Unstressed Material Research Articles

Application of NMR and Chemometric Analyses to Better Understand the Quality Attributes in pH and Thermally Degraded Monoclonal Antibodies

PurposeNuclear magnetic resonance (NMR) spectroscopy provides the sensitivity and specificity to probe the higher order structure (HOS) of monoclonal antibodies (mAbs) for potential changes. This study demonstrates an application of chemometric tools to measure differences in the NMR spectra of mAbs after forced degradation relative to the respective unstressed starting materials.MethodsSamples of adalimumab (Humira, ADL-REF) and trastuzumab (Herceptin, TRA-REF) were incubated in three buffer-pH conditions at 40°C for 4 weeks to compare to a control sample that was left unstressed. Replicate 1D 1H and 2D 1H-13C HMQC NMR spectra were collected on all samples. Chemometric analyses such as Easy Comparability of HOS (ECHOS), PROtein FIngerprinting by Lineshape Enhancement (PROFILE), and Principal Component Analysis (PCA) were applied to capture and quantitate differences between the spectra.ResultsVisual and statistical inspection of the 2D 1H-13C HMQC spectra of adalimumab and trastuzumab after forced degradation conditions shows no changes in the spectra relative to the unstressed material. Chemometric analysis of the 1D 1H NMR spectra shows only minor changes in the spectra of adalimumab after forced degradation, but significant differences in trastuzumab.ConclusionThe chemometric analyses support the lack of statistical differences in the structure of pH-thermal stressed adalimumab, however, it reveals conformational changes or chemical modifications in trastuzumab after forced degradation. Application of chemometrics in comparative NMR studies enables HOS characterization and showcases the sensitivity and specificity in detecting differences in the spectra of mAbs after pH-thermal forced degradation with respect to local and global protein structure.

Combined experimental/theoretical approach to residual stresses within multiplicative elasto-plasticity

The study is devoted to geometrically non-linear modelling of viscoplastic structures with residual stresses. We advocate and develop a special approach to residual stresses based on the transition between reference configurations. The finite strain kinematics of the viscoplastic material is modelled by the multiplicative decomposition of the deformation gradient tensor. Numerical algorithms originally developed for unstressed materials are extended to materials with pre-stresses. Owing to the weak invariance of constitutive equations, the incorporation of pre-stresses happens without additional costs. Thus, the advocated approach is especially efficient. A novel experimental/theoretical method for assessment of residual stresses in welded structures is presented; the method combines advantages of purely experimental and theoretical approaches. To demonstrate the applicability of the proposed procedure, we simulate plate welding. As an example we show that the procedure allows extrapolation of the field of residual stresses away from the measurement points. As another example, we address the reduction of weldment-related residual stresses by mechanical treatment.

Impact of specimen preparation method on photovoltaic backsheet degradation during accelerated aging test

AbstractIn this study, we highlight some important factors in the specimen preparation methods for evaluating photovoltaic backsheet properties after accelerated aging. Two different sequences are considered: Method (I) cut‐then‐age: cut into 1‐cm wide strips and then expose to stress, and Method (II) age‐then‐cut: expose a larger sheet to stress and then cut into 1‐cm widths for mechanical property measurements. We also compare the effect of three cutting methods, (a) tensile specimen punch, (b) paper cutter, and (c) fresh razor blade. Several commercial backsheets were evaluated, with stress exposures including (a) pressure cooker test (PCT), (b) dry ultraviolet (UV) radiation exposure, and (c) UV combined damp heat tests. Fourier transform infrared spectrometer (FTIR) and intrinsic viscosity (IV) were used to analyze the materials on unstressed materials and samples exposed to PCT. The results show that both the cutting method and the time of cutting have an impact on the backsheet mechanical properties. Under UV exposure, Method II, age‐then‐cut, generally resulted in a higher average value, with more variation than Method I; however, if the side strips from Method II were excluded, the variation dropped to the same level. This is because the specimens at the sides of the sheet get additional damage from UV light from the exposed sides of the sample. In contrast to UV exposure, PCT specimens prepared by Method II result in lower average values and higher variability. This is attributed to embrittlement through the bulk of the sample where the cutting of embrittled specimens appears to result in more edge defects which can then initiate a break at smaller strains. The data suggest that for UV exposures, the specimens should be cut after aging and the exposed side specimens discarded, and that for PCT exposures, the specimens should be cut before the exposure.

Shear wave velocity is sensitive to changes in muscle stiffness that occur independently from changes in force

Clinical assessments for many musculoskeletal disorders involve evaluation of muscle stiffness, although it is not yet possible to obtain quantitative estimates from individual muscles. Ultrasound elastography can be used to estimate the material properties of unstressed, homogeneous, and isotropic materials by tracking the speed of shear wave propagation; these waves propagate faster in stiffer materials. Although elastography has been applied to skeletal muscle, there is little evidence that shear wave velocity (SWV) can directly estimate muscle stiffness since this tissue violates many of the assumptions required for there to be a direct relationship between SWV and stiffness. The objective of this study was to evaluate the relationship between SWV and direct measurements of muscle force and stiffness in contracting muscle. Data were collected from six isoflurane-anesthetized cats. We measured the short-range stiffness in the soleus via direct mechanical testing in situ and SWV via ultrasound imaging. Measurements were taken during supramaximal activation at optimum muscle length, with muscle temperature varying between 26°C and 38°C. An increase in temperature causes a decrease in muscle stiffness at a given force, thus decoupling the tension-stiffness relationship normally present in muscle. We found that increasing muscle temperature decreased active stiffness from 4.0 ± 0.3 MPa to 3.3 ± 0.3 MPa and SWV from 16.9 ± 1.5 m/s to 15.9 ± 1.6 m/s while force remained unchanged (mean ± SD). These results demonstrate that SWV is sensitive to changes in muscle stiffness during active contractions. Future work is needed to determine how this relationship is influenced by changes in muscle structure and tension.NEW & NOTEWORTHY Shear wave ultrasound elastography is a noninvasive tool for characterizing the material properties of muscle. This study is the first to compare direct measurements of stiffness with ultrasound measurements of shear wave velocity (SWV) in a contracting muscle. We found that SWV is sensitive to changes in muscle stiffness, even when controlling for muscle tension, another factor that influences SWV. These results are an important step toward developing noninvasive tools for characterizing muscle structure and function.

Stressed Cylinder Dispersion Curves Based on Effective Elastic Constants and SAFE Method

A Semi-Analytical Finite Element (SAFE) formulation is applied to determinethe dispersion curves in homogeneous and isotropic cylindrical waveguides subject touniaxial stress. Bulk waves are required for estimating the guided wave dispersion curvesand acoustoelasticity states a stress dependence of the ultrasound bulk velocities. Therefore,acoustoelasticity influences the wave field of the guided waves. Effective Elastic Constants(EEC) has emerged as a less complex alternative to deal with the acoustoelasticity; allowinga stressed material to be assumed as an unstressed material with EEC which considers thedisturbance linked to the presence of stress. In this approach the isotropic specimen subjectto load is studied by proposing an equivalent stress-free with a modified elasticity matrixwhich terms are the EEC. EEC provides an approximate stress-strain relation facilitating thedetermination of the dispersion curves using the well-studied numerical solution for the stressfreecases reducing the complexity of the numerical implementation. Therefore, a numericalmethod combining the SAFE and EEC is presented as a tool for the dispersion curve generationin stressed cylindrical specimens. The results of this methodology are verified by comparingthem with an approach previously reported in the literature based on SAFE including the fullstrain-displacement relation

Inhibiting Effect of Additives on Pressure Solution of Calcite

The task of protection of cultural heritage requires a better understanding of combined effects of mechanical and chemical factors involved in environmental deterioration of monuments. The present paper deals with extending some known physicochemical methods proposed for inhibiting the decay of unstressed materials to their study during water-assisted deformation. The tests have been carried out on natural limestone samples and calcite powders in CaCO3 saturated aqueous solutions under static loads causing measurable pressure solution creep. In the solutions containing 1-hydroxyethylidene-1,1-diphosphonic acid, nitrilotriacetic acid, or ethylenediaminetetraacetic acid, the creep rate decreases considerably with increasing concentration of additives. The extent of creep deceleration has been found to be proportional to the independently estimated calcite surface area occupied by adsorbed species. This fact enables us to discriminate the adsorption-induced effect from other variables controlling the pressure solution rate and may be used in screening of compounds able to minimize the environmental impact on marble and limestone objects undergoing mechanical stresses.

Elastic constants of stressed and unstressed materials in the phase-field crystal model

A general procedure to investigate the elastic response and calculate the elastic constants of stressed and unstressed materials through continuum field modeling, particularly the phase field crystal (PFC) models, is presented. It is found that for a complete description of system response to elastic deformation, the variations of all the quantities of lattice wave vectors, their density amplitudes (including the corresponding anisotropic variation and degeneracy breaking), the average atomic density, and system volume should be incorporated. The quantitative and qualitative results of elastic constant calculations highly depend on the physical interpretation of the density field used in the model, and also importantly, on the intrinsic pressure that usually pre-exists in the model system. A formulation based on thermodynamics is constructed to account for the effects caused by constant pre-existing stress during the homogeneous elastic deformation, through the introducing of a generalized Gibbs free energy and an effective finite strain tensor used for determining the elastic constants. The elastic properties of both solid and liquid states can be well produced by this unified approach, as demonstrated by an analysis for the liquid state and numerical evaluations for the bcc solid phase. The numerical calculations of bcc elastic constants and Poisson's ratio through this method generate results that are consistent with experimental conditions, and better match the data of bcc Fe given by molecular dynamics simulations as compared to previous work. The general theory developed here is applicable to the study of different types of stressed or unstressed material systems under elastic deformation.

Stress impact on elastic anisotropy of triclinic porous and fractured rocks

AbstractUnderstanding the stress dependence of elastic properties of rocks is important for reservoir characterization and seismic‐hazard monitoring. Several known approaches describing this dependence are the following: the nonlinear elasticity theory, effective‐medium theories for fractured rocks with stress‐dependent crack densities, and the piezosensitivity approach (also called the porosity deformation approach). Here I propose a generalization of the piezosensitivity approach to triclinic rocks. I assume the isotropy of the tensor describing sensitivity of elasticity to small strains of the pore space, and generalize known linear and exponential stress dependencies of compliances. This generalization is capable of describing the effect of loads on elastic properties of anisotropic rocks when the principal stresses are not necessarily aligned with the symmetrical axes of the unstressed anisotropic material. For example, the generalization describes how monoclinic anisotropy changes under isostatic stress or pore pressure, and how tilted transverse isotropy changes to monoclinic anisotropy due to a pseudo‐triaxial (or a uniaxial) load. The results are expected to be valid up to several hundred megapascals. This theory is closely related to the two other approaches mentioned above. On the one hand, for unloaded rocks, the theory is consistent with the noninteracting scalar‐crack approximation. On the other hand, the theory's predictions of mutual relations between isotropic third‐order elastic moduli is in good agreement with literature data on corresponding laboratory measurements. Thus, using the piezosensitivity approach, the physical nonlinearity of rocks can quantitatively be rather well explained by the strain of compliant pores.

An analytical solution for the mechanochemical growth of an elliptical hole in an elastic plane under a uniform remote load

Abstract A closed-form solution is presented for the mechanochemical corrosion of an elastic infinite plane containing an elliptical hole and subjected to uniform remote tension or compression. The corrosion is defined as the dissolution of the material along the surface of the hole with a rate which is proportional to the maximum principal stress at the corresponding points on the surface. Moreover, the dissolution rate can decay exponentially with time. It is confirmed that there exists a threshold load, such that the hole's shape elongates/evolves towards a circle when the applied stress lies above/below this threshold in absolute value. This threshold is determined by the relationship between the general corrosion of unstressed material and corrosion sensitivity to stresses. Formulas for the assessment of the lifetime of a plane in the case of the stress growth are obtained with inhibition of corrosion being taken into account.

Free Form Deformation-Based Image Registration Improves Accuracy of Traction Force Microscopy.

Traction Force Microscopy (TFM) is a widespread method used to recover cellular tractions from the deformation that they cause in their surrounding substrate. Particle Image Velocimetry (PIV) is commonly used to quantify the substrate’s deformations, due to its simplicity and efficiency. However, PIV relies on a block-matching scheme that easily underestimates the deformations. This is especially relevant in the case of large, locally non-uniform deformations as those usually found in the vicinity of a cell’s adhesions to the substrate. To overcome these limitations, we formulate the calculation of the deformation of the substrate in TFM as a non-rigid image registration process that warps the image of the unstressed material to match the image of the stressed one. In particular, we propose to use a B-spline -based Free Form Deformation (FFD) algorithm that uses a connected deformable mesh to model a wide range of flexible deformations caused by cellular tractions. Our FFD approach is validated in 3D fields using synthetic (simulated) data as well as with experimental data obtained using isolated endothelial cells lying on a deformable, polyacrylamide substrate. Our results show that FFD outperforms PIV providing a deformation field that allows a better recovery of the magnitude and orientation of tractions. Together, these results demonstrate the added value of the FFD algorithm for improving the accuracy of traction recovery.

SHOCK COMPRESSION OF METAL CRYSTALS: A COMPARISON OF EULERIAN AND LAGRANGIAN ELASTIC-PLASTIC THEORIES

An unconventional nonlinear elastic theory is advocated for solids undergoing large compression as may occur in shock loading. This theory incorporates an Eulerian strain measure, in locally unstressed material coordinates. Analytical predictions of this theory and conventional Lagrangian theory for elastic shock stress in anisotropic single crystals of aluminum, copper and magnesium are compared. Eulerian solutions demonstrate greater accuracy compared to atomic simulation (aluminum) and faster convergence with increasing order of elastic constants entering the internal energy. A thermomechanical framework incorporating this Eulerian strain and accounting for elastic and plastic deformations is outlined in parallel with equations for Lagrangian finite strain crystal plasticity. For several symmetric crystal orientations, predicted values of volumetric compression at the Hugoniot elastic limit of the two theories begin to differ substantially when octahedral or prismatic slip system strengths exceed about 1% of the shear modulus. Predicted pressures differ substantially for volumetric compression in excess of 5%. Predictions of Eulerian theory are closer to experimental shock data for aluminum, copper, and magnesium polycrystals.

Analysis of the barley leaf transcriptome under salinity stress using mRNA-Seq

Salinity is a threat to crops in many parts of the world, and together with drought, it is predicted to be a serious constraint to food security. However, understanding the impact of this stressor on plants is a major challenge due to the involvement of numerous genes and regulatory pathways. While transcriptomic analyses of barley (Hordeum vulgare L.) under salt stress have been reported with microarrays, there are no reports as yet of the use of mRNA-Seq. We demonstrate the utility of mRNA-Seq by analysing cDNA libraries derived from acutely salt-stressed and unstressed leaf material of H. vulgare cv. Hindmarsh. The data yielded >50 million sequence tags which aligned to 26,944 sequences in the Unigene reference database. To gain maximum information, we performed de novo assembly of unaligned reads and discovered >3,800 contigs, termed novel tentative consensus sequences, which are either new, or significant improvements on current databases. Differential gene expression screening found 48 significantly up-regulated and 62 significantly down-regulated transcripts. The work provides comprehensive insights into genome-wide effects of salinity and is a new resource for the study of gene regulation in barley and wheat. Further, the bioinformatics workflow may be applicable to other non-model plants to establish their transcriptomes and identify unique sequences.

