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Iron Catalyzed Aryl–Aryl Kumada Cross‐Coupling: A Mechanistic and Computational Investigation
Get PDFThe widespread use of precious metal catalysts in C–C bond‐forming reactions is increasingly challenged by concerns over toxicity, cost, and limited availability. As a sustainable alternative, iron offers distinct advantages in cross‐coupling chemistry, but its broader application has been hindered by limited mechanistic understanding. Here, we report a mechanistically driven investigation of aryl–aryl Kumada cross‐coupling catalyzed by our previously reported iron complex [(PCNHCP)FeCl2] (2). Through a combination of multinuclear NMR, 57Fe Mössbauer spectroscopy, single‐crystal X‐ray diffraction, and reactivity studies, we identify and characterize key in situ formed intermediates, including mono‐ and bis‐arylated iron species, along the catalytic pathway. While PCP‐ligated Fe(II) complexes support two‐electron chemistry, our findings uncover a distinct radical mechanism responsible for the efficient formation of the biaryl products. Furthermore, we demonstrate that small coordinating molecules, such as N2, significantly influence the speciation and reactivity of the iron catalyst. These insights advance fundamental understanding of iron‐mediated cross‐coupling and provide new design principles for sustainable C(sp2)–C(sp2) bond construction
Rate variation and recurrent sequence errors in pandemic-scale phylogenetics
Get PDFPhylogenetic analyses of genome sequences from infectious pathogens reveal essential information regarding their evolution and transmission, as seen during the coronavirus disease 2019 pandemic. Recently developed pandemic-scale phylogenetic inference methods reduce the computational demand of phylogenetic reconstruction from genomic epidemiological datasets, allowing the analysis of millions of closely related genomes. However, widespread homoplasies, due to recurrent mutations and sequence errors, cause phylogenetic uncertainty and biases. We present algorithms and models to substantially improve the computational performance and accuracy of pandemic-scale phylogenetics. In particular, we account for, and identify, mutation rate variation and recurrent sequence errors. We reconstruct a reliable and public sequence alignment and phylogenetic tree of >2 million severe acute respiratory syndrome coronavirus 2 genomes encapsulating the evolutionary history and global spread of the virus up to February 2023
God as victim of human sin: a sin-based response to J. L. Schellenberg’s hiddenness argument
Get PDFIn this paper, I develop an extended sin-based response to J. L. Schellenberg’s hiddenness argument against the existence of God which claims that the existence of God is disproven by the existence of persons whom Schellenberg calls non-resistant non-believers. I aim to problematize Schellenberg’s claim that there are such persons by arguing that his understanding of resistance is too narrow and that there is a broader kind of resistance he has not adequately considered. My argument has two stages. In Stage One, I argue that by culpably gravely injuring other humans, humans injure God indirectly and this is a kind of resistance towards him. In Stage Two, I point out that, if Christianity is true, human sin led to the suffering and death of God incarnate; I then try to show that, if Christianity is true, humans who have committed gravely immoral acts bear some non-negligible moral responsibility for the death of Christ, and that this too is a kind of resistance towards God. Since virtually all humans have gravely injured another human and committed at least one gravely immoral act, virtually all humans are resistant to God in this broader sense. Finally, I try to account for the variation in belief and non-belief by arguing that temporary divine hiding is an acceptable but not necessary divine response to this kind of resistance
Stellar-mass black holes on the millimetre Fundamental Plane of black hole accretion
Get PDFRecent work revealed the existence of a galaxy ‘millimetre Fundamental Plane of black hole accretion’, a tight correlation between nuclear 1 mm luminosity, intrinsic 2–10 keV X-ray luminosity and supermassive black hole mass, originally discovered for nearby low- and high-luminosity active galactic nuclei. Here we use mm and X-ray data of five X-ray binaries (XRBs) to demonstrate that these stellar-mass black holes also lie on the mm Fundamental Plane, as they do at radio wavelengths. One source for which we have multi-epoch observations shows evidence of deviations from the plane after a state change, suggesting that the plane only applies to XRBs in the hard state, as is true again at radio wavelengths. We show that both advection-dominated accretion flows and compact jet models predict the existence of the plane across the entire range of black hole masses, although these models vary in their ability to accurately predict the XRB black hole masses
Effects of diffusion MRI spatial resolution on human brain short-range association fiber reconstruction and structural connectivity estimation
