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An important proposed mechanism in nanothermites reactions — reactive sintering — plays a significant role on the combustion performance of nanothermites by rapidly melting and coalescing aggregated metal nanoparticles, which increases the initial size of the reacting composite powders before burning. Here, we demonstrate a high-speed microscopy/thermometry capability that enables ~ µs time and ~ µm spatial resolution as applied to highly exothermic reaction propagation to directly observe reactive sintering and the reaction front at high spatial and temporal resolution. Experiments on the Al+CuO nanocomposite system reveal a reaction front thickness of ~30 μm and temperatures in excess of 3000 K, resulting in a thermal gradient in excess of 10 7  K m −1 . The local microscopic reactive sintering velocity is found to be an order of magnitude higher than macroscale flame velocity. In this observed mechanism, propagation is very similar to the general concept of laminar gas reaction theory in which reaction front velocity ~ (thermal diffusivity x reaction rate) 1/2 . Imaging highly exothermic reactions in high spatial and temporal resolution to understand their underlying reaction mechanisms is challenging. Here, the authors develop a high-speed microscopy/pyrometry imaging system to successfully observe reactive sintering in a nanothermite reaction in-operando.

Subsets of tumor-produced cell surface and secreted proteins can bind to IgG 1 type antibodies and suppress their immune-effector activities. As they affect antibody and complement-mediated immunity, we call these proteins humoral immuno-oncology (HIO) factors. Antibody-drug conjugates (ADCs) use antibody targeting to bind cell surface antigens, internalize into the cell, then kill target cells upon liberation of the cytotoxic payload. Binding of the ADC antibody component by a HIO factor may potentially hamper ADC efficacy due to reduced internalization. To determine the potential effects of HIO factor ADC suppression, we evaluated the efficacy of a HIO-refractory, mesothelin-directed ADC (NAV-001) and a HIO-bound, mesothelin-directed ADC (SS1). The HIO factor MUC16/CA125 binding to SS1 ADC was shown to have a negative effect on internalization and tumor cell killing. The MUC16/CA125 refractory NAV-001 ADC was shown to have robust killing of MUC16/CA125 expressing and non-expressing tumor cells in vitro and in vivo at single, sub-mg/kg dosing. Moreover, NAV-001-PNU, which contains the PNU-159682 topoisomerase II inhibitor, demonstrated good stability in vitro and in vivo as well as robust bystander activity of resident cells while maintaining a tolerable safety profile in vivo . Single-dose NAV-001-PNU demonstrated robust tumor regression of a number of patient-derived xenografts from different tumor types regardless of MUC16/CA125 expression. These findings suggest that identification of HIO-refractory antibodies to be used in ADC format may improve therapeutic efficacy as observed by NAV-001 and warrants NAV-001-PNU’s advancement to human clinical trials as a monotherapy to treat mesothelin-positive cancers.

The semiconductor industry continues to produce ever smaller devices that are ever more complex in shape and contain ever more types of materials. The ultimate sizes and functionality of these new devices will be affected by fundamental and engineering limits such as heat dissipation, carrier mobility and fault tolerance thresholds. At present, it is unclear which are the best measurement methods needed to evaluate the nanometre-scale features of such devices and how the fundamental limits will affect the required metrology. Here, we review state-of-the-art dimensional metrology methods for integrated circuits, considering the advantages, limitations and potential improvements of the various approaches. We describe how integrated circuit device design and industry requirements will affect lithography options and consequently metrology requirements. We also discuss potentially powerful emerging technologies and highlight measurement problems that at present have no obvious solution. This Review Article examines state-of-the-art metrology methods for integrated circuits and highlights how new integrated circuit device design and industry requirements affect lithography options and consequently metrology requirements.

Energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh–Taylor instability is thought to produce structure at the interface between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh–Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger than the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants. Radiation and conduction are generally considered as the main energy transport mechanisms for the evolution of early supernova remnants. Here the authors experimentally show the role of electron heat transfer on the growth of Rayleigh–Taylor instability in young supernova remnants.

Fusion fuel gains greater than unity — which are crucial to the generation of fusion energy — are achieved on the US National Ignition Facility using the ‘high-foot’ implosion method, which reduces instability in the implosion of the fuel. Fusion shows a return Efforts to develop fusion as a viable alternative energy source continue but progress has been slow. In the context of inertial confinement fusion, in which a fuel target is compressed and heated to initiate nuclear fusion, a key experimental goal is to reach a stage where the amount of energy deposited into the fuel during the compression/heating process is exceeded by the amount of energy generated by the induced fusion reactions. This threshold — the attainment of a 'fuel gain' that is greater than one — has now been reached at the National Ignition Facility in Livermore, California. They used 192 laser beams to heat and compress a fuel pellet to the point at which nuclear fusion reactions take place and obtained a yield 10 times greater than previously achieved. Further advances will be required, however, before the fusion energy yield exceeds the total energy required to compress the fuel pellet. Ignition is needed to make fusion energy a viable alternative energy source, but has yet to be achieved 1 . A key step on the way to ignition is to have the energy generated through fusion reactions in an inertially confined fusion plasma exceed the amount of energy deposited into the deuterium–tritium fusion fuel and hotspot during the implosion process, resulting in a fuel gain greater than unity. Here we report the achievement of fusion fuel gains exceeding unity on the US National Ignition Facility using a ‘high-foot’ implosion method 2 , 3 , which is a manipulation of the laser pulse shape in a way that reduces instability in the implosion. These experiments show an order-of-magnitude improvement in yield performance over past deuterium–tritium implosion experiments. We also see a significant contribution to the yield from α-particle self-heating and evidence for the ‘bootstrapping’ required to accelerate the deuterium–tritium fusion burn to eventually ‘run away’ and ignite.

