Pharmacotherapy for NASH: Current and emerging Konerman, Monica A.; Jones, Jacob C.; Harrison, Stephen A.
Journal of hepatology,
February 2018, 2018-02-00, 20180201, Letnik:
68, Številka:
2
Journal Article
Recenzirano
Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent forms of chronic liver disease worldwide, reflecting the epidemic of global obesity. Those with the progressive variant ...of NAFLD, non-alcoholic steatohepatitis (NASH), are at significantly increased risk of multisystem morbidity and mortality. However, there are currently no approved pharmacologic therapies for NASH. Given the disease burden, there is an important unmet need for pharmacologic treatment options for this patient population. The underlying pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex and reflected by the myriad of therapies, with different targets, currently under investigation. In broad strokes, drug development has focused on modulation of metabolic pathways, inflammatory cascades, and/or mechanisms impacting fibrosis. Although much progress has been made in enhancing our understanding of NAFLD pathogenesis, development of pharmacologic treatments has been hindered by challenges in clinical trial enrollment and complexities in clinical trial design. The compounds in phase IIa have provided promising results in terms of potential benefits on various aspects of histopathology. Agents in later stages of development have shown fairly modest results in terms of reduction of hepatic steatosis, necroinflammation and fibrosis. If longer term safety and efficacy are established among heterogeneous cohorts, these medications may help mitigate potential morbidity and mortality for this burgeoning patient population.
Piezoelectrics have widespread use in today's sensor and actuator technologies. However, most commercially available piezoelectric materials, e.g., Pb Zr(x)Ti(1-x) O(3) (PZT), are comprised of more ...than 60 weight percent lead (Pb). Due to its harmful effects, there is a strong impetus to identify new lead-free replacement materials with comparable properties to those of PZT. This review highlights recent developments in several lead-free piezoelectric materials including BaTiO(3), Na(0.5)Bi(0.5)TiO(3), K(0.5)Bi(0.5)TiO(3), Na(0.5)K(0.5)NbO(3), and their solid solutions. The factors that contribute to strong piezoelectric behavior are described and a summary of the properties for the various systems is provided.
A centrosymmetric stress cannot induce a polar response in centric materials; piezoelectricity is, for example, possible only in non-centrosymmetric structures. An exception is metamaterials with ...shape asymmetry, which may be polarized by stress even when the material is centric. In this case the mechanism is flexoelectricity, which relates polarization to a strain gradient. The flexoelectric response scales inversely with size, thus a large effect is expected in nanoscale materials. Recent experiments in polycrystalline, centrosymmetric perovskites (for example, (Ba, Sr)TiO3) have indicated values of flexoelectric coefficients that are orders of magnitude higher than theoretically predicted, promising practical applications based on bulk materials. We show that materials with unexpectedly large flexoelectric response exhibit breaking of the macroscopic centric symmetry through inhomogeneity induced by the high-temperature processing. The emerging electro-mechanical coupling is significant and may help to resolve the controversy surrounding the large apparent flexoelectric coefficients in this class of materials.
Bismuth ferrite (BiFeO3), a perovskite material, rich in properties and with wide functionality, has had a marked impact on the field of multiferroics, as evidenced by the hundreds of articles ...published annually over the past 10 years. Studies from the very early stages and particularly those on polycrystalline BiFeO3 ceramics have been faced with difficulties in the preparation of the perovskite free of secondary phases. In this review, we begin by summarizing the major processing issues and clarifying the thermodynamic and kinetic origins of the formation and stabilization of the frequently observed secondary, nonperovskite phases, such as Bi25FeO39 and Bi2Fe4O9. The second part then focuses on the electrical and electromechanical properties of BiFeO3, including the electrical conductivity, dielectric permittivity, high‐field polarization, and strain response, as well as the weak‐field piezoelectric properties. We attempt to establish a link between these properties and address, in particular, the macroscopic response of the ceramics under an external field in terms of the dynamic interaction between the pinning centers (e.g., charged defects) and the ferroelectric/ferroelastic domain walls.
Entropy-stabilized oxides Rost, Christina M; Sachet, Edward; Borman, Trent ...
Nature communications,
09/2015, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Configurational disorder can be compositionally engineered into mixed oxide by populating a single sublattice with many distinct cations. The formulations promote novel and entropy-stabilized forms ...of crystalline matter where metal cations are incorporated in new ways. Here, through rigorous experiments, a simple thermodynamic model, and a five-component oxide formulation, we demonstrate beyond reasonable doubt that entropy predominates the thermodynamic landscape, and drives a reversible solid-state transformation between a multiphase and single-phase state. In the latter, cation distributions are proven to be random and homogeneous. The findings validate the hypothesis that deliberate configurational disorder provides an orthogonal strategy to imagine and discover new phases of crystalline matter and untapped opportunities for property engineering.
