The structural characterization of dealloyed nanoporous metals is a fundamental and active area of research, needed for the optimization of these structures for catalytic, electrosensing, biomedical, ...and mechanical functions. The prediction of properties requires identifying and quantifying salient structural characteristics, while insights into the relevant mechanisms of dealloying and coarsening can be achieved through in situ observations of structural evolution. Three-dimensional structural characterization techniques have advanced such that nanoscale quantification of topology, morphology, and crystallographic parameters are achievable, yet the field is new enough that the assessment and comparison of such parameters of different nanoporous metals are just beginning. Here, we explore the state of the art in structural characterization, focusing on nanoporous gold to exemplify the challenges, the achievements, and the potential associated with establishing an appropriate set of structural parameters for this unique class of materials.
The accurate characterization of thermal conductivity κ, particularly at high temperature, is of paramount importance to many materials, thermoelectrics in particular. The ease and access of thermal ...diffusivity D measurements allows for the calculation of κ when the volumetric heat capacity, ρcp, of the material is known. However, in the relation κ = ρcpD, there is some confusion as to what value of cp should be used in materials undergoing phase transformations. Herein, it is demonstrated that the Dulong–Petit estimate of cp at high temperature is not appropriate for materials having phase transformations with kinetic timescales relevant to thermal transport. In these materials, there is an additional capacity to store heat in the material through the enthalpy of transformation ΔH. This can be described using a generalized model for the total heat capacity for a material ρcp = Cpϕ + ΔH (∂ϕ/∂T)p where φ is an order parameter that describes how much latent heat responds “instantly” to temperature changes. Here, Cpφ is the intrinsic heat capacity (e.g., approximately the Dulong–Petit heat capacity at high temperature). It is shown experimentally in Zn4Sb3 that the decrease in D through the phase transition at 250 K is fully accounted for by the increase in cp, while κ changes smoothly through the phase transition. Consequently, reports of κ dropping near phase transitions in widely studied materials such as PbTe and SnSe have likely overlooked the effects of excess heat capacity and overestimated the thermoelectric efficiency, zT.
Estimates of thermal conductivity from thermal diffusivity measurements are likely underestimated when latent heat contributions to the heat capacity are not considered. Latent heat effects are especially important when phase‐transformation kinetics are fast relative to the timescale of thermal transport. The importance of these effects in material measurements is highlighted, particularly for the estimation of thermoelectric efficiency.
Summary Background Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor ...with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma. Methods In this multicentre phase 1b trial, we recruited patients aged 18 years or older with previously treated relapsed or refractory multiple myeloma from five cancer centres in the USA. Inclusion criteria included a Karnofsky Performance Status score of at least 70, measureable disease, adequate bone marrow reserve, adequate hepatic function, and a creatinine clearance of at least 50 mL per min. Exclusion criteria included previous exposure to HDAC inhibitors; previous allogeneic stem-cell transplantation; previous autologous stem-cell transplantation within 12 weeks of baseline; active systemic infection; malignancy within the last 5 years; known or suspected HIV, hepatitis B, or hepatitis C infection; a QTc Fridericia of more than 480 ms; and substantial cardiovascular, gastrointestinal, psychiatric, or other medical disorders. We gave escalating doses (from 40–240 mg once daily to 160 mg twice daily) of oral ricolinostat according to a standard 3 + 3 design according to three different regimens on days 1–21 with a conventional 28 day schedule of oral lenalidomide (from 15 mg in one cohort to 25 mg in all other cohorts once daily) and oral dexamethasone (40 mg weekly). Primary outcomes were dose-limiting toxicities, the maximum tolerated dose of ricolinostat in this combination, and the dose and schedule of ricolinostat recommended for further phase 2 investigation. Secondary outcomes were the pharmacokinetics and pharmacodynamics of ricolinostat in this combination and the preliminary anti-tumour activity of this treatment. The trial is closed to accrual and is registered at ClinicalTrials.gov , number NCT01583283. Findings Between July 12, 2012, and Aug 20, 2015, we enrolled 38 patients. We observed two dose-limiting toxicities with ricolinostat 160 mg twice daily: one (2%) grade 3 syncope and one (2%) grade 3 myalgia event in different cohorts. A maximum tolerated dose was not reached. We chose ricolinostat 160 mg once daily on days 1–21 of a 28 day cycle as the recommended dose for future phase 2 studies in combination with lenalidomide 25 mg and dexamethasone 40 mg. The most common adverse events were fatigue (grade 1–2 in 14 37% patients; grade 3 in seven 18%) and diarrhoea (grade 1–2 in 15 39% patients; grade 3 in two 5%). Our pharmacodynamic studies showed that at clinically relevant doses, ricolinostat selectively inhibits HDAC6 while retaining a low and tolerable level of class I HDAC inhibition. The pharmacokinetics of ricolinostat and lenalidomide were not affected by co-administration. In a preliminary assessment of antitumour activity, 21 (55% 95% CI 38–71) of 38 patients had an overall response. Interpretation The findings from this study provide preliminary evidence that ricolinostat is a safe and well tolerated selective HDAC6 inhibitor, which might partner well with lenalidomide and dexamethasone to enhance their efficacy in relapsed or refractory multiple myeloma. Funding Acetylon Pharmaceuticals.
