solveME: fast and reliable solution of nonlinear ME models.

BackgroundGenome-scale models of metabolism and macromolecular expression (ME) significantly expand the scope and predictive capabilities of constraint-based modeling. ME models present considerable computational challenges: they are much (>30 times) larger than corresponding metabolic reconstructions (M models), are multiscale, and growth maximization is a nonlinear programming (NLP) problem, mainly due to macromolecule dilution constraints.ResultsHere, we address these computational challenges. We develop a fast and numerically reliable solution method for growth maximization in ME models using a quad-precision NLP solver (Quad MINOS). Our method was up to 45 % faster than binary search for six significant digits in growth rate. We also develop a fast, quad-precision flux variability analysis that is accelerated (up to 60× speedup) via solver warm-starts. Finally, we employ the tools developed to investigate growth-coupled succinate overproduction, accounting for proteome constraints.ConclusionsJust as genome-scale metabolic reconstructions have become an invaluable tool for computational and systems biologists, we anticipate that these fast and numerically reliable ME solution methods will accelerate the wide-spread adoption of ME models for researchers in these fields

Electronic structure of the molecule based magnet Cu PM(NO3)2 (H2O)2

We present density functional calculations on the molecule based S=1/2 antiferromagnetic chain compound Cu PM(NO3)2 (H2O)2; PM = pyrimidine. The properties of the ferro- and antiferromagnetic state are investigated at the level of the local density approximation and with the hybrid functional B3LYP. Spin density maps illustrate the exchange path via the pyrimidine molecule which mediates the magnetism in the one-dimensional chain. The computed exchange coupling is antiferromagnetic and in reasonable agreement with the experiment. It is suggested that the antiferromagnetic coupling is due to the possibility of stronger delocalization of the charges on the nitrogen atoms, compared to the ferromagnetic case. In addition, computed isotropic and anisotropic hyperfine interaction parameters are compared with recent NMR experiments

Hair Bundle Morphology on Surviving Hair Cells of the Chick Basilar Papilla Exposed to Intense Sound

Exposure to intense sound produces a well-defined patch lesion on the chick basilar papilla in which 30-35% of the short hair cells are lost. The present study compares various aspects of sensory hair bundle morphology on surviving hair cells in the patch lesion with hair bundles from matched locations on nonexposed control papilla immediately after removal from the exposure and 12-days post exposure. The height and thickness of the hairs, the total number of hairs in the bundle, the width of the bundle, and the area and perimeter of the apical surface of the hair cell were quantified from scanning electron microscope photomicrographs. An attempt was also made to determine if there was a consistent microstructure to the pattern of hair cell loss within the lesion area. Similar observations in 12-day recovered ears are also presented. The results indicated that stereocilia height increased and width decreased on surviving hair cells in the exposed ear. The width of the hair bundle, the hair cell surface area, and perimeter also decreased. However, the number of hairs per cell remained unchanged, and there was no evidence of any consistent organization to the hair cell loss within the patch across a number of specimens. These observations indicated that the hair bundles on short hair cells underwent changes as a consequence of intense sound exposure.The results after 12 days of recovery were complicated by developmental changes on the papilla and incomplete maturation of the newly regenerated hair cells. It remains to be seen whether these changes were the result of cell sampling in the sound-damaged ear or were due to true structural alterations within the sensory hairs themselves

Simulation Schiaparelli's Entry and Comparison to Aerothermal Flight Data

The European Space Agency recently flew an entry, descent, and landing demonstrator module called Schiaparelli that entered the atmosphere of Mars on the 19th of October, 2016. The instrumentation suite included heatshield and backshell pressure transducers and thermocouples (known as AMELIA - Atmospheric Mars Entry and Landing Investigations and Analysis) and backshell radiation and direct heat flux-sensing sensors (known as COMARS (Combined Aerothermal and Radiometer Sensors Instrument Package) and ICOTOM (narrow band radiometers)). Due to the failed landing of Schiaparelli, only a subset of the flight data was transmitted before and after plasma black-out. The goal of this paper is to present comparisons of the flight data with calculations from NASA simulation tools, DPLR (Data Parallel Line Relaxation) / NEQAIR (NonEQuilibrium AIr Radiation) and LAURA (Langley Aerothermodynamic Upwind Relaxation Algorithm) / HARA (High-temperature Aerothermodynamic RAdiation ). DPLR and LAURA are used to calculate the flowfield around the vehicle and surface properties, such as pressure and convective heating. The flowfield data are passed to NEQAIR and HARA to calculate the radiative heat flux. Comparisons will be made to the COMARS total heat flux, radiative heat flux and pressure measurements. Results will also be shown against the reconstructed heat flux which was calculated from an inverse analysis of the AMELIA thermocouple data performed by Astrium. Preliminary calculations are presented in this abstract

