indicates a single dimension. Additionally, network loadings (nodes) were examined, showing high values (>0.35) for most items except item 1, which had a moderate loading (>0.25). Structural reliability showed that a single dimension was identified 100% of the time. The post hoc CFA considering the unidimensional network structure obtained through EGA showed satisfactory fit (χ2/df = 3.48, CFI = 0.96, TLI = 0.92, SRMR = 0.02, RMSEA = 0.07 [90% CI 0.05, 0.08]). Finally, internal consistency reliability was acceptable (ω = 0.92). The SWLS measure is robust and consistent. These findings are a valuable reference for advancing research on aging in Peru, as they provide a practical, valid, and reliable measure.