The Crystal Structures of Epi-Limonol Iodoacetate and Azulene

The crystal structures of two organic molecules have been determined by the methods of X-ray diffraction. Epi-limonol iodoacetate, C28H33O9I, belongs to the monoclinic space group P2 1 with four molecules per unit cell. The crystal structure analysis has been based on the heavy-atom technique. Three-dimensional data have been used for the computations, the chief methods used being the Patterson synthesis and corresponding minimum function combined with Fourier syntheses. This analysis has led to a complete determination of the molecular structure and stereochemistry of epi-limonol iodoacetate and hence of the parent compound, limonin, C26H30O8. The latter is of great interest to organic chemists and the determination of its structure may make a significant contribution to the elucidation of other closely-related structures. Azulene, C10H8, is monoclinic, space group P2 1/a, with two molecules per unit cell. The partially refined structure, postulated as belonging to the space group Pa, has been analysed by the method of least-squares and found to be incapable of refinement. Re-examination of the space group requirements has led to a statistically disordered structure in the space group P2 1/a. This structure has been exhaustively refined by three-dimensional least-squares analysis but the results are rather unsatisfactory. The extreme 'closeness' of pairs of atoms prohibits a very accurate determination of atomic coordinates. However, the transannular C-C bond has been shown to he considerably larger than the other bonds in the molecule in agreement with theoretical considerations. Several programmes have been developed for use with English Electric 'DEUCE'. These programmes, written with interpretive coding schemes, facilitate various computations encountered in X-ray crystallographic analysis

Cardiac Depression Scale: Mokken scaling in heart failure patients

Background: There is a high prevalence of depression in patients with heart failure (HF) that is associated with worsening prognosis. The value of using a reliable and valid instrument to measure depression in this population is therefore essential. We validated the Cardiac Depression Scale (CDS) in heart failure patients using a model of ordinal unidimensional measurement known as Mokken scaling. Findings: We administered in face-to-face interviews the CDS to 603 patients with HF. Data were analysed using Mokken scale analysis. Items of the CDS formed a statistically significant unidimensional Mokken scale of low strength (H<0.40) and high reliability (Rho>0.8). Conclusions: The CDS has a hierarchy of items which can be interpreted in terms of the increasingly serious effects of depression occurring as a result of HF. Identifying an appropriate instrument to measure depression in patients with HF allows for early identification and better medical management. Keywords: Cardiac Depression Scale, Heart failure, Depression, Mokken scalin

Randomised controlled trial comparing rubber band ligation with stapled haemorrhoidopexy for Grade II circumferential haemorrhoids : Long-term results

Peer reviewedPostprin

The application of metabolomic profiling to the effects of physical activity

Physical activity and exercise are potent lifestyle interventions for the reduction of several psychosomatic risks, including cardiovascular disease, diabetes and mild-to-moderate depression. The current review describes the studies which have utilised a metabolomics/ metabolite profiling approach in combination with exercise in the period between 1999-2014 in predominantly healthy subjects (N:64) and in a smaller subset of patient cohorts (N:10) between 2011-2014. A broad range of intervention types were used in both healthy and patient cohorts with varying exercise regimes with or without supplement use. Effects on purine metabolism, which have been known for over 40 years, were by far the most well-cited and persistent finding. Other reported effects included observations of: glucocorticoid and androgen metabolism, glycolysis and Krebs cycle, gluconeogenesis, fatty acid metabolism, fatty acid oxidation and pantothenic acid, amino acid oxidation, tryptophan metabolism and effects on microbiome metabolites. The discussion section draws observations from the very disparate studies together and links them to the general aspects of human metabolism

Metabolomic profiling and stable isotope labelling of Trichomonas vaginalis and Tritrichomonas foetus reveal major differences in amino acid metabolism including the production of 2-hydroxyisocaproic acid, cystathionine and S-methylcysteine

Trichomonas vaginalis and Tritrichomonas foetus are pathogens that parasitise, respectively, human and bovine urogenital tracts causing disease. Using LC-MS, reference metabolomic profiles were obtained for both species and stable isotope labelling with D-[U-13C6] glucose was used to analyse central carbon metabolism. This facilitated a comparison of the metabolic pathways of T. vaginalis and T. foetus, extending earlier targeted biochemical studies. 43 metabolites, whose identities were confirmed by comparison of their retention times with authentic standards, occurred at more than 3-fold difference in peak intensity between T. vaginalis and T. foetus. 18 metabolites that were removed from or released into the medium during growth also showed more than 3-fold difference between the species. Major differences were observed in cysteine and methionine metabolism in which homocysteine, produced as a bi-product of trans-methylation, is catabolised by methionine γ-lyase in T. vaginalis but converted to cystathionine in T. foetus. Both species synthesise methylthioadenosine by an unusual mechanism, but it is not used as a substrate for methionine recycling. T. vaginalis also produces and exports high levels of S-methylcysteine, whereas only negligible levels were found in T. foetus which maintains significantly higher intracellular levels of cysteine. 13C-labeling confirmed that both cysteine and S-methylcysteine are synthesised by T. vaginalis; S-methylcysteine can be generated by recombinant T. vaginalis cysteine synthase using phosphoserine and methanethiol. T. foetus contained higher levels of ornithine and citrulline than T. vaginalis and exported increased levels of putrescine, suggesting greater flux through the arginine dihydrolase pathway. T. vaginalis produced and exported hydroxy acid derivatives of certain amino acids, particularly 2-hydroxyisocaproic acid derived from leucine, whereas negligible levels of these metabolites occurred in T. foetus

