Thermodynamic Destabilization Research Articles

Cumulative asparagine to aspartate deamidation fails to perturb γD-crystallin structure and stability.

Deamidation frequently is invoked as an important driver of crystallin aggregation and cataract formation. Here, we characterized the structural and biophysical consequences of cumulative Asn to Asp changes in γD-crystallin. Using NMR spectroscopy, we demonstrate that N- or C-terminal domain-confined or fully Asn to Asp changed γD-crystallin exhibits essentially the same 1H-15N HSQC spectrum as the wild-type protein, implying that the overall structure is retained. Only a very small thermodynamic destabilization for the overall Asn to Asp γD-crystallin variants was noted by chaotropic unfolding, and assessment of the colloidal stability, by measuring diffusion interaction parameters, yielded no substantive differences in association propensities. Furthermore, using molecular dynamics simulations, no significant changes in dynamics for proteins with Asn to Asp or iso-Asp changes were detected. Our combined results demonstrate that substitution of all Asn by Asp residues, reflecting an extreme case of deamidation, did not affect the structure and biophysical properties of γD-crystallin. This suggests that these changes alone cannot be the major determinant in driving cataract formation.

Unusual nanoscale amorphization of metallic chromium interfacing with SiC under high energy irradiation

Layered metal/silicon carbide (SiC) materials systems are becoming increasingly relevant to solve materials challenges in advanced fission and fusion nuclear energy systems, necessitating a deeper understanding of how interfaces between dissimilar materials behave under high energy irradiation. In this work, we use a Cr-SiC bilayer system as a model to study the behavior of such interfaces under high energy ion irradiation (80 MeV Xe26+ ions) at elevated temperatures (∼350 °C). Through high resolution characterization of the interface, we observed the formation of a nanoscale Cr-rich amorphous layer adjacent to crystalline SiC. We explain this phenomenon through a multi-scale computational approach incorporating ballistic mixing simulations, density functional theory calculations, and CALPHAD-based non-equilibrium modeling that shows the localized amorphization of Cr to be driven by the synergistic action of irradiation-induced point defects within Cr and transport of Si and C atoms across the interface. In particular, the accumulation of radiation damage results in the thermodynamic destabilization of the point-defect containing, metastable Cr-Si-C solid solution with respect to an amorphous phase of identical composition. This study advances the understanding of how metal/SiC interfaces behave under irradiation and establishes a modeling framework that can be applied to interfacial systems to understand irradiation-induced amorphization.

Destabilizing high-capacity high entropy hydrides via earth abundant substitutions: From predictions to experimental validation

The vast chemical space of high entropy alloys (HEAs) makes trial-and-error experimental approaches for materials discovery intractable and often necessitates data-driven and/or first principles computational insights to successfully target materials with desired properties. In the context of materials discovery for hydrogen storage applications, a theoretical prediction-experimental validation approach can vastly accelerate the search for substitution strategies to destabilize high-capacity hydrides based on benchmark HEAs, e.g. TiVNbCr alloys. Here, machine learning predictions, corroborated by density functional theory calculations, predict substantial hydride destabilization with increasing substitution of earth-abundant Fe content in the (TiVNb)75Cr25-xFex system. The as-prepared alloys crystallize in a single-phase bcc lattice for limited Fe content x < 7, while larger Fe content favors the formation of a secondary C14 Laves phase intermetallic. Short range order for alloys with x < 7 can be well described by a random distribution of atoms within the bcc lattice without lattice distortion. Hydrogen absorption experiments performed on selected alloys validate the predicted thermodynamic destabilization of the corresponding fcc hydrides and demonstrate promising lifecycle performance through reversible absorption/desorption. This demonstrates the potential of computationally expedited hydride discovery and points to further opportunities for optimizing bcc alloy ↔ fcc hydrides for practical hydrogen storage applications.

