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Diatoms are single cell microalgae enclosed in silica exoskeletons (frustules) that provide inspiration for advanced hybrid nanostructure designs mimicking multi-scale porosity to achieve outstanding mechanical and optical properties. Interrogating the structure and properties of diatoms down to nanometer scale leads to breakthrough advances reported here in the nanomechanical characterization of Coscinodiscus oculus-iridis diatom pure silica frustules, as well as of air-dried and wet cells with organic content. Static and dynamic mode Atomic Force Microscopy (AFM) and in-SEM nanoindentation revealed the peculiarities of diatom response with separate contributions from material nanoscale behavior and membrane deformation of the entire valve. Significant differences in the nanomechanical properties of the different frustule layers were observed. Furthermore, the deformation response depends strongly on silica hydration and on the support from the internal organic content. The cyclic loading revealed that the average compliance of the silica frustule is 0.019 m/N and increases with increasing number of cycles. The structure–mechanical properties relationship has a direct impact on the vibrational properties of the frustule as a complex micrometer-sized mechanical system. Lessons from Nature’s nanostructuring of diatoms open up pathways to new generations of nano- and microdevices for electronic, electromechanical, photonic, liquid, energy storage, and other applications.

As single-cell datasets grow in sample size, there is a critical need to characterize cell states that vary across samples and associate with sample attributes, such as clinical phenotypes. Current statistical approaches typically map cells to clusters and then assess differences in cluster abundance. Here we present co-varying neighborhood analysis (CNA), an unbiased method to identify associated cell populations with greater flexibility than cluster-based approaches. CNA characterizes dominant axes of variation across samples by identifying groups of small regions in transcriptional space-termed neighborhoods-that co-vary in abundance across samples, suggesting shared function or regulation. CNA performs statistical testing for associations between any sample-level attribute and the abundances of these co-varying neighborhood groups. Simulations show that CNA enables more sensitive and accurate identification of disease-associated cell states than a cluster-based approach. When applied to published datasets, CNA captures a Notch activation signature in rheumatoid arthritis, identifies monocyte populations expanded in sepsis and identifies a novel T cell population associated with progression to active tuberculosis.

We consider the task of Inverse Reinforcement Learning in Contextual Markov Decision Processes (MDPs). In this setting, contexts, which define the reward and transition kernel, are sampled from a distribution. In addition, although the reward is a function of the context, it is not provided to the agent. Instead, the agent observes demonstrations from an optimal policy. The goal is to learn the reward mapping, such that the agent will act optimally even when encountering previously unseen contexts, also known as zero-shot transfer. We formulate this problem as a non-differential convex optimization problem and propose a novel algorithm to compute its subgradients. Based on this scheme, we analyze several methods both theoretically, where we compare the sample complexity and scalability, and empirically. Most importantly, we show both theoretically and empirically that our algorithms perform zero-shot transfer (generalize to new and unseen contexts). Specifically, we present empirical experiments in a dynamic treatment regime, where the goal is to learn a reward function which explains the behavior of expert physicians based on recorded data of them treating patients diagnosed with sepsis.

Background Immunosuppressive and anti-cytokine treatment may have a protective effect for patients with COVID-19. Understanding the immune cell states shared between COVID-19 and other inflammatory diseases with established therapies may help nominate immunomodulatory therapies. Methods To identify cellular phenotypes that may be shared across tissues affected by disparate inflammatory diseases, we developed a meta-analysis and integration pipeline that models and removes the effects of technology, tissue of origin, and donor that confound cell-type identification. Using this approach, we integrated > 300,000 single-cell transcriptomic profiles from COVID-19-affected lungs and tissues from healthy subjects and patients with five inflammatory diseases: rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and interstitial lung disease. We tested the association of shared immune states with severe/inflamed status compared to healthy control using mixed-effects modeling. To define environmental factors within these tissues that shape shared macrophage phenotypes, we stimulated human blood-derived macrophages with defined combinations of inflammatory factors, emphasizing in particular antiviral interferons IFN-beta (IFN-β) and IFN-gamma (IFN-γ), and pro-inflammatory cytokines such as TNF. Results We built an immune cell reference consisting of > 300,000 single-cell profiles from 125 healthy or disease-affected donors from COVID-19 and five inflammatory diseases. We observed a CXCL10+ CCL2+ inflammatory macrophage state that is shared and strikingly abundant in severe COVID-19 bronchoalveolar lavage samples, inflamed RA synovium, inflamed CD ileum, and UC colon. These cells exhibited a distinct arrangement of pro-inflammatory and interferon response genes, including elevated levels of CXCL10, CXCL9, CCL2, CCL3, GBP1, STAT1, and IL1B. Further, we found this macrophage phenotype is induced upon co-stimulation by IFN-γ and TNF-α. Conclusions Our integrative analysis identified immune cell states shared across inflamed tissues affected by inflammatory diseases and COVID-19. Our study supports a key role for IFN-γ together with TNF-α in driving an abundant inflammatory macrophage phenotype in severe COVID-19-affected lungs, as well as inflamed RA synovium, CD ileum, and UC colon, which may be targeted by existing immunomodulatory therapies.

