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Modern climate projections lack adequate spatial and temporal resolution due to computational constraints. A consequence is inaccurate and imprecise predictions of critical processes such as storms. Hybrid methods that combine physics with machine learning (ML) have introduced a new generation of higher fidelity climate simulators that can sidestep Moore's Law by outsourcing compute-hungry, short, high-resolution simulations to ML emulators. However, this hybrid ML-physics simulation approach requires domain-specific treatment and has been inaccessible to ML experts because of lack of training data and relevant, easy-to-use workflows. We present ClimSim, the largest-ever dataset designed for hybrid ML-physics research. It comprises multi-scale climate simulations, developed by a consortium of climate scientists and ML researchers. It consists of 5.7 billion pairs of multivariate input and output vectors that isolate the influence of locally-nested, high-resolution, high-fidelity physics on a host climate simulator's macro-scale physical state.The dataset is global in coverage, spans multiple years at high sampling frequency, and is designed such that resulting emulators are compatible with downstream coupling into operational climate simulators. We implement a range of deterministic and stochastic regression baselines to highlight the ML challenges and their scoring. The data (https://huggingface.co/datasets/LEAP/ClimSim_high-res) and code (https://leap-stc.github.io/ClimSim) are released openly to support the development of hybrid ML-physics and high-fidelity climate simulations for the benefit of science and society. 

Abstract The brain vasculature maintains brain homeostasis by tightly regulating ionic, molecular, and cellular transport between the blood and the brain parenchyma. These blood–brain barrier (BBB) properties are impediments to brain drug delivery, and brain vascular dysfunction accompanies many neurological disorders. The molecular constituents of brain microvascular endothelial cells (BMECs) and pericytes, which share a basement membrane and comprise the microvessel structure, remain incompletely characterized, particularly in humans. To improve the molecular database of these cell types, we performed RNA sequencing on brain microvessel preparations isolated from snap-frozen human and mouse tissues by laser capture microdissection (LCM). The resulting transcriptome datasets from LCM microvessels were enriched in known brain endothelial and pericyte markers, and global comparison identified previously unknown microvessel-enriched genes. We used these datasets to identify mouse-human species differences in microvessel-associated gene expression that may have relevance to BBB regulation and drug delivery. Further, by comparison of human LCM microvessel data with existing human BMEC transcriptomic datasets, we identified novel putative markers of human brain pericytes. Together, these data improve the molecular definition of BMECs and brain pericytes, and are a resource for rational development of new brain-penetrant therapeutics and for advancing understanding of brain vascular function and dysfunction. 

According to the justified true belief (JTB) account of knowledge, people can truly know something only if they have a belief that is both justified and true (i.e., knowledge is JTB). This account was challenged by Gettier, who argued that JTB does not explain knowledge attributions in certain situations, later called “Gettier-type cases,” wherein protagonists are justified in believing something to be true, but their belief was correct only because of luck. Laypeople may not attribute knowledge to protagonists with justified but only luckily true beliefs. Although some research has found evidence for these so-called Gettier intuitions, Turri et al. found no evidence that participants attributed knowledge in a counterfeit-object Gettier-type case differently than in a matched case of JTB. In a large-scale, cross-cultural conceptual replication of Turri and colleagues’ Experiment 1 ( N = 4,724) using a within-participants design and three vignettes across 19 geopolitical regions, we did find evidence for Gettier intuitions; participants were 1.86 times more likely to attribute knowledge to protagonists in standard cases of JTB than to protagonists in Gettier-type cases. These results suggest that Gettier intuitions may be detectable across different scenarios and cultural contexts. However, the size of the Gettier intuition effect did vary by vignette, and the Turri et al. vignette produced the smallest effect, which was similar in size to that observed in the original study. Differences across vignettes suggest that epistemic intuitions may also depend on contextual factors unrelated to the criteria of knowledge, such as the characteristics of the protagonist being evaluated. 

Cellulose nanocrystals (CNCs) have great potential in many areas of research, applications, and future commercialization prospects. Recently, CNCs have emerged as attractive candidates for biomedical applications such as drug and gene delivery systems. As such, cytotoxicity studies have been the major focus in the past decade. However, despite the rod-like nature of CNCs, the potential immune response of surface-modified CNCs is not well investigated. The current study examined the potential immune and antioxidant response induced by CNCs grafted with β -cyclodextrin (CNCs- β -CD) in a human monocyte cell line (THP-1) and a mouse macrophage-like cell line (J774A.1). We analyzed the secretion of the proinflammatory cytokine, interleukin 1 β (IL-1 β ), by ELISA and mitochondria-derived reactive oxygen species (ROS) using fluorescence cell imaging and examined the intracellular levels of proteins involved in the immune and antioxidant response by immunoblotting. Our results indicated a dramatic increase neither in the IL-1 β secretion nor in the mitochondria-derived ROS resulting in no changes in the intracellular antioxidant response in THP-1 cells treated with different concentrations of CNCs- β -CD. Overall, CNCs- β -CD is nonimmunogenic and do not induce an increased antioxidant response under the conditions tested and hence has the potential to be used as a drug delivery carrier.