Tools for supporting solution scattering during the COVID-19 pandemic.

During the COVID-19 pandemic, synchrotron beamlines were forced to limit user access. Performing routine measurements became a challenge. At the Life Science X-ray Scattering (LiX) beamline, new instrumentation and mail-in protocols have been developed to remove the access barrier to solution scattering measurements. Our efforts took advantage of existing instrumentation and coincided with the larger effort at NSLS-II to support remote measurements. Given the limited staff-user interaction for mail-in measurements, additional software tools have been developed to ensure data quality, to automate the adjustments in data processing, as users would otherwise rely on the experience of the beamline staff, and produce a summary of the initial assessments of the data. This report describes the details of these developments.

The Quest to Quantify Selective and Synergistic Effects of Plasma for Cancer Treatment: Insights from Mathematical Modeling.

Cold atmospheric plasma (CAP) and plasma-treated liquids (PTLs) have recently become a promising option for cancer treatment, but the underlying mechanisms of the anti-cancer effect are still to a large extent unknown. Although hydrogen peroxide (H2O2) has been recognized as the major anti-cancer agent of PTL and may enable selectivity in a certain concentration regime, the co-existence of nitrite can create a synergistic effect. We develop a mathematical model to describe the key species and features of the cellular response toward PTL. From the numerical solutions, we define a number of dependent variables, which represent feasible measures to quantify cell susceptibility in terms of the H2O2 membrane diffusion rate constant and the intracellular catalase concentration. For each of these dependent variables, we investigate the regimes of selective versus non-selective, and of synergistic versus non-synergistic effect to evaluate their potential role as a measure of cell susceptibility. Our results suggest that the maximal intracellular H2O2 concentration, which in the selective regime is almost four times greater for the most susceptible cells compared to the most resistant cells, could be used to quantify the cell susceptibility toward exogenous H2O2. We believe our theoretical approach brings novelty to the field of plasma oncology, and more broadly, to the field of redox biology, by proposing new ways to quantify the selective and synergistic anti-cancer effect of PTL in terms of inherent cell features.

The Influence of UV Light on Photodegradation of Acetylsalicylic Acid.

Photodegradation of the aqueous solutions of acetylsalicylic acid, in the absence (ASA) and the presence of excipients (ASE), is demonstrated by the photoluminescence (PL). A shift of the PL bands from 342 and 338 nm to 358 and 361-397 nm for ASA and ASE in solid state and as aqueous solutions was reported. By exposure of the solution of ASA 0.3 M to UV light, a decrease in the PL band intensity was highlighted. This behavior was revealed for ASA in the presence of phosphate buffer (PB) having the pH equal to 6.4, 7, and 8 or by the interaction with NaOH 0.3 M. A different behavior was reported in the case of ASE. In the presence of PB, an increase in the intensity of the PL band of ASE simultaneously with a change of the ratio between the intensities of the bands at 361-364 and 394-397 nm was highlighted. The differences between PL spectra of ASA and ASE have their origin in the presence of salicylic acid (SAL). The interaction of ASE with NaOH induces a shift of the PL band at 405-407 nm. Arguments for the reaction of ASA with NaOH are shown by Raman scattering and FTIR spectroscopy.

Propagation of THz irradiation energy through aqueous layers: Demolition of actin filaments in living cells.

The effect of terahertz (THz) radiation on deep tissues of human body has been considered negligible due to strong absorption by water molecules. However, we observed that the energy of THz pulses transmits a millimeter thick in the aqueous solution, possibly as a shockwave, and demolishes actin filaments. Collapse of actin filament induced by THz irradiation was also observed in the living cells under an aqueous medium. We also confirmed that the viability of the cell was not affected under the exposure of THz pulses. The potential of THz waves as an invasive method to alter protein structure in the living cells is demonstrated.

Estimation of the fluorescence lifetime for optically inaccessible exciplexes in nonpolar solutions under ionizing irradiation.

