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Speciation is a key evolutionary process that is not yet fully understood. Combining population genomic and ecological data from multiple diverging pairs of marine snails (Littorina) supports the search for speciation mechanisms. Placing pairs on a one-dimensional speciation continuum, from undifferentiated populations to species, obscured the complexity of speciation. Adding multiple axes helped to describe either speciation routes or reproductive isolation in the snails. Divergent ecological selection repeatedly generated barriers between ecotypes, but appeared less important in completing speciation while genetic incompatibilities played a key role. Chromosomal inversions contributed to genomic barriers, but with variable impact. A multidimensional (hypercube) approach supported framing of questions and identification of knowledge gaps and can be useful to understand speciation in many other systems.
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Evolución Biológica , Selección Genética , Animales , Caracoles/genética , Genoma/genética , Especiación GenéticaRESUMEN
A major challenge in biology is to understand how mechanical interactions and cellular behavior affect the shapes of tissues and embryo morphology. The extension of the neural tube and paraxial mesoderm, which form the spinal cord and musculoskeletal system, respectively, results in the elongated shape of the vertebrate embryonic body. Despite our understanding of how each of these tissues elongates independently of the others, the morphogenetic consequences of their simultaneous growth and mechanical interactions are still unclear. Our study investigates how differential growth, tissue biophysical properties and mechanical interactions affect embryonic morphogenesis during axial extension using a 2D multi-tissue continuum-based mathematical model. Our model captures the dynamics observed in vivo by time-lapse imaging of bird embryos, and reveals the underestimated influence of differential tissue proliferation rates. We confirmed this prediction in quail embryos by showing that decreasing the rate of cell proliferation in the paraxial mesoderm affects long-term tissue dynamics, and shaping of both the paraxial mesoderm and the neighboring neural tube. Overall, our work provides a new theoretical platform upon which to consider the long-term consequences of tissue differential growth and mechanical interactions on morphogenesis.
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Proliferación Celular , Mesodermo , Modelos Biológicos , Morfogénesis , Tubo Neural , Animales , Mesodermo/embriología , Mesodermo/citología , Tubo Neural/embriología , Tubo Neural/citología , Codorniz/embriología , Embrión no Mamífero/citología , Desarrollo Embrionario/fisiología , ViscosidadRESUMEN
Grain rotation is commonly observed during the evolution of microstructures in polycrystalline materials of different kinds, including metals, ceramics, and colloidal crystals. It is widely accepted that interface migration in these systems is mediated by the motion of line defects with step and dislocation character, i.e., disconnections. We propose a crystallography-respecting continuum model for arbitrarily curved grain boundaries or heterophase interfaces, accounting for the disconnections' role in grain rotation. Numerical simulations demonstrate that changes in grain orientations, as well as interface morphology and internal stress field, are associated with disconnection flow. Our predictions agree with molecular dynamics simulation results for pure capillarity-driven evolution of grain boundaries and are interpreted through an extended Cahn-Taylor model.
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Soft materials often display complex behaviors that transition through apparent solid- and fluid-like regimes. While a growing number of microscale simulation methods exist for these materials, reduced-order models that encapsulate the macroscale physics are often desired to predict how external bodies interact with soft media. Such an approach could provide direct insights in diverse situations from impact and penetration problems to locomotion over natural terrains. This work proposes a systematic program to develop three-dimensional (3D) reduced-order models for soft materials from a fundamental basis using continuum symmetries and rheological principles. In particular, we derive a reduced-order, 3D resistive force theory (3D-RFT), which is capable of accurately and quickly predicting the resistive stress distribution on arbitrary-shaped bodies intruding through granular media. Aided by a continuum description of the granular medium, a comprehensive set of spatial symmetry constraints, and a limited amount of reference data, we develop a self-consistent and accurate 3D-RFT. We verify the model capabilities in a wide range of cases and show that it can be quickly recalibrated to different media and intruder surface types. The premises leading to 3D-RFT anticipate application to other soft materials with strongly hyperlocalized intrusion behavior.
