Spin squeezing of 1011 atoms by prediction and retrodiction measurements.

The measurement sensitivity of quantum probes using N uncorrelated particles is restricted by the standard quantum limit1, which is proportional to [Formula: see text]. This limit, however, can be overcome by exploiting quantum entangled states, such as spin-squeezed states2. Here we report the measurement-based generation of a quantum state that exceeds the standard quantum limit for probing the collective spin of 1011 rubidium atoms contained in a macroscopic vapour cell. The state is prepared and verified by sequences of stroboscopic quantum non-demolition (QND) measurements. We then apply the theory of past quantum states3,4 to obtain spin state information from the outcomes of both earlier and later QND measurements. Rather than establishing a physically squeezed state in the laboratory, the past quantum state represents the combined system information from these prediction and retrodiction measurements. This information is equivalent to a noise reduction of 5.6 decibels and a metrologically relevant squeezing of 4.5 decibels relative to the coherent spin state. The past quantum state yields tighter constraints on the spin component than those obtained by conventional QND measurements. Our measurement uses 1,000 times more atoms than previous squeezing experiments5-10, with a corresponding angular variance of the squeezed collective spin of 4.6 × 10-13 radians squared. Although this work is rooted in the foundational theory of quantum measurements, it may find practical use in quantum metrology and quantum parameter estimation, as we demonstrate by applying our protocol to quantum enhanced atomic magnetometry.

Cryo-EM Structure of the Mnx Protein Complex Reveals a Tunnel Framework for the Mechanism of Manganese Biomineralization.

The global manganese cycle relies on microbes to oxidize soluble Mn(II) to insoluble Mn(IV) oxides. Some microbes require peroxide or superoxide as oxidants, but others can use O2 directly, via multicopper oxidase (MCO) enzymes. One of these, MnxG from Bacillus sp. strain PL-12, was isolated in tight association with small accessory proteins, MnxE and MnxF. The protein complex, called Mnx, has eluded crystallization efforts, but we now report the 3D structure of a point mutant using cryo-EM single particle analysis, cross-linking mass spectrometry, and AlphaFold Multimer prediction. The ß-sheet-rich complex features MnxG enzyme, capped by a heterohexameric ring of alternating MnxE and MnxF subunits, and a tunnel that runs through MnxG and its MnxE3F3 cap. The tunnel dimensions and charges can accommodate the mechanistically inferred binuclear manganese intermediates. Comparison with the Fe(II)-oxidizing MCO, ceruloplasmin, identifies likely coordinating groups for the Mn(II) substrate, at the entrance to the tunnel. Thus, the 3D structure provides a rationale for the established manganese oxidase mechanism, and a platform for further experiments to elucidate mechanistic details of manganese biomineralization.

A G-Rich Motif in the lncRNA Braveheart Interacts with a Zinc-Finger Transcription Factor to Specify the Cardiovascular Lineage.

Long non-coding RNAs (lncRNAs) are an emerging class of transcripts that can modulate gene expression; however, their mechanisms of action remain poorly understood. Here, we experimentally determine the secondary structure of Braveheart (Bvht) using chemical probing methods and show that this âˆ¼590 nt transcript has a modular fold. Using CRISPR/Cas9-mediated editing of mouse embryonic stem cells, we find that deletion of 11 nt in a 5' asymmetric G-rich internal loop (AGIL) of Bvht (bvhtdAGIL) dramatically impairs cardiomyocyte differentiation. We demonstrate a specific interaction between AGIL and cellular nucleic acid binding protein (CNBP/ZNF9), a zinc-finger protein known to bind single-stranded G-rich sequences. We further show that CNBP deletion partially rescues the bvhtdAGIL mutant phenotype by restoring differentiation capacity. Together, our work shows that Bvht functions with CNBP through a well-defined RNA motif to regulate cardiovascular lineage commitment, opening the door for exploring broader roles of RNA structure in development and disease.

Identification of a specific exporter that enables high production of aconitic acid in Aspergillus pseudoterreus.