X-irradiation of nonpolar solutions likely provides a possibility to create exciplexes for any donor-acceptor pair that would energetically and sterically allow this. Thorough study and characterization of X-radiation generated exciplexes usually cannot be carried out with conventional methods because of the complex and non-exponential formation and decay dynamics of these species. In this paper, we present a simple and universal experimental approach for the estimation of fluorescence lifetimes (τF) of X-radiation generated exciplexes. The suggested procedure is based on the comparison of quenching of the exciplex emission band and the emission band from a standard luminophore with a known excited state lifetime by dissolved oxygen. Using this approach we report the τF values for two systems with optically inaccessible exciplexes, diphenylacetylene-N,N-dimethylaniline (DMA) and p-terphenyl-DMA, and for two typical exciplex forming systems, naphthalene-DMA and anthracene-DMA. All the found τF values for the X-radiation generated exciplexes lie in the range of 50-70 ns. The accuracy of this approach was checked by time-resolved measurements under X- or near-UV irradiation for those pairs, whose properties make this feasible. The proposed method gives a possibility to avoid a complex numerical evaluation of the non-exponential kinetics of recombination luminescence, and can be used to estimate the characteristic τF values for luminophores and excited complexes formed under X-radiation.

Substituent Effects on the Photodeprotection Reactions of Selected Ketoprofen Derivatives in Phosphate Buffered Aqueous Solutions.

Photodeprotection is an important reaction that has been attracting broad interest for use in a variety of applications. Recent advances in ultrafast and vibrational time-resolved spectroscopies can facilitate obtaining data to help unravel the reaction mechanisms involving in the photochemical reactions of interest. The kinetics and reaction mechanisms for the photodeprotection reactions of ketoprofen derivatives containing three different substituents (ibuprofen, Br and I) were investigated by femtosecond transient absorption (fs-TA) and nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy methods in phosphate buffered solutions (PBS). Fs-TA allows us to detect the decay kinetics of the triplet species as the key precursor for formation of a carbanion species for three different substituents attached to ketoprofen. To characterize the structural and electronic properties of the corresponding carbanion and triplet intermediates, TR(3) spectroscopic experiments were conducted. The transient spectroscopy work reveals that the different substituents affect the photodecarboxylation reaction to produce carbon dioxide which in turn influences the generation of the carbanion species which determines the rate of the photorelease of the functional groups attached on the ketoprofen parent molecule. The fingerprint TR(3) spectroscopy results suggest that ketoprofen derivatives may be deactivated to produce a triplet carbanion when increasing the atom mass of the halogen atoms.

Fluid Viscosity Affects the Fragmentation and Inertial Cavitation Threshold of Lipid-Encapsulated Microbubbles.

Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (∼4 cP). In this study, ultrahigh-speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25-2 MPa). The propensity for individual microbubble (n = 220) fragmentation was found to significantly decrease in 4-cP fluid compared with 1-cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4-cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g., ultraharmonic) with increasing pressure, compared with those in 1-cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations.

EPR-Spin Trapping and Flow Cytometric Studies of Free Radicals Generated Using Cold Atmospheric Argon Plasma and X-Ray Irradiation in Aqueous Solutions and Intracellular Milieu.

Electron paramagnetic resonance (EPR)-spin trapping and flow cytometry were used to identify free radicals generated using argon-cold atmospheric plasma (Ar-CAP) in aqueous solutions and intracellularly in comparison with those generated by X-irradiation. Ar-CAP was generated using a high-voltage power supply unit with low-frequency excitation. The characteristics of Ar-CAP were estimated by vacuum UV absorption and emission spectra measurements. Hydroxyl (·OH) radicals and hydrogen (H) atoms in aqueous solutions were identified with the spin traps 5,5-dimethyl-1-pyrroline N-oxide (DMPO), 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (M4PO), and phenyl N-t-butylnitrone (PBN). The occurrence of Ar-CAP-induced pyrolysis was evaluated using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS) in aqueous solutions of DNA constituents, sodium acetate, and L-alanine. Human lymphoma U937 cells were used to study intracellular oxidative stress using five fluorescent probes with different affinities to a number of reactive species. The analysis and quantification of EPR spectra revealed the formation of enormous amounts of ·OH radicals using Ar-CAP compared with that by X-irradiation. Very small amounts of H atoms were detected whereas nitric oxide was not found. The formation of ·OH radicals depended on the type of rare gas used and the yield correlated inversely with ionization energy in the order of krypton > argon = neon > helium. No pyrolysis radicals were detected in aqueous solutions exposed to Ar-CAP. Intracellularly, ·OH, H2O2, which is the recombination product of ·OH, and OCl- were the most likely formed reactive oxygen species after exposure to Ar-CAP. Intracellularly, there was no practical evidence for the formation of NO whereas very small amounts of superoxides were formed. Despite the superiority of Ar-CAP in forming ·OH radicals, the exposure to X-rays proved more lethal. The mechanism of free radical formation in aqueous solutions and an intracellular milieu is discussed.

