Nuclear Resonance Fluorescence Research Articles

Molecular basis of bacterial lectin recognition of eukaryotic glycans: The case of Mycoplasma pneumoniae and Mycoplasma genitalium cytoadhesins

Mycoplasma pneumoniae and Mycoplasma genitalium are two emerging bacterial pathogens that colonize the human respiratory and urogenital epithelia, respectively. Both pathogens express cell surface cytoadhesins that play a crucial role in the interaction with the host, mediating the attachment to sialylated glycan receptors and triggering infection. The design of competitive binding inhibitors of Mycoplasma cytoadhesins has potential to disrupt these interactions and lessen bacterial pathogenesis. To this end, we report here molecular insights into the adhesion mechanisms of M. pneumoniae and M. genitalium, which are largely mediated by sialylated glycans on the host cell surface. In detail, a combination of Nuclear Magnetic Resonance (NMR) spectroscopy, fluorescence analysis and computational studies allowed us to explore the recognition by the cytoadhesins P40/P90 in M. pneumoniae and P110 in M. genitalium of sialylated N- and O-glycans. We reveal that, unlike other bacterial adhesins, which are characterized by a wide binding pocket, Mycoplasma cytoadhesins principally accommodate the sialic acid residue, in a similar manner to mammalian Siglecs. These findings represent crucial insight into the future development of novel compounds to counteract Mycoplasma infections by inhibiting bacterial adherence to host tissues.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

Simulation study of physical cryptographic verification of nuclear warheads based on NRF excited by LCS γ-ray source

The nuclear resonance fluorescence (NRF) can provide a unique physical fingerprint, and had played an important role in the physical cryptographic verification of nuclear warheads on bremsstrahlung-based system. In this work, an alternative method using laser-Compton scattering (LCS) γ-ray source to excite NRF for physical cryptographic verification of nuclear warheads is proposed, and Monte Carlo simulation is performed by Geant4. This research indicates that the LCS-based system exhibits a high discernment capability for isotope hoaxes and geometric hoaxes, while maintaining low radiation dose. Moreover, it exhibits a more effective ability to avoid leakage of isotopic and geometric information, and is believed that the LCS-based system has better safety potential compared to the bremsstrahlung-based system. This work indicates that the LCS-based system can provide a possible and promising approach in verification of nuclear warheads in the future.

Nondestructive determination of isotopic abundance using multi-energy nuclear resonance fluorescence driven by laser Compton scattering source

We report on the quantitative nondestructive analysis of the natural isotopic abundances of hafnium and tungsten elements using nuclear resonance fluorescence. Metallic samples of hafnium and tungsten were irradiated to six quasi-monochromatic γ-ray beams generated by laser Compton scattering in the energy range of 2.4–3.2 MeV. Multiple nuclei were simultaneously excited at each of the six γ-ray beam energies. A high-purity germanium detector array detected deexcitations of the nuclei. In total, 51 transitions were unprecedentedly employed to estimate the isotopic abundances of heavy elements nondestructively. The estimated abundances of three hafnium isotopes and three tungsten isotopes are consistent with standard known natural abundances within the experimental uncertainties. The deviation from the standard values ranges from 0.18% to 1.36%.

A Monte Carlo simulation method for polarized gamma-ray nuclear resonance fluorescence

With the rapid development of inverse Compton scattering gamma-ray sources, highly polarized gamma rays play a significant role in fundamental nuclear physics research based on nuclear resonance fluorescence (NRF). To meet the requirements of those applications, especially for guiding experiments and optimizing detection systems, a Monte Carlo simulation method for linearly polarized gamma-ray NRF is developed and implemented in the general-purpose toolkit Geant4. To validate the effectiveness of this method, simulations are compared with both theoretical and experimental results and are found to agree well with both. As a typical application of the linearly polarized gamma-ray NRF technique, a gamma-ray polarization measurement method is proposed in the energy region from hundreds of keV to several MeV, and its feasibility is analyzed based on the developed simulation method. Compared with the conventional Compton scattering method, the analyzing power of the NRF method is improved about 3.7-fold by using a 28Si target, and reaches a value of more than 0.99 at a reasonable data acquisition time.

