Defective insulin receptor signaling in hPSCs skews pluripotency and negatively perturbs neural differentiation
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Van der Waals (vdW) ferroelectrics have attracted significant attention for their potential in next-generation nano-electronics. Two-dimensional (2D) group-IV monochalcogenides have emerged as a promising candidate due to their strong room temperature in-plane polarization down to a monolayer limit. However, their polarization is strongly coupled with the lattice strain and stacking orders, which impact their electronic properties. Here, we utilize four-dimensional scanning transmission electron microscopy (4D-STEM) to simultaneously probe the in-plane strain and out-of-plane stacking in vdW SnSe. Specifically, we observe large lattice strain up to 4% with a gradient across ~50 nm to compensate lattice mismatch at domain walls, mitigating defects initiation. Additionally, we discover the unusual ferroelectric-to-antiferroelectric domain walls stabilized by vdW force and may lead to anisotropic nonlinear optical responses. Our findings provide a comprehensive understanding of in-plane and out-of-plane structures affecting domain properties in vdW SnSe, laying the foundation for domain wall engineering in vdW ferroelectrics.
One-dimensional metallic transition-metal chalcogenide nanowires (TMC-NWs) hold promise for interconnecting devices built on two-dimensional (2D) transition-metal dichalcogenides, but only isotropic growth has so far been demonstrated. Here we show the direct patterning of highly oriented Mo 6 Te 6 NWs in 2D molybdenum ditelluride (MoTe 2 ) using graphite as confined encapsulation layers under external stimuli. The atomic structural transition is studied through in-situ electrical biasing the fabricated heterostructure in a scanning transmission electron microscope. Atomic resolution high-angle annular dark-field STEM images reveal that the conversion of Mo 6 Te 6 NWs from MoTe 2 occurs only along specific directions. Combined with first-principles calculations, we attribute the oriented growth to the local Joule-heating induced by electrical bias near the interface of the graphite-MoTe 2 heterostructure and the confinement effect generated by graphite. Using the same strategy, we fabricate oriented NWs confined in graphite as lateral contact electrodes in the 2H-MoTe 2 FET, achieving a low Schottky barrier of 11.5 meV, and low contact resistance of 43.7 Ω µm at the metal-NW interface. Our work introduces possible approaches to fabricate oriented NWs for interconnections in flexible 2D nanoelectronics through direct metal phase patterning.
This report documents the Applied Meteorology Unit's (AMU) evaluation of the effectiveness and utility of the Automated Surface Observing System (ASOS) in terms of spaceflight operations and user requirements. In particular, the evaluation determines which of the Shuttle Landing Facility (SLF) observation requirements can be satisfied by ASOS. This report also includes a summary of ASOS' background, current configuration and specifications, system performance, and the possible concepts of operations for use of ASOS at the SLF. This evaluation stems from a desire by the Air Force to determine if ASOS units could be used to reduce the cost of SLF meteorological observations.
Through the Minority University Research and Education Project (MUREP), NASA engages underrepresented populations via various initiatives, including by means of three year competitive awards for Data Science Equity, Access, and Priority in Research and Education (DEAP) Institutes led by Historically Black Colleges and Universities (HBCUs). MUREP DEAP Institutes, multi-institutional consortia, conduct data science research and capacity building initiatives that aim to enhance the research, academic, and technological capabilities of the participating HBCUs while providing NASA-specific knowledge, skills and opportunities for students and faculty who have historically been underrepresented and underserved in the STEM workforce. Three MUREP DEAP Institutes, led by Bethune-Cookman University, North Carolina A&T University, and North Carolina Central University, are conducting data science and natural hazard related research utilizing remote sensing and earth observations, with mentorship for the Institutes provided by scientists from NASA’s Marshall Space Flight Center. Each Institute has unique capabilities, needs, and goals, but overlap in their common interest to conduct cutting edge data science and natural hazard related research and to build capacity, broaden participation, and increase retention of a diverse group of participating students and faculty. Here, successes and challenges from the first year of activities at each MUREP DEAP institute are discussed, where activities focused primarily on the recruitment of a diverse group of students and the upskilling of students and faculty in data science and remote sensing concepts. The planned activities and goals of each DEAP Institute for the upcoming two years of activities will also be discussed, both from research and community-building perspectives.
