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We propose a simple microscopic model to numerically investigate the stability of a two-dimensional fractional topological insulator (FTI). The simplest example of an FTI consists of two decoupled copies of a Laughlin state with opposite chiralities, or double-semion phase. We focus on bosons at half filling. We study the stability of the FTI phase upon addition of two coupling terms of different nature: an interspin interaction term, and an inversion-symmetry-breaking term that couples the copies at the single-particle level. Using exact-diagonalization and entanglement spectra, we numerically show that the FTI phase is stable against both perturbations. We compare our system to a similar bilayer fractional Chern insulator. We show evidence that the time-reversal-invariant system survives the introduction of interaction coupling on a larger scale than the time-reversal-symmetry-breaking one, stressing the importance of time-reversal symmetry in the FTI phase stability. We also discuss possible fractional phases beyond ν=1/2. [ABSTRACT FROM AUTHOR]

We report the observation of a series of Abelian and non-Abelian topological states in fractional Chern insulators (FCIs). The states appear at bosonic filling ν=k/(C+1) (k,C integers) in several lattice models, in fractionally filled bands of Chern numbers C≥1 subject to on-site Hubbard interactions. We show strong evidence that the k=1 series is Abelian while the k>1 series is non-Abelian. The energy spectrum at both ground-state filling and upon the addition of quasiholes shows a low-lying manifold of states whose total degeneracy and counting matches, at the appropriate size, that of the fractional quantum Hall (FQH) SU(C) (color) singlet k-clustered states (including Halperin, non-Abelian spin singlet states and their generalizations). The ground-state momenta are correctly predicted by the FQH to FCI lattice folding. However, the counting of FCI states also matches that of a spinless FQH series, preventing a clear identification just from the energy spectrum. The entanglement spectrum lends support to the identification of our states as SU(C) color singlets, but offers anomalies in the counting for C > 1, possibly related to dislocations that call for the development of alternative counting rules of these topological states. [ABSTRACT FROM AUTHOR]

We report the first numerical observation of composite fermion (CF) states in fractional Chern insulators (FCI) using exact diagonalization. The ruby lattice Chern insulator model for both fermions and bosons exhibits a clear signature of CF states at filling factors 2/5 and 3/7 (2/3 and 3/4 for bosons). The topological properties of these states are studied through several approaches. Quasihole and quasielectron excitations in FCI display similar features as their fractional quantum hall (FQH) counterparts. The entanglement spectrum of FCI ground states shows an identical fingerprint to its FQH partner. We show that the correspondence between FCI and FQH obeys the emergent symmetry already established, proving the validity of this approach beyond the clustered states. We investigate other Chern insulator models and find similar signatures of CF states. However, some of these systems exhibit strong finite size effects. [ABSTRACT FROM AUTHOR]

Strongly interacting topological matter 1 exhibits fundamentally new phenomena with potential applications in quantum information technology 2,3 . Emblematic instances are fractional quantum Hall (FQH) states 4 , in which the interplay of a magnetic field and strong interactions gives rise to fractionally charged quasi-particles, long-ranged entanglement and anyonic exchange statistics. Progress in engineering synthetic magnetic fields 5-21 has raised the hope to create these exotic states in controlled quantum systems. However, except for a recent Laughlin state of light 22 , preparing FQH states in engineered systems remains elusive. Here we realize a FQH state with ultracold atoms in an optical lattice. The state is a lattice version of a bosonic ν = 1/2 Laughlin state 4,23 with two particles on 16 sites. This minimal system already captures many hallmark features of Laughlin-type FQH states 24-28 : we observe a suppression of two-body interactions, we find a distinctive vortex structure in the density correlations and we measure a fractional Hall conductivity of σ H /σ 0  = 0.6(2) by means of the bulk response to a magnetic perturbation. Furthermore, by tuning the magnetic field, we map out the transition point between the normal and the FQH regime through a spectroscopic investigation of the many-body gap. Our work provides a starting point for exploring highly entangled topological matter with ultracold atoms 29-33 ., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Quantum Hall (QH) edge channels propagating along the periphery of two-dimensional (2D) electron gases under perpendicular magnetic field are a major paradigm in physics. However, groundbreaking experiments that could use them in graphene are hampered by the conjecture that QH edge channels undergo a reconstruction with additional nontopological upstream modes. By performing scanning tunneling spectroscopy up to the edge of a graphene flake on hexagonal boron nitride, we show that QH edge channels are confined to a few magnetic lengths at the crystal edges. This implies that they are ideal 1D chiral channels defined by boundary conditions of vanishing electronic wave functions at the crystal edges, hence free of electrostatic reconstruction. We further evidence a uniform charge carrier density at the edges, incompatible with the existence of upstream modes. This work has profound implications for electron and heat transport experiments in graphene-based systems and other 2D crystalline materials.

We show that a chiral spin liquid spontaneously emerges in partially amorphous, polycrystalline, or ion-irradiated Kitaev materials. In these systems, time-reversal symmetry is broken spontaneously due to a nonzero density of plaquettes with an odd number of edges n_{odd}. This mechanism opens a sizable gap, at small n_{odd} compatible with that of typical amorphous materials and polycrystals, and which can alternatively be induced by ion irradiation. We find that the gap is proportional to n_{odd}, saturating at n_{odd}∼40%. Using exact diagonalization, we find that the chiral spin liquid is approximately as stable to Heisenberg interactions as Kitaev's honeycomb spin-liquid model. Our results open up a significant number of noncrystalline systems where chiral spin liquids can emerge without external magnetic fields.

Abstarct: When electrons populate a flat band their kinetic energy becomes negligible, forcing them to organize in exotic many-body states to minimize their Coulomb energy 1-5 . The zeroth Landau level of graphene under a magnetic field is a particularly interesting strongly interacting flat band because interelectron interactions are predicted to induce a rich variety of broken-symmetry states with distinct topological and lattice-scale orders 6-11 . Evidence for these states stems mostly from indirect transport experiments that suggest that broken-symmetry states are tunable by boosting the Zeeman energy 12 or by dielectric screening of the Coulomb interaction 13 . However, confirming the existence of these ground states requires a direct visualization of their lattice-scale orders 14 . Here we image three distinct broken-symmetry phases in graphene using scanning tunnelling spectroscopy. We explore the phase diagram by tuning the screening of the Coulomb interaction by a low- or high-dielectric-constant environment, and with a magnetic field. In the unscreened case, we find a Kekulé bond order, consistent with observations of an insulating state undergoing a magnetic-field driven Kosterlitz-Thouless transition 15,16 . Under dielectric screening, a sublattice-unpolarized ground state 13 emerges at low magnetic fields, and transits to a charge-density-wave order with partial sublattice polarization at higher magnetic fields. The Kekulé and charge-density-wave orders furthermore coexist with additional, secondary lattice-scale orders that enrich the phase diagram beyond current theory predictions 6-10 . This screening-induced tunability of broken-symmetry orders may prove valuable to uncover correlated phases of matter in other quantum materials., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Combinatorial methods enable the synthesis of chemical libraries on scales of millions to billions of compounds, but the ability to efficiently screen and sequence such large libraries has remained a major bottleneck for molecular discovery. We developed a novel technology for screening and sequencing libraries of synthetic molecules of up to a billion compounds in size. This platform utilizes the fiber-optic array scanning technology (FAST) to screen bead-based libraries of synthetic compounds at a rate of 5 million compounds per minute (∼83 000 Hz). This ultra-high-throughput screening platform has been used to screen libraries of synthetic "self-readable" non-natural polymers that can be sequenced at the femtomole scale by chemical fragmentation and high-resolution mass spectrometry. The versatility and throughput of the platform were demonstrated by screening two libraries of non-natural polyamide polymers with sizes of 1.77M and 1B compounds against the protein targets K-Ras, asialoglycoprotein receptor 1 (ASGPR), IL-6, IL-6 receptor (IL-6R), and TNFα. Hits with low nanomolar binding affinities were found against all targets, including competitive inhibitors of K-Ras binding to Raf and functionally active uptake ligands for ASGPR facilitating intracellular delivery of a nonglycan ligand., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Many graphene moiré superlattices host narrow bands with nonzero valley Chern numbers. We provide analytical and numerical evidence for a robust spin and/or valley polarized insulator at total integer band filling in nearly flat bands of several different moiré materials. In the limit of a perfectly flat band, we present analytical arguments in favor of the ferromagnetic state substantiated by numerical calculations. Further, we numerically evaluate its stability for a finite bandwidth. We provide exact diagonalization results for models appropriate for ABC trilayer graphene aligned with hBN, twisted double bilayer graphene, and twisted bilayer graphene aligned with hBN. We also provide DMRG results for a honeycomb lattice with a quasiflat band and nonzero Chern number, which extend our results to larger system sizes. We find a maximally spin and valley polarized insulator at all integer fillings when the band is sufficiently flat. We also show that interactions may induce effective dispersive terms strong enough to destabilize this state. These results still hold in the case of zero valley Chern number (for example, trivial side of TLG/hBN). We give an intuitive picture based on extended Wannier orbitals, and emphasize the role of the quantum geometry of the band, whose microscopic details may enhance or weaken ferromagnetism in moiré materials.

