SARS-CoV-2 infection can cause severe respiratory COVID-19. However, many individuals present with isolated upper respiratory symptoms, suggesting potential to constrain viral pathology to the ...nasopharynx. Which cells SARS-CoV-2 primarily targets and how infection influences the respiratory epithelium remains incompletely understood. We performed scRNA-seq on nasopharyngeal swabs from 58 healthy and COVID-19 participants. During COVID-19, we observe expansion of secretory, loss of ciliated, and epithelial cell repopulation via deuterosomal cell expansion. In mild and moderate COVID-19, epithelial cells express anti-viral/interferon-responsive genes, while cells in severe COVID-19 have muted anti-viral responses despite equivalent viral loads. SARS-CoV-2 RNA+ host-target cells are highly heterogenous, including developing ciliated, interferon-responsive ciliated, AZGP1high goblet, and KRT13+ “hillock”-like cells, and we identify genes associated with susceptibility, resistance, or infection response. Our study defines protective and detrimental responses to SARS-CoV-2, the direct viral targets of infection, and suggests that failed nasal epithelial anti-viral immunity may underlie and precede severe COVID-19.
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•scRNA-seq on nasopharyngeal swabs of 58 COVID-19 and healthy participants•SARS-CoV-2 induces ciliated cell loss with secretory and deuterosomal expansion•Early, muted anti-viral responses in nasal epithelia in severe COVID-19•Host-virus co-detection maps cell tropism and intrinsic responses to SARS-CoV-2
A study of nasopharyngeal swabs from healthy and COVID-19-infected individuals shows how infection leads to compositional changes in the respiratory epithelium, with early dampened antiviral responses in the nasal epithelia likely underlying and preceding severe disease.
The development of organic electro-optic (EO) materials that concurrently possess a high electro-optic coefficient (r 33), high index of refraction, and long-term or high-temperature stability of ...chromophore alignment has been a crucial goal. To address this challenge, we developed a crosslinkable EO system consisting of two chromophores, HLD1 and HLD2, which can be electric field poled and then thermally crosslinked in situ to form a stable EO material. This approach avoids the necessity for nonlinear optically inactive materials such as polymers or small molecule cross-linkers, thus resulting in high chromophore density (>5 × 1020 molecules/cm3) and high index of refraction (n = 1.89 at 1310 nm) for HLD1/HLD2. Different ratios of HLD1 and HLD2 were evaluated to optimize poling efficiency and thermal stability of the poling-induced order. With 2:1 HLD1/HLD2 (wt/wt), a maximum r 33 of 290 ± 30 pm/V was achieved in a cross-linked film. Thermal stability tests showed that after heating to 85 °C for 500 h, greater than 99% of the initial r 33 value was maintained. This combination of large EO activity, high index of refraction, and long-term alignment stability is an important breakthrough in EO materials. HLD1/HLD2 can also be poled without the subsequent cross-linking step, and even larger maximum r 33 (460 ± 30 pm/V) and n 3 r 33 figure of merit (3100 ± 200 pm/V) were achieved. Hyperpolarizabilities of HLD and control molecules were analyzed by hyper-Rayleigh scattering and computational modeling with good agreement, and they help explain the high acentric order achieved during poling.
Conspectus Organic glasses containing chromophores with large first hyperpolarizabilities (β) are promising for compact, high-bandwidth, and energy-efficient electro-optic devices. Systematic ...optimization of device performance requires development of materials with high acentric order and enhanced hyperpolarizability at operating wavelengths. One essential component of the design process is the accurate calculation of optical transition frequencies and hyperpolarizability. These properties can be computed with a wide range of electronic structure methods implemented within commercial and open-source software packages. A wide variety of methods, especially hybrid density-functional theory (DFT) variants have been used for this purpose. However, in order to provide predictions useful to chromophore designers, a method must be able to consistently predict the relative ordering of standard and novel materials. Moreover, it is important to distinguish between the resonant and nonresonant contribution to the hyperpolarizabiliy and be able to estimate the trade-off between improved β and unwanted absorbance (optical loss) at the target device’s operating wavelength. Therefore, we have surveyed a large variety of common methods for computing the properties of modern high-performance chromophores and compared these results with prior experimental hyper-Rayleigh scattering (HRS) and absorbance data. We focused on hybrid DFT methods, supplemented by more computationally intensive Møller–Plesset (MP2) calculations, to determine the relative accuracy of these methods. Our work compares computed hyperpolarizabilities in chloroform relative to standard chromophore EZ-FTC against HRS data versus the same reference. We categorized DFT methods used by the amount of Hartree–Fock (HF) exchange energy incorporated into each functional. Our results suggest that the relationship between percentage of long-range HF exchange and both βHRS and λmax is nearly linear, decreasing as the fraction of long-range HF exchange increases. Mild hybrid DFT methods are satisfactory for prediction of λmax. However, mild hybrid methods provided qualitatively incorrect predictions of the relative hyperpolarizabilities of three high-performance chromophores. DFT methods with approximately 50% HF exchange, and especially the Truhlar M062X functional, provide superior predictions of relative βHRS values but poorer predictions of λmax. The observed trends for these functionals, as well as range-separated hybrids, are similar to MP2, though predicting smaller absolute magnitudes for βHRS. Frequency dependence for βHRS can be calculated using time-dependent DFT and HF methods. However, calculation quality is sensitive not only to a method’s ability to predict static hyperpolarizability but also to its prediction of optical resonances. Due to the apparent trade-off in accuracy of prediction of these two properties and the need to use static finite-field methods for MP2 and higher-level hyperpolarizability calculations in most codes, we suggest that composite methods could greatly improve the accuracy of calculations of β and λmax.