Analytical solution for a rigid line inclusion embedded in an infinite-extended plane under non-uniform loading is still a challenging problem in inclusion mechanics, which has both theoretical and applied significance in material engineering. In this paper, by directly employing Kolosov–Muskhelishvili stress potentials, a rigid line inclusion interacting with a generalized singularity is addressed in the framework of plane deformation, with the help of the superposition principle. It should be pointed out that the generalized singularity in this study can represent a point force, an edge dislocation, a point moment, a point nucleus of strain, and even remote uniform load, etc. The solutions can be used as kernel functions for integral equation formulations of rigid line inclusion–substrate system models using the Green’s function method. With this framework, stress field and stress intensity factors at the line inclusion ends are analyzed. The application of the solutions is demonstrated with two simple examples: (i) the rigid line inclusion under remote loading is studied, and it is strictly confirmed with rigorous proof that the remote shear load will not arouse stress concentration; (ii) a rigid line inclusion interacting with a dislocation is investigated, and the full solution is given. These examples also partially validate the general solution derived this study.

How innate T cells (ITC), including invariant natural killer T (iNKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells, maintain a poised effector state has been unclear. Here we address this question using low-input and single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover a continuous ‘innateness gradient’, with adaptive T cells at one end, followed by MAIT, iNKT, γδ T and natural killer cells at the other end. Single-cell RNA-seq reveals four broad states of innateness, and heterogeneity within canonical innate and adaptive populations. Transcriptional and functional data show that innateness is characterized by pre-formed mRNA encoding effector functions, but impaired proliferation marked by decreased baseline expression of ribosomal genes. Together, our data shed new light on the poised state of ITC, in which innateness is defined by a transcriptionally-orchestrated trade-off between rapid cell growth and rapid effector function., Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

Systematische Entwicklungsmethoden koennen helfen, die steigende Komplexitaet moderner Hybridantriebsstraenge zu bewaeltigen. Ein weiteres Charakteristikum ist die zentrale Rolle der Hybridsteuerungssoftware bei der Erreichung der Fahrzeuganforderungen, denn erst das nach Systemgesichtspunkten optimierte Zusammenspiel von Verbrennungsmotor und E-Maschine erlaubt die volle Ausschoepfung einer bestimmten Hybridtechnologie. Die Hybridsoftware muss dazu nicht nur fuer ein einzelnes System optimiert werden, sondern fuer den breiten Einsatz muessen Modularitaet und Skalierbarkeit gegeben sein. Beschrieben wird zum einen das konsequente Herunterbrechen und Verknuepfen der Anforderungen von der Fahrzeugebene auf die einzelnen Subsysteme und Komponenten. Zum anderen ist die Notwendigkeit, moeglichst viele Anwendungsfaelle und Hybridtopologien abdecken zu koennen, Ausgangspunkt dafuer, dass diese Anforderungen bis auf die Hybridsteuerung heruntergebrochen werden muessen. Die modulare Architektur basierend auf den heruntergebrochenen Anforderungen erlaubt effiziente Testbarkeit, einfache Kalibrierbarkeit, gute Wartbarkeit und effektive Wiederverwendbarkeit.

Residual elastic strains in a bent bar of titanium alloy Ti-6Al-4V were measured using high energy diffraction on station 16.3 at SRS Daresbury. Using a single bounce Laue crystal monochromator, diffraction peaks were collected for reflections (00.2), (10.1), (10.2) and (11.0) from the hcp alpha phase of the titanium alloy. Reference values of the lattice spacing for each of the reflections were found from the diffraction pattern collected from a stress-free sampling volume. The residual elastic strain values calculated on the basis of each reflection were then computed and plotted as a function of position across the bent bar. The average macroscopic residual elastic strain was computed using an averaging procedure taking into account the multiplicity of each reflection. Energy dispersive white beam diffraction from the same bent bar was used to collect diffraction patterns over the range of lattice spacings between 0.8 and 2.2 A. Detector calibration was carried out using the procedure described in Liu et al. (2005) and detailed interpretation of the energy dispersive profiles was carried out allowing the identification of average residual elastic strains in the two principal phases present in the titanium alloy considered, the α-Ti hcp and the β-Ti bcc phases. Peak-specific residual strain profiles computed on the basis of monochromatic measurements show significant differences reflecting the variation in the elastic and plastic properties with grain orientation, i.e., crystal anisotropy. Using the contrast between the elastic and plastic properties of different directions within the α-Ti hcp lattice, the difference between residual elastic strains measured for (00.2) and (11.0) reflections was plotted, as well as the ‘difference strain’ between (00.2) and (10.1) reflections. These profiles show a good qualitative correlation with the plastic strain profile introduced by inelastic bending that was computed from the analysis of Pawley refinement of the energy-dispersive diffraction measurements.

