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Reconstructing the ancestral vertebrate brain using a lamprey neural cell type atlas
No full textThe vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey - a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits - based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of the core cell type composition, tissue structures, and gene expression programs of the ancestral brain. However, our analyses also revealed key tissues and cell types that arose later in evolution. For example, the ancestral vertebrate brain was likely devoid of cerebellar cell types and oligodendrocytes (myelinating cells); our data suggest that the latter emerged from astrocyte-like evolutionary precursors on the jawed vertebrate lineage. Our work illuminates the cellular and molecular architecture of the ancestral vertebrate brain and provides a foundation for exploring its diversification during evolution
Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models
No full textTo combat future SARS-CoV-2 variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles presenting randomly-arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against conserved/relatively-occluded, rather than variable/immunodominant/exposed, epitopes. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD-nanoparticles in mice and macaques, observing stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants including Omicron and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers
The prototype X-ray binary GX 339–4: using TeV γ-rays to assess LMXBs as Galactic cosmic ray accelerators
No full textSince the discovery of cosmic rays (CRs) over a century ago, their origin remains an open question. Galactic CRs with energy up to the knee (10¹⁵ eV) are considered to originate from supernova remnants, but this scenario has recently been questioned due to lack of TeV γ-ray counterparts in many cases. Extragalactic CRs, on the other hand, are thought to be associated with accelerated particles in the relativistic jets launched by supermassive accreting black holes at the centre of galaxies. Scaled down versions of such jets have been detected in X-ray binaries hosting a stellar black hole (BHXBs). In this work, we investigate the possibility that the smaller scale jets in transient outbursts of low-mass BHXBs could be sources of Galactic CRs. To better test this scenario, we model the entire electromagnetic spectrum of such sources focusing on the potential TeV regime, using the ‘canonical’ low-mass BHXB GX 339–4 as a benchmark. Taking into account both the leptonic radiative processes and the γ-rays produced via neutral pion decay from inelastic hadronic interactions, we predict the GeV and TeV γ-ray spectrum of GX 339–4 using lower frequency emission as constraints. Based on this test-case of GX 339–4, we investigate whether other, nearby low-mass BHXBs could be detected by the next-generation very-high-energy γ-ray facility the Cherenkov Telescope Array, which would establish them as additional and numerous potential sources of CRs in the Galaxy
Plastic Morphological Response to Spectral Shifts during Inorganic Phototropic Growth
No full textPlants exhibit phototropism in which growth is directed toward sunlight and demonstrate morphological plasticity in response to changes in the spectral distribution of the incident illumination. Inorganic phototropic growth via template-free, light-directed electrochemical deposition of semiconductor material can spontaneously generate highly ordered mesostructures with anisotropic, nanoscale lamellar features that exhibit a pitch proportional to the wavelength (λ) of the stimulating illumination. In this work, Se–Te films were generated via a two-step inorganic phototropic growth process using a series of narrowband light-emitting diode sources with discrete output wavelengths (λ₀ ≠ λ₁). Analogous to the plasticity observed in plants, changes in illumination wavelength from λ₀ to λ₁ resulted in morphological changes including feature branching, termination, and/or fusion along the growth direction. The interfacial feature pitch changed with the growth duration, in some cases in a notably nonmonotonic fashion, and eventually matched that obtained for growth using only λ₁. Simulated morphologies generated by modeling light–material interactions at the growth interface closely matched the evolved structures observed experimentally, indicating that the characteristics of the optical stimulation produce the observed plastic response during inorganic phototropic growth. Examination of the interfacial electric field modulation for λ1 illumination of simplified structures, representative of those generated experimentally, revealed the interfacial light scattering and concentration behavior that directed phototropic growth away from equilibrium, as well as the emergent nature of the phenomena that reestablish equilibrium
The Accessibility of YouTube Fitness Videos for Individuals Who Are Disabled Before and During the COVID-19 Pandemic: Preliminary Application of a Text Analytics Approach
No full textBackground: People with disabilities face barriers to in-person physical activity (PA), including a lack of adaptive equipment and knowledgeable instructors. Given this and the increased need for digital resources due to widespread COVID-19 lockdowns, it is necessary to assess the accessibility of digital fitness resources for people with disabilities. To investigate whether YouTube fitness content creators have made videos accessible to people with disabilities would be informative about access to PA during COVID-19 and could also provide insight into the feasibility of individuals who are disabled relying on YouTube for PA in a post–COVID-19 world.
Objective: This study aims to ascertain if disability-friendly PA videos on YouTube are accessible through searching general fitness terms and whether a change in the availability of accessible fitness resources for people with disabilities occurred on YouTube between before and during the COVID-19 pandemic on “Hospital/Medical Institutions,” “Individual(s),” and “Other(s)” channels. Secondary aims are to investigate if different categories of YouTube channels produce more accessible fitness content and highlight any disparities in disability-friendly PA content on YouTube.
