Evaluation of In vitro and In vivo Performance of Granisetron In situ Forming Implants: Effect of Sterilization, Storage Condition and Degradation

Purpose: To investigate the effect of various solvent systems and gamma irradiation on the in vitro and in vivo performance of granisetron HCl injectable phase-sensitive in situ forming implants (ISFIs).Methods: ISFIs were prepared by mixing and sterilized by gamma  irradiation. Effect of solvent system was studied. Injectability, polymer degradation and stability studies (4 and 25 oC for 4 months), viscositymeasurements, as well as in vitro and in vivo (in rabbits) drug release, and also histological examinations for biocompatibility studies (in rabbits and rats) were carried out.Results: ISFIs showed good injectability from 20-gauge needle and their in vitro drug release increased in the following rank order of solvent/solvent combinations: dimethylsulphoxide (DMSO) > DMSO:prophylenecarbonate (PC) > DMSO:triacetin(TA) > DMSO:benzylbenzoate (BB). DMSO:PC incorporating ISFI gave zero order (r2 = 0.9503) drug release for 21 days; application of gamma irradiation accelerated drug release with a difference factor (f1) of 53 but zero order release (r2 = 9690) was maintained. Following test results for DMSO:PC including ISFI as decrease in molecular weight of polymer was descriptive for drug release behavior and  sterilization effect, additionally dynamic viscosities decreased in line with polymer degradation and all forms of this ISFI showed plastic flow(fresh, irradiated, aged at 4 and 25 oC for 4 months). In vivo performance showed steady state plasma drug concentrations between 2 to 21 days with value of 0.55 ± 0.03 ìg/ml and biocompatibility was confirmed by  histological results obtained at specific stages of tissue reactions, and also by lack of fibrous capsule formation.Conclusion: An ISFI for long-term antiemetic therapy achieved in this  preliminary study is promising and, therefore, further investigations are required.Keywords: Implant, Poly(DL-lactide-co-glycolide), Granisetron, Gamma irradiation, Sterilization, Degradation, Viscosity, Stability, Pharmacokinetic, Biocompatibility

Direct Imaging, Three-dimensional Interaction Spectroscopy, and Friction Anisotropy of Atomic-scale Ripples on MoS2_{2}

Theory predicts that two-dimensional (2D) materials may only exist in the presence of out-ofplane deformations on atomic length scales, frequently referred to as ripples. While such ripples can be detected via electron microscopy, their direct observation via surface-based techniques and characterization in terms of interaction forces and energies remain limited, preventing an unambiguous study of their effect on mechanical characteristics, including but not limited to friction anisotropy. Here, we employ high-resolution atomic force microscopy to demonstrate the presence of atomic-scale ripples on supported samples of few-layer molybdenum disulfide (MoS$_{2}$). Three-dimensional force / energy spectroscopy is utilized to study the effect of ripples on the interaction landscape. Friction force microscopy reveals multiple symmetries for friction anisotropy, explained by studying rippled sample areas as a function of scan size. Our experiments contribute to the continuing development of a rigorous understanding of the nanoscale mechanics of 2D materials.Comment: 22 pages including 4 figures in the main text, 2 figures in the supplemental informatio

Probing three-dimensional surfaces force fields with atomic resolution: Measurement strategies, limitations, and artifact reduction

Cataloged from PDF version of article.Noncontact atomic force microscopy (NC-AFM) is being increasingly used to measure the interaction force between an atomically sharp probe tip and surfaces of interest, as a function of the three spatial dimensions, with picometer and piconewton accuracy. Since the results of such measurements may be affected by piezo nonlinearities, thermal and electronic drift, tip asymmetries, and elastic deformation of the tip apex, these effects need to be considered during image interpretation. In this paper, we analyze their impact on the acquired data, compare different methods to record atomic-resolution surface force fields, and determine the approaches that suffer the least from the associated artifacts. The related discussion underscores the idea that since force fields recorded by using NC-AFM always reflect the properties of both the sample and the probe tip, efforts to reduce unwanted effects of the tip on recorded data are indispensable for the extraction of detailed information about the atomic-scale properties of the surface

Structural lubricity under ambient conditions

Despite its fundamental importance, physical mechanisms that govern friction are poorly understood. While a state of ultra-low friction, termed structural lubricity, is expected for any clean, atomically flat interface consisting of two different materials with incommensurate structures, some associated predictions could only be quantitatively confirmed under ultra-high vacuum (UHV) conditions so far. Here, we report structurally lubric sliding under ambient conditions at mesoscopic (∼4,000-130,000 nm2) interfaces formed by gold islands on graphite. Ab initio calculations reveal that the gold-graphite interface is expected to remain largely free from contaminant molecules, leading to structurally lubric sliding. The experiments reported here demonstrate the potential for practical lubrication schemes for micro-and nano-electromechanical systems, which would mainly rely on an atomic-scale structural mismatch between the slider and substrate components, via the utilization of material systems featuring clean, atomically flat interfaces under ambient conditions

Structural superlubricity of platinum on graphite under ambient conditions: The effects of chemistry and geometry

