Electronic and magnetic properties of the graphene-ferromagnet interface

The article presents the work on the investigation of the surface structure as well as electronic and magnetic properties of graphene layer on a lattice matched surface of a ferromagnetic material, Ni(111).Comment: accepted in New J. Phy

SleepTransformer: Automatic Sleep Staging with Interpretability and Uncertainty Quantification.

BACKGROUND: Black-box skepticism is one of the main hindrances impeding deep-learning-based automatic sleep scoring from being used in clinical environments. METHODS: Towards interpretability, this work proposes a sequence-to-sequence sleep staging model, namely SleepTransformer. It is based on the transformer backbone and offers interpretability of the models decisions at both the epoch and sequence level. We further propose a simple yet efficient method to quantify uncertainty in the models decisions. The method, which is based on entropy, can serve as a metric for deferring low-confidence epochs to a human expert for further inspection. RESULTS: Making sense of the transformers self-attention scores for interpretability, at the epoch level, the attention scores are encoded as a heat map to highlight sleep-relevant features captured from the input EEG signal. At the sequence level, the attention scores are visualized as the influence of different neighboring epochs in an input sequence (i.e. the context) to recognition of a target epoch, mimicking the way manual scoring is done by human experts. CONCLUSION: Additionally, we demonstrate that SleepTransformer performs on par with existing methods on two databases of different sizes. SIGNIFICANCE: Equipped with interpretability and the ability of uncertainty quantification, SleepTransformer holds promise for being integrated into clinical settings

Robust co-immunoprecipitation with mass spectrometry for Caenorhabditis elegans using solid-phase enhanced sample preparation

Studying protein interactions in vivo can reveal key molecular mechanisms of biological processes. Co-immunoprecipitation with mass spectrometry detects protein–protein interactions with high throughput. The nematode Caenorhabditis elegans is a powerful genetic model organism for in vivo studies. Yet its rigid and complex tissues require optimization for biochemistry applications to ensure reproducibility. The authors optimized co-immunoprecipitation with mass spectrometry by combining a native co-immunoprecipitation procedure with single-pot, solid-phase enhanced sample preparation. The authors' results for the highly conserved chromatin regulator FACT subunits HMG-3 and HMG-4 demonstrated that single-pot, solid-phase enhanced sample preparation-integrated co-immunoprecipitation with mass spectrometry procedures for C. elegans samples are highly robust. Moreover, in an accompanying study about the chromodomain factor MRG-1 (MRG15 in humans), the authors demonstrated remarkably high reproducibility for ten replicate experiments

YAP and β-catenin co-operate to drive oncogenesis in basal breast cancer

Targeting cancer stem cells (CSCs) can serve as an effective approach toward limiting resistance to therapies and the development of metastases in many forms of cancer. While basal breast cancers encompass cells with CSC features, rational therapies remain poorly established. Here, we show that receptor tyrosine kinase Met signalling promotes the activity of the Hippo component YAP in basal breast cancer. Further analysis revealed enhanced YAP activity within the CSC population. Using both genetic and pharmaceutical approaches, we show that interfering with YAP activity delays basal cancer formation, prevents luminal to basal trans-differentiation and reduces CSC survival. Gene expression analysis of YAP knock-out mammary glands revealed a strong decrease in β-catenin target genes in basal breast cancer, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, we find that nuclear YAP interacts and overlaps with β-catenin and TEAD4 at common gene regulatory elements. Analysis of proteomic data from primary breast cancer patients identified a significant upregulation of the YAP activity signature in basal compared to other breast cancers, suggesting that YAP activity is limited to basal types. Our findings demonstrate that in basal breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal (triple-negative) breast cancers

X-ray magneto-optics of lanthanide materials: principles and applications

Lanthanide metals are a particular class of magnetic materials in which the magnetic moments are carried mainly by the localized electrons of the 4f shell. They are frequently found in technically relevant systems, to achieve, e.g., high magnetic anisotropy. Magneto-optical methods in the x-ray range are well suited to study complex magnetic materials in an element-specific way. In this work, we report on recent progress on the quantitative determination of magneto-optical constants of several lanthanides in the soft x-ray region and we show some examples of applications of magneto-optics to hard-magnetic interfaces and exchange-coupled layered structures containing lanthanide elements.Comment: 7 pages, 6 figures, invited contribution to the Symposium "X-ray magneto-optics" of the Spring Meeting of the German Physical Society held in Regensburg, Germany, 8-12 March 2004. Revised version, minor change

Review of biorthogonal coupled cluster representations for electronic excitation

Single reference coupled-cluster (CC) methods for electronic excitation are based on a biorthogonal representation (bCC) of the (shifted) Hamiltonian in terms of excited CC states, also referred to as correlated excited (CE) states, and an associated set of states biorthogonal to the CE states, the latter being essentially configuration interaction (CI) configurations. The bCC representation generates a non-hermitian secular matrix, the eigenvalues representing excitation energies, while the corresponding spectral intensities are to be derived from both the left and right eigenvectors. Using the perspective of the bCC representation, a systematic and comprehensive analysis of the excited-state CC methods is given, extending and generalizing previous such studies. Here, the essential topics are the truncation error characteristics and the separability properties, the latter being crucial for designing size-consistent approximation schemes. Based on the general order relations for the bCC secular matrix and the (left and right) eigenvector matrices, formulas for the perturbation-theoretical (PT) order of the truncation errors (TEO) are derived for energies, transition moments, and property matrix elements of arbitrary excitation classes and truncation levels. In the analysis of the separability properties of the transition moments, the decisive role of the so-called dual ground state is revealed. Due to the use of CE states the bCC approach can be compared to so-called intermediate state representation (ISR) methods based exclusively on suitably orthonormalized CE states. As the present analysis shows, the bCC approach has decisive advantages over the conventional CI treatment, but also distinctly weaker TEO and separability properties in comparison with a full (and hermitian) ISR method