Stable hydrogen storage of lithium borohydrides via the catalytic effect of Ni2B induced by thermodynamic destabilization reaction

Lithium borohydride (LiBH4) is regarded as a potential hydrogen storage material due to its high gravimetric and volumetric capacity, but its practical application suffers from high operating temperature and poor reversibility. Herein, porous hollow carbon microspheres composed of carbon-coated Ni nanoparticles with high content (denoted as Ni/C) are rationally designed as functional support, which not only induces effective nanoconfinement of LiBH4 but also promotes efficiently homogeneous destabilization reaction between LiBH4 and Ni nanoparticles. The introduction of Ni nanoparticles leads to the decrease of the Gibbs free energy change for H2 desorption of LiBH4 based on the formation of Ni2B down to −0.95 eV while this value reaches 1.19 eV for bulk LiBH4, validating the effective role of Ni in thermodynamically destabilizing H2 desorption. Impressively, the average B–H bond length of LiBH4 on Ni2B reaches 1.291 Å and thus the corresponding dissociation energy of removing one H atom from LiBH4 is lowered to 1.00 eV, much lower than bulk LiBH4 (4.22 eV) and even LiBH4 on Ni (1.27 eV), which verifies superior role of Ni2B than Ni in catalytically enhancing H2 desorption. Therefore, a capacity of 8.86 wt.% is obtained for LiBH4 confined into Ni/C at 320 °C after 10 cycles.

Isotope engineering achieved by local coordination design in Ti-Pd co-doped ZrCo-based alloys

Deuterium/Tritium (D/T) handling in defined proportions are pivotal to maintain steady-state operation for fusion reactors. However, the hydrogen isotope effect in metal-hydrogen systems always disturbs precise D/T ratio control. Here, we reveal the dominance of kinetic isotope effect during desorption. To reconcile the thermodynamic stability and isotope effect, we demonstrate a quantitative indicator of Tgap and further a local coordination design strategy that comprises thermodynamic destabilization with vibration enhancement of interstitial isotopes for isotope engineering. Based on theoretical screening analysis, an optimized Ti-Pd co-doped Zr0.8Ti0.2Co0.8Pd0.2 alloy is designed and prepared. Compared to ZrCo alloy, the optimal alloy enables consistent isotope delivery together with a three-fold lower Tgap, a five-fold lower energy barrier difference, a one-third lower isotopic composition deviation during desorption and an over two-fold higher cycling capacity. This work provides insights into the interaction between alloy and hydrogen isotopes, thus opening up feasible approaches to support high-performance fusion reactors.

Effect of Cr/Mn Addition in TiVNb on Hydrogen Sorption Properties: Thermodynamics and Phase Transition Study

High-entropy alloys (HEAs) are a promising class of materials that can grant remarkable functional performances for a large range of applications due to their highly tunable composition. Among these applications, recently, bcc HEAs capable of forming fcc hydrides have been proposed as high-capacity hydrogen storage materials with improved thermodynamics compared to classical metal hydrides. In this context, a single-phase bcc (TiVNb)0.90Cr0.05Mn0.05 HEA was prepared by arc melting to evaluate the effect of combined Cr/Mn addition in the ternary TiVNb. A thermodynamic destabilization of the fcc hydride phase was found in the HEA compared to the initial TiVNb. In situ neutron and synchrotron X-ray diffraction experiments put forward a fcc → bcc phase transition of the metallic subnetwork in the temperature range of 260–350 °C, whereas the H/D subnetwork underwent an order → disorder transition at 180 °C. The absorption/desorption cycling demonstrated very fast absorption kinetics at room temperature in less than 1 min with a remarkable total capacity (2.8 wt.%) without phase segregation. Therefore, the design strategy consisting of small additions of non-hydride-forming elements into refractory HEAs allows for materials with promising properties for solid-state hydrogen storage to be obtained.

