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Improvements in x-ray optics critically depend on the measurement of their optical performance. The knowledge of wavefront aberrations, for example, can be used to improve the fabrication of optical elements or to design phase correctors to compensate for these errors. At present, the characterization of such optics is made using intense x-ray sources, such as synchrotrons. However, the limited access to these facilities can substantially slow down the development process. Improvements in the brightness of lab-based x-ray micro-sources in combination with the development of new metrology methods, particularly ptychographic x-ray speckle tracking, enable characterization of x-ray optics in the lab with a precision and sensitivity not possible before. Here, we present a laboratory setup that utilizes a commercially available x-ray source and can be used to characterize different types of x-ray optics. The setup is used in our laboratory on a routine basis to characterize multilayer Laue lenses of high numerical aperture and other optical elements. This typically includes measurements of the wavefront distortions, optimum operating photon energy, and focal length of the lens. To check the sensitivity and accuracy of this laboratory setup, we compared the results to those obtained at the synchrotron and saw no significant difference. To illustrate the feedback of measurements on performance, we demonstrated the correction of the phase errors of a particular multilayer Laue lens using a 3D printed compound refractive phase plate. [ABSTRACT FROM AUTHOR]

Cell–cell signaling in microorganisms is still poorly characterized. In this Methods paper, we describe a genetic procedure for detecting cell-nonautonomous genetic effects, and in particular cell–cell signaling, termed the chimeric colony assay (CCA). The CCA measures the effect of a gene on a biological response in a neighboring cell. This assay can measure cell autonomy for range of biological activities including transcript or protein accumulation, subcellular localization, and cell differentiation. To date, the CCA has been used exclusively to investigate colony patterning in the budding yeast Saccharomyces cerevisiae. To demonstrate the wider potential of the assay, we applied this assay to two other systems: the effect of Grr1 on glucose repression of GAL1 transcription in yeast and the effect of rpsL on stop-codon translational readthrough in Escherichia coli. We also describe variations of the standard CCA that address specific aspects of cell–cell signaling, and we delineate essential controls for this assay. Finally, we discuss complementary approaches to the CCA. Taken together, this Methods paper demonstrates how genetic assays can reveal and explore the roles of cell–cell signaling in microbial processes. [ABSTRACT FROM AUTHOR]

Epigenetic therapy augments neoadjuvant chemotherapy (NACT) in breast cancer and may aid post-surgical wound healing affected by NACT. Our study investigates: (1) The cytotoxicity of classic paclitaxel chemotherapy on triple negative breast cancer (TNBC) independently and in combination with epigenetic drugs. (2) The sustainable inhibition of breast cancer regrowth following paclitaxel and epigenetic therapies. (3) The effects of paclitaxel with and without epigenetic therapy on the post-treatment viability and wound healing potential of adipose stem cells (ASCs). Cytotoxicity assays were performed on TNBC and ASCs. Cells were treated and recovered in drug-free medium. Cell viability was measured via cell counts and MTT assays. W -ound healing was tested with scratch assays. The combination of epigenetic drugs shows increased toxicity against TNBC cells compared to standard chemotherapy alone. Moreover, the combination of paclitaxel with epigenetic treatments causes cancer toxicity that is sustainable to TNBC cells after the drugs' removal with minimal effect on ASCs wound healing ability. The use of epigenetic drugs in addition to standard chemotherapy is cytotoxic to TNBC cells and prevents post-treatment recovery of TNBC while maintaining ASC wound healing ability. This strategy may be useful in maximizing post-surgical wound healing following NACT in TNBC. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has led to enormous practical and emotional challenges for healthcare workers globally, including NHS staff. Psychological support provisions have been established by an NHS healthcare trust in the North of England, including 1:1 psychological support provided by the in-house psychology team. This study sought to understand how staff experienced the service, what worked well and what could be improved. Five participants who had accessed the staff support service took part in semi-structured interviews. Data were analysed using Interpretative Phenomenological Analysis (IPA). Three main themes emerged from the data: 'The need for a flexible, responsive approach', 'Individual and group benefits' and 'The future of staff support: "we need to invest in staff mentally"'. Accessing the service was seen as personally and professionally rewarding for the NHS staff interviewed. These findings are discussed in relation to the relevant literature. Clinical implications, methodological limitations and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Learning accurate representations of robot models remains a challenging problem, and is typically approached though large, system-specific feature sets. This method inherently introduces practical shortcomings, as interpretability and transferability of the learned model typically decreases as more features are introduced into the learning framework in order to handle increasing task complexity. In this article, we examine the problem of developing transferable learned models for dexterous manipulation that are able to accurately predict the behavior of physically distinct systems without retraining. We introduce the notion of learning from visually-extracted grasp mechanics-based features, which are formulated by combining geometrically-inspired, analytical representations of the gripper into the feature set to more holistically represent the state of varied systems performing manipulation. We characterize the added utility of using such features through simulation and incorporate them into a classifier to predict specific phenomena, or modes of manipulation, that occur during prehensile within-hand movement. Four modes of manipulation—normal (rolling contact), drop, stuck, and sliding—are defined, collected physically, and trained via a self-supervised learning approach. The classifier is first trained on a single sensorless underactuated hand variant for all four modes. We, then, investigate the transferability of the learned classifier on five different planar gripper variants—analyzing applicability of this approach with both online and offline evaluation. [ABSTRACT FROM AUTHOR]

