Limitations of Preferential Enrichment: A Case Study on Tryptophan Ethyl Ester Hydrochloride

Since eutomer and distomer show different biological effects, access to pure enantiomers is essential. Preferential enrichment is a relatively new process of chiral resolution developed in the 90s. Extension of its scope was attempted with tryptophan ethyl ester hydrochloride. This salt meets one of the most important requirements for preferential enrichment, namely, a larger solubility for the pure enantiomers with reference to the racemic compound. But, due to the absence of a solid solution, this salt cannot perform preferential enrichment. This impossibility was endorsed by semi‐empirical molecular modeling.     

How Mixing and Light Heterogeneity Impact the Overall Growth Rate in Photobioreactors

The microalgae growth rate in photobioreactors responds with inertia to light stimuli. Here, light variations experienced by the algae are accessed through a coupling of an irradiance field calculation and a Lagrangian particle tracking. The response of algae to fluctuating light is then described by a relaxation model involving a single time constant, the value of which is identified from published data. The overall growth rate is calculated as the sum of individual growth rates of all particles. Instantaneous adaptation and full integration asymptotic behaviors are recovered whilst a finite time constant reveals that the overall growth rate is dependent both on mixing and light distribution. This methodology thus quantitatively relates the design parameters to the photobioreactor performance.     

Evaluation of interconnected production sites taking into account multidimensional uncertainties

The production sites of international companies are becoming increasingly interconnected. Due to the uncertainty of multiple factors, determining a location is a strategic choice entailing high financial risk. For this reason, a method for site evaluation was developed allowing multidimensional, i.e., both quantitative and qualitative, uncertainties to be taken into account. The uncertainties are modeled with both probability and fuzzy-set theory and integrated into a modular-structured monetary calculation model. For the analysis and interpretation of evaluation results, methods have been developed which allow risk assessment. The developed method provides a way to handle existing location risks and can thus ensure the success of manufacturing companies in the long term.     

Interactions between Polymeric Dispersants and Calcium Silicate Hydrates

To better understand the mechanism of interaction between hydrating silicate-based cements and polymeric dispersants of the type used as superplasticizers in modern construction concretes, two different types of polymeric dispersant were added (at concentrations of 1 and 10 g/L) during the synthesis of calcium silicate hydrate (C-S-H) via the pozzolanic reaction in dilute slurries of lime and reactive silica, at Ca/Si ratios in the range of 0.66–1.50. Although both polymers gave degrees of adsorption of >79% in all cases studied, no significant structural modifications of the resulting C-S-H products were observed via X-ray diffraction or ²⁹Si magic angle spinning–nuclear magnetic resonance. These results differ from recent work in which it was shown that similar types of polymer could intercalate into the interlayers of C-S-H that was made using an alternative process. It is suggested that the process by which the C-S-H is formed may have a strong influence on whether C-S-H can intercalate polymers. This observation is relevant to understanding the fate of such polymers in concrete.     

Near-Field Electron Energy Loss Spectroscopy in Porous Silicon

First results of an Electron Energy Loss Spectroscopy in the Near Field (NFEELS) mode of n⁺ porous silicon are described here. Sequences of EELS spectra in the low loss energy range (0–30 eV) were recorded, using a scanning transmission electron microscope, as the e-beam was scanned across a nano-hole surrounded by Si platelets. This technique is shown to be very sensitive to spectral and spatial changes in the electromagnetic field distribution outside the surface of nanoparticles, governed by their local nature and shape.     

Thermal Ageing Induced Effects on Pd/LaFeO3 for NOx Reduction by Hydrocarbons: Influence of the Preparation Method

The influence of the support synthesis for the preparation of supported Pd/LaFeO₃ perovskite based catalysts and the nature of the palladium precursor on the catalytic performances in the selective reduction of NO to N₂ by hydrocarbons have been investigated. According to the preparation method, subsequent surface and bulk characterisation revealed significant changes in the degree of dispersion and the chemical environment of oxidic palladium species depending on the extent of interaction with the support. Pd nitrate precursor leads to the stabilisation of the Pd surface concentration. The metal support interactions thus obtained strongly enhance the catalytic performances, particularly the resistance to thermal ageing whereas sol–gel synthesis produces the higher support activity.     