Vibration-based condition monitoring techniques are widely used for diagnosing faults in rotating machines. These techniques are implemented in the time domain, the frequency domain, or both. However, the composite and noisy nature of the raw data collected requires a preprocessing stage such as filtering and decomposition using in-depth processing techniques. Moreover, these methods require good frequency resolution and involve examining a broad frequency range to discern both healthy and faulty cases. In this work, we introduce a simple and fast diagnostic scheme for wind turbine gear teeth wear based on time domain analysis. The proposed method is based on the local minima interpolation of a filtered version of the vibration signal following time synchronous averaging (TSA) technique. Given tachometer signal, the TSA of the vibration data is performed using MTALAB software. Then, local minima of the filtered signal are interpolated using the Piecewise Cubic Hermite Interpolating Polynomial (PCHIP) function. The variance of the interpolated curve built a gear fault index. The derived fault index resulting of the proposed technique allows a substantial distinction between the healthy and faulty cases. Its efficiency is validated using 10 real-world datasets of vibration stemmed from a wind turbine planetary gearbox. The proposed method boasts a low computation time and ease of interpretation, specifically beneficial for gearbox fault diagnosis purposes.
Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
The era of the International Space Station (ISS) has finally arrived, providing researchers on Earth a unique opportunity to study long-term effects of weightlessness and the space environment on structures, materials and living systems. Many of the physical, biological and material science experiments planned for ISS will require significant input and expertise from astronauts who must conduct the research, follow complicated assay procedures and collect data and samples in space. Containment is essential for Much of this work, both to protect astronauts from potentially harmful biological, chemical or material elements in the experiments as well as to protect the experiments from contamination by air-born particles In the Space Station environment. When astronauts must open the hardware containing such experiments, glovebox facilities provide the necessary barrier between astronaut and experiment. On Earth, astronauts are laced with the demanding task of preparing for the many glovebox experiments they will perform in space. Only a short time can be devoted to training for each experimental task and gl ovebox research only accounts for a small portion of overall training and mission objectives on any particular ISS mission. The quality of the research also must remain very high, requiring very detailed experience and knowledge of instrumentation, anatomy and specific scientific objectives for those who will conduct the research. This unique set of needs faced by NASA has stemmed the development of a new computer simulation tool, the Virtual Glovebox (VGB), which is designed to provide astronaut crews and support personnel with a means to quickly and accurately prepare and train for glovebox experiments in space.
This NASA Conference Publication features select papers and PowerPoint presentations from the Education and Training Track of MODSIM World 2007 Conference and Expo. Invited speakers and panelists of national and international renown, representing academia, industry and government, discussed how modeling and simulation (M&S) technology can be used to accelerate learning in the K-16 classroom, especially when using M&S technology as a tool for integrating science, technology, engineering and mathematics (STEM) classes. The presenters also addressed the application ofM&S technology to learning and training outside of the classroom. Specific sub-topics of the presentations included: learning theory; curriculum development; professional development; tools/user applications; implementation/infrastructure/issues; and workforce development. There was a session devoted to student M&S competitions in Virginia too, as well as a poster session.
In higher plants, polyamines arise from arginine by one of two pathways: via ornithine and ornithine decarboxylase or via agmatine and arginine decarboxylase but in fungi, only the ornithine decarboxylase pathway is present. Since polyamines are required for normal growth of microorganisms and plants and since the ornithine pathway can be irreversibly blocked by alpha-difluoromethylornithine (DFMO) which has no effect on arginine decarboxylase, fungal infection of green plants might be controlled by the site-directed use of such a specific metabolic inhibitor. DFMO at relatively low concentrations provided effective control of the three biotrophic fungal pathogens studied, Puccinia recondita (leaf rust), P. graminis f. sp. tritici (stem rust), and Erysiphe graminis (powdery mildew) on wheat (Triticum aestivum L.) Effective control of infection by leaf or stem rust fungi was obtained with sprays of DFMO that ranged from about 0.01 to 0.20 mM in experiments where the inhibitor was applied after spore inoculation. The powdery mildew fungus was somewhat more tolerant of DFMO, but good control of the pathogen was obtained at less than 1.0 mM. In general, application of DFMO after spore inoculation was more effective than application before inoculation. Less control was obtained following treatment with alpha-difluoromethylarginine (DFMA) but the relatively high degree of control obtained raises the possibility of a DFMA to DFMO conversion by arginase.
The Cloud, Aerosol and Monsoon Processes Philippines Experiment (CAMP2Ex) is a NASA/NRL mission studying clouds and aerosols with the NASA P-3B aircraft, a Learet and an ocean research vessel. The mission is based in the Philippines from late August through early October 2019. This presentation is aimed at 8-12th grade students in the Philippines for education/outreach purposes to expose students to NASA Earth and Airborne Science research, the CAMP2Ex mission, and careers in science, technology, engineering and math (STEM).The presentation starts with an overview of NASA Earth science, including discussing how and why NASA studies the earth using satellites, airplanes, and sensors on the ground. We discuss the NASA Airborne Science Program and how NASA uses airplanes to study the Earth from the equator to the poles. We discuss the CAMP2Ex mission specifically, including mission science goals and why we are based in the Philippines. We will discuss basic cloud physics and remote sensing using demonstrations and activities. Finally, we discuss careers in STEM and at NASA, giving personal examples of the career paths of scientists, engineers and pilots on the CAMP2Ex mission.
