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Quantitative and volumetric assessment of filamentous actin fibers (F-actin) remains challenging due to their interconnected nature, leading researchers to utilize threshold based or qualitative measurement methods with poor reproducibility. Here we introduce a novel machine learning based methodology for accurate quantification and reconstruction of nuclei-associated F-actin. Utilizing a Convolutional Neural Network (CNN), we segment actin filaments and nuclei from 3D confocal microscopy images and then reconstruct each fiber by connecting intersecting contours on cross-sectional slices. This allowed measurement of the total number of actin filaments and individual actin filament length and volume in a reproducible fashion. Focusing on the role of F-actin in supporting nucleocytoskeletal connectivity, we quantified apical F-actin, basal F-actin, and nuclear architecture in mesenchymal stem cells (MSCs) following the disruption of the Linker of Nucleoskeleton and Cytoskeleton (LINC) Complexes. Disabling LINC in mesenchymal stem cells (MSCs) generated F-actin disorganization at the nuclear envelope characterized by shorter length and volume of actin fibers contributing a less elongated nuclear shape. Our findings not only present a new tool for mechanobiology but introduce a novel pipeline for developing realistic computational models based on quantitative measures of F- actin.

Mesenchymal stem cells (MSC) respond to environmental forces with both cytoskeletal re-structuring and activation of protein chaperones of mechanical information, β-catenin and Yes-Associated Protein 1 (YAP1). To function, MSCs must differentiate between dynamic forces such as cyclic strains of extracellular matrix due to physical activity and static strains due to ECM stiffening. To delineate how MSCs recognize and respond differently to both force types, we compared effects of dynamic (200 cycles x 2%) and static (1 × 2% hold) strain on nuclear translocation of β-catenin and YAP1 at 3h after force application. Dynamic strain induced nuclear accumulation of β-catenin, and increased cytoskeletal actin structure and cell stiffness, but had no effect on nuclear YAP1 levels. Critically, both nuclear actin and nuclear stiffness increased along with dynamic strain-induced β-catenin transport. Augmentation of cytoskeletal structure using either static strain or lysophosphatidic acid (LPA) did not increase nuclear content of β–catenin or actin, but induced robust nuclear increase in YAP1. As actin binds β-catenin, we considered whether β-catenin, which lacks a nuclear localization signal, was dependent on actin to gain entry to the nucleus. Knockdown of cofilin-1 (Cfl1) or importin-9 (Ipo9), which co-mediate nuclear transfer of G-actin, prevented dynamic strain-mediated nuclear transfer of both β-catenin and actin. In sum, dynamic strain induction of actin re-structuring promotes nuclear transport of G-actin, concurrently supporting nuclear access of β-catenin via mechanisms utilized for actin transport. Thus, dynamic and static strain activate alternative mechanoresponses reflected by differences in the cellular distributions of actin, β-catenin and YAP1.Significance statementCells integrate both static and dynamic mechanical signals through the actin cytoskeleton which is attached to the nuclear envelope, affecting nuclear transport of β-catenin and YAP1. Dynamic strain induces nuclear translocation of β-catenin, but not YAP1, while static strain causes nuclear translocation of YAP1, but not β-catenin. Importantly, nuclear transport of actin is induced by dynamic but not static force. Furthermore, nuclear import of β-catenin depends on cofilin/importin-9 dependent actin transport mechanisms. Thus the presence of β-catenin and YAP1 in the nucleus represent specific responses to regulatory mechanical signals.

An atomic force microscope (AFM) fundamentally measures the interaction between a nanoscale AFM probe tip and the sample surface. If the force applied by the probe tip and its contact area with the sample can be quantified, it is possible to determine the nanoscale mechanical properties (e.g., elastic or Young's modulus) of the surface being probed. A detailed procedure for performing quantitative AFM cantilever-based nanoindentation experiments is provided here, with representative examples of how the technique can be applied to determine the elastic moduli of a wide variety of sample types, ranging from kPa to GPa. These include live mesenchymal stem cells (MSCs) and nuclei in physiological buffer, resin-embedded dehydrated loblolly pine cross-sections, and Bakken shales of varying composition. Additionally, AFM cantilever-based nanoindentation is used to probe the rupture strength (i.e., breakthrough force) of phospholipid bilayers. Important practical considerations such as method choice and development, probe selection and calibration, region of interest identification, sample heterogeneity, feature size and aspect ratio, tip wear, surface roughness, and data analysis and measurement statistics are discussed to aid proper implementation of the technique. Finally, co-localization of AFM-derived nanomechanical maps with electron microscopy techniques that provide additional information regarding elemental composition is demonstrated.

