How auto-differentiation can improve CT workflows: classical algorithms in a modern framework.

Many of the recent successes of deep learning-based approaches have been enabled by a framework of flexible, composable computational blocks with their parameters adjusted through an automatic differentiation mechanism to implement various data processing tasks. In this work, we explore how the same philosophy can be applied to existing "classical" (i.e., non-learning) algorithms, focusing on computed tomography (CT) as application field. We apply four key design principles of this approach for CT workflow design: end-to-end optimization, explicit quality criteria, declarative algorithm construction by building the forward model, and use of existing classical algorithms as computational blocks. Through four case studies, we demonstrate that auto-differentiation is remarkably effective beyond the boundaries of neural-network training, extending to CT workflows containing varied combinations of classical and machine learning algorithms.

Foam-like phantoms for comparing tomography algorithms.

Tomographic algorithms are often compared by evaluating them on certain benchmark datasets. For fair comparison, these datasets should ideally (i) be challenging to reconstruct, (ii) be representative of typical tomographic experiments, (iii) be flexible to allow for different acquisition modes, and (iv) include enough samples to allow for comparison of data-driven algorithms. Current approaches often satisfy only some of these requirements, but not all. For example, real-world datasets are typically challenging and representative of a category of experimental examples, but are restricted to the acquisition mode that was used in the experiment and are often limited in the number of samples. Mathematical phantoms are often flexible and can sometimes produce enough samples for data-driven approaches, but can be relatively easy to reconstruct and are often not representative of typical scanned objects. In this paper, we present a family of foam-like mathematical phantoms that aims to satisfy all four requirements simultaneously. The phantoms consist of foam-like structures with more than 100000 features, making them challenging to reconstruct and representative of common tomography samples. Because the phantoms are computer-generated, varying acquisition modes and experimental conditions can be simulated. An effectively unlimited number of random variations of the phantoms can be generated, making them suitable for data-driven approaches. We give a formal mathematical definition of the foam-like phantoms, and explain how they can be generated and used in virtual tomographic experiments in a computationally efficient way. In addition, several 4D extensions of the 3D phantoms are given, enabling comparisons of algorithms for dynamic tomography. Finally, example phantoms and tomographic datasets are given, showing that the phantoms can be effectively used to make fair and informative comparisons between tomography algorithms.

Tomosipo: fast, flexible, and convenient 3D tomography for complex scanning geometries in Python.

Tomography is a powerful tool for reconstructing the interior of an object from a series of projection images. Typically, the source and detector traverse a standard path (e.g., circular, helical). Recently, various techniques have emerged that use more complex acquisition geometries. Current software packages require significant handwork, or lack the flexibility to handle such geometries. Therefore, software is needed that can concisely represent, visualize, and compute reconstructions of complex acquisition geometries. We present tomosipo, a Python package that provides these capabilities in a concise and intuitive way. Case studies demonstrate the power and flexibility of tomosipo.

Female-Produced Sex Pheromone of Tetrastichus planipennisi, a Parasitoid Introduced for Biological Control of the Invasive Emerald Ash Borer, Agrilus planipennis.

The Asian eulophid wasp Tetrastichus planipennisi is being released in North America as a biocontrol agent for the emerald ash borer (Agrilus planipennis), a very destructive invasive buprestid beetle that is devastating ash trees (Fraxinus spp.). We identified, synthesized, and tested a female-produced sex pheromone for the wasp. The key component eliciting behavioral responses from male wasps in flight tunnel bioassays was identified as (6S,10S)-(2E,4E,8E)-4,6,8,10-tetramethyltrideca-2,4,8-triene. Female specificity was demonstrated by gas chromatographic (GC) comparison of male and female volatile emissions and whole body extracts. The identification was aided by coupled gas chromatography/mass spectrometry analysis, microchemical reactions, NMR, GC analyses with a chiral stationary phase column, and matching GC retention times and mass spectra with those of synthetic standards. The tetramethyl-triene hydrocarbon was synthesized as a mixture of two enantiomeric pairs of diastereomers, and as the pure insect-produced stereoisomer. In flight-tunnel bioassays, males responded to both the natural pheromone and the chiral synthetic material by upwind flight and landing on the source. In contrast, the mixture of four stereoisomers was not attractive, indicating that one or more of the "unnatural" stereoisomers antagonized attraction. Field trials, using yellow pan traps baited with natural pheromone, captured significantly more male wasps than control traps over a four week trial. The identified pheromone could increase the efficiency and specificity of the current detection methods for Tetrastichus planipennisi and aid in the determination of parasitoid establishment at release sites.

