Spontaneous Atomic-Scale Polar Skyrmions and Merons on a SrTiO3 (001) Surface: Defect Engineering for Emerging Topological Orders.

The emergence of nontrivial topological order in condensed matter has been attracting a great deal of attention owing to its promising technological applications in novel functional nanodevices. In ferroelectrics, the realization of polar topological order at an ultimately small scale is extremely challenging due to the lack of chiral interaction and the critical size of the ferroelectricity. Here, we break through these limitations and demonstrate that the ultimate atomic-scale polar skyrmion and meron (∼2 nm) can be induced by engineering oxygen vacancies on the SrTiO3 (001) surface based on first-principles calculations. The paraelectric-to-antiferrodistortive phase transition leads to a novel topological transition from skyrmion to meron, indicating phase-topology correlations. We also discuss accumulating and driving polar skyrmions based on the oxygen divacancy model; these results and the recent discovery of defect engineering techniques suggest the possibility of arithmetic operations on topological numbers through the natural self-organization and diffusion features of oxygen vacancies.

Mechanical Rippling for Diverse Ferroelectric Topologies in Otherwise Nonferroelectric SrTiO_{3} Nanofilms.

Polar topological structures such as skyrmions and merons have become an emerging research field due to their rich functionalities and promising applications in information storage. Up to now, the obtained polar topological structures are restricted to a few limited ferroelectrics with complex heterostructures, limiting their large-scale practical applications. Here, we circumvent this limitation by utilizing a nanoscale ripple-generated flexoelectric field as a universal means to create rich polar topological configurations in nonpolar nanofilms in a controllable fashion. Our extensive phase-field simulations show that a rippled SrTiO_{3} nanofilm with a single bulge activates polarizations that are stabilized in meron configurations, which further undergo topological transitions to Néel-type and Bloch-type skyrmions upon varying the geometries. The formation of these topologies originates from the curvature-dependent flexoelectric field, which extends beyond the common mechanism of geometric confinement that requires harsh energy conditions and strict temperature ranges. We further demonstrate that the rippled nanofilm with three-dimensional ripple patterns can accommodate other unreported modulated phases of ferroelectric topologies, which provide ferroelectric analogs to the complex spin topologies in magnets. The present study not only unveils the intriguing nanoscale electromechanical properties but also opens exciting opportunities to design various functional topological phenomena in flexible materials.

Emergent ultrasmall multiferroics in paraelectric perovskite oxide by hole polarons.

Ultimately small multiferroics with coupled ferroelectric and ferromagnetic order parameters have drawn considerable attention for their tremendous technological potential. Nevertheless, these ferroic orders inevitably disappear below the critical size of several nanometers in conventional ferroelectrics or multiferroics. Here, based on first-principles calculations, we propose a new strategy to overcome this limitation and create ultrasmall multiferroic elements in otherwise nonferroelectric CaTiO3 by engineering the interplay of oxygen octahedral rotations and hole polarons, though both of them are generally believed to be detrimental to ferroelectricity. It is found that the hole doped in CaTiO3 spontaneously forms a localized polaronic state. The lattice distortions associated with a hole polaron interacting with the intrinsic oxygen octahedral rotations in CaTiO3 effectively break the inversion symmetry and create atomic-scale ferroelectricity beyond the critical size limitation. The hole polaron also causes highly localized magnetism attributed to the associated spin-polarized electric state and thus manifests as a multiferroic polaron. Moreover, the hole polaron exhibits high hopping mobility accompanied by rich switching of polarization and magnetic directions, indicating strong magnetoelectric coupling with a mechanism dissimilar from that of conventional multiferroics. The present work provides a new mechanism to engineer inversion symmetry and opens avenues for designing unusual multifunctional materials.

Intrinsic Atomic-Scale Antiferroelectric VOF3 Nanowire with Ultrahigh-Energy Storage Properties.

Antiferroelectrics with antiparallel dipoles are receiving tremendous attention for their technological importance and fundamental interest. However, intrinsic one-dimensional (1D) materials harboring antiferroelectric ordering have rarely been reported despite the promise of novel paradigms for miniaturized and high-density electronics. Herein, based on first- and second-principles calculations, we demonstrate the VOF3 atomic wire, exfoliated from an experimentally synthesized yet underexplored 1D van der Waals (vdW) bulk, as a new 1D antiferroelectric material. The energetic, thermal, and dynamic stabilities of the nanowire are confirmed theoretically. Moreover, the temperature-dependent phase transitions and double-hysteresis polarization-field loops are computed for the VOF3 nanowire by constructing the second-principles model. According to the hysteresis loops, high energy densities and efficiencies can be obtained simultaneously at room temperature in the VOF3 nanowire under moderate applied fields. Our identified 1D atomic wire not only expands the family of antiferroelectricity but also holds potential for novel high-power energy storage nanodevices.