H3.3K27M mutation is not a suitable target for immunotherapy in HLA-A2(+) patients with diffuse midline glioma

Diffuse midline glioma is the leading cause of solid cancer-related deaths in children with very limited treatment options. A majority of the tumors carry a point mutation in the histone 3 variant (H3.3) creating a potential HLA-A*02:01 binding epitope (H3.3K27M(26-35)). Here, we isolated an H3.3K27M-specific T cell receptor (TCR) from transgenic mice expressing a diverse human TCR repertoire. Despite a high functional avidity of H3.3K27M-specific T cells, we were not able to achieve recognition of cells naturally expressing the H3.3K27M mutation, even when overexpressed as a transgene. Similar results were obtained with T cells expressing the published TCR 1H5 against the same epitope. CRISPR/Cas9 editing was used to exclude interference by endogenous TCRs in donor T cells. Overall, our data provide strong evidence that the H3.3K27M mutation is not a suitable target for cancer immunotherapy, most likely due to insufficient epitope processing and/or amount to be recognized by HLA-A*02:01 restricted CD8(+) T cells

SUMOylation of the chromodomain factor MRG-1 in C. elegans affects chromatin-regulatory dynamics

Epigenetic mechanisms control chromatin accessibility and gene expression to ensure proper cell fate specification. Histone proteins are integral chromatin components, and their modification promotes gene expression regulation. Specific proteins recognize modified histones such as the chromodomain protein MRG-1. MRG-1 is the Caenorhabditis elegans ortholog of mammalian MRG15, which is involved in DNA repair. MRG-1 binds methylated histone H3 and is important for germline maturation and safeguarding. To elucidate interacting proteins that modulate MRG-1 activity, we performed in-depth protein-protein interaction analysis using immunoprecipitations coupled with mass spectrometry. We detected strong association with the Small ubiquitin-like modifier SUMO, and found that MRG-1 is post-translationally modified by SUMO. SUMOylation affects chromatin-binding dynamics of MRG-1, suggesting an epigenetic regulation pathway, which may be conserved

Prediction of huge X-ray Faraday rotation at the Gd N_4,5 threshold

X-ray absorption spectra in a wide energy range around the 4d-4f excitation threshold of Gd were recorded by total electron yield from in-plane magnetized Gd metal films. Matching the experimental spectra to tabulated absorption data reveals unprecedented short light absorption lengths down to 3 nm. The associated real parts of the refractive index for circularly polarized light propagating parallel or antiparallel to the Gd magnetization, determined through the Kramers-Kronig transformation, correspond to a magneto-optical Faraday rotation of 0.7 degrees per atomic layer. This finding shall allow the study of magnetic structure and magnetization dynamics of lanthanide elements in nanosize systems and dilute alloys.Comment: 4 pages, 2 figures, final version resubmitted to Phys. Rev. B, Brief Reports. Minor change

A CRISPR/Cas9-mediated screen identifies determinants of early plasma cell differentiation

INTRODUCTION: The differentiation of B cells into antibody-secreting plasma cells depends on cell division-coupled, epigenetic and other cellular processes that are incompletely understood. METHODS: We have developed a CRISPR/Cas9-based screen that models an early stage of T cell-dependent plasma cell differentiation and measures B cell survival or proliferation versus the formation of CD138+ plasmablasts. Here, we refined and extended this screen to more than 500 candidate genes that are highly expressed in plasma cells. RESULTS: Among known genes whose deletion preferentially or mostly affected plasmablast formation were the transcription factors Prdm1 (BLIMP1), Irf4 and Pou2af1 (OBF-1), and the Ern1 gene encoding IRE1a, while deletion of XBP1, the transcriptional master regulator that specifies the expansion of the secretory program in plasma cells, had no effect. Defective plasmablast formation caused by Ern1 deletion could not be rescued by the active, spliced form of XBP1 whose processing is dependent on and downstream of IRE1a, suggesting that in early plasma cell differentiation IRE1a acts independently of XBP1. Moreover, we newly identified several genes involved in NF-kB signaling (Nfkbia), vesicle trafficking (Arf4, Preb) and epigenetic regulators that form part of the NuRD complex (Hdac1, Mta2, Mbd2) to be required for plasmablast formation. Deletion of ARF4, a small GTPase required for COPI vesicle formation, impaired plasmablast formation and blocked antibody secretion. After Hdac1 deletion plasmablast differentiation was consistently reduced by about 50%, while deletion of the closely related Hdac2 gene had no effect. Hdac1 knock-out led to strongly perturbed protein expression of antagonistic transcription factors that govern plasma cell versus B cell identity (by decreasing IRF4 and BLIMP1 and increasing BACH2 and PAX5). DISCUSSION: Taken together, our results highlight specific and non-redundant roles for Ern1, Arf4 and Hdac1 in the early steps of plasma cell differentiation