Aconitic acid is an unsaturated tricarboxylic acid that is attractive for its potential use in manufacturing biodegradable and biocompatible polymers, plasticizers, and surfactants. Previously Aspergillus pseudoterreus was engineered as a platform to produce aconitic acid by deleting the cadA (cis-aconitic acid decarboxylase) gene in the itaconic acid biosynthetic pathway. In this study, the aconitic acid transporter gene (aexA) was identified using comparative global discovery proteomics analysis between the wild-type and cadA deletion strains. The protein AexA belongs to the Major Facilitator Superfamily (MFS). Deletion of aexA almost abolished aconitic acid secretion, while its overexpression led to a significant increase in aconitic acid production. Transportation of aconitic acid across the plasma membrane is a key limiting step in its production. In vitro, proteoliposome transport assay further validated AexA's function and substrate specificity. This research provides new approaches to efficiently pinpoint and characterize exporters of fungal organic acids and accelerate metabolic engineering to improve secretion capability and lower the cost of bioproduction.

Simulation of thermal field distribution in biological tissue and cell culture media irradiated with infrared wavelengths.

In recent years, there has been a growing interest in the singlet form of oxygen as a regulator of the physiological functions of cells. One of the ways to generate singlet oxygen is direct optical excitation of the triplet oxygen form. Since molecular oxygen weakly absorbs light, high power is required to obtain sufficient concentrations of singlet oxygen. However, the increase in the radiation power of laser can induce a local temperature increase around the laser spot. This may be critical considering the temperature governs every biological reaction within living cells, in particular. Here, the interaction of laser radiation of infrared wavelengths, generating singlet oxygen, with biological tissues and cell culture media was simulated. Using the COMSOL Multiphysics software, the thermal field distribution in the volume of skin, brain tissue and cell culture media was obtained depending on the wavelength, power and exposure time. The results demonstrate the importance of taking temperature into account when conducting experimental studies at the cellular and organismal levels.

Weak thermal state quadrature-noise shadow imaging.

In this work, we theoretically and experimentally demonstrate the possibility to create an image of an opaque object using a few-photon thermal optical field. We utilize the quadrature-noise shadow imaging (QSI) technique that detects the changes in the quadrature-noise statistics of the probe beam after its interaction with an object. We show that such a thermal QSI scheme has an advantage over the classical differential imaging when the effect of dark counts is considered. At the same time, the easy availability of thermal sources for any wavelength makes the method practical for broad range of applications, not accessible with, e.g., quantum squeezed light. As a proof of principle, we implement this scheme by two different light sources: a pseudo-thermal beam generated by rotating ground glass (RGG) method and a thermal beam generated by four-wave mixing (FWM) method. The RGG method shows simplicity and robustness of QSI scheme while the FWM method validates theoretical signal-to-noise ratio predictions. Finally, we demonstrate low-light imaging abilities with QSI by imaging a biological specimen on a CCD camera, detecting as low as 0.03 photons on average per pixel per 1.7 µs exposure.

Wave-front reconstruction via single-pixel homodyne imaging.

We combine single-pixel imaging and homodyne detection to perform full object recovery (phase and amplitude). Our method does not require any prior information about the object or the illuminating fields. As a demonstration, we reconstruct the optical properties of several semi-transparent objects and find that the reconstructed complex transmission has a phase precision of 0.02 radians and a relative amplitude precision of 0.01.

Coherent optical processes with an all-optical atomic simulator.

We show how novel photonic devices such as broadband quantum memory and efficient quantum frequency transduction can be implemented using three-wave mixing processes in a 1D array of nonlinear waveguides evanescently coupled to nearest neighbors. We do this using an analogy of an atom interacting with an external optical field using both classical and quantum models of the optical fields and adapting well-known coherent processes from atomic optics, such as electromagnetically induced transparency and stimulated Raman adiabatic passage to design. This approach allows the implementation of devices that are very difficult or impossible to implement by conventional techniques.

