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ABSTRACT: Our objective was to analyze the effect of selection for divergent traits in the domestic chicken on embryonic skeletal development, which could affect postnatal bird welfare. Development was compared between the Ross 308 broiler line (fast growth and muscle mass accrual) and Novoponte layers (high laying rate and egg quality).In Study 1 (Initial Conditions), we characterized egg composition prior to incubation and identified the onset of embryonic skeletal mineralization in the 2 strains. In Study 2 (Developmental Dynamics), we used 3D X-ray tomographic imaging (µCT) on incubation days ED11, ED13, ED15 and ED17 to track skeletal maturation trajectories as a pseudo-time series.Results showed that Ross 308 embryos, which are heavier than Novoponte embryos, possess higher levels of yolk nutrients including phosphorus and calcium, but lower eggshell mineral content, than Novoponte embryos. Skeletal mineralization started synchronously in both strains, on ED11. The higher mineral ion content in the larger yolk of Ross 308 eggs compared to Novoponte eggs may partly explain why skeletal mineralization in Ross 308 embryos advances faster: using µCT, we show that the mandible and tibiotarsi in Ross 308 embryos are larger at ED11 and ED13 compared with Novoponte embryos. However, Novoponte embryos catch up from this initial lag in mineralization by ED15. The timing of the Novoponte acceleration coincides with the functional activation of the chorioallantoic membrane in releasing calcium from the inner eggshell. This correlates with a decrease in eggshell thickness from ED11 to ED17 in Novoponte eggs, which was not observed during Ross 308 incubation.To conclude, while some temporal discrepancies exist in early skeletal development between the embryos of Ross 308 and Novoponte strains, overall prenatal skeletal maturation seems to be robustly regulated. Despite selection for antagonist production traits, layer and broiler prehatch skeletal morphology ultimately synchronizes.Practically, since the extent of skeletal maturity equalizes between strains towards the end of incubation, refinements of farming practices, postnatal environment, and diet should be considered for improving domestic fowl welfare.

Abstract We generalize the relativistic field-theoretic three-particle finite-volume scattering formalism to describe generic DDπ systems in the charm C = 2 sector. This includes the isospin-0 channel, in which the recently discovered doubly-charmed tetraquark T cc (3875)+ is expected to manifest as a pole in the DDπ → DDπ scattering amplitude. The formalism presented here can also be applied to lattice QCD settings in which the D * is bound and, in particular, remains valid below the left-hand cut in DD * scattering, thus resolving an issue in previous analyses of lattice-determined finite-volume energies.

The cuticle covering the outer surface of an eggshell functions as both a physical and chemical barrier against invading microorganisms. Contamination of eggs by microbial pathogens progresses in four stages: bacterial attachment to the egg surface, penetration through the cuticle and eggshell, multiplication within the underlying membranes, and the final stage of contaminating the egg contents. Therefore, it is important to study bacterial count at the first point of contact, i.e., on the surface of the eggs. In this study, we have evaluated the impact of differences in cuticle quality (due to egg washing and hen age) on bacterial load. We compared bacterial adherence on the eggshell surface of white eggs which were either washed (graded) or unwashed (ungraded), collected from Lohmann laying hens of different ages: early (24–28 weeks), mid-lay (44–48 weeks), and late (66–70 weeks). We aimed to determine the impact of hen age and egg washing on differences in cuticle quality and bacterial adherence. Our results indicate that hen age (up to 70 weeks) and commercial egg washing do not significantly impact bacterial adherence on eggshell surfaces. We have developed a novel method using green fluorescent protein (GFP)-expressing Salmonella typhimurium to estimate adherence of bacteria to the eggshell surface, with independent measurement of autofluorescence to quantitate cuticle deposition. S. typhimurium were localized, adhering to cracks visible on the outer cuticle in ungraded eggs, indicating that egg-associated pathogens usually enter the egg interior either through respiratory pores in eggshells or through shell micro-cracks. The results of this study can be utilized to optimize innovative methods for predictive microbiology in order to achieve egg safety.

Abstract Because of the mass gap, lattice QCD simulations exhibit stochastic locality: distant regions of the lattice fluctuate independently. There is a long history of exploiting this to increase statistics by obtaining multiple spatially-separated samples from each gauge field; in the extreme case, we arrive at the master-field approach in which a single gauge field is used. Here we develop techniques for studying hadronic observables using position-space correlators, which are more localized, and compare with the standard time-momentum representation. We also adapt methods for estimating the variance of an observable from autocorrelated Monte Carlo samples to the case of correlated spatially-separated samples.

Exploiting the power of quantum computation to realize superior machine learning algorithms has been a major research focus of recent years, but the prospects of quantum machine learning (QML) remain dampened by considerable technical challenges. A particularly significant issue is that generic QML models suffer from so-called barren plateaus in their training landscapes—large regions where cost function gradients vanish exponentially in the number of qubits employed, rendering large models effectively untrainable. A leading strategy for combating this effect is to build problem-specific models that take into account the symmetries of their data in order to focus on a smaller, relevant subset of Hilbert space. In this work, we introduce a family of rotationally equivariant QML models built upon the quantum Fourier transform, and leverage recent insights from the Lie-algebraic study of QML models to prove that (a subset of) our models do not exhibit barren plateaus. In addition to our analytical results we numerically test our rotationally equivariant models on a dataset of simulated scanning tunneling microscope images of phosphorus impurities in silicon, where rotational symmetry naturally arises, and find that they dramatically outperform their generic counterparts in practice.