Investigating Gabapentin Polymorphism Using Solid-State NMR Spectroscopy

Solid-state NMR spectroscopy (SSNMR), coupled with powder X-ray diffraction (PXRD), was used to identify the physical forms of gabapentin in samples prepared by recrystallization, spray drying, dehydration, and milling. Four different crystalline forms of gabapentin were observed: form I, a monohydrate, form II, the most stable at ambient conditions, form III, produced by either recrystallization or milling, and an isomorphous desolvate produced from desolvating the monohydrate. As-received gabapentin (form II) was ball-milled for 45 min in both the presence and absence of hydroxypropylcellulose (HPC). The samples were then stored for 2 days at 50°C under 0% relative humidity and analyzed by 13C SSNMR and PXRD. High-performance liquid chromatography was run on the samples to determine the amount of degradation product formed before and after storage. The 1HT1 values measured for the sample varied from 130 s for the as-received unstressed material without HPC to 11 s for the material that had been ball-milled in the presence of HPC. Samples with longer 1HT1 values were substantially more stable than samples that had shorter T1 values. Samples milled with HPC had detectable form III crystals as well. These results suggest that SSNMR can be used to predict gabapentin stability in formulated products.

Development of normal pressure and frictional traction along the walls of a steep conical hopper during filling

The filling process of particulate solids in silos presents a numerical challenge in finite element analysis because of the addition of unstressed material on top of stressed material. A novel progressive filling approach is adopted in this paper to represent the filling process. It was used here to explore the development of the pressure pattern on the wall of a steep axisymmetric conical hopper during the filling process. The loads are interpreted as normal pressure and frictional traction. The results are compared with those from an analysis that used the conventional ‘switched-on gravity’ filling. The results of both analyses are then compared with calculations based on classical theories for the pressures acting on the wall of a steep hopper. The close agreement found between the different treatments indicates that the chosen progressive filling numerical strategy is useful for applications where analytical solutions are limited.

Strong mechanoluminescence induced by elastic deformation of rare-earth-doped strontium aluminate phosphors

When rare-earth-doped strontium aluminate phosphor mixed in an epoxy resin, is deformed elastically by applying a uniaxial pressure, then initially the mechanoluminescence (ML) intensity increases with time, attains a peak value I m at a particular time t m , and later on it decreases with time. After t m , initially, the ML intensity decreases exponentially at a fast rate and then it decreases exponentially at a slow rate. The ML appears after a threshold pressure and then, initially at low pressure, the peak intensity I m of ML increases linearly with the magnitude of applied pressure, and for high pressure, I m increases exponentially with the magnitude of applied pressure. The value of I m increases linearly with the density of filled hole traps. The ML emission also takes place during the release of applied pressure. There should be a significant effect of temperature on the ML intensity of rare-earth-doped strontium aluminate phosphors. The ML intensity of rare-earth-doped strontium aluminates decreases with successive number of the applications of pressure and the diminished ML intensity can be recovered with the exposure of the samples to UV-radiation. The ML spectra of rare-earth-doped strontium aluminate phosphors are similar to their photoluminescence spectra. As only the piezoelectric-phase of the strontium aluminate phosphors exhibit ML during their elastic deformation, the ML emission can be attributed to the piezoelectrification of the crystals. Considering that the piezoelectric field causes decrease in the trap-depth of the hole traps and, therefore, the holes transferred from traps to the valence band recombine with (Eu 1+) * ions, whereby the Eu 2+ ions are excited, expressions are derived for different parameters of ML, which are able to satisfactorily explain the experimental results. It is shown that the lifetimes of holes in the shallow traps in stressed and unstressed materials, and the threshold pressure P t for the ML emission, and other parameters of the ML, can be determined from the ML measurements. Finally, the criteria for tailoring strong elasico-mechanoluminescent materials are explored.

Infrared spectroscopy of lattice vibrations in ZnTe/CdTe superlattices with quantum dots on the GaAs substrate with the ZnTe buffer layer

The results of the analysis of the infrared lattice reflectance spectra of multiperiod ZnTe/CdTe superlattices with CdTe quantum dots are reported. The samples are grown by molecular beam epitaxy on the GaAs substrate with the ZnTe buffer layer. Due to the large number of periods of the superlattices, it is possible to observe CdTe-like vibration modes in the quantum dots, i.e., the dislocation-free stressed islands formed during the growth due to relaxation of elastic stresses between the ZnTe and CdTe layers are markedly different in their lattice parameters. From the frequency shifts of the CdTe- and ZnTe-like vibration modes with respect to the corresponding modes in the unstressed materials, it is possible to estimate the level of elastic stresses.