Report on the CCT Supplementary comparison S2 on thermal conductivity measurements of insulating materials by guarded hot plate.

Seven National Metrology Institutes (NMIs) from France, United States, United Kingdom, Russia, Mexico, China and Germany participated in an inter-laboratory comparison on thermal conductivity measurements by the Guarded Hot Plate method. This action was part of a series of supplementary inter-laboratory comparisons (including infrared spectral emittance and thermal diffusivity) sponsored by the Consultative Committee on Thermometry (CCT) Task Group on Thermophysical Quantities (TG-ThQ). The objective of this collaborative work was to strengthen the consistency of thermal conductivity measurements carried out worldwide on low conductive materials. Measurements were conducted successively by all participants on the same sets of specimens of insulating materials (mineral wool and expanded polystyrene) at temperatures ranging from 10 °C to 40 °C, according to the International Standard ISO 8302. This protocol aimed to minimize issues of material variability by circulating the same pairs of specimens among the laboratories following the strict format of a round-robin test program. More than 120 data points (combinations of material, thickness and temperature) were compared. 92 % of the data points were in agreement, with differences to weighted mean values less than the expanded uncertainties calculated from the individual NMI uncertainties and uncertainties related to the comparison process.

Sustainable treatment systems for removal of pharmaceutical residues and other priority persistent substances.

Pharmaceutical residues and other emerging substances commonly summarised as micropollutants pass through wastewater treatment plants (WWTPs) and end up in the receiving waters and sludge. Many studies have investigated the removal efficiency of various techniques but a holistic evaluation of various relevant treatment alternatives regarding both the removal efficiency for various micropollutants, investment and operating costs, environmental impacts and future comprehensiveness is still lacking. This paper provides the results from a large 3-year project about the evaluation of sustainable treatment systems for removal of various micropollutants or disruptive effects at Swedish WWTPs and their environmental, economic and future sustainability. The presented results are based on our own pilot tests and related assessment and modelling efforts and provide a holistic view on advanced treatment of wastewater for removal of micropollutants.

Fluctuations of a membrane nanotube revealed by high-resolution force measurements.

Pulling membrane nanotubes from liposomes presents a powerful method to gain access to membrane mechanics. Here we extend classical optical tweezers studies to infer membrane nanotube dynamics with high spatial and temporal resolution. We first validate our force measurement setup by accurately measuring the bending modulus of EPC membrane in tube pulling experiments. Then we record the position signal of a trapped bead when it is connected, or not, to a tube. We derive the fluctuation spectrum of these signals and find that the presence of a membrane nanotube induces higher fluctuations, especially at low frequencies (10-1000 Hz). We analyse these spectra by taking into account the peristaltic modes of nanotube fluctuations. This analysis provides a new experimental framework for a quantitative study of the fluctuations of nanotubular membrane structures that are present in living cells, and now classically used for in vitro biomimetic approaches.

Discordant phylogenies suggest repeated host shifts in the Fusarium-Euwallacea ambrosia beetle mutualism.

The mutualism between xyleborine beetles in the genus Euwallacea (Coleoptera: Curculionidae: Scolytinae) and members of the Ambrosia Fusarium Clade (AFC) represents one of 11 known evolutionary origins of fungiculture by ambrosia beetles. Female Euwallacea beetles transport fusarial symbionts in paired mandibular mycangia from their natal gallery to woody hosts where they are cultivated in galleries as a source of food. Native to Asia, several exotic Euwallacea species were introduced into the United States and Israel within the past two decades and they now threaten urban landscapes, forests and avocado production. To assess species limits and to date the evolutionary diversification of the mutualists, we reconstructed the evolutionary histories of key representatives of the Fusarium and Euwallacea clades using maximum parsimony and maximum likelihood methods. Twelve species-level lineages, termed AF 1-12, were identified within the monophyletic AFC and seven among the Fusarium-farming Euwallacea. Bayesian diversification-time estimates placed the origin of the Euwallacea-Fusarium mutualism near the Oligocene-Miocene boundary ∼19-24 Mya. Most Euwallacea spp. appear to be associated with one species of Fusarium, but two species farmed two closely related fusaria. Euwallacea sp. #2 in Miami-Dade County, Florida cultivated Fusarium spp. AF-6 and AF-8 on avocado, and Euwallacea sp. #4 farmed Fusarium ambrosium AF-1 and Fusarium sp. AF-11 on Chinese tea in Sri Lanka. Cophylogenetic analyses indicated that the Euwallacea and Fusarium phylogenies were largely incongruent, apparently due to the beetles switching fusarial symbionts (i.e., host shifts) at least five times during the evolution of this mutualism. Three cospeciation events between Euwallacea and their AFC symbionts were detected, but randomization tests failed to reject the null hypothesis that the putative parallel cladogenesis is a stochastic pattern. Lastly, two collections of Euwallacea sp. #2 from Miami-Dade County, Florida shared an identical cytochrome oxidase subunit 1 (CO1) allele with Euwallacea validus, suggesting introgressive hybridization between these species and/or pseudogenous nature of this marker. Results of the present study highlight the importance of understanding the potential for and frequency of host-switching between Euwallacea and members of the AFC, and that these shifts may bring together more aggressive and virulent combinations of these invasive mutualists.

Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients.

BACKGROUND: An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences. METHODS: The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene. RESULTS: We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft-versus-host disease (GVHD) grade II-V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection. CONCLUSION: An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission.

A Culture Method for Darkling Beetles, Blapstinus spp. (Coleoptera:Tenebrionidae).

Darkling beetles, Blapstinus spp., have become a serious pest of Cucurbitaceae crops, especially in California. A culture method was sought to provide large numbers (>500) of adult beetles of known age and sex that could be used for laboratory testing when needed. A method previously developed for Alphitobius diaperinus (Panzer) using a diet of ground chick feed, with apple slices as a moisture source, was modified for use with Blapstinus spp. and then compared with the same method substituting apple slices with zucchini as the moisture source. Rearing boxes set up with apple slices produced significantly more pupae and adults than boxes containing zucchini slices. However, using either zucchini or apples as a moisture source yielded over the target of 500 adults per rearing box. A previous method designed to sex A. diaperinus based on the presence (♀) or absence (♂) of second valvifers in the pupal stage also proved to be effective for sexing the Blapstinus spp.

Deep-learning-based joint rigid and deformable contour propagation for magnetic resonance imaging-guided prostate radiotherapy.

BACKGROUND: Deep learning-based unsupervised image registration has recently been proposed, promising fast registration. However, it has yet to be adopted in the online adaptive magnetic resonance imaging-guided radiotherapy (MRgRT) workflow. PURPOSE: In this paper, we design an unsupervised, joint rigid, and deformable registration framework for contour propagation in MRgRT of prostate cancer. METHODS: Three-dimensional pelvic T2-weighted MRIs of 143 prostate cancer patients undergoing radiotherapy were collected and divided into 110, 13, and 20 patients for training, validation, and testing. We designed a framework using convolutional neural networks (CNNs) for rigid and deformable registration. We selected the deformable registration network architecture among U-Net, MS-D Net, and LapIRN and optimized the training strategy (end-to-end vs. sequential). The framework was compared against an iterative baseline registration. We evaluated registration accuracy (the Dice and Hausdorff distance of the prostate and bladder contours), structural similarity index, and folding percentage to compare the methods. We also evaluated the framework's robustness to rigid and elastic deformations and bias field perturbations. RESULTS: The end-to-end trained framework comprising LapIRN for the deformable component achieved the best median (interquartile range) prostate and bladder Dice of 0.89 (0.85-0.91) and 0.86 (0.80-0.91), respectively. This accuracy was comparable to the iterative baseline registration: prostate and bladder Dice of 0.91 (0.88-0.93) and 0.86 (0.80-0.92). The best models complete rigid and deformable registration in 0.002 (0.0005) and 0.74 (0.43) s (Nvidia Tesla V100-PCIe 32 GB GPU), respectively. We found that the models are robust to translations up to 52 mm, rotations up to 15 ∘ $^\circ$ , elastic deformations up to 40 mm, and bias fields. CONCLUSIONS: Our proposed unsupervised, deep learning-based registration framework can perform rigid and deformable registration in less than a second with contour propagation accuracy comparable with iterative registration.

Male-produced pheromone of Spathius agrili, a parasitoid introduced for the biological control of the invasive emerald ash borer, Agrilus planipennis.