Abstract There is tremendous interest in employing collective excitations of the lattice, spin, charge, and orbitals to tune strongly correlated electronic phenomena. We report such an effect in a ruthenate, Ca3Ru2O7, where two phonons with strong electron-phonon coupling modulate the electronic pseudogap as well as mediate charge and spin density wave fluctuations. Combining temperature-dependent Raman spectroscopy with density functional theory reveals two phonons, B 2 P and B 2 M, that are strongly coupled to electrons and whose scattering intensities respectively dominate in the pseudogap versus the metallic phases. The B 2 P squeezes the octahedra along the out of plane c-axis, while the B 2 M elongates it, thus modulating the Ru 4d orbital splitting and the bandwidth of the in-plane electron hopping; Thus, B 2 P opens the pseudogap, while B 2 M closes it. Moreover, the B 2 phonons mediate incoherent charge and spin density wave fluctuations, as evidenced by changes in the background electronic Raman scattering that exhibit unique symmetry signatures. The polar order breaks inversion symmetry, enabling infrared activity of these phonons, paving the way for coherent light-driven control of electronic transport.

Abstract We generalize the relativistic field-theoretic (RFT) three-particle finite-volume formalism to systems of three identical, massive, spin-1/2 fermions, such as three neutrons. This allows, in principle, for the determination of the three-neutron interaction from the finite-volume spectrum of three-neutron states, which can be obtained from lattice QCD calculations.

Cable bacteria embed a network of conductive protein fibers in their cell envelope that efficiently guides electron transport over distances spanning up to several centimeters. This form of long-distance electron transport is unique in biology and is mediated by a metalloprotein with a sulfur-coordinated nickel (Ni) cofactor. However, the molecular structure of this cofactor remains presently unknown. Here, we applied multi-wavelength Raman microscopy to identify cell compounds linked to the unique cable bacterium physiology, combined with stable isotope labeling, and orientation-dependent and ultralow-frequency Raman microscopy to gain insight into the structure and organization of this novel Ni-cofactor. Raman spectra of native cable bacterium filaments reveal vibrational modes originating from cytochromes, polyphosphate granules, proteins, as well as the Ni-cofactor. After selective extraction of the conductive fiber network from the cell envelope, the Raman spectrum becomes simpler, and primarily retains vibrational modes associated with the Ni-cofactor. These Ni-cofactor modes exhibit intense Raman scattering as well as a strong orientation-dependent response. The signal intensity is particularly elevated when the polarization of incident laser light is parallel to the direction of the conductive fibers. This orientation dependence allows to selectively identify the modes that are associated with the Ni-cofactor. We identified 13 such modes, some of which display strong Raman signals across the entire range of applied wavelengths (405–1,064 nm). Assignment of vibrational modes, supported by stable isotope labeling, suggest that the structure of the Ni-cofactor shares a resemblance with that of nickel bis(1,2-dithiolene) complexes. Overall, our results indicate that cable bacteria have evolved a unique cofactor structure that does not resemble any of the known Ni-cofactors in biology.

Quantum machine learning (QML) is emerging as an application of quantum computing with the potential to deliver quantum advantage, but its realization for practical applications remains impeded by challenges. Among these, a key barrier is the computationally expensive task of encoding classical data into a quantum state, which could erase any prospective speedups over classical algorithms. In this study, we implement methods for the efficient preparation of quantum states representing encoded image data using variational, genetic, and matrix product state algorithms. Our results show that these methods can approximately prepare states to a level suitable for QML using circuits 2 orders of magnitude shallower than a standard state preparation implementation, thus drastically reducing circuit depth and gate count without unduly sacrificing classification accuracy. Additionally, the QML models trained and evaluated on approximately encoded data displayed an increased robustness to adversarially generated input data perturbations. This partial alleviation of adversarial vulnerability, made possible by the retention of the meaningful large-scale features of the data despite the “drowning out” of adversarial perturbations, constitutes a considerable benefit for approximate state preparation in addition to lessening the requirements of the quantum hardware. Our results, based on simulations and experiments on IBM quantum devices, highlight a promising pathway for the future implementation of accurate and robust QML models on complex datasets relevant for practical applications, bringing the possibility of NISQ-era QML advantage closer to reality.

Abstract We present a strategy for calculating the rare decay of a Σ+(uus) baryon to a proton (uud) and di-lepton pair using lattice QCD. To determine this observable one needs to numerically evaluate baryonic two-, three-, and four-point correlation functions related to the target process. In particular, the four-point function arises from the insertion of incoming and outgoing baryons, together with a weak Hamiltonian mediating the s → d transition and an electromagnetic current creating the outgoing leptons. As is described in previous work in other contexts, this four-point function has a highly non-trivial relation to the physical observable, due to proton and proton-pion intermediate states. These lead to growing Euclidean time dependence and, in the case of the two-particle intermediate states, to power-like volume effects. We discuss how to treat these issues in the context of the Σ+ → pℓ + ℓ − decay and, in particular, detail the relation between the finite-volume estimator and the physical, complex-valued amplitude. In doing so, we also make connections between various approaches already described in the literature.

Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-β. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding.

Abstract The decreasing uncertainties in theoretical predictions and experimental measurements of several hadronic observables related to weak processes, which in many cases are now smaller than O(1%), require theoretical calculations to include subleading corrections that were neglected so far. Precise determinations of leptonic and semi-leptonic decay rates, including QED and strong isospin-breaking effects, can play a central role in solving the current tensions in the first-row unitarity of the CKM matrix. In this work we present the first RBC/UKQCD lattice calculation of the isospin-breaking corrections to the ratio of leptonic decay rates of kaons and pions into muons and neutrinos. The calculation is performed at fixed lattice spacing (a −1 ≃ 1.730 GeV) on a 483 × 96 volume with N f = 2 + 1 dynamical quarks close to the physical point and domain wall fermions in the Möbius formulation are employed. Long-distance QED interactions are included according to the QEDL prescription and the crucial role of finite-volume electromagnetic corrections in the determination of leptonic decay rates, which produce a large systematic uncertainty, is extensively discussed. Finally, we study the different sources of uncertainty on |V us|/|V ud| and observe that, if finite-volume systematics can be reduced, the error from isospin-breaking corrections is potentially sub-dominant in the final precision of the ratio of the CKM matrix elements.

