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Structure and mechanism of the alkane-oxidizing enzyme AlkB
No full textAlkanes are the most energy-rich form of carbon and are widely dispersed in the environment. Their transformation by microbes represents a key step in the global carbon cycle. Alkane monooxygenase (AlkB), a membrane-spanning metalloenzyme, converts straight chain alkanes to alcohols in the first step of the microbially-mediated degradation of alkanes, thereby playing a critical role in the global cycling of carbon and the bioremediation of oil. AlkB biodiversity is attributed to its ability to oxidize alkanes of various chain lengths, while individual AlkBs target a relatively narrow range. Mechanisms of substrate selectivity and catalytic activity remain elusive. Here we report the cryo-EM structure of AlkB, which provides a distinct architecture for membrane enzymes. Our structure and functional studies reveal an unexpected diiron center configuration and identify molecular determinants for substrate selectivity. These findings provide insight into the catalytic mechanism of AlkB and shed light on its function in alkane-degrading microorganisms
ESCRT recruitment to SARS-CoV-2 spike induces virus-like particles that improve mRNA vaccines
No full textPrime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain antibody levels. We present a natural infection-mimicking technology that combines features of mRNA- and protein nanoparticle-based vaccines through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- and ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins to induce eVLP budding from cells. Purified spike-EABR eVLPs presented densely arrayed spikes and elicited potent antibody responses in mice. Two immunizations with mRNA-LNP encoding spike-EABR elicited potent CD8+ T cell responses and superior neutralizing antibody responses against original and variant SARS-CoV-2 compared with conventional spike-encoding mRNA-LNP and purified spike-EABR eVLPs, improving neutralizing titers >10-fold against Omicron-based variants for 3 months post-boost. Thus, EABR technology enhances potency and breadth of vaccine-induced responses through antigen presentation on cell surfaces and eVLPs, enabling longer-lasting protection against SARS-CoV-2 and other viruses
Quantum microscopy of cells at the Heisenberg limit
No full textEntangled biphoton sources exhibit nonclassical characteristics and have been applied to imaging techniques such as ghost imaging, quantum holography, and quantum optical coherence tomography. The development of wide-field quantum imaging to date has been hindered by low spatial resolutions, speeds, and contrast-to-noise ratios (CNRs). Here, we present quantum microscopy by coincidence (QMC) with balanced pathlengths, which enables super-resolution imaging at the Heisenberg limit with substantially higher speeds and CNRs than existing wide-field quantum imaging methods. QMC benefits from a configuration with balanced pathlengths, where a pair of entangled photons traversing symmetric paths with balanced optical pathlengths in two arms behave like a single photon with half the wavelength, leading to a two-fold resolution improvement. Concurrently, QMC resists stray light up to 155 times stronger than classical signals. The low intensity and entanglement features of biphotons in QMC promise nondestructive bioimaging. QMC advances quantum imaging to the microscopic level with significant improvements in speed and CNR toward the bioimaging of cancer cells. We experimentally and theoretically prove that the configuration with balanced pathlengths illuminates an avenue for quantum-enhanced coincidence imaging at the Heisenberg limit
How Dark the Sky: The JWST Backgrounds
No full textWe describe the sources of stray light and thermal background that affect JWST observations, report actual backgrounds as measured from commissioning and early-science observations, compare these background levels to prelaunch predictions, estimate the impact of the backgrounds on science performance, and explore how the backgrounds probe the achieved configuration of the deployed observatory. We find that for almost all applications, the observatory is limited by the irreducible astrophysical backgrounds, rather than scattered stray light and thermal self-emission, for all wavelengths λ < 12.5 μm, thus meeting the level 1 requirement. This result was not assured given the open architecture and thermal challenges of JWST, and it is the result of meticulous attention to stray light and thermal issues in the design, construction, integration, and test phases. From background considerations alone, JWST will require less integration time in the near-infrared compared to a system that just met the stray-light requirements; as such, JWST will be even more powerful than expected for deep imaging at 1–5 μm. In the mid-infrared, the measured thermal backgrounds closely match prelaunch predictions. The background near 10 μm is slightly higher than predicted before launch, but the impact on observations is mitigated by the excellent throughput of MIRI, such that instrument sensitivity will be as good as expected prelaunch. These measured background levels are fully compatible with JWST’s science goals and the Cycle 1 science program currently underway
Quantum harmonic free energies for biomolecules and nanomaterials
No full textObtaining the free energy of large molecules from quantum mechanical energy functions is a long-standing challenge. We describe a method that allows us to estimate, at the quantum mechanical level, the harmonic contributions to the thermodynamics of molecular systems of large size, with modest cost. Using this approach, we compute the vibrational thermodynamics of a series of diamond nanocrystals, and show that the error per atom decreases with system size in the limit of large systems. We further show that we can obtain the vibrational contributions to the binding free energies of prototypical protein–ligand complexes where exact computation is too expensive to be practical. Our work raises the possibility of routine quantum mechanical estimates of thermodynamic quantities in complex systems
