Algorithm engineering for optimal alignment of protein structure distance matrices

Protein structural alignment is an important problem in computational biology. In this paper, we present first successes on provably optimal pairwise alignment of protein inter-residue distance matrices, using the popular Dali scoring function. We introduce the structural alignment problem formally, which enables us to express a variety of scoring functions used in previous work as special cases in a unified framework. Further, we propose the first mathematical model for computing optimal structural alignments based on dense inter-residue distance matrices. We therefore reformulate the problem as a special graph problem and give a tight integer linear programming model. We then present algorithm engineering techniques to handle the huge integer linear programs of real-life distance matrix alignment problems. Applying these techniques, we can compute provably optimal Dali alignments for the very first time

UDP-Galactose 4′-Epimerase Activities toward UDP-Gal and UDP-GalNAc Play Different Roles in the Development of Drosophila melanogaster

In both humans and Drosophila melanogaster, UDP-galactose 4′-epimerase (GALE) catalyzes two distinct reactions, interconverting UDP-galactose (UDP-gal) and UDP-glucose (UDP-glc) in the final step of the Leloir pathway of galactose metabolism, and also interconverting UDP-N-acetylgalactosamine (UDP-galNAc) and UDP-N-acetylglucosamine (UDP-glcNAc). All four of these UDP-sugars serve as vital substrates for glycosylation in metazoans. Partial loss of GALE in humans results in the spectrum disorder epimerase deficiency galactosemia; partial loss of GALE in Drosophila melanogaster also results in galactose-sensitivity, and complete loss in Drosophila is embryonic lethal. However, whether these outcomes in both humans and flies result from loss of one GALE activity, the other, or both has remained unknown. To address this question, we uncoupled the two activities in a Drosophila model, effectively replacing the endogenous dGALE with prokaryotic transgenes, one of which (Escherichia coli GALE) efficiently interconverts only UDP-gal/UDP-glc, and the other of which (Plesiomonas shigelloides wbgU) efficiently interconverts only UDP-galNAc/UDP-glcNAc. Our results demonstrate that both UDP-gal and UDP-galNAc activities of dGALE are required for Drosophila survival, although distinct roles for each activity can be seen in specific windows of developmental time or in response to a galactose challenge. By extension, these data also suggest that both activities might play distinct and essential roles in humans

G03-1501 Prudent Use of Antibiotics in Companion Animals

This NebGuide explains why antibiotics must be used with care and how to prudently use antibiotics to treat companion animals. Antibiotics are used to improve animal health and performance. You, as the animal owner or caregiver, make important decisions about how antibiotics are finally used in companion animals. Antibiotics should be used prudently to ensure they are effective and will continue to benefit man and animals in the future. Are you prepared to make the best decisions about using antibiotics in animals

G03-1485 Guidelines for the Prudent Use of Antibiotics in Food Animals

This NebGuide explains why antibiotics must be used with care and how to prudently use antibiotics to treat food animals. Antibiotics are used to improve animal health and productivity. You, the animal caregiver, make important decisions about how antibiotics are finally used in food producing animals. Antibiotics should be used prudently to ensure they are effective, do not leave residues in food, and will continue to benefit man and animals in the future. Are you prepared to make the best decisions about using antibiotics in animals

Central projections of fibers in the auditory and tensor nerves of cicadas (Homoptera: Cicadidae)

The auditory and tensor nerves of cicadas are mixed nerves containing both afferent and efferent elements. In 17-year cicadas, and in Okanagana rimosa , the auditory nerve contains afferents from body hairs, from the detensor tympani -chordotonal organ, and some 1300–1500 afferents from the hearing organ. Within the fused metathoracic-abdominal ganglionic complex the receptors from both the auditory and tensor nerves form a neuropilar structure that reveals the metameric organization of this complex. A few fibers run anteriorly, projecting into the meso and prothoracic ganglia. Within the ganglionic complex a division of auditory nerve afferents into a dense intermediate and a more diffuse ventral neuropile is observed. In addition, a dorsal motor neuropile is outlined by arborizations of the timbal motor neuron. This neuron is one of several efferent cell types associated with the auditory nerve, and there is an indication that several efferent fibers innervate the timbal muscle. There is anatomical evidence for a possible neuronal coupling between the bilaterally symmetrical large timbal motor neurons. In general, central projections from the auditory and tensor nerves support evidence of a structural “layering” within the CNS of insects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47673/1/441_2004_Article_BF00234327.pd

Predicting molecular vibronic spectra using time-domain analog quantum simulation