Quantum-enhanced two-photon spectroscopy using two-mode squeezed light.

We investigate the prospects of using two-mode intensity squeezed twin beams, generated in Rb vapor, to improve the sensitivity of spectroscopic measurements by engaging two-photon Raman transitions. As a proof-of-principle demonstration, we recorded quantum-enhanced measurements of the Rb 5D3/2 hyperfine structure with reduced requirements for the Raman pump laser power and Rb vapor number density.

De novo sequencing and native mass spectrometry revealed hetero-association of dirigent protein homologs and potential interacting proteins in Forsythia × intermedia.

The discovery of dirigent proteins (DPs) and their functions in plant phenol biochemistry was made over two decades ago with Forsythia × intermedia. Stereo-selective, DP-guided, monolignol-derived radical coupling in vitro was then reported to afford the optically active lignan, (+)-pinoresinol from coniferyl alcohol, provided one-electron oxidase/oxidant capacity was present. It later became evident that DPs have several distinct sub-families, presumably with different functions. Some known DPs require other essential enzymes/proteins (e.g. oxidases) for their functions. However, the lack of a fully sequenced genome for Forsythia × intermedia made it difficult to profile other components co-purified with the (+)-pinoresinol forming DP. Herein, we used an integrated bottom-up, top-down, and native mass spectrometry (MS) approach to de novo sequence the extracted proteins via adaptation of our initial report of DP solubilization and purification. Using publicly available transcriptome and genomic data from closely related species, we identified 14 proteins that were putatively associated with either DP function or the cell wall. Although their co-occurrence after extraction and chromatographic separation is suggestive for potential protein-protein interactions, none were found to form stable protein complexes with DPs in native MS under the specific experimental conditions we have explored. Interestingly, two new DP homologs were found and they formed hetero-trimers. Molecular dynamics simulations suggested that similar hetero-trimers were possible between Arabidopsis DP homologs with comparable sequence similarities. Nevertheless, our integrated mass spectrometry method development helped prepare for future investigations directed to the discovery of novel proteins and protein-protein interactions. These advantages can be highly beneficial for plant and microbial research where fully sequenced genomes may not be readily available.

In Liquid Infrared Scattering Scanning Near-Field Optical Microscopy for Chemical and Biological Nanoimaging.

Imaging biological systems with simultaneous intrinsic chemical specificity and nanometer spatial resolution in their typical native liquid environment has remained a long-standing challenge. Here, we demonstrate a general approach of chemical nanoimaging in liquid based on infrared scattering scanning near-field optical microscopy (IR s-SNOM). It is enabled by combining AFM operation in a fluid cell with evanescent IR illumination via total internal reflection, which provides spatially confined excitation for minimized IR water absorption, reduced far-field background, and enhanced directional signal emission and sensitivity. We demonstrate in-liquid IR s-SNOM vibrational nanoimaging and conformational identification of catalase nanocrystals and spatio-spectral analysis of biomimetic peptoid sheets with monolayer sensitivity and chemical specificity at the few zeptomole level. This work establishes the principles of in-liquid and in situ IR s-SNOM spectroscopic chemical nanoimaging and its general applicability to biomolecular, cellular, catalytic, electrochemical, or other interfaces and nanosystems in liquids or solutions.

Quantum-Limited Squeezed Light Detection with a Camera.

We present a technique for squeezed light detection based on direct imaging of the displaced-squeezed-vacuum state using a CCD camera. We show that the squeezing parameter can be accurately estimated using only the first two moments of the recorded pixel-to-pixel photon fluctuation statistics, with accuracy that rivals that of the standard squeezing detection methods such as a balanced homodyne detection. Finally, we numerically simulate the camera operation, reproducing the noisy experimental results with low signal samplings and confirming the theory with high signal samplings.

Polarization-based truncated SU(1,1) interferometer based on four-wave mixing in Rb vapor.