Photo-response of the N=Z nucleus ^{24}Mg

The electric E1 and magnetic M1 dipole responses of the N=Z nucleus ^{24}Mg were investigated in an inelastic photon scattering experiment. The 13.0 MeV electrons, which were used to produce the unpolarised bremsstrahlung in the entrance channel of the ^{24}Mg(gamma ,gamma ^{prime }) reaction, were delivered by the ELBE accelerator of the Helmholtz-Zentrum Dresden-Rossendorf. The collimated bremsstrahlung photons excited one J^{pi }=1^-, four J^{pi }=1^+, and six J^{pi }=2^+ states in ^{24}Mg. De-excitation gamma rays were detected using the four high-purity germanium detectors of the gamma ELBE setup, which is dedicated to nuclear resonance fluorescence experiments. In the energy region up to 13.0 MeV a total B(M1)uparrow = 2.7(3)~mu _N^2 is observed, but this N=Z nucleus exhibits only marginal E1 strength of less than sum B(E1)uparrow le 0.61 times 10^{-3} e^2 , fm^2. The B(varPi 1, 1^{pi }_i rightarrow 2^+_1)/B(varPi 1, 1^{pi }_i rightarrow 0^+_{gs}) branching ratios in combination with the expected results from the Alaga rules demonstrate that K is a good approximative quantum number for ^{24}Mg. The use of the known rho ^2(E0, 0^+_2 rightarrow 0^+_{gs}) strength and the measured B(M1, 1^+ rightarrow 0^+_2)/B(M1, 1^+ rightarrow 0^+_{gs}) branching ratio of the 10.712 MeV 1^+ level allows, in a two-state mixing model, an extraction of the difference varDelta beta _2^2 between the prolate ground-state structure and shape-coexisting superdeformed structure built upon the 6432-keV 0^+_2 level.

К программе фотоядерных исследований на пучке обратных комптоновских квазимонохроматических 𝛾–квантов с перестраиваемой энергией E𝛾 ≲ 40 МэВ

Based on the analysis of development of photonuclear reaction studding at 𝐸𝛾 ≲ 40 MeV and the unique parameters of the Compton source of 𝛾–quanta under projecting, a program of priority photonuclear research using this source is proposed. The program includes research on: structures of giant E1 resonances and pygmy resonances; cross sections for partial photonucleon reactions; nuclear resonant fluorescence; photofission; problems of astrophysics and nucleosynthesis.

Kernelizing: A way to increase accuracy in trilinear decomposition analysis of multiexponential signals

The unmixing of multiexponential decay signals into monoexponential components using soft modelling approaches is a challenging task due to the strong correlation and complete window overlap of the profiles. To solve this problem, slicing methodologies, such as PowerSlicing, tensorize the original data matrix into a three-way data array that can be decomposed based on trilinear models providing unique solutions. Satisfactory results have been reported for different types of data, e.g., nuclear magnetic resonance or time-resolved fluorescence spectra. However, when decay signals are described by only a few sampling (time) points, a significant degradation of the results can be observed in terms of accuracy and precision of the recovered profiles.In this work, we propose a methodology called Kernelizing that provides a more efficient way to tensorize data matrices of multiexponential decays. Kernelizing relies on the invariance of exponential decays, i.e., when convolving a monoexponential decaying function with any positive function of finite width (hereafter called “kernel”), the shape of the decay (determined by the characteristic decay constant) remains unchanged and only the preexponential factor varies. The way preexponential factors are affected across the sample and time modes is linear, and it only depends on the kernel used. Thus, using kernels of different shapes, a set of convolved curves can be obtained for every sample, and a three-way data array generated, for which the modes are sample, time and kernelizing effect. This three-way array can be afterwards analyzed by a trilinear decomposition method, such as PARAFAC-ALS, to resolve the underlying monoexponential profiles. To validate this new approach and assess its performance, we applied Kernelizing to simulated datasets, real time-resolved fluorescence spectra collected on mixtures of fluorophores and fluorescence-lifetime imaging microscopy data. When the measured multiexponential decays feature few sampling points (down to fifteen), more accurate trilinear model estimates are obtained than when using slicing methodologies.

Diverse Roles of ScSERF in Modifying the Fibril Growth of Amyloidogenic Proteins.