Spectroscopy is one of the most accurate probes of the molecular world. However, predicting molecular spectra accurately is computationally difficult because of the presence of entanglement between electronic and nuclear degrees of freedom. Although quantum computers promise to reduce this computational cost, existing quantum approaches rely on combining signals from individual eigenstates, an approach that is difficult to scale because the number of eigenstates grows exponentially with molecule size. Here, we introduce a method for scalable analog quantum simulation of molecular spectroscopy, by performing simulations in the time domain. Our approach can treat more complicated molecular models than previous ones, requires fewer approximations, and can be extended to open quantum systems with minimal overhead. We present a direct mapping of the underlying problem of time-domain simulation of molecular spectra to the degrees of freedom and control fields available in a trapped-ion quantum simulator. We experimentally demonstrate our algorithm on a trapped-ion device, exploiting both intrinsic electronic and motional degrees of freedom, showing excellent quantitative agreement for a single-mode vibronic photoelectron spectrum of SO$_2$.Comment: 13 pages, 8 figure

Genomic analysis of the kiwifruit pathogen Pseudomonas syringae pv. actnidiae provides insight into the origins of an emergent plant disease

The origins of crop diseases are linked to domestication of plants. Most crops were domesticated centuries – even millennia – ago, thus limiting opportunity to understand the concomitant emergence of disease. Kiwifruit (Actinidia spp.) is an exception: domestication began in the 1930s with outbreaks of canker disease caused by P. syringae pv. actinidiae (Psa) first recorded in the 1980s. Based on SNP analyses of two circularized and 34 draft genomes, we show that Psa is comprised of distinct clades exhibiting negligible within-clade diversity, consistent with disease arising by independent samplings from a source population. Three clades correspond to their geographical source of isolation; a fourth, encompassing the Psa-V lineage responsible for the 2008 outbreak, is now globally distributed. Psa has an overall clonal population structure, however, genomes carry a marked signature of within-pathovar recombination. SNP analysis of Psa-V reveals hundreds of polymorphisms; however, most reside within PPHGI-1-like conjugative elements whose evolution is unlinked to the core genome. Removal of SNPs due to recombination yields an uninformative (star-like) phylogeny consistent with diversification of Psa-V from a single clone within the last ten years. Growth assays provide evidence of cultivar specificity, with rapid systemic movement of Psa-V in Actinidia chinensis. Genomic comparisons show a dynamic genome with evidence of positive selection on type III effectors and other candidate virulence genes. Each clade has highly varied complements of accessory genes encoding effectors and toxins with evidence of gain and loss via multiple genetic routes. Genes with orthologs in vascular pathogens were found exclusively within Psa-V. Our analyses capture a pathogen in the early stages of emergence from a predicted source population associated with wild Actinidia species. In addition to candidate genes as targets for resistance breeding programs, our findings highlight the importance of the source population as a reservoir of new disease

Energy consumption of common desktop additive manufacturing technologies

Additive manufacturing (AM), also referred as 3D printing, is a small but fast-growing sub-sector of the manufacturing industry. Concerns over increasing worldwide energy consumption provides an impetus to quantify the energy use of the most common forms of AM technologies. To date, research efforts have focussed on the energy use of industrial AM machines, and little research has been conducted on the numerous low-cost desktop 3D printers. Additionally, there is a gap in our knowledge of how to minimise the energy consumption of desktop 3D printers and how to predict their energy use. To fill this gap, high resolution (1 Hz) power measurements were made for a range of low-cost fused filament fabrication and vat polymerisation desktop 3D printers. The volumetric specific energy use was found to be 24.8 – 85.7 kJ/cm3 and 10.8 – 21.5 kJ/cm3 for fused filament fabrication and vat polymerisation respectively. Semi-empirical equations were developed that can accurately predict the energy use for each printing technology based on simple 3D printing metrics

Evaluating additive manufacturing for the production of custom head supports: A comparison against a commercial head support under static loading conditions

The provision of wheelchair seating accessories, such as head supports, is often limited to the use of commercial products. Additive manufacturing has the potential to produce custom seating components, but there are very few examples of published work. This article reports a method of utilising 3D scanning, computer-aided design and additive manufacturing for the fabrication of a custom head support for a wheelchair. Three custom head supports, of the same shape, were manufactured in nylon using a continuous filament fabrication machine. The custom head supports were tested against an equivalent and widely used commercial head support using ISO 16840-3:2014. The head supports were statically loaded in two configurations, one modelling a posterior force on the inner rear surface and the other modelling a lateral force on the side. The posterior force resulted in failure of the supporting bracketry before the custom head support. A similar magnitude of forces was applied laterally for the custom and commercial head support. When the load was removed, the custom recovered to its original shape while the commercial sustained plastic deformation. The addition of a joint in the head support increased the maximum displacement, 128.6 mm compared to 71.7 mm, and the use of carbon fibre resulted in the head support sustaining a higher force at larger displacements, increase in 30 N. Based on the deformation and recovery characteristics, the results indicate that additive manufacturing could be an appropriate method to produce lighter weight, highly customised, cost-effective and safe head supports for wheelchair users