Search

Generation of chimeric antigen receptor (CAR) T cells from pluripotent stem cells (PSCs) will enable advances in cancer immunotherapy. Understanding how CARs affect T cell differentiation from PSCs is important for this effort. The recently described artificial thymic organoid (ATO) system supports in vitro differentiation of PSCs to T cells. Unexpectedly, PSCs transduced with a CD19-targeted CAR resulted in diversion of T cell differentiation to the innate lymphoid cell 2 (ILC2) lineage in ATOs. T cells and ILC2s are closely related lymphoid lineages with shared developmental and transcriptional programs. Mechanistically, we show that antigen-independent CAR signaling during lymphoid development enriched for ILC2-primed precursors at the expense of T cell precursors. We applied this understanding to modulate CAR signaling strength through expression level, structure, and presentation of cognate antigen to demonstrate that the T cell-versus-ILC lineage decision can be rationally controlled in either direction, providing a framework for achieving CAR-T cell development from PSCs.

Evolutionary compromises are thought to be common under fluctuating selection because the mutations that best enable adaptation to one environmental context can often be detrimental to others. Yet, prior experimental work has shown that generalists can sometimes perform as well as specialists in their own environments. Here we use a highly replicated evolutionary experiment (N  = 448 asexual lineages of the brewer's yeast) to show that even though fluctuation between two environmental conditions often induces evolutionary compromises (at least early on), it can also help reveal difficult to reach adaptive outcomes that ultimately improve performance in both environments. Specifically, we begin by showing that yeast adaptation to chemical stress can involve fitness trade-offs with stress-free environments and that, accordingly, lineages that are repeatedly exposed to occasional stress tend to respond by trading performance for breadth of adaptation. We then show that on rare occasions, fluctuating selection leads to the evolution of no-cost generalists that can even outcompete constant selection specialists in their own environments. We propose that the discovery of these broader and more effective adaptive outcomes under fluctuating selection could be partially facilitated by changes in the adaptive landscape that result from having to deal with fitness trade-offs across different environmental conditions. Overall, our findings indicate that reconciling the short- and long-term evolutionary consequences of fluctuating selection could significantly improve our understanding of the evolution of specialization and generalism. [ABSTRACT FROM AUTHOR]

Metal additive manufacturing technologies, such as electron beam powder bed fusion (PBF-EB), rely on layer heating to overcome the so-called "smoke" phenomenon. When scaled up for industrial manufacturing, PBF-EB becomes less productive due to the lengthy preheating process. Currently, only the electron beam (EB) is used for preheating in PBF-EB, resulting in increased manufacturing times, energy consumption, and in some cases limiting the applicability of the technology. In this study, a new preheating approach is suggested that incorporates a near-infrared radiation (NIR) emitter inside an PBF-EB system. The NIR unit eliminates the need for EB heating, reducing build time and powder charging. Successful builds using 316 L and Ti6Al4V precursor powders validate the feasibility of the proposed approach. The produced samples exhibit similar properties to those obtained by the standard PBF-EB process. The introduction of NIR technology also reduced build cost and increased the service intervals of the electron gun. [ABSTRACT FROM AUTHOR]

Highly ordered TiO2 nanotubes were obtained by anodization on Ti6Al4V substrates manufactured by electron beam powder bed fusion (E-PBF). Effects of anodization parameters such as anodizing time, stirring, fluoride concentration, and water content were analyzed in an organic electrolyte (ethylene glycol) that contains ammonium fluoride. The ordering of the nanotubes was measured by regularity ratio calculations based on fast Fourier transform (FFT) from SEM images. It was found that for the processed specimens, the highest ordering of the TiO2 nanotubes was reached at 30 V for 5000 s with a concentration of 9 vol% H2O and 0.4 wt.% NH4F, exhibiting nanotubes free of delamination, cracks, and coral-like structures with a regularity ratio (RR) of 1.91. This work offers a simple method for creating homogeneous and organized TiO2 nanotubes on Ti6Al4V substrates manufactured by E-PBF which potentially improves its functionality in diverse industrial applications such as nanosensors, controlled-release substances, solar cells, water splitting, electrochromic devices, and Li-ion battery anodes. [ABSTRACT FROM AUTHOR]