Ultrasmall-Scale Brittle Fracture Initiated from a Dislocation in SrTiO3.

Crystal defects often lead to an intriguing variety of catastrophic failures of materials and determine the mechanical properties. Here we discover that a dislocation, which was believed to be a source of plasticity, leads to brittle fracture in SrTiO3. The fracture mechanism, i.e., bond breaking at the dislocation core triggers crack initiation and subsequent fracture, is elucidated from an atomic view by hybrid quantum and molecular simulations and in situ nanomechanical experiments. The fracture strength of the dislocation-included SrTiO3 was theoretically evaluated to be 8.8-10.7 GPa, which was eminently lower than that of the pristine one (21.7 GPa). The experimental results agree well with the simulated ones. Moreover, the fracture toughness of the ultrasmall crack initiating from the dislocation is quantitatively evaluated. This study reveals not only the role of dislocations in brittle fracture but also provides an in-depth understanding of the fracture mechanism of dislocations at the atomic scale.

[Relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia responding to retreatment with inotuzumab ozogamicin].

A 72-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) was treated with dasatinib (week1: 50 mg/day, week2: 70 mg/day, week3-: 100 mg/day) and prednisolone from June 2017. However, in January 2018, it relapsed with the T315I mutation. Although the treatment was changed to ponatinib 30 mg/day, he experienced a second relapse in June 2018. Following confirmation of CD22 positivity, he was treated with three cycles of inotuzumab ozogamicin (InO), resulting in CR. He was CR for 2.9 years before relapsing for the third time in May 2021. Because the patient was still CD22-positive, InO was given again, and the patient achieved CR at the end of the second cycle. We had a case where re-administering InO was effective as a salvage therapy for relapsed/refractory Ph+ALL (r/r Ph+ALL) in an elderly patient.

High accuracy tracking reveals how small conservation areas can protect marine megafauna.

Space use estimates can inform conservation management but relaying high-accuracy locations is often not straightforward. We used Fastloc-GPS Argos satellite tags with the innovation of additional data relay via a ground station (termed a "Mote") to record high volumes (typically >20 locations per individual per day) of high accuracy tracking data. Tags were attached in the Chagos Archipelago (Indian Ocean) in 2018-2019 to 23 immature turtles of two species for which there have been long-standing conservation concerns: 21 hawksbill turtles (Eretmochelys imbricata) and two green turtles (Chelonia mydas). Over long tracking durations (mean 227.6 d per individual), most turtles moved very little. For example, 17 of 21 hawksbill turtles remained continuously in the lagoon where they were equipped, with 95% and 50% utilization distributions (UDs) averaging only 1.03 and 0.18 km2 , respectively. Many individuals, and both species, could use the same small spaces, i.e., individuals did not maintain unique home ranges. However, three hawksbill turtles travelled hundreds of kilometers from the tagging site. Our results show that, for some large marine vertebrates, even small protected areas of only a few square kilometers can encompass the movements of a large proportion of individuals over long periods. High accuracy tracking may likewise reveal the details of space use for many other animals that move little and/or use important focal areas and where previous low-accuracy tracking techniques have tended to overestimate space use.

Strategic structure-activity relationship study on a follistatin-derived myostatin inhibitory peptide.

Myostatin, a negative regulator of muscle mass is a promising target for the treatment of muscle atrophic diseases. The novel myostatin inhibitory peptide, DF-3 is derived from the N-terminal α-helical domain of follistatin, which is an endogenous inhibitor of myostatin and other TGF-ß family members. It has been suggested that the optimization of hydrophobic residues is important to enhance the myostatin inhibition. This study describes a structure-activity relationship study focused on hydrophobic residues of DF-3 and designed to obtain a more potent peptide. A methionine residue in DF-3, which is susceptible to oxidation, was successfully converted to homophenylalanine in DF-100, and a new derivative DF-100, with four amino acid substitutions in DF-3 shows twice the potent inhibitory ability as DF-3. This report provides a new platform of a 14-mer peptide muscle enhancer.

Fidelity to foraging sites after long migrations.

