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Prognostic impact of myelodysplasia-related gene mutations in FLT3-ITD-mutated acute myeloid leukemia
Get PDFThe inclusion of nine myelodysplasia-related gene (MRG) mutations (ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, ZRSR2) as adverse risk factors in the ELN risk classification has reshaped classification in acute myeloid leukemia (AML). AML with FLT3-ITD mutations and co-occurring MRG alterations is now classified to the ELN adverse risk group although supporting evidence remains limited. Among 4,078 patients with AML with available molecular information included in the HARMONY platform, 862 harbored FLT3-ITD mutations and underwent intensive chemotherapy. Of these, 171 (20%) exhibited co-occurring MRG mutations at diagnosis. In this cohort, MRGs were not independently associated with relapse-free survival (RFS) or overall survival (OS). In the FLT3-ITD/NPM1 co-mutated subgroup, MRG mutations were rare (9%) and showed no prognostic impact. Conversely, in FLT3-ITD/NPM1 wildtype AML, MRG mutations were predictive of shorter RFS (HR 1.37, 95%CI 1.01 - 1.88, p = 0.046) and OS (HR 1.34, 95%CI 1.02-1.74, p = 0.032) in multivariable analysis with survival times comparable to the ELN adverse risk category. The allelic ratio of FLT3-ITD did not further stratify OS and RFS in this subgroup. These findings suggest that the prognostic relevance of MRG mutations in FLT3-ITD AML is modulated by NPM1 co-mutational status and mirror findings in AML lacking FLT3-ITD
Computational Basis of Large Language Models’ Decision Making in Social Simulation
Get PDFLarge language models (LLMs) increasingly serve as humanlike decision-making agents in social science and applied settings. These LLM agents are typically assigned humanlike characters and placed in real-life contexts. However, how these characters and contexts shape an LLM’s behavior remains underexplored. In this study the author proposes and tests methods for probing, quantifying, and modifying an LLM’s internal representations in a dictator game, a classic behavioral experiment on fairness and prosocial behavior. The author extracts “vectors of variable variations” (e.g., “male” to “female”) from the LLM’s internal state. Manipulating these vectors during the model’s inference can substantially alter how those variables relate to the model’s decision making. This approach offers a principled way to study and regulate how social concepts can be encoded and engineered within transformer-based models, with implications for alignment, debiasing, and designing artificial intelligence agents for social simulations in both academic and commercial applications, strengthening sociological theory and measurement
Understanding the Role of Triple Phase Boundaries on Coating-Free Solid-State Cathodes
Get PDFSulfide solid electrolytes have high ionic conductivities necessary to achieve high-rate solid-state cathodes at room temperature and low pressure. Cathode active materials generally require coatings to avoid deleterious oxidative decomposition reactions with the electrolyte. Coatings add cost and complexity to the manufacture. Here we decouple the effect of double and triple phase boundaries on the decomposition in the thick (i.e., ∼110 μm) uncoated solid state cathode. We show that more severe oxidative decomposition of solid electrolytes occurs when the cathode active materials, carbon, and the solid electrolyte coexist, highlighting the importance of the triple phase boundary concerning the decomposition. By regulating the electronic pathways at the triple phase boundary, a thick uncoated electrode at 1 mA cm–2 and 2 MPa stack pressure, delivers an initial areal capacity of ∼4.6 mAh cm–2 at 30 °C and ∼85% capacity retention after 500 cycles
Humanoid robotic loading enhances mechanotransduction in tendon tissue engineering
Get PDFMechanical stimulation is essential in tissue engineering and regenerative medicine for proper tissue maturation. However, conventional uniaxial platforms fail to reproduce the multiaxial loading experienced in vivo. In this study, we present a humanoid robotic bioreactor capable of delivering human-like shoulder motions to engineered tendon constructs, enabling controlled multiaxial stimulation with real-time strain monitoring. Human mesenchymal stem cells were cultured on decellularised tendon scaffolds and subjected to adduction–abduction loading at peak strains of approximately 3.5% and 9.5% under external forces of 25 N and 50 N, respectively. Strain levels were directly quantified in situ using a flexible sensor integrated within the bioreactor. The transparent bioreactor membrane allowed non-invasive while simultaneously applying mechanical stimulation over 14 days, with continuous assessment of cellular morphology without fixation. Compared with static and traditional