Abstract Introduction Shared decision‐making, with an emphasis on patient autonomy, is often advised in healthcare decision‐making. However, this may be difficult to implement in emergent settings. We have previously demonstrated that when considering emergent operations for their children, parents prefer surgeon guidance as opposed to shared decision‐making. Here, we interviewed parents of paediatric patients who had undergone emergent operations to better understand parental decision‐making preferences. Methods Parents of paediatric patients who underwent surgery over the past 5 years at a University‐based, tertiary children's hospital for cancer, an emergent operation while in the neonatal intensive care unit (NICU) or extracorporeal membrane oxygenation (ECMO) were invited to complete a 60‐min semi‐structured interview. Interviews were digitally recorded and transcribed verbatim. Thematic content analysis was performed via deductive and inductive analysis. An iterative approach to thematic sampling/data analysis was used. Results Thematic saturation was achieved after 12 interviews (4 cancer, 5 NICU and 3 ECMO). Five common themes were identified: (1) recommendations from surgeons are valuable; (2) ‘lifesaving mode’: parents felt there were no decisions to be made; (3) effective ways of obtaining information about treatment; (4) shared decision‐making as a ‘dialogue’ or ‘discussion’ and (5) parents as a ‘valued voice’ to advocate for their children. Conclusions When engaging in decision‐making regarding emergent surgical procedures for their children, parents value a surgeon's recommendation. Parents felt that discussion or dialogue with surgeons defined shared decision‐making, and they believed that the opportunity to ask questions gave them a ‘valued voice’, even when they felt there were no decisions to be made. Patient or Public Contribution For this study, we interviewed parents of paediatric patients who had undergone emergent operations to better understand parental decision‐making preferences. Parents thus provided all the data for the study.

Quantum machine learning (QML) has received increasing attention due to its potential to outperform classical machine learning methods in problems, such as classification and identification tasks. A subclass of QML methods is quantum generative adversarial networks (QGANs), which have been studied as a quantum counterpart of classical GANs widely used in image manipulation and generation tasks. The existing work on QGANs is still limited to small-scale proof-of-concept examples based on images with significant downscaling. Here, we integrate classical and quantum techniques to propose a new hybrid quantum–classical GAN framework. We demonstrate its superior learning capabilities over existing quantum techniques by generating $28 \times 28$ pixels grayscale images without dimensionality reduction or classical pre/postprocessing on multiple classes of the standard Modified National Institute of Standards and Technology (MNIST) and Fashion MNIST datasets, which achieves comparable results to classical frameworks with three orders of magnitude less trainable generator parameters. To gain further insight into the working of our hybrid approach, we systematically explore the impact of its parameter space by varying the number of qubits, the size of image patches, the number of layers in the generator, the shape of the patches, and the choice of prior distribution. Our results show that increasing the quantum generator size generally improves the learning capability of the network. The developed framework provides a foundation for future design of QGANs with optimal parameter set tailored for complex image generation tasks.

Abstract This work employs the spectral reconstruction approach of ref. [1] to determine an inclusive rate in the 1 + 1 dimensional O(3) non-linear σ-model, analogous to the QCD part of e + e − → hadrons. The Euclidean two-point correlation function of the conserved current j is computed using Monte Carlo lattice field theory simulations for a variety of spacetime volumes and lattice spacings. The spectral density of this correlator is related to the inclusive rate for j → X in which all final states produced by the external current are summed. The ill-posed inverse problem of determining the spectral density from the correlation function is made tractable through the determination of smeared spectral densities in which the desired density is convolved with a set of known smearing kernels of finite width ϵ. The smooth energy dependence of the underlying spectral density enables a controlled ϵ → 0 extrapolation in the inelastic region, yielding the real-time inclusive rate without reference to individual finite-volume energies or matrix elements. Systematic uncertainties due to cutoff effects and residual finite-volume effects are estimated and taken into account in the final error budget. After taking the continuum limit, the results are consistent with the known analytic rate to within the combined statistical and systematic errors. Above energies where 20-particle states contribute, the overall precision is sufficient to discern the four-particle contribution to the spectral density.

Background: Previous studies have demonstrated that online patient educational materials are written at reading levels too advanced for the average patient. The average American reads at the eighth-grade reading level. To date, the readability of online educational material of academic centers for shoulder arthroplasty has not been analyzed. Methods: Online patient educational materials from the top 25 orthopedic institutions, as ranked by U.S. News & World Report, were assessed utilizing the following readability assessments: Flesch-Kincaid (FK), Flesch Reading Ease, Gunning Fog Index, Coleman-Liau Index, Simple Measure of the Gobbledygook Index, Automated Readability Index, FORCAST, and the New Dale and Chall Readability. All of these scores, with the exception of the Flesch Reading Ease, provide an output indicating reading difficulty based on grade level. Correlations between academic institutional ranking and FK scores were evaluated using a Spearman regression. Lastly, additional factors including geographical location, private versus public institution, and use of concomitant multi-media modalities that may impact institutional readability scores (as determined by FK) were evaluated. Results: Only 16.0% of the top 25 institutions included online material at or below the eighth-grade reading level. Moreover, half of the online resources evaluated (those with FK score ≥9.3) were not at a suitable reading level for more than two-thirds of the general United States population (∼70%). Overall, the composite mean scores were 9.5 ± 2.1 for FK, 52.8 ± 9. for 4 Flesch Reading Ease, 12.2 ± 2.4 for Gunning Fog, 11.6 ± 1.8 for Coleman-Liau, 12.3 ± 1.7 for Simple Measure of the Gobbledygook Index, 9.6 ± 2.6 for Automated Readability, 11.1 ± 0.6 for FORCAST, and 5.9 ± 0.6 for New Dale and Chall. There was no correlation between institutional ranking and FK scores (ρ = −0.15; P = .946). Geographical location, private versus public institution, and use of concomitant multi-media modalities were not significantly associated with readability. Conclusion: Shoulder arthroplasty online patient educational material at top-ranked orthopedic institutions have poor readability and are likely not suitable for the majority of patients in the United States.

