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The mechanism responsible for the damping of the large-scale, azimuthally directed jets observed at Jupiter's surface is not well known, but electromagnetic forces are suspected to play a role as the planet's electrical conductivity increases radially with depth. To isolate the jet damping process, we carry out a suite of direct numerical simulations of quasi-two-dimensional, horizontally periodic Rayleigh-Bénard convection with stress-free boundary conditions in the presence of an external, vertical magnetic field. Jets, punctuated by intermittent convective bursts, develop at Rayleigh numbers (Ra, ratio of buoyancy to diffusion) beyond 10^{5} when the magnetic field is relatively weak. Five primary flow regimes are found by varying 10^{3}≤Ra≤10^{10} and the Chandrasekhar number (Ch, ratio of Lorentz to viscosity) 0≤Ch≤10^{6}: (i) steady convection rolls, (ii) steady magneto-columns, (iii) unsteady to turbulent magneto-plumes, (iv) horizontally drifting magneto-plumes, and (v) jets with intermittent turbulent convective bursts. We parse the parameter space using transitions derived from the interaction parameter (N, ratio of Lorentz to inertia). The transition to the regime dominated by jets has the most immediate applications to the magnetic damping of Jovian jet flows, where the separation between jets and a magnetically constrained system occurs at a jet-based interaction parameter value of N_{J}≈1. We approximate the value of the Jovian interaction parameter as a function of depth, and find that the jets may brake at ≈6000 km below the surface, which is deeper than recent estimates from NASA's Juno mission. This suggests that mechanisms in addition to electromagnetic forces are likely required to fully truncate the jets.

In magnetostrophic rotating magnetoconvection, a fluid layer heated from below and cooled from above is equidominantly influenced by the Lorentz and the Coriolis forces. Strong rotation and magnetism each act separately to suppress thermal convective instability. However, when they act in concert and are near in strength, convective onset occurs at less extreme Rayleigh numbers ( Ra , thermal forcing) in the form of a stationary, large-scale, inertia-less, inviscid magnetostrophic mode. Estimates suggest that planetary interiors are in magnetostrophic balance, fostering the idea that magnetostrophic flow optimizes dynamo generation. However, it is unclear if such a mono-modal theory is realistic in turbulent geophysical settings. Donna Elbert first discovered that there is a range of Ekman ( Ek , rotation) and Chandrasekhar ( Ch , magnetism) numbers, in which stationary large-scale magnetostrophic and small-scale geostrophic modes coexist. We extend her work by differentiating five regimes of linear stationary rotating magnetoconvection and by deriving asymptotic solutions for the critical wavenumbers and Rayleigh numbers. Coexistence is permitted if Ek

The interplay between convective, rotational and magnetic forces defines the dynamics within the electrically conducting regions of planets and stars. Yet their triadic effects are separated from one another in most studies, arguably due to the richness of each subset. In a single laboratory experiment, we apply a fixed heat flux, two different magnetic field strengths and one rotation rate, allowing us to chart a continuous path through Rayleigh-Bénard convection (RBC), two regimes of magnetoconvection, rotating convection and two regimes of rotating magnetoconvection, before finishing back at RBC. Dynamically rapid transitions are determined to exist between jump rope vortex states, thermoelectrically driven magnetoprecessional modes, mixed wall- and oscillatory-mode rotating convection and a novel magnetostrophic wall mode. Thus, our laboratory 'pub crawl' provides a coherent intercomparison of the broadly varying responses arising as a function of the magnetorotational forces imposed on a liquid-metal convection system.

