Optical creation of a supercrystal with three-dimensional nanoscale periodicity.

Stimulation with ultrafast light pulses can realize and manipulate states of matter with emergent structural, electronic and magnetic phenomena. However, these non-equilibrium phases are often transient and the challenge is to stabilize them as persistent states. Here, we show that atomic-scale PbTiO3/SrTiO3 superlattices, counterpoising strain and polarization states in alternate layers, are converted by sub-picosecond optical pulses to a supercrystal phase. This phase persists indefinitely under ambient conditions, has not been created via equilibrium routes, and can be erased by heating. X-ray scattering and microscopy show this unusual phase consists of a coherent three-dimensional structure with polar, strain and charge-ordering periodicities of up to 30 nm. By adjusting only dielectric properties, the phase-field model describes this emergent phase as a photo-induced charge-stabilized supercrystal formed from a two-phase equilibrium state. Our results demonstrate opportunities for light-activated pathways to thermally inaccessible and emergent metastable states.

Quantification of flexoelectricity in PbTiO3/SrTiO3 superlattice polar vortices using machine learning and phase-field modeling.

Flexoelectricity refers to electric polarization generated by heterogeneous mechanical strains, namely strain gradients, in materials of arbitrary crystal symmetries. Despite more than 50 years of work on this effect, an accurate identification of its coupling strength remains an experimental challenge for most materials, which impedes its wide recognition. Here, we show the presence of flexoelectricity in the recently discovered polar vortices in PbTiO3/SrTiO3 superlattices based on a combination of machine-learning analysis of the atomic-scale electron microscopy imaging data and phenomenological phase-field modeling. By scrutinizing the influence of flexocoupling on the global vortex structure, we match theory and experiment using computer vision methodologies to determine the flexoelectric coefficients for PbTiO3 and SrTiO3. Our findings highlight the inherent, nontrivial role of flexoelectricity in the generation of emergent complex polarization morphologies and demonstrate a viable approach to delineating this effect, conducive to the deeper exploration of both topics.

Phase coexistence and electric-field control of toroidal order in oxide superlattices.

Systems that exhibit phase competition, order parameter coexistence, and emergent order parameter topologies constitute a major part of modern condensed-matter physics. Here, by applying a range of characterization techniques, and simulations, we observe that in PbTiO3/SrTiO3 superlattices all of these effects can be found. By exploring superlattice period-, temperature- and field-dependent evolution of these structures, we observe several new features. First, it is possible to engineer phase coexistence mediated by a first-order phase transition between an emergent, low-temperature vortex phase with electric toroidal order and a high-temperature ferroelectric a1/a2 phase. At room temperature, the coexisting vortex and ferroelectric phases form a mesoscale, fibre-textured hierarchical superstructure. The vortex phase possesses an axial polarization, set by the net polarization of the surrounding ferroelectric domains, such that it possesses a multi-order-parameter state and belongs to a class of gyrotropic electrotoroidal compounds. Finally, application of electric fields to this mixed-phase system permits interconversion between the vortex and the ferroelectric phases concomitant with order-of-magnitude changes in piezoelectric and nonlinear optical responses. Our findings suggest new cross-coupled functionalities.

Design of Heteronuclear Metalloenzymes.

Heteronuclear metalloenzymes catalyze some of the most fundamentally interesting and practically useful reactions in nature. However, the presence of two or more metal ions in close proximity in these enzymes makes them more difficult to prepare and study than homonuclear metalloenzymes. To meet these challenges, heteronuclear metal centers have been designed into small and stable proteins with rigid scaffolds to understand how these heteronuclear centers are constructed and the mechanism of their function. This chapter describes methods for designing heterobinuclear metal centers in a protein scaffold by giving specific examples of a few heme-nonheme bimetallic centers engineered in myoglobin and cytochrome c peroxidase. We provide step-by-step procedures on how to choose the protein scaffold, design a heterobinuclear metal center in the protein scaffold computationally, incorporate metal ions into the protein, and characterize the resulting metalloproteins, both structurally and functionally. Finally, we discuss how an initial design can be further improved by rationally tuning its secondary coordination sphere, electron/proton transfer rates, and the substrate affinity.

Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films.

Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180° domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band-excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices.

Observation of polar vortices in oxide superlattices.