The aggregation of amyloidogenic proteins is often related to the occurrence of neurodegenerative diseases, including fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Recently, the SERF protein family has been reported to have a significant regulatory effect on amyloid formation, but it is still unclear about the detailed mechanisms of SERF acting on different amyloidogenic proteins. Herein, nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy were used to explore interactions of ScSERF with three amyloidogenic proteins FUS-LC, FUS-Core, and α-Synuclein. NMR chemical shift perturbations reveal them sharing similar interaction sites on the N-terminal region of ScSERF. However, the amyloid formation of α-Synuclein protein is accelerated by ScSERF, while ScSERF inhibits fibrosis of FUS-Core and FUS-LC proteins. Both the primary nucleation and the total amount of fibrils produced are detained. Our results suggest a diverse role of ScSERF in regulating the fibril growth of amyloidogenic proteins.

Dual functions of the SARS-CoV-2 nucleocapsid domains mediate RNA binding and phase separation.

The primary purpose of the nucleocapsid (N) protein of the Sars-CoV-2 coronavirus is to interact with viral RNA and drive the formation of the viral capsid, mediated by multivalent interaction of both the N- and C-terminal domains (NTD and CTD) of N with RNA. N additionally forms liquid-liquid phase separated droplets with RNA, both in vitro and in infected cells, in a process believed to be important to viral transcription and replication. The degree to which N phase separates with RNA is dependent on the specific RNA being tested, suggesting that the secondary structure of the RNA plays a role in the propensity for phase separation. The ∼32 kb CoV-2 genomic RNA contains a heterogeneous mix of paired and unpaired bases, and while studies suggest that paired RNA is the primary driver of phase separation, little is known at the structural level about how different RNA structures interact with the nucleocapsid. Here we present investigation of binding between N and short designer oligos built to be homogenously single-stranded or double-stranded (ssRNA or dsRNA). Interestingly, we find that our 14-mer dsRNA phase separates readily with the nucleocapsid, while the ssRNA does not, indicating underlying structural differences between the two interactions. Further, we demonstrate by nuclear magnetic resonance (NMR) spectroscopy, fluorescence anisotropy and gel shift assays, that the NTD binds preferentially to ssRNA, and the CTD to dsRNA. We show that the NTD interacts nonspecifically with dsRNA, and that mutations in the NTD that disrupt RNA binding promote this nonspecific interaction. Lastly, we demonstrate that the tendency of N domains to phase separate correlates with weak, nonspecific binding interactions with RNA, suggesting that this weak, nonspecific binding is the primary driver of phase separation.

Neutral-current neutrino cross section and expected supernova signals for 40Ar from a three-fold increase in the magnetic dipole strength

In view of the great interest in liquid argon neutrino detectors, the 40Ar(γ,γ′)40Ar reaction was revisited to guide a calculation of the neutral current neutrino cross section at supernova energies. Using the nuclear resonance fluorescence technique with a monoenergetic, 99% linearly polarized photon beam, we report a three-fold increase in magnetic dipole strength at around 10 MeV in 40Ar. Based on shell-model calculations, and using the experimentally identified transitions, the neutral current neutrino cross sections for low-energy reactions on 40Ar are calculated.

Low-lying dipole strength distribution inPb204

Dipole and quadrupole strength distribution of $^{204}\mathrm{Pb}$ was investigated via a nuclear resonance fluorescence experiment using bremsstrahlung produced using an electron beam at a kinetic energy of 10.5 MeV at the linear accelerator ELBE. We identified 136 states resonantly excited at energies from 3.6 to 8.4 MeV. Spins of the excited states were deduced by angular distribution ratios of $\ensuremath{\gamma}$ rays observed at scattering angles of ${90}^{\ensuremath{\circ}}$ and ${127}^{\ensuremath{\circ}}$ with respect to the incident $\ensuremath{\gamma}$ beam. The analysis of the measured $\ensuremath{\gamma}$-ray spectra includes the quasicontinuum of levels at high energy. Monte Carlo simulation of $\ensuremath{\gamma}$-ray cascades were performed to obtain the intensities of inelastic transitions and branching ratios of the ground-state transitions. The present experimental results were used to investigate the electric dipole $(E1)$ strengths by comparison with predictions from the quasiparticle-phonon model with the self-consistent energy density functional.