Abstract Background Anchor institutions, by definition, have a long-term presence within their local communities, but it is uncertain as to whether for-profit hospitals meet this definition; most research on anchor institutions to date has been limited to nonprofit organizations such as hospitals and universities. Accordingly, this study aims to determine whether for-profit hospitals are stable enough to fulfill the role of anchor institutions through a long-term presence in communities which may help to stabilize local economies. Methods This longitudinal study analyzes national, secondary data between 2008 and 2017 compiled from the Dartmouth Atlas of Health Care, the American Hospital Association Annual Survey, and County Health Rankings. We use descriptive statistics to calculate the number of closures and mergers of hospitals of different ownership type, as well as staffing levels. Using logistic regression, we also assessed whether for-profit hospitals had higher odds of closing and merging, controlling for both organization and community factors. Results We found for-profit hospitals to be less stable than their public and nonprofit hospital counterparts, experiencing disproportionately more closures and mergers over time, with a multivariable analysis indicating a statistically significant difference. Furthermore, for-profit hospitals have fewer full-time employees relative to their size than hospitals of other ownership types, as well as lower total payroll expenditures. Conclusions Study findings suggest that for-profit hospitals operate more efficiently in terms of expenses, but this also may translate into a lower level of economic contributions to the surrounding community through employment and purchasing initiatives. For-profit hospitals may also not have the stability required to serve as long-standing anchor institutions. Future studies should consider whether for-profit hospitals make other types of community investments to offset these deficits and whether policy changes can be employed to encourage anchor activities from local businesses such as hospitals.

Elicitation of broadly neutralizing antibodies (bnAbs) is a goal of vaccine design as a strategy for targeting highly divergent strains of HIV-1. Current HIV-1 vaccine design efforts seek to elicit bnAbs by first eliciting their precursors through prime-boost regimens. This requires an understanding of the co-evolution between viruses and antibodies. Towards this goal, we have analyzed two cooperating antibodies, DH475 and DH272, which exerted pressure on the HIV population in an infected donor, called CH848, to evolve in such a way that it became sensitive to the V3-glycan supersite DH270 bnAb lineage. We obtained a 2.90Å crystal structure of DH475 in complex with the Man9 glycan and a negative stain EM model of DH272 in complex with the HIV-1 spike trimer, Env. Coupled with additional modeling studies and biochemical data, our studies reveal that DH475 contacts a V3- and V4-glycan dependent epitope accessible on an open or shed Env and that DH272 makes critical contacts with the V1V2 and V3 loops on HIV-1 Env. Using these data, we suggest a prime-boost regimen that may facilitate the initiation of DH270-like bnAb precursors.

The calcitic avian eggshell provides physical protection for the embryo during its development, but also regulates water and gaseous exchange, and is a calcium source for bone mineralization. The calcified eggshell has been extensively investigated in the chicken. It is characterized by an inventory of more than 900 matrix proteins. In addition to proteins involved in shell mineralization and regulation of its microstructure, the shell also contains numerous antimicrobial proteins and peptides (AMPPs) including lectin-like proteins, Bacterial Permeability Increasing/Lipopolysaccharide Binding Protein/PLUNC family proteins, defensins, antiproteases, and chelators, which contribute to the innate immune protection of the egg. In parallel, some of these proteins are thought to be crucial determinants of the eggshell texture and its resulting mechanical properties. During the progressive solubilization of the inner mineralized eggshell during embryonic development (to provide calcium to the embryo), some antimicrobials may be released simultaneously to reinforce egg defense and protect the egg from contamination by external pathogens, through a weakened eggshell. This review provides a comprehensive overview of the diversity of avian eggshell AMPPs, their three-dimensional structures and their mechanism of antimicrobial activity. The published chicken eggshell proteome databases are integrated for a comprehensive inventory of its AMPPs. Their biochemical features, potential dual function as antimicrobials and as regulators of eggshell biomineralization, and their phylogenetic evolution will be described and discussed with regard to their three-dimensional structural characteristics. Finally, the repertoire of chicken eggshell AMPPs are compared to orthologs identified in other avian and non-avian eggshells. This approach sheds light on the similarities and differences exhibited by AMPPs, depending on bird species, and leads to a better understanding of their sequential or dual role in biomineralization and innate immunity.

Abstract We derive relations between finite-volume matrix elements and infinite-volume decay amplitudes, for processes with three spinless, degenerate and either identical or non-identical particles in the final state. This generalizes the Lellouch-Lüscher relation for two-particle decays and provides a strategy for extracting three-hadron decay amplitudes using lattice QCD. Unlike for two particles, even in the simplest approximation, one must solve integral equations to obtain the physical decay amplitude, a consequence of the nontrivial finite-state interactions. We first derive the result in a simplified theory with three identical particles, and then present the generalizations needed to study phenomenologically relevant three-pion decays. The specific processes we discuss are the CP-violating K → 3π weak decay, the isospin-breaking η → 3π QCD transition, and the electromagnetic γ * → 3π amplitudes that enter the calculation of the hadronic vacuum polarization contribution to muonic g − 2.