Enhanced hydrogen sorption properties of uniformly dispersed Pd-decorated three-dimensional (3D) Mg@Pd architecture

This study demonstrates the hydrogen sorption improvement of Mg through the three-dimensional decoration of a noble catalyst. An Mg@Pd composite was synthesized by decorating Pd nanoparticles onto the Mg matrix via a facile solid-gas reduction method. Electron tomography analysis confirms the formation of a three-dimensional (3D) architecture of the Mg@Pd particulate composite. The Mg@Pd composite shows excellent hydrogenation/dehydrogenation kinetics even at low temperatures as compared to a catalyst-free Mg sample. Moreover, the hydrogenated Mg@Pd composite can desorb hydrogen at as low as 246 °C that is 87 °C lower than that of the pure MgH2. Hydrogenation of the Mg@Pd composite leads to the development of a multiphase system consisted of PdH0.706, MgPd and MgH2 whereas dehydrogenation occurred via two simultaneous desorption reactions results in Mg6Pd and Mg phases. The uniform dispersion of Pd nanoparticles on the surface of the 3D Mg matrix has provided with fast catalytic interfaces via the hydrogen “spillover” mechanism while the concomitant hydrogen diffusion processes are enhanced by the “hydrogen pump” effect of PdH0.706/MgPd interfaces. Furthermore, the low temperature hydrogen sorption performances of the Mg@Pd composite can be attributed to the interphase reversibility between MgPd and Mg6Pd leading to the thermodynamic destabilization of MgH2. This study suggests that strategically new approaches can govern significant improvements in hydrogen storage properties of Mg-based systems.

Elucidating Primary Degradation Mechanisms in High-Cycling-Capacity, Compositionally Tunable High-Entropy Hydrides.

The hydrogen sorption properties of single-phase bcc (TiVNb)100-xCrx alloys (x = 0-35) are reported. All alloys absorb hydrogen quickly at 25 °C, forming fcc hydrides with storage capacity depending on the Cr content. A thermodynamic destabilization of the fcc hydride is observed with increasing Cr concentration, which agrees well with previous compositional machine learning models for metal hydride thermodynamics. The steric effect or repulsive interactions between Cr-H might be responsible for this behavior. The cycling performances of the TiVNbCr alloy show an initial decrease in capacity, which cannot be explained by a structural change. Pair distribution function analysis of the total X-ray scattering on the first and last cycled hydrides demonstrated an average random fcc structure without lattice distortion at short-range order. If the as-cast alloy contains a very low density of defects, the first hydrogen absorption introduces dislocations and vacancies that cumulate into small vacancy clusters, as revealed by positron annihilation spectroscopy. Finally, the main reason for the capacity drop seems to be due to dislocations formed during cycling, while the presence of vacancy clusters might be related to the lattice relaxation. Having identified the major contribution to the capacity loss, compositional modifications to the TiVNbCr system can now be explored that minimize defect formation and maximize material cycling performance.

Thermal Characterisation and Isoconversional Kinetic Analysis of Osmotically Dried Pork Meat Proteins Longissimus dorsi.

The kinetic properties and thermal characteristics of fresh pork meat proteins (Longissimus dorsi), as well as osmotically dehydrated meat proteins, were investigated using differential scanning calorimetry. Two isoconversional kinetical methods, namely the differential Friedman and integral Ortega methods, were employed to analyze the data. The obtained kinetic triplet, activation energy, pre-exponential factor, and extent of conversion, has been discussed. The resulting activation energy for proteins of fresh meat ranges between 751 kJ·mol-1 for myosin, 152 kJ·mol-1 for collagen and sarcoplasmic proteins, and 331 kJ·mol-1 for actin at a conversion degree of 0.1 to 0.9. For osmotically dried pork meat proteins, the values range from 307 kJ·mol-1 for myosin 272 kJ·mol-1 for collagen and sarcoplasmic proteins, and 334.83 kJ·mol-1 for actin at a conversion degree from 0.1 to 0.9. The proteins of the dry meat obtained by osmotic dehydration in molasses could be described as partly unfolded as they retain the characteristic protein denaturation transition. Concerning the decrease in enthalpies of proteins denaturation, thermodynamic destabilization of dried meat proteins occurred. On the contrary, dried meat proteins were thermally stabilized with respect to increase in the temperatures of denaturation. Knowledge of the nature of meat protein denaturation of each kind of meat product is one of the necessary tools for developing the technology of meat product processing and to achieve desired quality and nutritional value. The kinetic analysis of meat protein denaturation is appropriate because protein denaturation gives rise to changes in meat texture during processing and directly affects the quality of product.