The robust quantization of observables in units of universal constants is a hallmark of topological phases. We show that chiral higher order topological insulators (HOTIs), bulk insulators with chiral hinge states, present two unusual features related to quantization. First, we show that circular dichroism is quantized to an integer or zero depending on the orientation of the sample. This probe locates the hinge states, and can be used to distinguish different types of chiral HOTIs. Second, we find that the average of the local Chern marker over a single surface, an observable related to the surface Hall conductivity known to be quantized in the infinite slab geometry, is nonuniversal for a finite surface. This is due to a nonuniversal contribution of the hinge states, previously unaccounted for, that distinguishes surfaces of chiral HOTIs from Chern insulators. Our findings are relevant to establish higher order topology in systems such as the axion insulator candidate EuIn_{2}As_{2}, and cold atomic realizations.

The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors is limited by the development of drug resistance. The irreversible EGFR kinase inhibitor WZ4002 is effective against the most common mechanism of drug resistance mediated by the EGFR T790M mutation. Here, we show, in multiple complementary models, that resistance to WZ4002 develops through aberrant activation of extracellular signal-regulated kinase (ERK) signaling caused by either an amplification of mitogen-activated protein kinase 1 (MAPK1) or by downregulation of negative regulators of ERK signaling. Inhibition of MAP-ERK kinase (MEK) or ERK restores sensitivity to WZ4002 and prevents the emergence of drug resistance. We further identify MAPK1 amplification in an erlotinib-resistant EGFR-mutant non-small cell lung carcinoma patient. In addition, the WZ4002-resistant MAPK1-amplified cells also show an increase both in EGFR internalization and a decrease in sensitivity to cytotoxic chemotherapy. Our findings provide insights into mechanisms of drug resistance to EGFR kinase inhibitors and highlight rational combination therapies that should be evaluated in clinical trials.

The structure and expression of 14-3-3 sigma(sigma) was analysed in squamous carcinomas (SCC) of the vulva and in the vulval pre-malignant lesion vulval intraepithelial neoplasia (VIN). Sequence analysis of the sigma coding region did not detect mutations in any case of SCC or VIN III and loss of heterozygosity (LOH) occurred in only 2 out of 27 informative cases. In contrast to the absence of genetic change, methylation-specific PCR (MSP) analysis revealed dense CpG methylation within the sigma gene in approximately 60% of cases of vulval SCC, but methylation was not detected in matched, normal epithelial tissue. Methylation was associated in all cases with reduced or absent expression of sigma mRNA. There was no correlation between sigma methylation and HPV or p53 status. Analysis of pre-malignant vulval intraepithelial neoplasia (VIN) revealed that sigma methylation was detectable early in neoplastic development. Co-incident methylation, accompanied by loss of expression, of sigma and p16INK4a was commonly detected in both SCC and VIN III, suggesting that epigenetic silencing of these two genes is an early and important event in vulval neoplasia.

The structure and expression of the human Rad53 homologue Chk2 was analysed in breast cancer. The previously described silent polymorphism at nucleotide 252 in codon 84 (GAA>GAG) was observed in 5/141 cases. Somatic Chk2 coding mutations were detected in 7/141 cases, these occurring in 4/18 BRCA1-associated breast cancers, 1/78 sporadic breast cancers and 2/25 typical medullary carcinomas. Each of the BRCA1-associated cancers with Chk2 mutations also contained mutations in p53, whereas the single sporadic cancer with Chk2 mutation was wild-type for p53. Expression of Chk2 was ubiquitously detected in normal ductal epithelium of the breast, but there was loss of expression in a significant proportion of breast carcinomas, and this occurred in cancers both with and without p53 mutation. A CpG island was identified 5' of the Chk2 transcriptional start site, but there was no evidence of cytosine methylation in any of the cancers with down-regulated Chk2 expression. Analysis of the germ-line of 45 individuals with hereditary or early onset breast cancer revealed wild-type Chk2 sequence in all cases. Thus, despite the rarity of somatic mutations in Chk2 in sporadic breast carcinomas, our results nevertheless reveal that concomitant loss of function in Chk2 (via down-regulation of expression) and p53 (via mutation) occurs in a proportion of sporadic cases. However, consistent with other studies, we show that germ-line mutations in Chk2 are unlikely to account for a significant proportion of non BRCA1-, non BRCA2-associated hereditary breast cancers.