Machine learning (ML) methods such as artificial neural networks are rapidly becoming ubiquitous in modern science, technology, and industry. Despite their accuracy and sophistication, neural networks can be easily fooled by carefully designed malicious inputs known as adversarial attacks. While such vulnerabilities remain a serious challenge for classical neural networks, the extent of their existence is not fully understood in the quantum ML setting. In this paper, we benchmark the robustness of quantum ML networks, such as quantum variational classifiers (QVC), at scale by performing rigorous training for both simple and complex image datasets and through a variety of high-end adversarial attacks. Our results show that QVCs offer a notably enhanced robustness against classical adversarial attacks by learning features, which are not detected by the classical neural networks, indicating a possible quantum advantage for ML tasks. Contrarily, and remarkably, the converse is not true, with attacks on quantum networks also capable of deceiving classical neural networks. By combining quantum and classical network outcomes, we propose an adversarial attack detection technology. Traditionally quantum advantage in ML systems has been sought through increased accuracy or algorithmic speed-up, but our study has revealed the potential for a kind of quantum advantage through superior robustness of ML models, whose practical realization will address serious security concerns and reliability issues of ML algorithms employed in a myriad of applications including autonomous vehicles, cybersecurity, and surveillance robotic systems.

The chicken eggshell (ES) consists of 95% calcium carbonate and 3.5% organic matter, and represents the first physical barrier to protect the developing embryo, while preventing water loss. During the second half of development, calcium ions from the inner ES are progressively solubilized to support mineralization of the embryonic skeleton. This process is mediated by the chorioallantoic membrane (CAM), which is an extraembryonic structure that adheres to the eggshell membranes (ESM) lining the inner ES. The CAM surrounds the embryo and all egg contents by day 11 of incubation (Embryonic Incubation Day 11, EID11) and is fully differentiated and functionally active by day 15 of incubation (Embryonic Incubation Day 15, EID15). In this study, we explored the simultaneous morphological modifications in the ES, ESM and the CAM at EID11 and EID15 by scanning electron microscopy. We observed that the tips of the mammillary knobs of the ES remain tightly attached to the ESM fibers, while their bases become progressively eroded and then detached from the bulk ES. Concomitantly, the CAM undergoes major structural changes that include the progressive differentiation of villous cells whose villi extend to reach the ESM and the ES. These structural data are discussed with respect to the importance of ES decalcification in providing the calcium necessary for mineralization of embryo’s skeleton. In parallel, eggshell decalcification and weakening during incubation is likely to impair the ability of the ES to protect the embryo. It is assumed that the CAM could counteract this apparent weakening as an additional layer of physical, cellular and molecular barriers against environmental pressures, including pathogens, dehydration and shocks. However, such hypothesis needs to be further investigated.

Abstract We present a generalization of the relativistic, finite-volume, three-particle quantization condition for non-identical pions in isosymmetric QCD. The resulting formalism allows one to use discrete finite-volume energies, determined using lattice QCD, to constrain scattering amplitudes for all possible values of two- and three-pion isospin. As for the case of identical pions considered previously, the result splits into two steps: the first defines a non-perturbative function with roots equal to the allowed energies, E n (L), in a given cubic volume with side-length L. This function depends on an intermediate three-body quantity, denoted K df , 3 , $$ {\mathcal{K}}_{\mathrm{df},3,} $$ which can thus be constrained from lattice QCD in- put. The second step is a set of integral equations relating K df , 3 $$ {\mathcal{K}}_{\mathrm{df},3} $$ to the physical scattering amplitude, ℳ3. Both of the key relations, E n (L) ↔ K df , 3 $$ {\mathcal{K}}_{\mathrm{df},3} $$ and K df , 3 ↔ ℳ 3 , $$ {\mathcal{K}}_{\mathrm{df},3}\leftrightarrow {\mathrm{\mathcal{M}}}_3, $$ are shown to be block-diagonal in the basis of definite three-pion isospin, I πππ , so that one in fact recovers four independent relations, corresponding to I πππ = 0, 1, 2, 3. We also provide the generalized threshold expansion of K df , 3 $$ {\mathcal{K}}_{\mathrm{df},3} $$ for all channels, as well as parameterizations for all three-pion resonances present for I πππ = 0 and I πππ = 1. As an example of the utility of the generalized formalism, we present a toy implementation of the quantization condition for I πππ = 0, focusing on the quantum numbers of the ω and h 1 resonances.

Cleidoic eggs possess very efficient and orchestrated systems to protect the embryo from external microbes until hatch. The cuticle is a proteinaceous layer on the shell surface in many bird and some reptile species. An intact cuticle forms a pore plug to occlude respiratory pores and is an effective physical and chemical barrier against microbial penetration. The interior of the egg is assumed to be normally sterile, while the outer eggshell cuticle hosts microbes. The diversity of the eggshell microbiome is derived from both maternal microbiota and those of the nesting environment. The surface characteristics of the egg, outer moisture layer and the presence of antimicrobial molecules composing the cuticle dictate constituents of the microbial communities on the eggshell surface. The avian cuticle affects eggshell wettability, water vapor conductance and regulates ultraviolet reflectance in various ground-nesting species; moreover, its composition, thickness and degree of coverage are dependent on species, hen age, and physiological stressors. Studies in domestic avian species have demonstrated that changes in the cuticle affect the food safety of eggs with respect to the risk of contamination by bacterial pathogens such as Salmonella and Escherichia coli. Moreover, preventing contamination of internal egg components is crucial to optimize hatching success in bird species. In chickens there is moderate heritability (38%) of cuticle deposition with a potential for genetic improvement. However, much less is known about other bird or reptile cuticles. This review synthesizes current knowledge of eggshell cuticle and provides insight into its evolution in the clade reptilia. The origin, composition and regulation of the eggshell microbiome and the potential function of the cuticle as the first barrier of egg defense are discussed in detail. We evaluate how changes in the cuticle affect the food safety of table eggs and vertical transmission of pathogens in the production chain with respect to the risk of contamination. Thus, this review provides insight into the physiological and microbiological characteristics of eggshell cuticle in relation to its protective function (innate immunity) in egg-laying birds and reptiles.