Model-independent determination of the dipole response of Zn66 using quasimonoenergetic and linearly polarized photon beams

[Background] Photon strength functions are an important ingredient in calculations relevant for the nucleosynthesis of heavy elements. The relation to the photoabsorption cross section allows to experimentally constrain photon strength functions by investigating the photo-response of atomic nuclei. [Purpose] We determine the photoresponse of $^{66}$Zn in the energy region of 5.6 MeV to 9.9 MeV and analyze the contribution of the "elastic" decay channel back to the ground state. In addition, for the elastic channel electric and magnetic dipole transitions were separated. [Methods] Nuclear resonance fluorescence experiments were performed using a linearly-polarized quasi-monoenergetic photon beam at the High Intensity $\gamma$-ray Source. Photon beam energies from 5.6 to 9.9 MeV with an energy spread of about 3% were selected in steps of 200-300 keV. Two High Purity Germanium detectors were used for the subsequent $\gamma$-ray spectroscopy. [Results] Full photoabsorption cross sections are extracted from the data making use of the monoenergetic character of the photon beam. For the ground-state decay channel, the average contribution of electric and magnetic dipole strengths is disentangled. The average branching ratio back to the ground state is determined as well. [Conclusions] The new results indicate lower cross sections when compared to the values extracted from a former experiment using bremsstrahlung on $^{66}$Zn. In the latter, the average branching ratio to the ground state is estimated from statistical-model calculations in order to analyze the data. Corresponding estimates from statistical-model calculations underestimate this branching ratio compared to the values extracted from the present analysis, which would partly explain the high cross sections determined from the bremsstrahlung data.

Temperature-dependent relative self-absorption measurements in 27Al

Nuclear resonance fluorescence measurements provide direct sensitivity to ground-state transition widths by probing the photoexcitation process of nuclear resonances. A technique in Relative Self-Absorption (RSA) measurements, in which measurements are done at multiple absorber temperatures, was developed and tested with 27Al at the Darmstadt High Intensity Photon Setup of the Superconducting Darmstadt Linear Accelerator. The advantage of this technique, over the regular RSA, is the possibility to overcome the need for theory input on the effective temperatures and the uncertainties that they introduce in the measured level widths. The technique and the preliminary results of the first test-measurements are presented in this proceedings.

Investigation ofB11andCa40levels at 8–9 MeV by nuclear resonance fluorescence

We report on the measurement of $^{11}$B and $^{40}$Ca levels between excitation energies of 8 and 9 MeV using nuclear resonance fluorescence (NRF). The experiment was carried out with nearly-monoenergetic and linearly polarized photon beams provided by the High-Intensity $\gamma$-ray Source (HI$\gamma$S) facility at the Triangle Universities Nuclear Laboratory (TUNL). States in $^{11}$B are important for calibrations of NRF measurements, while the properties of $^{40}$Ca levels impact potassium nucleosynthesis in globular clusters. For $^{40}$Ca, we report on improved excitation energies and an unambiguous $2^-$ assignment for the state at 8425 keV. For $^{11}$B, we obtained improved values for $\gamma$-ray multipolarity mixing ratios and branching ratios of the 8920 keV level.

Calculating off-axis efficiency of coaxial HPGe detectors by Monte Carlo simulation

In beam geometries where a directed γ-ray beam hits the surface of a coaxial high purity germanium detector (HPGe), the detector efficiency is sensitive to the position where γ-rays initially hit the detector surface because the structure of the detector is nonuniform. This may cause inaccuracy of the detector efficiency when measured using standard sources that are point-like sources emitting γ-rays isotropically. Obtaining a precise estimation of the full energy peak efficiency of the coaxial HPGe detector in the beam geometry for on-axis and off-axis measurements requires a Monte Carlo simulation. We performed Monte Carlo simulations that calculate the detector efficiency in the beam geometry. The effects of the off-axis distance and γ-ray beam size on the efficiency are quantitatively analyzed. We found that the intrinsic efficiency in the beam geometry is maximized when the beam hits the detector at specific off-axis distances. Our Monte Carlo calculations have been supported by nuclear resonance fluorescence experiments using laser Compton scattering γ-ray beams.

