41 research outputs found
Attention, Filling in The Gaps for Generalization in Routing Problems
Machine Learning (ML) methods have become a useful tool for tackling vehicle
routing problems, either in combination with popular heuristics or as
standalone models. However, current methods suffer from poor generalization
when tackling problems of different sizes or different distributions. As a
result, ML in vehicle routing has witnessed an expansion phase with new
methodologies being created for particular problem instances that become
infeasible at larger problem sizes.
This paper aims at encouraging the consolidation of the field through
understanding and improving current existing models, namely the attention model
by Kool et al. We identify two discrepancy categories for VRP generalization.
The first is based on the differences that are inherent to the problems
themselves, and the second relates to architectural weaknesses that limit the
model's ability to generalize. Our contribution becomes threefold: We first
target model discrepancies by adapting the Kool et al. method and its loss
function for Sparse Dynamic Attention based on the alpha-entmax activation. We
then target inherent differences through the use of a mixed instance training
method that has been shown to outperform single instance training in certain
scenarios. Finally, we introduce a framework for inference level data
augmentation that improves performance by leveraging the model's lack of
invariance to rotation and dilation changes.Comment: Accepted at ECML-PKDD 202
Influenza A virus-derived defective interfering particles for antiviral treatment
Here, we report on genetically engineered, propagation-incompetent influenza A virus (IAV) particles, so-called defective interfering particles (DIPs) that have been suggested as a promising novel antiviral agent. Typically, IAV DIPs harbor a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Further, DIPs are capable of hijacking cellular and viral resources upon co-infection with fully infectious standard virus (STV), resulting in an antiviral effect. Besides this replication interference, DIP infection also stimulates innate immunity, adding to the antiviral efficacy.
So far, DIPs were produced in embryonated chicken eggs. To improve scalability and flexibility of processes as well as to increase product quality, we established a cell culture-based DIP production system [1,2]. This includes the development of a genetically engineered virus-cell propagation system that allows production of DIPs without the need to add infectious STV to complement missing gene functions of DIPs. Specifically, the MDCK suspension cell line generated expresses the PB2 protein [2], encoded by segment 1 (S1) of IAV, which is not expressed by “DI244” - a prototypic, well-characterized DIP harboring a deletion in S1. Using this cell culture-based production process in batch [2,3] and perfusion mode [4] at laboratory scale, we show that we can achieve very high DI244 titers of up to 2.6E+11 DIPs/mL. Infections of mice demonstrated that intranasal administration of the produced DI244 material resulted in no apparent toxic effects and in a full rescue of mice co-treated with an otherwise lethal dose of IAV [2].
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Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry
The expanding role of lipoprotein apheresis in the treatment of raised lipoprotein(a) in ischaemic heart disease and refractory angina
Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation
Altered NO Function Contributes to Impairment of uPA and tPA Cerebrovasodilation after Brain Injury
Emerging biomarkers for heart failure: an update
A growing array of biological pathways underpins the syndrome we recognize as heart failure. These include both deleterious pathways promoting its development and progression, as well as compensatory cardioprotective pathways. Components of these pathways can be utilized as biomarkers of this condition to aid diagnosis, prognostication and potentially guide management. As our understanding of the pathophysiology of heart failure deepens further candidate biomarkers are being identified. We provide an overview of the more recently emerging biomarkers displaying potential promise for future clinical use
Influenza A Virus Defective Interfering Particles for Antiviral Treatment of the Influenza Disease and COVID-19
Neutrophil a-defensins promote thrombosis in vivo by altering fibrin formation, structure, and stability
© 2019 by The American Society of Hematology. Inflammation and thrombosis are integrated, mutually reinforcing processes, but the interregulatory mechanisms are incompletely defined. Here, we examined the contribution of a-defensins (a-defs), antimicrobial proteins released from activated human neutrophils, on clot formation in vitro and in vivo. Activation of the intrinsic pathway of coagulation stimulates release of a-defs from neutrophils. a-Defs accelerate fibrin polymerization, increase fiber density and branching, incorporate into nascent fibrin clots, and impede fibrinolysis in vitro. Transgenic mice (Def 11 ) expressing human a-Def-1 developed larger, occlusive, neutrophil-rich clots after partial inferior vena cava (IVC) ligation than those that formed in wild-type (WT) mice. IVC thrombi extracted from Def 11 mice were composed of a fibrin meshwork that was denser and contained a higher proportion of tightly packed compressed polyhedral erythrocytes than those that developed in WT mice. Def 11 mice were resistant to thromboprophylaxis with heparin. Inhibiting activation of the intrinsic pathway of coagulation, bone marrow transplantation from WT mice or provision of colchicine to Def 11 mice to inhibit neutrophil degranulation decreased plasma levels of a-defs, caused a phenotypic reversion characterized by smaller thrombi comparable to those formed in WT mice, and restored responsiveness to heparin. These data identify a-defs as a potentially important and tractable link between innate immunity and thrombosis