Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Anomalous electrons in a metallic kagome ferromagnet.

Ordinary metals contain electron liquids within well-defined 'Fermi' surfaces at which the electrons behave as if they were non-interacting. In the absence of transitions to entirely new phases such as insulators or superconductors, interactions between electrons induce scattering that is quadratic in the deviation of the binding energy from the Fermi level. A long-standing puzzle is that certain materials do not fit this 'Fermi liquid' description. A common feature is strong interactions between electrons relative to their kinetic energies. One route to this regime is special lattices to reduce the electron kinetic energies. Twisted bilayer graphene1-4 is an example, and trihexagonal tiling lattices (triangular 'kagome'), with all corner sites removed on a 2 × 2 superlattice, can also host narrow electron bands5 for which interaction effects would be enhanced. Here we describe spectroscopy revealing non-Fermi-liquid behaviour for the ferromagnetic kagome metal Fe3Sn2 (ref. 6). We discover three C3-symmetric electron pockets at the Brillouin zone centre, two of which are expected from density functional theory. The third and most sharply defined band emerges at low temperatures and binding energies by means of fractionalization of one of the other two, most likely on the account of enhanced electron-electron interactions owing to a flat band predicted to lie just above the Fermi level. Our discovery opens the topic of how such many-body physics involving flat bands7,8 could differ depending on whether they arise from lattice geometry or from strongly localized atomic orbitals9,10.

Charge fluctuations in the intermediate-valence ground state of SmCoIn5.

The microscopic mechanism of heavy band formation, relevant for unconventional superconductivity in CeCoIn5 and other Ce-based heavy fermion materials, depends strongly on the efficiency with which f electrons are delocalized from the rare earth sites and participate in a Kondo lattice. Replacing Ce3+ (4f1, J = 5/2) with Sm3+ (4f5, J = 5/2), we show that a combination of the crystal electric field and on-site Coulomb repulsion causes SmCoIn5 to exhibit a Γ7 ground state similar to CeCoIn5 with multiple f electrons. We show that with this single-ion ground state, SmCoIn5 exhibits a temperature-induced valence crossover consistent with a Kondo scenario, leading to increased delocalization of f holes below a temperature scale set by the crystal field, Tv ≈ 60 K. Our result provides evidence that in the case of many f electrons, the crystal field remains the dominant tuning knob in controlling the efficiency of delocalization near a heavy fermion quantum critical point, and additionally clarifies that charge fluctuations play a general role in the ground state of "115" materials.

Two-dimensional characterization of three-dimensional magnetic bubbles in Fe3Sn2 nanostructures.

We report differential phase contrast scanning transmission electron microscopy (TEM) of nanoscale magnetic objects in Kagome ferromagnet Fe3Sn2 nanostructures. This technique can directly detect the deflection angle of a focused electron beam, thus allowing clear identification of the real magnetic structures of two magnetic objects including three-ring and complex arch-shaped vortices in Fe3Sn2 by Lorentz-TEM imaging. Numerical calculations based on real material-specific parameters well reproduced the experimental results, showing that the magnetic objects can be attributed to integral magnetizations of two types of complex three-dimensional (3D) magnetic bubbles with depth-modulated spin twisting. Magnetic configurations obtained using the high-resolution TEM are generally considered as two-dimensional (2D) magnetic objects previously. Our results imply the importance of the integral magnetizations of underestimated 3D magnetic structures in 2D TEM magnetic characterizations.

Comprehensive Profiling of Mutations to Influenza Virus PB2 That Confer Resistance to the Cap-Binding Inhibitor Pimodivir.

Antivirals are used not only in the current treatment of influenza but are also stockpiled as a first line of defense against novel influenza strains for which vaccines have yet to be developed. Identifying drug resistance mutations can guide the clinical deployment of the antiviral and can additionally define the mechanisms of drug action and drug resistance. Pimodivir is a first-in-class inhibitor of the polymerase basic protein 2 (PB2) subunit of the influenza A virus polymerase complex. A number of resistance mutations have previously been identified in treated patients or cell culture. Here, we generate a complete map of the effect of all single-amino-acid mutations to an avian PB2 on resistance to pimodivir. We identified both known and novel resistance mutations not only in the previously implicated cap-binding and mid-link domains, but also in the N-terminal domain. Our complete map of pimodivir resistance thus enables the evaluation of whether new viral strains contain mutations that will confer pimodivir resistance.