The complex interplay of spin, charge, orbital and lattice degrees of freedom provides a plethora of exotic phases and physical phenomena. In recent years, complex spin topologies have emerged as a consequence of the electronic band structure and the interplay between spin and spin-orbit coupling in materials. Here we produce complex topologies of electrical polarization--namely, nanometre-scale vortex-antivortex (that is, clockwise-anticlockwise) arrays that are reminiscent of rotational spin topologies--by making use of the competition between charge, orbital and lattice degrees of freedom in superlattices of alternating lead titanate and strontium titanate layers. Atomic-scale mapping of the polar atomic displacements by scanning transmission electron microscopy reveals the presence of long-range ordered vortex-antivortex arrays that exhibit nearly continuous polarization rotation. Phase-field modelling confirms that the vortex array is the low-energy state for a range of superlattice periods. Within this range, the large gradient energy from the vortex structure is counterbalanced by the corresponding large reduction in overall electrostatic energy (which would otherwise arise from polar discontinuities at the lead titanate/strontium titanate interfaces) and the elastic energy associated with epitaxial constraints and domain formation. These observations have implications for the creation of new states of matter (such as dipolar skyrmions, hedgehog states) and associated phenomena in ferroic materials, such as electrically controllable chirality.

The ABCs of entrustable professional activities: an overview of 'entrustable professional activities' in medical education.

Consultants regularly need to decide whether a trainee can be entrusted to perform a clinical activity independently. 'Entrustable professional activities' (EPA) provide a framework for justifying and better utilising supervisor entrustment decisions for trainee feedback and assessment in the workplace. Since being proposed by Olle ten Cate in 2005, EPA are emerging as an integral part of many international medical curricula, and are being considered by the Royal Australasian College of Physicians in the current review of physician training. EPA are defined as tasks or responsibilities that can be entrusted to a trainee once sufficient competence is reached to allow for unsupervised practice. An example might be to entrust a trainee to 'Initiate and co-ordinate care of the palliative patient' with only off-site or indirect supervision. Rather than attempting to measure directly each of the many separate competencies required to undertake such a complex task, EPA direct the trainee and supervisor's attention to the trainee's performance in a limited number of selected, representative, important day-to-day activities. EPA-based assessment is gaining momentum, amongst significant concerns regarding feasibility of implementation. While the optimal process for designing and implementing EPA remains to be determined, it is an assessment strategy where the over-arching goal of optimal patient care remains in clear sight. This review explores the central role of trust in medical training, the case for EPA and potential barriers to implementing EPA-based assessment.

Mitotic phosphorylation of Bloom helicase at Thr182 is required for its proteasomal degradation and maintenance of chromosomal stability.

Mutations in Bloom helicase (BLM) lead to Bloom Syndrome (BS). BS is characterized by multiple clinical manifestations including predisposition to a wide spectrum of cancers. Studies have revealed the mechanism of BLM recruitment after stalled replication and its role during the repair of DNA damage. We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3ß- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates. Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges. Consequently lack of Thr182 phosphorylation leads to multiple manifestations of chromosomal instability including increased levels of DNA damage, lagging chromatin, micronuclei formation, breaks and quadriradials. Hence Thr182 phosphorylation on BLM has two functions-it regulates BLM turnover during mitosis and also helps to maintain the chromosomal stability.

Measurement of transient atomic displacements in thin films with picosecond and femtometer resolution.

We report measurements of the transient structural response of weakly photo-excited thin films of BiFeO3, Pb(Zr,Ti)O3, and Bi and time-scales for interfacial thermal transport. Utilizing picosecond x-ray diffraction at a 1.28 MHz repetition rate with time resolution extending down to 15 ps, transient changes in the diffraction angle are recorded. These changes are associated with photo-induced lattice strains within nanolayer thin films, resolved at the part-per-million level, corresponding to a shift in the scattering angle three orders of magnitude smaller than the rocking curve width and changes in the interlayer lattice spacing of fractions of a femtometer. The combination of high brightness, repetition rate, and stability of the synchrotron, in conjunction with high time resolution, represents a novel means to probe atomic-scale, near-equilibrium dynamics.

Improved pyroelectric figures of merit in compositionally graded PbZr1-xTixO3 thin films.

Pyroelectric materials have been widely used for a range of thermal-related applications including thermal imaging/sensing, waste heat energy conversion, and electron emission. In general, the figures of merit for applications of pyroelectric materials are proportional to the pyroelectric coefficient and inversely proportional to the dielectric permittivity. In this context, we explore single-layer and compositionally graded PbZr1-xTixO3 thin-film heterostructures as a way to independently engineer the pyroelectric coefficient and dielectric permittivity of materials and increase overall performance. Compositional gradients in thin films are found to produce large strain gradients which generate large built-in potentials in the films that can reduce the permittivity while maintaining large pyroelectric response. Routes to enhance the figures of merit of pyroelectric materials by 3-12 times are reported, and comparisons to standard materials are made.