Patterns of animal movement associated with foraging lie at the heart of many ecological studies and often animals face decisions of staying in an environment they know versus relocating to new sites. The lack of knowledge of new foraging sites means there is risk associated with a decision to relocate (e.g. poor foraging) as well as a potential benefit (e.g. improved foraging). Using a unique long-term satellite tracking dataset for several sea turtle species, combined with capture-mark-recapture data extending over 50 years, we show how, across species, individuals generally maintain tight fidelity to specific foraging sites after extended (up to almost 10,000 km) migration to and from distant breeding sites as well as across many decades. Migrating individuals often travelled through suitable foraging areas en route to their 'home' site and so extended their journeys to maintain foraging site fidelity. We explore the likely mechanistic underpinnings of this trait, which is also seen in some migrating birds, and suggest that individuals will forgo areas of suitable forage encountered en route during migration when they have poor knowledge of the long-term suitability of those sites, making relocation to those sites risky.

Conservation and Enforcement Capacity index (CECi): Integrating human development, economy, and marine turtle status.

Human societies are closely linked to their ecological environments. Natural ecosystems and wildlife populations are often in better condition in countries with healthy, educated and economically prosperous populations compared to countries with lower health and literacy conditions, and depressed economies. In the latter countries, these socio-economic factors can compromise government's capacity to manage their natural resources. Thus, the conservation capacity of a government is likely to play key role in the protection of threatened species, such as marine turtles. This paper aims: (1) to evaluate the conservation capacity and enforcement within the 58 Regional Management Units (RMUs) of the seven species of marine turtles throughout the world, and (2) to develop a proxy that predicts the conservation status of RMUs. We developed a Conservation and Enforcement Capacity index (CECi) by integrating the following indices: (a) the economic level and, (b) the Human Development Index (HDI) of each country, plus (c) the risks and threats in the RMUs. We used the conservation status of 15 RMUs recently assessed by the International Union for Conservation of Nature - IUCN to predict the conservation status of the 43 RMUs without updated IUCN categorisation. CECi values ranged from 0 to 1, where lower values represent a better capacity for implementation of conservation initiatives. We found that using our multi-index model, we predicted the status of 33 of 58 RMUs, 57% of which may be of threatened conservation status due to their high CECi values. This study highlighted how socio-economic aspects may impact conservation of endangered species.

Topological ferroelectric nanostructures induced by mechanical strain in strontium titanate.

Ferroelectric materials exhibit novel topological polarization configurations due to geometric confinements originating from the material shapes and interfaces at the nanoscale. In this study, we demonstrate that those nontrivial topological ferroelectric nanostructures can be tailored in paraelectric nanoporous materials by mechanical loads using phase-field modeling. That is, in nanoporous strontium titanate, periodically-arrayed ferroelectric nanostructures in the shape of networks are formed due to strain concentrations by mechanical loads, and topological polarization configurations, such as hierarchical vortices, woven fabrics and nested structures of spiral like Hopf fibration, are stabilized in the structures strongly affected by the pore arrangements. Our work indicates that various ferroelectric nanostructures with novel shapes and topologies can be designed by controlling the pore arrangements and strain conditions in nanoporous SrTiO3, and thus provides a new pathway to realize novel topological ferroelectric nanostructures, which are essential for future nanodevices.

Periodically-arrayed ferroelectric nanostructures induced by dislocation structures in strontium titanate.

A dislocation induces ferroelectricity around it in incipient ferroelectric SrTiO3 due to some reasons such as electro-mechanical coupling and it being a one-dimensional ferroelectric nanostructure. Furthermore, this microstructure is arrayed periodically in the material and dislocation structures such as a dislocation wall are formed. Due to these facts, periodically-arrayed ferroelectric nanostructures, which show various intriguing polarization configurations and functionalities depending on the internal periodic structure, may be fabricated by dislocations. The phase-field simulation exhibits that a ferroelectric nano-region induced by the strain concentration and incidental electric field around a dislocation connects with each other in a dislocation wall. As a result, a periodic ferroelectric nano-region, which is a periodically-arrayed ferroelectric nanostructure embedded in paraelectric matrices, is formed. Our findings provide a new pathway for the fabrication of novel functional nanodevices in ferroelectric systems.

Intrinsic and extrinsic effects on the electrotoroidic switching in a ferroelectric notched nanodot by a homogeneous electric field.