Developmental trajectories regarding the age onset of violence and offending have not routinely considered the role of major mental illness (MMI). In parallel, despite several studies investigating the relationship between MMI, violence and offending, fewer have identified motivational processes that may link illness to these outcomes in a more direct and proximal manner. This study investigates whether subtypes of forensic psychiatric patients deemed Not Criminally Responsible on account of Mental Disorder (N = 91) can be identified based on the age onset of mental illness and offending behavior, and whether information on motivational influences for offending—elicited both from the patient directly and detailed collateral information—contributes to the clinical utility of this typology. Results indicated that most patients reported engaging in violence (51%) or antisocial behaviors (72%) prior to the onset of MMI, but that the index offense(s) resulting in forensic admission were predominantly psychotically motivated. In contrast to patients for whom the onset of MMI occurred prior to offending, patients exhibiting premorbid violence had higher levels of risk and criminogenic need; they were more likely to be diagnosed with personality and substance use disorders, and to have conventional (i.e., non-illness-related) motivations ascribed to their index offense. Findings are consistent with the existing literature regarding subgroups of mentally disordered offenders, but provide new information regarding proximal risk factors for violence through better identification of motivational processes. [ABSTRACT FROM AUTHOR]

Background: Newly emerged mutations within the Plasmodium falciparum chloroquine resistance transporter (PfCRT) can confer piperaquine resistance in the absence of amplified plasmepsin II (pfpm2). In this study, we estimated the prevalence of co-circulating piperaquine resistance mutations in P. falciparum isolates collected in northern Cambodia from 2009 to 2017.Methods: The sequence of pfcrt was determined for 410 P. falciparum isolates using PacBio amplicon sequencing or whole genome sequencing. Quantitative polymerase chain reaction was used to estimate pfpm2 and pfmdr1 copy number.Results: Newly emerged PfCRT mutations increased in prevalence after the change to dihydroartemisinin-piperaquine in 2010, with >98% of parasites harboring these mutations by 2017. After 2014, the prevalence of PfCRT F145I declined, being outcompeted by parasites with less resistant, but more fit PfCRT alleles. After the change to artesunate-mefloquine, the prevalence of parasites with amplified pfpm2 decreased, with nearly half of piperaquine-resistant PfCRT mutants having single-copy pfpm2.Conclusions: The large proportion of PfCRT mutants that lack pfpm2 amplification emphasizes the importance of including PfCRT mutations as part of molecular surveillance for piperaquine resistance in this region. Likewise, it is critical to monitor for amplified pfmdr1 in these PfCRT mutants, as increased mefloquine pressure could lead to mutants resistant to both drugs. [ABSTRACT FROM AUTHOR]

De novo mutations are central for evolution, since they provide the raw material for natural selection by regenerating genetic variation. However, studying de novo mutations is challenging and is generally restricted to model species, so we have a limited understanding of the evolution of the mutation rate and spectrum between closely related species. Here, we present a mutation accumulation (MA) experiment to study de novo mutation in the unicellular green alga Chlamydomonas incerta and perform comparative analyses with its closest known relative, Chlamydomonas reinhardtii. Using whole-genome sequencing data, we estimate that the median single nucleotide mutation (SNM) rate in C. incerta is μ  = 7.6 × 10−10, and is highly variable between MA lines, ranging from μ  = 0.35 × 10−10 to μ  = 131.7 × 10−10. The SNM rate is strongly positively correlated with the mutation rate for insertions and deletions between lines (r  >   0.97). We infer that the genomic factors associated with variation in the mutation rate are similar to those in C. reinhardtii , allowing for cross-prediction between species. Among these genomic factors, sequence context and complexity are more important than GC content. With the exception of a remarkably high C→T bias, the SNM spectrum differs markedly between the two Chlamydomonas species. Our results suggest that similar genomic and biological characteristics may result in a similar mutation rate in the two species, whereas the SNM spectrum has more freedom to diverge. [ABSTRACT FROM AUTHOR]

The process of modeling a series of hand-object parameters is crucial for precise and controllable robotic in-hand manipulation because it enables the mapping from the hand's actuation input to the object's motion to be obtained. Without assuming that most of these model parameters are known a priori or can be easily estimated by sensors, we focus on equipping robots with the ability to actively self-identify necessary model parameters using minimal sensing. Here, we derive algorithms, on the basis of the concept of virtual linkage-based representations (VLRs), to self-identify the underlying mechanics of hand-object systems via exploratory manipulation actions and probabilistic reasoning and, in turn, show that the self-identified VLR can enable the control of precise in-hand manipulation. To validate our framework, we instantiated the proposed system on a Yale Model O hand without joint encoders or tactile sensors. The passive adaptability of the underactuated hand greatly facilitates the self-identification process, because they naturally secure stable hand-object interactions during random exploration. Relying solely on an in-hand camera, our system can effectively self-identify the VLRs, even when some fingers are replaced with novel designs. In addition, we show in-hand manipulation applications of handwriting, marble maze playing, and cup stacking to demonstrate the effectiveness of the VLR in precise in-hand manipulation control. [ABSTRACT FROM AUTHOR]

Humans use all surfaces of the hand for contact-rich manipulation. Robot hands, in contrast, typically use only the fingertips, which can limit dexterity. In this work, we leveraged a potential energy–based whole-hand manipulation model, which does not depend on contact wrench modeling like traditional approaches, to design a robotic manipulator. Inspired by robotic caging grasps and the high levels of dexterity observed in human manipulation, a metric was developed and used in conjunction with the manipulation model to design a two-fingered dexterous hand, the Model W. This was accomplished by simulating all planar finger topologies composed of open kinematic chains of up to three serial revolute and prismatic joints, forming symmetric two-fingered hands, and evaluating their performance according to the metric. We present the best design, an unconventional robot hand capable of performing continuous object reorientation, as well as repeatedly alternating between power and pinch grasps—two contact-rich skills that have often eluded robotic hands—and we experimentally characterize the hand's manipulation capability. This hand realizes manipulation motions reminiscent of thumb–index finger manipulative movement in humans, and its topology provides the foundation for a general-purpose dexterous robot hand. [ABSTRACT FROM AUTHOR]