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role in macroautophagy. We also show that the lipid scramblase ATG-9 is needed for autophagosome formation in early embryos but is dispensable for timely polar body membrane breakdown or protein cargo degradation. These findings demonstrate that macroautophagy is not required to promote polar body degradation, in contrast to recent findings with apoptotic corpse clearance in C . elegans embryos. Determining how factors regulating Atg8/LC3 promote the breakdown of different types of cell corpses in distinct cell types or metabolic states is likely to give insights into the mechanisms of immunoregulation during normal development, physiology, and disease.

Optimizing the number and utility of features to use in a classification analysis has been the subject of many research studies. Most current models use end-classifications as part of the feature reduction process, leading to circularity in the methodology. The approach demonstrated in the present research uses item response theory (IRT) to select features independent of the end-classification results without the biased accuracies that this circularity engenders. Dichotomous and polytomous IRT models were used to analyze 30 histological breast cancer features from 569 patients using the Wisconsin Diagnostic Breast Cancer data set. Based on their characteristics, three features were selected for use in a machine learning classifier. For comparison purposes, two machine learning–based feature selection protocols were run—recursive feature elimination (RFE) and ridge regression—and the three features selected from these analyses were also used in the subsequent learning classifier. Classification results demonstrated that all three selection processes performed comparably. The non-biased nature of the IRT protocol and information provided about the specific characteristics of the features as to why they are of use in classification help to shed light on understanding which attributes of features make them suitable for use in a machine learning context.

Roadside exclusionary fencing is commonly used on highways to prevent wildlife-vehicle collisions. Although it can mitigate wildlife road mortality by limiting their access to the road, it can also create a barrier for wildlife stranded within the right-of-way. On State Highway 100 in Texas, the Texas Department of Transportation installed 10 wildlife exits (WEs) to allow endangered ocelots and other wildlife to escape the fenced roadway and minimize wildlife-vehicle collisions. Our study compared three types of WE designs within the same area from 2019 to 2024 to assess their effectiveness. The first design (Design A) was without a door and berm, and the second design (Design B) had a raised berm (10 WE sites) with a door (six WE sites) and no door (four WE sites). Lastly, a third design (Design C) had all the structural features of Design B, except for the raised berm removed from all ten WE sites. We used the approaches of four meso-carnivore target species (coyote, bobcat, northern raccoon, and striped skunk) as a metric and binomial generalized linear model as a statistical method to evaluate the effectiveness between three designs. The statistical analysis showed that the raised berm in Design B was the major cause for a decline in the approaches of meso-carnivore communities toward the WE sites. With the berm removal in Design C, the approaches of target species from road to habitat increased significantly in the sites without a door. Our study indicates that the WE door design might be another structural cause for limiting its effectiveness, where significantly lower approaches were recorded for meso-carnivores in the sites with a door compared to those without a door in Design C.

Roads negatively impact wildlife through habitat fragmentation, loss of habitat connectivity, and wildlife-vehicle collisions, thus road mitigation structures, such as wildlife crossing structures (WCS), wildlife guards (WG), and fencing are commonly used to address this issue all over the world, including in the United States. In South Texas, such structures were built or modified along a State Highway in an effort to address road mortality for the endangered ocelot ( Leopardus pardalis ) and non-target wildlife species. The goal of this study was to examine temporal changes in wildlife interactions with WCS and WG during and after their construction and modification along a South Texas highway and to determine whether environmental factors influenced use of WCS. Using camera traps deployed to monitor the road mitigation structures, we compared crossing rates, repel rates, and species richness of all species that interacted with the structures, and we examined whether differential wildlife use of WCS and WG was affected by one or more structural dimensions, distance to nearby vegetation, and water presence. Crossings through WCS by wildlife decreased following the completion of construction of mitigation structures; however, repel interactions at WG increased. Overall, crossings decreased at WCS that had higher openness ratios and during periods of precipitation and higher daily temperatures, but distance to vegetation had minimal influence. These factors were shown to influence crossings of each of the five most frequently observed species differently. Lastly, the presence of pooled water at one WCS caused a decrease in crossings when the water level was highest but was not a barrier at lower water levels. By examining influences on wildlife interaction with road mitigation structures, we conclude that a variety of structures, including different WCS configurations, can be beneficial in facilitating movement and restricting entry into the right-of-way for a diversity of wildlife species beyond the target species.

Wildlife populations are in decline due to human threats, including highways. Strategies for reducing road impacts on wildlife include wildlife fencing which keep animals off roads and wildlife crossing structures (WCSs) which provide safe passage across roads. Wildlife crossing structures are diverse and transportation managers are often interested in identifying which WCS designs are effective for target species so a model that predicts target species usage of WCSs is likely to be beneficial to managers and biologists. Wildlife crossing structures are typically built for select species but are utilized by other species, so it may be beneficial to examine WCS use at the community level. We used camera trap data to develop a predictive model of mammal community composition at WCSs built for ocelots ( Leopardus pardalis ) to predict total detections, successful crossings, and failed crossings using spatial, temporal, structural, environmental, and anthropogenic characteristics. During the first-year after construction of WCSs, structural and anthropogenic characteristics of the WCSs were more important than the environmental characteristics although we expect environmental characteristics to become more important with time. Our models reasonably predicted total detections but were less effective at predicting successful and failed crossings, likely due to potential finer-scale, more dynamic effects like noise or microclimate conditions that may drive an animal’s decision to use a WCS. While our study focused on WCSs built for ocelots, to our knowledge, our model is the first model of WCS effectiveness for mammal communities and provide a generalized framework for predicting WCS use which can be applied anywhere where WCSs are being built.