Position dependent rate dampening in any active hand controller

A control system for an active hand controller, for example, uses a control stick connected to and controlled by a motor. Electronics are provided to control the motor to eliminate oscillations due to motor torque and high gain due to breakout at the control stick when the control stick is at about its null position. Both hardware as well as software implementations can provide position dependent dampening to the control sticks such that when the control stick is located about a null position, a higher rate of dampening is provided than when the control stick is located outside the null position, when a lower rate of dampening is provided. The system provides a stable active hand controller control stick without degraded force and feel characteristics of the system

Effects of X-ray dose on rhizosphere studies using X-ray computed tomography

X-ray Computed Tomography (CT) is a non-destructive imaging technique originally designed for diagnostic medicine, which was adopted for rhizosphere and soil science applications in the early 1980s. X-ray CT enables researchers to simultaneously visualise and quantify the heterogeneous soil matrix of mineral grains, organic matter, air-filled pores and water-filled pores. Additionally, X-ray CT allows visualisation of plant roots in situ without the need for traditional invasive methods such as root washing. However, one routinely unreported aspect of X-ray CT is the potential effect of X-ray dose on the soil-borne microorganisms and plants in rhizosphere investigations. Here we aimed to i) highlight the need for more consistent reporting of X-ray CT parameters for dose to sample, ii) to provide an overview of previously reported impacts of X-rays on soil microorganisms and plant roots and iii) present new data investigating the response of plant roots and microbial communities to X-ray exposure. Fewer than 5% of the 126 publications included in the literature review contained sufficient information to calculate dose and only 2.4% of the publications explicitly state an estimate of dose received by each sample. We conducted a study involving rice roots growing in soil, observing no significant difference between the numbers of root tips, root volume and total root length in scanned versus unscanned samples. In parallel, a soil microbe experiment scanning samples over a total of 24 weeks observed no significant difference between the scanned and unscanned microbial biomass values. We conclude from the literature review and our own experiments that X-ray CT does not impact plant growth or soil microbial populations when employing a low level of dose (<30 Gy). However, the call for higher throughput X-ray CT means that doses that biological samples receive are likely to increase and thus should be closely monitored

Assessing Physicochemical Properties of Drug Molecules via Microsolvation Measurements with Differential Mobility Spectrometry

Definitive version is available here: Liu, C., Le Blanc, J. C. Y., Schneider, B. B., Shields, J., Federico, J. J., Zhang, H., … Campbell, J. L. (2017). Assessing Physicochemical Properties of Drug Molecules via Microsolvation Measurements with Differential Mobility Spectrometry. ACS Central Science, 3(2), 101–109. https://doi.org/10.1021/acscentsci.6b00297. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.http://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlThe microsolvated state of a molecule, represented by its interactions with only a small number of solvent molecules, can play a key role in determining the observable bulk properties of the molecule. This is especially true in cases where strong local hydrogen bonding exists between the molecule and the solvent. One method that can probe the microsolvated states of charged molecules is differential mobility spectrometry (DMS), which rapidly interrogates an ion’s transitions between a solvated and desolvated state in the gas phase (i.e., few solvent molecules present). However, can the results of DMS analyses of a class of molecules reveal information about the bulk physicochemical properties of those species? Our findings presented here show that DMS behaviors correlate strongly with the measured solution phase pKa and pKb values, and cell permeabilities of a set of structurally related drug molecules, even yielding high-resolution discrimination between isomeric forms of these drugs. This is due to DMS’s ability to separate species based upon only subtle (yet predictable) changes in structure: the same subtle changes that can influence isomers’ different bulk properties. Using 2-methylquinolin-8-ol as the core structure, we demonstrate how DMS shows promise for rapidly and sensitively probing the physicochemical properties of molecules, with particular attention paid to drug candidates at the early stage of drug development. This study serves as a foundation upon which future drug molecules of different structural classes could be examined.Natural Sciences and Engineering Research Council of Canada || ENGAGE grant (EGP No. 449354-13) ENGAGE Plus grant || (EGP No.463974-14) Collaborative Research and Development grant || (490885). Ontario Centres of Excellence(OCE) || Voucher for Innovation and Productivity II grant (25050

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Provision of quality of service for active services

A novel approach to quality of service control in an active service network (application layer active network) is described. The approach makes use of a distributed genetic algorithm based on the unique methods that bacteria use to transfer and share genetic material. We have used this algorithm in the design of a robust adaptive control system for the active nodes in an active service network. The system has been simulated and results show that it can offer clear differentiation of active services. The algorithm places the right software, at the right place, in the right proportions; allows different time dependencies to be satisfied and simple payment related increases in performance

Interpretable, Probability-Based Confidence Metric for Continuous Quantitative Structure–Activity Relationship Models

A great deal of research has gone into the development of robust confidence in prediction and applicability domain (AD) measures for quantitative structure–activity relationship (QSAR) models in recent years. Much of the attention has historically focused on structural similarity, which can be defined in many forms and flavors. A concept that is frequently overlooked in the realm of the QSAR applicability domain is how the local activity landscape plays a role in how accurate a prediction is or is not. In this work, we describe an approach that pairs information about both the chemical similarity and activity landscape of a test compound’s neighborhood into a single calculated confidence value. We also present an approach for converting this value into an interpretable confidence metric that has a simple and informative meaning across data sets. The approach will be introduced to the reader in the context of models built upon four diverse literature data sets. The steps we will outline include the definition of similarity used to determine nearest neighbors (NN), how we incorporate the NN activity landscape with a similarity-weighted root-mean-square distance (wRMSD) value, and how that value is then calibrated to generate an intuitive confidence metric for prospective application. Finally, we will illustrate the prospective performance of the approach on five proprietary models whose predictions and confidence metrics have been tracked for more than a year

Quantitative Assessment of the Impact of Fluorine Substitution on P‑Glycoprotein (P-gp) Mediated Efflux, Permeability, Lipophilicity, and Metabolic Stability

Strategic replacement of one or more hydrogen atoms with fluorine atom(s) is a common tactic to improve potency at a given target and/or to modulate parameters such as metabolic stability and p<i>K</i>_a. Molecular weight (MW) is a key parameter in design, and incorporation of fluorine is associated with a disproportionate increase in MW considering the van der Waals radius of fluorine versus hydrogen. Herein we examine a large compound data set to understand the effect of introducing fluorine on the risk of encountering P-glycoprotein mediated efflux (as measured by MDR efflux ratio), passive permeability, lipophilicity, and metabolic stability. Statistical modeling of the MDR ER data demonstrated that an increase in MW as a result of introducing fluorine atoms does not lead to higher risk of P-gp mediated efflux. Fluorine-corrected molecular weight (MW_FC), where the molecular weight of fluorine has been subtracted, was found to be a more relevant descriptor