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Locomoción , Fenómenos Mecánicos , ReologíaRESUMEN
Critical state and continuum plasticity theories have been used in research and engineering practice in soil and rock mechanics for decades. These theories rely on postulated relationships between material stresses and strains. Some classical postulates include coaxiality between stress and strain rates, stress-dilatancy relationships, and kinematic assumptions in shear bands. Although numerical and experimental data have quantified the strains and grain kinematics in such experiments, little data quantifying grain stresses are available. Here, we report the first-known grain stress and local strain measurements in triaxial compression tests on synthetic quartz sands using synchrotron X-ray tomography and 3D X-ray diffraction. We use these data to examine the micromechanics of shear banding, with a focus on coaxiality, stress-dilatancy, and kinematics within bands. Our results indicate the following: 1) elevated deviatoric stress, strain, and stress ratios in shear bands throughout experiments; 2) coaxial principal compressive stresses and strains throughout samples; 3) significant contraction along shear bands; 4) vanishing volumetric strain but nonvanishing stress fluctuations throughout samples at all stages of deformation. Our results provide some of the first-known in situ stress and strain measurements able to aid in critically evaluating postulates employed in continuum plasticity and strain localization theories for sands.
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Despite the growing interest in the rabbit model for developmental and stem cell biology, the characterization of embryos at the molecular level is still poorly documented. We conducted a transcriptome analysis of rabbit preimplantation embryos from E2.7 (morula stage) to E6.6 (early primitive streak stage) using bulk and single-cell RNA-sequencing. In parallel, we studied oxidative phosphorylation and glycolysis, and analysed active and repressive epigenetic modifications during blastocyst formation and expansion. We generated a transcriptomic, epigenetic and metabolic map of the pluripotency continuum in rabbit preimplantation embryos, and identified novel markers of naive pluripotency that might be instrumental for deriving naive pluripotent stem cell lines. Although the rabbit is evolutionarily closer to mice than to primates, we found that the transcriptome of rabbit epiblast cells shares common features with those of humans and non-human primates.
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Células Madre Pluripotentes , Transcriptoma , Animales , Blastocisto/metabolismo , Epigénesis Genética , Estratos Germinativos , Ratones , Células Madre Pluripotentes/metabolismo , Conejos , Transcriptoma/genéticaRESUMEN
The dorsal premotor cortex (DPC) has classically been associated with a role in preparing and executing the physical motor variables during cognitive tasks. While recent work has provided nuanced insights into this role, here we propose that DPC also participates more actively in decision-making. We recorded neuronal activity in DPC while two trained monkeys performed a vibrotactile categorization task, utilizing two partially overlapping ranges of stimulus values that varied on two physical attributes: vibrotactile frequency and amplitude. We observed a broad heterogeneity across DPC neurons, the majority of which maintained the same response patterns across attributes and ranges, coding in the same periods, mixing temporal and categorical dynamics. The predominant categorical signal was maintained throughout the delay, movement periods and notably during the intertrial period. Putting the entire population's data through two dimensionality reduction techniques, we found strong temporal and categorical representations without remnants of the stimuli's physical parameters. Furthermore, projecting the activity of one population over the population axes of the other yielded identical categorical and temporal responses. Finally, we sought to identify functional subpopulations based on the combined activity of all stimuli, neurons, and time points; however, we found that single-unit responses mixed temporal and categorical dynamics and couldn't be clustered. All these point to DPC playing a more decision-related role than previously anticipated.
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Corteza Motora , Corteza Motora/fisiología , Neuronas/fisiología , Movimiento/fisiologíaRESUMEN
The embryonic mouse brain undergoes drastic changes in establishing basic anatomical compartments and laying out major axonal connections of the developing brain. Correlating anatomical changes with gene-expression patterns is an essential step toward understanding the mechanisms regulating brain development. Traditionally, this is done in a cross-sectional manner, but the dynamic nature of development calls for probing gene-neuroanatomy interactions in a combined spatiotemporal domain. Here, we present a four-dimensional (4D) spatiotemporal continuum of the embryonic mouse brain from E10.5 to E15.5 reconstructed from diffusion magnetic resonance microscopy (dMRM) data. This study achieved unprecedented high-definition dMRM at 30- to 35-µm isotropic resolution, and together with computational neuroanatomy techniques, we revealed both morphological and microscopic changes in the developing brain. We transformed selected gene-expression data to this continuum and correlated them with the dMRM-based neuroanatomical changes in embryonic brains. Within the continuum, we identified distinct developmental modes comprising regional clusters that shared developmental trajectories and similar gene-expression profiles. Our results demonstrate how this 4D continuum can be used to examine spatiotemporal gene-neuroanatomical interactions by connecting upstream genetic events with anatomical changes that emerge later in development. This approach would be useful for large-scale analysis of the cooperative roles of key genes in shaping the developing brain.
