77Se-Enriched Selenoglycoside Enables Significant Enhancement in NMR Spectroscopic Monitoring of Glycan–Protein Interactions

Detailed investigation of ligand–protein interactions is essential for better understanding of biological processes at the molecular level. Among these binding interactions, the recognition of glycans by lectins is of particular importance in several diseases, such as cancer; therefore, inhibition of glycan-lectin/galectin interactions represents a promising perspective towards developing therapeutics controlling cancer development. The recent introduction of 77Se NMR spectroscopy for monitoring the binding of a selenoglycoside to galectins prompted interest to optimize the sensitivity by increasing the 77Se content from the natural 7.63% abundance to 99%. Here, we report a convenient synthesis of 77Se-enriched selenodigalactoside (SeDG), which is a potent ligand of the medically relevant human galectin-3 protein, and proof of the expected sensitivity gain in 2D 1H, 77Se correlation NMR experiments. Our work opens perspectives for adding isotopically enriched selenoglycans for rapid monitoring of lectin-binding of selenated as well as non-selenated ligands and for ligand screening in competition experiments.

Strain Sensitivity Enhancement of Broadband Ultrasonic Signals in Plates Using Spectral Phase Filtering

The focused signal obtained by the time-reversal or the cross-correlation techniques of ultrasonic guided waves in plates changes when the medium is subject to strain, which can be used to monitor the medium strain level. In this paper, the sensitivity to strain of cross-correlated signals is enhanced by a post-processing filtering procedure aiming to preserve only strain-sensitive spectrum components. Two different strategies were adopted, based on the phase of either the Fourier transform or the short-time Fourier transform. Both use prior knowledge of the system impulse response at some strain level. The technique was evaluated in an aluminum plate, effectively providing up to twice higher sensitivity to strain. The sensitivity increase depends on a phase threshold parameter used in the filtering process. Its performance was assessed based on the sensitivity gain, the loss of energy concentration capability, and the value of the foreknown strain. Signals synthesized with the time–frequency representation, through the short-time Fourier transform, provided a better tradeoff between sensitivity gain and loss of energy concentration.

Frequency Selective Phase-Optimized Recoupling for Protons in Ultra-Fast Solid-State Magic-Angle Spinning NMR

<p>We propose a new category of homonuclear frequency-selective recoupling methods for protons under ultra-fast MAS ranging from 40 kHz to 150 kHz. The methods, named as Selective Phase-optimized Recoupling (SPR) are simple in the form with defined phase schemes and RF amplitudes. SPR are robust to RF variations and efficient in frequency-selective recoupling. We demonstrated that SPR can provide a sensitivity gain of ~ 3 over the widely-used RFDR for selective ¹H_N-¹H_N correlations under 150 kHz MAS using a protonated tripeptide N-formyl-Met-Leu-Phe (fMLF). Moreover, SPR requires small ratios (~ 0.5) of RF power with respect to MAS frequency, making it perfect to probe long-range ¹H-¹H distance under ultra-fast MAS up to 150 kHz.</p>

Frequency Selective Phase-Optimized Recoupling for Protons in Ultra-Fast Solid-State Magic-Angle Spinning NMR

<p>We propose a new category of homonuclear frequency-selective recoupling methods for protons under ultra-fast MAS ranging from 40 kHz to 150 kHz. The methods, named as Selective Phase-optimized Recoupling (SPR) are simple in the form with defined phase schemes and RF amplitudes. SPR are robust to RF variations and efficient in frequency-selective recoupling. We demonstrated that SPR can provide a sensitivity gain of ~ 3 over the widely-used RFDR for selective ¹H_N-¹H_N correlations under 150 kHz MAS using a protonated tripeptide N-formyl-Met-Leu-Phe (fMLF). Moreover, SPR requires small ratios (~ 0.5) of RF power with respect to MAS frequency, making it perfect to probe long-range ¹H-¹H distance under ultra-fast MAS up to 150 kHz.</p>

Toward a quantum-enhanced strontium optical lattice clock at INRIM

The new strontium atomic clock at INRIM seeks to establish a new frontier in quantum measurement by joining state-of-the-art optical lattice clocks and the quantized electromagnetic field provided by a cavity QED setup. The goal of our experiment is to apply advanced quantum techniques to state-of-the-art optical lattice clocks, demonstrating enhanced sensitivity while preserving long coherence times and the highest accuracy. In this paper we describe the current status of the experiment and the prospected sensitivity gain for the designed cavity QED setup.

