Nuclear quantum memory for hard x-ray photon wave packets.

Optical quantum memories are key elements in modern quantum technologies to reliably store and retrieve quantum information. At present, they are conceptually limited to the optical wavelength regime. Recent advancements in x-ray quantum optics render an extension of optical quantum memory protocols to ultrashort wavelengths possible, thereby establishing quantum photonics at x-ray energies. Here, we introduce an x-ray quantum memory protocol that utilizes mechanically driven nuclear resonant 57Fe absorbers to form a comb structure in the nuclear absorption spectrum by using the Doppler effect. This room-temperature nuclear frequency comb enables us to control the waveform of x-ray photon wave packets to a high level of accuracy and fidelity using solely mechanical motions. This tunable, robust, and highly flexible system offers a versatile platform for a compact solid-state quantum memory at room temperature for hard x-rays.

Resonant X-ray excitation of the nuclear clock isomer 45Sc.

Resonant oscillators with stable frequencies and large quality factors help us to keep track of time with high precision. Examples range from quartz crystal oscillators in wristwatches to atomic oscillators in atomic clocks, which are, at present, our most precise time measurement devices1. The search for more stable and convenient reference oscillators is continuing2-6. Nuclear oscillators are better than atomic oscillators because of their naturally higher quality factors and higher resilience against external perturbations7-9. One of the most promising cases is an ultra-narrow nuclear resonance transition in 45Sc between the ground state and the 12.4-keV isomeric state with a long lifetime of 0.47 s (ref. 10). The scientific potential of 45Sc was realized long ago, but applications require 45Sc resonant excitation, which in turn requires accelerator-driven, high-brightness X-ray sources11 that have become available only recently. Here we report on resonant X-ray excitation of the 45Sc isomeric state by irradiation of Sc-metal foil with 12.4-keV photon pulses from a state-of-the-art X-ray free-electron laser and subsequent detection of nuclear decay products. Simultaneously, the transition energy was determined as [Formula: see text] with an uncertainty that is two orders of magnitude smaller than the previously known values. These advancements enable the application of this isomer in extreme metrology, nuclear clock technology, ultra-high-precision spectroscopy and similar applications.

Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation.

BACKGROUND: Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19. METHODS: We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR-7-EM/KK-46 (3.7 mg and 11.1 mg/day: low and high dose, respectively) in comparison with standard etiotropic drug treatment (control group) in patients hospitalized with moderate COVID-19 (N = 52 for each group). The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization. RESULTS: Patients from the low-dose group achieved the primary endpoint defined by simultaneous achievement of relief of fever, normalization of respiratory rate, reduction of coughing, and oxygen saturation of >95% for 48 h significantly earlier (median 6 days; 95% confidence interval [CI]: 5-7, HR 1.75, p = .0005) than patients from the control group (8 days; 95% CI: 7-10). No significant clinical efficacy was observed for the high-dose group. Adverse events were reported in 26 (50.00%), 25 (48.08%), and 28 (53.85%) patients from the low-, high-dose and control group, respectively. None of them were associated with siR-7-EM/KK-46. CONCLUSIONS: siR-7-EM/KK-46, a SARS-CoV-2-specific siRNA-peptide dendrimer formulation is safe, well tolerated and significantly reduces time to clinical improvement in patients hospitalized with moderate COVID-19 compared to standard therapy in a randomized controlled trial.

Silencing of SARS-CoV-2 with modified siRNA-peptide dendrimer formulation.

BACKGROUND: First vaccines for prevention of Coronavirus disease 2019 (COVID-19) are becoming available but there is a huge and unmet need for specific forms of treatment. In this study we aimed to evaluate the anti-SARS-CoV-2 effect of siRNA both in vitro and in vivo. METHODS: To identify the most effective molecule out of a panel of 15 in silico designed siRNAs, an in vitro screening system based on vectors expressing SARS-CoV-2 genes fused with the firefly luciferase reporter gene and SARS-CoV-2-infected cells was used. The most potent siRNA, siR-7, was modified by Locked nucleic acids (LNAs) to obtain siR-7-EM with increased stability and was formulated with the peptide dendrimer KK-46 for enhancing cellular uptake to allow topical application by inhalation of the final formulation - siR-7-EM/KK-46. Using the Syrian Hamster model for SARS-CoV-2 infection the antiviral capacity of siR-7-EM/KK-46 complex was evaluated. RESULTS: We identified the siRNA, siR-7, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) as the most efficient siRNA inhibiting viral replication in vitro. Moreover, we showed that LNA-modification and complexation with the designed peptide dendrimer enhanced the antiviral capacity of siR-7 in vitro. We demonstrated significant reduction of virus titer and lung inflammation in animals exposed to inhalation of siR-7-EM/KK-46 in vivo. CONCLUSIONS: Thus, we developed a therapeutic strategy for COVID-19 based on inhalation of a modified siRNA-peptide dendrimer formulation. The developed medication is intended for inhalation treatment of COVID-19 patients.

Coherent control of collective nuclear quantum states via transient magnons.