Abrasive wear in ceramic laminated composites

Laminated ceramic structures in the system Al 2O 3/Al 2O 3 + 3Y-TZP (A/AZ) were prepared using a tape casting technique in order to obtain ceramic layers with different compositions and thicknesses. Piezo-spectroscopy was used to evaluate the residual stresses arisen from a calibrated mismatch in thermal expansion coefficients of the layers during the sintering process of the composite. The dependence of the residual stresses in the A and AZ layers on their thickness ratio was established. A microscale ball cratering method was used to investigate the influence that the surface compressive stress can play on the abrasive wear resistance of the composite structures. The results were compared with those obtained with an unstressed reference material prepared either by lamination of pure alumina green-sheets or by cold isostatic pressing of alumina powder. The experimental results have shown that the abrasive wear resistance is higher for samples with compressive residual stresses within the surface regions.

Predictions for weak mechanical ignition of strain hardened granular explosive

Predictions are given for the coupled bulk and grain scale response of initially unstressed, strain hardened granular HMX (C4H8N8O8) due to mild piston impact (impact speeds <100 m/s). Importantly, this response depends on the material’s strain history as the stress necessary for bulk inelastic compaction (crush up) increases with the solid volume fraction. Although the quasistatic compaction behavior of HMX is well characterized, the influence of strain history on the bulk and grain scale dynamic loading response has largely been unexplored. In this study, the initial solid volume fraction of the unstressed material is varied over the range of φf⩽φ0⩽1, where φf=0.655 is its free pour value. A Hugoniot analysis for the bulk material identifies three dispersed compaction wave structures that depend on the impact speed and initial solid volume fraction, and are analogous to elastic-plastic waves in dynamically loaded solids. For increasing impact speed, these structures consist of (1) a single viscoelastic wave; (2) a leading viscoelastic wave and a trailing viscoplastic wave; and (3) a single viscoplastic wave. It is shown that the resulting localized heating near intergranular contact surfaces can trigger sustained combustion of the material. Predictions for the grain scale thermochemical response indicate that significant bulk viscoplastic heating is required for ignition of materials with φf⩽φ0⩽0.88, whereas bulk viscoelastic heating leads to the ignition of denser materials (φ0>0.91). Both viscoelastic and viscoplastic heating are predicted to be important for ignition of materials having 0.88⩽φ0⩽0.91. Within this transition range there is predicted a sharp increase in impact sensitivity as the power input needed for ignition rapidly decreases to a value close to that for the free pour density (0.40 MW/cm2) before increasing again. This result is important for assessing the impact sensitivity and deflagration-to-detonation transition of damaged explosives.

An automated system for the measurement of magnetostriction in electrical steel sheet under applied stress

The design of an automated system for the rapid assessment of the AC magnetostriction in electrical steel sheet under linear applied stress in the range ±10 MPa is described in detail. Typical results are presented showing the effect of induction on the unstressed material together with plots of the harmonics of magnetostriction and specific total loss versus applied stress.

Temperature dependence of residual stress in epitaxial GaAs/Si(100) films determined from photoreflectance spectroscopy data

In the temperature range T=10–300 K, photoreflectance spectroscopy was used to study the temperature dependence of residual stress in epitaxial n-GaAs films (1–5 µm thick, electron concentration of 1016–1017 cm−3) grown on Si(100) substrates. A qualitative analysis showed that the photoreflectance spectra measured in the energy region of the E0 transition in GaAs had two components. They consisted of the electromodulation component caused by the valence subband |3/2; ±1/2〉-conduction band transition and the low-energy excitonic component. The magnitude of stress was determined from the value of the strain-induced energy shift of the fundamental transition from the subband |3/2; ±1/2〉 with respect to the band gap of the unstressed material E0(T)-E0|3/2; ±1/2〉(T). The increase in the energy shift E0-E0|3/2; ±1/2〉 from 22 ± 3 meV at 296 K to 29 ± 3 meV at 10 K, which was found in the experiments, gives evidence of an increase in biaxial stress with decreasing temperature.