The braconid wasp, Spathius agrili, has been released in the U.S. as a biocontrol agent for the invasive emerald ash borer (Coleoptera: Buprestidae: Agrilus planipennis), a destructive pest of ash trees (Fraxinus spp.). We identified and synthesized seven male-specific volatile compounds. Three of these, dodecanal, (4R,11E)-tetradecen-4-olide, and (Z)-10-heptadecen-2-one, were the key behaviorally active components in flight tunnel bioassays. Male specificity was demonstrated by gas chromatographic comparison of male and female volatile emissions and whole body extracts. Identifications were aided by coupled gas chromatographic-mass spectrometric (GC-MS) analysis, microchemical reactions, NMR, chiral GC analysis, and GC and MS comparison with authentic standards. Both the racemic and chiral forms of the γ-lactone, as well as both E- and Z-isomers were synthesized. Flight tunnel behavioral tests showed positive male and female S. agrili responses to both natural pheromone and synthetic blends, with upwind flight and landing on the source. Large field-cage tests, using yellow sticky traps baited with pheromone, captured approximately 50% of the released male and female wasps in 24-h periods. The use of pheromone-baited traps in the field could simplify the current detection method for determining parasitoid establishment (i.e., laboriously felling and peeling ash trees for recovery of S. agrili from infested EAB larvae).

Follicle development in cryopreserved bitch ovarian tissue grafted to immunodeficient mouse.

The present study evaluated: (1) in vivo follicular development in canine ovarian tissue after slow freezing and xenotransplantation; and (2) the use of erythropoietin (EPO) as an angiogenic factor to optimise the transplantation procedure. Frozen-thawed ovarian tissue from five bitches was grafted into severe combined immunodeficient (SCID) mice (n=47) treated with or without EPO (500 IU kg(-1), once daily for 3 days) (Groups A and B, respectively) and analysed after 0, 1, 8 or 16 weeks. Follicle grade, follicle density, follicle morphology and stromal cells density were assessed by histological analysis, whereas vascularisation of the graft was quantified by immunohistochemistry with anti-α-smooth muscle actin antibody. Despite a massive loss of follicles after grafting, secondary follicle density was higher at 8 and 16 weeks than at 1 week regardless of EPO treatment. EPO significantly improved early follicle morphology and stromal cell density after 8 weeks and blood vessel density at 16 weeks after transplantation (P<0.05). Intact secondary follicles with more than three granulosa cells layers were observed 16 weeks after transplantation. The results suggest that canine ovarian tissue can be successfully preserved by our slow-freezing protocol because the tissue showed follicular growth after xenotransplantation. EPO treatment did not lessen the massive loss of follicles after transplantation.

Absolute configuration of 7-epi-sesquithujene.

7-epi-sesquithujene (1) is a bicyclic sesquiterpene isolated from phoebe oil, an essential oil of the Brazilian walnut tree, Phoebe porosa. It is also produced by stressed ash trees and has been shown to elicit strong electrophysiological responses on emerald ash borer, Agrilus planipennis, antennae. In the course of the development of a synthetic 7-epi-sesquithujene lure for field testing against the emerald ash borer, we found that the absolute configuration of this compound had not been determined. We isolated >95% pure 7-epi-sesquithujene from phoebe oil via successive fractionation and conventional and argentation (HPLC) chromatographies. The specific optical rotation of this compound matched that of a synthetic product of known configuration. We also synthesized two other stereoisomers of sesquithujene and developed a chiral GC method to separate all four. Based on the specific rotation, stereoselective syntheses, and chiral GC analyses, 7-epi-sesquithujene present in phoebe oil and white ash was found to have the 2S,6S,7R absolute configuration.

Male-specific sesquiterpenes from Phyllotreta flea beetles.

Flea beetles in several genera are known to possess male-specific sesquiterpenes, at least some of which serve as aggregation pheromones that attract both sexes. In continuing research on the chemical ecology of Phyllotreta flea beetles, six new male-specific sesquiterpenes were identified, one from P. striolata (hydroxyketone 9) and five from P. pusilla (aldehydes 10-12 and 14 and alcohol 13); both species are crop pests. The minute amounts from beetles provided mass spectra and chromatographic data but were insufficient for complete structure determination. However, it was discovered that the new compounds could all be produced by applying organic reactions to previously identified flea beetle sesquiterpenes, and the resulting, larger amounts of material permitted definitive structure analysis by NMR. Molecular modeling was used in conjunction with NMR to define relative configurations of several newly created stereogenic centers. The absolute configurations of natural 9-14 were established by chiral gas chromatography/mass spectrometry. In electrophysiological tests (GC-EAD) conducted with P. striolata, compound 9 was detected with high sensitivity by the beetle antennae, which is consistent with a pheromonal function. The research opens new possibilities for using behavioral chemicals to monitor or manage these pest species.

