Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

Effect of CeO_2 on Electrical Properties of (Nb,Mn)-Doped TiO_2 Varistor Ceramics

The electrical properties of TiO2-based varistor ceramics with different amount of CeO2 were investigated by measuring the properties of V-I, permittivity, density and boundary defect barriers. It is found that an optimal composition doped with 0.7% CeO2 exhibits the highest nonlinear coefficient of 10.5, the highest breakdown voltage of 12.77 V·mm^-1, the ultrahigh permittivity of 82900（measured at 1 kHz）, and the highest density of 4.15 g·cm^-3, which is consistent with the highest and narrowest grain-boundary defect barriers. In order to illustrate the grain boundary barriers formation in TiO2-Nb2O5-MnCO3-CeO2 varistor, an grain-boundary defect barrier model was also introduced.

Dynamic Control of Defective Gap Mode Through Defect Location

A one dimensional model is developed for defective gap mode（DGM）with two types of boundary conditions：conducting mesh and conducting sleeve.For a periodically modulated system without defect,the normalized width of spectral gaps equals to the modulation factor,which is consistent with previous studies.For a periodic system with local defects introduced by the boundary conditions,it shows that the conducting-mesh-induced DGM is always well confined by spectral gaps while the conducting-sleeve-induced DGM is not.The defect location can be a useful tool to dynamically control the frequency and spatial periodicity of DGM inside spectral gaps.This controllability can be potentially applied to the interaction between gap eigenmodes and energetic particles in fusion plasmas,and optical microcavities and waveguides in photonic crystals.

Statistical modeling of total crash frequency at highway intersections

Intersection-related crashes are associated with high proportion of accidents involving drivers, occupants, pedestrians, and cyclists. In general, the purpose of intersection safety analysis is to determine the impact of safety-related variables on pedestrians, cyclists and vehicles, so as to facilitate the design of effective and efficient countermeasure strategies to improve safety at intersections. This study investigates the effects of traffic, environ- mental, intersection geometric and pavement-related characteristics on total crash fre- quencies at intersections. A random-parameter Poisson model was used with crash data from 357 signalized intersections in Chicago from 2004 to 2010. The results indicate that out of the identified factors, evening peak period traffic volume, pavement condition, and unlighted intersections have the greatest effects on crash frequencies. Overall, the results seek to suggest that, in order to improve effective highway-related safety countermeasures at intersections, significant attention must be focused on ensuring that pavements are adequately maintained and intersections should be well lighted. It needs to be mentioned that, projects could be implemented at and around the study intersections during the study period （7 years）, which could affect the crash frequency over the time. This is an important variable which could be a part of the future studies to investigate the impacts of safety related works at intersections and their marginal effects on crash frequency at signalized intersections.

Yield modeling of elliptical defect

Physical defects have always played an important role in integrated circuit(IC)yields,and the design sensitivity to these physical elements has continued to increase in today’s nanometer technologies.The modeling of defect out-lines that exhibit a great variety of defect shapes is usually modeled as a circle,which causes the errors of critical area estimation.Since the outlines of 70%defects approximate to elliptical shapes,a novel yield model associated with elliptical outlines of defects is presented.This model is more general than the circular defects model as the latter is only an instance of the proposed model.Comparisons of the new and circular models in the experiment show that the new model can predict yield caused by real defects more accurately than what the circular model does,which is of significance for the prediction and improvement of the yield.

Exosome-functionalized magnesium-organic framework-based scaffoldswith osteogenic, angiogenic and anti-inflammatory properties foraccelerated bone regeneration

Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study,motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized anexosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of thebenefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhanceosteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated thebeneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bonemarrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells(HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells,stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and acceleratedbone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed thatPLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, weprovide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesisproperty.

Vacancy formation enthalpies of high-entropy FeCoCrNi alloy via first-principles calculations and possible implications to its superior radiation tolerance