Dystonia is a chronic and incurable movement disorder. This qualitative study aimed to enhance understanding of the condition by exploring the experience of living with dystonia. Interpretative phenomenological analysis was used to analyse data gathered through semi-structured interviews. Eight participants were recruited via a UK-based dystonia charity. Three superordinate themes emerged from the data: (1) dealing with ignorance and uncertainty: navigating health services with a rare, poorly understood condition; (2) the challenge of social isolation: overcoming barriers to positive social identity; and (3) fear of psychological explanations: the impact of stigmatised attitudes towards psychological explanations for dystonia symptoms. Coping with a rare and chronic condition led to participants feeling isolated and stigmatised by health care services and their communities. Participants were able to overcome this challenge to their identities through the use of social support, particularly from other people with dystonia. Recommendations for reducing the stigmatising experiences of people with dystonia can help to ease the process of adjustment to the illness and enable people to pursue meaningful lives and positive identities. Recommendations for research are aimed at increasing knowledge about these processes. Dystonia has a pervasive, negative impact on the lives of people with the condition. The struggle for diagnosis marks the beginning of a period of psychological adjustment, the difficulty of which is compounded by social isolation and stigma. Support groups and peer interaction help people to integrate dystonia into their concept of a meaningful life and identity. Health professionals should play a pivotal role in assisting patients during the process of adjustment and on-going self-management through sensitive communication and signposting to wider support services. [ABSTRACT FROM AUTHOR]

BACKGROUND: To date, we lack U.S. data on the effects of the long-used Russian tilt-table training protocol known as the Russian pre-launch tilt-table training protocol on internal jugular vein cross sectional area (IJV-CSA) in microgravity. CASE REPORT: A case study of a single healthy male astronaut volunteer was used for this study. The right IJV-CSA was measured using real time ultrasound at set times throughout the Russian pre-launch tilt-table training protocol, a method of physiological preparation for microgravity using tilt-table training. In microgravity, the subject's right IJV-CSA was measured again for comparison. The mean difference from in-flight right IJV-CSA for pre-tilt (0°) was 20.438 cm2, for 215° was 0.887 cm2, for 230° was 0.864 cm2, for +50° was 21.15 cm2, and for post-tilt (0°) the difference was 20.305 cm2. DISCUSSION: The cross-sectional areas of the subject's right IJV-CSA were significantly different between in-flight values and several angles of the Russian tilt-table protocol, except for the 0° measurement. In summary, this case-study represents the first time IJV-CSA has been compared between various angles of a tilt-table training protocol and microgravity in the same astronaut subject. The findings support prior cohort studies studying the same principles. Further investigation is merited; both to better describe the relationship between the cardiovascular effects of tilt-table simulations of microgravity and their correlating in-flight values, and to evaluate and study the Russian tilt-table protocol effects on cardiovascular physiology from a training and preparation perspective. [ABSTRACT FROM AUTHOR]

A phasing algorithm for macromolecular crystallography is proposed that utilizes diffraction data from multiple crystal forms – crystals of the same molecule with different unit‐cell packings (different unit‐cell parameters or space‐group symmetries). The approach is based on the method of iterated projections, starting with no initial phase information. The practicality of the method is demonstrated by simulation using known structures that exist in multiple crystal forms, assuming some information on the molecular envelope and positional relationships between the molecules in the different unit cells. With incorporation of new or existing methods for determination of these parameters, the approach has potential as a method for ab initio phasing. [ABSTRACT FROM AUTHOR]

Polypropylene as one of the world's top commodity polymers is also widely used in the textile industry. However, its non-polar nature and partially crystalline structure significantly complicate the process of industrial coloring of polypropylene. Currently, textiles made of polypropylene or with a significant proportion of polypropylene are dyed under quite harsh conditions, including the use of high pressures and temperatures, which makes this process energy intensive. This research presents a three-step synthesis of coloring agents, capable of adhering onto synthetic polypropylene yarns without harsh energy-consuming conditions. This is possible by encapsulation of organic pigments using trimethoxyphenylsilane, introduction of surface double bonds via modification of the silica shell with trimethoxysilylpropylmethacrylate and final attachment of highly adhesive anchor peptides using thiol-ene chemistry. We demonstrate the applicability of this approach by dyeing polypropylene yarns in a simple process under ambient conditions after giving a step-by-step guide for the synthesis of these new dyeing agents. Finally, the successful dyeing of the yarns is visualized, and its practicability is discussed. [ABSTRACT FROM AUTHOR]

In recent years, X‐ray speckle‐tracking techniques have emerged as viable tools for wavefront metrology and sample imaging applications. These methods are based on the measurement of near‐field images. Thanks to their simple experimental setup, high angular sensitivity and compatibility with low‐coherence sources, these methods have been actively developed for use with synchrotron and laboratory light sources. Not only do speckle‐tracking techniques give the potential for high‐resolution imaging, but they also provide rapid and robust characterization of aberrations of X‐ray optical elements, focal spot profiles, and sample position and transmission properties. In order to realize these capabilities, software implementations are required that are equally rapid and robust. To address this need, a software suite has been developed for the ptychographic X‐ray speckle‐tracking technique, an X‐ray speckle‐based method suitable for highly divergent wavefields. The software suite is written in Python 3, with an OpenCL back end for GPU and multi‐CPU core processing. It is accessible as a Python module, through the command line or through a graphical user interface, and is available as source code under Version 3 or later of the GNU General Public License. [ABSTRACT FROM AUTHOR]

The classical definition posits hybrid sterility as a phenomenon when two parental taxa each of which is fertile produce a hybrid that is sterile. The first hybrid sterility gene in vertebrates, Prdm9 , coding for a histone methyltransferase, was identified in crosses between two laboratory mouse strains derived from Mus mus musculus and M. m. domesticus subspecies. The unique function of PRDM9 protein in the initiation of meiotic recombination led to the discovery of the basic molecular mechanism of hybrid sterility in laboratory crosses. However, the role of this protein as a component of reproductive barrier outside the laboratory model remained unclear. Here, we show that the Prdm9 allelic incompatibilities represent the primary cause of reduced fertility in intersubspecific hybrids between M. m. musculus and M. m. domesticus including 16 musculus and domesticus wild-derived strains. Disruption of fertility phenotypes correlated with the rate of failure of synapsis between homologous chromosomes in meiosis I and with early meiotic arrest. All phenotypes were restored to normal when the domesticus Prdm9dom2 allele was substituted with the Prdm9dom2H humanized variant. To conclude, our data show for the first time the male infertility of wild-derived musculus and domesticus subspecies F1 hybrids controlled by Prdm9 as the major hybrid sterility gene. The impairment of fertility surrogates, testes weight and sperm count, correlated with increasing difficulties of meiotic synapsis of homologous chromosomes and with meiotic arrest, which we suppose reflect the increasing asymmetry of PRDM9-dependent DNA double-strand breaks. [ABSTRACT FROM AUTHOR]