Get PDFShort-range association fibers (SAFs) are critical for cortical communications but are often underestimated in conventional resolution diffusion magnetic resonance imaging (dMRI) since they locate within a ~1.5 mm thin layer of superficial white matter. With the advent of high-resolution diffusion imaging techniques, this study evaluated the effects of image spatial resolution on SAF reconstruction using two datasets: (1) prospectively acquired dMRI data from 20 healthy subjects, each scanned at 3 resolutions (i.e., 2, 1.5, and 0.96 mm iso.), and (2) retrospectively down-sampled dMRI data from the Human Connectome Project dataset, as well as 20 representative MRtrix3-based tractography pipelines. It was found that lower resolution degraded superficial white matter model fitting, lowered the SAF streamline counts, and reduced global and regional short-range connectivity fraction (SCF), defined as the fraction of SAF connections among all association fiber connections, across all tested methods. Temporal lobe cortical regions exhibited the greatest SCF declines at lower resolutions. Tractography methods differed in resolution sensitivity, with diffusion tensor imaging (DTI)-based single-tissue single-fiber tractography showing greater decreases in SCF than constrained spherical deconvolution (CSD)-based multi-tissue multi-fiber tractography at lower resolutions. Probabilistic, anatomically constrained tractography combined with spherical-deconvolution informed filtering of tractograms was more robust to decreases in resolution. Up-sampling to a nominally higher resolution partially improved model fitting and SCF accuracy across the evaluated pipelines, with the greatest effect observed for DTI. Using the 0.96 mm iso. gSlider data and optimized tractography pipelines from this study, we constructed the first human brain atlas of RSCF. In summary, this study provides a systematic and quantitative evaluation using MRtrix3 of how spatial resolution, fiber models, and tracking methodologies affect SAF reconstruction and structural connectivity estimation, serving as a reference framework for methodological choices. These advances may enhance the characterization of both healthy and diseased human brains across a wide range of neuroscientific and clinical applications
A Near-Earth Object Model Calibrated to Earth Impactors
Get PDFThe population of Earth-impacting meteoroids and their size-dependent orbital elements are key to understanding the origin of meteorites and informing planetary defense efforts. Outstanding questions include the role of collisions in depleting meteoroids on highly evolved orbits and the relative importance of delivery resonances. Those depend on size, with current dynamical models considering only asteroids larger than 10 m in diameter. Based on 1202 sporadic meteoroids observed by the Global Fireball Observatory, we created a debiased model of the near-Earth meteoroid population in the 10 g–150 kg size range (approximately 1 cm–0.5 m in diameter) as they dynamically evolved from the main asteroid belt onto Earth-crossing orbits. The observed impact population is best matched with a collisional half-life decreasing from 3 Myr for meteoroids of 0.6 kg (7 cm) or higher to 1 Myr below this size, extending to the model lower bound of 10 g. Placing our results in context with near-Earth object models for larger sizes, we find that the inner main belt continues to dominate feeding the small 1–10 m diameter population primarily via the ν6 secular resonance and the 3:1J mean-motion resonance. We also evaluated the potential significance of physical processes other than collisions on Earth-impacting meteoroids, such as low-perihelion disruptions from thermal stresses
Glucocorticoid-dependence and independence of the circadian liver transcriptome
Get PDFThe liver, a key metabolic organ, shows clear day-night variation in gene and protein expression, and in metabolic pathway activity. Liver cells possess molecular circadian clocks, but systemic factors are critical contributors to the circadian rhythmicity of liver gene expression. Glucocorticoid action is reported to be one such factor. Glucocorticoids are essential hormones, with strong circadian oscillations, which control multiple cellular processes via the glucocorticoid receptor (GR). We compare clock factor and GR binding at promoters and enhancers linked to rhythmic genes and find increased clock factor binding at those promoter elements where GR is also present. Genes with GR binding at the promoter are more highly expressed and more likely to be detected as rhythmic. We then test the role of GR directly, by profiling rhythmic gene expression in mice with/without hepatocyte-targeted GR deletion. Notably, we observe only a small effect of GR deletion, with most rhythmic genes showing unchanged rhythmicity, despite evidence for local GR binding. We find a small number of genes showing lost or gained rhythmicity with GR deletion; genes which lose rhythmicity associate with GR binding sites. Contrary to expectations, GR appears redundant for conveying timing information to most of the rhythmic liver transcriptome
The Mandatory Open Door: The United States and the League of Nations mandates