Effective sensor properties and sensitivity considerations of a dynamic co-resonantly coupled cantilever sensor

Background: Co-resonant coupling of a micro- and a nanocantilever can be introduced to significantly enhance the sensitivity of dynamic-mode cantilever sensors while maintaining the ease of detection. Experimentally, a low-stiffness nanocantilever is coupled to an easy to read out microcantilever and the eigenfrequencies of both beams are brought close to one another. This results in a strong interplay between both beams and, hence, any interaction applied at the nanocantilever alters the oscillatory state of the coupled system as a whole and can be detected at the microcantilever. The amplitude response curve of the microcantilever exhibits two resonance peaks and their response to an interaction applied to the sensor depends on the properties of the individual beams and the degree of frequency matching. Consequently, while an individual cantilever is characterized by its eigenfrequency, spring constant, effective mass and quality factor, the resonance peaks of the co-resonantly coupled system can be described by effective properties which are a mixture of both subsystem’s characteristics. These effective properties give insight into the amount of sensitivity of the nanocantilever that can be accessed and, consequently, into the sensitivity gain associated with the co-resonance. In order to design sensors based on the co-resonant principle and predict their behaviour it is crucial to derive a description for these effective sensor properties. Results: By modeling the co-resonantly coupled system as a coupled harmonic oscillator and using electromechanical analogies, analytical expressions for the effective sensor properties have been derived and discussed. To illustrate the findings, numerical values for an exemplary system based on experimental sensor realizations have been employed. The results give insight into the complex interplay between the individual subsystem’s properties and the frequency matching, leading to a rather large parameter space for the co-resonant system’s effective properties. While the effective spring constant and effective mass mainly define the sensitivity of the coupled cantilever sensor, the effective quality factor primarily influences the detectability. Hence, a balance has to be found in optimizing both parameters in sensor design which becomes possible with the derived analytic expressions. Besides the description of effective sensor properties, it was studied how the thermal noise and, consequently, minimal detectable frequency shift for the co-resonantly coupled sensor represented by a coupled harmonic oscillator could be derived. Due to the complex nature of the coupled system’s transfer function and the required analysis, it is beyond the scope of this publication to present a full solution. Instead, a simplified approach to estimate the minimal detectable frequency shift for the co-resonant system based on the effective sensor properties is given. Conclusion: By establishing a theoretical description for the effective sensor properties of a co-resonantly coupled system, the design of such systems is facilitated as sensor parameters can easily be predicted and adapted for a desired use case. It allows to study the potential sensitivity (gain) and detectability capabilities before sensor fabrication in a fast and easy way, even for large parameter spaces. So far, such an analysis of a co-resonantly coupled sensor was only possible with numerical methods and even then only with very limited capability to include and understand the complex interplay between all contributions. The outlined calculation steps regarding the noise considerations in a coupled harmonic oscillator system can provide the basis for a thorough study of that question. Furthermore, in a broader scope, the investigations presented within this work contribute towards extending and completing the already established theoretical basics of this novel co-resonant sensor concept and open up new ways of studying the coupled system’s behaviour.

A new operating mode in experiments searching for free neutron-antineutron oscillations based on coherent neutron and antineutron mirror reflections

An observation of neutron-antineutron oscillations (n - n¯), which violate both B and B - L by 2 units, would constitute a fundamental discovery and contribute to our understanding of the baryon asymmetry of the universe. A sufficiently stringent upper constraint on this process would also make a major contribution by ruling out the possibility of post-sphaleron baryogenesis (PSB) involving first-generation quarks, which would mean that sphaleron transitions at the electroweak scale are essential for baryogenesis within the Sakharov paradigm. We show that one can design an experiment with free n using existing or projected neutron sources that can reach the sensitivity needed to rule out PSB if one allows the n and n¯, with sufficiently small tangential velocity, to coherently reflect from n/n¯ mirrors composed of certain nuclei. We show that the sensitivity of a future experiment can be greatly improved, and a more compact and less expensive apparatus can be realized. A sensitivity gain of ~ 104 in the oscillation probability relative to the existing free-n limit can be reached if one is willing to adopt a long flight path with a horizontal guide viewing a cold neutron source, or a significantly shorter flight path with a vertical guide viewing a very cold neutron source.