Because atoms in high-entropy alloys （HEAs） coordinate in very different and distorted local environ- ments in the lattice sites, even for the same type of constituent, their point defects could highly vary. Therefore, theoretical determination of the thermodynamic quantities （i.e., defect formation enthalpies） of various point defects is rather challenging because each corresponding thermodynamic quantity of all involve constituents is not unique. The knowledge of these thermodynamic quantities is prerequisite for designing novel HEAs and understanding the mechanical and physical behaviors of HEAs. However, to date there has not been a good method to theoretically derive the defect formation enthalpies of HEAs. Here, using first-principles calculations within the density functional theory （DFT） in combina- tion of special quasi-random structure models （SQSs）, we have developed a general method to derive corresponding formation enthalpies of point defects in HEAs, using vacancy formation enthalpies of a four-component equiatomic fcc-type FeCoCrNi HEA as prototypical and benchmark examples. In difference from traditional ordered alloys, the vacancy formation enthalpies of FeCoCrNi HEA vary in a highly wide range from 0.72 to 2.89 eV for Fe, 0.88-2.90 eV for Co, 0.78-3.09 eV for Cr, and 0.91-2.95 eV for Ni due to high-level site-to-site lattice distortions and compositional complexities. On average, the vacancy formation enthalpies of 1.58 eV for Fe, 1.61 eV for Cr, 1.70 eV for Co and 1.89 eV for Ni are all larger than that （1.41 eV） of pure fcc nickel. This fact implies that the vacancies are much more difficult to be created than in nickel, indicating a reasonable agreement with the recent experimental observation that FeCoCrNi exhibits two orders of amplitudes enhancement of radiation tolerance with the suppression of void formation at elevated temperatures than in pure nickel.

Numerical simulation of the effect of the free carrier motilities on light-soaked a-Si:H p–i–n solar cell

Using a previous model, which was developed to describe the light-induced creation ofthe defect density in the a-Si：H gap states, we present in this work a computer simulation of the a-Si：H p-i-n solar cell behavior under continuous illumination. We have considered the simple case of a monochromatic light beam nonuniformly absorbed. As a consequence of this light-absorption profile, the increase of the dangling bond density is assumed to be inhomogeneous over the intrinsic layer （i-layer）. We investigate the internal variable profiles during illumination to understand in more detail the changes resulting from the light-induced degradation effect. Changes in the cell external parameters including the open circuit voltage, Voc, the short circuit current density, Jsc, the fill factor, FF, and the maximum power density, Pmax, are also presented. This shows, in addition, the free carrier mobility influence. The obtained results show that Voc seems to be the less affected parameter by the light-induced increase of the dangling bond density. Moreover, its degradation is very weak-sensitive to the free carrier mobility. Finally, the free hole mobility effect is found to be more important than that of electrons in the improvement of the solar cell performance.

Next-generation resorbable polymer scaffolds with surface-precipitated calcium phosphate coatings

Next-generation synthetic bone graft therapies will most likely be composed of resorbable polymers in combination with bioactive components.In this article,we continue our exploration of E1001(1k),a tyrosine-derived polycarbonate,as an orthopedic implant material.Specifically,we use E1001(1k),which is degradable,nontoxic,and osteoconductive,to fabricate porous bone regeneration scaffolds that were enhanced by two different types of calcium phosphate(CP)coatings:in one case,pure dicalcium phosphate dihydrate was precipitated on the scaffold surface and throughout its porous structure(E1001(1k)+CP).In the other case,bone matrix minerals(BMM)such as zinc,manganese and fluoride were co-precipitated within the dicalcium phosphate dihydrate coating(E1001(1k)+BMM).These scaffold compositions were compared against each other and against ChronOS(Synthes USA,West Chester,PA,USA),a clinically used bone graft substitute(BGS),which served as the positive control in our experimental design.This BGS is composed of poly(lactide co-e-caprolactone)and beta-tricalcium phosphate.We used the established rabbit calvaria critical-sized defect model to determine bone regeneration within the defect for each of the three scaffold compositions.New bone formation was determined after 2,4,6,8 and 12 weeks by micro-computerized tomography(mCT)and histology.The experimental tyrosine-derived polycarbonate,enhanced with dicalcium phosphate dihydrate,E1001(1k)+CP,supported significant bone formation within the defects and was superior to the same scaffold containing a mix of BMM,E1001(1k)+BMM.The comparison with the commercially available BGS was complicated by the large variability in bone formation observed for the laboratory preparations of E1001(1k)scaffolds.At all time points,there was a trend for E1001(1k)+CP to be superior to the commercial BGS.However,only at the 6-week time point did this trend reach statistical significance.Detailed analysis of the μCT data suggested an increase in bone formation from 2 through 12 weeks in implant sites treated with E1001(1k)+CP.At 2 and 4 weeks post-implantation,bone formation occurred at the interface where the E1001(1k)+CP scaffold was in contact with the bone borders of the implant site.Thereafter,during weeks 6,8 and 12 bone formation progressed throughout the E1001(1k)+CP test implants.This trend was not observed with E1001(1k)+BMM scaffolds or the clinically used BGS.Our results suggest that E1001(1k)+CP should be tested further for osteoregenerative applications.