Abstract Lesions involving the osteochondral unit are difficult to treat. Biomimetic scaffolds are previously shown as promising alternative. Such devices often lack multiple functional layers that mimic bone, cartilage, and the interface. In this study, multilayered scaffolds are developed based on the use of natural extracellular matrix (ECM)‐like biopolymers. Particular attention is paid to obtain a complex matrix that mimics the native osteochondral transition. Porous, sponge‐like chitosan‐collagen‐octacalcium phosphate (OCP) scaffolds are obtained. Collagen content increases while the amount of OCP particles decreases toward the cartilage layer. The scaffolds are bioactive as a mineral layer is deposited containing hydroxyapatite at the bony side. The scaffolds stimulate proliferation of human adipose‐derived mesenchymal stem cells, but the degree of proliferation depends on the cell seeding density. The scaffolds give rise to a zone‐specific gene expression. RUNX2, COL1A1, BGLAP, and SPP1 are upregulated in the bony layer of the scaffold. SOX9 is upregulated concomitant with COL2A1 expression in the cartilage zone. Mineralization in presence of the cells is prominent in the bone area with Ca and P steadily increasing over time. These results are encouraging for the fabrication of biomimetic scaffolds using ECM‐like materials and featuring gradients that mimic native tissues and their interface.
Plant and fungal cell walls are essential for growth, adaptation, and survival, with their intricate architectures dictating both resistance to stress and susceptibility to antifungal or biomass-degrading strategies. Understanding how these walls are built, remodeled, and function at the molecular level is therefore central to both clinical and biotechnological applications. Solid-state nuclear magnetic resonance (ssNMR) has emerged as a uniquely powerful tool for this purpose, as it reveals the structure, dynamics, and interactions of intact biopolymers without disrupting their native organization. Using this approach, recent studies have shown how structural polymorphism, polymer-polymer interactions, and species-specific remodeling govern mechanical integrity, drug resistance, and stress adaptation. Applications highlighted here include lignin-carbohydrate packing during plant stem maturation, fungal wall reorganization under treatment by wall-targeting antifungals such as echinocandin and nikkomycin, and the functional diversity of glucans, chitins, and mannans. Together, these insights uncover conserved principles of polymer assembly across kingdoms while informing new opportunities for antifungal development and biomass utilization. Ongoing advances in sensitivity and resolution are expected to broaden the reach of ssNMR and further accelerate its role in linking structural heterogeneity to biosynthetic complexity and biological function.
Biopolymer sequences dictate their functions, and protein-based polymers are a promising platform to establish sequence–function relationships for novel biopolymers. To efficiently explore vast sequence spaces of natural proteins, sequence repetition is a common strategy to tune and amplify specific functions. This strategy is applied to repeats-in-toxin (RTX) proteins with calcium-responsive folding behavior, which stems from tandem repeats of the nonapeptide GGXGXDXUX in which X can be any amino acid and U is a hydrophobic amino acid. To determine the functional range of this nonapeptide, we modified a naturally occurring RTX protein that forms β-roll structures in the presence of calcium. Sequence modifications focused on calcium-binding turns within the repetitive region, including either global substitution of nonconserved residues or complete replacement with tandem repeats of a consensus nonapeptide GGAGXDTLY. Some sequence modifications disrupted the typical transition from intrinsically disordered random coils to folded β rolls, despite conservation of the underlying nonapeptide sequence. Proteins enriched with smaller, hydrophobic amino acids adopted secondary structures in the absence of calcium and underwent structural rearrangements in calcium-rich environments. In contrast, proteins with bulkier, hydrophilic amino acids maintained intrinsic disorder in the absence of calcium. In conclusion, these results indicate a significant role of nonconserved amino acids in calcium-responsive folding, thereby revealing a strategy to leverage sequences in the design of tunable, calcium-responsive biopolymers.
