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Primate-conserved carbonic anhydrase IV and murine-restricted LY6C1 enable blood-brain barrier crossing by engineered viral vectors
No full textThe blood-brain barrier (BBB) presents a major challenge for delivering large molecules to study and treat the central nervous system. This is due in part to the scarcity of targets known to mediate BBB crossing. To identify novel targets, we leverage a panel of adeno-associated viruses (AAVs) previously identified through mechanism-agnostic directed evolution for improved BBB transcytosis. Screening potential cognate receptors for enhanced BBB crossing, we identify two targets: murine-restricted LY6C1 and widely conserved carbonic anhydrase IV (CA-IV). We apply AlphaFold-based in silico methods to generate capsid-receptor binding models to predict the affinity of AAVs for these identified receptors. Demonstrating how these tools can unlock target-focused engineering strategies, we create an enhanced LY6C1-binding vector, AAV-PHP.eC, that, unlike our prior PHP.eB, also works in Ly6a-deficient mouse strains such as BALB/cJ. Combined with structural insights from computational modeling, the identification of primate-conserved CA-IV enables the design of more specific and potent human brain–penetrant chemicals and biologicals, including gene delivery vectors
Ru-loaded pyrrolic-N-doped extensively graphitized porous carbon for high performance electrochemical hydrogen evolution
No full textHerein, we report a novel methodology for preparation of new N-doped extensively graphitized porous carbon (N-GPC) as a new catalyst support for Ru nanoparticles (NPs) with dramatically improved hydrogen evolution reaction (HER) activity. Our method is remarkably simple: pyrolyzing g-C3N4 in the presence of Mg metal. Here, we show that Mg plays marvelous dual roles as a reducing agent to graphitize the g-C3N4 precursor at low temperature and as a precursor for Mg3N2, which generates network-structured porous carbon as a new porogen. This offers highly robust graphitized carbon with high electrical conductivity, network-structured high porosity, and proper N content, most desired as a catalyst support. As-prepared Ru/N-GPC catalyst shows a remarkably low overpotential of 9.6 mV (vs. RHE) at 10 mA/cm2, which is near ideal, providing 12 times faster hydrogen production rate than state-of-the-art Pt/C. We explain the atomistic basis for this low overpotential and superb stability via Grand canonical quantum mechanics calculations. These calculations show that pyrrolic-N in the support strengthens the coupling to the Ru NP while weakening the binding of H to Ru NP to accelerate the Tafel step
Early Results from GLASS-JWST. XVII. Building the First Galaxies—Chapter 1. Star Formation Histories for 5 < z < 7 Galaxies
No full textThe JWST observations of high-redshift galaxies are used to measure their star formation histories—the buildup of stellar mass in the earliest galaxies. Here we use a novel analysis program, SEDz*, to compare near-IR spectral energy distributions for galaxies with redshifts 5 < z < 7 to combinations of stellar population templates evolved from z = 12. We exploit NIRCam imaging in seven wide bands covering 1–5 μm taken in the context of the GLASS-JWST-ERS program and use SEDz* to solve for well-constrained star formation histories for 24 exemplary galaxies. In this first look, we find a variety of histories, from long, continuous star formation over 5 < z < 12 to short but intense starbursts, sometimes repeating, and, most commonly, contiguous mass buildup lasting ∼0.5 Myr, possibly the seeds of today's typical M* galaxies
Stellar prospects for FRB gravitational lensing
No full textGravitational lensing of fast radio bursts (FRBs) offers an exciting avenue for several cosmological applications. However, it is not yet clear how many such events future surveys will detect nor how to optimally find them. We use the known properties of FRBs to forecast detection rates of gravitational lensing on delay time-scales from microseconds to years, corresponding to lens masses spanning 15 orders of magnitude. We highlight the role of the FRB redshift distribution on our ability to observe gravitational lensing. We consider cosmological lensing of FRBs by stars in foreground galaxies and show that strong stellar lensing will dominate on microsecond time-scales. Upcoming surveys such as DSA-2000 and CHORD will constrain the fraction of dark matter in compact objects (e.g. primordial black holes) and may detect millilensing events from intermediate mass black holes (IMBHs) or small dark matter halos. Coherent all-sky monitors will be able to detect longer-duration lensing events from massive galaxies, in addition to short time-scale lensing. Finally, we propose a new application of FRB gravitational lensing that will measure directly the circumgalactic medium of intervening galaxies
Nonresonant cavity for multipass laser intensity buildup
No full textA nonresonant cavity to build up laser intensity is modeled, developed, and tested. It can be used for overlapping multiple lasers of different wavelengths, increasing their intensities by more than an order of magnitude while maintaining good uniformity. It is simple to set up, has flexible optical characteristics, and is robust against perturbations. The intensity buildup requires no resonances, and the wavelength dependence of the performance is limited only by the mirror coatings. The cavity can be used, for example, in applications requiring a spatially constrained intensity buildup, such as in atomic and molecular traps
