Classification of the effectiveness of combination treatments

According to FDA regulations, a combination drug is not efficacious unless each component contributes to the claimed effects. For a univariate endpoint, this implies that the combination at specific doses must be superior to each of its components at the same doses. More demanding is the property of synergy, in which the effect of the combination must be superior to the effect expected based on those of its components. If it is equal to those effects, it is additive, and if it is inferior, it is antagonistic. We give regions in the combination dose plane where these concepts are well defined. If the effect of the combination is greater than the greatest effect achievable by any of its components it is therapeutically synergistic. A combination can be antagonistic, yet its components can still contribute to the claimed effects. If it is additive, synergistic or therapeutically synergistic, its components must contribute to the claimed effects. We relate these concepts and provide designs and sequential procedures for determining whether a combination is therapeutically synergistic, synergistic, additive, antagonistic and contributing or antagonistic and non-contributing.     

1H-NMR spectroscopic investigation of polyamide fibers grafted with vinyl monomers

Nuclear magnetic resonance spectroscopy was used to investigate the position of active centers in polyamide fibers subjected to graft copolymerization with poly(acrylic acid), poly(itaconic acid), and poly(2-vinylpyridine) initiated by thermal oxidation in air. As a result, structural changes in polyamide fibers brought about by oxidation and subsequent grafting of the above mentioned polymers were observed. It was estimated that the generation of active centers that initiate the copolymerization take place at the nitrogen atoms of the amide groups in the polyamide chain. This was confirmed by the broadening of the absorption band for the methylone group adjacent to the nitrogen as well as by the absence of a new absorption band for the methine groups, assuming that the generation of active centers and grafting would take place at the carbon atom of the methylene group in position α to the amide group. © 1996 John Wiley & Sons, Inc.     

A Holistic Approach to Determining Stereochemistry of Potential Pharmaceuticals by Circular Dichroism with β-Lactams as Test Cases

This paper’s main objective is to show that many different factors must be considered when solving stereochemical problems to avoid misleading conclusions and obtain conclusive results from the analysis of spectroscopic properties. Particularly in determining the absolute configuration, the use of chiroptical methods is crucial, especially when other techniques, including X-ray crystallography, fail, are not applicable, or give inconclusive results. Based on various β-lactam derivatives as models, we show how to reliably determine their absolute configuration (AC) and preferred conformation from circular dichroism (CD) spectra. Comprehensive CD analysis, employing both approaches, i.e., traditional with their sector and helicity rules, and state-of-the-art supported by quantum chemistry (QC) calculations along with solvation models for both electronic (ECD) and vibrational (VCD) circular dichroism ranges, allows confident defining stereochemistry of the β-lactams studied. Based on an in-depth analysis of the results, we have shown that choosing a proper chiroptical method/s strictly depends on the specific case and certain structural features.     

Effect of high-fat cholesterol enriched diets on hypolipemic action of Oenothera paradoxa oil in rats. Part 1. Blood serum and liver lipids

The effect on Oenothera paradoxa oil on blood serum and liver lipids metabolism in rats fed a semisynthetic high-fat cholesterol enriched diets was investigated. The source of fats was sunflower oil or lard in 15% quantities and the source of protein was soybean protein isolate in 27% quantity. The diets were enriched with 0.5% cholesterol. This dietary experiment was carried on for 8 weeks. For the first 4 weeks rats were fed standard diet and for the next 4 weeks Oe. paradoxa oil (300 mg/day/rat) was additionally given by stomach-tube. At the end of experiment the contents of total cholesterol, HDL-cholesterol, triglycerides and free fatty acids in blood serum as well as cholesterol and triglycerides level in liver were determined. It was found, that the addition of cholesterol to the diet decreased the hypocholesterolemic and hypotriglyceridemic effects of Oe. paradoxa oil both in blood serum and liver. It have not had any significant effect on the free fatty acid concentration in blood serum decrease by Oe. paradoxa oil intake.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.     