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Encéfalo/embriología , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Imagen por Resonancia Magnética/métodos , Animales , Encéfalo/metabolismo , Simulación por Computador , Ratones , Modelos BiológicosRESUMEN
Dynamic access to quasi-bound states in the continuum (q-BICs) offers a highly desired platform for silicon-based active nanophotonic applications, while the prevailing tuning approaches by free carrier injections via an all-optical stimulus are yet limited to THz and infrared ranges and are less effective in visible bands. In this work, we present the realization of active manipulations on q-BICs for nanoscale optical switching in the visible by introducing a local index perturbation through a photothermal mechanism. The sharp q-BIC resonance exhibits an ultrasensitive susceptibility to the complex index perturbation, which can be flexibly fulfilled by optical heating of silicon. Consequently, a mild pump intensity of 1 MW/cm2 can yield a modification of the imaginary part of the refractive index of less than 0.05, which effectively suppresses the sharp q-BIC resonances and renders an active modulation depth of reflectance exceeding 80%. Our research might open up an enabling platform for ultrasensitive dynamic nanophotonic devices.
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The operation of photonic devices often relies on modulation of their refractive index. While the sub-bandgap index change through bound-electron optical nonlinearity offers a faster response than utilizing free carriers with an overbandgap pump, optical switching often suffers from inefficiency. Here, we use a recently observed metasurface based on mirror-induced optical bound states in the continuum, to enable superior modulation characteristics. We achieve a pulsewidth-limited switching time of 100 fs, reflectance change of 22%, remarkably low energy consumption of 255 µJ/cm2, and an enhancement of modulation contrast by a factor of 440 compared to unpatterned silicon. Additionally, the narrow photonic resonance facilitates the detection of the dispersive nondegenerate two-photon nonlinearity, allowing tunable pump and probe excitation. These findings are explained by a two-band theoretical model for the dispersive nonlinear index. The demonstrated efficient and rapid switching holds immense potential for applications, including quantum photonics, sensing, and metrology.
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We study, both theoretically and experimentally, strong interaction between a quasi-bound state in the continuum (QBIC) supported by a resonant metasurface with an epsilon-near-zero (ENZ) guided mode excited in an ultrathin ITO layer. We observe and quantify the strong coupling regime of the QBIC-ENZ interaction in the hybrid metasurface manifested through the mode splitting over 200 meV. We also measure experimentally the resonant nonlinear response enhanced near the ENZ frequency and observe the effective nonlinear refractive index up to â¼4 × 10-13 m2/W in the ITO-integrated dielectric nanoresonators, which provides a promising platform for low-power nonlinear photonic devices.
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Chiral nanostructures allow engineering of chiroptical responses; however, their design usually relies on empirical approaches and extensive numerical simulations. It remains unclear if a general strategy exists to enhance and maximize the intrinsic chirality of subwavelength photonic structures. Here, we suggest a microscopic theory and uncover the origin of strong chiral responses of resonant nanostructures. We reveal that the reactive helicity density is critically important for achieving maximum chirality at resonances. We demonstrate our general concept on the examples of planar photonic crystal slabs and metasurfaces, where out-of-plane mirror symmetry is broken by a bilayer design. Our findings provide a general recipe for designing photonic structures with maximum chirality, paving the way toward many applications, including chiral sensing, chiral emitters and detectors, and chiral quantum optics.
