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Autism spectrum disorders (ASDs) are neurodevelopmental disorders caused by various genetic and environmental factors that result in synaptic abnormalities. ASD development is suggested to involve microglia, which have a role in synaptic refinement during development. Autophagy and related pathways are also suggested to be involved in ASDs. However, the precise roles of microglial autophagy in synapses and ASDs are unknown. Here, we show that microglial autophagy is involved in synaptic refinement and neurobehavior regulation. We found that deletion of atg7, which is vital for autophagy, from myeloid cell-specific lysozyme M-Cre mice resulted in social behavioral defects and repetitive behaviors, characteristic features of ASDs. These mice also had increases in dendritic spines and synaptic markers and altered connectivity between brain regions, indicating defects in synaptic refinement. Synaptosome degradation was impaired in atg7-deficient microglia and immature dendritic filopodia were increased in neurons co-cultured with atg7-deficient microglia. To our knowledge, our results are the first to show the role of microglial autophagy in the regulation of the synapse and neurobehaviors. We anticipate our results to be a starting point for more comprehensive studies of microglial autophagy in ASDs and the development of putative therapeutics.

Topological defects can markedly alter nanomaterial properties. This presents opportunities for \"defect engineering,\" where desired functionalities are generated through defect manipulation. However, imaging defects in working devices with nanoscale resolution remains elusive. We report three-dimensional imaging of dislocation dynamics in individual battery cathode nanoparticles under operando conditions using Bragg coherent diffractive imaging. Dislocations are static at room temperature and mobile during charge transport. During the structural phase transformation, the lithium-rich phase nucleates near the dislocation and spreads inhomogeneously. The dislocation field is a local probe of elastic properties, and we find that a region of the material exhibits a negative Poisson's ratio at high voltage. Operando dislocation imaging thus opens a powerful avenue for facilitating improvement and rational design of nanostructured materials.

The recent advancement of high-intensity lasers has made all-optical Compton scattering become a promising way to produce ultrashort brilliant γ-rays in an ultra-compact system. However, so far achieved Compton γ-ray sources are limited by low conversion efficiency and spectral intensity. Here we present a highly efficient gamma photon emitter obtained by irradiating a high-intensity laser pulse on a miniature plasma device consisting of a plasma lens and a plasma mirror. This concept exploits strong spatiotemporal laser-shaping process and high-charge electron acceleration process in the plasma lens, as well as an efficient nonlinear Compton scattering process enabled by the plasma mirror. Our full three-dimensional particle-in-cell simulations demonstrate that in this novel scheme, brilliant γ-rays with very high conversion efficiency (higher than 10−2) and spectral intensity (∼109 photons 0.1 % BW ) can be achieved by employing currently available petawatt-class lasers with intensity of 1021 W cm−2. Such efficient and intense γ-ray sources would find applications in wide-ranging areas.

Chitosans have been proposed as alternative, biocompatible cationic polymers for nonviral gene delivery. However, the low transfection efficiency and low specificity of chitosan need to be addressed before clinical application. We prepared galactosylated chitosan-graft-polyethylenimine (GC-g-PEI) copolymer by an imine reaction between periodate-oxidized GC and low-molecular-weight PEI. The molecular weight and composition were characterized using gel permeation chromatography column with multi-angle laser scattering and 1 H nuclear magnetic resonance, respectively. The copolymer was complexed with plasmid DNA in various copolymer/DNA (N/P) charge ratios, and the complexes were characterized. GC-g-PEI showed good DNA-binding ability and superior protection of DNA from nuclease attack and had low cytotoxicity compared to PEI 25K. GC-g-PEI/DNA complexes showed higher transfection efficiency than PEI 25K in both HepG2 and HeLa cell lines. Transfection efficiency into HepG2, which has asialoglycoprotein receptors, was higher than that into HeLa, which does not. GC-g-PEI/DNA complexes also transfected liver cells in vivo after intraperitoneal (i.p.) administration more effectively than PEI 25K. These results suggest that GC-g-PEI can be used in gene therapy to improve transfection efficiency and hepatocyte specificity in vitro and in vivo .

A new mechanism for electromagnetic emission in the terahertz (THz) frequency regime from laser-plasma interactions is described. A localized and long-lasting transverse current is produced by two counter-propagating short laser pulses in weakly magnetized plasma. We show that the electromagnetic wave radiating from this current source, even though its frequency is close to cut-off of the ambient plasma, grows and diffuses towards the plasma-vacuum boundary, emitting a strong monochromatic THz wave. With driving laser pulses of moderate power, the THz wave has a field strength of tens of MV m−1, a frequency of a few THz and a quasi-continuous power that exceeds all previous monochromatic THz sources. The novelty of the mechanism lies in a diffusing electromagnetic wave close to cut-off, which is modelled by a continuously driven complex diffusion equation.