A unique 16-year time series of deep video surveys in Monterey Bay reveals that the Humboldt squid, Dosidicus gigas, has substantially expanded its perennial geographic range in the eastern North ...Pacific by invading the waters off central California. This sustained range expansion coincides with changes in climate-linked oceanographic conditions and a reduction in competing top predators. It is also coincident with a decline in the abundance of Pacific hake, the most important commercial groundfish species off western North America. Recognizing the interactive effects of multiple changes in the environment is an issue of growing concern in ocean conservation and sustainability research.
Herein are reported initial efforts to develop a generally accessible flow process, applying a heterogenous nanocatalyst to aqueous micelle-enabled Suzuki-Miyaura coupling reactions. Also disclosed ...is a new engineering solution (
i.e.
, a self-draining back pressure regulator), which, when applied, enabled 1.5 hours of continuous operation leading to the production of 20 grams of a pharmaceutical intermediate.
Plugged flow chemistry in water has been developed using a heterogeneous catalyst and applied to Suzuki-Miyaura cross-couplings.
Organic electro-optic (OEO) materials integrated into silicon–organic hybrid devices afford significant improvements in size, weight, power, and bandwidth performance of integrated ...electronic/photonic systems critical for current and next generation telecommunication, computer, sensor, transportation, and defense technologies. Improvement in molecular first hyperpolarizability (β), and in turn electro-optic activity, is crucial to optimizing device performance. Common hybrid density functional theory (DFT) methods, while attractive due to their computational scaling, often perform poorly for optical properties in systems with substantial intramolecular charge-transfer character, such as OEO chromophores. This study evaluates the utility of the long-range corrected (LC) DFT methods for computation of the molecular second-order nonlinear optical response. We compare calculated results for a 14-molecule benchmark set of OEO chromophores with the corresponding experimentally measured β and one-photon absorption energy, λmax. We analyze the distance dependence of the fraction of exact exchange in LC-DFT methods for accurately computing these properties for OEO chromophores. We also examine systematic tuning of the range-separation parameter to enforce Koopmans’/ionization potential theorem. This tuning method improves prediction of excitation energies but is not reliable for predicting the hyperpolarizabilities of larger chromophores since the tuning parameter value can be too small, leading to instabilities in the computation of βHRS. Additionally, we find that the size dependence of the optimal tuning parameter for the ionization potential has the opposite size dependence of optimal tuning parameter for best agreement with the experimental λmax, suggesting the tuning for the ionization potential is unreliable for extended conjugated systems.
Chip-scale integration of electronics and photonics is recognized as important to the future of information technology, as is the exploitation of the best properties of electronics, photonics, and ...plasmonics to achieve this objective. However, significant challenges exist including matching the sizes of electronic and photonic circuits; achieving low-loss transition between electronics, photonics, and plasmonics; and developing and integrating new materials. This review focuses on a hybrid material approach illustrating the importance of both chemical and engineering concepts. Silicon–organic hybrid (SOH) and plasmonic–organic hybrid (POH) technologies have permitted dramatic improvements in electro-optic (EO) performance relevant to both digital and analog signal processing. For example, the voltage–length product of devices has been reduced to less than 40 Vμm, facilitating device footprints of <20 μm2 operating with digital voltage levels to frequencies above 170 GHz. Energy efficiency has been improved to around a femtojoule/bit. This improvement has been realized through exploitation of field enhancements permitted by new device architectures and through theory-guided improvements in organic electro-optic (OEO) materials. Multiscale theory efforts have permitted quantitative simulation of the dependence of OEO activity on chromophore structure and associated intermolecular interactions. This has led to new classes of OEO materials, including materials of reduced dimensionality and neat (pure) chromophore materials that can be electrically poled. Theoretical simulations have helped elucidate the observed dependence of device performance on nanoscopic waveguide dimensions, reflecting the importance of material interfaces. The demonstration and explanation of the dependence of in-device electro-optic activity, voltage–length product, and optical insertion loss on device architecture (e.g., slot width) suggest new paradigms for further dramatic improvement of performance.