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This paper reports a silicon-organic hybrid lattice that can lase with vortex emission and allow all-optical control. We combine an array of amorphous silicon nanodisks with gain from dye molecules in organic solvents to generate vortex lasing from bound states in the continuum under pulsed optical pumping. Irradiating the device with an additional continuous wave green laser beam can cause optical heating in silicon and lead to negative change in the refractive index of the organic solvents; meanwhile, the green laser beam can provide additional gain. Dynamic tuning of the lasing wavelength is achieved by varying the intensity of the controlling beam. Furthermore, the vortex beam lasing can be switched to single-lobed beam lasing by moving the controlling spot to break the in-plane symmetry within the pumping spot. Our findings could shed new light on active silicon topological devices.
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The metasurface analogue of electromagnetically induced transparency (EIT) provides a chip-scale platform for achieving light delay and storage, high Q factors, and greatly enhanced optical fields. However, the literature relies on the coupling between localized and localized or localized and collective resonances, limiting the Q factor and related performance. Here, we report a novel approach for realizing collective EIT-like bands with a measured Q factor reaching 2750 in silicon metasurfaces in the near-infrared regime, exceeding the state of the art by more than 5 times. It employs the coupling between two collective resonances, the Mie electric dipole surface lattice resonance (SLR) and the out-of-plane/in-plane electric quadrupole SLR (EQ-SLR). Remarkably, the collective EIT-like resonance can have diverging Q factor and group delay due to the bound state in the continuum characteristics of the in-plane EQ-SLR. With these findings, our study opens a new route for tailoring light flow in metasurfaces.
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This paper reports how a hybrid system composed of transparent dielectric lattices over a metal mirror can produce high-quality lattice resonances for unidirectional lasing. The enhanced electromagnetic fields are concentrated in the cladding of the periodic dielectric structures and away from the metal. Based on a mirror-image model, we reveal that such high-quality lattice resonances are governed by bound states in the continuum resulting from destructive interference. Using hexagonal arrays of titanium dioxide nanoparticles on a silica-coated silver mirror, we observed lattice resonances with quality factors of up to 2750 in the visible regime. With the lattice resonances as optical feedback and dye solution as the gain medium, we demonstrated unidirectional lasing under optical pumping, where the array size was down to 100 µm × 100 µm. Our scheme can be extended to other spectral regimes to simultaneously achieve strongly enhanced surface fields and high quality factors.
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Human Immunodeficiency Virus (HIV)-positive individuals lost to follow-up from particular clinics may not be lost to care (LTC). After linking Vanderbilt's Comprehensive Care Clinic cohort to Tennessee's statewide HIV surveillance database, LTC decreased from 48.4% to 35.0% at 10 years. Routine surveillance linkage by domestic HIV clinics would improve LTC and retention measure accuracy.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , VIH , Fármacos Anti-VIH/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Instituciones de Atención AmbulatoriaRESUMEN
BACKGROUND: Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and subsequent complications. We describe the hepatitis C care continuum within the Veterans Health Administration 1 January 2014 to 31 December 2022. METHODS: We included individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment 1 January 2014 to 31 December 2022. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia. RESULTS: We identified 133 732 Veterans with hepatitis C viremia. Hepatitis C treatment was initiated in 107 134 (80.1%), with sustained virologic response achieved in 98 136 (91.6%). In those who achieved sustained virologic response, 1097 (1.1%) had repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum. CONCLUSIONS: The Veterans Health Administration has treated 80% of Veterans with hepatitis C in care 2021-2022 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders.
