Introduction

May you live in interesting times, runs the legendary Chinese curese. These are interesting times: almost anything can happen except a return to the delicate but enduring balance between two blocs that marked international relations for nearly half a century after World War II. The possibilities include nuclear war, not in the form of the long-feared mutual destruction of the Soviet Union and the United States, but as a last resort in the course of escalating regional conflicts in the Middle East or South Asia. In the aftermath of the 1991 Gulf War, United Nations inspectors found evidence of strong steps toward the production of nuclear weapons in Iraq, a country whose leaders did not hesitate to rain missiles on noncombatant Israel during their struggle to hold Kuwait; the same science is available to many other small, rich despots throughout the world. While the chances that two of the world\u27s largest countries would annihilate each other simultaneously have surely receded, the risk of nuclear war has by no means vanished

The dietary impact of the Norman Conquest: A multiproxy archaeological investigation of Oxford, UK

Archaeology has yet to capitalise on the opportunities offered by bioarchaeological approaches to examine the impact of the 11th-century AD Norman Conquest of England. This study utilises an integrated multiproxy analytical approach to identify and explain changes and continuities in diet and foodways between the 10th and 13th centuries in the city of Oxford, UK. The integration of organic residue analysis of ceramics, carbon (δ13C) and nitrogen (δ15N) isotope analysis of human and animal bones, incremental analysis of δ13C and δ15N from human tooth dentine and palaeopathological analysis of human skeletal remains has revealed a broad pattern of increasing intensification and marketisation across various areas of economic practice, with a much lesser and more short-term impact of the Conquest on everyday lifestyles than is suggested by documentary sources. Nonetheless, isotope data indicate short-term periods of instability, particularly food insecurity, did impact individuals. Evidence of preferences for certain foodstuffs and cooking techniques documented among the elite classes were also observed among lower-status townspeople, suggesting that Anglo-Norman fashions could be adopted across the social spectrum. This study demonstrates the potential for future archaeological research to generate more nuanced understanding of the cultural impact of the Norman Conquest of England, while showcasing a method which can be used to elucidate the undocumented, everyday implications of other large-scale political events on non-elites

Optimized media and workflow for the expansion of human pluripotent stem cells as aggregates in suspension cultures

3D suspension culture enables scale-up of human pluripotent stem cell (hPSC) manufacturing. However, media and methods optimized for 2D adherent cultures can lead to low volumetric productivity and laborious workflow in suspension cultures. To overcome these limitations we developed fed-batch media based on either mTeSRTM1 (BSA-containing) or TeSRTM-E8TM (animal component-free) for hPSC expansion as aggregates in suspension cultures. Fed-batch feeding protocols are more efficient and cost-effective than batch media changes because only exhausted components are replenished. Optimization studies were performed using human embryonic (H7 and H9), and human induced pluripotent (WLS-1C and STiPS-M001) stem cell lines. Suspension cultures were fed daily using either 50% medium exchanges of standard 2D media, or fed-batch optimized media and protocols. hPSC aggregate diameter must be kept below 350 μm to maintain cell viability and phenotype. With observed growth rates, aggregates required passaging every 3 or 4 days into clumps of 5-10 cells with Gentle Cell Dissociation Reagent. Clumps were re-seeded into fresh test medium plus 10 μM Y-27632. Passaging and feeding cycles were repeated for at least 5 passages. Optimization was performed by iteratively modifying the feed solution to maintain consistent nutrient levels and maximal growth rate while maintaining cell quality. Control and optimized fed-batch formulations demonstrated between 1.4 and 1.8-fold expansion per day, \u3e90% viability, Oct4 and TRA-1-60 expression \u3e90%, in vitro trilineage differentiation, and normal karyotype (n=8 independent cultures). Suspension culture optimized mTeSRTM-3D or TeSRTM-E8TM3D fed-batch media enables the cost-effective production of hPSCs as aggregates with efficient workflow and high cell quality

Optimized media and workflow for the expansion of human pluripotent stem cells as aggregates in suspension