uniaxial controls, the robot motions significantly enhance cell alignment and activation of mechanotransduction pathways, while inducing notable gene and protein expression changes, particularly within the PI3K-Akt signalling pathway. Although dynamic loading resulted in a moderate reduction in cell viability, the transcriptional profile was consistent with mechanically driven phenotypic adaptation toward tenogenic-related programmes rather than dominant signatures of acute cytotoxic damage. These findings demonstrate that replicating human-like multiaxial mechanics in vitro fundamentally alters cellular mechanosensing and may provide a mechanobiological foundation for the future development of more physiologically relevant tendon grafts
Digital nature in the AI era: How human and AI ‐generated representations shape future visions of rewilding
Get PDFRewilding has gained significant influence in nature conservation, offering hopeful narratives that address the interconnected challenges of climate change and biodiversity loss while enabling people to reconnect with ‘wildness’ in the Anthropocene. Rewilding powerfully shapes imaginaries of possible futures and is being implemented through numerous projects across the UK. These projects fundamentally transform landscape aesthetics and determine which human and non‐human species are rendered visible, desirable and legitimate in rewilded futures. In this study, we interrogate the aesthetics of rewilding through a qualitative approach that examines visual and textual materials from advocacy organisation websites, their social media accounts on Instagram and artificial intelligence (AI)‐generated representations of rewilding produced by AI chatbots. Our analysis focuses on the framing and content of visual materials, such as what is represented and what is absent, as well as how these materials construct visions of desirable future natures. We find that representations of rewilding focus on conventional nature aesthetics, predominantly excluding aesthetically challenging ecosystem processes, non‐charismatic species and a diversity of people. We argue that visual and textual materials reveal not only how nature is represented in rewilding discourses but also embody normative assumptions about what recovered or rewilded nature should look like. These visual representations act politically by normalising the presence or absence of particular people and activities in landscapes, thereby perpetuating narrow conceptualisations of environmental futures. We discuss how our findings may inform the development of more socially just environmental imaginaries, contributing to more inclusive future land management both in policy and practice. Read the free Plain Language Summary for this article on the Journal blog
Pulsations Change the Structures of Massive Stars before Explosion: Interpreting SN 2023ixf and SN 2024ggi
Get PDFMassive red supergiants (RSGs) are known to become hydrodynamically unstable before they explode. Still, the vast majority of supernova (SN) models assume RSG progenitors in hydrostatic equilibrium. Here we follow the hydrodynamic evolution of RSGs with different masses and the development of radial envelope pulsations. Pulsations significantly alter the observable pre- and post-SN properties, and their importance increases substantially as a function of initial mass. We demonstrate that inferring core masses, let alone initial masses, from a single pre-SN luminosity and effective temperature of high-mass RSGs is inadvisable, as these can vary by an order of magnitude during the pulsation. We find that pulsations can naturally lead to “early-excess” emission in SN light curves and to variations in early photospheric velocities, which can help break degeneracies in Type II SNe. We compare to SN 2023ixf and SN 2024ggi, for which pulsating RSG progenitors were reported. We demonstrate that the pre- and post-SN characteristics of SN 2023ixf agree very well with our exploding pulsating RSG model and exhibit meaningful differences from hydrostatic models. The data coverage is insufficient to break all degeneracies. We find insufficient evidence for the claimed pulsation period of the SN 2024ggi progenitor, as it matches Spitzer’s orbital period. This study underscores the importance of hydrodynamical pre-SN stellar models, in particular for massive stars from ≳15 M⊙. It implies an important shift in our understanding of the last stages of massive star evolution, the interpretation of pre-SN properties, the connection between SNe and their progenitors, and the missing RSG problem
Class origin closure: economic advantages of occupational elitism
