Search

The prospect of employing nanophotonic methods for controlling photon–electron interactions has ignited substantial interest within the particle accelerator community. Silicon-based integrated dielectric laser acceleration (DLA) has emerged as a viable option by leveraging localized photonic effects to emit, accelerate, and measure electron bunches using exclusively light. Here, using highly regular nanopatterning over large areas while preserving the crystalline structure of silicon is imperative to enhance the efficiency and yield of photon-electron effects. While several established fabrication techniques may be used to produce the required silicon nanostructures, alternative techniques are beneficial to enhance scalability, simplicity and cost-efficiency. In this study, we demonstrate the nano-synthesis of silicon structures over arbitrarily large areas utilizing exclusively deep ultraviolet (DUV) ultrafast laser excitation. This approach delivers highly concentrated electromagnetic energy to the material, thus producing nanostructures with features well beyond the diffraction limit. At the core of our demonstration is the production of silicon laser-induced surface structures with an exceptionally high aspect-ratio -reaching a height of more than 100 nm- for a nanostructure periodicity of 250 nm. This result is attained by exploiting a positive feedback effect on the locally enhanced laser electric field as the surface morphology dynamically emerges, in combination with the material properties at DUV wavelengths. We also observe strong nanopattern hybridization yielding intricate 2D structural features as the onset of amorphization takes place at high laser pulse fluence. This technique offers a simple, yet efficient and attractive approach to produce highly uniform and high aspect ratio silicon nanostructures in the 200–300 nm range.

We present a dedicated end-station for solution phase high repetition rate (MHz) picosecond hard x-ray spectroscopy at beamline 15-2 of the Stanford Synchrotron Radiation Lightsource. A high-power ultrafast ytterbium-doped fiber laser is used to photoexcite the samples at a repetition rate of 640 kHz, while the data acquisition operates at the 1.28 MHz repetition rate of the storage ring recording data in an alternating on-off mode. The time-resolved x-ray measurements are enabled via gating the x-ray detectors with the 20 mA/70 ps camshaft bunch of SPEAR3, a mode available during the routine operations of the Stanford Synchrotron Radiation Lightsource. As a benchmark study, aiming to demonstrate the advantageous capabilities of this end-station, we have conducted picosecond Fe K-edge x-ray absorption spectroscopy on aqueous [FeII(phen)3]2+, a prototypical spin crossover complex that undergoes light-induced excited spin state trapping forming an electronic excited state with a 0.6-0.7 ns lifetime. In addition, we report transient Fe Kβ main line and valence-to-core x-ray emission spectra, showing a unique detection sensitivity and an excellent agreement with model spectra and density functional theory calculations, respectively. Notably, the achieved signal-to-noise ratio, the overall performance, and the routine availability of the developed end-station have enabled a systematic time-resolved science program using the monochromatic beam at the Stanford Synchrotron Radiation Lightsource.

Shock experiments are widely used to understand the mechanical and electronic properties of matter under extreme conditions. However, after shock loading to a Hugoniot state, a clear description of the post-shock thermal state and its impacts on materials is still lacking. We used diffraction patterns from 100-fs x-ray pulses to investigate the temperature evolution of laser-shocked Al–Zr metal film composites at time delays ranging from 5 to 75 ns driven by a 120-ps short-pulse laser. We found significant heating of both Al and Zr after shock release, which can be attributed to heat generated by inelastic deformation. A conventional hydrodynamic model that employs (i) typical descriptions of Al and Zr mechanical strength and (ii) elevated strength responses (which might be attributed to an unknown strain rate dependence) did not fully account for the measured temperature increase, which suggests that other strength-related mechanisms (such as fine-scale void growth) could play an important role in thermal responses under shock wave loading/unloading cycles. Our results suggest that a significant portion of the total shock energy delivered by lasers becomes heat due to defect-facilitated plastic work, leaving less converted to kinetic energy. This heating effect may be common in laser-shocked experiments but has not been well acknowledged. High post-shock temperatures may induce phase transformation of materials during shock release. Another implication for the study is the preservability of magnetic records from planetary surfaces that have a shock history from frequent impact events. [ABSTRACT FROM AUTHOR]