The investigations of gas‐powder two phase flow in packed bed

Gas‐powder two‐phase flow in packed beds was investigated and the results are presented in this paper. The experimental system, in which the glass powder and air gas were injected into the lower part of the packed bed allowed the estimation of the influence of gas velocity, powder feed rate, powder and packed particles diameter on pressure loss and total hold up of powder in the packed bed. On the base of the experimental results, a one‐dimensional mathematical model for gas‐powder two‐phase flow in the packed bed was developed. This model allows satisfactory prediction of the pressure loss and the hold ups of powders. The maximum deviation between calculated and measured values was less than ±15%. Futhermore, the conditions when the blockade of the flow occurs were defined. The additional pressure loss (expressed by F_k) due to the gravitional force of powders and the collision and the friction between powders and packed particles, was correlated with Froude number as: for the void fraction in the packed bed ?₀ of between 0.36 to 0.41 or .     

Computer design of super-orthogonal space-time trellis codes

Super-orthogonal space-time trellis codes (SOSTTCs) designed by hand can significantly improve the performance of space-time trellis codes. This paper introduces a new representation of SOSTTCs based on a generator matrix that allows a systematic and exhaustive search of all possible codes. This will verify that some of the known codes are optimal, and provides a means to easily implement encoders and decoders with a large number of states without relying on a graphical representation. New codes with up to 256 states that outperform previously known codes are presented     

MAC-layer rate control for 802.11 networks: a survey

Rate control at the MAC-layer is one of the fundamental building blocks in many wireless networks. Over the past two decades, around thirty mechanisms have been proposed in the literature. Among them, there are mechanisms that make rate selection decisions based on sophisticated measurements of wireless link quality, and others that are based on straight-forward heuristics. Minstrel, for example, is an elegant mechanism that has been adopted by hundreds of millions of computers, yet, not much was known about its performance until recently. The purpose of this paper is to provide a comprehensive survey and analysis of the existing solutions from the two fundamental aspects of rate control—metrics and algorithms. We also review how these solutions were evaluated and compared against each other. Based on our detailed studies and observations, we share important insights on future development of rate control mechanisms at the MAC-layer. This discussion also takes into account the recent developments in wireless technologies and emerging applications, such as Internet-of-Things, and shows issues that need to be addressed in the design of new rate control mechanisms suitable for these technologies and applications.

     

Sex-Specific Differences in Olfactory Sensitivity for Putative Human Pheromones in Nonhuman Primates.

In humans, the volatile C19-steroids androsta-4,16-dien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST) have been shown to modulate autonomic nervous system responses, and to cause hypothalamic activation in a gender-specific manner. Using two conditioning paradigms, the authors here show that pigtail macaques and squirrel monkeys of both sexes were able to detect AND and EST at concentrations in the micromolar and mM range, respectively. Male and female spider monkeys, in contrast, differed markedly in their sensitivity to these two odorous steroids, with males not showing any behavioral responses to the highest concentrations of AND tested and females not responding to the highest concentrations of EST. These data provide the first examples of sex-specific bimodal distributions of olfactory sensitivity in a nonhuman primate species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drying Conditions and Processability of Dried Rapeseed

The possibility of using the oil-point and compression tests for evaluation of dried rapeseeds processability was examined. Seeds of initial moisture 10, 14, 18 and 22% (w/w) were dried at 60, 80, 100 and 120°C to a final moisture of 6·5% (w/w). The values of pressure ( P ₀ ), work ( L ₀ ) and strain (ε₀) determined by the oil-point test, and pressure at strain ε=0·45 mm mm⁻¹ ( P_ε ) and degree of elasticity ( D ) determined by the compression test for bulk dried seeds differed markedly from those found for non-dried seeds. The P ₀ , L ₀ and P_ε values were strongly correlated with the initial moisture of rapeseeds and drying temperature. All the strain values (ε₀) were lower than those for non-dried seeds, and their changes depended solely on the initial moisture of seeds. Changes in the degree of elasticity were irregular and did not reach the value characteristic for overdried seeds, ie 100%. High correlation of the agglomeration test data (Δ_1–3 values) with those of the P ₀ , L ₀ and P_ε made it possible to develop appropriate equations that proved the usefulness of the variables for determining the dried rapeseed processability.