Lanedudley4012

Are female founding CEOs penalized when raising funds for their ventures based on industry served? Across an observational study conducted on ventures seeking funding (N = 392) and an experimental study conducted on investors allocating venture funding (N = 130), we find evidence for a "lack of fit" effect Female-led ventures catering to male-dominated industries receive significantly less funding at significantly lower valuations than female-led ventures catering to female-dominated industries. In contrast, male-led ventures attain similar funding and valuation outcomes regardless of the gender dominance of the industries to which they cater. We confirm that this is because investors perceive lower degrees of fit between founding CEO and venture for female-led ventures catering to male- as opposed to female-dominated industries (with no perceived fit differences for male-led ventures across industries). Ro 20-1724 in vitro Degree of investor sophistication emerges as a potential attenuating factor, appearing to help reduce gender bias from perceived lack of fit.The rapid clearance of intravenously administered nanoparticles (NPs) from the bloodstream is a major unsolved problem in nanomedicine. Here, we describe the first use of biocompatible protein-avoidant ionic liquids (PAILs) as NP surface modifiers to reduce opsonization. An ionic liquid choline hexenoate, selected for its aversion to serum proteins, was used to stably coat the surface of poly(lactic-co-glycolic acid) (PLGA) NPs. Compared with bare PLGA and poly(ethylene glycol)-coated PLGA particles, the PAIL-PLGA NPs showed resistance to protein adsorption in vitro and greater retention in blood of mice at 24 hours. Choline hexenoate redirected biodistribution of NPs, with preferential accumulation in the lungs with 50% of the administered dose accumulating in the lungs and less then 5% in the liver. Lung accumulation was attributed to spontaneous attachment of the PAIL-coated NPs on red blood cells in vivo. Overall, ionic liquids are a promising class of materials for NP modification for biomedical applications.We report a feedback control method to remove grain boundaries and produce circular shaped colloidal crystals using morphing energy landscapes and reinforcement learning-based policies. We demonstrate this approach in optical microscopy and computer simulation experiments for colloidal particles in ac electric fields. First, we discover how tunable energy landscape shapes and orientations enhance grain boundary motion and crystal morphology relaxation. Next, reinforcement learning is used to develop an optimized control policy to actuate morphing energy landscapes to produce defect-free crystals orders of magnitude faster than natural relaxation times. Morphing energy landscapes mechanistically enable rapid crystal repair via anisotropic stresses to control defect and shape relaxation without melting. This method is scalable for up to at least N = 103 particles with mean process times scaling as N0.5 Further scalability is possible by controlling parallel local energy landscapes (e.g., periodic landscapes) to generate large-scale global defect-free hierarchical structures.Peripheral blood mononuclear cells (PBMCs) may provide insight into the pathogenesis of Alzheimer's disease (AD) or Parkinson's disease (PD). We investigated PBMC samples from 132 well-characterized research participants using seven canonical immune stimulants, mass cytometric identification of 35 PBMC subsets, and single-cell quantification of 15 intracellular signaling markers, followed by machine learning model development to increase predictive power. From these, three main intracellular signaling pathways were identified specifically in PBMC subsets from people with AD versus controls reduced activation of PLCγ2 across many cell types and stimulations and selectively variable activation of STAT1 and STAT5, depending on stimulant and cell type. Our findings functionally buttress the now multiply-validated observation that a rare coding variant in PLCG2 is associated with a decreased risk of AD. Together, these data suggest enhanced PLCγ2 activity as a potential new therapeutic target for AD with a readily accessible pharmacodynamic biomarker.Conventional hydrogeologic framework models used to compute ocean island sustainable yields and aquifer storage neglect the complexity of the nearshore and offshore submarine environment. However, the onshore aquifer at the island of Hawai'i exhibits a notable volumetric discrepancy between high-elevation freshwater recharge and coastal discharge. In this study, we present a novel transport mechanism of freshwater moving from onshore to offshore through a multilayer formation of water-saturated layered basalts with interbedded low-permeability layers of ash/soil. Marine electromagnetic imaging reveals ∼35 km of laterally continuous resistive layers that extend to at least 4 km from west of Hawai'i's coastline, containing about 3.5 km3 of freshened water. We propose that this newly found transport mechanism of fresh groundwater may be the governing mechanism in other volcanic islands. In such a scenario, volcanic islands worldwide can use these renewable offshore reservoirs, considered more resilient to climate change-driven droughts, as new water resources.The Moon's tidal potential is slightly asymmetric, giving rise to so-called third-degree ocean tides, which are small and never before observed on a global