Structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 Acta Materialia Inc.The aim of this study was to investigate an in vivo tissue response to a biodegradable polyesterurethane, specifically the cellular and angiogenic response evoked by varying implant architectures in a subcutaneous rabbit implant model. A synthetic biodegradable polyesterurethane was synthesized and processed into three different configurations: a non-porous film, a porous mesh and a porous membrane. Glutaraldehyde cross-linked bovine pericardium was used as a control. Sterile polyesterurethane and control samples were implanted subcutaneously in six rabbits (n = 12). The rabbits were killed at 21 and 63 days and the implant sites were sectioned and histologically stained using haemotoxylin and eosin (H&E), Masson’s trichrome, picosirius red and immunostain CD31. The tissue–implant interface thickness was measured from the H&E slides. Stereological techniques were used to quantify the tissue reaction at each time point that included volume fraction of inflammatory cells, fibroblasts, fibrocytes, collagen and the degree of vascularization. Stereological analysis inferred that porous scaffolds with regular topography are better tolerated in vivo compared to non-porous scaffolds, while increasing scaffold porosity promotes angiogenesis and cellular infiltration. The results suggest that this biodegradable polyesterurethane is better tolerated in vivo than the control and that structural variants of biodegradable polyesterurethane in vivo evoke a cellular and angiogenic response that is dictated by architecture.Irish Research Council for Science, Engineering and Technology: funded by the National Development Plan. Enterprise Ireland: Research Innovation Partnership

Shuttle TPS thermal performance and analysis methodology

Thermal performance of the thermal protection system was approximately as predicted. The only extensive anomalies were filler bar scorching and over-predictions in the high Delta p gap heating regions of the orbiter. A technique to predict filler bar scorching has been developed that can aid in defining a solution. Improvement in high Delta p gap heating methodology is still under study. Minor anomalies were also examined for improvements in modeling techniques and prediction capabilities. These include improved definition of low Delta p gap heating, an analytical model for inner mode line convection heat transfer, better modeling of structure, and inclusion of sneak heating. The limited number of problems related to penetration items that presented themselves during orbital flight tests were resolved expeditiously, and designs were changed and proved successful within the time frame of that program

Empirical structure models of Uranus and Neptune

Uranus and Neptune are still poorly understood. Their gravitational fields, rotation periods, atmosphere dynamics, and internal structures are not well determined. In this paper, we present empirical structure models of Uranus and Neptune where the density profiles are represented by polytropes. By using these models that are set to fit the planetary gravity field, we predict the higher order gravitational coefficients J6 and J8 for various assumed rotation periods, wind depths, and uncertainty of the low-order harmonics. We show that faster rotation and/or deep winds favour centrally concentrated density distributions. We demonstrate that an accurate determination of J6 or J8 with a relative uncertainty no larger than 10 per cent could constrain wind depths of Uranus and Neptune. We also confirm that the Voyager II rotation periods are inconsistent with the measured shapes of Uranus and Neptune. We next demonstrate that more accurate determination of the gravity field can significantly reduce the possible range of internal structures. Finally, we suggest that an accurate measurement of the moment of inertia of Uranus and Neptune with a relative uncertainty of ∼ 1 per cent and ∼ 0.1 per cent, could constrain their rotation periods and depths of the winds, respectively

Facile synthesis of N-acyl-2-pyrrolines

In conjunction with our studies of the amidoalkylation reaction,\u27 multigram quantities of N-acyl-2-pyrrolines (1) were needed. Interestingly, only a few methods for the synthesis of this class of compounds had been reported. Stille and co-workers prepared 1 by a novel transition metal mediated isomerization of N-acyl-3-pyrrolines2 and also cyclized (acy1amino)butyraldehydes to produce le3 Although these methods are excellent for qmall-scale preparation, large-scale reactions would entail considerable expense

Long-term conservation and rehabilitation of threatened rain forest patches under different human population pressures in West Africa