Facilitators and Barriers to Post-partum Diabetes Screening Among Mothers With a History of Gestational Diabetes Mellitus-A Qualitative Study From Singapore.

Introduction: Gestational Diabetes Mellitus (GDM) affects one in six births worldwide. Mothers with GDM have an increased risk of developing post-partum Type-2 Diabetes Mellitus (T2DM). However, their uptake of post-partum diabetes screening is suboptimal, including those in Singapore. Literature reports that the patient-doctor relationship, mothers' concerns about diabetes, and family-related practicalities are key factors influencing the uptake of such screening. However, we postulate additional factors related to local society, healthcare system, and policies in influencing post-partum diabetes screening among mothers with GDM. Aim: The qualitative research study aimed to explore the facilitators and barriers to post-partum diabetes screening among mothers with GDM in an Asian community. Methods: In-depth interviews were carried out on mothers with GDM at a public primary care clinic in Singapore. Mothers were recruited from those who brought their child for vaccination appointments and their informed consent was obtained. Both mothers who completed post-partum diabetes screening within 12 weeks after childbirth and those who did not were purposively recruited. The social ecological model (SEM) provides the theoretical framework to identify facilitators and barriers at the individual, interpersonal, organizational, and policy levels. Results: Twenty multi-ethnic Asian mothers with GDM were interviewed. At the individual and interpersonal level, self-perceived risk of developing T2DM, understanding the need for screening and the benefits of early diagnosis, availability of confinement nanny in Chinese family, alternate caregivers, emotional, and peer support facilitated post-partum diabetes screening. Barriers included fear of the diagnosis and its consequences, preference for personal attention and care to child, failure to find trusted caregiver, competing priorities, and unpleasant experiences with the oral glucose tolerance test. At the organizational and public policy level, bundling of scheduled appointments, and standardization of procedure eased screening but uptake was hindered by inconvenient testing locations, variable post-partum care practices and advice in the recommendations for diabetes screening. Conclusion: Based on the SEM, facilitators and barriers towards post-partum diabetes screening exist at multiple levels, with some contextualized to local factors. Interventions to improve its uptake should be multi-pronged, targeting not only at personal but also familial, health system, and policy factors to ensure higher level of success.

Target Bubbles in Fe3Sn2 Nanodisks at Zero Magnetic Field.

We report a vortex-like magnetic configuration in uniaxial ferromagnet Fe3Sn2 nanodisks using differential phase contrast scanning transmission electron microscopy. This magnetic configuration is transferred from a conventional magnetic vortex using a zero-magnetic-field warming process and is characterized by a series of concentric cylinder domains. We termed them as "target bubbles" that are identified as three-dimensional depth-modulated magnetic objects in combination with numerical simulations. Target bubbles have room-temperature stability even at zero magnetic field and multiple stable magnetic configurations. These advantages render the target bubble an ideal bit to be an information carrier and can advance magnetic target bubbles toward functionalities in the long term by incorporating emergent degrees of freedom and purely electrically controllable magnetism.

Comparison of Pre-Treatment vs. Post-Treatment Retinal Vessel Density in Children with Amblyopia.

BACKGROUND: Prior studies have reported a lower retinal vessel density (RVD) in amblyopic vs. non-amblyopic eyes. No studies have shown if amblyopic eye RVD changes following patching therapy. We assessed for RVD differences between pre-treatment vs. post-treatment amblyopic eyes. METHODS: Participants were included if they were <10 years old with unilateral amblyopia. All subjects were required to visit the pediatric eye clinic for examination. Exclusion criteria included: deprivation amblyopia, bilateral amblyopia, nystagmus, media opacity, intraocular inflammation, or any retinal disease. All participants underwent optical coherence tomography angiography (OCTA) before and after refraction and patching treatment. Outcomes included superficial (SCP) and deep (DCP) capillary plexus RVD. RESULTS: 12 patients (12 amblyopic eyes) were included. Mean (SD) age, gestational age (GA), birth weight (BW), and follow-up time were: 6.5 (1.7) years, 39.4 weeks (1.4 w), 3271 g (262 g), and 114 days (46d), respectively. There was a significant increase in the RVD of the DCP in 3 × 3-mm scans after treatment, specifically in the whole image (52.6 ± 5.75 vs 56.5 ± 2.48%, p = .046) and superior hemisphere regions (52.47 ± 6.17 vs 56.73 ± 2.27%, p = .048). CONCLUSIONS: Amblyopic eye RVD potentially increases after amblyopia treatment in specific regions of the retina. Further research is required to refine this clinical parameter.

