ΔCp Values Research Articles

Computational Analysis of Heat Capacity Effects in Protein-Ligand Binding.

Heat capacity effects in protein-ligand binding as measured by calorimetric experiments have recently attracted considerable attention, particularly in the field of enzyme inhibitor design. A significant negative heat capacity change upon ligand binding implies a marked temperature dependence of the binding enthalpy, which is of high relevance for attempts to optimize protein-ligand interactions. In this work, we address the question of how well such heat capacity changes can be predicted by computer simulations. We examine a series of human thrombin inhibitors that all bind with ΔCp values of about -0.4 kcal/mol/K and calculate heat capacity changes from plain molecular dynamics simulations of the bound and free states of the enzyme and ligand. The results show that accurate ΔCp estimates within a few tenths of a kcal/mol/K of the experimental values can be obtained with this approach. This allows us to address the structural and energetic origin of the negative heat capacity changes for the thrombin inhibitors, and it is found that conformational equilibria of the free ligands in solution make a major contribution to the observed effect.

Cooperative Conformational Transitions Underpin the Activation Heat Capacity in the Temperature Dependence of Enzyme Catalysis.

Many enzymes display non-Arrhenius behavior with curved Arrhenius plots in the absence of denaturation. There has been significant debate about the origin of this behavior and recently the role of the activation heat capacity (ΔCP⧧) has been widely discussed. If enzyme-catalyzed reactions occur with appreciable negative values of ΔCP⧧ (arising from narrowing of the conformational space along the reaction coordinate), then curved Arrhenius plots are a consequence. To investigate these phenomena in detail, we have collected high precision temperature-rate data over a wide temperature interval for a model glycosidase enzyme MalL, and a series of mutants that change the temperature-dependence of the enzyme-catalyzed rate. We use these data to test a range of models including macromolecular rate theory (MMRT) and an equilibrium model. In addition, we have performed extensive molecular dynamics (MD) simulations to characterize the conformational landscape traversed by MalL in the enzyme-substrate complex and an enzyme-transition state complex. We have crystallized the enzyme in a transition state-like conformation in the absence of a ligand and determined an X-ray crystal structure at very high resolution (1.10 Å). We show (using simulation) that this enzyme-transition state conformation has a more restricted conformational landscape than the wildtype enzyme. We coin the term "transition state-like conformation (TLC)" to apply to this state of the enzyme. Together, these results imply a cooperative conformational transition between an enzyme-substrate conformation (ES) and a transition-state-like conformation (TLC) that precedes the chemical step. We present a two-state model as an extension of MMRT (MMRT-2S) that describes the data along with a convenient approximation with linear temperature dependence of the activation heat capacity (MMRT-1L) that can be used where fewer data points are available. Our model rationalizes disparate behavior seen for MalL and previous results for a thermophilic alcohol dehydrogenase and is consistent with a raft of data for other enzymes. Our model can be used to characterize the conformational changes required for enzyme catalysis and provides insights into the role of cooperative conformational changes in transition state stabilization that are accompanied by changes in heat capacity for the system along the reaction coordinate. TLCs are likely to be of wide importance in understanding the temperature dependence of enzyme activity and other aspects of enzyme catalysis.

Pioneering dielectric materials of Sn-doped Nb0.025Ti0.975O2 ceramics with excellent temperature and humidity stability for advanced ceramic capacitors.