Measurement-induced entanglement phase transition on a superconducting quantum processor with mid-circuit readout
No full textQuantum many-body systems subjected to unitary evolution with the addition of interspersed measurements exhibit a variety of dynamical phases that do not occur under pure unitary evolution. However, these systems remain challenging to investigate on near-term quantum hardware owing to the need for numerous ancilla qubits or repeated high-fidelity mid-circuit measurements, a capability that has only recently become available. Here we report the realization of a measurement-induced entanglement phase transition with a hybrid random circuit on up to 14 superconducting qubits with mid-circuit readout capability. We directly observe extensive and sub-extensive scaling of entanglement entropy in the volume- and area-law phases, respectively, by varying the rate of the measurements. We also demonstrate phenomenological critical behaviour by performing a data collapse of the measured entanglement entropy. Our work establishes the use of mid-circuit measurement as a powerful resource for quantum simulation on near-term quantum computers
Autonomous metal-organic framework nanorobots for active mitochondria-targeted cancer therapy
No full textNanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy
Next Generation Planetary Geodesy
No full textGeodesy has the capability to address some of the highest-priority questions in planetary science. Despite their utility, geodetic measurements have been limited at other planets and moons, and have not received the same focus as they have at the Earth and the Moon. This issue motivated our Keck Institute for Space Studies (KISS) study program. We reviewed the state-of-the-art methods for next-generation geodesy, and identified science questions that could be advanced by future geodetic investigations at Mars, Venus, and Ocean Worlds. Essential geodetic investigations at Venus would be conducted by NASA’s VERITAS mission, and we recommend that mission be flown as planned as soon as possible. By the conclusion of our study, we determined that Mars, Europa, and Enceladus were the solar system destinations where currently unplanned next-generation geodesy investigations would lead to the most transformative advances in the near future. For these worlds, we identified a set of priority science themes:
Priority Science Themes for Mars: Terrestrial planet geodynamics and climate change.
Priority Science Themes for Europa and Enceladus: Ocean World interior structure, mass and energy budget, and habitability.
We identified four mission concepts that would provide compelling tests of key science hypotheses related to these priority science themes. These mission concepts are, in no particular order:
1. Mars Gravity Mapper with InSAR: an orbital mission at Mars that collects gravity data using spacecraft-to-spacecraft tracking and collects surface deformation measurements using InSAR,
2. Mars Geophysical Helicopter : a mobile aerial platform at the Martian surface with geophysics-focused instrumentation including a gravimeter and magnetometer,
3. Enceladus Geophysical Orbiter : a geophysical orbiter at Enceladus that collects gravity, topography, and deformation measurements, and
4. Europa Geophysical Orbiter : an orbiter at Europa with a gravity gradiometer and magnetometer.
We conclude that the geodesy community should continue to be established as an important subfield within planetary science, including through topical meetings, conference sessions, and mission concept studies
Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay
No full textWe present a new determination of the smallest neutrino mixing angle θ₁₃ and the mass-squared difference Δm²₃₂ using a final sample of 5.55 × 10⁶ inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin²2θ₁₃ = 0.0851±0.0024, Δm²₃₂ = (2.466±0.060)×10⁻³ eV² for the normal mass ordering or Δm²₃₂ = −(2.571±0.060)×10⁻³ eV² for the inverted mass ordering
A quantum electromechanical interface for long-lived phonons
No full textIn single crystals, the suppression of intrinsic loss channels at low temperatures leads to exceptionally long mechanical lifetimes. Quantum electrical control of such long-lived mechanical oscillators would enable the development of phononic memory elements, sensors and transducers. The integration of piezoelectric materials is one approach to introducing electrical control, but the challenges of combining heterogeneous materials lead to severely limited phonon lifetimes. Here we present a non-piezoelectric silicon electromechanical system capable of operating in the gigahertz frequency band. Relying on a driving scheme based on electrostatic fields and the kinetic inductance effect in disordered superconductors, we demonstrate a parametrically enhanced electromechanical coupling of g/2π = 1.1 MHz, sufficient to enter the strong-coupling regime with a cooperativity of C = 1,200. In our best devices, we measure mechanical quality factors approaching Q ≈ 10⁷, measured at low-phonon numbers and millikelvin temperatures. Despite using strong electrostatic fields, we find the cavity mechanics system in the quantum ground state, verified by thermometry measurements. Simultaneously achieving ground-state operation, long mechanical lifetimes and strong coupling sets the stage for employing silicon electromechanical devices in hybrid quantum systems and as a tool for studying the origins of acoustic loss in the quantum regime