In the next decade, new ground-based cosmic microwave background (CMB) experiments such as Simons Observatory, CCAT-prime, and CMB-S4 will increase the number of detectors observing the CMB by an order of magnitude or more, dramatically improving our understanding of cosmology and astrophysics. These projects will deploy receivers with as many as hundreds of thousands of transition edge sensor (TES) bolometers coupled to superconducting quantum interference device (SQUID)-based readout systems. It is well known that superconducting devices such as TESes and SQUIDs are sensitive to magnetic fields. However, the effects of magnetic fields on TESes are not easily predicted due to the complex behavior of the superconducting transition, which motivates direct measurements of the magnetic sensitivity of these devices. We present comparative four-lead measurements of the critical temperature versus applied magnetic field of AlMn TESes varying in geometry, doping, and leg length, including Advanced ACT and POLARBEAR-2/Simons Array bolometers. MoCu ACTPol TESes are also tested and are found to be more sensitive to magnetic fields than the AlMn devices. We present an observation of weak-link-like behavior in AlMn TESes at low critical currents. We also compare measurements of magnetic sensitivity for time division multiplexing SQUIDs and frequency division multiplexing microwave ( μ MUX) rf-SQUIDs. We discuss the implications of our measurements on the magnetic shielding required for future experiments that aim to map the CMB to near-fundamental limits.

We report on the status of an ongoing effort to develop arrays of horn-coupled, polarization-sensitive microwave kinetic inductance detectors (MKIDs) that are each sensitive to two spectral bands between 125 and 280 GHz. These multi-chroic MKID arrays are tailored for next-generation, large-detector-count experiments that are being designed to simultaneously characterize the polarization properties of both the cosmic microwave background and Galactic dust emission. We present our device design and describe laboratory-based measurement results from two 23-element prototype arrays. From dark measurements of our first engineering array, we demonstrated a multiplexing factor of 92, showed the resonators respond to bath temperature changes as expected, and found that the fabrication yield was 100%. From our first optically loaded array, we found the MKIDs respond to millimeter-wave pulses; additional optical characterization measurements are ongoing. We end by discussing our plans for scaling up this technology to kilo-pixel arrays over the next 2 years.

The transition-edge sensor (TES) is a mature, high-resolution x-ray spectrometer technology that provides a much higher efficiency than dispersive spectrometers such as gratings and crystal spectrometers. As larger arrays are developed, time-division multiplexing schemes operating at MHz frequencies are being replaced by microwave SQUID multiplexers using frequency-division multiplexing at GHz frequencies. However, the multiplexing factor achievable with microwave SQUIDs is limited by the high slew rate on the leading edge of x-ray pulses. In this paper, we propose a new multiplexing scheme for high-slew-rate TES x-ray calorimeters: the spread-spectrum SQUID multiplexer, which has the potential to enable higher multiplexing factors, especially in applications with lower photon-arrival rates.

This paper describes MUSTANG 2, a 338 element focal plane array that is being built for the Green Bank Telescope. Each element consists of a profiled feedhorn coupled to two transition edge sensor bolometers, one for each polarization. Initial deployment will be with 32 detectors, but once fully populated, MUSTANG 2 will be capable of mapping a 8 ′ × 8 ′ area to 23 μ Jy in 1 h with good image fidelity on angular scales from 9 ′ ′ to 6 ′ . As well as an instrument overview, the choice of bandpass and the design of the feeds, detectors and readout are given.

Genetic and epidemiologic evidence suggests that cellular energy homeostasis is critically associated with Parkinson’s disease (PD) pathogenesis. Here we demonstrated that genetic deletion of Poly (ADP-ribose) polymerase 1 completely blocked 6-hydroxydopamine-induced dopaminergic neurodegeneration and related PD-like symptoms. Hyperactivation of PARP-1 depleted ATP pools in dopaminergic (DA) neurons, thereby activating AMP-activated protein kinase (AMPK). Further, blockade of AMPK activation by viral infection with dominant-negative AMPK strongly inhibited DA neuronal atrophy with moderate suppression of nuclear translocation of apoptosis-inhibiting factor (AIF), whereas overactivation of AMPK conversely strengthened the 6-OHDA-induced DA neuronal degeneration. Collectively, these results suggest that manipulation of PARP-1 and AMPK signaling is an effective therapeutic approach to prevent PD-related DA neurodegeneration.