We consider the problem of in-hand dexterous manipulation with a focus on unknown or uncertain hand–object parameters, such as hand configuration, object pose within hand, and contact positions. In particular, in this work we formulate a generic framework for hand–object configuration estimation using underactuated hands as an example. Owing to the passive reconfigurability and the lack of encoders in the hand's joints, it is challenging to estimate, plan, and actively control underactuated manipulation. By modeling the grasp constraints, we present a particle filter-based framework to estimate the hand configuration. Specifically, given an arbitrary grasp, we start by sampling a set of hand configuration hypotheses and then randomly manipulate the object within the hand. While observing the object's movements as evidence using an external camera, which is not necessarily calibrated with the hand frame, our estimator calculates the likelihood of each hypothesis to iteratively estimate the hand configuration. Once converged, the estimator is used to track the hand configuration in real time for future manipulations. Thereafter, we develop an algorithm to precisely plan and control the underactuated manipulation to move the grasped object to desired poses. In contrast to most other dexterous manipulation approaches, our framework does not require any tactile sensing or joint encoders, and can directly operate on any novel objects, without requiring a model of the object a priori. We implemented our framework on both the Yale Model O hand and the Yale T42 hand. The results show that the estimation is accurate for different objects, and that the framework can be easily adapted across different underactuated hand models. In the end, we evaluated our planning and control algorithm with handwriting tasks, and demonstrated the effectiveness of the proposed framework. [ABSTRACT FROM AUTHOR]

The deterioration of both the signal‐to‐noise ratio and the spatial resolution in the electron‐density distribution reconstructed from diffraction intensities collected at different orientations of a sample is analysed theoretically with respect to the radiation damage to the sample and the variations in the X‐ray intensities illuminating different copies of the sample. The simple analytical expressions and numerical estimates obtained for models of radiation damage and incident X‐ray pulses may be helpful in planning X‐ray free‐electron laser (XFEL) imaging experiments and in analysis of experimental data. This approach to the analysis of partially coherent X‐ray imaging configurations can potentially be used for analysis of other forms of imaging where the temporal behaviour of the sample and the incident intensity during exposure may affect the inverse problem of sample reconstruction. [ABSTRACT FROM AUTHOR]

Among the physiological consequences of extended spaceflight are loss of skeletal muscle and bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. Here, we used both genetic and pharmacological approaches to investigate the effect of targeting MSTN/activin A signaling in mice that were sent to the International Space Station. Wild type mice lost significant muscle and bone mass during the 33 d spent in microgravity. Muscle weights of Mstn −/− mice, which are about twice those of wild type mice, were largely maintained during spaceflight. Systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions. [ABSTRACT FROM AUTHOR]

The ever‐increasing brightness of synchrotron radiation sources demands improved X‐ray optics to utilize their capability for imaging and probing biological cells, nano‐devices and functional matter on the nanometre scale with chemical sensitivity. Hard X‐rays are ideal for high‐resolution imaging and spectroscopic applications owing to their short wavelength, high penetrating power and chemical sensitivity. The penetrating power that makes X‐rays useful for imaging also makes focusing them technologically challenging. Recent developments in layer deposition techniques have enabled the fabrication of a series of highly focusing X‐ray lenses, known as wedged multi‐layer Laue lenses. Improvements to the lens design and fabrication technique demand an accurate, robust, in situ and at‐wavelength characterization method. To this end, a modified form of the speckle tracking wavefront metrology method has been developed. The ptychographic X‐ray speckle tracking method is capable of operating with highly divergent wavefields. A useful by‐product of this method is that it also provides high‐resolution and aberration‐free projection images of extended specimens. Three separate experiments using this method are reported, where the ray path angles have been resolved to within 4 nrad with an imaging resolution of 45 nm (full period). This method does not require a high degree of coherence, making it suitable for laboratory‐based X‐ray sources. Likewise, it is robust to errors in the registered sample positions, making it suitable for X‐ray free‐electron laser facilities, where beam‐pointing fluctuations can be problematic for wavefront metrology. [ABSTRACT FROM AUTHOR]

This paper builds on recent studies of institutional diversity in Australian tertiary education by modifying this model and using it to profile Australian pathway providers. The results offer insight into the role and work of this under-represented part of Australian tertiary education, as well as highlighting key strategic issues for these institutions and encourages a self-reflexive stance towards profiling methodologies. [ABSTRACT FROM AUTHOR]

Interactions with an object during within-hand manipulation (WIHM) constitutes an assortment of gripping, sliding, and pivoting actions. In addition to manipulation benefits, the re-orientation and motion of the objects within-the-hand also provides a rich array of additional haptic information via the interactions to the sensory organs of the hand. In this article, we utilize variable friction (VF) robotic fingers to execute a rolling WIHM on a variety of objects, while recording ‘proprioceptive’ actuator data, which is then used for object classification (i.e., without tactile sensors). Rather than hand-picking a select group of features for this task, our approach begins with 66 general features, which are computed from actuator position and load profiles for each object-rolling manipulation, based on gradient changes. An Extra Trees classifier performs object classification while also ranking each feature's importance. Using only the six most-important ‘Key Features’ from the general set, a classification accuracy of 86% was achieved for distinguishing the six geometric objects included in our data set. Comparatively, when all 66 features are used, the accuracy is 89.8%. [ABSTRACT FROM AUTHOR]