Thermodynamic destabilization and kinetic optimization for the de-/hydrogenation of Mg85Ni15 alloy by tailoring Mg(In) and Mg2Ni(In) double solid solution

To increase the hydrogen de-/absorption rate and reduce the stability of MgH2, element indium (In) is introduced into the hypereutectic Mg85Ni15 alloy. The results show that solid solution phases of Mg(In) and Mg2Ni(In) are formed simultaneously, and the lattice parameters of Mg crystals decrease while that of Mg2Ni crystals increase. The hydrogen storage capacity of Mg85Ni14.5In0.5 alloy reaches 3.5 wt% at 125 ℃ with the hydrogenation rates accelerated significantly, which is higher than the 2.4 wt% of Mg85Ni15 alloy. For dehydrogenation, Mg85Ni14In1.0 hydride can release 4.1 wt% hydrogen at 225 ℃ in 15 min. The main peak temperature in DSC test for dehydrogenation is decreased to 226.6 ℃ of Mg85Ni13.5In1.5 hydride from 246.1 ℃ of Mg85Ni15 hydride and decomposition enthalpy (ΔH) of Mg85Ni13.5In1.5 hydride is decreased to 60.9 kJ/mol. The rapid hydrogenation rate is owing to the dissolved In atoms in Mg2Ni lattice causing lattice expansion, which acts as fast diffusion path for hydrogen atoms. In Mg(In)H2 phase, the strong interaction between Mg and In weakens the affinity of Mg and H, which accounts for the reduced ΔH of Mg(In)H2. The weakened strength of Ni-H bond in Mg2Ni(In)H4 also results in the decreased stability of hydride.

The adaptable effect of Ru on hydrogen sorption characteristics of the MgH2 system

In this study, a MgH2–Ru composite is prepared by mechanical ball milling of MgH2 and Ru powders. The microstructural analysis revealed the uniform distribution of Ru nanoparticles in the MgH2 matrix and the formation of intermetallic compounds (i.e. Mg6.2Ru and Mg1.5Ru) after dehydrogenation of the composite. The substantial improvements in the de/hydrogenation properties of MgH2 are due to the adjustable catalytic role of Ru under low temperature and pressure conditions. MgH2–Ru composite started to release hydrogen at an onset temperature of 300 °C, much lower than the mechanically milled pure MgH2 (350 °C). Hydrogen absorption of the MgH2–Ru composite is relatively fast at 350 °C and stored 6.1 wt% in 5 min. At the same temperature, the hydrogenated MgH2–Ru composite released all stored hydrogen in less than 5 min. Compared with the catalyst-free MgH2, the hydrogenation and dehydrogenation activation energies of the MgH2–Ru composite are reduced to 65.12 ± 2.4 kJ/mol H2, and 97.46 ± 4.15 kJ/mol H2, respectively. In addition, it further demonstrated how the reversible transformation of Mg–Ru intermetallic phases induces the thermodynamic destabilization of the MgH2 system. The presence of Ru not only facilitated the breaking of the Mg–H bond but also provided very good catalytic interfaces for enhanced de/hydrogenation properties of MgH2.

Physicochemical stability study of a biosimilar of Bevacizumab in vials and after dilution in 0.9% NaCl in polyolefin intravenous bags

Abstract Objectives Bevacizumab was first marketed in 2005. Since then, its stability has been extensively studied. The arrival of numerous biosimilars on the market has called into question these stabilities and organisation within reconstitution units. To study the stability of the Bevacizumab biosimilar Alymsys® marketed by Zentiva laboratory in ready-to-use vials at a concentration of 25 mg/mL and following dilution to obtain final concentrations of 1.4 and 16.5 mg/mL and storage in polyolefin IV bags at 4 °C. In parallel, the impact of a storage temperature excursion at 25 °C for three days and storage of the vial before opening at room temperature (25 ± 2 °C) and after opening at 4 °C was studied. Methods The vials were supplied by Zentiva laboratory. The vials (three batches) were diluted to the final concentrations of 1.4 or 16.5 mg/mL in 100 mL IV bags of NaCl. The IV bags and vials were stored at 4 °C and at room temperature throughout the duration of the study. The physico-chemical stability was tested using the following methods: turbidimetry, UV spectrometry and fluorescence, dynamic light scattering, ion exchange and steric exclusion chromatography, pH, osmolality and density. Results Out of all the parameters studied, for the two concentrations and standard storage conditions (90 days at +4 °C) or after a three-day temperature excursion at +25 °C, no modification was detected for the three batches tested with respect to physical and chemical stability. Hence, no signs of physical instability were observed, with, in particular, the absence of formation of submicron or micron sized aggregates and particles. The steric exclusion chromatography profiles did not demonstrate any oligomer formation or molecular structure rupture. Ion exchange chromatography did not demonstrate any significant modification in the distribution of charge variants. Derivative UV and fluorescence spectral analysis did not demonstrate any modification. The thermal denaturation curves were identical, suggesting the absence of thermodynamic destabilisation. Identical results were observed for the vials stored for 60 days at 4 °C after opening. Finally, only ion exchange chromatography demonstrated a slight change after 45 days of storage at 25 °C for vials before opening. Conclusions After dilution in sterile conditions with 0.9% NaCl in polyolefin IV bags, at the usual concentrations of 1.4 and 16.5 mg/mL, the Bevacizumab biosimilar Alymsys® is stable for at least three months at 4 °C protected from light and after a three-day temperature excursion at +25 °C. The same conclusions can be reached for the 25 mg/mL vials stored for 60 days at +4 °C after opening. However, the stability of vials stored at 25 °C before opening is no longer guaranteed beyond 15 days.

Insights into thermodynamic destabilization in Mg-In-D hydrogen storage system: A combined synchrotron X-ray and neutron diffraction study

In this study, ultrafine Mg(In) solid-solution particles were successfully prepared through an arc plasma method and their deuterium uptake/release performances were systematically estimated with respect to the identically processed pure Mg particles. Thermodynamic destabilization and kinetic enhancement of Mg-In-D system were achieved simultaneously with lower deuterium ab/desorption enthalpies and decreased desorption temperatures. For the first time, an in-situ synchrotron X-ray diffraction (ISXRD) coupled with neutron powder diffraction (NPD) technique and density functional theory (DFT) calculations clearly substantiated that an indium diffusion-dominated phase transition is the driving force for the evolution from mixture of MgD2 and Mg-In intermetallic to Mg-based solid solution during the deuterium release (DR). The ISXRD results clarified the real-time phase transition from MgIn to Mg3In at 515 K and the interreaction of MgD2 and Mg3In at 640 K, by which the matrix could be destabilized to trigger an indium-diffusion governed DR reaction in deuteride. Moreover, with the aid of NPD experiment, the microstructure evolution of Mg-In-D system demonstrated the continuous diffusion of indium into Mg/MgD2 upon desorption. The solubilized indium in MgD2 effectively reduced the D-migration energy barrier and stabilized the lattice structure to restrain the constriction of Mg-D bonds, through which the noticeable improvement on both thermodynamic and kinetic performances of the Mg-In system was achieved. The combination of synchrotron X-ray and neutron diffraction offers a high-efficiency strategy to fathom the hydrogen discharging mechanism from the viewpoint of real-time phase transitions and crystalline structure evolutions.

Effect of isostructural phase transition on cycling stability of ZrCo-based alloys for hydrogen isotopes storage

ZrCo alloy as a promising candidate for hydrogen isotopes storage and delivery in the international thermonuclear experimental reactor (ITER) has attracted considerable attention. However, its capacity retention after 50 cycles is 22.4%, resulting from the disproportionation reaction during repeated phase transitions between cubic ZrCo phase and orthorhombic ZrCoH3 phase. Herein, a single isostructural phase transition with high thermal stability and structural stability in ZrCo-H system is achieved by multicomponent substitution for the first time. Considering the computational screening results, cost and gravimetric hydrogen capacity, a series of Zr0.8Nb0.2Co0.6Cu0.4−xNix (x = 0.2–0.3) alloys are designed and synthesized. The compositional dependence of phase component is further discussed in detail. Specifically, Zr0.8Nb0.2Co0.6Cu0.15Ni0.25 alloy with single orthorhombic phase exhibits high thermal stability (up to 550 °C) and maintains the orthorhombic structure during the de-/hydrogenation process at 380 °C. Thermodynamic destabilization of hydride (ΔH = 71.95 kJ·mol−1 H2) and nearly no de-/hydrogenation hysteresis contribute to a significantly low desorption temperature of 283 °C at 100 kPa. Thanks to superior thermal stability and structural stability, no attenuation of hydrogen storage performances including thermodynamics and kinetics can be observed during 200 de-/hydrogenation cycles, and the supereminent cycling stability of 100% and cyclic hydrogen capacity of 1.65 wt% are achieved. Combined with first-principles calculations, the improved cycling stability of Zr0.8Nb0.2Co0.6Cu0.15Ni0.25 alloy can be ascribed to the reduced lattice expansion and atomic motion during the orthorhombic isostructural phase transition.

An S-glutathiomimetic Provides Structural Insights into Stromal Interaction Molecule-1 Regulation

Stromal interaction molecule 1 (STIM1) is an endo/sarcoplasmic reticulum (ER/SR) calcium (Ca2+) sensing protein that regulates store-operated calcium entry (SOCE). In SOCE, STIM1 activates Orai1-composed Ca2+ channels in the plasma membrane (PM) after ER stored Ca2+ depletion. S-Glutathionylation of STIM1 at Cys56 evokes constitutive SOCE in DT40 cells; however, the structural and biophysical mechanisms underlying the regulation of STIM1 by this modification are poorly defined. By establishing a protocol for site-specific STIM1 S-glutathionylation using reduced glutathione and diamide, we have revealed that modification of STIM1 at either Cys49 or Cys56 induces thermodynamic destabilization and conformational changes that result in increased solvent-exposed hydrophobicity. Further, S-glutathionylation or point-mutation of Cys56 reduces Ca2+ binding affinity, as measured by intrinsic fluorescence and far-UV circular dichroism spectroscopies. Solution NMR showed S-glutathionylated-induced perturbations in STIM1 are localized to the α1 helix of the canonical EF-hand, the α3 and α4 helices of the non-canonical EF-hand and α6 and α8 helices of the SAM domain. Finally, we designed an S-glutathiomimetic mutation that strongly recapitulates the structural, biophysical and functional effects within the STIM1 luminal domain and we envision to be another tool for understanding the effects of protein S-glutathionylation in vitro, in cellulo and in vivo.

