Assessing the use of NMR chemical shifts for prediction of VLE in non-ideal binary liquid mixtures

A method of estimating vapour liquid equilibrium (VLE) using NMR chemical shift data has been proposed by Xu et al. (2012). This method is based on the concept that the average local composition around each species is determined by the thermodynamics of the system, and also determines the screening of the NMR active groups within that molecule, and so their NMR chemical shifts. Xu et al.‘s method has been replicated and verified; results are confirmed to be accurate for alcohol + hydrocarbon mixtures, giving VLE predictions of comparable accuracy to the UNIFAC, generally considered the best predictive activity coefficient model available. However, for more strongly non-ideal mixtures, the method becomes less reliable, giving significantly less accurate predictions of total pressure than UNIFAC. Several causes for this are identified. The model proposed by Xu et al. (2012) is unable to fit minima or maxima in chemical shifts, which are observed experimentally in some binary mixtures. Different NMR resonances within the same molecule lead to different predictions of VLE, clearly an un-physical result. The thermodynamics of strongly non-ideal mixtures are determined by more complex interactions than a simple description of average local composition around each component in the mixtures, for example strong and directional hydrogen bonds. Different groups within the same molecule may have different local compositions in their immediate vicinity; for example in the case of alcohol + water mixtures, one would expect a clustering of water molecules around the hydroxyl group but not the aliphatic group. Hence, the concept of a simple local composition model is not valid for these more complex cases, and it is therefore not surprising that a model based on this simple concept is often not effective in predicting VLE.C. D’Agostino would like to acknowledge Wolfson College, Cambridge, for supporting his research activities.This is the accepted manuscript. The final version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0009250914004461

The time-dependent expression of keratins 5 and 13 during the reepithelialization of human skin wounds

The time-dependent reepithelialization of 55 human surgical skin wounds with a wound age between 8h and more than 2 months was investigated by the immunohistochemical localization of cytokeratins 5 and 13. A complete, rebuilt epidermal layer over the wound area was first detectable in a 5-day-old wound, while all wounds of more than 18 days duration contained a completely reepithelialized wound area. Between 5 and 18 days the basal layer of keratinocytes showed — in contrast to normal skin — only some cells positive for cytokeratin 5. In some, but not all lesions with a wound age of 13 days or more, a basal cell layer completely staining for cytokeratin 5 was demonstrable. This staining pattern was found in all skin wounds with a wound age of more than 23 days. The immunohistochemical detection of cytokeratin 13 which can be observed regularly in non-cornifying squamous epithelia provides no information for the time-estimation of human skin wounds, since no significant temporary expression of this polypeptide seems to occur during the healing of human skin wounds

Recovery of the crucian carp Carassius carassius (L.): Approach and early results of an English conservation project

Aquatic Conservation: Marine and Freshwater Ecosystems published by John Wiley & Sons Ltd The crucian carp Carassius carassius, a cyprinid fish characteristic of small ponds, is in decline throughout most of its European range, including in England where it is currently thought to be non-native. The present study, undertaken by the Norfolk Crucian Project, reports on reductions in pond populations of crucian carp in Norfolk, eastern England as well as the success of recent introduction/re-introduction efforts in terms of crucian survival, recruitment and growth over the last 10 years. A 72% decline in crucian carp distribution was observed between the 1950s–1980s and the 2010s. Of 18 crucian carp introductions/re-introductions to restored and suitable existing ponds, 17 were successful in terms of survival, increasing the number of current crucian sites in Norfolk by 37%. Recruitment of young crucian carp was demonstrated for 12 of the 18 stocked ponds, with apparent elevated juvenile growth relative to other English and European populations. Delays in, or a lack of, crucian recruitment in some ponds appeared to result from the presence of other fish species (especially threespine stickleback Gasterosteus aculeatus) with predation and interspecific competition possible contributory factors. This study shows that, through combinations of pond rehabilitation and stocking, it has been possible to achieve a substantial recovery of crucian carp populations in the study region. Although the crucian carp is currently presumed to be non-native within England, given other scientific studies that show a lack of adverse impacts of this species on native biota, and because it is greatly threatened in its native range, the call is sounded for more crucian carp conservation projects in other parts of England as well as in Europe more generally

Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog

Thermoelastic properties of magnesiowustite, (Mg1-xFex)O: determination of the Anderson-Gruneisen parameter by time-of-flight neutron powder diffraction at simultaneous high pressures and temperatures

The ability to perform neutron diffraction studies at simultaneous high pressures and high temperatures is a relatively recent development. The suitability of this technique for determining P-V-T equations of state has been investigated by measuring the lattice parameters of Mg1-xFexO ( x = 0.2, 0.3, 0.4), in the range P < 10.3 GPa and 300 < T < 986 K, by time-of-flight neutron powder diffraction. Pressures were determined using metallic Fe as a marker and temperatures were measured by neutron absorption resonance radiography. Within the resolution of the experiment, no evidence was found for any change in the temperature derivative of the isothermal incompressibility, partial derivative K-T/partial derivative T, with composition. By assuming that the equation-of-state parameters either varied linearly or were invariant with composition, the 60 measured state points were fitted simultaneously to a P-V-T-x equation of state, leading to values of partial derivative K-T/partial derivative T = -0.024 (9) GPa K-1 and of the isothermal Anderson-Gruneisen parameter delta(T) = 4.0 (16) at 300 K. Two designs of simultaneous high-P/T cell were employed during this study. It appears that, by virtue of its extended pressure range, a design using toroidal gaskets is more suitable for equation-of-state studies than is the system described by Le Godec, Dove, Francis, Kohn, Marshall, Pawley, Price, Redfern, Rhodes, Ross, Schofield, Schooneveld, Syfosse, Tucker & Welch [Mineral. Mag. (2001), 65, 737-748]. (c) 2008 International Union of Crystallography Printed in Singapore - all rights reserved

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort

Human 13N-ammonia PET studies: the importance of measuring 13N-ammonia metabolites in blood

Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways, using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements

Patent Human Infections with the Whipworm, Trichuris trichiura, Are Not Associated with Alterations in the Faecal Microbiota

Background: The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. Materials and Methods: School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Results: Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Discussion: Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al