Human behavior is dependent on the ability of neuronal circuits to predict the outside world. Neuronal circuits in early visual areas make these predictions based on internal models that are delivered via non-feedforward connections. Despite our extensive knowledge of the feedforward sensory features that drive cortical neurons, we have a limited grasp on the structure of the brain's internal models. Progress in neuroscience therefore depends on our ability to replicate the models that the brain creates internally. Here we record human fMRI data while presenting partially occluded visual scenes. Visual occlusion allows us to experimentally control sensory input to subregions of visual cortex while internal models continue to influence activity in these regions. Because the observed activity is dependent on internal models, but not on sensory input, we have the opportunity to map visual features conveyed by the brain's internal models. Our results show that activity related to internal models in early visual cortex are more related to scene-specific features than to categorical or depth features. We further demonstrate that behavioral line drawings provide a good description of internal model structure representing scene-specific features. These findings extend our understanding of internal models, showing that line drawings provide a window into our brains' internal models of vision. [ABSTRACT FROM AUTHOR]

Faithful segregation of homologous chromosomes at meiosis requires pairing and recombination. In taxa with dimorphic sex chromosomes, pairing between them in the heterogametic sex is limited to a narrow interval of residual sequence homology known as the pseudoautosomal region (PAR). Failure to form the obligate crossover in the PAR is associated with male infertility in house mice (Mus musculus) and humans. Yet despite this apparent functional constraint, the boundary and organization of the PAR is highly variable in mammals, and even between subspecies of mice. Here, we estimate the genetic map in a previously documented expansion of the PAR in the M. musculus castaneus subspecies and show that the local recombination rate is 100-fold higher than the autosomal background. We identify an independent shift in the PAR boundary in the M. musculus musculus subspecies and show that it involves a complex rearrangement, but still recombines in heterozygous males. Finally, we demonstrate pervasive copy-number variation at the PAR boundary in wild populations of M. m. domesticus, M. m. musculus, and M. m. castaneus. Our results suggest that the intensity of recombination activity in the PAR, coupled with relatively weak constraints on its sequence, permit the generation and maintenance of unusual levels of polymorphism in the population of unknown functional significance. [ABSTRACT FROM AUTHOR]

The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD+) by the mycobacterial catalase-peroxidase enzyme, KatG, was known to be the major component of the mode of action of isoniazid (INH), an anti-tuberculosis drug. However, there are other enzymes that may catalyze this reaction. We have previously reported that neutrophil myeloperoxidase (MPO) is capable of metabolizing INH through the formation of INH-NAD+ adduct, which could be attributed to being a possible mode of action of INH. However, eosinophilic infiltration of the lungs is more pronounced and characteristic of granulomas in Mycobacterium tuberculosis -infected patients. Thus, the aim of the present study is to investigate the role of eosinophil peroxidase (EPO), a key eosinophil enzyme, during INH metabolism and the formation of its active metabolite, INH-NAD+ using purified EPO and eosinophils isolated from asthmatic donors. UV–Vis spectroscopy revealed INH oxidation by EPO led to a new product (λ max = 326 nm) in the presence of NAD+. This adduct was confirmed to be INH-NAD+ using LC-MS analysis where the intact adduct was detected (m / z = 769). Furthermore, EPO catalyzed the oxidation of INH and formed several free radical intermediates as assessed by electron paramagnetic resonance (EPR) spin-trapping; a carbon-centred radical, which is considered to be the reactive metabolite that binds with NAD+, was found when superoxide dismutase was included in the reaction. Our findings suggest that eosinophilic EPO may also play a role in the pharmacological activity of INH through the formation of INH-NAD+ adduct, and supports further evidence that human cells and enzymes are capable of producing the active metabolite involved in tuberculosis treatment. Image 1 • Eosinophil peroxidase (EPO) oxidizes isoniazid (INH). • Purified EPO formed a new product between INH and NAD+. • A carbon radical, formed by catalytic oxidation of INH by EPO, binds with NAD+. • EPO may contribute to the activity of INH by forming INH-NAD+ adduct. [ABSTRACT FROM AUTHOR]

In this article I offer an account of normative thought inspired by Plato's proposal in the Theaetetus that judgement is 'speech spoken ... silently.' After arguing that force conventionalism is the speech act theory best suited for modeling dialogic inner speech, I close the article by sketching the picture of normative thought that results. Though I defend a particular theory of normative speech elsewhere, the core insights of this article can be used by other theorists as well. The arguments offered here also serve as an important step forward for the more general program of using social speech to better understand thought. [ABSTRACT FROM AUTHOR]

To date X‐ray protein crystallography is the most successful technique available for the determination of high‐resolution 3D structures of biological molecules and their complexes. In X‐ray protein crystallography the structure of a protein is refined against the set of observed Bragg reflections from a protein crystal. The resolution of the refined protein structure is limited by the highest angle at which Bragg reflections can be observed. In addition, the Bragg reflections alone are typically insufficient (by a factor of two) to determine the structure ab initio, and so prior information is required. Crystals formed from an imperfect packing of the protein molecules may also exhibit continuous diffraction between and beyond these Bragg reflections. When this is due to random displacements of the molecules from each crystal lattice site, the continuous diffraction provides the necessary information to determine the protein structure without prior knowledge, to a resolution that is not limited by the angular extent of the observed Bragg reflections but instead by that of the diffraction as a whole. This article presents an iterative projection algorithm that simultaneously uses the continuous diffraction as well as the Bragg reflections for the determination of protein structures. The viability of this method is demonstrated on simulated crystal diffraction. This article reports on the combined use of Bragg reflections and diffuse scatter for structure determination in crystallography. [ABSTRACT FROM AUTHOR]