The surprising ferroelectricity displayed by hafnia thin films has been attributed to a metastable polar orthorhombic (Pca21) phase. Nevertheless, the conditions under which this (or another ...competing) ferroelectric phase may be stabilized remain unresolved. It has been hypothesized that a variety of factors, including strain, grain size, electric field, impurities and dopants, may contribute to the observed ferroelectricity. Here, we use first-principles computations to examine the influence of mechanical and electrical boundary conditions (i.e., strain and electric field) on the relative stability of a variety of relevant nonpolar and polar phases of hafnia. We find that although strain or electric field, independently, do not lead to a ferroelectric phase, the combined influence of in-plane equibiaxial deformation and electric field results in the emergence of the polar Pca21 structure as the equilibrium phase. The results provide insights for better controlling the ferroelectric characteristics of hafnia thin films by adjusting the growth conditions and electrical history.
Recently simulation groups have reported the lanthanide series elements as the dopants that have the strongest effect on the stabilization of the ferroelectric non-centrosymmetric orthorhombic phase ...in hafnium oxide. This finding confirms experimental results for lanthanum and gadolinium showing the highest remanent polarization values of all hafnia-based ferroelectric films until now. However, no comprehensive overview that links structural properties to the electrical performance of the films in detail is available for lanthanide-doped hafnia. La:HfO2 appears to be a material with a broad window of process parameters, and accordingly, by optimization of the La content in the layer, it is possible to improve the performance of the material significantly. Variations of the La concentration leads to changes in the crystallographic structure in the bulk of the films and at the interfaces to the electrode materials, which impacts the spontaneous polarization, internal bias fields, and with this the field cycling behavior of the capacitor structure. Characterization results are compared to other dopants like Si, Al, and Gd to validate the advantages of the material in applications such as semiconductor memory devices.
Dynamic structural changes during the first electrochemical charge and discharge cycle in the Li-excess layered oxide compound, LiLi1/5Ni1/5Mn3/5O2, are studied with synchrotron X-ray diffraction ...(SXRD), aberration corrected scanning transmission electron microscopy (a-S/TEM), and electron energy loss spectroscopy (EELS). At different states of charge, we carefully examined the crystal structures and electronic structures within the bulk and have found that increased microstrain is accompanied with the cation migration and a second phase formation which occurs during the first cycle voltage plateau as well as into the beginning of the discharge cycle. The evidence indicates that the oxygen vacancy formation and activation may facilitate cation migration and results in the formation of a second phase. The EELS results reveal a Mn valence change from 4+ to 3+ upon oxygen vacancy formation and recovers back to 4+ at the discharge. The oxygen vacancy formation and activation at the partially delithiated state leads to the generation of several crystal defects which are observed in TEM. Identification of the correlation between microstrain and oxygen vacancy formation during the first electrochemical cycle clarifies the complex intercalation mechanisms that accounts for the anomalous capacities exceeding 200 mAh/g in the Li-excess layered oxide compounds.
Non-toxic and air-stable silver bismuth iodide semiconductors are promising light absorber candidates for photovoltaic applications owing to a suitable band gap for multi- or single-junction solar ...cells. Recently, solution-based film fabrication approaches for several silver bismuth iodide stoichiometries have been investigated. The current work reports on a facile and reproducible two-step coevaporation/annealing approach to deposit compact and pinhole-free films of AgBi
2
I
7
, AgBiI
4
and Ag
2
BiI
5
. X-ray diffraction (XRD) in combination with scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX) analysis reveals formation of pure cubic (
Fd
3̄
m
) phase AgBi
2
I
7
, cubic (
Fd
3̄
m
) or rhombohedra (
R
3̄
m
) phase AgBiI
4
, each with >3 μm average grain size, or the rhombohedral phase (
R
3̄
m
) Ag
2
BiI
5
with >200 nm average grain size. A phase transition from rhombohedral to cubic structure is investigated
via
temperature-dependent X-ray diffraction (TD-XRD). Planar-junction photovoltaic (PV) devices are prepared based on the coevaporated rhombohedral AgBiI
4
films, with titanium dioxide (TiO
2
) and poly(3-hexylthiophene) (P3HT) as electron- and hole-transport layers, respectively. The best-performing device exhibited a power conversion efficiency (PCE) of as high as 0.9% with open-circuit voltage (
V
OC
) > 0.8 V in the reverse scan direction (with significant hysteresis).
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