We propose and demonstrate a polarization-based truncated SU(1,1) interferometer that outputs the desired optical joint-quadrature of a two-mode squeezed vacuum field and allows its measurements using a single balanced homodyne detector. Using such a setup, we demonstrate up to ≈2dB of quantum noise suppression below the shot-noise limit in intensity-difference and phase-sum joint-quadratures, and confirm entanglement between the two quantum fields. Our proposed technique results in a better balance between the two ports of the detector and, consequently, in better common noise suppression for differential measurements. As a result, we are able to observe flat joint-quadrature squeezing and entanglement at a wide range of detection frequencies: from several MHz (limited by the photodiode gain bandwidth) down to a few hundred Hz (limited by electronic noises).

Optical angular momentum manipulations in a four-wave mixing process.

We investigate the spatial and quantum intensity correlations between the probe and Stokes optical fields produced via four-wave mixing in a double-Λ configuration, when both incoming probe and control fields carry non-zero optical orbital angular momentum (OAM). We observed that the topological charge of the generated Stokes field obeyed the OAM conservation law. However, the maximum values and optimal conditions for the intensity squeezing between the probe and Stokes fields were largely independent of the angular momenta of the beams, even when these two fields had significantly different OAM charges. We also investigated the case of a composite-vortex pump field, containing two closely positioned optical vortices, and showed that the generated Stokes field carried the OAM corresponding to the total topological charge of the pump field, further expanding the range of possible OAM manipulation techniques.

Spatial Multiplexing of Squeezed Light by Coherence Diffusion.

Spatially splitting nonclassical light beams is in principle prohibited due to noise contamination during beam splitting. We propose a platform based on thermal motion of atoms to realize spatial multiplexing of squeezed light. Light channels of separate spatial modes in an antirelaxation coated vapor cell share the same long-lived atomic coherence jointly created by all channels through the coherent diffusion of atoms, which in turn enhances the individual channel's nonlinear process responsible for light squeezing. Consequently, it behaves as squeezed light in one optical channel transferring to other distant channels even with laser powers below the threshold for squeezed light generation. An array of squeezed light beams is created with low laser power ∼ milliwatt. This approach holds great promise for applications in a multinode quantum network and quantum enhanced technologies such as quantum imaging and sensing.

Tailorable dispersion in a four-wave mixing laser.

We present experimental results demonstrating controllable dispersion in a ring laser by monitoring the lasing-frequency response to cavity-length variations. Pumping on an N-type level configuration in Rb87, we tailor the intra-cavity dispersion slope by varying experimental parameters, such as pump-laser frequency, atomic density, and pump power. As a result, we can tune the pulling factor, i.e., the ratio of the laser frequency shift to the empty cavity frequency shift, of our laser by more than an order of magnitude.

Arithmetic with optical topological charges in stepwise-excited Rb vapor.

We report on experimentally observed addition, subtraction, and cancellation of orbital angular momentum (OAM) in the process of parametric four-wave mixing that results in frequency up- and down-converted emission in Rb vapor. Specific features of OAM transfer from resonant laser fields with different optical topological charges to the spatially and temporally coherent blue light (CBL) have been considered. We have observed the conservation of OAM in nonlinear wave mixing in a wide range of experimental conditions, including a noncollinear geometry of the applied laser beams, and furthermore, that the CBL accumulates the total OAM of the applied laser light. Spectral and power dependences of vortex and plane wavefront blue light beams have been compared.

Distinguishing nonlinear processes in atomic media via orbital angular momentum transfer.

We suggest a technique based on the transfer of topological charge from applied laser radiation to directional and coherent optical fields generated in ladder-type excited atomic media to identify the major processes responsible for their appearance. As an illustration, in Rb vapors, we analyze transverse intensity and phase profiles of the forward-directed collimated blue and near-IR light using self-interference and astigmatic transformation techniques when either or both of two resonant laser beams carry orbital angular momentum. Our observations unambiguously demonstrate that emission at 1.37 µm is the result of a parametric four-wave mixing process involving only one of the two applied laser fields.