Bicuspid aortic valve and coarctation of the aorta are risk factors for infective endocarditis and endarteritis. We describe a case of a 4-year-old boy whose severe aortic coarctation was diagnosed only when he presented with endarteritis due to Streptococcus pneumoniae , which evolved into a mycotic pseudoaneurysm requiring urgent repair. • Mycotic (pseudo-)aneurysm of the aorta is very rare in children but is associated with aortic coarctation. • Prompt recognition is important, as surgical repair is usually required. • Sensitivity of transthoracic echocardiography is limited so multimodal imaging is useful for diagnosis. • We describe a case of mycotic pseudoaneurysm due to a non-vaccine strain of Streptococcus pneumoniae in a 4 year old boy. [ABSTRACT FROM AUTHOR]

• COVID-19 patients are at increased risk of thromboembolic complications. • Escalated-dose thromboprophylaxis may help reduce the rate of thromboembolic events. • The bleeding risk is highest for patients treated with therapeutic anticoagulation. [ABSTRACT FROM AUTHOR]

We study the computational power of deciding whether a given truth table can be described by a circuit of a given size (the minimum circuit size problem, or MCSP for short) and of the variant denoted as MKTP, where circuit size is replaced by a polynomially related Kolmogorov measure. Prior to our work, all reductions from supposedly intractable problems to MCSP/MKTP hinged on the power of MCSP/MKTP to distinguish random distributions from distributions produced by hardness-based pseudorandom generator constructions. We develop a fundamentally different approach inspired by the well-known interactive proof system for the complement of graph isomorphism (GI). It yields a randomized reduction with zero-sided error from GI to MKTP. We generalize the result and show that GI can be replaced by any isomorphism problem for which the underlying group satisfies some elementary properties. Instantiations include linear code equivalence, permutation group conjugacy, and matrix subspace conjugacy. Along the way we develop encodings of isomorphism classes that are efficiently decodable and achieve compression that is at or near the information-theoretic optimum; those encodings may be of independent interest. [ABSTRACT FROM AUTHOR]

High‐resolution Bragg diffraction from aerosolized single granulovirus nanocrystals using an X‐ray free‐electron laser is demonstrated. The outer dimensions of the in‐vacuum aerosol injector components are identical to conventional liquid‐microjet nozzles used in serial diffraction experiments, which allows the injector to be utilized with standard mountings. As compared with liquid‐jet injection, the X‐ray scattering background is reduced by several orders of magnitude by the use of helium carrier gas rather than liquid. Such reduction is required for diffraction measurements of small macromolecular nanocrystals and single particles. High particle speeds are achieved, making the approach suitable for use at upcoming high‐repetition‐rate facilities. [ABSTRACT FROM AUTHOR]

Poly(ethylene terephthalate) (PET) was treated with vacuum UV (VUV) (λ= 104.8 and 106.7 nm) photo-oxidation using a microwave (MW) plasma of Ar as the radiation source and the results were compared to treatment with O atoms produced from a remote MW plasma of a gaseous mixture of Ar-O2in the absence of radiation. X-ray photo-electron spectroscopy (XPS) detected a lower saturation level for the atomic % of O with VUV photo-oxidation (32 at%) than with O atom treatment (34 at% O). The C 1s curve fitting results for both treatment methods show a decrease in aromatic sp2carbons and an increase in the amount of carbon-oxygen bonding due to the formation of the carbonyl (C=O) and carbonate-like (O-(C=O)-O) moieties for VUV photo-oxidation; and C-O-C, C=O, and O-C=O moieties for O atom treatment, respectively. Advancing water contact angle measurements showed more of an increase in hydrophilicity with the O atom treated samples than VUV photo-oxidation. Atomic Force Microscopy images displayed smoother surfaces after VUV photo-oxidation while O atom treatment resulted in insignificant changes in surface roughness. Rinsing the treated surfaces with ethanol solvent partially decreased the at% O indicating the formation of a weak boundary during treatment. [ABSTRACT FROM AUTHOR]

In this essay, I propose a novel hybrid metanormative theory. According to this theory, speakers making normative claims express both cognitive and motivational attitudes in virtue of the constitutive norms of the particular speech acts they perform. This view has four principal virtues: (1) it is consistent with traditional semantic theories, (2) it supports a form of motivational judgment internalism that does justice to externalist intuitions, (3) it illuminates the connection between normative language and normative thought, and (4) it explains how speakers can express different conative states when speaking in different normative domains. In the first section, I discuss the theories of Stephen Finlay and David Copp. I show that they each come very close to having it both ways but ultimately fail. Understanding the shortcomings of these views is instrumental to a clear presentation of my own Hybrid Speech Act theory in section two. In the final section, I demonstrate how my view achieves its four advantages. [ABSTRACT FROM AUTHOR]

Quantitative trait locus (QTL) analyses of intercross populations between widely used mouse inbred strains provide a powerful approach for uncovering genetic factors that influence susceptibility to atherosclerosis. Epistatic interactions are common in complex phenotypes and depend on genetic backgrounds. To dissect genetic architecture of atherosclerosis, we analyzed F2 progeny from a cross between apolipoprotein E-null mice on DBA/2J (DBA-apoE) and C57BL/6J (B6-apoE) genetic backgrounds and compared the results with those from two previous F2 crosses of apolipoprotein E-null mice on 129S6/SvEvTac (129-apoE) and DBA-apoE backgrounds, and B6-apoE and 129-apoE backgrounds. In these round-robin crosses, in which each parental strain was crossed with two others, large-effect QTLs are expected to be detectable at least in two crosses. On the other hand, observation of QTLs in one cross only may indicate epistasis and/or absence of statistical power. For atherosclerosis at the aortic arch, Aath4 on chromosome (Chr)2:66 cM follows the first pattern, with significant QTL peaks in (DBAx129)F2 and (B6xDBA)F2 mice but not in (B6x129)F2 mice. We conclude that genetic variants unique to DBA/2J at Aath4 confer susceptibility to atherosclerosis at the aortic arch. A similar pattern was observed for Aath5 on chr10:35 cM, verifying that the variants unique to DBA/2J at this locus protect against arch plaque development. However, multiple loci, including Aath1 (Chr1:49 cM), and Aath2 (Chr1:70 cM) follow the second type of pattern, showing significant peaks in only one of the three crosses (B6-apoE x 129-apoE). As for atherosclerosis at aortic root, the majority of QTLs, including Ath29 (Chr9:33 cM), Ath44 (Chr1:68 cM) and Ath45 (Chr2:83 cM), was also inconsistent, being significant in only one of the three crosses. Only the QTL on Chr7:37 cM was consistently suggestive in two of the three crosses. Thus QTL analysis of round-robin crosses revealed the genetic architecture of atherosclerosis. [ABSTRACT FROM AUTHOR]

