Enhancement of Upconverted Fluorescence by Interference Layers

Upconverting nanoparticles show potential applications in the field of photovoltaics and array‐based detection devices. While fluorescence enhancement using interference of incident radiation is well known in Stokes‐shift type systems such as fluorescent dyes; the effect of such interference geometry in nonlinear Anti‐Stokes type emission, such as in upconversion rare earth photophysics is demonstrated for the first time. This work describes in detail the influence of the interference modulation on both the excitation (interion energy transfer) and radiative decay with nonradiative decay processes active between emissive levels. These effects are illustrated in the thickness dependence of the decay rate and rise time. Single particle upconverted spectra and time‐resolved measurements show concurrent optimization of the infrared absorption and emission at 540 and 650 nm, with an average enhanced emission of 20 times at λ = 540 and 45 times at λ = 650 nm, dependent on the interference layer thickness and on the excitation intensity. The experimental results are correlated with finite element modeling. Both experiments and calculations show emission enhancement at an interference layer thickness of about 740 ± 20 nm, where such tolerance and the planar design, leads to ease in implementation in applications.     

Recent progress in continuous and semi-continuous processing of solid oral dosage forms: a review

Context: Continuous processing is an innovative production concept well known and successfully used in other industries for many years. The modern pharmaceutical industry is facing the challenge of transition from a traditional manufacturing approach based on batch-wise production to a continuous manufacturing model.

Objective: The aim of this article is to present technological progress in manufacturing based on continuous and semi-continuous processing of the solid oral dosage forms.

Methods: Single unit processes possessing an alternative processing pathway to batch-wise technology or, with some modification, an altered approach that may run continuously, and are thus able to seamlessly switch to continuous manufacturing are briefly presented. Furthermore, the concept of semi-continuous processing is discussed. Subsequently, more sophisticated production systems created by coupling single unit processes and comprising all the steps of production, from powder to final dosage form, were reviewed. Finally, attempts of end-to-end production approach, meaning the linking of continuous synthesis of API from intermediates with the production of final dosage form, are described.

Results: There are a growing number of scientific articles showing an increasing interest in changing the approach to the production of pharmaceuticals in recent years. Numerous scientific publications are a source of information on the progress of knowledge and achievements of continuous processing. These works often deal with issues of how to modify or replace the unit processes in order to enable seamlessly switching them into continuous processing. A growing number of research papers concentrate on integrated continuous manufacturing lines in which the production concept of “from powder to tablet” is realized. Four main domains are under investigation: influence of process parameters on intermediates or final dosage forms properties, implementation of process analytical tools, control-managing system responsible for keeping continuous materials flow through the whole manufacturing process and the development of new computational methods to assess or simulate these new manufacturing techniques. The attempt to connect the primary and secondary production steps proves that development of continuously operating lines is possible.

Conclusion: A mind-set change is needed to be able to face, and fully assess, the advantages and disadvantages of switching from batch to continuous mode production.     

Efficient data management in a large-scale epidemiology research project

This article describes the concept of a "Central Data Management" (CDM) and its implementation within the large-scale population-based medical research project "Personalized Medicine". The CDM can be summarized as a conjunction of data capturing, data integration, data storage, data refinement, and data transfer. A wide spectrum of reliable "Extract Transform Load" (ETL) software for automatic integration of data as well as "electronic Case Report Forms" (eCRFs) was developed, in order to integrate decentralized and heterogeneously captured data. Due to the high sensitivity of the captured data, high system resource availability, data privacy, data security and quality assurance are of utmost importance. A complex data model was developed and implemented using an Oracle database in high availability cluster mode in order to integrate different types of participant-related data. Intelligent data capturing and storage mechanisms are improving the quality of data. Data privacy is ensured by a multi-layered role/right system for access control and de-identification of identifying data. A well defined backup process prevents data loss. Over the period of one and a half year, the CDM has captured a wide variety of data in the magnitude of approximately 5terabytes without experiencing any critical incidents of system breakdown or loss of data. The aim of this article is to demonstrate one possible way of establishing a Central Data Management in large-scale medical and epidemiological studies.     