Two-carbon homologation of aldehydes and ketones to α,ß-unsaturated aldehydes.

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,ß-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.

Deep denoising for multi-dimensional synchrotron X-ray tomography without high-quality reference data.

Synchrotron X-ray tomography enables the examination of the internal structure of materials at submicron spatial resolution and subsecond temporal resolution. Unavoidable experimental constraints can impose dose and time limits on the measurements, introducing noise in the reconstructed images. Convolutional neural networks (CNNs) have emerged as a powerful tool to remove noise from reconstructed images. However, their training typically requires collecting a dataset of paired noisy and high-quality measurements, which is a major obstacle to their use in practice. To circumvent this problem, methods for CNN-based denoising have recently been proposed that require no separate training data beyond the already available noisy reconstructions. Among these, the Noise2Inverse method is specifically designed for tomography and related inverse problems. To date, applications of Noise2Inverse have only taken into account 2D spatial information. In this paper, we expand the application of Noise2Inverse in space, time, and spectrum-like domains. This development enhances applications to static and dynamic micro-tomography as well as X-ray diffraction tomography. Results on real-world datasets establish that Noise2Inverse is capable of accurate denoising and enables a substantial reduction in acquisition time while maintaining image quality.

Deep learning based classification of dynamic processes in time-resolved X-ray tomographic microscopy.

Time-resolved X-ray tomographic microscopy is an invaluable technique to investigate dynamic processes in 3D for extended time periods. Because of the limited signal-to-noise ratio caused by the short exposure times and sparse angular sampling frequency, obtaining quantitative information through post-processing remains challenging and requires intensive manual labor. This severely limits the accessible experimental parameter space and so, prevents fully exploiting the capabilities of the dedicated time-resolved X-ray tomographic stations. Though automatic approaches, often exploiting iterative reconstruction methods, are currently being developed, the required computational costs typically remain high. Here, we propose a highly efficient reconstruction and classification pipeline (SIRT-FBP-MS-D-DIFF) that combines an algebraic filter approximation and machine learning to significantly reduce the computational time. The dynamic features are reconstructed by standard filtered back-projection with an algebraic filter to approximate iterative reconstruction quality in a computationally efficient manner. The raw reconstructions are post-processed with a trained convolutional neural network to extract the dynamic features from the low signal-to-noise ratio reconstructions in a fully automatic manner. The capabilities of the proposed pipeline are demonstrated on three different dynamic fuel cell datasets, one exploited for training and two for testing without network retraining. The proposed approach enables automatic processing of several hundreds of datasets in a single day on a single GPU node readily available at most institutions, so extending the possibilities in future dynamic X-ray tomographic investigations.

Methyl 6-methylsalicylate: a female-produced pheromone component of the parasitoid wasp Spalangia endius.

Sex-pheromone-related behavior and chemistry were studied in the wasp Spalangia endius Walker (Hymenoptera: Pteromalidae), a pupal parasitoid of the house fly, Musca domestica L. (Diptera: Muscidae). Males responded behaviorally to female extracts by arrestment, whereas females did not arrest to male extracts. In a comparison of male and female extracts by gas chromatography-mass spectrometry (GC-MS), two female-specific compounds were found. One was identified as methyl 6-methylsalicylate (gas chromatographic retention time and mass spectrum versus an authentic standard), but the chemical structure of the second compound is still unknown. Male antennae were sensitive to both compounds in electrophysiological tests (GC-EAD). Males responded behaviorally to methyl 6-methylsalicylate by arrestment, but did not arrest to the second compound. Methyl 6-methylsalicylate has been reported previously from some ant and beetle species, but never from the Pteromalidae. Chemical analysis of the extracts and the male behavioral results are consistent with the hypothesis that methyl 6-methylsalicylate functions as a female-emitted pheromone component at short range, but the exact role of both compounds in intersexual interactions in S. endius remains to be determined.

Fluctuations of a membrane nanotube covered with an actin sleeve.

Many biological functions rely on the reshaping of cell membranes, in particular into nanotubes, which are covered in vivo by dynamic actin networks. Nanotubes are subject to thermal fluctuations, but the effect of these on cell functions is unknown. Here, we form nanotubes from liposomes using an optically trapped bead adhering to the liposome membrane. From the power spectral density of this bead, we study the nanotube fluctuations in the range of membrane tensions measured in vivo. We show that an actin sleeve covering the nanotube damps its high-frequency fluctuations because of the network viscoelasticity. Our work paves the way for further studies of the effect of nanotube fluctuations on cellular functions.