The introduction of invasive microbes compromises the structure, biodiversity, and function of naïve ecosystems. Sphaerulina musiva, a hemibiotrophic pathogen that causes leaf spot and stem cankers in Populus species, exemplifies an invasive fungal pathogen spread by human activities. However, the genetic mechanisms of pathogenicity and virulence are poorly understood, impeding mitigation strategies. We utilized RNA sequencing to identify fungal effectors linked to stem canker formation, informing the development of future strategies for effective disease management. Our analysis revealed 70 genes differentially expressed at 2 weeks and 110 genes at 3 weeks between inoculated trees and controls. Notably, the gene with the highest expression at 2 weeks and the second highest at 3 weeks was homologous to Extracellular protein 2 (Ecp2). Complementary genome-wide association studies linked sequence polymorphisms in this locus to phenotypic variation in disease severity. Infiltration of S. musiva Ecp2 into Populus trichocarpa leaves induced necrosis in susceptible genotypes. Gene disruption using a CRISPR-Cas9 RNP system resulted in a genotype-dependent reduction of stem canker and disease severity. Tracing the evolutionary history of this effector across the fungal kingdom, we uncovered clade-specific gene-family expansions and orthologs in new species. These findings raise questions about the function and adaptive significance of these gene families in fungal lifestyles. Our study provides the first tractable target for breeding resistant poplar genotypes, addressing the challenges of managing S. musiva and uncovering mechanisms that drive its virulence, and provides deeper insights into the evolutionary dynamics of a conserved small-secreted protein with a diversity of functions.
Understanding how broadly neutralizing antibodies (bnAbs) to influenza hemagglutinin (HA) naturally develop in humans is critical to the design of universal influenza vaccines. Several classes of bnAbs directed to the conserved HA stem were found in multiple individuals, including one encoded by heavy-chain variable domain V H 6-1. We describe two genetically similar V H 6-1 bnAb clonotypes from the same individual that exhibit different developmental paths toward broad neutralization activity. One clonotype evolved from a germline precursor recognizing influenza group 1 subtypes to gain breadth to group 2 subtypes. The other clonotype recognized group 2 subtypes and developed binding to group 1 subtypes through somatic hypermutation. Crystal structures reveal that the specificity differences are primarily mediated by complementarity-determining region H3 (CDR H3). Thus, while V H 6-1 provides a framework for development of HA stem-directed bnAbs, sequence differences in CDR H3 junctional regions during VDJ recombination can alter reactivity and evolutionary pathways toward increased breadth.
Abstract Delafossite thin films exhibit a range of intriguing physical properties derived from their layered structure, which consists of alternating noble metal ( A + ) and ( B O 2 − ) sublayers in an AB O 2 stoichiometry. The integration of these properties into functional devices requires the successful epitaxial growth of delafossites as thin films on appropriate substrates. Unfortunately, their unique lattice geometry complicates growth, as different delafossites display variable behavior on the same substrate, often unrelated to lattice mismatch. This suggests the presence of yet unidentified stabilization mechanisms that enable the selective growth of certain delafossites, allowing them to be grown either as films themselves or to be used as buffer layers for subsequent deposition. In this study, advanced scanning transmission electron microscopy (STEM) is employed to investigate the nucleation mechanisms governing the stable growth of Cu‐based delafossites on Al 2 O 3 , specifically CuCrO 2 and CuFeO 2 thin films synthesized via molecular‐beam epitaxy. These findings reveal that a combination of a misfit dislocation network at the interface and monolayer‐deep chemical intermixing effectively relieves lattice mismatch strain. This mechanism, which differs fundamentally from that observed in Pd‐based delafossites, provides key insights into the controlled epitaxy of delafossite materials.
Na 2 Ni 2 TeO 6 has a layered hexagonal structure with a honeycomb lattice constituted by Ni 2+ and a chiral charge distribution of Na + that resides between the Ni layers. In the present work, the antiferromagnetic transition temperature of Na 2 Ni 2 TeO 6 is confirmed at TN˜ 27 K, and further, it is found to be robust up to 8 T magnetic field and 1.2 GPa external pressure; and, without any frequency-dependence. Slight deviations from nominal Na-content (up to 5%) does not seem to influence the magnetic transition temperature, TN. Isothermal magnetization curves remain almost linear up to 13 T. Our analysis of neutron diffraction data shows that the magnetic structure of Na 2 Ni 2 TeO 6 is faithfully described by a model consisting of two phases described by the commensurate wave vectors vec kc, (0.5 0 0) and (0.5 0 0.5), with an additional short-range order component incorporated in to the latter phase. Consequently, a zig-zag long-range ordered magnetic phase of Ni 2+ results in the compound, mixed with a short-range ordered phase, which is supported by our specific heat data. Theoretical computations based on density functional theory (DFT) predict predominantly in-plane magnetic exchange interactions that conform to a J1-J2-J3 model with a strong J3 term. The computationally predicted parameters lead to a reliable estimate for TN and the experimentally observed zig-zag magnetic structure. A spin wave excitation in Na 2 Ni 2 TeO 6 at E ˜ 5 meV at T = 5 K is mapped out through inelastic neutron scattering experiments, which is reproduced by linear spin wave theory calculations using the J values from our computations. Our specific heat data and inelastic neutron scattering data strongly indicate the presence of short-range spin correlations, at T > TN, stemming from incipient antiferromagnetic clusters.