The Fricke dosimeter as an absorbed dose to water primary standard for Ir-192 brachytherapy.

The aim of this project was to develop an absorbed dose to water primary standard for Ir-192 brachytherapy based on the Fricke dosimeter. To achieve this within the framework of the existing TG-43 protocol, a determination of the absorbed dose to water at the reference position, D(r0,θ0), was undertaken. Prior to this investigation, the radiation chemical yield of the ferric ions (G-value) at the Ir-192 equivalent photon energy (0.380 MeV) was established by interpolating between G-values obtained for Co-60 and 250 kV x-rays.An irradiation geometry was developed with a cylindrical holder to contain the Fricke solution and allow irradiations in a water phantom to be conducted using a standard Nucletron microSelectron V2 HDR Ir-192 afterloader. Once the geometry and holder were optimized, the dose obtained with the Fricke system was compared to the standard method used in North America, based on air-kerma strength.Initial investigations focused on reproducible positioning of the ring-shaped holder for the Fricke solution with respect to the Ir-192 source and obtaining an acceptable type A uncertainty in the optical density measurements required to yield the absorbed dose. Source positioning was found to be reproducible to better than 0.3 mm, and a careful cleaning and control procedure reduced the variation in optical density reading due to contamination of the Fricke solution by the PMMA holder. It was found that fewer than 10 irradiations were required to yield a type A standard uncertainty of less than 0.5%.Correction factors to take account of the non-water components of the geometry and the volume averaging effect of the Fricke solution volume were obtained from Monte Carlo calculations. A sensitivity analysis showed that the dependence on the input data used (e.g. interaction cross-sections) was small with a type B uncertainty for these corrections estimated to be 0.2%.The combined standard uncertainty in the determination of absorbed dose to water at the reference position for TG-43 (1 cm from the source on the transverse axis, in a water phantom) was estimated to be 0.8% with the dominant uncertainty coming from the determination of the G-value. A comparison with absorbed dose to water obtained using the product of air-kerma strength and the dose rate constant gave agreement within 1.5% for three different Ir-192 sources, which is within the combined standard uncertainties of the two methods.

Rayleigh surface acoustic wave as an efficient heating system for biological reactions: investigation of microdroplet temperature uniformity.

When a microdroplet is put on the Rayleigh surface acoustic wave path, longitudinal waves are radiated into the liquid and induce several phenomena such as the wellknown surface acoustic wave streaming. At the same time, the temperature of the microdroplet increases as it has been shown. In this paper, we study the temperature uniformity of a microdroplet heated by Rayleigh surface acoustic wave for discrete microfluidic applications such as biological reactions. To precisely ascertain the temperature uniformity and not interfere with the biological reaction, we used an infrared camera. We then tested the temperature uniformity as a function of three parameters: the microdroplet volume, the Rayleigh surface acoustic wave frequency, and the continuous applied radio frequency power. Based on these results, we propose a new device structure to develop a future lab on a chip based on reaction temperatures.

Limiting radiation damage for high-brilliance biological solution scattering: practical experience at the EMBL P12 beamline PETRAIII.