Structural and electrical properties of grain boundaries in Ce0.85Gd0.15O1.925 solid electrolyte modified by addition of transition metal ions

In this work we present studies on applicability of transition metal additives as sintering and electrical conductivity aids for cerium gadolinium oxide electrolyte. The nanosized Ce_0.85Gd_0.15O_1.925 powder obtained by coprecipitation method was modified with Cr³⁺, Fe³⁺, Ni²⁺ or Cu²⁺ ions. Using high-intensity high-resolution X-ray powder diffraction data we have determined that Cr, Fe and Ni ions do not incorporate into the cerium gadolinium oxide surface or bulk when sintered at 1300 °C, but react with Gd ions to form Cr_0.9Gd_0.1O, GdFeO₃ and GdNiO₃ phases, while Cu incorporates in the material up to 0.7 mol% with a significant fraction of remaining material showing poorly crystalline CuO phase. The nanosized Ce_0.85Gd_0.15O_1.925 material shows already improved sintering properties than previous reports but full sintering is not achieved below 1300 °C, however Cr, Fe and mainly Cu impregnation allows full sintering at 1300 °C. 0.5 mol% Ni impregnated material sintered at 1500 °C shows enhanced grain boundary conductivity that probably indicates that Ni incorporates into Ce_0.84Gd_0.15O_1.925 above 1300 °C. The global results indicate, however, that optimization of ceria microstructure is at least of equal importance for sinterability and grain boundary conductivity than impregnation of the material with transition metal ions.     

Modeling of Nonlinear Surface Impedance of High-Tc Superconductors Using an Exponential Vortex Penetration Model

We have modeled surface impedance of YBa₂Cu₃O_7– thin films, using an exponential dependence on an applied rf magnetic field. For verification of the model we compared simulation results with experimental data of Nguyen et al. [2] and of Hein [14] at differing temperatures, frequencies and rf power levels. Obtained temperature dependence of the model fitting coefficients exhibited the same character in both cases.     

Pressure distribution in an assembly of wooden cylinders with various aspect ratios under uniaxial confined compression

Understanding how forces propagate in granular assemblages is important for equipment design and process control in many technologies. Yet, it remains poorly understood. In this study, a cuboidal assembly comprising cylinders of various lengths (aspect ratios AR ranging from 0.9 to 3.6) were subjected to uniaxial confined compression tests. Samples were vertically compressed until the top platen exerted a pressure of 50 kPa on the uppermost particles. This maximum pressure corresponds to the hydrostatic pressure of an approximately 15 m high column of chopped wood that may be encountered in real storage structures. The nonlinear loading curves were obtained depended on the aspect ratios of the cylinders. The modulus of elasticity, calculated from the linear elastic part of the stress–strain curve, monotonically decreased from 10.2 to 8.6 MPa as the aspect ratio increased from 1.2 to 3.6. The elastic modulus and volume fraction exhibited similar trends as functions of the aspect ratio. The horizontal-to-vertical pressure ratio was calculated as the horizontal pressure exerted on the wider walls to the vertical pressure exerted on the top lid during loading–unloading cycles. For ARs up to 3.6, the pressure ratio was approximately 0.31; for the longest cylinders (AR = 3.6), it decreased to approximately 0.27, probably because the assumption of the representative chamber volume was invalidated at this AR.     

The Synthesis of Vicinal Diacylamines via Bamberger Ring Cleavage of Substituted Imidazoles. 1,2,4-Triacylaminobutanes Bearing Different Acyl Groups

Bamberger ring cleavage acylation of N-p-toluenesulfonyl (tosyl) histamine followed by hydrogenation yields 3,4-diacylaminobutanetosylamine, a triamine containing groups with different chemical reactivities.     

Sintering of Colloidal Ru/γ-Al2O3 Catalyst in Hydrogen

Colloidal 5.1 wt% Ru/γ-Al₂O₃ catalyst was prepared by a microwave assisted, solvothermal reduction of RuCl₃ in ethylene glycol in the presence of γ-Al₂O₃. The catalyst subjected to heat-treatment in hydrogen up to 700 °C, was characterized by BET, XRD, TEM and H₂ chemisorption. As-prepared catalyst contained Ru nanoparticles with mean size of 1.5 nm and narrow size distribution uniformly distributed over the support. The nanoparticles were stable on the alumina to 500 °C, but treatment at 600–700 °C caused some sintering of Ru due to migration and coalescence of a part of smallest ruthenium nanoparticles. However, even after H₂ treatment at 700 °C, large amount of Ru nanoparticles with sizes of 1–3 nm remained in the catalyst. H₂ chemisorption data revealed decrease of Ru dispersion from 0.28 to 0.19 by hydrogen treatment at 700 °C and were in good correspondence with TEM results. On the contrary, mean crystallite sizes obtained from XRD were strongly overestimated.     

Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors

Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S is the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low‐molecular‐weight inhibitors for cathepsin F have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent–reversible inhibitors, was performed to draw structure–activity relationships for the non‐primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N‐(4‐phenylbenzoyl)‐leucylglycine nitrile) and 12 (N‐(4‐phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsin F, with K_i values <10 nM . With all dipeptide nitriles from our study, a 3D activity landscape was generated to visualize structure–activity relationships for this series of cathepsin F inhibitors.