This paper presents a method for the calibration of parameters of coupled damage-plasticity models for concrete. The determination procedure uses the experimental fact that during the fracture process in concrete in tension a considerable part of energy dissipation occurs via a plastic frictional mechanism hitherto disregarded in many constitutive models. The procedure developed provides a consistent and rational way of determining the parameters for coupled damage-plasticity models of concrete. We highlight the advantages of the thermodynamic approach that serves as the basis for the constitutive model used here, and give a simple one-dimensional example as an illustration of the calibration process. © Springer 2006.

The progression of structural material towards failure may be thought of in terms of the evolution of the population of defects that it contains. An important statistical characteristic of the defect population is its size distribution. In the present paper we review the results of experimental observations of defect size evolution during damage accumulation due to different mechanisms and at different scales, i.e. creep bubbles, pores and cavities. We consider the probability density functions and cumulative density functions for defect size distributions, and identify several types of evolution observed. We also focus on the appearance of a 'tail' of large size defects, and discuss whether it could be used as an indicator of the transition to a new structural level or scale. © 2004 Kluwer Academic Publishers.

Resistance to dislocation glide in slip bands due to the presence of other dislocations may be represented by an additional term in the integral equation formulation of the equilibrium state. As a consequence, the asymptotic behaviour of dislocation density at the edge of interval is modified from the conventional square root singularity. We propose an efficient and fast numerical method that is suitable for solving the resulting singular equations of the second kind based on the Gauss-Jacobi quadrature. The quadrature formulae involve fixed nodal points and provide exact results for polynomials up to degree 2n-1, where n is the number of nodes. A numerical example of the application of the Gauss-Jacobi rule to a slip band problem is provided as a demonstration of the validity of the method.

A through thickness crack traversing a laminate and approaching an interface weakened by the presence of a small debonding defect is analysed in the case when the defect is fully embedded in the K-field of the main crack. Plane approximation estimates of critical interfacial strength for crack deflection are compared with 3D calculations using integral equation and weight function formulations.

Propagation of a crack through inhomogeneous media is considered in the variational formulation, whereby the path corresponding to the extremum of energy release during fracture is sought. A non-linear differential equation is obtained for the crack trajectory in an inhomogeneous medium subjected to specified tensile loading. A linearized form of this equation is investigated in order to characterise the crack propagation in media with different effective characteristics.

Frequency conversion process is studied in a medium of atoms with a $\Lambda$ configuration of levels, where transition between two lower states is driven by a microwave field. In this system, conversion efficiency can be very high by virtue of the effect of electromagnetically induced transparency (EIT). Depending on intensity of the microwave field, two regimes of EIT are realized: ''dark-state'' EIT for the weak field, and Autler-Townes-type EIT for the strong one. We study both cases via analytical and numerical solution and find optimum conditions for the conversion., Comment: 15 pages, 5 figures

A numerically efficient and fast method of solution for cracks or slip bands with a crack opening or shearing displacement-dependent cohesive stress can be developed on the basis of a Gauss-Chebyshev quadrature rule for hypersingular integrals. The resulting iterative scheme allows different 'hardening' or 'bridging' laws to be explored in a consistent manner.

This paper focuses on the study of linear and non-linear surface and internal waves, in a complete setting, using a two-layer model of a stratified fluid. The respective Korteweg-de Vries evolutionary equations have been obtained, analysed, and compared with the ‘rigid lid’ model data. Boussinesq-type equations have been derived for the interacting modes pertaining to one type and to different types. It is shown that in addition to the known mechanisms of interaction between internal and surface waves, interaction between long non-linear baroclinic modes and barotropic modes, propagating in the same direction, is likely in such a system.

We show that laser cooling by coherent population trapping in case of zero radiation force — when atomic evolution is due to only momentum diffusion — can be effectively described by use of the Fokker-Planck equation for the atomic distribution function. Our quasiclassical approach allows numerically and analytically to investigate the dynamics and the efficiency of the cooling process. It is shown that both the evolution of the momentum distribution and the limit of the cooling are determined by the degree of incompleteness of coherent population trapping.

Non-linear and solitary surface waves represent one of the most intriguing and thoroughly investigated phenomena in ocean dynamics. Up to now, a considerable number of results have been obtained, which are related to the study of solitary waves in the coastal shelf zone, and their propagation and transformation under the effect of various factors. In the majority of such studies, the sea bottom surface was assumed to be impervious to fluid. Only some of them, e.g. refs 1–4, considered the propagation of waves in the limited layers of fluids on the pervious (porous) bases. At the same time, Shepard [5] and Nikolaevsky [6] pointed out that the bottom surface structure on the shelf is often porous. In this case, the pervious layer represents a porous matrix (possibly deformable) completely filled with fluid. Its density is different from the free fluid density.

A prototype of the Hilbert-transform spectrum analyzer based on the Josephson junctions is described and first spectral measurements are demonstrated in millimeter-wave band. The measurements in the whole millimeter-wave band may be carried out by this spectrum analyzer with resolution as low as 2 GHz and during a time interval as low as a few milliseconds. According to this set of parameters, this Josephson-effect spectrum analyzer may be used for microwave diagnostics of the thermonuclear plasma.