3D suspension culture enables the efficient and cost-effective scale-up of human pluripotent stem cell (hPSCs) manufacturing. However, media optimized for 2D adherent cultures can lead to low volumetric productivity and inefficient workflow. To overcome these limitations we developed mTeSRTM3D, a defined medium based on mTeSRTM1, and novel protocols for fed-batch culture of hPSC aggregates. Human embryonic stem cell (hESC) lines (H1 or H9) or human induced pluripotent stem cell (hiPSC) lines (WLS-1C or STiPS-M001) that were previously maintained in 2D mTeSRTM1 culture were seeded into multiple suspension culture vessels containing mTeSRTM3D Seed Medium plus 10 μM Y-27632 ROCK inhibitor. 3D cultures were maintained using either daily 50% mTeSRTM1 medium exchanges (control) or using a fed-batch protocol whereby the culture medium was supplemented daily with mTeSRTM3D Feed Medium. After 3 or 4 days in suspension culture, aggregates were harvested, dissociated into small clumps with Gentle Cell Dissociation Reagent (GCDR) or single cell suspensions enzymatically, and re-seeded in mTeSRTM3D Seed Medium plus 10 μM Y-27632. Passaging and feeding cycles were repeated for at least 5 passages. 3D cultures were assessed for growth, viability, hPSC marker expression, in vitro differentiation potential, and karyotype. In addition, media was analyzed for molar glucose to lactate yield to characterize metabolism. By day 4, aggregates cultured in mTeSRTM3D typically grew to a mean diameter of 350 μm, with a 5-fold increase in cell number. Using mTeSRTM3D up to 109 cells can be produced from a single plate within 2-3 weeks representing a greater than 500-fold expansion. hPSC cultures maintained in mTeSRTM3D differentiated into all 3 germ layers with high efficiency. The average volumetric productivities were 0.7, 3.1 and 6.9 (x105) viable cells / mL in 2D, daily 50% media exchange, and mTeSRTM3D cultures, respectively. Using the GCDR clump passaging protocol, mTeSRTM3D cultured hPSCs retained normal karyotypes. Culture performance was evaluated in shaker bottles, spinner flasks and bioreactors. Performance in each culture system was comparable confirming straightforward scale-up and wide applicability. Typical growth rates were on the order of 1.5-fold expansion per day. Metabolic activity as assessed by the moles lactate produced to glucose consumed was 1.7, consistent with a primarily glycolytic metabolism. Image analysis was performed to estimate aggregate size during growth. Adaptation times for cells moving from 2D to 3D aggregate culture varied with different cell lines; typically one passage in 3D was required before consistent expansion passage over passage was obtained. Additionally, protocols were developed for use on a Hamilton® robotic platform for reproducible, matrix-free, high-throughput hPSC suspension culture at a small scale. mTeSRTM3D enables efficient scale-up and scale-down of hPSC cultures with greatly simplified workflow

Breakdown of Scaling in the Nonequilibrium Critical Dynamics of the Two-Dimensional XY Model

The approach to equilibrium, from a nonequilibrium initial state, in a system at its critical point is usually described by a scaling theory with a single growing length scale, $\xi(t) \sim t^{1/z}$, where z is the dynamic exponent that governs the equilibrium dynamics. We show that, for the 2D XY model, the rate of approach to equilibrium depends on the initial condition. In particular, $\xi(t) \sim t^{1/2}$ if no free vortices are present in the initial state, while $\xi(t) \sim (t/\ln t)^{1/2}$ if free vortices are present.Comment: 4 pages, 3 figure

Observation of Zn Dendrite Growth via Operando Digital Microscopy and Time-Lapse Tomography

The zinc-ion battery is one of the promising candidates for next-generation energy storage devices beyond lithium technology due to the earth’s abundance of Zn materials and their high volumetric energy density (5855 mA h cm–3). To date, the formation of Zn dendrites during charge–discharge cycling still hinders the practical application of zinc-ion batteries. It is, therefore, crucial to understand the formation mechanism of the zinc dendritic structure before effectively suppressing its growth. Here, the application of operando digital optical microscopy and in situ lab-based X-ray computed tomography (X-ray CT) is demonstrated to probe and quantify the morphologies of zinc electrodeposition/dissolution under multiple galvanostatic plating/stripping conditions in symmetric Zn||Zn cells. With the combined microscopy approaches, we directly observed the dynamic nucleation and subsequent growth of Zn deposits, the heterogeneous transportation of charged clusters/particles, and the evolution of ‘dead’ Zn particles via partial dissolution. Zn electrodeposition at the early stage is mainly attributed to activation, while the subsequent dendrite growth is driven by diffusion. The high current not only facilitates the formation of sharp dendrites with a larger mean curvature at their tips but also leads to dendritic tip splitting and the creation of a hyper-branching morphology. This approach offers a direct opportunity to characterize dendrite formation in batteries with a metal anode in the laboratory