Enhanced Raman scattering from aromatic dithiols electrosprayed into plasmonic nanojunctions.

We describe surface enhanced Raman spectroscopy (SERS) experiments in which molecular coverage is systematically varied from 3.8 × 10(5) to 3.8 × 10(2) to 0.38 molecules per µm(2) using electrospray deposition of ethanolic 4,4'-dimercaptostilbene (DMS) solutions. The plasmonic SERS substrate used herein consists of a well-characterized 2-dimensional (2D) array of silver nanospheres (see El-Khoury et al., J. Chem. Phys., 2014, 141, 214308), previously shown to feature uniform topography and plasmonic response, as well as intense SERS activity. When compared to their ensemble averaged analogues, the spatially and temporally averaged spectra of a single molecule exhibit several unique features including: (i) distinct relative intensities of the observable Raman-active vibrational states, (ii) more pronounced SERS backgrounds, and (iii) broader Raman lines indicative of faster vibrational dephasing. The first observation may be understood on the basis of an intuitive physical picture in which the removal of averaging over multiple molecules exposes the tensorial nature of Raman scattering. When an oriented single molecule gives rise to the recorded SERS spectra, the relative orientation of the molecule with respect to vector components of the local electric field determines the relative intensities of the observable vibrational states. Using a single molecule SERS framework, described herein, we derive a unique molecular orientation in which a single DMS molecule is isolated at a nanojunction formed between two silver nanospheres in the 2D array. The DMS molecule is found lying nearly flat with respect to the metal. The derived orientation of a single molecule at a plasmonic nanojunction is consistent with observations (ii) and (iii). In particular, a careful inspection of the temporal spectral variations along the recorded single molecule SERS time sequences reveals that the time-averaged SERS backgrounds arise from individual molecular events, marked by broadened SERS signatures. We assign the broadened spectra along the SERS time sequence--which sum up to a SERS background in the averaged spectra--to instances in which the π-framework of the DMS molecule is parallel to the metal at a classical plasmonic nanojunction. This also accounts for Raman line broadening as a result of fast vibrational dephasing, and driven by molecular reorientation at a plasmonic nanojunction. Furthermore, we report on the molecular orientation dependence of single molecule SERS enhancement factors. We find that in the case of a single DMS molecule isolated at a plasmonic nanojunction, molecular orientation may affect the derived single molecule SERS enhancement factor by up to 5 orders of magnitude. Taking both chemical effects as well as molecular orientation into account, we were able to estimate a single molecule enhancement factor of ∼10(10) in our measurements.

The expression platform and the aptamer: cooperativity between Mg2+ and ligand in the SAM-I riboswitch.

Riboswitch operation involves the complex interplay between the aptamer domain and the expression platform. During transcription, these two domains compete against each other for shared sequence. In this study, we explore the cooperative effects of ligand binding and Magnesium interactions in the SAM-I riboswitch in the context of aptamer collapse and anti-terminator formation. Overall, our studies show the apo-aptamer acts as (i) a pre-organized aptamer competent to bind ligand and undergo structural collapse and (ii) a conformation that is more accessible to anti-terminator formation. We show that both Mg(2+) ions and SAM are required for a collapse transition to occur. We then use competition between the aptamer and expression platform for shared sequence to characterize the stability of the collapsed aptamer. We find that SAM and Mg(2+) interactions in the aptamer are highly cooperative in maintaining switch polarity (i.e. aptamer 'off-state' versus anti-terminator 'on-state'). We further show that the aptamer off-state is preferentially stabilized by Mg(2+) and similar divalent ions. Furthermore, the functional switching assay was used to select for phosphorothioate interference, and identifies potential magnesium chelation sites while characterizing their coordinated role with SAM in aptamer stabilization. In addition, we find that Mg(2+) interactions with the apo-aptamer are required for the full formation of the anti-terminator structure, and that higher concentrations of Mg(2+) (>4 mM) shift the equilibrium toward the anti-terminator on-state even in the presence of SAM.