Machine learning is among the most widely anticipated use cases for near-term quantum computers, however there remain significant theoretical and implementation challenges impeding its scale up. In particular, there is an emerging body of work which suggests that generic, data agnostic quantum machine learning (QML) architectures may suffer from severe trainability issues, with the gradient of typical variational parameters vanishing exponentially in the number of qubits. Additionally, the high expressibility of QML models can lead to overfitting on training data and poor generalisation performance. A promising strategy to combat both of these difficulties is to construct models which explicitly respect the symmetries inherent in their data, so-called geometric quantum machine learning (GQML). In this work, we utilise the techniques of GQML for the task of image classification, building new QML models which are equivariant with respect to reflections of the images. We find that these networks are capable of consistently and significantly outperforming generic ansatze on complicated real-world image datasets, bringing high-resolution image classification via quantum computers closer to reality. Our work highlights a potential pathway for the future development and implementation of powerful QML models which directly exploit the symmetries of data.

We have found an error in a statement following eq. (2.5) of our paper, concerning the function f (a, b, k) that first appears in that equation. The issue arises in the statement that it is convenient to take the function f (a, b, k) to be exchange symmetric with respect to its three arguments. This has the unwanted consequence of making six of the seven operators in the column vector of eq. (2.4) identically equal. This, in turn, implies that many operators are identically zero in the definite isospin basis, considered in section 2.4. To repair this, the last sentence of the paragraph containing eq. (2.4), starting “It is convenient for the subsequent…”, should be removed, as should footnote 3 and the next paragraph, beginning with “At this point, the reader may wonder why…”.

Abstract In this work, we use an extension of the quantization condition, given in ref. [1], to numerically explore the finite-volume spectrum of three relativistic particles, in the case that two-particle subsets are either resonant or bound. The original form of the relativistic three-particle quantization condition was derived under a technical assumption on the two- particle K matrix that required the absence of two-particle bound states or narrow two- particle resonances. Here we describe how this restriction can be lifted in a simple way using the freedom in the definition of the K-matrix-like quantity that enters the quantization condition. With this in hand, we extend previous numerical studies of the quantization condition to explore the finite-volume signature for a variety of two- and three-particle interactions. We determine the spectrum for parameters such that the system contains both dimers (two-particle bound states) and one or more trimers (in which all three particles are bound), and also for cases where the two-particle subchannel is resonant. We also show how the quantization condition provides a tool for determining infinite-volume dimer- particle scattering amplitudes for energies below the dimer breakup. We illustrate this for a series of examples, including one that parallels physical deuteron-nucleon scattering. All calculations presented here are restricted to the case of three identical scalar particles.

The chicken egg is a well-known complete food of human daily consumption which serves as a cost-effective, high-quality nutrient resource. About 30% of table eggs are directed to breaker plants in developed countries, leading to the generation of substantial eggshell (ES) waste, which is increasingly explored for potential value-added applications. The number of patents describing ES-based applications has increased dramatically in recent years. This review provides insight into the most recent patents published between 2015 and 2020, with focus on different engineering technologies for the screening, separation, and processing of ES. Screening technologies include detection of ES surface spots and glossiness, ES cracks, and mechanical properties, along with identification of chicken breed and enumeration of surface bacterial count. Collection and separation technologies describe separation strategies of ES from egg white (EW), egg yolk (EY), liquid egg, eggshell membrane (ESM), hatchlings, and cooked egg. Separation of ES from liquid eggs utilizes gravity, rotational forces, or air pressure. Processing of ES involves washing and sterilization along with cutting, crushing, and pulverization technologies that enable the collection of ES suitable for value-added applications. In addition, ES carving (mechanical and laser) opens up the realm of artwork and decoration. Furthermore, intact ES can be utilized for food serving. The exponential increase in innovative screening, separation, collection, and processing technologies reflects industrial interest to upscale low-value ES waste material, and is a first crucial step in the emergence of advanced technologies that exploit the biomedical, chemical, engineering, and environmental applications for ES.