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Antivirales , Continuidad de la Atención al Paciente , Hepatitis C , Respuesta Virológica Sostenida , United States Department of Veterans Affairs , Veteranos , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Persona de Mediana Edad , Antivirales/uso terapéutico , Veteranos/estadística & datos numéricos , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Anciano , Hepacivirus/efectos de los fármacos , Viremia/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Adulto , Salud de los VeteranosRESUMEN
Solvation effects profoundly influence the characteristics and behavior of chemical systems in liquid solutions. The interaction between solute and solvent molecules intricately impacts solubility, reactivity, stability, and various chemical processes. Continuum solvation models gained prominence in quantum chemistry by implicitly capturing these interactions and enabling efficient investigations of diverse chemical systems in solution. In comparison, continuum solvation models in condensed matter simulation are very recent. Among these, the self-consistent continuum solvation (SCCS) and the soft-sphere continuum solvation models (SSCS) have been among the first to be successfully parameterized and extended to model periodic systems in aqueous solutions and electrolytes. As most continuum approaches, these models depend on a number of parameters that are linked to experimental or theoretical properties of the solvent, or that can be tuned based on reference data. Here, we present a systematic parameterization of the SSCS model for over 100 nonaqueous solvents. We validate the model's efficacy across diverse solvent environments by leveraging experimental solvation-free energies and partition coefficients from comprehensive databases. The average root means square error over all the solvents was calculated as 0.85 kcal/mol which is below the chemical accuracy (1 kcal/mol). Similarly to what has been reported by Hille et al. (J. Chem. Phys. 2019, 150, 041710.) for the SCCS model, a single-parameter model accurately reproduces experimental solvation energies, showcasing the transferability and predictive power of these continuum approaches. Our findings underscore the potential for a unified approach to predict solvation properties, paving the way for enhanced computational studies across various chemical environments.
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In the present study, we have investigated factors affecting the accuracy of computational chemistry calculation of redox potentials, namely the gas-phase ionization energy (IE) and electron affinity (EA), and the continuum solvation effect. In general, double-hybrid density functional theory methods yield IEs and EAs that are on average within ~0.1 eV of our high-level W3X-L benchmark, with the best performing method being DSD-BLYP/ma-def2-QZVPP. For lower-cost methods, the average errors are ~0.2-0.3 eV, with ωB97X-3c being the most accurate (~0.15 eV). For the solvation component, essentially all methods have an average error of ~0.3 eV, which shows the limitation of the continuum solvation model. Curiously, the directly calculated redox potentials show errors of ~0.3 eV for all methods. These errors are notably smaller than what can be expected from error propagation with the two components (IE and EA, and solvation effect). Such a discrepancy can be attributed to the cancellation of errors, with the lowest-cost GFN2-xTB method benefiting the most, and the most accurate ωB97X-3c method benefiting the least. For organometallic species, the redox potentials show large deviations exceeding ~0.5 eV even for DSD-BLYP. The large errors are attributed to those for the gas-phase IEs and EAs, which represents a major barrier to the accurate calculation of redox potentials for such systems.
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PURPOSE: To examine racial-ethnic variation in adherence to established quality metrics (NCCN guidelines and ASCO quality metrics) for breast cancer, accounting for individual-, facility-, and area-level factors. METHODS: Data from women diagnosed with invasive breast cancer at 66+ years of age from 2000 to 2017 were examined using SEER-Medicare. Associations between race and ethnicity and guideline-concordant diagnostics, locoregional treatment, systemic therapy, documented stage, and oncologist encounters were estimated using multilevel logistic regression models to account for clustering within facilities or counties. RESULTS: Black and American Indian/Alaska Native (AIAN) women had consistently lower odds of guideline-recommended care than non-Hispanic White (NHW) women (Diagnostic workup: ORBlack 0.83 (0.79-0.88), ORAIAN 0.66 (0.54-0.81); known stage: ORBlack 0.87 (0.80-0.94), ORAIAN 0.63 (0.47-0.85); seeing an oncologist: ORBlack 0.75 (0.71-0.79), ORAIAN 0.60 (0.47-0.72); locoregional treatment: ORBlack 0.80 (0.76-0.84), ORAIAN 0.84 (0.68-1.02); systemic therapies: ORBlack 0.90 (0.83-0.98), ORAIAN 0.66 (0.48-0.91)). Commission on Cancer accreditation and facility volume were significantly associated with higher odds of guideline-concordant diagnostics, stage, oncologist visits, and systemic therapy. Black residential segregation was associated with significantly lower odds of guideline-concordant locoregional treatment and systemic therapy. Rurality and area SES were associated with significantly lower odds of guideline-concordant diagnostics and oncologist visits. CONCLUSIONS: This is the first study to examine guideline-concordance across the continuum of breast cancer care from diagnosis to treatment initiation. Disparities were present from the diagnostic phase and persisted throughout the clinical course. Facility and area characteristics may facilitate or pose barriers to guideline-adherent treatment and warrant future investigation as mediators of racial-ethnic disparities in breast cancer care.