Fuchs endothelial corneal dystrophy and corneal endothelial diseases: East meets West.

Fuchs endothelial corneal dystrophy (FECD) is amongst one of the most common indications for endothelial keratoplasty worldwide. Despite being originally described among Caucasians, it is now known to be prevalent among a large number of populations, including Asians. While the FECD phenotype is classically described as that of central guttate and pigment deposits associated with corneal endothelial dysfunction, there are subtle yet important differences in how FECD and its phenocopies may present in Caucasians vs Asians. Such differences are paralled by genotypic variations and disease management preferences which appear to be geographically and ethnically delineated. This article provides a succinct review of such differences, with a focus on diagnostic and management issues which may be encountered by ophthalmologists practicing in the different geographic regions, when evaluating a patient with FECD.

Identification of soluble microbial products (SMPs) from the fermentation and methanogenic phases of anaerobic digestion.

The production and transformation of Soluble Microbial Products (SMPs) in biological treatment systems is complex, and their genesis and reasons for production are still unclear. SMPs are important since they constitute the main fraction of effluent COD (both aerobic and anaerobic), and hence are the main precursors for disinfection by-products (DBPs). In addition, they are a key component of fouling in membrane bioreactors. Hence, it is important to identify the chemical composition of SMPs, determine their origin, and understand what system parameters influence their production so we can possibly develop strategies to control their production. This study focuses on the production and identification of SMPs in an anaerobic batch process being fed a synthetic feed. To further understand the origins of SMPs, and how they are produced, we analysed the processes of fermentation and methanogenesis independently which has never been done in detail before. SMP concentration, molecular weight distribution and carbohydrate analyses were used to estimate the amount of SMPs in the supernatants. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-Time-of-Flight mass spectrometry (LC-ESI-Q-ToF) were used to identify many of the SMPs which have relative masses up to 2 kDa. Our results showed that fermentation released much higher SMP concentrations compared to methanogenesis, especially in the range of 70 k-1000 k Da and 106-1500 Da. Alkanes, alkenes, alcohols, acids, and nitrogen-compounds were the major group of compounds identified in the supernatant of both fermentation and methanogenesis, and 71% of the compounds identified were found in both phases of digestion. Results from LC-ESI-Q-ToF analysis identified components of the cell membrane, such as phosphatidylglycerol, phosphatidylethanolamine and phosphatidylserine, as well as other compounds such as flavonoids, acylglycerol, terpene and terpenoids, benzenoid, glyceride, steroid and steroid derivatives.

Meioc maintains an extended meiotic prophase I in mice.

The meiosis-specific chromosomal events of homolog pairing, synapsis, and recombination occur over an extended meiotic prophase I that is many times longer than prophase of mitosis. Here we show that, in mice, maintenance of an extended meiotic prophase I requires the gene Meioc, a germ-cell specific factor conserved in most metazoans. In mice, Meioc is expressed in male and female germ cells upon initiation of and throughout meiotic prophase I. Mouse germ cells lacking Meioc initiate meiosis: they undergo pre-meiotic DNA replication, they express proteins involved in synapsis and recombination, and a subset of cells progress as far as the zygotene stage of prophase I. However, cells in early meiotic prophase-as early as the preleptotene stage-proceed to condense their chromosomes and assemble a spindle, as if having progressed to metaphase. Meioc-deficient spermatocytes that have initiated synapsis mis-express CYCLIN A2, which is normally expressed in mitotic spermatogonia, suggesting a failure to properly transition to a meiotic cell cycle program. MEIOC interacts with YTHDC2, and the two proteins pull-down an overlapping set of mitosis-associated transcripts. We conclude that when the meiotic chromosomal program is initiated, Meioc is simultaneously induced so as to extend meiotic prophase. Specifically, MEIOC, together with YTHDC2, promotes a meiotic (as opposed to mitotic) cell cycle program via post-transcriptional control of their target transcripts.

A Gene Regulatory Program for Meiotic Prophase in the Fetal Ovary.

