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- El Yaagoubi, A., et al.
(författare)
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A logistic model for a french intermodal rail/road freight transportation system
- 2022
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Ingår i: Transportation Research Part E. - : Elsevier BV. - 1366-5545 .- 1878-5794. ; 164
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Tidskriftsartikel (refereegranskat)abstract
- In Europe, there are major obstacles limiting the growth of rail freight. In this paper, we investigate problems related to the development of small multimodal terminals which are usually utilized to ensure a more environmentally friendly freight transport and serve metropolitan areas with daily train shuttles arriving from ports. The small size of such terminals and limitations of the storing area, and service and cost constraints, require that resource use is optimal, handling operations for overnight train shuttle schedules are timely, and final truck delivery is optimized. Besides designing the complete service, an optimization-simulation approach is proposed for container transportation, handling operations and container stacking in the small rail/road terminal, as well as for final delivery, to optimize resource use and time. In an original multidisciplinary perspective, the case of a Le Havre-Paris intermodal shuttle is presented using real data. Optimization/simulation results are fed into the economic model to ensure cost efficiency and conditions for efficiency, profitability for investors and also to measure the environmental impact. Our experimental results show the efficiency of our optimization-simulation approach, and the methodology used delivers full guidelines for the implementation of similar terminals. Several important research directions are finally pointed out.
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| 2. |
- Velghe, AI, et al.
(författare)
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PDGFRA alterations in cancer : characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations
- 2014
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Ingår i: Oncogene. - : Nature Publishing Group. - 0950-9232 .- 1476-5594. ; 33:20, s. 2568-2576
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Tidskriftsartikel (refereegranskat)abstract
- Activating mutations in the platelet-derived growth factor (PDGF) receptor alpha (PDGFRA) have been described in patients with gastrointestinal stromal tumors or myeloid malignancies associated with hypereosinophilia. These patients respond well to imatinib mesylate, raising the question as to whether patients with a PDGF receptor mutation in other tumor types should receive a tyrosine kinase inhibitor treatment. We characterized 10 novel somatic point mutations in PDGFRA that have been reported in isolated cases of glioblastoma, melanoma, acute myeloid leukemia, peripheral nerve sheath tumors and neuroendocrine carcinoma. The PDGFRA transmembrane domain mutation V536E stimulated Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand. This mutant, identified in glioblastoma, was strongly inhibited by imatinib. Modeling suggested that the mutation modulates the packing of the transmembrane domain helices in the receptor dimer. By contrast, two mutations in highly conserved residues affected the receptor traffic to the cell surface or kinase activity, thereby preventing the response to PDGF. The other mutations had no significant impact on the receptor activity. This functional analysis matched the predictions of SIFT and PolyPhen for only five mutations and these algorithms do not discriminate gain from loss of function. Finally, an E996K variant that had been identified in a melanoma cell line was not expressed in these cells. Altogether, several newly identified PDGFRA mutations do not activate the receptor and may therefore represent passenger mutations. Our results also underline the importance of characterizing novel kinase alterations in cancer patients.
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| 3. |
- Duparc, T., et al.
(författare)
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Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism
- 2017
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 66:4, s. 620-632
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Tidskriftsartikel (refereegranskat)abstract
- Objective To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. Design To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing nonalcoholic steatohepatitis (NASH). Results Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-alpha, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. Conclusions Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans.
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