Photocathodes are key elements in high-brightness electron sources and ubiquitous in the operation of large-scale accelerators, although their operation is often limited by their quantum efficiency and lifetime. Here, we propose to overcome these limitations by utilizing direct-laser nanostructuring techniques on copper substrates, improving their efficiency and robustness for next-generation electron photoinjectors. When the surface of a metal is nanoengineered with patterns and particles much smaller than the optical wavelength, it can lead to the excitation of localized surface plasmons that produce hot electrons, ultimately contributing to the overall charge produced. In order to quantify the performance of laser-produced plasmonic photocathodes, we measured their quantum efficiency in a typical electron gun setup. Our experimental results suggest that plasmon-induced hot electrons lead to a significant increase in quantum efficiency, showing an overall charge enhancement factor of at least 4.5 and up to 25. A further increase in their efficiency was observed when combined with semiconductor thin-films deposited over the laser processed surfaces, pointing at potential pathways for further optimization. We demonstrate that simple laser-produced plasmonic photocathodes outperform standard metallic photocathodes, and can be directly produced in-situ at the electron gun level in vacuum environments and without any disruptive intervention. This approach could lead to unprecedented efficient and continuous operation of electron sources, and is useful in many applications across scientific disciplines requiring high average and peak current electron beams.

BackgroundThere is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense.ObjectiveWe sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2.MethodsAn invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI.ResultsWe gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died.ConclusionsThis study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.

Background: The use of next-generation sequencing in inborn errors of immunity (IEI) has considerably increased the identification of novel gene variants, many of which are identified in patients without the described clinical phenotype or with variants of uncertain pathogenic significance in previously described genes. Properly designed functional and cellular assays, many necessarily accomplished by research-based laboratories, reveal the pathogenic consequences of the gene variants and contribute to diagnosis. Activated PI3Kδ syndrome (APDS) is a rare disease that can be divided into APDS1, caused by gain of function (GOF) mutations in PIK3CD gene, and APDS2, with loss of function (LOF) variants in the PIK3R1 gene. Both entities present hyperactivation of the PI3K pathway, which can be analyzed through Akt and S6 phosphorylation status. Methods: Our objective was to perform an accurate, robust, and reproducible functional assay to analyze the phosphorylation status of proteins in the PI3K-Akt-S6 pathway by flow cytometry, to contribute to diagnosis, to monitor treatments, and to establish intra-assay standardization. Results: We illustrate the robustness and reproducibility of our experimental procedure in patients with APDS who had high Akt and/or S6 phosphorylation levels at baseline, and after anti-IgM stimulation in B cells. We show the relevance of an appropriate cohort of samples from healthy donors, processed within the same conditions as the suspected samples, in particular the time frame for sample processing once blood is collected. Discussion: We highlight the importance of B cell stimulation through B cell receptor signaling, which is highly recommended, especially for samples that would be processed more than 24 hours after blood extraction. Also, having a defined experimental procedure is important, including the cytometer setup, which allows cytometer reproducibility for a period of time, enabling the comparison of a sample at different times. [ABSTRACT FROM AUTHOR]

Background: Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients. Methods: Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency. Results: Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81). Conclusion: Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults. [ABSTRACT FROM AUTHOR]

Analysis of genetically defined immunodeficient patients allows study of the effect of the absence of specific proteins on human immune function in real‐world conditions. Here we have addressed the importance of type I interferon signalling for human NK cell development by studying the phenotype and function of circulating NK cells isolated from patients suffering primary immunodeficiency disease due to mutation of either the human interferon regulatory factor 9 (IRF9) or the signal transducer and activator of transcription 2 (STAT2) genes. IRF9, together with phosphorylated STAT1 and STAT2, form a heterotrimer called interferon stimulated gene factor 3 (ISGF3) which promotes the expression of hundreds of IFN‐stimulated genes that mediate antiviral function triggered by exposure to type I interferons. IRF9‐ and STAT2‐deficient patients are unable to respond efficiently to stimulation by type I interferons and so our experiments provide insights into the importance of type I interferon signalling and the consequences of its impairment on human NK cell biology. Surprisingly, the NK cells of these patients display essentially normal phenotype and function. [ABSTRACT FROM AUTHOR]

