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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early‐diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre‐mRNA processing factor 8 (PRPF8) and RNA‐binding motif protein X‐linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non‐tumor levels and resulted in decreased key tumor‐related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.

We used attitude data from the Mars Ingenuity helicopter with a simple steady-state model to estimate wind speeds and directions at altitudes between 3 and 24 m, the first time winds at such altitudes have been probed on Mars. We compared our estimates to wind data from the meteorology package MEDA on board the Mars 2020 Perseverance rover and to predictions from meteorological models. Wind directions inferred from Ingenuity data agreed with the directions measured by MEDA, when the latter were available, but deviated from model-predicted directions by as much as 180° in some cases. The inferred wind speeds are often much higher than expected. For example, meteorological predictions suggest that Ingenuity should not have seen wind speeds above about 15 m s ^−1 during its 59th flight, but we inferred speeds reaching nearly 25 m s ^−1 . For flights during which we have MEDA data to compare to, inferred wind speeds imply friction velocities >1 m s ^−1 and roughness lengths >10 cm, which seem implausibly large. These results suggest that Ingenuity was probing winds sensitive to aerodynamic conditions hundreds of meters upwind instead of the conditions very near Mars 2020, but they may also reflect a need for updated boundary layer wind models. An improved model for Ingenuity’s aerodynamic response that includes the effects of transient winds may also modify our results. In any case, the work here provides a foundation for exploration of planetary boundary layers using drones and suggests important future avenues for research and development.

Ozone plays a key role in both atmospheric chemistry and UV absorption in planetary atmospheres. On Mars, upper-tropospheric ozone has been widely characterized by space-based instruments. However, surface ozone remains poorly characterized, hindered by the limited sensitivity of orbiters to the lowest scale height of the atmosphere and challenges in delivering payloads to the surface of Mars, which have prevented, to date, the measurement of ozone from the surface of Mars. Systematic measurements from the Martian surface could advance our knowledge of the atmospheric chemistry and habitability potential of this planet. NASA’s Mars 2020 mission includes the first ozone detector deployed on the Martian surface, which is based on discrete photometric observations in the ultraviolet band, a simple technology that could obtain the first insights into total ozone abundance in preparation for more sophisticated measurement techniques. This paper describes the Mars 2020 ozone detector and its retrieval algorithm, including its performance under different sources of uncertainty and the potential application of the retrieval algorithm on other missions, such as NASA’s Mars Science Laboratory. Pre-landing simulations using the UVISMART radiative transfer model suggest that the retrieval is robust and that it can deal with common issues affecting surface operations in Martian missions, although the expected low ozone abundance and instrument uncertainties could challenge its characterization in tropical latitudes of the planet. Other space missions will potentially include sensors of similar technology.

The tumor microenvironment (TME) is an intricate complex and dynamic structure composed of various cell types, including tumor, stromal and immune cells. Within this complex network, lymphatic endothelial cells (LECs) play a crucial role in regulating immune responses and influencing tumor progression and metastatic dissemination to lymph node and distant organs. Interestingly, LECs possess unique immunomodulatory properties that can either promote or inhibit anti-tumor immune responses. In fact, tumor-associated lymphangiogenesis can facilitate tumor cell dissemination and metastasis supporting immunoevasion, but also, different molecular mechanisms involved in LEC-mediated anti-tumor immunity have been already described. In this context, the crosstalk between cancer cells, LECs and immune cells and how this communication can shape the immune landscape in the TME is gaining increased interest in recent years. In this review, we present a comprehensive and updated report about the immunomodulatory properties of the lymphatic endothelium within the TME, with special focus on primary tumors and tumor-draining lymph nodes. Furthermore, we outline emerging research investigating the potential therapeutic strategies targeting the lymphatic endothelium to enhance anti-tumor immune responses. Understanding the intricate mechanisms involved in LEC-mediated immune modulation in the TME opens up new possibilities for the development of innovative approaches to fight cancer.

The multipolar spherical vortex solutions to the Euler and Navier–Stokes equations in background cylindrical flow with swirl admit an additional background divergent radial flow with arbitrary time-dependent amplitude. In this case the radial wavenumber $k$ , fundamental frequency $\omega$ and overall amplitude $U$ of the multipolar mode superposition become time-dependent and related functions. Assumption of an additional constraint, as a constitutive equation defining the time evolution of the spatially homogeneous divergence of the background flow, is required for the time evolution of the total flow to be completely evaluated from the initial conditions. It is found that flow compression implies an increase of the absolute values of the fundamental frequency $\omega$ and overall velocity amplitude $U$ of the oscillations. [ABSTRACT FROM AUTHOR]

We explore and evaluate various processes that could drive the variations in the volume mixing ratio (VMR) of atmospheric O _2 observed by the quadrupole mass spectrometer (QMS) of the Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity rover. First reported by Trainer et al. ( 2019 ), these ∼20% variations in the O _2 VMR on a seasonal timescale over Mars Years 31–34, in excess of circulation and transport effects driven by the seasonal condensation and sublimation of CO _2 at the poles, are significantly shorter than the modeled O _2 photochemical lifetime. While there remains significant uncertainty about the various processes we investigated (atmospheric photochemistry, surface oxychlorines and H _2 O _2 , dissolution from brines, and airborne dust), the most plausible driver is surface oxychlorines, exchanging O _2 with the atmosphere through decomposition by solar ultraviolet and regeneration via O _3 . A decrease in O _3 from increased atmospheric H _2 O would reduce the removal rate of O _2 from the atmosphere to form oxychlorines at the surface. This is consistent with the tentative observation that increases in O _2 are associated with increases in water vapor. A lack of correlation with the local surface geology along Curiosity’s traverse within Gale crater, the nonuniqueness of the relevant processes to Gale crater, and the short mixing timescales of the atmosphere all suggest that the O _2 variations are a regional, or even global, phenomenon. Nonetheless, further laboratory experiments and modeling are required to accurately scale the laboratory-measured rates to Martian conditions and to fully elucidate the driving mechanisms.