Synthesis, cytotoxicity, and COMPARE analysis of ferrocene and [3]ferrocenophane tetrasubstituted olefin derivatives against human cancer cells

Herein we report the antiproliferative effects of a series of 28 compounds against the MDA-MB-231 breast cancer cell line, including the synthesis of seven new [3]ferrocenophanyl and four new ferrocenyl compounds. For each p-R-phenyl substitution pattern investigated, the [3]ferrocenophanyl derivatives were more cytotoxic than the corresponding ferrocenyl derivative, with the highest activity found for compounds with protic substituents. Theoretical calculations of the HOMO-LUMO gap for the molecules in the Fe3(+) oxidation state suggest a higher reactivity for the [3]ferrocenophanyl derivatives. A lead compound from each series, a [3]ferrocenophanyl and a ferrocenyl compound, possessing two phenol groups, were screened against the NCI/DTP 60-cell-line panel. The mean activity over all cell lines was better than cisplatin for both compounds, and both compounds showed subpanel selectivity for leukemia, CNS cancer, and renal cancer. Low systemic toxicity and lack of interaction with DNA (when in the reduced form), suggest that the compounds may act as prodrugs.     

Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound. Even agreeing upon a definition of a "valid" surrogate endpoint has not been a straightforward exercise; this article begins by highlighting differences in how this term has been previously captured and applied, as well as laying out the basic criteria essential for its application in advanced colorectal cancer. Ideally, these elements include (but are not limited to) ease of measurement, rapid indication of treatment effect, and, most importantly, reliable and consistent prediction of the true impact of a treatment on the ultimate outcome of interest: overall survival. The strengths and weaknesses of current potential surrogate endpoints in advanced colorectal cancer, including performance status, carcinoembryonic antigen plasma level, overall response rate, time to progression, and disease-free survival, are each considered in turn. Finally, limitations of surrogate endpoints in the clinical setting, including challenges in extrapolation to new therapies, and the incomplete provision of information about potential adverse effects, are discussed. Work remains to be done between physicians and statisticians to bridge the gap between that which is statistically demonstrable and that which will be clinically useful.The term ;surrogate endpoint' was virtually unknown by most oncologists 15 years ago. A search in PubMed [http://www.ncbi.nlm.nih.gov] based on the words ;surrogate and cancer' shows that more than 2000 papers were published in medical journals in the last 20 years, with a dramatic increase of interest in the last five years. Interestingly, the same trend is observed when the words ;surrogate and heart' are entered into PubMed, suggesting that the issue of surrogate endpoints goes beyond the field of oncology, although the frequency of discussion varies (Figure 1; note different y-axis scales for oncology and cardiology).The goal of the present paper is to discuss the main issues surrounding surrogate endpoints from a clinician's point of view, using as an example surrogate endpoints of overall survival (OS) in advanced colorectal cancer (ACC).     

Generation of carrier peptides for the delivery of nucleic acid drugs in primary cells

Now that the human genome has been decoded, the demand for novel therapeutic concepts, such as gene and stem cell therapy, is higher than ever before. Although new and better pharmaceutical agents are available, their efficient delivery to the intracellular site of action is still a serious challenge. A possible solution to this problem is the use of cell-penetrating peptides as delivery vectors, including derivatives of human calcitonin (hCT). The aim of this study was to synthesise novel branched hCT-derived peptides for the noncovalent delivery of nucleic acids. The uptake of the resulting oligocationic peptides into various cell lines as well as primary cells was monitored by fluorescence microscopy. To determine the appropriate peptide-plasmid charge ratios for efficient cell transfection, electromobility shift assays were carried out. Finally, flow cytometric and fluorescence microscopic studies of gene expression highlighted two novel hCT-derived peptides as highly effective in the delivery of noncovalently complexed plasmid DNA. Thus, the absence of cytotoxicity paired with highly efficient cell internalisation and transfection rates, in primary cells as well, make both peptides powerful candidates as drug delivery vectors, especially for plasmid DNA, for both in vivo and ex vivo therapeutic applications.     

Silicon Substitution for Aluminum in Calcium Silicate Hydrates

²⁷Al MAS and multiquantum (MQ) MASNMR (magic-angle spinning nuclear magnetic resonance) spectroscopy were used to study the substitution of silicon by aluminum in calcium silicate hydrates (C-S-H), which are the main component of hydrated portland cement. Synthetic C-S-H samples were prepared, and their chemical stability was studied. Two-dimensional 3Q-MASNMR spectra revealed the chemical shift and quadrupolar parameters (delta_iso, nu_Q) that labeled aluminum sites in the C-S-H. Tetrahedral aluminum was observed in the bridging and nonbridging sites of the silicate chains.