Radiation damage is the general curse of structural biologists who use synchrotron small-angle X-ray scattering (SAXS) to investigate biological macromolecules in solution. The EMBL-P12 biological SAXS beamline located at the PETRAIII storage ring (DESY, Hamburg, Germany) caters to an extensive user community who integrate SAXS into their diverse structural biology programs. The high brilliance of the beamline [5.1 × 10(12) photons s(-1), 10 keV, 500 (H) µm × 250 (V) µm beam size at the sample position], combined with automated sample handling and data acquisition protocols, enable the high-throughput structural characterization of macromolecules in solution. However, considering the often-significant resources users invest to prepare samples, it is crucial that simple and effective protocols are in place to limit the effects of radiation damage once it has been detected. Here various practical approaches are evaluated that users can implement to limit radiation damage at the P12 beamline to maximize the chances of collecting quality data from radiation sensitive samples.

A feasibility study of Fricke dosimetry as an absorbed dose to water standard for 192Ir HDR sources.

High dose rate brachytherapy (HDR) using 192Ir sources is well accepted as an important treatment option and thus requires an accurate dosimetry standard. However, a dosimetry standard for the direct measurement of the absolute dose to water for this particular source type is currently not available. An improved standard for the absorbed dose to water based on Fricke dosimetry of HDR 192Ir brachytherapy sources is presented in this study. The main goal of this paper is to demonstrate the potential usefulness of the Fricke dosimetry technique for the standardization of the quantity absorbed dose to water for 192Ir sources. A molded, double-walled, spherical vessel for water containing the Fricke solution was constructed based on the Fricke system. The authors measured the absorbed dose to water and compared it with the doses calculated using the AAPM TG-43 report. The overall combined uncertainty associated with the measurements using Fricke dosimetry was 1.4% for k = 1, which is better than the uncertainties reported in previous studies. These results are promising; hence, the use of Fricke dosimetry to measure the absorbed dose to water as a standard for HDR 192Ir may be possible in the future.

Dynamics and electrorheology of sheared immiscible fluid mixtures.

We analyze the electrorheological effect in immiscible fluid mixtures with dielectric mismatch. By taking the electric field effect into account, which couples to the dynamics of domain morphology under flow, we propose a set of electrorheological constitutive equations valid under the condition where the relative magnitude of the flow field is stronger than that of the electric field. Through comparison with recent experiments, we point out a unique dynamical stress response inherent in situations where the cross-coupling between different fields is essential.

Unpinning of spiral waves by electrical forcing in excitable chemical media.

We present experimental observations on the electrically forced release of spiral waves pinned to unexcitable circular obstacles in the Belosov-Zhabotinsky reaction. When the applied electric current density reaches the necessary current density J(unpin), the spiral tip is detached and subsequently drifts away from the obstacle. J(unpin) is found to increase with the obstacle diameter d. The growth rate ΔJ(unpin)/Δd is much higher for obstacles larger than the free spiral core compared to that for smaller obstacles. The experimental findings are confirmed by numerical simulations using the Oregonator model. The results imply that it is more difficult to release spiral waves pinned to larger obstacles, especially when the obstacle size exceeds that of the free spiral core.

Hydroxyl radical-induced crosslinking and radiation-initiated hydrogel formation in dilute aqueous solutions of carboxymethylcellulose.

Ionizing radiation causes chain scission of polysaccharides in the absence of crosslinking agents. It has been demonstrated before that degradation of carboxyalkylated polysaccharides may be prevented, despite presence of strong electrostatic repulsing forces between chains, at very high polymer concentration in water (paste-like state) when physical proximity promotes recombination of radiation-generated polymer radicals. In such conditions, crosslinking dominates over chain scission and covalent, macroscopic gels can be formed. In an approach proposed in this work, neutralizing the charges on carboxymethylcellulose (CMC) by lowering the pH results in retracting the electrostatic repulsion between chain segments and thus allows for substantial reduction of polymer concentration required to achieve gelation due to domination of crosslinking reactions. Electron-beam irradiation of aqueous solutions of low pH containing 0.5-2% CMC results in hydrogel formation with 70% yield, while both concentration and dose determine their swelling properties. Time-resolved studies by laser flash photolysis clearly indicate strong pH influence on decay kinetics of CMC radicals.