The control of topological defects in ferroelectrics, in particular by a homogeneous electric field, has emerged as an active research direction. A polarization vortex, which is a fundamental topological defect formed in ferroelectric nanodots, has recently been demonstrated to be switchable by a homogeneous electric field through the control of the built-in electrical distribution using low-symmetry nanodots. Such electrotoroidic switching is investigated for nearly ideal systems, e.g., free-standing nanodots. However, the electrotoroidic switching may be impacted by several factors, for instance, the nanoscale effect of flexoelectricity (intrinsic effect), epitaxial strain and the frequency of the applied field (extrinsic effects). In the present study, the switching of the polarization vortex in a notched nanodot under a homogeneous electric field is investigated. The emphasis is put on a comparison between intrinsic and extrinsic effects on the vortex switching. The results show that the vortex switching takes place through alternate vortex-to-polar and polar-to-vortex transformations due to the appearance of the notch. Although the flexoelectricity breaks the symmetry of the polarization field in the notched nanodot during the polarization transformation and gives rise to an unusual behavior of the vortex core, which departs from the symmetry axis of the notched nanodot, this intrinsic effect plays a relatively insignificant role in the switching behavior of the polarization vortex. In comparison to the intrinsic effect, interestingly, the extrinsic effects strongly influence the vortex switching behavior. Specifically, the frequency of the applied electric field can alter both the shape of the toroidal hysteresis loop and the domain transformation process of the vortex switching. In addition, under substrate constraints, the magnitude of the coercive electric fields at which the vortex-to-polar and polar-to-vortex transformations occur linearly decreases with the increase of strain. The present study provides instructive information on the efficient control of a polarization vortex, which is dominated by extrinsic factors rather than intrinsic ones.

Multiferroic Dislocations in Ferroelectric PbTiO3.

Ultrathin multiferroics with coupled ferroelectric and ferromagnetic order parameters hold promise for novel technological paradigms, such as extremely thin magnetoelectric memories. However, these ferroic orders and their functions inevitably disappear below a fundamental size limit of several nanometers. Herein, we propose a novel design strategy for nanoscale multiferroics smaller than the critical size limit by engineering the dislocations in nonmagnetic ferroelectrics, even though these lattice defects are generally believed to be detrimental. First-principles calculations demonstrate that Ti-rich PbTiO3 dislocations exhibit magnetism due to the local nonstoichiometry intrinsic to the core structures. Highly localized spin moments in conjunction with the host ferroelectricity enable these dislocations to function as atomic-scale multiferroic channels with a pronounced magnetoelectric effect that are associated with the antiferromagnetic-ferromagnetic-nonmagnetic phase transitions in response to polarization switching. The present results thus suggest a new field of dislocation (or defect) engineering for the fabrication of ultrathin magnetoelectric multiferroics and ultrahigh density electronic devices.

Strain-induced ferroelectricity and lattice coupling in BaSnO3 and SrSnO3.

Perovskite stannates such as BaSnO3 and SrSnO3 exhibit promising photovoltaic properties, and hold promise for application in solar cell devices. However, the lack of ferroelectricity and the wide band gap in these materials limit their potential for photovoltaic applications. Here, by first-principles calculations, we demonstrate the realization of a primary ferroelectric polarization in non-ferroelectric BaSnO3 and SrSnO3 through strain engineering. In addition to the appearance of polarization, the band gaps of the materials are greatly narrowed when the paraelectric to ferroelectric phase transition takes place under compressive strain. Furthermore, an intriguing Q2 mode triggered by lattice coupling with the polar mode is found in the stannates subjected to a sufficient tensile strain and this mode has a significant effect on the band gap, which suggests another pathway to narrow the band gap through the electric field control of the Q2 mode. The fruitful electronic, structural, and energetic properties are discussed in detail to achieve a fundamental understanding of the strain-induced ferroelectricity, tunable band gap, and lattice couplings between the Q2 mode and different polar/rotational distortions in the perovskite stannates.

Multiferroic Domain Walls in Ferroelectric PbTiO3 with Oxygen Deficiency.

Atomically thin multiferroics with the coexistence and cross-coupling of ferroelectric and (anti)ferromagnetic order parameters are promising for novel magnetoelectric nanodevices. However, such ferroic order disappears at a critical thickness in nanoscale. Here, we show a potential path toward ultrathin multiferroics by engineering an unusual domain wall (DW)-oxygen vacancy interaction in nonmagnetic ferroelectric PbTiO3. We demonstrate from first-principles that oxygen vacancies formed at the DW unexpectedly bring about magnetism with a localized spin moment around the vacancy. This magnetism originates from the orbital symmetry breaking of the defect electronic state due to local crystal symmetry breaking at the DW. Moreover, the energetics of defects shows the self-organization feature of oxygen vacancies at the DW, resulting in a planar-arrayed concentration of magnetic oxygen vacancies, which consequently changes the deficient DWs into multiferroic atomic layers. This DW-vacancy engineering opens up a new possibility for novel ultrathin multiferroic.

Unusual Multiferroic Phase Transitions in PbTiO3 Nanowires.