Get PDFThis study investigates the role of class origin compositions of micro-occupations in creating economic inequalities using three decades of British longitudinal surveys. Drawing on social closure theory, we analyze how class origin contributes to between-occupation earnings disparities and class origin earnings inequality at the individual level. Using fine-grained data on the class origins of occupational incumbents, we construct a robust indicator of the concentration of privileged class origins within labor market niches, “occupational elitism,” measured as the percentage of incumbents with parents in the higher salariat (ESeC class 1) within an occupation. Our results reveal that occupational elitism of micro-occupations is positively associated with earnings, after accounting for indicators of positional closure mechanisms, such as educational credentialing, licensure, and unionization. However, these collective earnings premiums are unevenly distributed, with earnings advantages for individuals from upper-class families emerging in occupations with higher levels of occupational elitism
The Sorrows of Young Chatbot Users: Harm and Responsibility in Human-AI Relationships
Get PDFAbstract
This paper argues that interactions with chatbots are a form of engaging with fictional characters; so, by comparing chatbots with novels and video games as mediums of fictional engagement, we can gain a clearer understanding of who, if anyone, is responsible when users’ interactions with chatbots lead to self-harm or harm to others. We explore the differences between novels, video games, and chatbots across four dimensions: the degree of creators’ control over the content and user experience, the nature of the fictional world, the type of engagement each medium fosters, and the structure of the engagement experience. We take a minimal account of what it takes to be morally responsible and consider how responsibility can be assigned when engagement with fictional worlds results in harm caused to or by users. We argue that because AI companies have some control over chatbots after public release, and because they can monitor user engagement, they are morally responsible when chatbot use leads to harm, even if they can’t perfectly control chatbots’ outputs. In the last section, we point to what AI companies can do to mitigate chatbots’ negative influence on users
Macrostructural, microstructural, and cellular effects of neuroinflammation on the mouse brain
Get PDFNeuroinflammation is increasingly implicated in post-infectious brain atrophy and cognitive impairment, as well as the etiology of neurodegenerative and psychiatric disorders. Here, we employed an established mouse model of neuroinflammation (systemic lipopolysaccharide [LPS]) and studied its macrostructural, microstructural, and cellular effects on the mouse brain. We combined whole-brain two-photon microscopy, multiparametric magnetic resonance imaging, and in silico transcriptomics. We demonstrate that LPS increases microglial soma size, a marker of microglial proinflammatory transformation, throughout the brain. LPS also induces in vivo volumetric increases of multiple brain regions, but not of the cerebral cortex. These in vivo increases are no longer observed ex vivo (post-fixation), suggesting they may be due to brain edema. Moreover, LPS induces microstructural alterations, as indicated by ex vivo reductions in fractional anisotropy and magnetization transfer ratio, which were most pronounced in the cerebral cortex. These reductions had the largest effect size in regions with higher expression of genes specific to parvalbumin inhibitory neurons and excitatory layer 4/5 intratelencephalic neurons, which were enriched in genes encoding synapse components. Thus, these results suggest that LPS-induced neuroinflammation may lead to brain edema, which spares the cerebral cortex, and microstructural alterations, which impact the cerebral cortex and may involve specific subtypes of inhibitory and excitatory neurons and their synapses
Which theories have a measurement problem?
Get PDFIt is shown that any theory that has certain properties has a measurement problem, in the sense that it makes predictions that are incompatible with measurement outcomes being absolute (that is, unique and non-relational). These properties are Bell Nonlocality, Information Preservation, and Local Dynamics. The result is extended by deriving Local Dynamics from No Superluminal Influences, Separable Dynamics, and Consistent Embeddings. These results are achieved using a framework of perspectival theories that generalizes the notion of a Heisenberg cut beyond quantum theory. As well as explaining why the existing Wigner’s-friend-inspired no-go theorems hold for quantum theory, the results also shed light on whether a future theory of physics might overcome the measurement problem. In particular, they suggest the possibility of a theory in which absoluteness is maintained, but without rejecting relativity theory (as in Bohm theory) or embracing objective collapses (as in GRW theory)