Abstract Atmospheric local-to-regional dispersion models are widely used on Earth to predict and study the effects of chemical species emitted into the atmosphere and to contextualize sparse data acquired at particular locations and/or times. However, to date, no local-to-regional dispersion models for Mars have been developed; only mesoscale/microscale meteorological models have some dispersion and chemical capabilities, but they do not offer the versatility of a dedicated atmospheric dispersion model when studying the dispersion of chemical species in the atmosphere, as it is performed on Earth. Here, a new three-dimensional local-to-regional-scale Eulerian atmospheric dispersion model for Mars (DISVERMAR) that can simulate emissions to the Martian atmosphere from particular locations or regions including chemical loss and predefined deposition rates, is presented. The model can deal with topography and non-uniform grids. As a case study, the model is applied to the simulation of methane spikes as detected by NASA’s Mars Science Laboratory (MSL); this choice is made given the strong interest in and controversy regarding the detection and variability of this chemical species on Mars.

Atmospheric dispersion and chemical transport models (CTMs) are a key tool in both atmospheric chemistry and environmental sciences [...]

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early‐diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre‐mRNA processing factor 8 (PRPF8) and RNA‐binding motif protein X‐linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non‐tumor levels and resulted in decreased key tumor‐related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets. [ABSTRACT FROM AUTHOR]

Ozone plays a key role in both atmospheric chemistry and UV absorption in planetary atmospheres. On Mars, upper-tropospheric ozone has been widely characterized by space-based instruments. However, surface ozone remains poorly characterized, hindered by the limited sensitivity of orbiters to the lowest scale height of the atmosphere and challenges in delivering payloads to the surface of Mars, which have prevented, to date, the measurement of ozone from the surface of Mars. Systematic measurements from the Martian surface could advance our knowledge of the atmospheric chemistry and habitability potential of this planet. NASA's Mars 2020 mission includes the first ozone detector deployed on the Martian surface, which is based on discrete photometric observations in the ultraviolet band, a simple technology that could obtain the first insights into total ozone abundance in preparation for more sophisticated measurement techniques. This paper describes the Mars 2020 ozone detector and its retrieval algorithm, including its performance under different sources of uncertainty and the potential application of the retrieval algorithm on other missions, such as NASA's Mars Science Laboratory. Pre-landing simulations using the UVISMART radiative transfer model suggest that the retrieval is robust and that it can deal with common issues affecting surface operations in Martian missions, although the expected low ozone abundance and instrument uncertainties could challenge its characterization in tropical latitudes of the planet. Other space missions will potentially include sensors of similar technology. [ABSTRACT FROM AUTHOR]

Este trabajo de investigación revela las pruebas documentales que han hecho posible la reconstrucción genealógica de los descendientes del emir Muley Hacén; la familia conocida como Muley Fez. Hemos logrado reconstruir genealógicamente a la familia en el decurso de seis generaciones consecutivas, desde finales del s. XV hasta finales del s. XVI, identificando y documentando a un elenco familiar que asciende a treinta y siete individuos en total. El cruce y puesta en común de más de una veintena de manuscritos inéditos, de diversa procedencia y naturaleza, han puesto al descubierto una extensa red de parentesco familiar. La reconstrucción del árbol genealógico, pese a ser un fin en sí mismo, es también un paso previo y necesario para rehacer la historia y el devenir de uno de los más importantes linajes de la aristocracia morisca del s. XVI.

Checkpoint with forkhead-associated and ring finger domains (CHFR) has been proposed as a predictive and prognosis biomarker for different tumor types, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was two-pronged: to review the role of CHFR in PDAC and evaluating CHFR as a potential predictive biomarker in this disease. For this purpose, we first explored the CHFR messenger (m)RNA expression and promoter methylation through the TCGA database. Secondly, the CHFR expression and promoter methylation were prospectively evaluated in a cohort of patients diagnosed with borderline (n = 19) or resectable (n = 16) PDAC by immunohistochemistry (IHC), methylation specific-PCR (MSP), and pyrosequencing. The results from the TCGA database showed significant differences in terms of progression-free survival (PFS) and overall survival (OS) based on the CHFR mRNA expression, which was likely independent from the promoter methylation. Importantly, our results showed that in primarily resected patients and also the entire cohort, a higher CHFR expression as indicated by the higher IHC staining intensity might identify patients with longer disease-free survival (DFS) and OS, respectively. Similarly, in the same cohorts, patients with lower methylation levels by pyrosequencing showed significantly longer OS than patients without this pattern. Both, the CHFR expression intensity and its promoter methylation were established as independent prognostic factors for PFS and OS in the entire cohort. In contrast, no significant differences were found between different methylation patterns for CHFR and the response to taxane-based neoadjuvant treatment. These results suggest the potential role of the higher expression of CHFR and the methylation pattern of its promoter as potential prognostic biomarkers in PDAC, thus warranting further comprehensive studies to extend and confirm our preliminary findings.