In the mid-2000s, the term Two-Eyed Seeing was introduced by Mi’kmaw Elder Albert Marshall to suggest the complementarity of Western and Indigenous sciences. The concept has since been adopted and applied in a diverse range of research. This article examines the latent tension in Two-Eyed Seeing between a desire to foster dialogue—in order, ideally, to generate a trans-cultural “third space” of understanding—and the denial or suppression of major contradictions between predominantly wholistic Indigenous and predominantly reductionist Eurocentric worldviews. Examples are considered of both fruitful Two-Eyed Seeing collaborations and areas where antithetical approaches cannot be combined, for reasons that a more critical application of the Two-Eyed Seeing concept could help make clear. Conversely, revisioned in this way, Two-Eyed Seeing can deepen appreciation of those areas of Western science, such as the delicate empiricism of Goethean science, authentically resonant with Indigenous approaches.

Significance There is an intense ongoing search for two-level quantum systems with long lifetimes for applications in quantum communication and computation. Much research has been focused on studying isolated spins in semiconductors or band insulators. Mott insulators provide an interesting alternative platform but have been far less explored. In this work we use a technique capable of resolving individual spins at atomic length scales, to measure the two-level switching of spin states in 1T-TaS 2 . We find quasi-1D chains of spin-1/2 electrons embedded in 1T-TaS 2 which have exceptionally long lifetimes. The discovery of long-lived spin states in a tractable van der Waal material opens doors to using Mott systems in future quantum information applications.

Critical to the mechano-regulation of mesenchymal stem cells (MSC), Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex transduces cytoskeletal forces to the nuclei. The LINC complex contains outer nuclear membrane Nesprin proteins that associate with the cytoskeleton and their inner nuclear membrane couplers, Sun proteins. In addition to coupling Nesprin-associated cytoskeletal elements to inner nuclear membrane, Sun proteins also function in regulating nuclear mechanics and chromatin tethering to inner nuclear membrane. This suggests that release of LINC-mediated cytoskeletal connections from cell nuclei may have different effects on chromatin organization and MSC differentiation than those due to ablation of intra-nuclear Sun proteins. To test this hypothesis we compared Sun1/2 depletion with expression of the dominant-negative KASH domain (dnKASH) that inhibits Nesprin-Sun association. In cells cultured under adipogenic conditions, disconnecting LINC from the cytoskeleton through dnKASH expression, increased adipogenic gene expression and fat droplet formation; heterochromatin H3K27 and H3K9 methylation was unaltered. In contrast, Sun1/2 depletion inhibited adipogenic gene expression and fat droplet formation; as well the anti-adipogenic effect of Sun1/2 depletion was accompanied by increased H3K9me3, which was enriched on Adipoq, silencing this fat locus. We conclude that releasing the nucleus from cytoskeletal constraints via dnKASH accelerates adipogenesis while depletion of Sun1/2 increases heterochromatin accrual on adipogenic genes in a fashion independent of LINC complex function. Therefore, while these two approaches both disable LINC functions, their divergent effects on the epigenetic landscape indicate they cannot be used interchangeably to study mechanical regulation of cell differentiation.

The Canadian Liberal government of Justin Trudeau claims to be ushering in a new era of a “feminist” foreign policy. While serious steps have been taken in this direction, this paper focuses on the government’s opposition to the Treaty on the Prohibition of Nuclear Weapons, a treaty that has been negotiated with a logic and language explicitly linking issues of disarmament and gender, reframing “security” as fundamentally a question not of state but of human (and environmental) security. Ignoring its own public statements that repeatedly link women with peace and security, the Trudeau government’s opposition to the Treaty exposes the hollowness of its claims.

Monolayer films of transition metal dichalcogenides can have very different electronic and structural properties compared to their bulk counterparts. Here, the authors stabilize different structural phases of VSe${}_{2}$ monolayer and bilayer films and study the effects on the electronic properties, charge density wave state, and magnetic properties, using a combination of techniques including scanning tunneling microscopy and first-principles calculations. They find that a new distorted 1$T$ phase can be stabilized in the films that is not found in the bulk compound.