In this study, the rutile TiO2 system, widely acclaimed for its superior properties, was enhanced through co-doping with isovalent Sn4+ ions and 2.5% Nb5+ donor ions, diverging from traditional acceptor doping practices. This novel doping strategy was implemented by employing a conventional solid-state reaction method, resulting in the synthesis of Sn-doped Nb0.025Ti0.975O2 (Sn-NTO) ceramics. These ceramics demonstrated remarkable dielectric characteristics, with a high dielectric constant (ε') ranging from ∼27 000 to 34 000 and an exceptionally low loss tangent between 0.005 and 0.056 at ∼25 °C and 1 kHz. Notably, the temperature coefficient of ε', , aligned with the stringent specifications for X7/8/9R capacitors. Furthermore, the Sn-NTO ceramics exhibited a stable Cp response across various frequencies within a humidity range of 50 to 95% RH, with ΔCp (%) values within ±0.3%, and no hysteresis loop was detected, suggesting the absence of water molecule adsorption and desorption during humidity assessments. This behavior is primarily attributed to the effective suppression of oxygen vacancy formation by the Sn4+ ions, which also affects the grain growth diffusion process in the Sn-NTO ceramics. The observed heterogeneous electrical responses between semiconducting grains and insulating grain boundaries in these polycrystalline ceramics are attributed to the internal barrier layer capacitor effect.

The ESS𝜈SB+ Project

The European Spallation Source neutrino Super Beam (ESS𝜈SB) is a long-baseline neutrino project that will measure the CP-violation in the leptonic sector at the second, rather than the first, oscillation maximum, where the sensitivity of the experiment is ∼3 times higher. The physics simulations have shown that the ESS𝜈SB, after 10 years of data taking, will be able to cover more than 70% of the CP-violating phase, δCP , parameterrange with 5 σ C.L. to reject the no-CP-violation hypothesis. The expected measurement error of δCP is smaller than 8° for all δCP values, making it the most precise proposed experiment in the field by a large margin. The extension project, ESS𝜈SB+ to be performed between 2023 and 2026, aims in measuring the neutrino-nucleus cross-section (the dominant term of the systematic uncertainty) in the energy range of 0.2 – 0.6 GeV, using a Low Energy nuSTORM (LEnuSTORM) and a Low Energy Monitored Neutrino Beam (LEMNB) facilities.

Effect of K2WO4 on structure and properties of low melting glasses in K2O–Fe2O3–P2O5 system as sealing materials

New phosphate glasses based on the K2O–Fe2O3–P2O5 system, with variable K2WO4 content in place of Fe2O3, are prepared through the melt quenching route. The thermal and structural characteristics and water resistance properties are studied for sealing applications by means of XRD, DSC, and FTIR spectroscopic and dilatometry measurements. The results showed an amorphous nature and a linear increase in the parameters of the glass density and molar volume with the addition of K2WO4. While the glass transition (Tg), crystallization (Tc) temperatures, the thermal stability (ΔT), and the relative criterion (H) values were decreased are decreased. Inversely, the ΔCp values were markedly increased with growing NBO bonds that led to markedly increase in the O/P ratio. Also, the coefficient of thermal expansion (CTE) is increased (from 124 to 211 × 10−7/oC). The glass with high K2WO4 content is a suitable sample for excellent sealing properties with a low transition temperature (Tg < 300 °C), a very low melting point, and a high thermal expansion value (211 × 10−7/oC). As well, the durability values of the examined samples decreased, but they were in the range of those for commercial sealing glass. The study offers fresh suggestions for the development of sealant materials that are both low-temperature and environmentally safe.

Exploring models with modular symmetry in neutrino oscillation experiments

Our study aims to investigate the viability of neutrino mass models that arise from discrete non-Abelian modular symmetry groups, i.e., ΓN with (N = 1, 2, 3, . ) in the future neutrino experiments T2HK, DUNE, and JUNO. Modular symmetry reduces the usage of flavon fields compared to the conventional discrete flavor symmetry models. Theories based on modular symmetries predict the values of leptonic mixing parameters, and therefore, these models can be tested in future neutrino experiments. In this study, we consider three models based on the A4 modular symmetry, i.e., Model-A, B, and C such a way that they predict different values of the oscillation parameters but still allowed with respect to the current data. In the future, it is expected that T2HK, DUNE, and JUNO will measure the neutrino oscillation parameters very precisely, and therefore, some of these models can be excluded in the future by these experiments. We have estimated the prediction of these models numerically and then used them as input to scrutinize these models in the neutrino experiments. Assuming the future best-fit values of θ23 and δCP remain the same as the current one, our results show that at 5σ C.L, Model-A can be excluded by T2HK whereas Model-B can be excluded by both T2HK and DUNE. Model-C cannot be excluded by T2HK and DUNE at 5σ C.L. Further; our results show that JUNO alone can exclude Model-B at an extremely high confidence level if the future best-fit of θ12 remains at the current-one. We have also identified the region in the θ23 - δCP parameter space, for which Model-A cannot be separated from Model-B in T2HK and DUNE.

