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Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signalling networks. Synthetic silicon-based circuitry similarly relies on spatial constraints to process information. Here, we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations and logic gates are modularly combined into circuits that establish the universality of our approach. Because reactions preferentially occur between neighbours, identical DNA hairpins can be reused across circuits. Co-localization of circuit elements decreases computation time from hours to minutes compared to circuits with diffusible components. Detailed computational models enable predictive circuit design. We anticipate our approach will motivate using spatial constraints for future molecular control circuit designs. Fast and scalable molecular logic circuits can be created through the spatial organization of DNA hairpins on DNA origami scaffolds.

Turbulent magnetic fields abound in nature, pervading astrophysical, solar, terrestrial and laboratory plasmas. Understanding the ubiquity of magnetic turbulence and its role in the universe is an outstanding scientific challenge. Here, we report on the transition of magnetic turbulence from an initially electron-driven regime to one dominated by ion-magnetization in a laboratory plasma produced by an intense, table-top laser. Our observations at the magnetized ion scale of the saturated turbulent spectrum bear a striking resemblance with spacecraft measurements of the solar wind magnetic-field spectrum, including the emergence of a spectral kink. Despite originating from diverse energy injection sources (namely, electrons in the laboratory experiment and ion free-energy sources in the solar wind), the turbulent spectra exhibit remarkable parallels. This demonstrates the independence of turbulent spectral properties from the driving source of the turbulence and highlights the potential of small-scale, table-top laboratory experiments for investigating turbulence in astrophysical environments. Understanding the role of magnetic turbulence in the atmosphere is difficult as direct access is limited, but latest laser technology can enable such studies in the lab. Here the authors probe the evolution of such turbulence in laser-generated plasma with its implications to astrophysical environments.

We report on an ultrafast infrared optical parametric chirped-pulse amplifier (OPCPA), pumped by a 200-W thin-disk Yb-based regenerative amplifier at a repetition rate of 100 kHz. The OPCPA is tunable in the spectral range 1.4–3.9 μ m, generating up to 23 W of < 100-fs signal and 13 W of < 200-fs idler pulses for infrared spectroscopy, with additional spectral filtering capabilities for Raman spectroscopy. The OPCPA can also yield 19 W of 49-fs 1.75- μ m signal or 5 W of 62-fs 2.8- μ m idler pulses with active carrier-to-envelope-phase (CEP) stabilisation for high-harmonic generation (HHG). We illustrate the versatility of the laser design, catering to various experimental requirements for probing ultrafast science.

BackgroundUltivue InSituPlex technology (ISP) enables whole-slide multiplex immune-fluorescence (mIF) staining of multiple protein targets on an autostainer and for conducting multiple rounds of ISP imaging and a terminal or initial H&E stain of the same slide. But to accurately phenotype each cell, one must co-register or ‘stack’ the images of each round with sub-cellular accuracy. This can be a demanding task due to scanner artifacts (e.g., field selection, stitching deformations, focus errors), staining variations and possible tissue damage during the staining process. Here we describe Ultivue’s UltiStacker™, an easy-to-use Windows OS application that performs whole slide image co-registration from a variety of scanners with high accuracy and high throughput.MethodsThe DAPI channel of each ISP round is used to perform the co-registration. For H&E images, a ‘synthetic DAPI’ image is produced by defining the color of the nuclear stain in Hue Saturation Value color space. H&E images may also need to be corrected for pixel size differences and rotation with respect to the IF images. The base (1st round) image is divided into a regular grid of overlapping tiles and the offset of each base tile to its location in each round image is found using Normalized Cross-Correlation. The offsets are then regularized and used to restitch each round image to match the base image. The accuracy and precision of the co-registration of the final stack is then independently validated.ResultsWe show evidence that the algorithm can routinely co-register IF rounds with an accuracy of 1µm (~3 pixels at 20X) over the whole slide. Similar results are also seen for H&E matching for good quality samples with high nuclear density. The algorithm is also tolerant to regions of scanning or staining artifacts, tissue damage or loss, etc. With built-in parallel processing, most samples can be co-registered in a few minutes to an hour, depending on tissue area, staining quality, scanner type, hardware performance, etc.ConclusionsUltiStacker provides a convenient means to co-register and therefore phenotype all the cells of whole slide images across multiple rounds of fluorescent and brightfield scanning. It reads several common image formats and can combine IF, RNA-ISH UltiStacker can routinely obtain 1µm co-registration needed to accurately phenotype cells across multiple rounds of mIF imaging and it enables visualization and analysis of those cells in multiple modalities for a greater understanding of the Tumor Microenvironment.