Large genome‐scale studies are deposited in various public sequence repositories. However, their access and analysis can be non‐trivial to infrequent users. Here, we present a new database connecting whole transcriptomes with clinical data for straight‐forward access and analysis of patient‐specific samples. Users can perform association tests of survival and gene expression across different cohorts, identify cell‐type expressions, or correlate the presence of immune cells. In summary, we present a new data hub for bench scientists to perform replication and discovery studies. [ABSTRACT FROM AUTHOR]

Figure 2( I a i ) shows the spatio-temporal map of the velocity component Graph $u x$ at Graph $Ra=1.2\times 10^{5}$ recorded by the ultrasonic sensor Graph $Bottom$ at a height of Graph $z = 0.25 H$. According to figure 13, Graph $Nu$ reaches a maximum value at time points Graph $t = 0$ and Graph $t = 0.5\tau {OS}$, while minima occur at Graph $t = 0.25\tau {OS}$ and Graph $t = 0.75\tau {OS}$. Graph $Middle \textit {1}$ and Graph $Middle \textit {2}$ are at the mid-height of the container (Graph $z = 0.5H$) and Graph $Bottom$ is situated close to the bottom plate (Graph $z = 0.25H$). The symbols Graph $g$ and Graph $\Delta T$ denote the gravitational acceleration and the vertical temperature difference in a fluid layer of thickness Graph $H$ and characteristic horizontal dimension Graph $L$. In particular, for a temperature of Graph $25\,^{\circ } \textrm {C}$ the following values are reported: density Graph $\rho = 6360\ \textrm {kg}\ \textrm {m}^{-3}$, thermal expansion coefficient Graph $\alpha = 1.24 \times 10^{-4}\ \textrm {K}^{-1}$, kinematic viscosity Graph $\nu = 3.4 \times 10^{-7}\ \textrm {m}^{2} \ \textrm {s}^{-1}$ and thermal diffusivity Graph $\kappa = 1.03 \times 10^{-5} \textrm {m}^{2}\ \textrm {s}^{-1}$. [Extracted from the article]

Background: Cancer immunotherapy has transformed metastatic cancer treatment, yet challenges persist regarding therapeutic efficacy. RECQL4, a RecQ-like helicase, plays a central role in DNA replication and repair as part of the DNA damage response, a pathway implicated in enhancing efficacy of immune checkpoint inhibitor (ICI) therapies. However, its role in patient response to ICI remains unclear., Methods: We analysed whole exome and bulk RNA sequencing data from a pan-cancer cohort of 25 775 patients and cutaneous melanoma cohorts (untreated: n = 471, anti-progressive disease [PD]-1 treated: n = 212). RECQL4 copy number variations and expression levels were assessed for patient outcomes. We performed gene set enrichment analysis to identify RECQL4-dependent signalling pathways and explored the association between RECQL4 levels and immunoscores. We evaluated the interplay of ICI response and RECQL4 expression in melanoma cohorts of 95 responders and 85 non-responders prior to and after ICI-targeted therapy and tested the prognostic power of RECQL4. Finally, we generated genetically engineered RECQL4 variants and conducted comprehensive multi-omic profiling, employing techniques such as liquid chromatography with tandem mass spectrometry, to elucidate mechanistic insights., Results: We identified RECQL4 as a critical negative regulator of poor prognosis and response to ICI therapy, but also demonstrated its suitability as an independent biomarker in melanoma. High tumour purity and limited signatures of tumour immunogenicity associated with response to anti-PD-1 correlated with high RECQL4 activity. We found alterations in the secretion profile of immune regulatory factors and immune-related pathways robustly suppressed in tumours with high RECQL4 levels, underscoring its crucial role in fostering immune evasion. Mechanistically, we identified RECQL4-mediated regulation of major histocompatibility complex class II molecule expression and uncovered class II major histocompatibility complex transactivator as a mediator bridging this regulation., Conclusions: Our findings unraveled the pivotal role of RECQL4 in immune modulation and its potential as both a predictive biomarker and therapeutic target for optimising immunotherapeutic strategies across various cancer types., Highlights: High RECQL4 expression limits survival and can act as an independent prognostic factor in melanoma patients. RECQL4 has the potential to act as a negative feedback mediator of immune checkpoint-targeted therapy by limiting signatures associated with therapeutic efficacy. RECQL4 favours an immune-evasive phenotype by downregulating major histocompatibility complex class II molecules., (© 2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Most patients with unresectable locally advanced cutaneous squamous cell carcinoma (cSCC) benefit from cemiplimab, but some do not respond. Our study aims to identify clinical and histopathological features predicting response to cemiplimab., Patients and Methods: We analyzed 15 patients treated with cemiplimab, assessing clinical, demographic, histopathological, and immunohistochemical characteristics and correlating them with treatment response. Furthermore, effectiveness and safety were evaluated in our cohort., Results: Our cohort included 12 males and 3 females, with a mean age of 78.1 years. The majority of tumors, accounting for 66.7%, were located in the head and neck region. Treatment was well-tolerated, with only one grade 3 colitis. There was no correlation between immune-related adverse events and treatment response. Non-responders were younger (69.4 vs. 82.5 years). A history of hematological malignancy correlated with poorer response. High mitotic rate, poor tumor differentiation, high vimentin and p53, and low E-cadherin expression were associated with worse response. Conversely, higher intratumoral inflammatory infiltrate density, presence of necrotic areas, and lower mismatch repair-protein staining correlated with better response., Conclusions: Cemiplimab is a safe and effective therapy, particularly in elderly patients. Well-differentiated tumors with low proliferative index, intratumoral inflammatory infiltrate, and tumor necrosis may predict better clinical response., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Discerning the mechanisms driving type 2 diabetes (T2D) pathophysiology from genome-wide association studies (GWAS) remains a challenge. To this end, we integrated omics information from 16 multi-tissue and multi-ancestry expression, protein, and metabolite quantitative trait loci (QTL) studies and 46 multi-ancestry GWAS for T2D-related traits with the largest, most ancestrally diverse T2D GWAS to date. Of the 1,289 T2D GWAS index variants, 716 (56%) demonstrated strong evidence of colocalization with a molecular or T2D-related trait, implicating 657 cis -effector genes, 1,691 distal-effector genes, 731 metabolites, and 43 T2D-related traits. We identified 773 of these cis - and distal-effector genes using either expression QTL data from understudied ancestry groups or inclusion of T2D index variants enriched in underrepresented populations, emphasizing the value of increasing population diversity in functional mapping. Linking these variants, genes, metabolites, and traits into a network, we elucidated mechanisms through which T2D-associated variation may impact disease risk. Finally, we showed that drugs targeting effector proteins were enriched in those approved to treat T2D, highlighting the potential of these results to prioritize drug targets for T2D. These results represent a leap in the molecular characterization of T2D-associated genetic variation and will aid in translating genetic findings into novel therapeutic strategies., Competing Interests: Disclosures J.B.M is an academic associate for Quest Diagnostics Inc. Endocrine R&D. MIMcC is now an employee of Genentech and a holder of Roche stock.

