Modifications of Hyaluronan Influence the Interaction with Human Bone Morphogenetic Protein-4 (hBMP-4).

n this study, we have demonstrated that the modification of hyaluronan (hyaluronic acid; Hya) with sulfate groups led to different binding affinities for recombinant human bone morphogenetic protein-4 (rhBMP-4). The high-sulfated sHya2.8 (average degree of sulfation (D.S.) 2.8) exhibited the tightest interaction with rhBMP-4, followed by the low-sulfated sHya1.0, as determined with surface plasmon resonance (SPR), ELISA, and competition ELISA. Unmodified Hya, chondroitin-sulfate (CS), and heparan sulfate (HS) showed significantly less binding affinity. SPR data could be fitted to an A + B = AB Langmuir model and binding constants were evaluated ranging from 13 pM to 5.45 microM. The interaction characteristics of the differentially sulfated Hyas are promising for the incorporation of these modified polysaccharides in bioengineered coatings of biomaterials for medical applications

Watching others in a positive state does not induce optimism bias in common marmosets (Callithrix jacchus), but leads to behaviour indicative of competition

Emotional contagion is suggested to facilitate group life by enhancing synchronized responses to the environment. Cooperative breeders are an example of a social system that requires such intricate coordination between individuals. Therefore, we studied emotional contagion in common marmosets by means of a judgement bias test. Demonstrators were exposed to an emotion manipulation (i.e., positive, negative, control), and observers perceived only the demonstrator’s behaviour. We predicted that the positive or negative states of the demonstrator would induce matching states in the observer, indicating emotional contagion. All subjects’ emotional states were assessed through behaviour and cognition, the latter by means of a judgement bias test. Behavioural results showed a successful emotion manipulation of demonstrators, with manipulation-congruent expressions (i.e., positive calls in the positive condition, and negative calls and pilo-erect tail in the negative condition). Observers showed no manipulation-congruent expressions, but showed more scratching and arousal after the positive manipulation. Concerning the judgement bias test, we predicted that subjects in a positive state should increase their response to ambiguous cues (i.e., optimism bias), and subjects in a negative state should decrease their response (i.e., pessimism bias). This prediction was not supported as neither demonstrators nor observers showed such bias in either manipulation. Yet, demonstrators showed an increased response to the near-positive cue, and additional analyses showed unexpected responses to the reference cues, as well as a researcher identity effect. We discuss all results combined, including recently raised validation concerns of the judgement bias test, and inherent challenges to empirically studying emotional contagion

ERCP in Total Situs Viscerum Inversus

A 69-year-old cholecystectomized female with known total situs viscerum inversus presented recurrent colicky pain in the left upper abdominal quadrant and jaundice. Laboratory parameters showed increased neutrophils and coniugated bilirubin of 5.53 mg/dl. US and MRCP confirmed total situs viscerum inversus and a dilatation of the intra- and extrahepatic ducts with a peripapillary 13 mm stone. ERCP, sphincterotomy and successful common bile duct stone extraction were performed in the conventional way. ERCP was carried out successfully despite situs inversus maintaining the patient in the prone position with the endoscopist on the right side of the table. Some authors have reported similar cases in whom ERCP was performed in other positions, while this report shows that an experienced endoscopist can achieve the same results in the conventional way as it is possible when anatomical changes, Billroth II or Roux-en-Y, or different positions of the patient, supine or on the left side, are present