Pontoscolex corethrurus (Müller, 1857) plays an important role in tropical soil ecosystems and has been widely used as an animal model for a large variety of ecological studies, in particular due to its common presence and generally high abundance in human-disturbed tropical soils. In this study we describe the complete mitochondrial genome of the peregrine earthworm P. corethrurus. This is the first record of a mitochondrial genome within the Rhinodrilidae family. Its mitochondrial genome is 14 835 bp in length containing 37 genes (13 protein-coding genes (PCG), 2 rRNA genes and 22 tRNA genes). It has the same gene content and structure as in other sequenced earthworms, but unusual among invertebrates it has several overlapping open reading frames. All genes are encoded on the same strand. Most of the PCGs use ATG as the start codon except for ND3, which uses GTG as the start codon. The A+T content of the mitochondrial genome is 59.9% (31.8% A, 28.1% T, 14.6% G, and 25.6% for C). The annotated genome sequence has been deposited in GenBank under the accession number KT988053. [ABSTRACT FROM AUTHOR]

The intensities of far-field diffraction patterns of orientationally aligned molecules obey Wilson statistics, whether those molecules are in isolation (giving rise to a continuous diffraction pattern) or arranged in a crystal (giving rise to Bragg peaks). Ensembles of molecules in several orientations, but uncorrelated in position, give rise to the incoherent sum of the diffraction from those objects, modifying the statistics in a similar way as crystal twinning modifies the distribution of Bragg intensities. This situation arises in the continuous diffraction of laser-aligned molecules or translationally disordered molecular crystals. This paper develops the analysis of the intensity statistics of such continuous diffraction to obtain parameters such as scaling, beam coherence and the number of contributing independent object orientations. When measured, continuous molecular diffraction is generally weak and accompanied by a background that far exceeds the strength of the signal. Instead of just relying upon the smallest measured intensities or their mean value to guide the subtraction of the background, it is shown how all measured values can be utilized to estimate the background, noise and signal, by employing a modified `noisy Wilson' distribution that explicitly includes the background. Parameters relating to the background and signal quantities can be estimated from the moments of the measured intensities. The analysis method is demonstrated on previously published continuous diffraction data measured from crystals of photosystem II [Ayyer et al. (2016), Nature, 530, 202-206]. [ABSTRACT FROM AUTHOR]

After a functional analysis yielded undifferentiated results, a subsequent assessment suggested self-injury exhibited by a young boy with autism was sensitive to physical restraint. Canvas arm splints with metal stays were initially effective to reduce self-injury. Although we successfully faded the number of stays in each sleeve to 3, self-injury reemerged. We then used a withdrawal design to evaluate a behind-the-back belt connected to the arm splints. When the belt and splints were on, self-injury did not occur. When the belt was removed, self-injury increased, even though the splints remained intact. Finally, we faded the length of the belt to allow increased range of motion, and rates of self-injury remained low. [ABSTRACT FROM AUTHOR]

Meiotic recombination is an essential feature of sexual reproduction that ensures faithful segregation of chromosomes and redistributes genetic variants in populations. Multiparent populations such as the Diversity Outbred (DO) mouse stock accumulate large numbers of crossover (CO) events between founder haplotypes, and thus present a unique opportunity to study the role of genetic variation in shaping the recombination landscape. We obtained high-density genotype data from 6886 DO mice, and localized 2.2 million CO events to intervals with a median size of 28 kb. The resulting sex-averaged genetic map of the DO population is highly concordant with large-scale (order 10 Mb) features of previously reported genetic maps for mouse. To examine fine-scale (order 10 kb) patterns of recombination in the DO, we overlaid putative recombination hotspots onto our CO intervals. We found that CO intervals are enriched in hotspots compared to the genomic background. However, as many as 26% of CO intervals do not overlap any putative hotspots, suggesting that our understanding of hotspots is incomplete. We also identified coldspots encompassing 329 Mb, or 12% of observable genome, in which there is little or no recombination. In contrast to hotspots, which are a few kilobases in size, and widely scattered throughout the genome, coldspots have a median size of 2.1 Mb and are spatially clustered. Coldspots are strongly associated with copy-number variant (CNV) regions, especially multi-allelic clusters, identified from whole-genome sequencing of 228 DO mice. Genes in these regions have reduced expression, and epigenetic features of closed chromatin in male germ cells, which suggests that CNVs may repress recombination by altering chromatin structure in meiosis. Our findings demonstrate how multiparent populations, by bridging the gap between large-scale and fine-scale genetic mapping, can reveal new features of the recombination landscape. [ABSTRACT FROM AUTHOR]

The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 303 coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 6 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (.10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources. [ABSTRACT FROM AUTHOR]