The chromosomal program of meiotic prophase, comprising events such as laying down of meiotic cohesins, synapsis between homologs, and homologous recombination, must be preceded and enabled by the regulated induction of meiotic prophase genes. This gene regulatory program is poorly understood, particularly in organisms with a segregated germline. We characterized the gene regulatory program of meiotic prophase as it occurs in the mouse fetal ovary. By profiling gene expression in the mouse fetal ovary in mutants with whole tissue and single-cell techniques, we identified 104 genes expressed specifically in pre-meiotic to pachytene germ cells. We characterized the regulation of these genes by 1) retinoic acid (RA), which induces meiosis, 2) Dazl, which is required for germ cell competence to respond to RA, and 3) Stra8, a downstream target of RA required for the chromosomal program of meiotic prophase. Initial induction of practically all identified meiotic prophase genes requires Dazl. In the presence of Dazl, RA induces at least two pathways: one Stra8-independent, and one Stra8-dependent. Genes vary in their induction by Stra8, spanning fully Stra8-independent, partially Stra8-independent, and fully Stra8-dependent. Thus, Stra8 regulates the entirety of the chromosomal program but plays a more nuanced role in governing the gene expression program. We propose that Stra8-independent gene expression enables the stockpiling of selected meiotic structural proteins prior to the commencement of the chromosomal program. Unexpectedly, we discovered that Stra8 is required for prompt down-regulation of itself and Rec8. Germ cells that have expressed and down-regulated Stra8 are refractory to further Stra8 expression. Negative feedback of Stra8, and subsequent resistance to further Stra8 expression, may ensure a single, restricted pulse of Stra8 expression. Collectively, our findings reveal a gene regulatory logic by which germ cells prepare for the chromosomal program of meiotic prophase, and ensure that it is induced only once.

Conversion of cell-survival activity of Akt into apoptotic death of cancer cells by two mutations on the BIM BH3 domain.

Survival and proliferation of cancer cells are often associated with hyperactivity of the serine/threonine kinase, Akt. Herein, we show that prosurvival activity of Akt can be converted into prodeath activity by embedding an Akt recognition sequence in the apoptogenic BH3 domain of human BIM. The recognition sequence was created by introducing two mutations, I155R and E158S, into the core region of the BIM BH3 domain. Although a 21-mer BIM BH3 peptide containing these two mutations bound weakly to BCL-XL and BCL-2, this peptide with phosphorylation of Ser158 bound to these proteins with a dissociation constant of <10 nM. The crystal structure of the phosphorylated peptide bound to BCL-XL revealed that the phospho-Ser158 makes favorable interactions with two BCL-XL residues, which cannot be formed with unphosphorylated Ser158. Remarkably, the designed peptide showed a cytotoxic effect on PTEN-null PC3 tumor cells whose Akt activity is aberrantly high. The cell-killing activity disappeared when the cellular Akt activity was lowered by ectopic PTEN expression. Thus, these results lay a foundation for developing a peptide or protein agent that is dormant in normal cells but is transformed into a potent apoptogenic molecule upon phosphorylation by hyperactivity of Akt in cancer cells.

Licensing of primordial germ cells for gametogenesis depends on genital ridge signaling.

In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell licensing has been considered to be a cell-autonomous and gonad-independent event, based on observations that some PGCs, having migrated not to the gonad but to the adrenal gland, nonetheless enter meiosis in a time frame parallel to ovarian germ cells -- and do so regardless of the sex of the embryo. Here we test the hypothesis that germ cell licensing is cell-autonomous by examining the fate of PGCs in Gata4 conditional mutant (Gata4 cKO) mouse embryos. Gata4, which is expressed only in somatic cells, is known to be required for genital ridge initiation. PGCs in Gata4 cKO mutants migrated to the area where the genital ridge, the precursor of the gonad, would ordinarily be formed. However, these germ cells did not undergo licensing and instead retained characteristics of PGCs. Our results indicate that licensing is not purely cell-autonomous but is induced by the somatic genital ridge.

Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about 700 protein-coding genes. Only 2% of the MSY derives from the ancestral autosomes that gave rise to the mammalian sex chromosomes. Instead, all but 45 of the MSY's genes belong to three acquired, massively amplified gene families that have no homologs on primate MSYs but do have acquired, amplified homologs on the mouse X chromosome. The complete mouse MSY sequence brings to light dramatic forces in sex chromosome evolution: lineage-specific convergent acquisition and amplification of X-Y gene families, possibly fueled by antagonism between acquired X-Y homologs. The mouse MSY sequence presents opportunities for experimental studies of a sex-specific chromosome in its entirety, in a genetically tractable model organism.