Cross-Disciplinary Genomics Approaches to Studying Emerging Fungal Infections

Emerging fungal pathogens pose a serious, global and growing threat to food supply systems, wild ecosystems, and human health. However, historic chronic underinvestment in their research has resulted in a limited understanding of their epidemiology relative to bacterial and viral pathogens. Therefore, the untargeted nature of genomics and, more widely, -omics approaches is particularly attractive in addressing the threats posed by and illuminating the biology of these pathogens. Typically, research into plant, human and wildlife mycoses have been largely separated, with limited dialogue between disciplines. However, many serious mycoses facing the world today have common traits irrespective of host species, such as plastic genomes; wide host ranges; large population sizes and an ability to persist outside the host. These commonalities mean that -omics approaches that have been productively applied in one sphere and may also provide important insights in others, where these approaches may have historically been underutilised. In this review, we consider the advances made with genomics approaches in the fields of plant pathology, human medicine and wildlife health and the progress made in linking genomes to other -omics datatypes and sets; we identify the current barriers to linking -omics approaches and how these are being underutilised in each field; and we consider how and which -omics methodologies it is most crucial to build capacity for in the near future

Influence of association state and DNA binding on the O2-reactivity of [4Fe-4S] fumarate and nitrate reduction (FNR) regulator

The fumarate and nitrate reduction (FNR) regulator is the master switch for the transition between anaerobic and aerobic respiration in Escherichia coli. Reaction of dimeric [4Fe-4S] FNR with O2 results in conversion of the cluster into a [2Fe-2S] form, via a [3Fe-4S] intermediate, leading to the loss of DNA binding through dissociation of the dimer into monomers. In the present paper, we report studies of two previously identified variants of FNR, D154A and I151A, in which the form of the cluster is decoupled from the association state. In vivo studies of permanently dimeric D154A FNR show that DNA binding does not affect the rate of cluster incorporation into the apoprotein or the rate of O2-mediated cluster loss. In vitro studies show that O2-mediated cluster conversion for D154A and the permanent monomer I151A FNR is the same as in wild-type FNR, but with altered kinetics. Decoupling leads to an increase in the rate of the [3Fe-4S]1+ into [2Fe-2S]2+ conversion step, consistent with the suggestion that this step drives association state changes in the wild-type protein. We have also shown that DNA-bound FNR reacts more rapidly with O2 than FNR free in solution, implying that transcriptionally active FNR is the preferred target for reaction with O2

Domesticating the Exotic? An Online Survey of Attitudes towards the International Wildlife Pet Trade

There are a variety of perspectives on wildlife management and conservation, necessitating interdisciplinary research to develop better management strategies. We answered the call to action provided by Teel et al. (2018) to integrate social sciences into conservation and explored an important but understudied issue: views on the international pet-trade of exotic animals. Some pet owners advocate the pet trade as a means to promote conservation, where removing wild animals from their natural habitat could protect them from degraded environments. To gauge how prevalent this attitude is in a cross-national sample, we conducted an online survey that asked 882 participants worldwide to evaluate the pet trade and its relationship with biological conservation. Overall, our survey results showed regional patterns and indicated that younger respondents were more likely to consider international pet trade as a form of acceptable conservation practice compared to older respondents. Education also played a role in shaping views on the pet-trade and indicated that respondents with higher education degrees were less prone to accept pet trade as a substitute for conservation practices. Our research provides novel insights applicable to education programmes and international conservation efforts while highlighting variation in attitudes even among professionals with formal training in natural sciences and ecology

Exploring cycling induced crystallographic change in NMC with X-ray diffraction computed tomography

This study presents the application of X-ray diffraction computed tomography for the first time to analyze the crystal dimensions of LiNi0.33Mn0.33Co0.33O2 electrodes cycled to 4.2 and 4.7 V in full cells with graphite as negative electrodes at 1 μm spatial resolution to determine the change in unit cell dimensions as a result of electrochemical cycling. The nature of the technique permits the spatial localization of the diffraction information in 3D and mapping of heterogeneities from the electrode to the particle level. An overall decrease of 0.4% and 0.6% was observed for the unit cell volume after 100 cycles for the electrodes cycled to 4.2 and 4.7 V. Additionally, focused ion beam-scanning electron microscope cross-sections indicate extensive particle cracking as a function of upper cut-off voltage, further confirming that severe cycling stresses exacerbate degradation. Finally, the technique facilitates the detection of parts of the electrode that have inhomogeneous lattice parameters that deviate from the bulk of the sample, further highlighting the effectiveness of the technique as a diagnostic tool, bridging the gap between crystal structure and electrochemical performance