The management schemes of four rain forest patches in southern Benin and south-western Nigeria, which led to the successful protection of numerous threatened plants and animals over the last 20 plus years, are analysed. Since climatic conditions are similar, tree composition depends largely on different availability of water and documented biodiversity mostly on the availability of taxonomic expertise. Management differs according to accessibility and human population pressure, from total closing off of the forest by an international institute near the mega-polis Ibadan to unmarked borders near Lanzron, a remote village in the lower Ouémé Valley, where foreigners are mostly excluded from visiting the site. In Benin, trees and wildlife (antelopes and monkeys) seem best protected where the local vodoun beliefs are adhered to. This is, however, not sufficient and development aid to support and benefit the local population is needed as exemplified in Zinvié. At the Ibadan and Drabo sites, long-term protection is assured by legally-binding land-titles. Since for all of Lanzron and part of Zinvié these are lacking securing them is a priority. In Ibadan, Nigeria, a major rehabilitation effort is concentrated on bringing relatively old grass land and former village sites under forest cover by planting local trees. Rehabilitation in Drabo, in southern Benin, relies on enriching the naturally occurring fallow succession with rare species from nearby threatened sacred forests. We demonstrate that reversing biodiversity loss is possible but requires a long-term commitment. Recommendations for protecting, stabilizing and enhancing similar small hotspots of biodiversity are made

Polymorphisms in DMRT1 coding and promoter regions are probably not causative for swine sex reversal (XX, SRY-negative) syndrome

SRY-negative XX sex reversal is an inherited or sporadically occurring disorder, where testis development appears in the absence of the SRY gene. Although the molecular background of this intersexuality syndrome in pigs is unknown, it was proposed that familial cases might be inherited as a single autosomal recessive trait. Because DMRT1 (Doublesex and Mab-3 related transcription factor 1) is an autosomal locus in pig (SSC1q21), shows sexually dimorphic expression in swine gonads and has strong significance in vertebrate testis development, the molecular analysis of this gene was performed in previously reported three intersexes (38,XX, SRY-negative), the progeny of a single boar from a Polish farm. The first two exons encoding functional DM (double sex and mab-3) domain and the promoter region (the 5'flanking sequence) (altogether 3894 bp) were sequenced and compared with male and female control pigs (n = 16) and with publicly available sequences. Three different polymorphisms were found in the coding region, one Indel type polymorphism (DNA 142_144indelAGC) causing a deletion of an amino acid (protein S47_G48indelS) and two silent SNPs (DNA G432A and G492A). The promoter region seems to be highly polymorphic, since 17 SNPs and 5 indels were detected. However, the sequences of control males and females were concordant with those of the intersexes. These results indicate that DMRT1 is an unlikely candidate gene for SRY-negative XX sex reversal in pig

Revealing cytotoxic substructures in molecules using deep learning

In drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico methods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the field of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic effects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds

Conversion of lactones into ethers

Although tetrahydrofurans and tetrahydropyrans are important structural subunits of many classes of natural products,l comparatively few general synthetic methods are known? Since y- and &lactones are readily available: an efficient and versatile transformation to the ether would significantly extend current methodology. The conversion of a lactone to an ether has been accomplished by hydride reduction to a diol followed by cyclization by way of a monotosylate4 or other activated ester.

The influence of lithium excess in the target on the properties andcompositions of Li1+ x Mn2O4− δ thin films prepared by PLD

Li-Mn-O thin films were deposited by pulsed laser deposition (PLD) onto stainless steel substrates using targets containing different concentrations of added Li2O. The influence of the target composition on the stoichiometry of the resulting thin films, the surface morphology and the electrochemical properties was studied. The application of the target with added 7.5 mol% Li2O results in an almost ideal lithium content, while all films were still oxygen deficient. The thin films were applied as electrodes in Li//Li1+x Mn2O4−δ cells (i.e. model cells for a rechargeable Li-ion battery) and characterized by cyclic voltammetry and galvanostatic charge/discharge experiments. The electrochemical measurements of the thin films confirmed that the thin films can serve as good model systems and that they show a sufficient cyclabilit