In magnetostrophic rotating magnetoconvection, a fluid layer heated from below and cooled from above is equidominantly influenced by the Lorentz and the Coriolis forces. Strong rotation and magnetism each act separately to suppress thermal convective instability. However, when they act in concert and are near in strength, convective onset occurs at less extreme Rayleigh numbers ( R a , thermal forcing) in the form of a stationary, large-scale, inertia-less, inviscid magnetostrophic mode. Estimates suggest that planetary interiors are in magnetostrophic balance, fostering the idea that magnetostrophic flow optimizes dynamo generation. However, it is unclear if such a mono-modal theory is realistic in turbulent geophysical settings. Donna Elbert first discovered that there is a range of Ekman ( E k , rotation) and Chandrasekhar ( C h , magnetism) numbers, in which stationary large-scale magnetostrophic and small-scale geostrophic modes coexist. We extend her work by differentiating five regimes of linear stationary rotating magnetoconvection and by deriving asymptotic solutions for the critical wavenumbers and Rayleigh numbers. Coexistence is permitted if E k < 16 / ( 27 π ) 2 and C h ≥ 27 π 2 . The most geophysically relevant regime, the Elbert range , is bounded by the Elsasser numbers 4 3 ( 4 4 π 2   E k ) 1 / 3 ≤ Λ ≤ 1 2 ( 3 4 π 2 E k ) - 1 / 3 . Laboratory and Earth's core predictions both exhibit stationary, oscillatory, and wall-attached multi-modality within the Elbert range., (© 2022 The Authors.)