Origin of Structural Degradation in Li-Rich Layered Oxide Cathode

The problem Many commercial lithium-ion batteries rely on cathodes that contain alternating layers of transition metal, oxygen, and lithium (e.g. LiCoO2, LiNixMnyCozO2). During charging/discharging, lithium ions diffuse in and out of lithium layers in the cathode to store and release charge. This inevitably changes the material’s crystalline structure, affecting its stability and electrochemical performance. One possible battery failure mechanism is thought to involve the release of oxygen from layered oxide cathodes. This issue is particularly pronounced in lithium- and manganese-rich (LMR) layered cathode materials, which experience rapid voltage fade. Yet these low-cost materials also offer a high energy density that far surpasses commercial cathodes. Although researchers have tried to enhance LMR’s lattice oxygen stability using strategies such as doping or coating, they have had limited success. LMR also contains two distinct types of crystalline regions that undergo different structural changes at the nanoscale during charging/discharging. This could affect the properties of the entire material, but technical limitations have made it difficult to study. Given the ineffectiveness of oxygen stabilizing methods, we suspected that oxygen release might be a symptom, rather than a cause, of voltage fade — and that the problem originates in the material’s unique nanoscale domains. The solution Although the failure mechanism of LMR has been studied extensively with statistical X-ray diffraction and atomic-scale microscopes, less is known about how its structure changes at the mesoscale, spanning nanometers to micrometers. Such observations are technically challenging because they require characterizations at multiple length scales while the cathode is operating. This is particularly difficult for LMR, because its two different nanoscale domains are electrochemically activated at different voltages and involve distinct redox chemistries. This leads to non-equilibrium structural dynamics at the lattice level that contribute to nanoscale lattice strain.These processes were poorly understood, so we conducted a comprehensive investigation of mesoscale lattice evolution in an LMR cathode. In-situ Bragg coherent diffraction imaging (BCDI) results revealed that LMR suffers from severe lattice strain accumulation, which serves as the original driving force to trigger thermodynamic destabilization and oxygen release. By leveraging spinning length X-ray diffraction techniques, we further probed the material from the nanoscale to the macroscale. This showed that the heterogeneous structure dynamics of LMR — in other words, the different responses of its two domains — is the underlying reason that the insertion or deinsertion of lithium ions generates lattice strain. These detrimental reactions play an undeniable role in structure decomposition and electrochemical fade, and we expect they are common in many other cathode materials that host lithium diffusion. The implications We have thoroughly described the origin of lattice strains, lithiation behavior in heterogeneous phases, and their role in oxygen release in LMR. Our discoveries provide solid evidence that the lattice strain we observed in LMR could be affecting the structure, and thus electrochemical performance, of other lithium-based cathodes. This has enabled us to propose potential strategies to effectively suppress strain generation and improve the electrochemical properties of all other layered oxide cathodes, commercial or academic.Previous research into the failure mechanisms of cathode materials have not accounted for lattice strain effects, and these studies should be revisited to properly understand the role of strain. Modifications that have relied on traditional methods like doping or coating to restrict oxygen release — long thought to be the origin of voltage fade in LMR, as well as other cathode types — should also be reevaluated. Our findings suggest that researchers do not completely understand the impact of these modifications on the stability of cathode materials, and they may have actually exacerbated lattice strain behavior. Therefore, our insights into the role of lattice strain have not only opened up a new way to investigate the origin of failure in LMR and lithium-based cathode materials; they have also shown that resolving lattice strain challenges could be a valuable strategy to improve lithium-ion battery performance. Figure 1

Effect of nitrogen concentration on creep strength and microstructure of 9Cr-ODS ferritic/martensitic steel

9Cr oxide dispersion strengthened steels with slightly different nitrogen concentrations (0.0034 − 0.029 wt%) were prepared and their creep property at 973 K was investigated with microstructural characterization before and after the creep test. The creep strength decreased significantly as the nitrogen concentration increased. Microstructural observation revealed that, in the higher nitrogen concentration specimen, coarse Y-rich inclusions were found along the boundary between transformed ferrite region and residual ferrite region. The solubility difference of nitrogen in α and γ phase would induce the localized increment of nitrogen concentration in the boundary region during the austenitizing process, resulting in the thermodynamic destabilization and subsequent coarsening of the dispersed oxide particles. The rows of creep voids were found near the rupture part of the crept specimen, and their fraction increased with increasing nitrogen concentration. This suggests that the coarse inclusions were one of the main starting points of creep void formation, leading to premature fracture in the higher nitrogen specimen.