Objective: Towards Safer Radiotherapy recommended that radiotherapy (RT) centres should have protocols in place for in vivo dosimetry (IVD) monitoring at the beginning of patient treatment courses (Donaldson S. Towards safer radiotherapy. R Coll Radiol 2008). This report determines IVD implementation in the UK in 2014, the methods used and makes recommendations on future use. Methods: Evidence from peer-reviewed journals was used in conjunction with the first survey of UK RT centre IVD practice since the publication of Towards Safer Radiotherapy. In March 2014, profession-specific questionnaires were sent to radiographer, clinical oncologist and physics staff groups in each of the 66 UK RT centres. Results: Response rates from each group were 74%, 45% and 74%, respectively. 73% of RT centres indicated that they performed IVD. Diodes are the most popular IVD device. Thermoluminescent dosimeter (TLD) is still in use in a number of centres but not as a sole modality, being used in conjunction with diodes and/or electronic portal imaging device (EPID). The use of EPID dosimetry is increasing and is considered of most potential value for both geometric and dosimetric verification. Conclusion: Owing to technological advances, such as electronic data transfer, independent monitor unit checking and daily image-guided radiotherapy, the overall risk of adverse treatment events in RT has been substantially reduced. However, the use of IVD may prevent a serious radiation incident. Point dose IVD is not considered suited to the requirements of verifying advanced RT techniques, leaving EPID dosimetry as the current modality likely to be developed as a future standard. [ABSTRACT FROM AUTHOR]

Wild-derived mouse inbred strains are becoming increasingly popular for complex traits analysis, evolutionary studies, and systems genetics. Here, we report the whole-genome sequencing of two wild-derived mouse inbred strains, LEWES/EiJ and ZALENDE/EiJ, of Mus musculus domesticus origin. These two inbred strains were selected based on their geographic origin, karyotype, and use in ongoing research. We generated 14× and 18× coverage sequence, respectively, and discovered over 1.1 million novel variants, most of which are private to one of these strains. This report expands the number of wild-derived inbred genomes in the Mus genus from six to eight. The sequence variation can be accessed via an online query tool; variant calls (VCF format) and alignments (BAM format) are available for download from a dedicated ftp site. Finally, the sequencing data have also been stored in a lossless, compressed, and indexed format using the multi-string Burrows-Wheeler transform. All data can be used without restriction. [ABSTRACT FROM AUTHOR]

Gene duplication and loss are major sources of genetic polymorphism in populations, and are important forces shaping the evolution of genome content and organization. We have reconstructed the origin and history of a 127-kbp segmental duplication, R2d, in the house mouse (Mus musculus). R2d contains a single protein-coding gene, Cwc22. De novo assembly of both the ancestral (R2d1) and the derived (R2d2) copies reveals that they have been subject to nonallelic gene conversion events spanning tens of kilobases. R2d2 is also a hotspot for structural variation: its diploid copy number ranges from zero in the mouse reference genome to >80 in wild mice sampled from around the globe. Hemizygosity for high copy-number alleles of R2d2 is associated in cis with meiotic drive; suppression of meiotic crossovers; and copy-number instability, with a mutation rate in excess of 1 per 100 transmissions in some laboratory populations. Our results provide a striking example of allelic diversity generated by duplication and demonstrate the value of de novo assembly in a phylogenetic context for understanding the mutational processes affecting duplicate genes. [ABSTRACT FROM AUTHOR]

This article describes a free and open-source data analysis utility designed for fast online feedback during serial X-ray diffraction and scattering experiments: OnDA (online data analysis). Three complete real-time monitors for common types of serial X-ray imaging experiments are presented. These monitors are capable of providing the essential information required for quick decision making in the face of extreme rates of data collection. In addition, a set of modules, functions and algorithms that allow developers to modify the provided monitors or develop new ones are provided. The emphasis here is on simple, modular and scalable code that is based on open-source libraries and protocols. OnDA monitors have already proven to be invaluable tools in several experiments, especially for scoring and monitoring of diffraction data during serial crystallography experiments at both free-electron laser and synchrotron facilities. It is felt that in the future the kind of fast feedback that OnDA monitors provide will help researchers to deal with the expected very high throughput data flow at next-generation facilities such as the European X-ray free-electron laser. [ABSTRACT FROM AUTHOR]

A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfis" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps0-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation ofmouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding inmultiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. [ABSTRACT FROM AUTHOR]

Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the genetic integrity of laboratory stocks. We have developed the third generation of the Mouse Universal Genotyping Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array for the house mouse (Mus musculus). The bulk of the content of GigaMUGA is optimized for genetic mapping in the Collaborative Cross and Diversity Outbred populations, and for substrain-level identification of laboratory mice. In addition to 141,090 single nucleotide polymorphism probes, GigaMUGA contains 2006 probes for copy number concentrated in structurally polymorphic regions of the mouse genome. The performance of the array is characterized in a set of 500 high-quality reference samples spanning laboratory inbred strains, recombinant inbred lines, outbred stocks, and wild-caught mice. GigaMUGA is highly informative across a wide range of genetically diverse samples, from laboratory substrains to other Mus species. In addition to describing the content and performance of the array, we provide detailed probe-level annotation and recommendations for quality control. [ABSTRACT FROM AUTHOR]

Genotyping microarrays are an important and widely-used tool in genetics. I present argyle, an R package for analysis of genotyping array data tailored to Illumina arrays. The goal of the argyle package is to provide simple, expressive tools for nonexpert users to perform quality checks and exploratory analyses of genotyping data. To these ends, the package consists of a suite of quality-control functions, normalization procedures, and utilities for visually and statistically summarizing such data. Formatconversion tools allow interoperability with popular software packages for analysis of genetic data including PLINK, R/qtl and DOQTL. Detailed vignettes demonstrating common use cases are included as supporting information. argyle bridges the gap between the low-level tasks of quality control and high-level tasks of genetic analysis. It is freely available at https://github.com/andrewparkermorgan/argyle and has been submitted to Bioconductor. [ABSTRACT FROM AUTHOR]

The article discusses databases, analysis tools, and other informatics resources related to the use of the Collaborative Cross (CC) and complementary Diversity Outbred (DO) population of mice for analyzing genetic and molecular networks underlying complex traits like mouse behavior. It focuses on computational tools used for genetic mapping and analyzing CC and DO genomes. It also focuses on how these tools help in getting a comprehensive view of the polymorphism segregation in CC and DO mice.