scale. High-precision satellite altimeters have collected sea level records for almost three decades, providing a massive database from which tiny, time-coherent signals can be extracted. Here, four third-degree tides are mapped one diurnal, two semidiurnal, and one terdiurnal. Aside from practical benefits, such as improved tide prediction for geodesy and oceanography, the new maps reveal unique ways the ocean responds to a precisely known, but hitherto unexplored, force. An unexpected example involves the two semidiurnals, where the smaller lunar force is seen to generate the larger ocean tide, especially in the South Pacific. An explanation leads to new information about an ocean normal mode that spatially correlates with the third-degree astronomical potential. The maps also highlight previously unknown shelf resonances in all three tidal bands.Frameshift mutations in CALR (calreticulin) are associated with essential thrombocythemia (ET), but the stages at and mechanisms by which mutant CALR drives transformation remain incompletely defined. Here, we use single-cell approaches to examine the hematopoietic stem/progenitor cell landscape in a mouse model of mutant CALR-driven ET. We identify a trajectory linking hematopoietic stem cells (HSCs) with megakaryocytes and prospectively identify a previously unknown intermediate population that is overrepresented in the disease state. We also show that mutant CALR drives transformation primarily from the earliest stem cell compartment, with some contribution from megakaryocyte progenitors. Last, relative to wild-type HSCs, mutant CALR HSCs show increases in JAK-STAT signaling, the unfolded protein response, cell cycle, and a previously undescribed up-regulation of cholesterol biosynthesis. Overall, we have identified a novel megakaryocyte-biased cell population that is increased in a mouse model of ET and described transcriptomic changes linking CALR mutations to increased HSC proliferation and megakaryopoiesis.Exchange between a magma ocean and vapor produced Earth's earliest atmosphere. Its speciation depends on the oxygen fugacity (fO2) set by the Fe3+/Fe2+ ratio of the magma ocean at its surface. Here, we establish the relationship between fO2 and Fe3+/Fe2+ in quenched liquids of silicate Earth-like composition at 2173 K and 1 bar. Mantle-derived rocks have Fe3+/(Fe3++Fe2+) = 0.037 ± 0.005, at which the magma ocean defines an fO2 0.5 log units above the iron-wüstite buffer. At this fO2, the solubilities of H-C-N-O species in the magma ocean produce a CO-rich atmosphere. Cooling and condensation of H2O would have led to a prebiotic terrestrial atmosphere composed of CO2-N2, in proportions and at pressures akin to those observed on Venus. Present-day differences between Earth's atmosphere and those of her planetary neighbors result from Earth's heliocentric location and mass, which allowed geologically long-lived oceans, in-turn facilitating CO2 drawdown and, eventually, the development of life.Space manifolds act as the boundaries of dynamical channels enabling fast transportation into the inner- and outermost reaches of the Solar System. Besides being an important element in spacecraft navigation and mission design, these manifolds can also explain the apparent erratic nature of comets and their eventual demise. Here, we reveal a notable and hitherto undetected ornamental structure of manifolds, connected in a series of arches that spread from the asteroid belt to Uranus and beyond. The strongest manifolds are found to be linked to Jupiter and have a profound control on small bodies over a wide and previously unconsidered range of three-body energies. Orbits on these manifolds encounter Jupiter on rapid time scales, where they can be transformed into collisional or escaping trajectories, reaching Neptune's distance in a mere decade. All planets generate similar manifolds that permeate the Solar System, allowing fast transport throughout, a true celestial autobahn.Resident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in muscle and MacL in the lamina propria, each with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to an anti-inflammatory profile, whereas MacL macrophages died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Macrophage depletion resulted in the induction of a type 1-biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their responses to an exceedingly common infection in a largely overlooked organ, the bladder.Acute respiratory distress syndrome is associated with a robust inflammatory response that damages the vascular endothelium, impairing gas exchange. While restoration of microcapillaries is critical to avoid mortality, therapeutic targeting of this process requires a greater understanding of endothelial repair mechanisms. Here, we demonstrate that lung endothelium possesses substantial regenerative capacity and lineage tracing reveals that native endothelium is the source of vascular repair after influenza injury. Ablation of chicken ovalbumin upstream promoter-transcription factor 2 (COUP-TF2) (Nr2f2), a transcription factor implicated in developmental angiogenesis, reduced endothelial proliferation, exacerbating viral lung injury in vivo. In vitro, COUP-TF2 regulates proliferation and migration through activation of cyclin D1 and neuropilin 1. Upon influenza injury, nuclear factor κB suppresses COUP-TF2, but surviving endothelial cells ultimately reestablish vascular homeostasis dependent on restoration of COUP-TF2.