Methods: A cross-sectional text analysis of exercise-related YouTube videos was conducted. The authors used Python (version 3.0) to access the YouTube database via its data application programming interface. Terms pertaining to PA that were searched on YouTube were at-home exercise, exercise at home, exercise no equipment, home exercise, home-based exercise, no equipment workout, and workout no equipment. Various elements (eg, view count and content generation) of the videos published between January 1 and June 30, 2019 (n=700), were compared to the elements of videos published between January 1 and June 30, 2020 (n=700). To capture a broad idea of disability-friendly videos on YouTube, videos were labeled “accessible” if they were found in the first 100 video results and if their title, description, or tags contained the following terms: para, paralympic, adaptive, adapted, disabled, disability, differently abled, disability-friendly, wheelchair accessible, and inclusive. Each video and channel were categorized as “Hospitals/Medical Institutions,” “Individuals,” or “Other(s).”
Results: The analysis revealed a statistically significant increase in viewership of fitness content on YouTube (P=.001) and in fitness content generated by Hospitals/Medical Institutions (P=.004). Accessible terms applicable to people with disabilities had minimal appearances in 2019 (21 videos) and 2020 (19 videos). None of the top viewed fitness videos that populated on YouTube from 2019 or 2020 were accessible.
Conclusions: The proportion of accessible disability-friendly videos remains diminutive relative to the prevalence of disability in the general population, revealing that disability-friendly videos are seldom findable on YouTube. Thus, the need for disability-friendly fitness content to be easily searched and found remains urgent if access to digital fitness resources is to improve
Rapid fabrication of microrings with complex cross section using annular vortex beams
No full textA ring-shaped focus, such as a focused vortex beam, has played an important role in microfabrication and optical tweezers. The shape and diameter of the ring-shaped focus can be easily adjusted by the topological charge of the vortex. However, the flow energy is also related to the topological charge, making the individual control of diameter and flow energy of the vortex beam impossible. Meanwhile, the shape of the focus of the vortex beam remains in the hollow ring. Expanding the shape of focus of structural light broadens the applications of the vortex beam in the field of microfabrication. Here, we proposed a ring-shaped focus with controllable gaps by multiplexing the vortex beam and annular beam. The multiplexed beam has several advantages, such as the diameter and flow energy of the focal point can be individually controlled and are not affected by the zero-order beam, and the gap size and position are controllable
Development, construction and tests of the Mu2e electromagnetic calorimeter mechanical structures
No full textThe "muon-to-electron conversion" (Mu2e) experiment at Fermilab will search for the charged lepton flavour violating neutrino-less coherent conversion of a muon into an electron in the field of an aluminum nucleus. The observation of this process would be the unambiguous evidence of the existence of physics beyond the standard model. Mu2e detectors comprise a straw-tracker, an electromagnetic calorimeter and an external veto for cosmic rays. In particular, the calorimeter provides excellent electron identification, a fast calorimetric online trigger, and complementary information to aid pattern recognition and track reconstruction. The detector has been designed as a state-of-the-art crystal calorimeter and employs 1348 pure Cesium Iodide (CsI) crystals readout by UV-extended silicon photosensors and fast front-end and digitization electronics. A design consisting of two identical annular matrices (named "disks") positioned at the relative distance of 70 cm downstream the aluminum target along the muon beamline satisfies the Mu2e physics requirements. The hostile Mu2e operational conditions, in terms of radiation levels (total expected ionizing dose of 12 krad and a neutron fluence of 5 × 10¹⁰ n/cm² @ 1 MeV_(eq) (Si)/y), magnetic field intensity (1 T) and vacuum level (10⁻⁴ Torr) have posed tight constraints on scintillating materials, sensors, electronics and on the design of the detector mechanical structures and material choice. The support structure of each 674 crystal matrix is composed of an aluminum hollow ring and parts made of open-cell vacuum-compatible carbon fiber. The photosensors and front-end electronics for the readout of each crystal are inserted in a machined copper holder and make a unique mechanical unit. The resulting 674 mechanical units are supported by a machined plate of vacuum-compatible plastic material. The plate also integrates the cooling system made of a network of copper lines flowing a low temperature radiation-hard fluid and placed in thermal contact with the copper holders to constitute a low resistance thermal bridge. The data acquisition electronics are hosted in aluminum custom crates positioned on the external lateral surface of the disks. The crates also integrate the electronics cooling system as lines running in parallel to the front-end system. In this paper we report on the calorimeter mechanical structure design, the mechanical and thermal simulations that have determined the design technological choices, and the status of component production, quality assurance tests and plans for assembly at Fermilab
Evaluating the predictive value of comorbidity indices in pituitary surgery: a mixed-effects modeling study using the Nationwide Readmissions Database
No full textObjective: Although pituitary adenomas (PAs) are common intracranial tumors, literature evaluating the utility of comorbidity indices for predicting postoperative complications in patients undergoing pituitary surgery remains limited, thereby hindering the development of complex models that aim to identify high-risk patient populations. We utilized comparative modeling strategies to evaluate the predictive validity of various comorbidity indices and combinations thereof in predicting key pituitary surgery outcomes.