Ultrafast and precise control of quantum systems at x-ray energies involves photons with oscillation periods below 1 as. Coherent dynamic control of quantum systems at these energies is one of the major challenges in hard x-ray quantum optics. Here, we demonstrate that the phase of a quantum system embedded in a solid can be coherently controlled via a quasi-particle with subattosecond accuracy. In particular, we tune the quantum phase of a collectively excited nuclear state via transient magnons with a precision of 1 zs and a timing stability below 50 ys. These small temporal shifts are monitored interferometrically via quantum beats between different hyperfine-split levels. The experiment demonstrates zeptosecond interferometry and shows that transient quasi-particles enable accurate control of quantum systems embedded in condensed matter environments.

Molecular mechanism of light-driven sodium pumping.

The light-driven sodium-pumping rhodopsin KR2 from Krokinobacter eikastus is the only non-proton cation active transporter with demonstrated potential for optogenetics. However, the existing structural data on KR2 correspond exclusively to its ground state, and show no sodium inside the protein, which hampers the understanding of sodium-pumping mechanism. Here we present crystal structure of the O-intermediate of the physiologically relevant pentameric form of KR2 at the resolution of 2.1 Å, revealing a sodium ion near the retinal Schiff base, coordinated by N112 and D116 of the characteristic NDQ triad. We also obtained crystal structures of D116N and H30A variants, conducted metadynamics simulations and measured pumping activities of putative pathway mutants to demonstrate that sodium release likely proceeds alongside Q78 towards the structural sodium ion bound between KR2 protomers. Our findings highlight the importance of pentameric assembly for sodium pump function, and may be used for rational engineering of enhanced optogenetic tools.

Identification of a novel splice variant for mouse and human interleukin-5.

Expression of interleukins and their receptors is often regulated by alternative splicing. Alternative isoform of IL-5 receptor α-chain is well studied; however, no data on functional alternative splice variants of IL-5 has been reported up today. In the present study, we describe a novel splice variant for the mouse and human IL-5. The new form was found during analysis of PCR-products amplified from different mouse lymphoid tissues with a pair of primers designed to clone full-length mIL-5 ORF. A single short isoform of mIL-5 was detected along with the canonical full-length mRNA in ConA-stimulated lymphoid cells isolated from spleen, thymus, lymph nodes and blood. It was 30-40 nt shorter, and less abundant than classical form. The sequence analysis of an additional form of mIL-5 revealed that it lacks exon-2 (δ2). Using RT-PCR with the splice-specific primers we obtained an additional evidence for δ2 form expression. To verify whether mIL-5δ2 transcript is translated into protein, the coding sequences corresponding to full and δ2 forms of mIL-5 were cloned into an expression plasmid. After transfection into the human 293T cell line, we found that the short form of mIL-5 protein is expressed in cells and secreted into the supernatant, but at the reduced level than that detected for full isoform of mIL-5. Fluorescence microscopy examination revealed a partial translocation of mIL-5δ2 into cytoplasm, whereas mIL-5 resided mostly within endoplasmic reticulum. This can explain why the level of δ2 protein expression was reduced. Using a similar set of experimental approaches, we received the evidence that the human IL-5 mRNA has the δ2 splice form (hIL-5δ2) as well. It can be firmly detected by RT-PCR in PHA-activated mononuclear cells isolated from peripheral blood of healthy persons or patients with asthma. Altogether, our results showed that the human and mouse IL-5 have an alternative mRNA splice isoform, which loses exon-2, but nevertheless is expressed at protein level. However, more comprehensive studies will be required for evaluation of IL-5δ2 expression, regulation, biological function and clinical significance.

Elucidating the Structural Composition of an Fe-N-C Catalyst by Nuclear- and Electron-Resonance Techniques.

Fe-N-C catalysts are very promising materials for fuel cells and metal-air batteries. This work gives fundamental insights into the structural composition of an Fe-N-C catalyst and highlights the importance of an in-depth characterization. By nuclear- and electron-resonance techniques, we are able to show that even after mild pyrolysis and acid leaching, the catalyst contains considerable fractions of α-iron and, surprisingly, iron oxide. Our work makes it questionable to what extent FeN4 sites can be present in Fe-N-C catalysts prepared by pyrolysis at 900 °C and above. The simulation of the iron partial density of phonon states enables the identification of three FeN4 species in our catalyst, one of them comprising a sixfold coordination with end-on bonded oxygen as one of the axial ligands.

Performance of a silicon monochromator under high heat load.

The performance of a cryogenically cooled double-crystal silicon monochromator was studied under high-heat-load conditions with total absorbed powers and power densities ranging from 8 to 780 W and from 8 to 240 W mm(-2), respectively. When the temperature of the first crystal is maintained close to the temperature of zero thermal expansion of silicon, the monochromator shows nearly ideal performance with a thermal slope error of 0.6 µrad. By tuning the size of the first slit, the regime of the ideal performance can be maintained over a wide range of heat loads, i.e. from power densities of 110 W mm(-2) (at total absorbed power of 510 W) to 240 W mm(-2) (at total absorbed power of 240 W).