Unconventional phases and their transitions in nanoscale systems are recognized as an intriguing avenue for both unique physical properties and novel technological paradigms. Although the multiferroic phase has attracted considerable attention due to the coexistence and cross-coupling of electric and magnetic order parameters, mutually exclusive mechanism between ferroelectricity and ferromagnetism leaves conventional ferroelectrics such as PbTiO3 simply nonmagnetic. Here, we demonstrate from first-principles that ultrathin PbTiO3 nanowires exhibit unconventional multiferroic phases with emerging ferromagnetism and coexisting ferroelectric/ferrotoroidic ordering. Nanometer-scale and nonstoichiometric effects intrinsic to the nanowires bring about nonzero and nontrivial magnetic moments that coexist with the host ferroelectricity. The multiferroic order is susceptible to surface termination and nanowire morphology. Furthermore, calculations suggest that the nanowires undergo size-dependent ferroelectric-multiferroic-ferromagnetic phase transitions. This work therefore provides a route to multiferroic transitions in conventional nonmagnetic ferroelectric oxides.

[Successful treatment of secondary graft failure with donor lymphocyte infusion in a post-allogeneic stem cell transplant acute myeloid leukemia patient].

Here we report a case of secondary graft failure that was effectively treated with donor lymphocyte infusion (DLI). A 64-year-old female patient with acute myeloid leukemia obtained partial remission with azacitidine therapy and subsequently underwent unrelated allogeneic bone marrow transplantation (BMT). After confirming successful engraftment and achieving complete remission with incomplete blood count recovery, she was subsequently followed up at an outpatient clinic. A routine test performed by day 110 after BMT revealed the presence of pancytopenia. A bone marrow aspirate did not reveal any evidence of disease relapse or hemophagocytic syndrome but demonstrated hematopoietic insufficiency. Donor chimerism also declined over time; thus, the patient was diagnosed with secondary graft failure. Supportive treatment, including granulocyte-colony stimulating factor and blood transfusion, failed to improve the blood parameters. Because the patient refused a second BMT, we performed DLI on day 147 after BMT (CD3+ cells: 1.0×107/kg, single dose). Consequently, the blood cell count improved promptly and dramatically without adverse events. Following this, we discussed the case and analyzed the related literature.

Azacitidine therapy for low-risk myelodysplastic syndrome developing after solid organ transplantation.

Immunosuppressive therapy after solid organ transplantation is known to be a risk factor for the development of myelodysplastic syndromes (MDS). Herein, we report 2 patients, both of whom developed low-risk MDS after solid organ transplantation and were successfully treated with azacitidine (AZA). The 1st case was a 74-year-old man who had received liver transplantation. The initial immunosuppressive therapy consisted of cyclosporine and prednisolone. Nine years after transplantation, he was diagnosed as having MDS (RCMD). The 2nd case was a 47-year-old woman who had received cadaveric renal transplantation. The initial immunosuppressive therapy was comprised of cyclosporine, azathioprine, and prednisolone. Twenty-seven years after transplantation, she developed MDS (RA). Both patients received 75 mg/m2 AZA once daily for five consecutive days on a 28-day cycle. After 2 courses of therapy, both patients achieved hematological improvement (IWG 2006 criteria) without severe (grade 3/4) non-hematological adverse events. Moreover, AZA did not affect the status of organ transplantation in terms of engraftment and function of the graft. In conclusion, AZA would be a safe and effective agent for patients with MDS after solid organ transplantation. However, long-term follow-up is needed to confirm the safety and efficacy of AZA for patients undergoing solid organ transplantations.

Hybrid improper ferroelectricity in SrZrO3/BaZrO3 superlattice.

Incipient ferroelectrics, which show a unique dielectric property, arouse tremendous interests due to their potential application in microwave dielectric devices. However, ferroelectric transition in incipient ferroelectrics is suppressed entirely by quantum fluctuation. Here, by means of first-principles calculations, we demonstrate that there exists hybrid improper ferroelectricity in a layered artificial superlattice composed of the incipient ferroelectrics of SrZrO3 and BaZrO3. The hybrid improper ferroelectric polarization stems from oxygen octahedral rotation and coexists with the strain-induced ferroelectric distortion. The coexistence of oxygen octahedral rotation and ferroelectric distortion results in an enhanced polarization in the superlattice. It is further found that the total polarization in the superlattice is mainly contributed by the oxygen octahedral rotation for zero or small strain, whereas the contribution from strain-induced ferroelectric distortion gradually becomes predominant as the strain increases. The phonon dispersion, energy surface and atomic displacements are calculated to shed light on the underlying mechanism of the hybrid improper ferroelectricity in the SrZrO3/BaZrO3 superlattice.