Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity

A partition-based match making algorithm for dynamic ridesharing

Ridesharing offers the opportunity to make more efficient use of vehicles while preserving the benefits of individual mobility. Presenting ridesharing as a viable option for commuters, however, requires minimizing certain inconvenience factors. One of these factors includes detours which result from picking up and dropping off additional passengers. This paper proposes a method which aims to best utilize ridesharing potential while keeping detours below a specific limit. The method specifically targets ridesharing systems on a very large scale and with a high degree of dynamics which are difficult to address using classical approaches known from operations research. For this purpose, the road network is divided into distinct partitions which define the search space for ride matches. The size and shape of the partitions depend on the topology of the road network as well as on two free parameters. This allows optimizing the partitioning with regard to sharing potential utilization and inconvenience minimization. Match making is ultimately performed using an agent-based approach. As a case study, the algorithm is applied to investigate the potential for taxi sharing in Singapore. This is done by considering about 110 000 daily trips and allowing up to two sharing partners. The outcome shows that the number of trips could be reduced by 42% resulting in a daily mileage savings of 230 000 km. It is further shown that the presented approach exceeds the mileage savings achieved by a greedy heuristic by 6% while requiring 30% lower computational efforts

The Human Brain Project-Synergy between neuroscience, computing, informatics, and brain-inspired technologies.

The Human Brain Project (HBP) is a European flagship project with a 10-year horizon aiming to understand the human brain and to translate neuroscience knowledge into medicine and technology. To achieve such aims, the HBP explores the multilevel complexity of the brain in space and time; transfers the acquired knowledge to brain-derived applications in health, computing, and technology; and provides shared and open computing tools and data through the HBP European brain research infrastructure. We discuss how the HBP creates a transdisciplinary community of researchers united by the quest to understand the brain, with fascinating perspectives on societal benefits

Packaged BiCMOS embedded RF-MEMS switches with integrated inductive loads

This paper presents packaged BiCMOS embedded RF-MEMS switches with integrated inductive loads for frequency tuning at mm-wave frequencies. The developed technique provides easy optimization to maximize the RF performance at the desired frequency without having an effect on the switch mechanics. Insertion loss less than 0.25 dB and isolation better than 20 dB are achieved from 30 to 100 GHz. A glass cap with a silicon frame is used to package the switch. Single-pole-double-throw (SPDT) switches and a 24-77 GHz reconfigurable LNA is also demonstrated as a first time implementation of single chip BiCMOS reconfigurable circuit at such high frequencies