The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions

peer-reviewedData set for article is also provided.Research is needed to validate lesions recorded at meat inspection as indicators of pig welfare on farm. The aims were to determine the influence of mixing pigs on carcass lesions and to establish whether such lesions correlate with pig behaviour and lesions scored on farm. Aggressive and mounting behaviour of pigs in three single sex pens was recorded on Day −5, −2, and −1 relative to slaughter (Day 0). On Day 0 pigs were randomly allocated to 3 treatments (n = 20/group) over 5 replicates: males mixed with females (MF), males mixed with males (MM), and males unmixed (MUM). Aggressive and mounting behaviours were recorded on Day 0 at holding on farm and lairage. Skin/tail lesions were scored according to severity at the farm (Day −1), lairage, and on the carcass (Day 0). Effect of treatment and time on behaviour and lesions were analysed by mixed models. Spearman rank correlations between behaviour and lesion scores and between scores recorded at different stages were determined. In general, MM performed more aggressive behaviour (50.4 ± 10.72) than MUM (20.3 ± 9.55, P < 0.05) and more mounting (30.9 ± 9.99) than MF (11.4 ± 3.76) and MUM (9.8 ± 3.74, P < 0.05). Skin lesion scores increased between farm (Day −1) and lairage (P < 0.001), but this tended to be significant only for MF and MM (P = 0.08). There was no effect of treatment on carcass lesions and no associations were found with fighting/mounting. Mixing entire males prior to slaughter stimulated mounting and aggressive behaviour but did not influence carcass lesion scores. Carcass skin/tail lesions scores were correlated with scores recorded on farm (rskin = 0.21 and rtail = 0.18, P < 0.01) suggesting that information recorded at meat inspection could be used as indicators of pig welfare on farm.This study was part of the PIGWELFIND project funded by the Department of Agriculture, Food and the Marine (DAFM), Ireland

Transitions and Probes in Turbulent Helium

Previous analysis of a Paris turbulence experiment \cite{zoc94,tab95} shows a transition at the Taylor Reynolds number \rel \approx 700. Here correlation function data is analyzed which gives further evidence for this transition. It is seen in both the power spectrum and in structure function measurements. Two possible explanations may be offered for this observed transition: that it is intrinsic to the turbulence flow in this closed box experiment or that it is an effect of a change in the flow around the anemometer. We particularly examine a pair of ``probe effects''. The first is a thermal boundary layer which does exist about the probe and does limit the probe response, particularly at high frequencies. Arguments based on simulations of the response and upon observations of dissipation suggests that this effect is only crucial beyond \rel\approx 2000. The second effect is produced by vortex shedding behind the probe. This has been seen to produce a large modification in some of the power spectra for large \rel. It might also complicate the interpretation of the experimental results. However, there seems to be a remaining range of data for \rel < 1300 uncomplicated by these effects, and which are thus suggestive of an intrinsic transition.Comment: uuencoded .ps files. submitted to PRE. 12 figures are sent upon request to jane wang ([email protected]

Evolving Gaussian Process Kernels for Translation Editing Effort Estimation

In many Natural Language Processing problems the combination of machine learning and optimization techniques is essential. One of these problems is estimating the effort required to improve, under direct human supervision, a text that has been translated using a machine translation method. Recent developments in this area have shown that Gaussian Processes can be accurate for post-editing effort prediction. However, the Gaussian Process kernel has to be chosen in advance, and this choice in- fluences the quality of the prediction. In this paper, we propose a Genetic Programming algorithm to evolve kernels for Gaussian Processes. We show that the combination of evolutionary optimization and Gaussian Processes removes the need for a-priori specification of the kernel choice, and achieves predictions that, in many cases, outperform those obtained with fixed kernels.TIN2016-78365-

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix.

Diffraction (X-ray, neutron and electron) and electron cryo-microscopy are powerful methods to determine three-dimensional macromolecular structures, which are required to understand biological processes and to develop new therapeutics against diseases. The overall structure-solution workflow is similar for these techniques, but nuances exist because the properties of the reduced experimental data are different. Software tools for structure determination should therefore be tailored for each method. Phenix is a comprehensive software package for macromolecular structure determination that handles data from any of these techniques. Tasks performed with Phenix include data-quality assessment, map improvement, model building, the validation/rebuilding/refinement cycle and deposition. Each tool caters to the type of experimental data. The design of Phenix emphasizes the automation of procedures, where possible, to minimize repetitive and time-consuming manual tasks, while default parameters are chosen to encourage best practice. A graphical user interface provides access to many command-line features of Phenix and streamlines the transition between programs, project tracking and re-running of previous tasks