Implications of the DLMA Solution of θ12 for IceCube Data Using Different Astrophysical Sources

In this paper, we study the implications of the Dark Large Mixing Angle (DLMA) solutions of θ12 in the context of the IceCube data. We study the consequences in the measurement of the neutrino oscillation parameters, namely the octant of θ23 and δCP in light of both Large Mixing Angle (LMA) and DLMA solutions of θ12. We find that it will be impossible for IceCube to determine the δCP and the true nature of θ12, i.e., LMA or DLMA, at the same time. This is because of the existence of an intrinsic degeneracy at the Hamiltonian level between these parameters. Apart from that, we also identify a new degeneracy between θ23 and two solutions of θ12 for a fixed value of δCP. We perform a chi-square fit using three different astrophysical sources, i.e., μ source, π source, and n source, to find that both μ source and π source are allowed within 1σ, whereas the n source is excluded at 2σ. It is difficult to make any conclusion regarding the measurement of θ23, δCP for μ source. However, the π (n) source prefers the higher (lower) octant of θ23 for both LMA and DLMA solution of θ12. The best-fit value of δCP is around 180∘ (0∘/360∘) for the LMA (DLMA) solution of θ12, whereas for the DLMA (LMA) solution of θ12, the best-fit value is around 0∘/360∘ (180∘) for the π (n) source. If we assume the current best-fit values of θ23 and δCP to be true, then the μ and π sources prefer the LMA solution of θ12, whereas the n source prefers the DLMA solution of θ12.

Heat capacity changes associated with G-quadruplex unfolding.

G-quadruplexes are four-stranded DNA structures that have been found in the cell and are thought to act as elements of control in genomic events. The measurements of the thermodynamic stability, ΔG, of G-quadruplexes shed light on the molecular forces involved in the stabilization of these structures. In thermodynamic studies, the differential heat capacity, ΔCP, of the folded and unfolded states of a G-quadruplex is a fundamental property that describes the temperature dependences of the differential enthalpy, ΔH, entropy, ΔS, and free energy, ΔG. Despite its recognized importance, the ΔCP of G-quadruplex unfolding has not been measured directly. Here, we use differential scanning calorimetry to evaluate changes in heat capacity, ΔCP, accompanying the unfolding transitions of G-quadruplexes formed by modified DNA sequences from the promoter regions of the c-MYC, VEGF, and Bcl-2 oncogenes. The average value of ΔCP is 0.49 ± 0.12kcal mol-1K-1. Our analysis revealed that disregarding ΔCP leads to significant errors in extrapolated values of the differential enthalpy, ΔH, and entropy, ΔS, of the folded and unfolded DNA conformations. Although the compensation between ΔH and ΔS weakens the effect of ΔCP on the differential free energy, ΔG, neglecting ΔCP may still result in relative errors in ΔG extrapolated to room temperature as great as 140%. We emphasize the importance of proper consideration of the effect of ΔCP in conformational studies of guanine-rich DNA molecules.

A Phenylboronic Acid-Based Transition State Analogue Yields Nanomolar Inhibition of Mandelate Racemase.

Mandelate racemase (MR) catalyzes the Mg2+-dependent interconversion of (R)- and (S)-mandelate by stabilizing the altered substrate in the transition state (TS) by ∼26 kcal/mol. The enzyme has been employed as a model to explore the limits to which the free energy of TS stabilization may be captured by TS analogues to effect strong binding. Herein, we determined the thermodynamic parameters accompanying binding of a series of bromo-, chloro-, and fluoro-substituted phenylboronic acids (PBAs) by MR and found that binding was predominately driven by favorable entropy changes. 3,4-Dichloro-PBA was discovered to be the most potent inhibitor yet identified for MR, binding with a Kdapp value of 11 ± 2 nM and exceeding the binding of the substrate by ∼72,000-fold. The ΔCp value accompanying binding (-488 ± 18 cal·mol-1 K-1) suggested that dispersion forces contribute significantly to the binding. The pH-dependence of the inhibition revealed that MR preferentially binds the anionic, tetrahedral form of 3,4-dichloro-PBA with a pH-independent Ki value of 5.7 ± 0.5 nM, which was consistent with the observed upfield shift of the 11B NMR signal. The linear free energy relationship between log(kcat/Km) and log(1/Ki) for wild-type and 11 MR variants binding 3,4-dichloro-PBA had a slope of 0.8 ± 0.2, indicating that MR recognizes the inhibitor as an analogue of the TS. Hence, halogen substitution may be utilized to capture additional free energy of TS stabilization arising from dispersion forces to enhance the binding of boronic acid inhibitors by MR.

Thermal Properties and Morphological Studies of Poly(ethylene oxide) with the Addition of Salt or Nanofiller

AbstractThe increasing demand of the functional polymers in the global industry has led to extensive development of new polymeric materials with enhanced properties. This work focuses on the effect of addition of lithium perchlorate (LiClO4) or titanium dioxide (TiO2) on the thermal properties (i.e., glass transition temperature [Tg], change in heat capacity [ΔCP], crystallinity [X*], melting temperature [Tm]) and morphology of poly(ethylene oxide) (PEO) investigated by using differential scanning calorimetry (DSC) and polarized optical microscope (POM). The Tg and ΔCP of PEO at a mass fraction of salt, WS ≤ 0.0196, increase with the addition of salt. Whereas the values of crystallinity and Tm of PEO at the same salt fraction decrease slightly with increasing salt fraction, suggesting the presence of an interaction between the salt molecules and PEO matrix. However, at WS ≥ 0.107, the Tg, crystallinity, and Tm of PEO decrease significantly with the addition of salt, suggesting the phase separation of the binary mixtures of PEO and salt into salt‐rich and salt‐poor phases are developed. This observation is supported by optical inspections where the salt precipitations can be seen. Meanwhile, the values of Tg, ΔCP, crystallinity, and Tm of PEO show insignificant changes with increasing nanofiller fraction indicating no interaction between PEO and the nanofiller. The two‐phase of PEO and nanofiller in the PEO‐TiO2 can be observed clearly from the optical inspection for all PEO‐nanofiller compositions. Hence, the addition of LiClO4 at low content exhibits relatively prominence on the PEO matrix than the TiO2. LiClO4 possesses better molecular interaction with PEO than TiO2 with PEO.

Encapsulated resistive anode bulk Micromegas detectors for the T2K experiment TPC upgrade

In order to establish accurate leptonic CP violation at 3 σ level for a significant fraction of the possible δCP values, the T2K collaboration plan to upgrade the beam intensity and to upgrade the near detector ND280.The T2K experiment consists of a totally active Super-Fine-Grained-Detector, two High Angle Time Projection Chamber and six time of flight planes. The HA-TPC will be used for 3D track reconstruction, momentum measurement and particle identification. These time projection chambers, with overall dimensions of 2 × 2 × 0.8 m3, will be equipped with 32 encapsulated resistive anode bulk Micromegas detectors. The thin field cage (3 cm thickness, 4% radiation length) will consist of composite material with a Kapton foil with copper strips as inner layer. The 42 × 34 cm2 ERAM detector will use a 400 kΩ/sq diamond-like carbon foil to spread the charge over the pad plane, each pad being approximately 1 cm2. New front-end electronic cards, based on the AFTER chip, directly mounted on the back of the detector and parallel to its plane have been developed and used for the signal readout.The first production ERAM detector modules have been tested in a lab using a X-ray bench and a cosmic bench. In July 2021, data have also been taken in a test beam at DESY in 0.2 T magnetic field. Performance characterization and results from these measurement campaigns will be shown.

Optimal configuration of Protvino to ORCA experiment for hierarchy and non-standard interactions

In this paper, we study the hierarchy sensitivity of Protvino to ORCA (P2O) experiment in three flavour scenario as well as its sensitivity to non-standard interactions (NSI) in neutrino propagation. Because of the largest possible baseline length of 2595 km, P2O is expected to have strong sensitivity towards neutrino mass hierarchy and NSI parameters. In our study, we show that even though the number of appearance channel events for the minimal configuration of P2O are higher compared to DUNE, still the hierarchy sensitivity of P2O is less than DUNE because of large background events. Our results show that for a background reduction factor of 0.46 and appearance channel background systematic normalization error of 4%, the hierarchy sensitivity of P2O becomes equivalent of DUNE for δCP = 195°. We call this configuration of P2O as optimized P2O. Regarding the study of NSI, we find that, for ϵeμ (ϵeτ) sensitivity of DUNE is similar (better) as compared to optimized P2O when both ϵeμ and ϵeτ are included in the analysis. Our results show that in presence of NSI, the change of hierarchy sensitivity with respect to standard three flavor scenario, is higher in P2O as compared to DUNE. Further, hierarchy sensitivity in presence of NSI is lower (higher) than sensitivity in the standard three flavour scenario for δCP = 270°(90°). It is important to note that hierarchy sensitivity of optimized P2O does not get significantly better than DUNE for the current favourable values of δCP which is 180° < δCP< 360° as obtained by the global analysis in both standard three flavour and in presence of NSI.

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE’s sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-calendar years (kt-MW-CY), where calendar years include an assumption of 57% accelerator uptime based on past accelerator performance at Fermilab. The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 4σ (5σ) level with a 66 (100) kt-MW-CY far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters, with a median sensitivity of 3σ for almost all true δCP values after only 24 kt-MW-CY. We also show that DUNE has the potential to make a robust measurement of CPV at a 3σ level with a 100 kt-MW-CY exposure for the maximally CP-violating values δCP=±π/2. Additionally, the dependence of DUNE’s sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest.14 MoreReceived 8 September 2021Accepted 14 March 2022DOI:https://doi.org/10.1103/PhysRevD.105.072006Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. Funded by SCOAP3.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasNeutrino interactionsNeutrino oscillationsParticles & Fields

Non-zero θ13 and δCP phase with A4 flavor symmetry and deviations to tri-bi-maximal mixing via Z2 × Z2 invariant perturbations in the neutrino sector

In this work, a flavour theory of a neutrino mass model based on A4 symmetry is considered to explain the phenomenology of neutrino mixing. The spontaneous symmetry breaking of A4 symmetry in this model leads to tribimaximal mixing in the neutrino sector at a leading order. We consider the effect of Z2×Z2 invariant perturbations in neutrino sector and find the allowed region of correction terms in the perturbation matrix that is consistent with 3σ ranges of the experimental values of the mixing angles. We study the entanglement of this formalism on the other phenomenological observables, such as δCP phase, the neutrino oscillation probability P(νμ→νe), the effective Majorana mass |mee| and |mνeeff|. A Z2×Z2 invariant perturbations in this model is introduced in the neutrino sector which leads to testable predictions of θ13 and CP violation. By changing the magnitudes of perturbations in neutrino sector, one can generate viable values of δCP and neutrino oscillation parameters. Next we investigate the feasibility of charged lepton flavour violation in type-I seesaw models with leptonic flavour symmetries at high energy that leads to tribimaximal neutrino mixing. We consider an effective theory with an A4×Z2×Z2 symmetry, which after spontaneous symmetry breaking at high scale which is much higher than the electroweak scale leads to charged lepton flavour violation processes once the heavy Majorana neutrino mass degeneracy is lifted either by renormalisation group effects or by a soft breaking of the A4 symmetry. In this context the implications for charged lepton flavour violation processes like μ→eγ, τ→eγ, τ→μγ are discussed.

DUNE Physics Program and Status

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino experiment with a 70-kt liquid argon detector at the Sanford Underground Research Facility (SURF) 1300 km from Fermilab. This programme includes studies of neutrino oscillations with a high-intensity muon-neutrino beam from Fermilab; as well as, proton decay and supernova neutrino burst searches. DUNE will resolve the neutrino mass hierarchy to a precision of 5σ, for all δCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δCP values. The status and schedule of the project is also presented.

Prediction of the Synergistic Glass Transition Temperature of Coamorphous Molecular Glasses Using Activity Coefficient Models.

The glass transition temperature (Tg) of a binary miscible mixture of molecular glasses, termed a coamorphous glass, is often synergistically increased over that expected for an athermal mixture due to the strong interactions between the two components. This synergistic interaction is particularly important for the formulation of coamorphous pharmaceuticals since the molecular interactions and resulting Tg strongly impact stability against crystallization, dissolution kinetics, and bioavailability. Current models that describe the composition dependence of Tg for binary systems, including the Gordon-Taylor, Fox, Kwei, and Braun-Kovacs equations, fail to describe the behavior of coamorphous pharmaceuticals using parameters consistent with experimental ΔCP and Δα. Here, we develop a robust thermodynamic approach extending the Couchman and Karasz method through the use of activity coefficient models, including the two-parameter Margules, non-random-two-liquid (NRTL), and three-suffix Redlich-Kister models. We find that the models, using experimental values of ΔCP and fitting parameters related to the binary interactions, successfully describe observed synergistic elevations and inflections in the Tg versus composition response of coamorphous pharmaceuticals. Moreover, the predictions from the NRTL model are improved when the association-NRTL version of that model is used. Results are reported and discussed for four different coamorphous systems: indomethacin-glibenclamide, indomethacin-arginine, acetaminophen-indomethacin, and fenretinide-cholic acid.

Negative Interdomain Coupling of Dystrophin Spectrin Repeats

Spectrin repeat domains are a highly conserved biological motif found in many human structural proteins. Dystrophin contains 24 tandem spectrin repeats which provide structural support through mediating interactions between intracellular actin filaments and the extracellular matrix. However, the molecular mechanism by which dystrophin provides this support is unknown. Understanding this underlying structure/function relationship is important because mutations in dystrophin directly cause muscular dystrophy. Thus far, the following constructs have been expressed in E. coli, purified using chromatography, and thermodynamically characterized: S17, S17-18, S17-19. Parameters were determined through globally fitting thermal denaturation signals from Fluorescence Spectroscopy (FS), Circular Dichroism (CD), and Fluorescence Lifetime Spectroscopy (FLT) to a two-state model of unfolding. Fits were constrained using ΔCp values determined using Differential Scanning Calorimetry (DSC). This parameterization then allowed for determination of the free energy of stability (ΔGunfolding) of each construct. Results indicate that the ΔGunfolding of S17 is nearly double that of S17-19. This pronounced non-additivity indicates that tandem spectrin repeats mutually destabilize each other, termed negative coupling. Additionally, the comparison of Electron Paramagnetic Resonance (EPR) spectra of S17 and S17-19 indicate that the trimer exhibits greater local confirmational flexibility, consistent with decreased stability. To further test this negative coupling hypothesis, we are purifying S19 for thermodynamic characterization. This will allow for the comparison of the sum of S19 and S17-18's ΔGunfolding values with that of the trimer, helping further reveal the energetic and structural basis of dystrophin's mechanism.

Evidence for Many Unique Solution Structures for Chymotrypsin Inhibitor 2: A Thermodynamic Perspective Derived from vT-ESI-IMS-MS Measurements.

Chymotrypsin inhibitor 2 (CI-2) is a classic model for two-state cooperative protein folding and is one of the most extensively studied systems. Alan Fersht, a pioneer in the field of structural biology, has studied the wild-type (wt) and over 100 mutant forms of CI-2 with traditional analytical and biochemical techniques. Here, we examine wt CI-2 and three mutant forms (A16G, K11A, L32A) to demonstrate the utility of variable-temperature (vT) electrospray ionization (ESI) paired with ion mobility spectrometry (IMS) and mass spectrometry (MS) to map the free energy folding landscape. As the solution temperature is increased, the abundance of each of the six ESI charge states for wt CI-2 and each mutant is found to vary independently. These results require that at least six unique types of CI-2 solution conformers are present. Ion mobility analysis reveals that within each charge state there are additional conformers having distinct solution temperature profiles. A model of the data at ∼30 different temperatures for all four systems suggests the presence of 41 unique CI-2 solution conformations. A thermodynamic analysis of this system yields values of ΔCp as well as ΔG, ΔH, and ΔS for each state at every temperature studied. Detailed energy landscapes derived from these data provide a rare glimpse into Anfinsen's thermodynamic hypothesis and the process of thermal denaturation, normally thought of as a cooperative two-state transition involving the native state and unstructured denatured species. Specifically, as the temperature is varied, the entropies and enthalpies of different conformers undergo dramatic changes in magnitude and relative order to maintain the delicate balance associated with equilibrium.

A DSC and XPS characterization of core–shell morphology of block copolymer nanoparticles

Self-assembly of amphiphilic block copolymer chains is known to produce core–shell nanoparticles, but imaging techniques have generally failed to provide clear evidence about the multiphase structure. We report herein the advantages and limitations of modulated temperature differential scanning calorimetry (MDSC) and X-ray photoelectron spectroscopy (XPS) for the morphology study of spherical poly(hydroxyethyl acrylate)-b-polystyrene diblock copolymer nanoparticles with an intensity-average diameter of 40 nm. Using lyophilized particles, MDSC is more informative than XPS since it allows the three morphological features of composite latex particles to be distinguished: polystyrene core, poly(hydroxyethyl acrylate) shell, and interface. In MDSC, phase separation is evidenced by two distinct increments of heat capacity (ΔCp) in the glass transition regions of the two blocks. By measuring ΔCp values, an interface weight fraction of 70% is measured that gradually decreases to 50% with annealing time (150 °C, 2 h), indicating a higher extent of phase separation.

Agave fructans as fat and sugar replacers in ice cream: Sensory, thermal and texture properties

The principal aim of the present study was to investigate the feasibility of replacing fat and sugar with agave fructans to produce both low-fat, and low-fat and sugar ice cream. For this purpose, agave fructans (0–3.0%) were added to several ice cream formulations to explore relationships between their sensory perception, and their previously reported thermal and texture properties. Formulations with less than 1.2% of agave fructans contributed sensory attributes linked to the amount and size of ice crystals, such as crystallized (both texture and appearance), grainy and cold sensation. These were related to frozen water, ice fraction, enthalpy and maximum temperature, as well as hardness, melting rate and compression force. On the other hand, the samples with concentrations between 1.2 and 3.0% of agave fructans showed ice cream formulations with longer melting times, smooth, creamy and fluid texture, and with fatty sensation. These properties were directly related to low non-frozen water concentrations, high glass transition temperatures and ΔCp values, as well as textural properties, such as apparent viscosity and overrun. Even though consumers liked the samples with higher amounts of fat and sugar, all the samples showed liking values in a quite narrow range around the neutral point on the liking scale. Thus, agave fructans were able to enhance several sensory, thermal and textural properties, making them a feasible alternative as a fat and sugar replacer.