Assessing the clinical utility of protein structural analysis in genomic variant classification: experiences from a diagnostic laboratory

BackgroundThe widespread clinical application of genome-wide sequencing has resulted in many new diagnoses for rare genetic conditions, but testing regularly identifies variants of uncertain significance (VUS). The remarkable rise in the amount of genomic data has been paralleled by a rise in the number of protein structures that are now publicly available, which may have clinical utility for the interpretation of missense and in-frame insertions or deletions.MethodsWithin a UK National Health Service genomic medicine diagnostic laboratory, we investigated the number of VUS over a 5-year period that were evaluated using protein structural analysis and how often this analysis aided variant classification.ResultsWe found 99 novel missense and in-frame variants across 67 genes that were initially classified as VUS by our diagnostic laboratory using standard variant classification guidelines and for which further analysis of protein structure was requested. Evidence from protein structural analysis was used in the re-assessment of 64 variants, of which 47 were subsequently reclassified as pathogenic or likely pathogenic and 17 remained as VUS. We identified several case studies where protein structural analysis aided variant interpretation by predicting disease mechanisms that were consistent with the observed phenotypes, including loss-of-function through thermodynamic destabilisation or disruption of ligand binding, and gain-of-function through de-repression or escape from proteasomal degradation.ConclusionsWe have shown that using in silico protein structural analysis can aid classification of VUS and give insights into the mechanisms of pathogenicity. Based on our experience, we propose a generic evidence-based workflow for incorporating protein structural information into diagnostic practice to facilitate variant classification.

Interactions between curcumin and cell membrane models by Langmuir monolayers

Studying interactions between potential anticancer drugs and cell membrane models is of great interest to explore the capability of novel drugs in the development of anticancer treatments. Lipid membrane models are useful to understand cellular interactions and to discern drug mechanism action. Here, the interactions of curcumin, as a bioactive natural compound with anti-cancer properties, with both healthy and cancerous or tumor cell membrane models, based on Langmuir monolayers, have been studied. The healthy-cell membrane model is composed of cholesterol 67%, and saturated lipid dipalmitoylphosphatidylcholine 33%. The cancerous-cell-membrane-model is composed of a lower proportion of cholesterol, 25%, and unsaturated lipid sphingomyelin 75%. To compare their interaction with curcumin we report the compression isotherms registered for both lipid membrane models and curcumin in different proportions, their compression moduli and the thermodynamic interaction parameters. From this analysis, we evidence a destabilizing interaction between curcumin and the cancerous cell membrane model in comparison with the healthy one. This interaction is further visualized by micro-Brewster Angle and Atomic Force Microscopies. Our experiments show that the drug enhances cohesion in the healthy membrane model whereas it fluidifies the cancerous cell membrane model causing thermodynamic destabilization. These are useful results to improve the selectivity of the drug avoiding adverse side effects of most current anticancer therapies.

Interaction between Triton X100 and Brij 58 in their binary mixed micelles: Micellization in aqueous solution and aqueous solution of Poloxamer 188 at the range of temperature T = (273.15–323.15) K

The micellization of the binary mixture of surfactants Triton X100 – Brij 58 in an aqueous solution (with and without Poloxamer 188) was investigated using a spectrofluorimetric method with pyrene as a probe molecule. There are synergistic interactions between the micellar building units in the binary mixed micelles Triton X100 – Brij 58, which increase with increasing temperature. The analyzed binary mixed micelles possess molar excess entropy. The molar excess Gibbs free energy is a first-order Margules function from the surfactant (Triton X100 or Brij 58) molar fraction in the binary mixed micelles Triton X100 – Brij 58. Poloxamer 188, in the temperature range T = (273.15–323.15) K, does not form micelles. Poloxamer 188 in an aqueous surfactant solution (0.01 w/w) reduces the thermodynamic stabilization of the binary mixed micelle Triton X100 – Brij 58 concerning the state of the same binary mixed micelle when this polymer is not present in an aqueous solution. In the presence of Poloxamer 188, the thermodynamic destabilization of the binary mixed micelle Triton X100 – Brij 58 increases with increasing temperature.