13 research outputs found
Efficient Circulation of Railway Rolling Stock
Railway rolling stock (locomotives, carriages, and train units) is one
of the most significant cost sources for operatorsof passenger trains,
both public and private. Rolling stock costsare due to material
acquisition, power supply, and material maintenance. The efficient
circulation of rolling stock material is therefore one of the
objectives pursued. In this paper we focus on the circulation of train
units on a single line. In order to utilize the train units on this
line in an efficient way, they are added to or removed from the trains
in certain stations, according to the passengers
Unsupervised machine learning to classify the confinement of waves in periodic superstructures
Unsupervised Machine Learning to Classify the Confinement of Waves in Periodic Superstructures
We employ unsupervised machine learning to enhance the accuracy of our
recently presented scaling method for wave confinement analysis [1]. We employ
the standard k-means++ algorithm as well as our own model-based algorithm. We
investigate cluster validity indices as a means to find the correct number of
confinement dimensionalities to be used as an input to the clustering
algorithms. Subsequently, we analyze the performance of the two clustering
algorithms when compared to the direct application of the scaling method
without clustering. We find that the clustering approach provides more
physically meaningful results, but may struggle with identifying the correct
set of confinement dimensionalities. We conclude that the most accurate outcome
is obtained by first applying the direct scaling to find the correct set of
confinement dimensionalities and subsequently employing clustering to refine
the results. Moreover, our model-based algorithm outperforms the standard
k-means++ clustering.Comment: 24 pages, 11 figure
Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thromboembolic infrainguinal disease (DUET): design and rationale
Background: The use of thrombolytic therapy in the treatment of thrombosed infrainguinal native arteries and bypass grafts has increased over the years. Main limitation of this treatment modality, however, is the occurrence of bleeding complications. Low intensity ultrasound (US) has been shown to accelerate enzymatic thrombolysis, thereby reducing therapy time. So far, no randomized trials have investigated the application of US-accelerated thrombolysis in the treatment of thrombosed infra-inguinal native arteries or bypass grafts. The DUET study (Dutch randomized trial comparing standard catheter-directed thrombolysis versus Ultrasound-accElerated Thrombolysis for thrombo-embolic infrainguinal disease) is designed to assess whether US-accelerated thrombolysis will reduce therapy time significantly compared with standard catheter-directed thrombolysis.Methods/design: Sixty adult patients with recently (between 1 and 7 weeks) thrombosed infrainguinal native arteries or bypass grafts with acute limb ischemia class I or IIa, according to the Rutherford classification for acute ischemia, will be randomly allocated to either standard thrombolysis (group A) or US-accelerated thrombolysis (group B). Patients will be recruited from 5 teaching hospitals in the Netherlands during a 2-year period. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infrainguinal native artery or bypass graft, with outflow through at least 1 crural artery.Discussion: The DUET study is a randomized controlled trial that will provide evidence of whether US-accelerated thrombolysis will significantly reduce therapy time in patients with recently thrombosed infrainguinal native arteries or bypass grafts, without an increase in complications. Trial registration: Current Controlled Trials ISRCTN72676102
Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells.
Immunoparalysis is a compensatory and persistent anti-inflammatory response to trauma, sepsis or another serious insult, which increases the risk of opportunistic infections, morbidity and mortality. Here, we show that in cultured primary human monocytes, interleukin-4 (IL4) inhibits acute inflammation, while simultaneously inducing a long-lasting innate immune memory named trained immunity. To take advantage of this paradoxical IL4 feature in vivo, we developed a fusion protein of apolipoprotein A1 (apoA1) and IL4, which integrates into a lipid nanoparticle. In mice and non-human primates, an intravenously injected apoA1-IL4-embedding nanoparticle targets myeloid-cell-rich haematopoietic organs, in particular, the spleen and bone marrow. We subsequently demonstrate that IL4 nanotherapy resolved immunoparalysis in mice with lipopolysaccharide-induced hyperinflammation, as well as in ex vivo human sepsis models and in experimental endotoxemia. Our findings support the translational development of nanoparticle formulations of apoA1-IL4 for the treatment of patients with sepsis at risk of immunoparalysis-induced complications.We thank M. Jaeger (Radboudumc) for kindly providing flourescein
isothiocyanate-labelled Candida albicans. D. Williams (East
Tennessee State University) provided the β-glucan we used in our
initial experiments. H. Lemmers (Radboudumc) kindly prepared the
purified lipopolysaccharide used for stimulation of primary human
monocytes and macrophages. Part of the figures were prepared
using (among other software) Biorender.com. B.N. is supported
by a National Health and Medical Research Council (Australia)
Investigator Grant (APP1173314). This work was supported by
National Institutes of Health grants R01 HL144072, R01 CA220234
and P01 HL131478, as well as a Vici grant from the Dutch Research
Council NWO and an ERC Advanced Grant (all to W.J.M.M.). M.G.N.
was supported by a Spinoza grant from Dutch Research Council
NWO and an ERC Advanced Grant (#833247).S
Tilting the Scale : A Theoretical Framework to re-direct Public Policy away from Economic Growth towards Sustainable and Inclusive Wellbeing
Efficient Circulation of Railway Rolling Stock
Railway rolling stock is one of the most significant cost components for operators of passenger trains. The efficient circulation of rolling stock is therefore one of the main objectives pursued in practice. This paper focuses on the determination of appropriate numbers of train units of different types together with their efficient circulation on a single line. To utilize the train units on this line in an efficient way, they are coupled to or uncoupled from the trains in certain stations according to the passengers' seat demand in peak and off-peak hours. Because coupling and uncoupling train units must respect specific rules related to the shunting possibilities in the stations, it is important to take into account the order of the train units in the trains. This aspect strongly increases the complexity of the rolling stock circulation problem. This paper presents a solution approach based on an integer multicommodity flow model with several additional constraints related to the shunting processes at the stations. The approach is applied to a real-life case study based on the timetable of NS Reizigers, the main Dutch operator of passenger trains
Efficient Circulation of Railway Rolling Stock
Railway rolling stock is one of the most significant cost components for operators of passenger trains. The efficient circulation of rolling stock is therefore one of the main objectives pursued in practice. This paper focuses on the determination of appropriate numbers of train units of different types together with their efficient circulation on a single line. To utilize the train units on this line in an efficient way, they are coupled to or uncoupled from the trains in certain stations according to the passengers' seat demand in peak and off-peak hours. Because coupling and uncoupling train units must respect specific rules related to the shunting possibilities in the stations, it is important to take into account the order of the train units in the trains. This aspect strongly increases the complexity of the rolling stock circulation problem. This paper presents a solution approach based on an integer multicommodity flow model with several additional constraints related to the shunting processes at the stations. The approach is applied to a real-life case study based on the timetable of NS Reizigers, the main Dutch operator of passenger train