An investigation of the frictional behavior of platinum nanoparticles laterally manipulated on graphite has been conducted to answer the question of whether the recent observation of structural superlubricity under ambient conditions [E. Cihan, S. Ipek, E. Durgun, and M. Z. Baykara, Nat. Commun. 7, 12055 (2016)] is exclusively limited to the gold-graphite interface. Platinum nanoparticles have been prepared by e-beam evaporation of a thin film of platinum on graphite, followed by post-deposition annealing. Morphological and structural characterization of the nanoparticles has been performed via scanning electron microscopy and transmission electron microscopy, revealing a crystalline structure with no evidence of oxidation under ambient conditions. Lateral manipulation experiments have been performed via atomic force microscopy under ambient conditions, whereby results indicate the occurrence of structural superlubricity at mesoscopic interfaces of 4000-75 000 nm2, with a noticeably higher magnitude of friction forces when compared with gold nanoparticles of similar contact areas situated on graphite. Ab initio simulations of sliding involving platinum and gold slabs on graphite confirm the experimental observations, whereby the higher magnitude of friction forces is attributed to stronger energy barriers encountered by platinum atoms sliding on graphite, when compared with gold. On the other hand, as predicted by theory, the scaling power between friction force and contact size is found to be independent of the chemical identity of the sliding atoms, but to be determined by the geometric qualities of the interface, as characterized by an average "sharpness score" assigned to the nanoparticles. © 2017 Author(s)

Inverse Layer Dependence of Friction on Chemically Doped MoS_{2}

We present the results of atomic-force-microscopy-based friction measurements on Re-doped molybdenum disulfide (MoS2). In stark contrast to the seemingly universal observation of decreasing friction with increasing number of layers on two-dimensional (2D) materials, friction on Re-doped MoS2 exhibits an anomalous, i.e. inverse dependency on the number of layers. Raman spectroscopy measurements revealed signatures of Re intercalation, leading to a decoupling between neighboring MoS2 layers and enhanced electron-phonon interactions, thus resulting in increasing friction with increasing number of layers: a new paradigm in the mechanics of 2D materials.Comment: 15 pages incl. Supplemental Material, 5 figure

Exploring atomic-scale lateral forces in the attractive regime: a case study on graphite (0001)

Cataloged from PDF version of article.A non-contact atomic force microscopy-based method has been used to map the static lateral forces exerted on an atomically sharp Pt/Ir probe tip by a graphite surface. With measurements carried out at low temperatures and in the attractive regime, where the atomic sharpness of the tip can be maintained over extended time periods, the method allows the quantification and directional analysis of lateral forces with piconewton and picometer resolution as a function of both the in-plane tip position and the vertical tip-sample distance, without limitations due to a finite contact area or to stick-slip-related sudden jumps of tip apex atoms. After reviewing the measurement principle, the data obtained in this case study are utilized to illustrate the unique insight that the method offers. In particular, the local lateral forces that are expected to determine frictional resistance in the attractive regime are found to depend linearly on the normal force for small tip-sample distances

2000 Families: identifying the research potential of an origins - of migration study

Despite extensive recent advances in the empirical and theoretical study of migration, certain critical areas in the analysis of European migration remain relatively underdeveloped both theoretically and empirically. Specifically, we lack studies that both incorporate an origin comparison and trace processes of intergenerational transmission across migrants over multiple generations and incorporating family migration trajectories. This paper outlines the development, data and design of such a study, the 2000 Families study, framed within a theoretical perspective of ?dissimilation? from origins and over generations. We term the study an origins-of-migration study, in that it captures the country of origin, the family origins and potentially the originating causes of migration processes and outcomes. The resulting data comprised nearly 2,000 migrant and non-migrant Turkish families with members across three or more generations, covering. 50,000 individuals. We reflect on the potential of this study for migration research

Understanding Scanning Tunneling Microscopy Contrast Mechanisms on Metal Oxides: A Case Study

Cataloged from PDF version of article.A comprehensive analysis of contrast formation mechanisms in scanning tunneling microscopy (STM) experiments on a metal oxide surface is presented with the oxygen-induced (2√2 √2)R45 missing row reconstruction of the Cu(100) surface as a model system. Density functional theory and electronic transport calculations were combined to simulate the STM imaging behavior of pure and oxygen-contaminated metal tips with structurally and chemically different apexes while systematically varying bias voltage and tip sample distance. The resulting multiparameter database of computed images was used to conduct an extensive comparison with experimental data. Excellent agreement was attained for a large number of cases, suggesting that the assumed model tips reproduce most of the commonly encountered contrast-determining effects. Specifically, we find that depending on the bias voltage polarity, copper-terminated tips allow selective imaging of two structurally distinct surface Cu sites, while oxygenterminated tips show complex contrasts with pronounced asymmetry and tip sample distance dependence. Considering the structural and chemical stability of the tips reveals that the copper-terminated apexes tend to react with surface oxygen at small tip sample distances. In contrast, oxygenterminated tips are considerably more stable, allowing exclusive surface oxygen imaging at small tip sample distances. Our results provide a conclusive understanding of fundamental STM imaging mechanisms, thereby providing guidelines for experimentalists to achieve chemically selective imaging by properly selecting imaging parameters