Effect of growth induced (non)stoichiometry on interfacial conductance in LaAlO3/SrTiO3.

We demonstrate a link between the growth process, the stoichiometry of LaAlO(3), and the interfacial electrical properties of LaAlO(3)/SrTiO(3) heterointerfaces. Varying the relative La:Al cation stoichiometry by a few atomic percent in films grown at 1×10(-3) Torr results in a 2 and 7 order-of-magnitude change in the 300 and 2 K sheet resistance, respectively, with highly conducting states occurring only in La-deficient or Al-excess films. Further reducing the growth pressure results in an increase of the carrier density and a dramatic change in mobility. We discuss the relative contributions of intrinsic and extrinsic effects in controlling the physical properties of this widely studied system.

Note: electrical and thermal characterization of a ferroelectric thin film with an electro-thermal nanoprobe.

The localized temperature-dependent piezoelectric response of ferroelectric barium strontium titanate (BST) thin films is studied using an electro-thermal (ET) nanoprobe. The ET probe provides independent electrical and thermal excitation to a nanometer-scale volume of the specimen and is capable of detecting the phase transition temperature of the BST thin films. The piezoresponse measured by the ET probe follows the temperature dependence of the piezoelectric constant, whereas with bulk heating the response follows the temperature dependence of the spontaneous polarization. The observed differences stem from the localized inhomogeneous electro-thermal field distribution at the specimen.

Effect of 90° domain walls on the low-field permittivity of PbZr(0.2)Ti(0.8)O3 thin films.

We report on the contribution of 90° ferroelastic domain walls in strain-engineered PbZr(0.2)Ti(0.8)O(3) thin films to the room-temperature permittivity. Using a combination of phenomenological Ginzburg-Landau-Devonshire polydomain thin-film models and epitaxial thin-film growth and characterization, the extrinsic or domain wall contribution to the low-field, reversible dielectric response is evaluated as a function of increasing domain wall density. Using epitaxial thin-film strain we have engineered a set of samples that possess a known quantity of 90° domain walls that act as a model system with which to probe the contribution from these ferroelastic domain walls. We observe a strong enhancement of the permittivity with increasing domain wall density that matches the predictions of the phenomenological models. Additionally, we report experimentally measured bounds to domain wall stiffness in such PbZr(0.2)Ti(0.8)O(3) thin films as a function of domain wall density and frequency.

X-ray linear dichroism dependence on ferroelectric polarization.

X-ray absorption spectroscopy and photoemission electron microscopy are techniques commonly used to determine the magnetic properties of thin films, crystals, and heterostructures. Recently, these methods have been used in the study of magnetoelectrics and multiferroics. The analysis of such materials has been compromised by the presence of multiple order parameters and the lack of information on how to separate these coupled properties. In this work, we shed light on the manifestation of dichroism from ferroelectric polarization and atomic structure using photoemission electron microscopy and x-ray absorption spectroscopy. Linear dichroism arising from the ferroelectric order in the PbZr0:2Ti0:8O3 thin films was studied as a function of incident x-ray polarization and geometry to unambiguously determine the angular dependence of the ferroelectric contribution to the dichroism. These measurements allow us to examine the contribution of surface charges and ferroelectric polarization as potential mechanisms for linear dichroism. The x-ray linear dichroism from ferroelectric order revealed an angular dependence based on the angle between the ferroelectric polarization direction and the x-ray polarization axis, allowing a formula for linear dichroism in ferroelectric samples to be defined.

Direct observation of ferroelectric domain switching in varying electric field regimes using in situ TEM.