Saturation of nonaxisymmetric instabilities of magnetized spherical Couette flow.

We numerically investigate the saturation of the hydromagnetic instabilities of a magnetized spherical Couette flow. Previous simulations demonstrated a region where the axisymmetric flow, calculated from a 2D simulation, was linearly unstable to nonaxisymmetric perturbations. Full, nonlinear, 3d simulations showed that the saturated state would consist only of harmonics of one azimuthal wave number, though there were bifurcations and transitions as nondimensional parameters (Re, Ha) were varied. Here, the energy transfer between different azimuthal modes is formulated as a network. This demonstrates a mechanism for the saturation of one mode and for the suppression of other unstable modes. A given mode grows by extracting energy from the axisymmetric flow, and then saturates as the energy transfer to its second harmonic equals this inflow. At the same time, this mode suppresses other unstable modes by facilitating an energy transfer to linearly stable modes.

Capillary filling under electro-osmotic effects in the presence of electromagneto-hydrodynamic effects.

We report various regimes of capillary filling dynamics under electromagneto-hydrodynamic interactions, in the presence of electrical double layer effects. Our chosen configuration considers an axial electric field and transverse magnetic field acting on an electrolyte. We demonstrate that for positive interfacial potential, the movement of the capillary front resembles capillary rise in a vertical channel under the action of gravity. We also evaluate the time taken by the capillary front to reach the final equilibrium position for positive interfacial potential and show that the presence of a transverse magnetic field delays the time of travel of the liquid front, thereby sustaining the capillary motion for a longer time. Our scaling estimates reveal that the initial linear regime starts, as well as ends, much earlier in the presence of electrical and magnetic body forces, as compared to the corresponding transients observed under pure surface tension driven flow. We further obtain a long time solution for the capillary imbibition for positive interfacial potential, and derive a scaling estimate of the capillary stopping time as a function of the applied magnetic field and an intrinsic length scale delineating electromechanical influences of the electrical double layer. Our findings are likely to offer alternative strategies of controlling dynamical features of capillary imbibition, by modulating the interplay between electromagnetic interactions, electrical double layer phenomena, and hydrodynamics over interfacial scales.

Dynamo efficiency controlled by hydrodynamic bistability.

Hydrodynamic and magnetic behaviors in a modified experimental setup of the von Kármán sodium flow-where one disk has been replaced by a propeller-are investigated. When the rotation frequencies of the disk and the propeller are different, we show that the fully turbulent hydrodynamic flow undergoes a global bifurcation between two configurations. The bistability of these flow configurations is associated with the dynamics of the central shear layer. The bistable flows are shown to have different dynamo efficiencies; thus for a given rotation rate of the soft-iron disk, two distinct magnetic behaviors are observed depending on the flow configuration. The hydrodynamic transition controls the magnetic field behavior, and bifurcations between high and low magnetic field branches are investigated.

Retarded photooxidation of cyamemazine in biomimetic microenvironments.

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within α1 -acid glycoproteins, ß- and γ-cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355 nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+•)). Upon addition of glycoprotein, the contribution of CMZ(+•) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.

Photophysical properties and singlet oxygen generation efficiencies of water-soluble fullerene nanoparticles.

As various fullerene derivatives have been developed, it is necessary to explore their photophysical properties for potential use in photoelectronics and medicine. Here, we address the photophysical properties of newly synthesized water-soluble fullerene-based nanoparticles and polyhydroxylated fullerene as a representative water-soluble fullerene derivative. They show broad emission band arising from a wide-range of excitation energies. It is attributed to the optical transitions from disorder-induced states, which decay in the nanosecond time range. We determine the kinetic properties of the singlet oxygen ((1)O2) luminescence generated by the fullerene nanoparticles and polyhydroxylated fullerene to consider the potential as photodynamic agents. Triplet state decay of the nanoparticles was longer than (1)O2 lifetime in water. Singlet oxygen quantum yield of a series of the fullerene nanoparticles is comparably higher ranging from 0.15 to 0.2 than that of polyhydroxylated fullerene, which is about 0.06.