Strengthening impact assessment: a call for integration and focus

We suggest that the impact assessment community has lost its way based on our observation that impact assessment is under attack because of a perceived lack of efficiency. Specifically, we contend that the proliferation of different impact assessment types creates separate silos of expertise and feeds arguments for not only a lack of efficiency but also a lack of effectiveness of the process through excessive specialisation and a lack of interdisciplinary practice. We propose that the solution is a return to the basics of impact assessment with a call for increased integration around the goal of sustainable development and focus through better scoping. We rehearse and rebut counter arguments covering silo-based expertise, advocacy, democracy, sustainability understanding and communication. We call on the impact assessment community to rise to the challenge of increasing integration and focus, and to engage in the debate about the means of strengthening impact assessment

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Following a severe outbreak of clinical scrapie in 2006–2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated PrP (PrP$^{\rm d}$), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for PrP$^{\rm d}$ in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrP$^{\rm d}$ accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrP$^{\rm d}$ within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrP$^{\rm d}$ in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrP$^{\rm d}$ different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats

The genome sequence and effector complement of the flax rust pathogen Melampsora lini

Rust fungi cause serious yield reductions on crops, including wheat, barley, soybean, coffee, and represent real threats to global food security. Of these fungi, the flax rust pathogen Melampsora lini has been developed most extensively over the past 80 years as a model to understand the molecular mechanisms that underpin pathogenesis. During infection, M. lini secretes virulence effectors to promote disease. The number of these effectors, their function and their degree of conservation across rust fungal species is unknown. To assess this, we sequenced and assembled de novo the genome of M. lini isolate CH5 into 21,130 scaffolds spanning 189 Mbp (scaffold N50 of 31 kbp). Global analysis of the DNA sequence revealed that repetitive elements, primarily retrotransposons, make up at least 45% of the genome. Using ab initio predictions, transcriptome data and homology searches, we identified 16,271 putative protein-coding genes. An analysis pipeline was then implemented to predict the effector complement of M. lini and compare it to that of the poplar rust, wheat stem rust and wheat stripe rust pathogens to identify conserved and species-specific effector candidates. Previous knowledge of four cloned M. lini avirulence effector proteins and two basidiomycete effectors was used to optimize parameters of the effector prediction pipeline. Markov clustering based on sequence similarity was performed to group effector candidates from all four rust pathogens. Clusters containing at least one member from M. lini were further analyzed and prioritized based on features including expression in isolated haustoria and infected leaf tissue and conservation across rust species. Herein, we describe 200 of 940 clusters that ranked highest on our priority list, representing 725 flax rust candidate effectors. Our findings on this important model rust species provide insight into how effectors of rust fungi are conserved across species and how they may act to promote infection on their hosts.This work was funded by a grant from the CSIRO Transformational Biology Capability Platform to Adnane Nemri. Claire Anderson was supported by an ARC Discovery Grant (DP120104044) awarded to David A. Jones and Peter N. Dodds

The functions of self‐harm in young people and their perspectives about future general practitioner‐led care: A qualitative study

Background Self-harm in young people is a serious concern but a deeper understanding of the functions of self-harm in young people can tailor care and inform new clinical interventions to reduce repeat self-harm and suicide risk. General practitioners (GPs), as frontline healthcare professionals, have an important role in managing self-harm in young people. This study aimed to explore the functions of self-harm in young people and their perspectives on future GP-led care. Methods A qualitative study using interviews with young people aged between 16 and 25 years with a personal history of self-harm was conducted. Interviews were transcribed and analysed using reflexive thematic analysis. Findings Four distinct functions were identified: (1) handling emotional states; (2) self-punishment; (3) coping with mental illness and trauma; and (4) positive thoughts and protection. Young people valued GP-led support and felt future GP interventions should include self-help and be personalised. Conclusions These findings support clinicians, including GPs, to explore the functions of self-harm in young people aged 16–25 in a personalised approach to self-harm care. It should be noted that self-harm may serve more than one function for a young person and thus interventions should recognise this. Patient and Public Contribution A group consisting of young people with lived experience of self-harm, carers, the public, and those who work with young people who harm themselves conceived this study idea, informed recruitment methods and the interview topic guide, and supported the interpretation of findings

From supported membranes to tethered vesicles: lipid bilayers destabilisation at the main transition

We report results concerning the destabilisation of supported phospholipid bilayers in a well-defined geometry. When heating up supported phospholipid membranes deposited on highly hydrophilic glass slides from room temperature (i.e. with lipids in the gel phase), unbinding was observed around the main gel to fluid transition temperature of the lipids. It lead to the formation of relatively monodisperse vesicles, of which most remained tethered to the supported bilayer. We interpret these observations in terms of a sharp decrease of the bending rigidity modulus $\kappa$ in the transition region, combined with a weak initial adhesion energy. On the basis of scaling arguments, we show that our experimental findings are consistent with this hypothesis.Comment: 11 pages, 3 figure