The influence of micro/nanostructure on thermal conductivity is a topic of great scientific interest, particularly to thermoelectrics. The current understanding is that structural defects decrease ...thermal conductivity through phonon scattering where the phonon dispersion and speed of sound are assumed to remain constant. Experimental work on a PbTe model system is presented, which shows that the speed of sound linearly decreases with increased internal strain. This softening of the materials lattice completely accounts for the reduction in lattice thermal conductivity, without the introduction of additional phonon scattering mechanisms. Additionally, it is shown that a major contribution to the improvement in the thermoelectric figure of merit (zT > 2) of high‐efficiency Na‐doped PbTe can be attributed to lattice softening. While inhomogeneous internal strain fields are known to introduce phonon scattering centers, this study demonstrates that internal strain can modify phonon propagation speed as well. This presents new avenues to control lattice thermal conductivity, beyond phonon scattering. In practice, many engineering materials will exhibit both softening and scattering effects, as is shown in silicon. This work shines new light on studies of thermal conductivity in fields of energy materials, microelectronics, and nanoscale heat transfer.
Two fundamentally different avenues for controlling thermal conductivity are phonon scattering and lattice softening, or the reduction of phonon speed. The latter mechanism is particularly attractive when phonon–phonon scattering is inherently very strong, such as in thermoelectric materials and/or at high temperatures. In this work, the importance of lattice softening is shown in two specific cases, PbTe and nanocrystalline Si.
The phase‐field method is an attractive tool in modeling microstructural evolution due to rapid solidification under additive manufacturing conditions, but typical polycrystalline models are prone to ...grain coalescence. Grain tracking and remapping schemes can eliminate artificial coalescence and increase the number of grains and crystallographic orientations that may be considered in a simulation, but previous tracking and remapping schemes may not efficiently capture the complex grain morphologies that form during additive manufacturing. A new recursive scheme is derived from a binary tree of axis‐aligned bounding boxes that can efficiently represent columnar and irregularly shaped grains. We demonstrate the power of this approach by simulating microstructures with hundreds to thousands of grains and quantify the reduction in the number of order parameters required to represent the microstructure. The new scheme leads to orders of magnitude fewer computational resources as compared to the naïve paradigm of one grain per order parameter, and also offers a substantial improvement over algorithms derived from bounding spheres.
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A unified thermodynamic description of moving non-equilibrium interfaces is developed for both solid/solid and solid/liquid transformations. The theory is applicable to concentrated ...multicomponent alloys where diffusion is possible in both phases or in just the parent phase, and where energy is dissipated due to solute drag. To be consistent with energy dissipation, we find that solute drag affects both the velocity of the interface and distribution coefficients for the compositions of the two phases at the interface. In the limit of binary alloy solidification, the theory predicts significant changes in the interfacial compositions from that given by the equilibrium phase diagram at velocities commonly found during additive manufacturing. Since the distribution coefficient is affected by solute drag, the solute-trapping behavior observed in molecular dynamics simulations implies that the interfacial diffusivity lies between the diffusivity of the bulk solid and liquid. A comparison to past work on non-equilibrium interfaces during solid/solid and solid/liquid phase transformations is also given.
Understanding the kinetics of passive oxide formation and breakdown has been an ongoing problem for corrosion scientists for several decades. Here, we present a model for the formation of a passive ...oxide film on a metal that is an extension of the Point Defect Model (PDM) by Macdonald and coworkers. We replace the potential description of the PDM with a boundary value problem and ensure that Gauss's law is satisfied at the oxide-solution interface by considering the presence of the Helmholtz layer in solution. Our model predicts the observed linear variation of the steady-state film thickness with anode potential, and an increasing film thickness with increasing pH. We perform a linear stability analysis of the model and show that, depending on the parameters, the passive film may be unstable to morphological perturbations of the film interfaces, leading to nonplanar films and potentially the formation of a pit in the oxide. This also implies that one-dimensional models, which assume planar interfaces, can be inapplicable in broad classes of corrosion processes. The analysis shows that a morphological instability exists if the oxide dissolution mechanism is such that an increasing Helmholtz layer potential drop leads to an increasing dissolution rate. The instability behavior is consistent with the literature on breakdown of passivity in the presence of chloride ions. The theory provides insights on the initiation of passivity breakdown leading to pitting corrosion and the role that interfacial energy plays in determining stability.
We propose a general theory of Ostwald ripening for prolate spheroidal particles in a nonideal nondilute multicomponent alloy. The diffusion problem of a growing or shrinking particle is solved using ...prolate spheroidal coordinates under the assumption that the spheroidal particle has a constant Wulff shape. The result shows that the diffusional growth rate increases with an increasing particle aspect ratio due to the increased surface area per volume. The anisotropic interfacial energy necessary to guarantee that the particles are always prolate spheroids with a given aspect ratio is also determined. We find that the chemical potential decreases with an increasing particle aspect ratio under a constant volume-equivalent radius. Based on the two correction factors, asymptotic analysis reveals that the temporal exponents for the coarsening laws for spheroid particles are identical to that for spherical particles. However, as the aspect ratio increases the amplitudes of the temporal power laws of the average equivalent radius, the matrix supersaturations, and the particle composition decrease, whereas the amplitude of the number of particles per volume increases. It is also shown that the particle shape anisotropy affects the amplitudes, but not the direction of the vector representing the matrix supersaturation and particle composition.
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