Identification of drug candidates targeting monocyte reprogramming in people living with HIV

INTRODUCTION: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers. METHODS: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as ex vivo drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study. RESULTS: Single-cell RNA-seq analysis revealed that most immune cells in peripheral blood of PLHIV are altered in their transcriptomes and that a specific functional monocyte state previously described in acute HIV infection is still existing in PLHIV while other monocyte cell states are only occurring acute infection. Further, a reverse transcriptome approach on a rather small number of PLHIV was sufficient to identify drug candidates for reversing the transcriptional phenotype of monocytes in PLHIV. DISCUSSION: These scientific findings and technological advancements for clinical application of single-cell transcriptomics form the basis for the larger 2000-HIV multicenter cohort study on PLHIV, for which a combination of bulk and single-cell transcriptomics will be included as the leading technology to determine disease endotypes in PLHIV and to predict disease trajectories and outcomes

Portable Rapid Visual Workflow Simulation Tool for Human Robot Coproduction

Within the European Factory-in-a-day project, the aim is to improve communication between automation integrator and factory owner, in their analysis of feasibility and appropriateness of automating a manual task. A visualisation tool with preconfigured workflows and working principles, with specific focus on efficient human-robot coproduction workflows can improve this process. This paper describes the Workflow Simulation Tool, which is part of the Human-Robot Coproduction Methodology, currently in development. The tool encompasses a portable tablet PC, which runs a visual modelling environment combined with a handheld 3D scanning solution. The tool also features pre-modelled template layouts, implementation of a checklist of persistent notes and portable visual documentation. The tool's appropriateness was iteratively validated in collaboration with automation integrators. This evaluation showed that offering an interactive visual simulation enriches the dialogue during conceptual design and helps in revealing requirements that otherwise only appear during or after implementation.Special issue: 27th International Conference on Flexible Automation and Intelligent ManufacturingMaterials and ManufacturingMechatronic Desig

Comparing Human Factors for Augmented Reality Supported Single-User and Collaborative Repair Operations of Industrial Robots

In order to support the decision-making process of industry on how to implement Augmented Reality (AR) in production, this article wants to provide guidance through a set of comparative user studies. The results are obtained from the feedback of 160 participants who performed the same repair task on a switch cabinet of an industrial robot. The studies compare several AR instruction applications on different display devices (head-mounted display, handheld tablet PC and projection-based spatial AR) with baseline conditions (paper instructions and phone support), both in a single-user and a collaborative setting. Next to insights on the performance of the individual device types for the single mode operation, the study is able to show significant indications on AR techniques are being especially helpful in a collaborative setting.Internet of ThingsMechatronic DesignSystem Engineerin

Simulated car driving and its association with cognitive abilities in patients with schizophrenia

Objectives: Patients with schizophrenia commonly suffer from impairments in various aspects of cognition . These deficits were shown to have detrimental effects on daily life functioning and might also impair car driving. This study is the first to examine driving behaviour of patients with schizophrenia using an advanced driving simulator, and to explore the role of cognitive abilities of people with schizophrenia for driving. Methods: Non-acute patients with schizophrenia (n = 31) and healthy comparison participants (n = 31) performed a comprehensive neuropsychological assessment and driving simulator rides. Neuropsychological and driving performances were compared between groups. Moreover, associations were explored between cognitive functions and driving behaviour in the entire group. Results: Patients with schizophrenia revealed impairments in multiple aspects of cognition. In the driving simulator, patients with schizophrenia showed no indication of deviant driving in terms of number of collisions or reacting to critical situations, and even showed better lane control compared to healthy individuals. However, patients with schizophrenia drove significantly slower than healthy individuals, and caused more hindrance to the car behind while merging on the motorway. Slower driving was associated with lower test scores on attention and processing speed. Hindering the car behind was associated with test performance on planning and inhibition. Conclusions: It is concluded that driving of patients with schizophrenia is characterized by a relatively slow speed, and can also be impaired in certain aspects, i.e. hindering a car behind while merging. Cognitive functions are crucial for driving, and should be target of treatment. (C) 2018 Elsevier B.V. All rights reserved

Crystal Structures of SARS-CoV-2 main protease with screening fragments and COVID Moonshot compounds from the XChem facility at Diamond Light Source

<p>Bulk repositiory of structures of SARS-CoV-2 main protease in complex with fragment molecules from inital XChem screen and designed COVID Moonshot inhibtor compounds. Each structure has a PDB ID, coordinate file, structure factor file, ligand restraint (cif) and PANDDA event maps (as appropriate).</p><p>2023-10-26 - updated to include <strong>all </strong>initial fragment screening hits alongside follow up compounds</p&gt