Methods: The Nationwide Readmissions Database was used to identify patients who underwent pituitary tumor operations (n = 19,653) in 2016–2017. Patient frailty was assessed using the Johns Hopkins Adjusted Clinical Groups (ACG) System. The Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) were calculated for each patient. Five sets of generalized linear mixed-effects models were developed, using as the primary predictors 1) frailty, 2) CCI, 3) ECI, 4) frailty + CCI, or 5) frailty + ECI. Complications of interest investigated included inpatient mortality, nonroutine discharge (e.g., to locations other than home), length of stay (LOS) within the top quartile (Q1), cost within Q1, and 1-year readmission rates.
Results: Postoperative mortality occurred in 73 patients (0.4%), 1-year readmission was reported in 2994 patients (15.2%), and nonroutine discharge occurred in 2176 patients (11.1%). The mean adjusted all-payer cost for the procedure was USD 26,518.91 (Q1 $28,261.20), and the mean LOS was 4.8 ± 7.4 days (Q1 5.0 days). The model using frailty + ECI as the primary predictor consistently outperformed other models, with statistically significant p values as determined by comparing areas under the curve (AUCs) for most complications. For prediction of mortality, however, the frailty + ECI model (AUC 0.831) was not better than the ECI model alone (AUC 0.831; p = 0.95). For prediction of readmission, the frailty + ECI model (AUC 0.617) was not better than the frailty model alone (AUC 0.606; p = 0.10) or the frailty + CCI model (AUC 0.610; p = 0.29).
Conclusions: This investigation is to the authors’ knowledge the first to implement mixed-effects modeling to study the utility of common comorbidity indices in a large, nationwide cohort of patients undergoing pituitary surgery. Knowledge gained from these models may help neurosurgeons identify high-risk patients who require additional clinical attention or resource utilization prior to surgical planning
Zinc Titanium Nitride Semiconductor toward Durable Photoelectrochemical Applications
No full textPhotoelectrochemical fuel generation is a promising route to sustainable liquid fuels produced from water and captured carbon dioxide with sunlight as the energy input. Development of these technologies requires photoelectrode materials that are both photocatalytically active and operationally stable in harsh oxidative and/or reductive electrochemical environments. Such photocatalysts can be discovered based on co-design principles, wherein design for stability is based on the propensity for the photocatalyst to self-passivate under operating conditions and design for photoactivity is based on the ability to integrate the photocatalyst with established semiconductor substrates. Here, we report on the synthesis and characterization of zinc titanium nitride (ZnTiN₂) that follows these design rules by having a wurtzite-derived crystal structure and showing self-passivating surface oxides created by electrochemical polarization. The sputtered ZnTiN₂ thin films have optical absorption onsets below 2 eV and n-type electrical conduction of 3 S/cm. The band gap of this material is reduced from the 3.36 eV theoretical value by cation-site disorder, and the impact of cation antisites on the band structure of ZnTiN₂ is explored using density functional theory. Under electrochemical polarization, the ZnTiN₂ surfaces have TiO₂- or ZnO-like character, consistent with Materials Project Pourbaix calculations predicting the formation of stable solid phases under near-neutral pH. These results show that ZnTiN₂ is a promising candidate for photoelectrochemical liquid fuel generation and demonstrate a new materials design approach to other photoelectrodes with self-passivating native operational surface chemistry
The Many-faceted Light Curves of Young Disk-bearing Stars in Taurus as Seen by K2
No full textWe present a comprehensive study of the variability properties of young disk-bearing stars in the Taurus star-forming region, paralleling our previous investigation in ρ Oph and Upper Sco. A sample of 99 confirmed Taurus association members is placed in the diagnostic Q − M plane of flux asymmetry (M) and (Q), which guides our assignment of variability classes. We find a similar proportion of flux-symmetric variables in Taurus, but more bursters and fewer dippers relative to Upper Sco. The regions also differ in that the amplitudes for periodic and sources are larger in Taurus relative to the more evolved Upper Sco star/disk systems. The relationship between photometric variability patterns at optical wavelengths, which arise in the inner disk and at the stellar surface, are assessed relative to available disk inclination measurements