High performance organic electro‐optic (OEO) materials enable ultrahigh bandwidth, small footprint, and extremely low drive voltage in silicon‐organic hybrid and plasmonic‐organic hybrid photonic ...devices. However, practical OEO materials under device‐relevant conditions are generally limited to performance of ≈300 pm V−1 (10× the EO response of lithium niobate). By means of theory‐guided design, a new series of OEO chromophores is demonstrated, based on strong bis(4‐dialkylaminophenyl)phenylamino electron donating groups, capable of EO coefficients (r33) in excess of 1000 pm V−1. Density functional theory modeling and hyper‐Rayleigh scattering measurements are performed and confirm the large improvement in hyperpolarizability due to the stronger donor. The EO performance of the exemplar chromophore in the series, BAY1, is evaluated neat and at various concentrations in polymer host and shows a nearly linear increase in r33 and poling efficiency (r33/Ep, Ep is poling field) with increasing chromophore concentration. 25 wt% BAY1/polymer composite shows a higher poling efficiency (3.9 ± 0.1 nm2 V−2) than state‐of‐the‐art neat chromophores. Using a high‐ε charge blocking layer with BAY1, a record‐high r33 (1100 ± 100 pm V−1) and poling efficiency (17.8 ± 0.8 nm2 V−2) at 1310 nm are achieved. This is the first reported OEO material with electro‐optic response larger than thin‐film barium titanate.
Using theory‐guided design, a new series of organic electro‐optic chromophores is demonstrated, based on strong bis(4‐dialkylaminophenyl)phenylamino electron‐donating groups. Density functional theory modeling and hyper‐Rayleigh scattering measurements confirm large improvements in hyperpolarizability. The best electro‐optic coefficient (r33 = 1100 ± 100 pm V−1) is nearly twice as high as the previous best example and higher than for thin‐film barium titanate.
Two new highly hyperpolarizable chromophores, based on N,N-bis-(4-methoxyphenyl)aryl-amino donors and phenyl-trifluoromethyl-tricyanofuran (CF 3 -Ph-TCF) acceptor linked together via π-conjugation ...through 2,5-divinylenethienyl moieties as the bridge, have been designed and synthesized successfully for the first time. The aryl moieties on the donor side of the chromophore molecules were varied as to be thiophene and 1-n-hexylpyrrole. The linear and nonlinear optical (NLO) properties of all compounds were evaluated in addition to recording relevant thermal and electrochemical data. The properties of the two new molecules were comparatively studied. These results are critically analyzed along with two other compounds, reported earlier from our laboratories and our collaborator’s, that contain (i) aliphatic chain-bearing aniline and (ii) dianisylaniline as donors, keeping the bridge (2,5-divinylenethienyl-), and the acceptor (CF 3 -Ph-TCF), constant. Trends in theoretically (density functional theory, DFT) predicted, zero-frequency gas-phase hyperpolarizability β(0;0,0) values are shown to be consistent with the trends in βHRS(−2ω;ω,ω), as measured by Hyper-Rayleigh Scattering (HRS), when corrected to zero-frequency using the two-level model (TLM) approximation. Similarly, trends in poling efficiency data (r 33/E p) and wavelength dispersion measured by reflection ellipsometry (using a Teng−Man apparatus) and attenuated total reflection (ATR) are found to fit the TLM and DFT predictions. A 3-fold enhancement in bulk nonlinearity (r 33) is realized as the donor subunits are changed from alkylaniline to dianisylaminopyrrole donors. The results of these studies provide insight into the complicated effects on molecular hyperpolarizability of substituting heteroaromatic subunits into the donor group structures. These studies also demonstrate that, when frequency dependence and electric-field-induced ordering behavior are correctly accounted for, ab initio DFT generated β(0;0,0) is effective as a predictor of changes in r 33 behavior based on chromophore structure modification. Thus DFT can provide valuable insight into the electronic structure origin of complex optical phenomena in organic media.
Physiological feelings Pace-Schott, Edward F.; Amole, Marlissa C.; Aue, Tatjana ...
Neuroscience & biobehavioral reviews/Neuroscience and biobehavioral reviews,
08/2019, Letnik:
103
Journal Article, Web Resource
Recenzirano
Odprti dostop
•Peripheral physiological changes can be perceived as feelings via interoception.•Both perceived and unperceived interoceptive information contribute to emotions.•The forebrain can generate ...physiological feelings without actual peripheral events.•Interacting networks of afferent and efferent signals generate physiological feelings.•Physiological feelings contribute to survival, reproduction and emotion regulation.
The role of peripheral physiology in the experience of emotion has been debated since the 19th century following the seminal proposal by William James that somatic responses to stimuli determine subjective emotion. Subsequent views have integrated the forebrain's ability to initiate, represent and simulate such physiological events. Modern affective neuroscience envisions an interacting network of “bottom-up” and “top-down” signaling in which the peripheral (PNS) and central nervous systems both receive and generate the experience of emotion. “Feelings” serves as a term for the perception of these physical changes whether emanating from actual somatic events or from the brain's representation of such. “Interoception” has come to represent the brain's receipt and representation of these actual and “virtual” somatic changes that may or may not enter conscious awareness but, nonetheless, influence feelings. Such information can originate from diverse sources including endocrine, immune and gastrointestinal systems as well as the PNS. We here examine physiological feelings from diverse perspectives including current and historical theories, evolution, neuroanatomy and physiology, development, regulatory processes, pathology and linguistics.
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