The ability to study chemical dynamics on ultrafast timescales has greatly advanced with the introduction of X-ray free electron lasers (XFELs) providing short pulses of intense X-rays tailored to probe atomic structure and electronic configuration. Fully exploiting the full potential of XFELs requires specialized experimental endstations along with the development of techniques and methods to successfully carry out experiments. The liquid jet endstation (LJE) at the Linac Coherent Light Source (LCLS) has been developed to study photochemistry and biochemistry in solution systems using a combination of X-ray solution scattering (XSS), X-ray absorption spectroscopy (XAS), and X-ray emission spectroscopy (XES). The pump–probe setup utilizes an optical laser to excite the sample, which is subsequently probed by a hard X-ray pulse to resolve structural and electronic dynamics at their intrinsic femtosecond timescales. The LJE ensures reliable sample delivery to the X-ray interaction point via various liquid jets, enabling rapid replenishment of thin samples with millimolar concentrations and low sample volumes at the 120 Hz repetition rate of the LCLS beam. This paper provides a detailed description of the LJE design and of the techniques it enables, with an emphasis on the diagnostics required for real-time monitoring of the liquid jet and on the spatiotemporal overlap methods used to optimize the signal. Additionally, various scientific examples are discussed, highlighting the versatility of the LJE.

Bright, energetic, and directional electron bunches are generated through efficient energy transfer of relativistic intense (~ 10 19  W/cm 2 ), 30 femtosecond, 800 nm high contrast laser pulses to grating targets (500 lines/mm and 1000 lines/mm), under surface plasmon resonance (SPR) conditions. Bi-directional relativistic electron bunches (at 40° and 150°) are observed exiting from the 500 lines/mm grating target at the SPR conditions. The surface plasmon excited grating target enhances the electron flux and temperature by factor of 6.0 and 3.6, respectively, compared to that of the plane substrate. Particle-in-Cell simulations indicate that fast electrons are emitted in different directions at different stages of the laser interaction, which are related to the resultant surface magnetic field evolution. This study suggests that the SPR mechanism can be used to generate multiple, bright, ultrafast relativistic electron bunches for a variety of applications.

In this work, we describe the instrumentation used to perform the first operando transmission X-ray microscopy (TXM) and simultaneous X-ray diffraction of laser melting simulating laser powder bed fusion on the XCS instrument at the Linac Coherent Light Source (LCLS) X-ray free-electron laser (XFEL). Our TXM with 40× magnification in the X-ray regime at 11 keV gave spatial resolutions down to 940 nm per line pair, with effective pixel sizes down to 206 nm, image integration times of <100 fs, and frame rates tunable between 2.1 and 119 ns for two probe frames (0.48 GHz to 8.4 MHz). Images were recorded on Zyla and Icarus (UXI) detectors to trade off between spatial resolution and time dynamics. A 1 kW CW IR laser was coupled into the interaction point to conduct pump–probe studies of laser melting and solidification dynamics. Our temporal and spatial resolution with attenuation-based contrast exceeds that currently possible with synchrotron-based high-speed radiography. This system was sensitive to feature velocities of 10–12000 m s −1 but we did not observe any motion in this range in the laser melting of Al6061 alloy. Shockwaves were not observed and hot cracking proceeded at velocities below the detection limits. Pore accumulation was observed between successive shots, indicating that bubble escape mechanisms were not active. With proper experimental design, the spatial resolution, contrast and field of view could be further improved or modified. The increased brightness and narrower bandwidth of the XFEL allowed for this imaging technique and it lays the groundwork for a wide range of operando techniques to study additive manufacturing.