Comparative Models of Hydrocarbon Emissions for a Diesel Engine Operating at Constant Loads and Speeds

Linear multiple regression (LMR) and nonlinear polynomial network (NPN) models were developed from data collected from ISO 8178‐4 (1996) test cycle B‐type tests (ISO) and an expanded set of tests (EXP) to predict hydrocarbon (HC) emissions from a diesel engine. LMR using the ISO training data (R2 = 0.94) resulted in overfitting of the model as applied to the evaluation data (R2 = 0.49). LMR based on the expanded data (R2 = 0.68) was a better LMR model when applied to the evaluation data (R2 = 0.64). NPN using the expanded training data (R2 = 0.99) resulted in the best model when applied to the evaluation data (R2 = 0.98) and is preferred for predicting HC when the larger set of test mode data are available. NPN using the ISO training data (R2 = 0.99) resulted in a satisfactory fit for the evaluation data (R2 = 0.91), although with a higher average absolute error (0.52 vs. 0.42 g/kWh) than NPN using the EXP training data. This model was also considered suitable for predicting HC. Results of this initial study suggest that data could be collected during ISO 8178‐4 emission tests and modeled with NPN to predict HC emissions for a diesel engine operating at various constant speeds and loads

Generating samples of extreme winters to support climate adaptation

Recent extreme weather across the globe highlights the need to understand the potential for more extreme events in the present-day, and how such events may change with global warming. We present a methodology for more efficiently sampling extremes in future climate projections. As a proof-of-concept, we examine the UK’s most recent set of national Climate Projections (UKCP18). UKCP18 includes a 15-member perturbed parameter ensemble (PPE) of coupled global simulations, providing a range of climate projections incorporating uncertainty in both internal variability and forced response. However, this ensemble is too small to adequately sample extremes with very high return periods, which are of interest to policy-makers and adaptation planners. To better understand the statistics of these events, we use distributed computing to run three 1000-member initial-condition ensembles with the atmosphere-only HadAM4 model at 60km resolution on volunteers’ computers, taking boundary conditions from three distinct future extreme winters within the UKCP18 ensemble. We find that the magnitude of each winter extreme is captured within our ensembles, and that two of the three ensembles are conditioned towards producing extremes by the boundary conditions. Our ensembles contain several extremes that would only be expected to be sampled by a UKCP18 PPE of over 500 members, which would be prohibitively expensive with current supercomputing resource. The most extreme winters we simulate exceed those within UKCP18 by 0.85 K and 37% of the present-day average for UK winter means of daily maximum temperature and precipitation respectively. As such, our ensembles contain a rich set of multivariate, spatio-temporally and physically coherent samples of extreme winters with wide-ranging potential applications

Modeling NO Emissions of an Off-road Diesel Engine Based on Emission Tests

Emissions values determined by the ISO 8178 emission certification tests do not necessarily represent emissions of a tractor in operation (Hansson et al., 2001). Rather than using ISO 8178 tests solely for certification, data collected during the tests may be suitable for predicting nitrogen oxide (NOx) emissions of an engine operating at constant loads and speeds. Linear multiple regression (LMR) and nonlinear polynomial network (NPN) models were developed with data collected from ISO 8178-4 (1996) test cycle B-type tests (ISO) and an expanded set of tests (EXP) to predict NOx emissions from a diesel engine. LMR using the ISO training data (R2 = 0.94) resulted in over-training of the model, as applied to the evaluation data (R2 = 0.51). LMR based on the expanded data (R2 = 0.60) was a better LMR model, when applied to the evaluation data (R2 = 0.73). NPN using the ISO training data (R2 = 0.99) resulted in a considerable improvement over the LMR models for the evaluation data (R2 = 0.81). NPN using the EXP training data (R2 = 0.96) resulted in the best model when applied to the evaluation data (R2 = 0.95). When applied to the evaluation data, the mean absolute error of the NPN EXP based model was significantly less than from the NPN ISO based model. The NPN model based on EXP data is recommended for predicting NOx. Data could be collected during ISO 8178-4 emission tests that included additional test modes and modeled with NPN to predict NOx emissions for a diesel engine operating at various constant speeds and loads

Protein Fingerprinting: A Domain-Free Approach to Protein Analysis

An alternative method for analyzing proteins is proposed. Currently, protein search engines available on the internet utilize domains (predefined sequences of amino acids) to align proteins. The method presented converts a protein sequence with the use of 1200 numeric codes that represent a unique three—amino-acid protein sequence. Each numeric code starts with one of three specific amino acids, followed by any two additional amino acids. With the use of the FPC (FingerPrinted Contig) program, the total protein database (including “redundant” records) from the National Center for Biotechnology Information (NCBI) has been processed and placed into “bins/contigs” based on associations of these triplet codes. When analyzed with FPC, proteins are “contigged” together based on the number of shared fragments, regardless of order. These associations were supported by additional analysis with the standard BLASTP utility from NCBI. Within the created contig sets, there are numerous examples of proteins (allotypes and orthotypes) that have evolved into different, seemingly unrelated proteins. The power of this domain-free technique has yet to be explored; however, the ability to bin proteins together with no a priori knowledge of domains may prove a powerful tool in the characterization of the hundreds of thousands of available, yet undescribed expressed protein and open reading frame sequences

Changes in the milk metabolome of the Giant Panda (Ailuropoda melanoleuca) with time after birth: three phases in early lactation and progressive individual differences

Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth