Generator voltage stabilisation for series-hybrid electric vehicles

This paper presents a controller for use in speed control of an internal combustion engine for series-hybrid electric vehicle applications. Particular reference is made to the stability of the rectified DC link voltage under load disturbance. In the system under consideration, the primary power source is a four-cylinder normally aspirated gasoline internal combustion engine, which is mechanically coupled to a three-phase permanent magnet AC generator. The generated AC voltage is subsequently rectified to supply a lead-acid battery, and permanent magnet traction motors via three-phase full bridge power electronic inverters. Two complementary performance objectives exist. Firstly to maintain the internal combustion engine at its optimal operating point, and secondly to supply a stable 42 V supply to the traction drive inverters. Achievement of these goals minimises the transient energy storage requirements at the DC link, with a consequent reduction in both weight and cost. These objectives imply constant velocity operation of the internal combustion engine under external load disturbances and changes in both operating conditions and vehicle speed set-points. An electronically operated throttle allows closed loop engine velocity control. System time delays and nonlinearities render closed loop control design extremely problematic. A model-based controller is designed and shown to be effective in controlling the DC link voltage, resulting in the well-conditioned operation of the hybrid vehicle

Dendritic cells are defective in breast cancer patients: a potential role for polyamine in this immunodeficiency

INTRODUCTION: Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs. METHODS: The IL-4/GM-CSF (granulocyte–macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells. RESULTS: Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR(-)Lin(- )cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-γ production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR(-)Lin(- )cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid. CONCLUSION: These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest

Airway structural cells regulate TLR5-mediated mucosal adjuvant activity

Antigen-presenting cell (APC) activation is enhanced by vaccine adjuvants. Most vaccines are based on the assumption that adjuvant activity of Toll-like receptor (TLR) agonists depends on direct, functional activation of APCs. Here, we sought to establish whether TLR stimulation in non-hematopoietic cells contributes to flagellin’s mucosal adjuvant activity. Nasal administration of flagellin enhanced T-cell-mediated immunity, and systemic and secretory antibody responses to coadministered antigens in a TLR5-dependent manner. Mucosal adjuvant activity was not affected by either abrogation of TLR5 signaling in hematopoietic cells or the presence of flagellin-specific, circulating neutralizing antibodies. We found that flagellin is rapidly degraded in conducting airways, does not translocate into lung parenchyma and stimulates an early immune response, suggesting that TLR5 signaling is regionalized. The flagellin-specific early response of lung was regulated by radioresistant cells expressing TLR5 (particularly the airway epithelial cells). Flagellin stimulated the epithelial production of a small set of mediators that included the chemokine CCL20, which is known to promote APC recruitment in mucosal tissues. Our data suggest that (i) the adjuvant activity of TLR agonists in mucosal vaccination may require TLR stimulation of structural cells and (ii) harnessing the effect of adjuvants on epithelial cells can improve mucosal vaccines.Fil: Van Maele, Laurye. Institut Pasteur de Lille. Lille; Francia. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; FranciaFil: Fougeron, Delphine. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; FranciaFil: Janot, Laurent. University of Orléans. Orléans; Francia. Institut de Transgenose. Orleans; FranciaFil: Didierlaurent, A.. Imperial College of London. Londres; Reino UnidoFil: Cayet, D.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; FranciaFil: Tabareau, J.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; FranciaFil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Corvo Chamaillard, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; FranciaFil: Boulenoir, S.. Institut Pasteur de Lille. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Univ Lille Nord de France. Lille; FranciaFil: Jeffs, S. Imperial College of London. Londres; Reino UnidoFil: Vande Walle, L. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; BélgicaFil: Lamkanfi, M.. Department of Medical Protein Research. Ghent; Bélgica. University of Ghent; BélgicaFil: Lemoine, Y.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; FranciaFil: Erard, F.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; FranciaFil: Hot, D.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; FranciaFil: Hussell, Tracy. Imperial College of London. Londres; Reino Unido. University of Manchester; Reino UnidoFil: Ryffel, B.. Institut de Transgenose. Orleans; Francia. University of Orléans. Orléans; FranciaFil: Benecke, Arndt G.. Institut des Hautes Études Scientifiques and Centre National de la Recherche Scientifique; FranciaFil: Sirard, J.C.. Univ Lille Nord de France. Lille; Francia. Institut National de la Santé et de la Recherche Médicale; Francia. Institut Pasteur de Lille. Lille; Franci