BackgroundH&E-based histopathology is a cost-effective and reliable method that is widely utilized in clinical practice to examine human tissue specimens for routine diagnosis. However, molecular diagnostic techniques such as multiplexed immunofluorescence (mIF) offer promise for a better understanding of the tissue microenvironment beyond tissue and cell morphology. Developing a method to combine the two techniques on the same FFPE slide could empower researchers and pathologists with significantly better-informed prognosis. We developed a simple strategy for rapid and efficient H&E removal for subsequent biomarker detection with mIF, bridging traditional histopathology and the phenotypic and functional features identified using digital pathology tools.MethodsMultiple new and archived human tonsil and non-small cell lung cancer (NSCLC) FFPE tissue slides previously stained with H&E were evaluated in this study. After the initial brightfield scan to detect H&E, slides were processed with Ultivue’s proprietary H&E de-staining workflow. After confirming the H&E stain removal, the slides were stained using Ultivue PD-L1 FixVUE® kit including anti-CK, PD-L1, CD68, and CD8 on a Leica Bond RX autostainer. The resultant mIF-stained slides were then scanned on Zeiss Axioscan.Z1. The brightfield and mIF images from the same slide were co-registered using UltiStacker® software, and the signal evaluated for concordance with appropriate controls.ResultsWe found that hematoxylin and eosin strongly absorbed fluorescence from most fluorophores in mIF assays. Our chemical de-staining process removed both hematoxylin and eosin, abating their quenching activity in less than ten minutes, permitting subsequent staining with quantitative mIF. The fluorescence signal distribution and the signal-to-noise ratio were comparable to those of freshly stained tissue sections. We observed that the mIF staining intensity was reduced in some tissues, likely requiring further optimization.ConclusionsDe-staining H&E tissue slides for multiplexed tissue analysis such as mIF could enable the investigation of rare, pre-screened, or archival FFPE tissue sections. This is particularly useful when the number of tissue sections is limited, or if H&E and biomarkers need to be visualized on the same tissue. Follow-up studies are currently ongoing to evaluate the de-staining workflow on multiple tissue types, specimen conditions, and assays.

The absorption of ultraintense, femtosecond laser pulses by a solid unleashes relativistic electrons, thereby creating a regime of relativistic optics. This has enabled exciting applications of relativistic particle beams and coherent X-ray radiation and fundamental leaps in high energy density science and laboratory astrophysics. Obviously, central to these possibilities lies the basic problem of understanding and if possible, manipulating laser absorption. Surprisingly, the absorption of intense light largely remains an open question, despite the extensive variations in target and laser pulse structures. Moreover, there are only few experimental measurements of laser absorption carried out under very limited parameter ranges. Here we present an extensive investigation of absorption of intense 30 femtosecond laser pulses by solid metal targets. The study, performed under varying laser intensity and contrast ratio over four orders of magnitude, reveals a significant and non-intuitive dependence on these parameters. For contrast ratio of 10 −9 and intensity of 2 × 10 19  W cm −2 , three observations are revealed: preferential acceleration of electrons along the laser axis, a ponderomotive scaling of electron temperature and red shifting of emitted second-harmonic. These point towards the role of J  ×  B absorption mechanism at relativistic intensity. The experimental results are supported by particle-in-cell simulations.

Contemporary African speculative fictions, by constructing alternative fantastical worlds, along with different knowledge production systems, frequently resist and counter the epistemic violence instituted by the denial and silencing of the voices of colonial subjects. By coexisting with and negotiating within the contemporary neocolonial social order, these alternative fantastical structures, often modeled after a \"precolonial\" African past or a hypothetical \"decolonized\" African culture and myth, create an epistemological framework that draws elements from both. This hybrid knowledge production system presents animistic, supernatural African belief structures against rationalist Euro-American epistemic constructs while retaining certain components from the epistemes established by the West. This paper focuses on the epistemic dilemma induced by this coexistence and clash between indigenous and Western systems of knowledge and beliefs in postcolonial Africa through a textual analysis of Nnedi Okorafor's Akata Witch (2011) and Jennifer Nansubuga Makumbi Kintu (2014).