Get PDFThe Mandatory Open Door is a global history of US engagement with the League of Nations mandates. Although the United States never joined the League of Nations, nor took on any mandates, American officials played a sustained and influential role in shaping how the mandates functioned in the Pacific, Africa, and the Middle East. This thesis explores how US officials, particularly within the State Department, used the mandates to promote American interests, strategic, ideological, and commercial. In so doing, it identifies the Open Door as the dominant policy instrument through which the United States pursued access to mandated territories. It notes that although the Open Door had been a longstanding policy approach developed in earlier US engagement with China and the Caribbean, its application to the mandates significantly altered and expanded the meanings of the policy.This thesis examines the mandates system as a framework for managing empire through international oversight, and considers how American actors, operating from a position of formal detachment, shaped its development. It highlights how US officials capitalized on the system’s institutional pliability and the United States’ ability to selectively engage with the mandates to exert influence while avoiding deeper political entanglements. The mandates appear less as a fixed structure than as a contested arena in which sovereignty, access, and imperial authority were continuously negotiated. In tracing these dynamics, the study reveals how the United States participated in reconfiguring both colonial governance and the global order in the first half of the twentieth century
Solar Flow Synthesis of Polymer Nanoparticles: Scaling Local Experiments to Global Potential
Get PDFWe present the scalable, additive‐free synthesis of polymer nanoparticles in continuous flow, using solely solar radiation. Using a custom‐made flow reactor, the UV radiation from the sun induces a Diels–Alder step‐growth polymerization between a bismaleimide and a difunctional o‐methylbenzaldehyde. The resulting photopolymer subsequently precipitates as nanoparticles without the need for any additional additives, stimuli or processing steps. The solar flow reactor was designed by first carefully assessing the underpinning photochemistry of the photo‐induced Diels–Alder reaction using photochemical action plots and then performing a kinetic investigation of the particle formation under solar irradiation. The determined kinetics allow us to extrapolate our experimental results to a worldwide particle yield by using global UV index data, validated by two highly different geographical locations, Australia and Germany. Our results clearly demonstrate the applicability of our system for the scalable, sustainable, solar‐powered production of polymeric nanoparticles in regions of high levels of solar radiation. Furthermore, our calculations function as a blueprint for how local experimental data can be extrapolated to assess the global solar photochemical potential of photochemical systems, thus making their performance comparable
An autonomous network of acoustic detectors to map tiger risk by eavesdropping on prey alarm calls
Get PDFTiger (Panthera tigris) attacks are a frequent source of injuries and fatalities among villagers in Nepal, where many communities make extensive use of dense forests for foraging and grazing of livestock. As conservation efforts have boosted the tiger population in the country, a conflict exists between maintaining traditional practises whilst ensuring human safety and protecting endangered predators. Hence, there is a need for cost‐effective management strategies that do not reduce habitat use by humans or wildlife. Passive acoustic monitoring (PAM) offers a promising approach to mapping tiger presence in real‐time and providing a warning system for villagers. Although tigers vocalize infrequently, their presence triggers alarm calls from prey species, meaning these alarm calls could potentially act as a proxy for detecting tigers. To explore the potential for tracking tigers and other dangerous predators such as leopards using these alarm calls, we designed and tested a PAM system in the Terai region of southern Nepal. We implemented a TinyML low‐memory convolutional neural network (~1000 parameters) for chital deer (Axis axis) automatic detection—a species that reliably produce loud predator‐specific alarm calls—and deployed a distributed network of 10 autonomous interconnected sensors for continuous operation over 3 months. The network transmits chital deer alarm call events via a cellular‐connected gateway to a remote base station to generate a heatmap of predator risk. Incidences of high predator risk can be used to alert local forest rangers, who can then inform nearby villagers of areas with a higher likelihood of predator presence. The neural net achieved an F1 score of 0.91 in training and 0.72 in the field. We suggest that this proof of concept indicates that automated PAM could be an effective tool for detecting and tracking tigers and other predators and a potentially valuable tool for facilitating human‐wildlife co‐existence