Preconditioning the 2023 Kahramanmaraş (Türkiye) earthquake disaster
No full textThe 2023 Kahramanmaraş earthquakes occurred on active faults that were known to be a high seismic hazard, yet the devastating impacts of these earthquakes show that the risk was not adequately considered. Vulnerabilities arising from exposure, corruption and poverty led to a lack of seismic preparedness which amplified the earthquake risk into a tragic disaster
Unitary Esprit for Coprime Arrays
No full textCoprime arrays are normally used to identify more sources than sensors, using the coarray domain. They can also be used directly in element-space and still have benefits of better accuracy and resolution compared to ULAs. An invariance is buried in each of the two sparse ULAs which constitute a coprime array. In this paper, ESPRIT is applied separately to each ULA to yield a set of residues of DOAs, and residues from the ULAs are paired to resolve DOAs. With unitary ESPRIT, residues are automatically paired in the real and imaginary parts of the eigenvalues of a matrix obtained from outputs of the two ULAs. These eigenvalues are proved to be distinct, so the eigendecomposition is unique. Previous works used traditional ESPRIT for similar application, so the eigenvalues corresponding to each invariance were complex; elaborate steps were taken to pair residues. Advantages of the proposed method are demonstrated by simulations
Towards Robust, Resilient Ocean World Science Sampling Systems
No full textNASA's search for life and habitable regions in our solar system could lead to future landed missions on Europa and Enceladus, whose ocean worlds may support life. However, these destinations pose significant operational challenges - distance makes for a long communications lag, the lifetime of landed assets will be limited by radiation damage and hostile conditions, and any mission will be constrained by finite duration power. These conditions demand a high degree of autonomy in order to carry out the excavation, collection, and transfer of samples to in-situ scientific instruments, and to communicate results back to Earth. Our Robust, Explainable Autonomy for Scientific Icy Moon Operations (REASIMO) effort aims to improve the science yield and robustness of these kinds of missions by increasing the level of flight-qualifiable autonomy that can be applied to such operations. This is to be achieved by recognizing, and where possible, handling anomalies in situ, whether caused by faults, degradations, failures, or other unexpected conditions
Nature and Nurture? Comparing Lyα Detections in UV-bright and Fainter [O iii]+Hβ Emitters at z ∼ 8 with Keck/MOSFIRE
No full textThe 100% detection rate of Lyα emission in a sample of four luminous z ∼ 8 galaxies with red Spitzer/IRAC colors suggests objects with unusual ionizing capabilities that created early ionized bubbles in a neutral era. Whether such bubbles reflect enhanced ionizing properties (nature) or an overdense environment (nurture), however, remains unclear. Here we aim to distinguish between these hypotheses via a search for Lyα emission in five fainter galaxies drawn from the CANDELS-GOODS fields using a similar IRAC excess and UV magnitudes that should reflect reduced clustering effects. Using Keck/MOSFIRE we tentatively detect >4σ line emission in only two targets at redshifts z_(Lyα) = 7.1081 and 7.9622 with rest-frame EWs of 16–17 Å, ∼1.5× weaker compared to their brighter counterparts. Thus, we find a reduced rate for Lyα emission of 0.40^(+0.30)_(-0.25) compared to 1.00^(+0.00)_(-0.44) for more luminous examples. The lower rate agrees with predictions from simulations of a mostly neutral intergalactic medium and an intrinsic EW_(0,Lyα) distribution for z ∼ 6 galaxies. However, even with an extreme EW_(0,Lyα) model, it is challenging to match the detection rate for the luminous objects. Spectral energy distribution fitting of our fainter sample indicates young and star-forming systems, albeit with less extreme star formation rates and ionization parameters compared to their luminous counterparts. The enhanced Lyα rate in luminous galaxies is thus likely a byproduct of both extreme ionizing properties as well as environmental effects. Further studies with JWST may be required to resolve the physical nature of this puzzling population
Light-Induced Giant Rashba Spin–Orbit Coupling at Superconducting KTaO₃(110) Heterointerfaces
No full textThe 2D electron system (2DES) at the KTaO₃ surface or heterointerface with 5d orbitals hosts extraordinary physical properties, including a stronger Rashba spin–orbit coupling (RSOC), higher superconducting transition temperature, and potential of topological superconductivity. Herein, a huge enhancement of RSOC under light illumination achieved at a superconducting amorphous-Hf_(0.5)Zr_(0.5)O₂/KTaO₃(110) heterointerfaces is reported. The superconducting transition is observed with T꜀ = 0.62 K and the temperature-dependent upper critical field reveals the interaction between spin–orbit scattering and superconductivity. A strong RSOC with Bₛₒ = 1.9 T is revealed by weak antilocalization in the normal state, which undergoes sevenfold enhancement under light illumination. Furthermore, RSOC strength develops a dome-shaped dependence of carrier density with the maximum of Bₛₒ = 12.6 T achieved near the Lifshitz transition point nc ≈ 4.1 × 10¹³ cm⁻². The highly tunable giant RSOC at KTaO₃(110)-based superconducting interfaces show great potential for spintronics