The Quantum Motion of the Nerve with a Local Defect

We consider the nerve as the elastic string, the left end of which is fixed at the beginning of the coordinate system, the right end is fixed at point l and mass m is fixed between the ends of the string. We determine the classical and the quantum vibration of such system. The quantum motion is obtained by the so-called non-conventional oscillator quantization method by author. The proposed model can be also related in the modified form to the problem of the Mossbauer effect, being the recoilless nuclear resonance fluorescence, which is the resonant and recoil-free emission and absorption of gamma radiation by atomic nuclei bound in a solid. (Mossbauer,1958). It is not excluded that our oscillator quantization of the string can be extended to generate the new way of the string theory of matter and physiology of nerves.

Experimental investigation on remaining oil distribution and recovery performances after different flooding methods

Nowadays most of the oilfield in China have entered the middle-late development stages with the problem of high water cut and low permeability. Many studies have been conducted on the mechanism of chemical flooding to enhance oil recovery. However, there has been less previous evidence for accurate identification and distribution of remaining oil. Therefore, we proposed a new nuclear magnetic resonance (NMR) interpretation method as well as a new residual oil fluorescence analysis method. In this study, we conducted core displacement experiments with different methods. The nuclear magnetic resonance (NMR) tests and fluorescence analysis of frozen slides were performed in each stage after flooding to study the effect of different displacement methods on the recovery degree and the remaining oil distribution. The results showed that alkali can only slightly improve the recovery of macropores and free-state oil due to its poor sweep volume and oil washing efficiency. Surfactants can increase oil recovery in mesopores and the type of bound-state remaining oil by reducing interfacial tension (IFT). Although the injection of polymer can enlarge the sweep volume, the effect of displacement efficiency is poor in narrow space. Therefore, it can only improve the recovery factor in smallpores and mesopores as well as the type of free-state remaining oil. The synergistic effect of ASP system not only can form ultra-low interfacial tension to enhance the recovery of bound-state and half-bound state, but also can help surfactants and alkali enter smallpores according to the injection of polymer. Thus, the oil recovery is significantly improved. Moreover, our study provided a micro-level understanding as the occurrence state and distribution of remaining oil. The result also lays the foundation for further enhance oil recovery in oilfield.

Animal Species Authentication in Dairy Products.

Milk is one of the most important nutritious foods, widely consumed worldwide, either in its natural form or via dairy products. Currently, several economic, health and ethical issues emphasize the need for a more frequent and rigorous quality control of dairy products and the importance of detecting adulterations in these products. For this reason, several conventional and advanced techniques have been proposed, aiming at detecting and quantifying eventual adulterations, preferentially in a rapid, cost-effective, easy to implement, sensitive and specific way. They have relied mostly on electrophoretic, chromatographic and immunoenzymatic techniques. More recently, mass spectrometry, spectroscopic methods (near infrared (NIR), mid infrared (MIR), nuclear magnetic resonance (NMR) and front face fluorescence coupled to chemometrics), DNA analysis (real-time PCR, high-resolution melting analysis, next generation sequencing and droplet digital PCR) and biosensors have been advanced as innovative tools for dairy product authentication. Milk substitution from high-valued species with lower-cost bovine milk is one of the most frequent adulteration practices. Therefore, this review intends to describe the most relevant developments regarding the current and advanced analytical methodologies applied to species authentication of milk and dairy products.

Ultrafast probing of plasma ion temperature in proton–boron fusion by nuclear resonance fluorescence emission spectroscopy

Aneutronic fusion reactions such as proton–boron fusion could efficiently produce clean energy with quite low neutron doses. However, as a consequence, conventional neutron spectral methods for diagnosing plasma ion temperature would no longer work. Therefore, finding a way to probe the ion temperature in aneutronic fusion plasmas is a crucial task. Here, we present a method to realize ultrafast in situ probing of 11B ion temperature for proton–boron fusion by Doppler broadening of the nuclear resonance fluorescence (NRF) emission spectrum. The NRF emission is excited by a collimated, intense γ-ray beam generated from submicrometer wires irradiated by a recently available petawatt (PW) laser pulse, where the γ-ray beam generation is calculated by three-dimensional particle-in-cell simulation. When the laser power is higher than 1 PW, five NRF signatures of a 11B plasma can be clearly identified with high-resolution γ-ray detectors, as shown by our Geant4 simulations. The correlation between the NRF peak width and 11B ion temperature is discussed, and it is found that NRF emission spectroscopy should be sensitive to 11B ion temperatures Ti > 2.4 keV. This probing method can also be extended to other neutron-free-fusion isotopes, such as 6Li and 15N.