Photocathodes are key elements in high-brightness electron sources and ubiquitous in the operation of large-scale accelerators, although their operation is often limited by their quantum efficiency and lifetime. Here, we propose to overcome these limitations by utilizing direct-laser nanostructuring techniques on copper substrates, improving their efficiency and robustness for next-generation electron photoinjectors. When the surface of a metal is nanoengineered with patterns and particles much smaller than the optical wavelength, it can lead to the excitation of localized surface plasmons that produce hot electrons, ultimately contributing to the overall charge produced. In order to quantify the performance of laser-produced plasmonic photocathodes, we measured their quantum efficiency in a typical electron gun setup. Our experimental results suggest that plasmon-induced hot electrons lead to a significant increase in quantum efficiency, showing an overall charge enhancement factor of at least 4.5 and up to 25. A further increase in their efficiency was observed when combined with semiconductor thin-films deposited over the laser processed surfaces, pointing at potential pathways for further optimization. We demonstrate that simple laser-produced plasmonic photocathodes outperform standard metallic photocathodes, and can be directly produced in-situ at the electron gun level in vacuum environments and without any disruptive intervention. This approach could lead to unprecedented efficient and continuous operation of electron sources, and is useful in many applications across scientific disciplines requiring high average and peak current electron beams. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T‐cell therapy is a breakthrough in hematologic malignancies, such as acute B lymphoblastic leukemia (B‐ALL). Monitoring this treatment is recommended, although standardized protocols have not been developed yet. This work compares two flow cytometry monitoring strategies and correlates this technique with qPCR method. CAR‐T cells were detected by two different flow‐cytometry protocols (A and B) in nine blood samples from one healthy donor and five B‐ALL patients treated with Tisagenlecleucel (Kymriah®, USA). HIV‐1 viral load allowed CAR detection by qPCR, using samples from seven healthy donors and nine B‐ALL patients. CAR detection by protocol A and B did not yield statistically significant differences (1.9% vs. 11.8% CD3 + CAR+, p = 0.07). However, protocol B showed a better discrimination of the CD3 + CAR+ population. A strong correlation was observed between protocol B and qPCR (r = 0.7, p < 0.0001). CD3 + CAR+ cells were detected by flow cytometry only when HIV‐1 viral load was above 104 copies/mL. In conclusion, protocol B was the most specific flow‐cytometry procedure for the identification of CAR‐T cells and showed a high correlation with qPCR. Further efforts are needed to achieve a standardized monitoring approach. [ABSTRACT FROM AUTHOR]

The response of rapidly compressed highly oriented pyrolytic graphite (HOPG) normal to its basal plane was investigated at a pressure of ∼80 GPa. Ultrafast x-ray diffraction using ∼100 fs pulses at the Materials Under Extreme Conditions sector of the Linac Coherent Light Source was used to probe the changes in crystal structure resulting from picosecond timescale compression at laser drive energies ranging from 2.5 to 250 mJ. A phase transformation from HOPG to a highly textured hexagonal diamond structure is observed at the highest energy, followed by relaxation to a still highly oriented, but distorted graphite structure following release. We observe the formation of a highly oriented lonsdaleite within 20 ps, subsequent to compression. This suggests that a diffusionless martensitic mechanism may play a fundamental role in phase transition, as speculated in an early work on this system, and more recent static studies of diamonds formed in impact events. [ABSTRACT FROM AUTHOR]

Colorizing metals using micrometer and nanometer scale surface modifications has been vastly investigated and presents many advantages for applications across scientific and technological fields. By tuning the surface chemical composition or controlling its morphology, it is possible to produce a wide range of chromatic effects. Ultrafast laser processing presents here an interesting asset, as it allows to simultaneously provide chemical and morphological modifications at the micro‐scale in a single step. In this article, the composite colorization of copper surfaces with mW‐class average power deep ultraviolet (DUV) femtosecond laser pulses is demonstrated. The advantages of this setup are twofold: first, thanks to the increased absorption of copper in the DUV, the technique allows scaling down the requirement for laser power. Second, under ultrafast short‐wavelength illumination molecular oxygen bond‐breaks occur, enhancing the oxidation rate of the copper. The technique allows for highly controllable and efficient copper oxidation with the irradiation parameters. Taking these two effects into account, the generation of a wide spectrum of colors—from dark blue to shiny red—is demonstrated, and the role of the surface oxidation rate, the laser fluence, and laser scanning strategies in the colorization of copper surfaces employing DUV lasers is discussed. [ABSTRACT FROM AUTHOR]

Tunable single‐frequency lasers are the most prominent tool for high‐resolution spectroscopy, allowing for the study and exploitation of the electronic structure of atoms. A significant milestone relies on the demonstration of integrated laser technology for performing such a task. The device presented here is composed of a compact Fabry–Perot monolithic resonator capable of producing tunable and Fourier‐limited nanosecond pulses with a MHz‐class frequency stability without active cavity stabilization elements. It also has the remarkable capability of exploiting the Raman effect to funnel efficiently the broad spectrum of an input laser to a spectrally‐bright Stokes pulse at hard‐to‐access wavelength ranges. The targeted atom for the demonstrations is 152Sm, released as an atomic vapor in a hot cavity environment. Here, the Stokes field is tuned to a wavelength of 433.9 nm, while a crossed‐beams spectroscopy setup is used to minimize the Doppler broadened spectral features of the atoms. With this work, the suitability of integrated diamond Raman lasers as a high‐resolution in‐source spectroscopy tool is demonstrated, enabling many applications in atomic and nuclear physics. The integrated form‐factor and inherent simplicity makes such a laser an interesting prospect for quantum‐technology based sensing systems and related applications. [ABSTRACT FROM AUTHOR]