In situ Transmission Electron Microscopy (TEM) techniques can potentially fill in gaps in the current understanding interfacial phenomena in complex oxides. Select multiferroic oxide materials, such as BiFeO(3) (BFO), exhibit ferroelectric and magnetic order, and the two order parameters are coupled through a quantum-mechanical exchange interaction. The magneto-electric coupling in BFO allows control of the ferroelectric and magnetic domain structures via applied electric fields. Because of these unique properties, BFO and other magneto-electric multiferroics constitute a promising class of materials for incorporation into devices such as high-density ferroelectric and magnetoresistive memories, spin valves, and magnetic field sensors. The magneto-electric coupling in BFO is mediated by volatile ferroelastically switched domains that make it difficult to incorporate this material into devices. To facilitate device integration, an understanding of the microstructural factors that affect ferroelastic relaxation and ferroelectric domain switching must be developed. In this article, a method of viewing ferroelectric (and ferroelastic) domain dynamics using in situ biasing in TEM is presented. The evolution of ferroelastically switched ferroelectric domains in BFO thin films during many switching cycles is investigated. Evidence of partial domain nucleation, propagation, and switching even at applied electric fields below the estimated coercive field is revealed. Our observations indicate that the occurrence of ferroelastic relaxation in switched domains and the stability of these domains is influenced the applied field as well as the BFO microstructure. These biasing experiments provide a real time view of the complex dynamics of domain switching and complement scanning probe techniques. Quantitative information about domain switching under bias in ferroelectric and multiferroic materials can be extracted from in situ TEM to provide a predictive tool for future device development.

Effect of 90° domain walls and thermal expansion mismatch on the pyroelectric properties of epitaxial PbZr0.2Ti0.8O3 thin films.

We have investigated the contribution of 90° domain walls and thermal expansion mismatch to pyroelectricity in PbZr(0.2)Ti(0.8)O(3) thin films. The first phenomenological models to include extrinsic and secondary contributions to pyroelectricity in polydomain films predict significant extrinsic contributions (arising from the temperature-dependent motion of domain walls) and large secondary contributions (arising from thermal expansion mismatch between the film and the substrate). Phase-sensitive pyroelectric current measurements are applied to model thin films for the first time and reveal a dramatic increase in the pyroelectric coefficient with increasing fraction of in-plane oriented domains and thermal expansion mismatch.

Replication of Japanese encephalitis virus in mouse brain induces alterations in lymphocyte response.

The experimental model using intracerebral (i.c.) challenge was employed in many studies evaluating the protection against disease induced by Japanese encephalitis virus (JEV). We investigated alterations in peripheral lymphocyte response caused by i.c. infection of mice with JEV. Splenocytes from the i.c.-infected mice showed suppressed proliferative response to concanavalin A (con A) and anti-CD3 antibody stimulation. At the same time, the expression of CD25 (IL-2R) and production of IL-2 was inhibited. Addition of anti-CD28 antibody restored the decreased anti-CD3 antibody-mediated proliferation in the splenocytes. Moreover, the number of con A-stimulated cells secreting IL-4 was significantly reduced in splenocytes from i.c.-infected mice. These studies suggested that the i.c. infection with JEV might involve additional immune modulation effects due to massive virus replication in the brain.

Safety evaluation of a standardized phytochemical composition extracted from Bacopa monnieri in Sprague--Dawley rats.

BacoMind is an enriched phytochemical composition derived from Bacopa monnieri, a common medicinal plant having multiple uses in the traditional system of medicine and particularly used as a memory enhancing agent for centuries. The plant and its extracts have been evaluated for anti-inflammatory, cardio tonic, sedative and neuro-muscular blocking activities. In view of the extensive use of this plant, BacoMind , standardized to bioactive compounds was evaluated in a series of toxicity studies, to confirm the safety of its usage. BacoMind , on single oral administration had a median lethal dose of 2,400 mg/kg in Sprague-Dawley rats. In a 14 day repeated dose oral toxicity study in rats, except for mild lowering in body weight gain in male rats, it was found to be tolerated well up to the dose of 500 mg/kg. A subchronic oral toxicity study for 90 days in rats at the dose levels of 85, 210 and 500 mg/kg did not reveal any evidence of toxicity with respect to clinical signs, neurological examination, food consumption, body weight gain, haematological and blood biochemistry parameters. The absolute and relative organ weight of vital organs did not differ significantly from that of the control. Necropsy and histopathological examination, did not reveal any remarkable and treatment related changes. A no-observed adverse effect level of 500 mg/kg body weight was established in rats.

Coastal resource complexes of South India: options for sustainable management.

India's coastal resource complexes were traditionally characterized by a continuum of 'common property resources' or 'commons' that stretched from the shores to the seas. The continuum aided the existence of sustainable livelihood systems for local communities. Today, fragmented policy approaches and economic welfare schemes have caused the disintegration of community control over the continuum. As a consequence, livelihood systems of local communities have declined. The introduction of coastal management guidelines in the 1990s has exacerbated the situation. With reference to a coastal village located in the State of Kerala in South West India, the paper describes the trajectory of unsustainable change that has taken place in the coastal area resource complexes of the country. The paper argues for restoring the continuum of commons in the study area through community driven systems of natural resource management that are based on networks of nested institutions.