Realizing smart scanning transmission electron microscopy using high performance computing.

Scanning Transmission Electron Microscopy (STEM) coupled with Electron Energy Loss Spectroscopy (EELS) presents a powerful platform for detailed material characterization via rich imaging and spectroscopic data. Modern electron microscopes can access multiple length scales and sampling rates far beyond human perception and reaction time. Recent advancements in machine learning (ML) offer a promising avenue to enhance these capabilities by integrating ML algorithms into the STEM-EELS framework, fostering an environment of active learning.

Azide-based preparation of fused heterocyclic imines and their multicomponent reactions.

Structurally diverse pyrroles, indoles and imidazoles bearing an -ω-azidoalkyl moiety and an aldehyde or ketone function were prepared and successfully introduced into imine generation the intramolecular Staudinger/aza-Wittig tandem reaction. Reduction of the generated imines led to medicinally relevant nitrogen-containing fused heterocycles such as tetrahydropyrrolo[1,2-]pyrazines and diazepines. Rare 8-membered hexahydropyrrolo[1,2-][1,4]diazocine and 9-membered dihydro-4,8-(metheno)pyrrolo[1,2-][1,4]diazacycloundecine were also synthesized.

Dynamic STEM-EELS for single-atom and defect measurement during electron beam transformations.

This study introduces the integration of dynamic computer vision-enabled imaging with electron energy loss spectroscopy (EELS) in scanning transmission electron microscopy (STEM). This approach involves real-time discovery and analysis of atomic structures as they form, allowing us to observe the evolution of material properties at the atomic level, capturing transient states traditional techniques often miss. Rapid object detection and action system enhances the efficiency and accuracy of STEM-EELS by autonomously identifying and targeting only areas of interest.

Nanoscale core-shell structure and recrystallization of swift heavy ion tracks in SrTiO.

It is widely accepted that the interaction of swift heavy ions with many complex oxides is predominantly governed by the electronic energy loss that gives rise to nanoscale amorphous ion tracks along the penetration direction. The question of how electronic excitation and electron-phonon coupling affect the atomic system through defect production, recrystallization, and strain effects has not yet been fully clarified. To advance the knowledge of the atomic structure of ion tracks, we irradiated single crystalline SrTiO with 629 MeV Xe ions and performed comprehensive electron microscopy investigations complemented by molecular dynamics simulations.

Bromine Incorporation Affects Phase Transformations and Thermal Stability of Lead Halide Perovskites.

Mixed-cation and mixed-halide lead halide perovskites show great potential for their application in photovoltaics. Many of the high-performance compositions are made of cesium, formamidinium, lead, iodine, and bromine. However, incorporating bromine in iodine-rich compositions and its effects on the thermal stability of the perovskite structure has not been thoroughly studied.

Direct Fabrication of Atomically Defined Pores in MXenes Using Feedback-Driven STEM.

Controlled fabrication of nanopores in 2D materials offer the means to create robust membranes needed for ion transport and nanofiltration. Techniques for creating nanopores have relied upon either plasma etching or direct irradiation; however, aberration-corrected scanning transmission electron microscopy (STEM) offers the advantage of combining a sub-Å sized electron beam for atomic manipulation along with atomic resolution imaging. Here, a method for automated nanopore fabrication is utilized with real-time atomic visualization to enhance the mechanistic understanding of beam-induced transformations.

Discovery and characterization of potent spiro-isoxazole-based cereblon ligands with a novel binding mode.

The vast majority of current cereblon (CRBN) ligands is based on the thalidomide scaffold, relying on glutarimide as the core binding moiety. With this architecture, most of these ligands inherit the overall binding mode, interactions with neo-substrates, and thereby potentially also the cytotoxic and teratogenic properties of the parent thalidomide. In this work, by incorporating a spiro-linker to the glutarimide moiety, we have generated a new chemotype that exhibits an unprecedented binding mode for glutarimide-based CRBN ligands.

New Biocides Based on -Alkylcytidines: Effects on Microorganisms and Application for the Protection of Cultural Heritage Objects of Painting.

The rapid increase in the antibiotic resistance of microorganisms, capable of causing diseases in humans as destroying cultural heritage sites, is a great challenge for modern science. In this regard, it is necessary to develop fundamentally novel and highly active compounds. In this study, a series of -alkylcytidines, including 5- and 6-methylcytidine derivatives, with extended alkyl substituents, were obtained in order to develop a new generation of antibacterial and antifungal biocides based on nucleoside derivatives.

Explainability and human intervention in autonomous scanning probe microscopy.

The broad adoption of machine learning (ML)-based autonomous experiments (AEs) in material characterization and synthesis requires strategies development for understanding and intervention in the experimental workflow. Here, we introduce and realize a post-experimental analysis strategy for deep kernel learning-based autonomous scanning probe microscopy. This approach yields real-time and post-experimental indicators for the progression of an active learning process interacting with an experimental system.

Cryosurgery for Basal Cell Skin Cancer of the Head: 15 Years of Experience.

The clinical relevance of head and neck (H&N) tumors is related to the potential disfiguration of anatomical structures (by the tumor or surgical intervention), defining patients' individual features and emotional expression, loss or restraint of vital structures functions, and untoward socio-economic sequelae. This study is aimed to improve clinical outcomes of cryosurgery in patients with H&N basal cell skin cancer by refining the indications for cryosurgical treatment. In this study, cryosurgery was used in 234 patients with different stages of cutaneous basal cell carcinoma (BCC) of the head, including 101 patients with T1 tumors, 86-with T2, 5-T3, and 42 patients with tumors relapsing after failure of preceding various treatment modalities.

Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells.

Ewing sarcoma (ES) is one of the most frequent types of malignant tumors among children. The active metabolic state of ES cells presents a new potential target for therapeutic interventions. As a primary regulator of cellular homeostasis, carbonic anhydrases (CAs; EC 4.

Stress and Curvature Effects in Layered 2D Ferroelectric CuInPS.

Nanoscale ferroelectric 2D materials offer the opportunity to investigate curvature and strain effects on materials functionalities. Among these, CuInPS (CIPS) has attracted tremendous research interest in recent years due to combination of room temperature ferroelectricity, scalability to a few layers thickness, and ferrielectric properties due to coexistence of 2 polar sublattices. Here, we explore the local curvature and strain effect on polarization in CIPS via piezoresponse force microscopy and spectroscopy.

Astrocyte lipocalin-2 modestly effects disease severity in a mouse model of multiple sclerosis while reducing mature oligodendrocyte protein and mRNA expression.

Roles for lipocalin-2 (LCN2, also referred to as neutrophil gelatinase associated lipocalin, NGAL) in the progression of disease in multiple sclerosis and its animal models have been reported; however, the importance of astrocyte-derived LCN2, a major source of LCN2, have not been defined. We found that clinical scores in experimental autoimmune encephalomyelitis (EAE) were modestly delayed in mice with conditional knockout of LCN2 from astrocytes, associated with a small decrease in astrocyte GFAP expression. Immunostaining and qPCR of spinal cord samples showed decreased oligodendrocyte proteolipid protein and transcription factor Olig2 expression, but no changes in PDGFRα expression.

Substrate-Controlled Three-Component Synthesis of Diverse Fused Heterocycles.

A chemoselective strategy toward a variety of fused heterocyclic scaffolds relying on a three-component condensation of heterocyclic ketene aminals (HKAs) or corresponding thioaminals with aryl glyoxals and cyclic 1,3-dicarbonyl compounds has been developed and explored. Depending on the applied combination of substrates, the strategy can be tuned to provide straightforward access to imidazo[1,2-]quinoline, pyrrolo[1,2-]imidazole, and pyrrolo[2,1-]thiazole frameworks.

Genetic deletion of c-Jun amino-terminal kinase 3 (JNK3) modestly increases disease severity in a mouse model of multiple sclerosis.

The c-Jun amino terminal kinases (JNKs) regulate transcription, and studies suggest they contribute to neuropathology in the EAE model of MS. To examine the role of the JNK3 isoform, we compared EAE in JNK3 null mice to wild type (WT) littermates. Although disease severity was similar in female mice, in male JNK3 null mice the day of onset and time to reach 100% incidence occurred sooner, and disease severity was increased.

Disentangling Electronic Transport and Hysteresis at Individual Grain Boundaries in Hybrid Perovskites via Automated Scanning Probe Microscopy.

Underlying the rapidly increasing photovoltaic efficiency and stability of metal halide perovskites (MHPs) is the advancement in the understanding of the microstructure of polycrystalline MHP thin film. Over the past decade, intense efforts have been aimed at understanding the effect of microstructures on MHP properties, including chemical heterogeneity, strain disorder, phase impurity, etc. It has been found that grain and grain boundary (GB) are tightly related to lots of microscale and nanoscale behavior in MHP thin films.

Versatile Diazomethane Sulfonamide for Expedited Exploration of Azole-Based Carbonic Anhydrase Inhibitors via [3+2] Cycloaddition.

A newly introduced diazo reagent, 1-diazo-N,N-bis(4-methoxybenzyl)methanesulfonamide, enables access to a range of azole-based primary sulfonamides via [3+2] cycloaddition followed by protecting group removal. Such compounds are representative of the sulfonamide chemical space highly relevant but hitherto not investigated in the context of inhibition of therapeutically relevant isoforms of carbonic anhydrase enzyme. Using this reagent, three sets of primary sulfonamides based on pyrazole, 1,2,3-triazole and tetrazole cores were synthesized and profiled for inhibition of tumor-associated hCA IX and XII isoforms as well as abundant cytosolic hCA I and II isoforms.

Exploring the Relationship of Microstructure and Conductivity in Metal Halide Perovskites via Active Learning-Driven Automated Scanning Probe Microscopy.

Electronic transport and hysteresis in metal halide perovskites (MHPs) are key to the applications in photovoltaics, light emitting devices, and light and chemical sensors. These phenomena are strongly affected by the materials microstructure including grain boundaries, ferroic domain walls, and secondary phase inclusions. Here, we demonstrate an active machine learning framework for "driving" an automated scanning probe microscope (SPM) to discover the microstructures responsible for specific aspects of transport behavior in MHPs.

Autonomous scanning probe microscopy with hypothesis learning: Exploring the physics of domain switching in ferroelectric materials.

Using hypothesis-learning-driven automated scanning probe microscopy (SPM), we explore the bias-induced transformations that underpin the functionality of broad classes of devices and materials from batteries and memristors to ferroelectrics and antiferroelectrics. Optimization and design of these materials require probing the mechanisms of these transformations on the nanometer scale as a function of a broad range of control parameters, leading to experimentally intractable scenarios. Meanwhile, often these behaviors are understood within potentially competing theoretical hypotheses.