Use of the analysis of the volatile faecal metabolome in screening for colorectal cancer

Diagnosis of colorectal cancer is an invasive and expensive colonoscopy, which is usually carried out after a positive screening test. Unfortunately, existing screening tests lack specificity and sensitivity, hence many unnecessary colonoscopies are performed. Here we report on a potential new screening test for colorectal cancer based on the analysis of volatile organic compounds (VOCs) in the headspace of faecal samples. Faecal samples were obtained from subjects who had a positive faecal occult blood sample (FOBT). Subjects subsequently had colonoscopies performed to classify them into low risk (non-cancer) and high risk (colorectal cancer) groups. Volatile organic compounds were analysed by selected ion flow tube mass spectrometry (SIFT-MS) and then data were analysed using both univariate and multivariate statistical methods. Ions most likely from hydrogen sulphide, dimethyl sulphide and dimethyl disulphide are statistically significantly higher in samples from high risk rather than low risk subjects. Results using multivariate methods show that the test gives a correct classification of 75% with 78% specificity and 72% sensitivity on FOBT positive samples, offering a potentially effective alternative to FOBT

Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd

Genetic Variants of Wnt Transcription Factor TCF-4 (TCF7L2) Putative Promoter Region Are Associated with Small Intestinal Crohn's Disease

Reduced expression of Paneth cell antimicrobial α-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.1 kb of the 5′ flanking region of TCF-4 in a small group of ileal CD patients and controls (n = 10 each). We identified eight single nucleotide polymorphisms (SNPs), of which three (rs3814570, rs10885394, rs10885395) were in linkage disequilibrium and found more frequently in patients; one (rs3814570) was thereby located in a predicted regulatory region. We carried out high-throughput analysis of this SNP in three cohorts of inflammatory bowel disease (IBD) patients and controls. Overall 1399 healthy individuals, 785 ulcerative colitis (UC) patients, 225 CD patients with colonic disease only and 784 CD patients with ileal involvement were used to determine frequency distributions. We found an association of rs3814570 with ileal CD but neither with colonic CD or UC, in a combined analysis (allele positivity: OR 1.27, 95% CI 1.07 to 1.52, p = 0.00737), which was the strongest in ileal CD patients with stricturing behaviour (allele frequency: OR 1.32, 95% CI 1.08 to1.62, p = 0.00686) or an additional involvement of the upper GIT (allele frequency: OR 1.38, 95% CI 1.03 to1.84, p = 0.02882). The newly identified genetic association of TCF-4 with ileal CD provides evidence that the decrease in Paneth cell α-defensins is a primary factor in disease pathogenesis

Resistance to Mucosal Lysozyme Compensates for the Fitness Deficit of Peptidoglycan Modifications by Streptococcus pneumoniae

The abundance of lysozyme on mucosal surfaces suggests that successful colonizers must be able to evade its antimicrobial effects. Lysozyme has a muramidase activity that hydrolyzes bacterial peptidoglycan and a non-muramidase activity attributable to its function as a cationic antimicrobial peptide. Two enzymes (PgdA, a N-acetylglucosamine deacetylase, and Adr, an O-acetyl transferase) that modify different sites on the peptidoglycan of Streptococcus pneumoniae have been implicated in its resistance to lysozyme in vitro. Here we show that the antimicrobial effect of human lysozyme is due to its muramidase activity and that both peptidoglycan modifications are required for full resistance by pneumococci. To examine the contribution of lysozyme and peptidoglycan modifications during colonization of the upper respiratory tract, competition experiments were performed with wild-type and pgdAadr mutant pneumococci in lysozyme M-sufficient (LysM+/+) and -deficient (LysM−/−) mice. The wild-type strain out-competed the double mutant in LysM+/+, but not LysM−/− mice, indicating the importance of resistance to the muramidase activity of lysozyme during mucosal colonization. In contrast, strains containing single mutations in either pgdA or adr prevailed over the wild-type strain in both LysM+/+ and LysM−/− mice. Our findings demonstrate that individual peptidoglycan modifications diminish fitness during colonization. The competitive advantage of wild-type pneumococci in LysM+/+ but not LysM−/− mice suggests that the combination of peptidoglycan modifications reduces overall fitness, but that this is outweighed by the benefits of resistance to the peptidoglycan degrading activity of lysozyme