Retinoic acid activates two pathways required for meiosis in mice.

In all sexually reproducing organisms, cells of the germ line must transition from mitosis to meiosis. In mice, retinoic acid (RA), the extrinsic signal for meiotic initiation, activates transcription of Stra8, which is required for meiotic DNA replication and the subsequent processes of meiotic prophase. Here we report that RA also activates transcription of Rec8, which encodes a component of the cohesin complex that accumulates during meiotic S phase, and which is essential for chromosome synapsis and segregation. This RA induction of Rec8 occurs in parallel with the induction of Stra8, and independently of Stra8 function, and it is conserved between the sexes. Further, RA induction of Rec8, like that of Stra8, requires the germ-cell-intrinsic competence factor Dazl. Our findings strengthen the importance of RA and Dazl in the meiotic transition, provide important details about the Stra8 pathway, and open avenues to investigate early meiosis through analysis of Rec8 induction and function.

Effect of chronic anti-glaucoma medications and trabeculectomy on tear osmolarity.

PURPOSE: To evaluate the tear film osmolarity (TFO) and ocular surface clinical signs and symptoms in chronically medicated glaucoma patients and post-trabeculectomy patients. METHODS: This is a single-center, prospective case-controlled study. One-hundred and thirty eyes of 130 participants aged ≥ 45 years were included (49 normal controls, 50 glaucoma patients on chronic preserved anti-glaucoma medication ≥ 6 months, and 31 post-trabeculectomy patients not on medication ≥ 6 months). TFO, tear break-up time (TBUT), Schirmer's test I and dry eye symptoms were evaluated. Data from both groups of glaucoma patients were compared with age and sex-matched controls. Logistic regression was performed to calculate the odds ratios. RESULTS: Mean TFO in the three groups were 301.4 ± 7.7, 307.0 ± 9.3, and 307.4 ± 11.6 mOsm/l, respectively. Compared with normal controls, chronically medicated glaucoma patients and post-trabeculectomy patients were more likely to have a raised TFO, with odds ratios (95% CI) of 4.43 (1.74-11.32) and 2.76 (1.02-7.94), respectively. Both groups of glaucoma patients were also more likely to experience dry eye symptoms, with ORs of 4.72 (1.92-11.59) and 4.24 (1.54-11.72). There was no significant difference in TFO and symptoms between both groups of glaucoma patients, and in TBUT and Schirmer's test across all three groups. CONCLUSIONS: Patients on chronic topical anti-glaucoma medication and post-trabeculectomy patients were more likely to have raised TFO and dry eye symptoms, suggesting significant ocular surface disease. Glaucoma practitioners should be aware that dry eye symptoms and raised TFO may occur in the absence of TBUT and Schirmer's test abnormality.

Five-year experience with congenital cardiac surgery at National University Heart Centre, Singapore.

INTRODUCTION: Surgical procedures performed for congenital heart disease are usually complex and variable. The aims of this paper were to analyse patient demographics in a centre that caters to congenital cardiac surgery, compare departmental standards to international centres, and investigate the relationship between patient volume and clinical outcome. METHODS: A total of 163 patients who presented to the Cardiac, Thoracic and Vascular Surgery Department of the National University Hospital , Singapore between 2002 and 2006 were identified and studied retrospectively. Patient demographics were analysed. The mortality rates and patient volume were compared with those observed at international centres. RESULTS: The mean annual patient volume was 32.6 cases. The mean age of the patients was 15.7 years, with the oldest patient being 73 years old. 57.1 percent of the patients were Chinese, 23.3 percent were Malay and 19.6 percent were Indian and other races. Foreigners made up nearly half of the patient cohort (45.4 percent). Atrial septal defect was found to be the most common diagnosis (n is 64), with the secundum being most commonly involved (76.9 percent). The commonest postoperative morbidities encountered were arrhythmias and pleural effusions. Patient volume was not found to be a significant factor affecting clinical outcomes. CONCLUSION: With a growing population of adults with congenital heart disease and a significant number of foreign patients, improvements to our resources and infrastructure need to be considered in order to cope with the increasing demands. Despite having a low patient volume, the centre is still able to provide congenital heart surgery with good clinical outcomes that are comparable to those of international centres with similar or higher patient volumes.