The avian eggshell is a remarkable biomineral, which is essential for avian reproduction; its properties permit embryonic development in the desiccating terrestrial environment, and moreover, are critically important to preserve unfertilized egg quality for human consumption. This calcium carbonate (CaCO3) bioceramic is made of 95% calcite and 3.5% organic matrix; it protects the egg contents against microbial penetration and mechanical damage, allows gaseous exchange, and provides calcium for development of the embryonic skeleton. In vertebrates, eggshell occurs in the Sauropsida and in a lesser extent in Mammalia taxa; avian eggshell calcification is one of the fastest known CaCO3 biomineralization processes, and results in a material with excellent mechanical properties. Thus, its study has triggered a strong interest from the researcher community. The investigation of eggshell biomineralization in birds over the past decades has led to detailed characterization of its protein and mineral constituents. Recently, our understanding of this process has been significantly improved using high-throughput technologies (i.e., proteomics, transcriptomics, genomics, and bioinformatics). Presently, more or less complete eggshell proteomes are available for nine birds, and therefore, key proteins that comprise the eggshell biomineralization toolkit are beginning to be identified. In this article, we review current knowledge on organic matrix components from calcified eggshell. We use these data to analyze the evolution of selected matrix proteins and underline their role in the biological toolkit required for eggshell calcification in avian species. Amongst the panel of eggshell-associated proteins, key functional domains are present such as calcium-binding, vesicle-binding and protein-binding. These technical advances, combined with progress in mineral ultrastructure analyses, have opened the way for new hypotheses of mineral nucleation and crystal growth in formation of the avian eggshell, including transfer of amorphous CaCO3 in vesicles from uterine cells to the eggshell mineralization site. The enrichment of multi-omics datasets for bird species is critical to understand the evolutionary context for development of CaCO3 biomineralization in metazoans, leading to the acquisition of the robust eggshell in birds (and formerly dinosaurs).

Half-Heusler materials are strong candidates for thermoelectric applications due to their high weighted mobilities and power factors, which is known to be correlated to valley degeneracy in the electronic band structure. However, there are over 50 known semiconducting half-Heusler phases, and it is not clear how the chemical composition affects the electronic structure. While all the n-type electronic structures have their conduction band minimum at either the Γ- or X-point, there is more diversity in the p-type electronic structures, and the valence band maximum can be at either the Γ-, L-, or W-point. Here, we use high throughput computation and machine learning to compare the valence bands of known half-Heusler compounds and discover new chemical guidelines for promoting the highly degenerate W-point to the valence band maximum. We do this by constructing an “orbital phase diagram” to cluster the variety of electronic structures expressed by these phases into groups, based on the atomic orbitals that contribute most to their valence bands. Then, with the aid of machine learning, we develop new chemical rules that predict the location of the valence band maximum in each of the phases. These rules can be used to engineer band structures with band convergence and high valley degeneracy.

The bacterial load on the eggshell surface is a key factor in predicting the bacterial penetration and contamination of the egg interior. The eggshell cuticle is the first line of defense against vertical penetration by microbial food-borne pathogens such as Salmonella Enteritidis. Egg producers are increasingly introducing alternative caging systems into their production chain as animal welfare concerns become of greater relevance to today’s consumer. Stress that is introduced by hen aggression and modified nesting behavior in furnished cages can alter the physiology of egg formation and affect the cuticle deposition/quality. The goal of this study was to determine the impact of caging systems (conventional, enriched, free-run, and free-range), on eggshell cuticle parameters and the eggshell bacterial load. The cuticle plug thickness and pore length were higher in the free-range eggs as compared to conventional eggs. The eggshells from alternative caging (enriched and free-range) had a higher total cuticle as compared to conventional cages. A reduction in bacterial cell counts was observed on eggshells that were obtained from free-range eggs as compared to the enriched systems. An inverse correlation between the contact angle and Salmonella adherence was observed. These results indicate that the housing systems of layer hens can modify the cuticle quality and thereby impact bacterial adherence and food safety.

The eggshell membrane (ESM), mainly composed of collagen-like proteins, is readily available as a waste product of the egg industry. As a novel biomaterial, ESM is attractive for its applications in the nutraceutical, cosmetic, and pharmaceutical fields. This review provides the main information about the structure and chemical composition of the ESM as well as some approaches for its isolation and solubilization. In addition, the review focuses on the role and performance of bioactive ESM-derived products in various applications, while a detailed literature survey is provided. The evaluation of the safety of ESM is also summarized. Finally, new perspectives regarding the potential of ESM as a novel biomaterial in various engineering fields are discussed. This review provides promising future directions for comprehensive application of ESM.

Antibodies that can neutralize diverse HIV-1 strains develop in ~10–20% of HIV-1 infected individuals, and their elicitation is a goal of vaccine design. Such antibodies can also serve as therapeutics for those who have already been infected with the virus. Structural characterizations of broadly reactive antibodies in complex with the HIV-1 spike indicate that there are a limited number of sites of vulnerability on the spike. Analysis of their structures can help reveal commonalities that would be useful in vaccine design and provide insights on combinations of antibodies that can be used to minimize the incidence of viral resistance mutations. In this review, we give an update on recent structures determined of the spike in complex with broadly neutralizing antibodies in the context of all epitopes on the HIV-1 spike identified to date.

Excited-state contamination is one of the dominant uncertainties in lattice calculations of the nucleon axial-charge, gA. Recently published results in leading-order chiral perturbation theory (ChPT) predict the excited-state contamination to be independent of the nucleon interpolator and positive [1–3]. We reproduce these results using ChPT in infinite volume along with the Lellouch–Lüscher formalism to relate finite- and infinite-volume matrix elements. We then go beyond ChPT by using the experimentally determined Nπ scattering phase to estimate the correction due to the final-state interactions, both on the discrete energy levels and on the Lellouch–Lüscher factors. We find that, while individual Lellouch–Lüscher factors differ significantly, the overall effect on the excited-state contamination is small. However, empirical results from numerical lattice calculations show negative contamination (downward curvature), indicating that present-day calculations are not in the regime where the leading-order ChPT predictions apply. We show that, under plausible assumptions, one can reproduce the behavior of lattice correlators by postulating a sign change in the infinite-volume N→Nπ axial-vector transition amplitude roughly in the region of the Roper resonance. Improved data, either from experiment or from a lattice QCD calculation, would allow for a direct test of this postulate.