In this study, the structural integrity of mullite (3Al2O3·2SiO2) films, deposited on silicon carbide (SiC) substrates using chemical vapor deposition (CVD), was investigated via increasing load nanoscratch tests. The films were configured by mullite columns of stoichiometric composition growing from a silica-rich layer in contact with the SiC substrate. Controlled damage was induced in the 3Al2O3·2SiO2 films at relatively low scratch loads. Radial and lateral cracking were applied until final delamination and repeated chipping were achieved as the load increased. The intrinsic integrity of the 3Al2O3∙2SiO2 film and the performance of the coated 3Al2O3·2SiO2/SiC system, regarded as a structural unit, were analyzed. With the aid of advanced characterization techniques at the surface and subsurface levels, the configuration and morphology of the damage induced in the coated system by the nanoscratch tests were characterized, and the scratch damage micromechanisms were identified. Finally, the adhesion of the film, in terms of energy of adhesion and interfacial fracture toughness, was determined using different models proposed in the literature. The results from this investigation contribute to the understanding of the mechanical performance and structural integrity of EBC/SiC-based systems, which over the past few years have increasingly been implemented in novel applications for gas turbines and aircraft engines. [ABSTRACT FROM AUTHOR]

Understanding variation in abundance within species' ranges is fundamental for ecological and evolutionary theory and applied conservation science. The abundant‐center model provides a general hypothesis based on basic ecological principles and macroscale biogeographic patterns: abundance should peak near the center of a species' range, where environmental conditions are most favorable, and decline towards the periphery. Despite longstanding influence in ecological thinking, consistent support for the ubiquity of abundant‐center distributions remains elusive, and recent assessments have questioned the value of this paradigm altogether. We suggest that revisiting the simplifying assumptions that underly the model provides a productive path forward by clarifying predictions and revealing expectations for alternative distribution patterns. Towards this end, we use standardized abundance surveys of North American birds to reassess the prevalence of abundant‐center distributions in geographic and climate space, test whether deviations are associated with predictable violations of assumptions, and provide more robust expectations. After accounting for common methodological pitfalls, we find that geographic centrality is generally indicative of centrality in climate space (confirming a key model assumption) and that abundant‐center distributions occurred in 71% of passerines. To better understand exceptions, we introduce the concept of abundant‐core distributions, of which the abundant‐center is a special case. We find that 87% of species fit abundant‐core expectations, with abundances peaked and generally declining from a core region within the range. Abundance cores tended to deviate from geographic center where topographic features complicate correspondence between geography and environmental conditions (e.g. the climatically heterogenous west). Such deviations were often associated with truncated climatic availability, with core regions offset towards the continental edge or climate extremes. Overall, our analyses suggest that abundant‐center thinking provides a useful generalization for understanding spatial variation in abundance for many species. However, as with any model, its assumptions must be assessed within the context of given applications. [ABSTRACT FROM AUTHOR]

Many coaches have used the vertical jump as an indicator of neuromuscular performance. In this study, a total of 119 high-performance athletes from different sports disciplines were selected in a non-probabilistic and convenient manner. Jump performance was evaluated through the CMJ in a training session using the Chronojump Boscosystem contact platform, the OptoGait photoelectric system and the My Jump 2 mobile application as measurement tools, comparing the results with the values obtained with the Wheeler Jump sensor. Statistically significant validity and reliability were established (Wheeler Jump vs OptoGait ICC .997 - .998, p < .001; Wheeler Jump vs My Jump 2 ICC .991 - .995, p < .001; Wheeler Jump vs ChronoJump ICC .995 - .997, p < .001), thus determining that the Wheeler Jump sensor is a reliable tool that provides professionals and researchers with accurate information regarding changes in the physical performance of athletes. [ABSTRACT FROM AUTHOR]

There is an imperative for conservation practitioners to help biodiversity adapt to accelerating environmental change. Evolutionary biologists are well‐positioned to inform the development of evidence‐based management strategies that support the adaptive capacity of species and ecosystems. Conservation practitioners increasingly accept that management practices must accommodate rapid environmental change, but harbour concerns about how to apply recommended changes to their management contexts. Given the interest from both conservation practitioners and evolutionary biologists in adjusting management practices, we believe there is an opportunity to accelerate the required changes by promoting closer collaboration between these two groups. We highlight how evolutionary biologists can harness lessons from other disciplines about how to foster effective knowledge exchange to make a substantive contribution to the development of effective conservation practices. These lessons include the following: (1) recognizing why practitioners do and do not use scientific evidence; (2) building an evidence base that will influence management decisions; (3) translating theory into a format that conservation practitioners can use to inform management practices; and (4) developing strategies for effective knowledge exchange. Although efforts will be required on both sides, we believe there are rewards for both practitioners and evolutionary biologists, not least of which is fostering practices to help support the long‐term persistence of species. [ABSTRACT FROM AUTHOR]