Spin-triplet superconductors are condensates of electron pairs with spin 1 and an odd-parity wavefunction

Electronics designed for NASA planetary missions such as the Martian surface environment require wide-temperature survivable electronics packaging designs to ensure high-reliability avionics and instrumentation. Planetary surface temperature range of −135C to +40C dictate that electronics packaging solutions provide resiliency to large thermal excursions to counteract mismatches in the coefficient of thermal expansion in the myriad of materials found within space born electronics. The Mars2020 Enhanced Engineering Cameras (EECAMs) are a collection of medium- and wide-angle cameras used across the Mar2020 Flight System. The EECAMs use a commercial off the shelf (COTS) image sensor [1] packaged in a 143-pin Ceramic Pin Grid Array (PGA). Early in the EECAM development, breadboard camera electronics that used conventional thru-hole soldering techniques was subjected to limited thermal cycling to investigate packaging survivability in Martian surface thermal environments from −135C to +70C. Functional testing following 2000 cycles showed that the detector was inoperable. Visual inspection of the part exhibited sever solder joint cracking in a substantial number of pins, and in some cases resulted in complete sheering of the pins from the ceramic package substrate. We will present the steps taken to derive the thermally-resilient electronics packaging design of the Mars2020 EECAM detector. We will highlight analyses and empirical test results that lead to a wide-temperature-survivable COTS component packaging design. Details of thermal cycle testing, in-process inspections, and final packaging design will be presented.

The possible realization of Majorana fermions as quasiparticle excitations in condensed matter physics has created much excitement. Most recent studies have focused on Majorana bound states which can serve as topological qubits. More generally, akin to elementary particles, Majorana fermions can propagate and display linear dispersion. These excitations have not yet been directly observed, and can also be used for quantum information processing. One route to realizing this is in a line junction between two phase-shifted superconductors coupled to topological surface states. Recent theory indicates that in iron-based superconductors, a particular type of crystalline defect, i.e., a domain wall (DW) between two regions with a half-unit cell shift between them, should create a $\pi$-phase shift in the superconducting order parameter. Combined with recent data showing topological surface states in FeSe$_x$Te$_{1-x}$ we find that this is the ideal system to realize helical 1D-dispersing Majorana modes. Here we report scanning tunneling spectroscopic (STS) measurements of crystalline DWs in FeSe$_{0.45}$Te$_{0.55}$. By analyzing large-area superconducting gap maps, we identify the gap in the topological surface state, demonstrating that our sample is an effective Fu-Kane proximitized topological system. We further locate DWs across which the atoms shift by half a unit cell. STS data on these DWs reveal a flat density of states inside the superconducting gap, a hallmark of linearly dispersing modes in 1D. This unique signature is absent in DWs in the related superconductor, FeSe which is not in the topological phase. Our combined data are consistent with the observation of dispersing Majorana states at a $\pi$-phase shift DW in a proximitized topological material.

In this paper we discuss the optimum shape of a target for photonuclear production of radioisotopes using an electron linear accelerator. Different target geometries such as right cylinder, conical frustum, Gaussian volume of revolution and semi-ellipsoid have been considered for the production of (67)Cu via (68)Zn(γ,p)(67)Cu photonuclear reaction. The specific activity (SA) of (67)Cu was simulated for each target shape. Optimum ratio of radius to height for cylindrical targets was found to be between 0.2 and 0.25 for target masses ranging from 20 g to 100 g. It was shown that while some unconventional target shapes, such as semi-elliptical volume of revolution, result in slightly higher specific activities than cylindrical targets, the advantage is not significant and is outweighed by the complexity of the target production and handling. Power deposition into the target was modeled and the trade-off between the maximization of (67)Cu yield and the minimization of target heating has been discussed. The (67)Cu case can easily be extended for production of many other isotopes.

AS GOVERNMENT consultation on the NHS white paper proposals for England comes to an end this month, the health service faces one of the largest overhauls in its history.

This paper approaches the ‘Drexler-Smalley’ debate on nanotechnology from a neglected angle – the common denominator of ‘the frontier’ as a metaphor for scientific exploration. For Bensaude-Vincent, the debate exemplifies the clash of ‘two cultures’ – the ‘artificialist’ and biomimetic’ schools. For us, the portrayal of nanosphere as ‘new frontier’ stymies the prospect of genuine inter-cultural debate on the direction of molecular engineering. Drawing on Brandon, the‘dominium’ impulse of European imperialism is contrasted to the ‘communitas’ tradition of Native America. Proposing a single label – hybridist – for both schools, we juxtapose to this approach the holistic disposition of indigenous North American science.

This article engages with the concept of sustainable science as articulated by those eager to address and correct environmentally destructive tendencies in western scientific theory and practice. We first reflect on the widespread resistance among western scientists to accord the designation of ‘science’ to other cultural enterprises of inquiry. Focusing on the example of Native American approaches to nature and knowledge, we caution that this pervasive sense of superiority has blocked recognition of reasonable paths to a new science even amongst those eager to incorporate elements of Indigenous thinking into their worldviews. Finally, we argue that the explorations of the natural world as found in Indigenous science can be seen to represent an alternative mode of rigorous, systematic inquiry – a ‘full-spectrum’ approach – demonstrating the practical potential for truly sustainable science. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.