Eggshell (ES) and eggshell membrane (ESM) is a significant byproduct of the egg producing industry (Ahmed et al., 2019). Many studies have been undertaken to utilize ES waste for potential value added applications (Cordeiro and Hincke, 2011). Described here are the datasets from our evaluation of processed eggshell membrane powder (PEP) as a wound healing product using the mouse excisional wound splinting model (Ahmed et al., 2019). PEP biomaterial was characterized by proteomics using various extraction and solubilization strategies including moderate (lithium dodecyl sulphate (LDS) and urea/ammonium bicarbonate) and harsh conditions (3-mercaptopropionic acid (3-MPA) and NaOH/dimethylsulfoxide) in order to progressively overcome its stable, insoluble nature (Ahmed et al., 2019, Ahmed et al., 2017). Analysis of proteomic data allowed the relative abundance of the main PEP protein constituents to be determined. The efficacy of PEP for promotion of wound healing was assessed using the mouse excisional wound splinting model, and well-established semi-quantitative histological scoring. (More details about the PEP biomaterial characterization and its in vivo evaluation can be found in the related research article (Ahmed et al., 2019)). Keywords: Processed eggshell membrane powder, Proteomics, Wound healing, Histological scoring

The impact of Alzheimer's disease (AD) on the pupillary light response (PLR) is controversial, being dependent on the stage of the disease and on the experimental pupillometric protocols. The main hypothesis driving pupillometry research in AD is based on the concept that the AD-related neurodegeneration affects both the parasympathetic and the sympathetic arms of the PLR (cholinergic and noradrenergic theory), combined with additional alterations of the afferent limb, involving the melanopsin expressing retinal ganglion cells (mRGCs), subserving the PLR. Only a few studies have evaluated the value of pupillometry as a potential biomarker in AD, providing various results compatible with parasympathetic dysfunction, displaying increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum velocity of constriction (MCV) and maximum constriction acceleration (MCA) compared to controls. Decreased MCV and MCA appeared to be the most accurate of all PLR parameters allowing differentiation between AD and healthy controls while increased post-illumination pupillary response was the most consistent feature, however, these results could not be replicated by more recent studies, focusing on early and pre-clinical stages of the disease. Whether static or dynamic pupillometry yields useful biomarkers for AD screening or diagnosis remains unclear. In this review, we synopsize the current knowledge on pupillometric features in AD and other neurodegenerative diseases, and discuss potential roles of pupillometry in AD detection, diagnosis and monitoring, alone or in combination with additional biomarkers.

Coronavirus research has gained tremendous attention because of the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (nCoV or SARS-CoV-2). In this review, we highlight recent studies that provide atomic-resolution structural details important for the development of monoclonal antibodies (mAbs) that can be used therapeutically and prophylactically and for vaccines against SARS-CoV-2. Structural studies with SARS-CoV-2 neutralizing mAbs have revealed a diverse set of binding modes on the spike’s receptor-binding domain and N-terminal domain and highlight alternative targets on the spike. We consider this structural work together with mAb effects in vivo to suggest correlations between structure and clinical applications. We also place mAbs against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses in the context of the SARS-CoV-2 spike to suggest features that may be desirable to design mAbs or vaccines capable of conferring broad protection.

Seaweeds comprise ca. 12,000 species. Global annual harvest is ca. 30.13 million metric tonnes, (valued ca. $11.7 billion USD in 2016) for various commercial applications. The growing scope of seaweed-based applications in food, agricultural fertilizers, animal feed additives, pharmaceuticals, cosmetics and personal care is expected to boost market demand. Agriculture and animal feed applications held the second largest seaweed market share in 2017, and the combined market is anticipated to reach much higher values by 2024 due to the impacts of current research and development targeting enhanced animal health and productivity. In general, seaweeds have been utilized in animal feed as a rich source of carbohydrates, protein, minerals, vitamins and dietary fibers with relatively well-balanced amino acid profiles and a unique blend of bioactive compounds. Worldwide, the animal nutrition market is largely driven by rising demand for poultry feeds, which represents ca. 47% of the total consumption for all animal nutrition. This review provides an overview of the utilization of specific seaweeds as sustainable feed sources for poultry production, including a detailed survey of seaweed-supplemented diets on growth, performance, gastrointestinal flora, disease, immunity and overall health of laying/broiler hens. Anti-microbial effects of seaweeds are also discussed.

Avian eggshell membrane (ESM) is a natural biomaterial that has been used as an alternative natural bandage to cure wounds, and is available in large quantities from egg industries. We have previously demonstrated that processed eggshell membrane powder (PEP), aiming to be used in a low cost wound healing product, possesses anti-inflammatory properties. In this study, we further investigated effects of PEP on MMP activities in vitro (a dermal fibroblast cell culture system) and in vivo (a mouse skin wound healing model). Three days incubation with PEP in cell culture led to rearrangement of the actin-cytoskeleton and vinculin in focal adhesions and increased syndecan-4 shedding. In addition, we observed increased matrix metalloproteinase type 2 (MMP-2) enzyme activation, without effects on protein levels of MMP-2 or its regulators (membrane type 1 (MT1)-MMP and tissue inhibitor of matrix metalloproteinase type 2 (TIMP-2). Longer incubation (10 days) led to increased protein levels of MMP-2 and its regulators. We also observed an increased alpha-smooth muscle actin (α-SMA) production, suggesting an effect of PEP on myofibroblast differentiation. In vivo, using the mouse skin wound healing model, PEP treatment (3 days) increased MMP activity at the wound edges, along with increased MMP-2 and MMP-9 protein levels, and increased keratinocyte cell proliferation. Altogether, our data suggest PEP stimulates MMP activity, and with a positive effect on early cellular events during wound healing.