176 research outputs found

    Fermilab SRF cryomodule operational experience

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    Fermi National Accelerator Laboratory is constructing an Advanced Accelerator Research and Development facility at New Muon Lab. The cryogenic infrastructure in support of the initial phase of the facility consists of two Tevatron style standalone refrigerators, cryogenic distribution system as well as an ambient temperature pumping system to achieve 2 K operations with supporting purification systems. During this phase of the project a single Type III plus 1.3 GHz cryomodule was installed, cooled and tested. Design constraints of the cryomodule required that the cryomodule individual circuits be cooled at predetermined rates. These constraints required special design solutions to achieve. This paper describes the initial cooldown and operational experience of a 1.3 GHz cryomodule using the New Muon Lab cryogenic system.Comment: 7 pp. Cryogenic Engineering Conference and International Cryogenic Materials Conference CEC-ICMC 2011 13-17 June 2011, Spokane, Washingto

    Enterococcus faecalis Glycolipids Modulate Lipoprotein-Content of the Bacterial Cell Membrane and Host Immune Response

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    In this study, we investigated the impact of the cell membrane composition of E. faecalis on its recognition by the host immune system. To this end, we employed an E. faecalis deletion mutant (Delta bgsA) that does not synthesize the major cell membrane glycolipid diglycosyl-diacylglycerol (DGlcDAG). Proteomic analysis revealed that 13 of a total of 21 upregulated surface-associated proteins of E. faecalis Delta bgsA were lipoproteins. This led to a total lipoprotein content in the cell membrane of 35.8% in Delta bgsA compared to only 9.4% in wildtype bacteria. Increased lipoprotein content strongly affected the recognition of Delta bgsA by mouse macrophages in vitro with an increased stimulation of TNF-alpha production by heat-fixed bacteria and secreted antigens. Inactivation of the prolipoprotein diacylglycerol transferase (lgt) in Delta bgsA abrogated TNF-alpha induction by a Delta bgsA_lgt double mutant indicating that lipoproteins mediate increased activation of mouse macrophages by Delta bgsA. Heatfixed Delta bgsA bacteria, culture supernatant, or cell membrane lipid extract activated transfected HEK cells in a TLR2-dependent fashion;the same was not true of wild-type bacteria. In mice infected intraperitoneally with a sublethal dose of E. faecalis we observed a 70% greater mortality in mice infected with Delta bgsA compared with wild-type-infected mice. Increased mortality due to Delta bgsA infection was associated with elevated plasma levels of the inflammatory cytokines TNF-alpha, IL-6 and MIP-2. In summary, our results provide evidence that an E. faecalis mutant lacking its major bilayer forming glycolipid DGlcDAG upregulates lipoprotein expression leading to increased activation of the host innate immune system and virulence in vivo

    Baseline Configuration of the Cryogenic System for the International Linear Collider

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    The paper discusses the main constraints and boundary conditions and describes the baseline configuration of the International Linear Collider (ILC) cryogenic system. The cryogenic layout, architecture and the cooling principle are presented. The paper addresses a plan for study and development required to demonstrate and improve the performance, to reduce cost and to attain the desired reliability

    Prevalence of Pneumococcal Serotypes in Community-Acquired Pneumonia among Older Adults in Italy: A Multicenter Cohort Study.

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    Pneumococcal community-acquired pneumonia (CAP) is a leading cause of mortality. Following the introduction of pneumococcal conjugate vaccines (PCVs) in children, a decrease in the burden of the disease was reported. In parallel, an increase in non-vaccine serotypes was also noted. The objective of this study was to assess the current serotype-specific epidemiology of pneumococci among Italian older adults hospitalized for CAP. A prospective study was conducted between 2017 and 2020 in four Italian regions. Subjects aged ≄65 years hospitalized with confirmed CAP were tested for pneumococci using both pneumococcal urinary antigen and serotype-specific urine antigen tests able to identify all 24 serotypes included in the available vaccines. Of the 1155 CAP cases, 13.1% were positive for pneumococci. The most prevalent serotypes were 3 (2.0%), 8 (1.7%), 22F (0.8 %) and 11A (0.7%). These serotypes are all included in the newly licensed PCV20. The serotypes included in PCV13, PCV15 and PCV20 contributed to 3.3%, 4.4% and 7.5% of the CAP cases, respectively. In the context of a low PCV13 coverage among older adults and a high PCV coverage in children, a substantial proportion of CAP is caused by PCV13 serotypes. Higher valency PCV15 and PCV20 may provide additional benefits for the prevention of CAP in vaccinated older adults

    Role of mprF1 and mprF2 in the Pathogenicity of Enterococcus faecalis

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    Aujourd hui, Enterococcus faecalis est considĂ©rĂ© comme l un des plus importants agents pathogĂšnes causant des maladies nosocomiales. En raison de sa rĂ©sistance innĂ©e et acquise aux antibiotiques, l identification de nouvelles cibles pour le traitement de cette bactĂ©rie est une grande prioritĂ©. Le facteur Multiple Peptide RĂ©sistance (MprF), qui a Ă©tĂ© dĂ©crit en premier chez Staphylococcus aureus, modifie le phosphatidylglycĂ©rol avec de la lysine et rĂ©duit ainsi la charge nĂ©gative de l enveloppe cellulaire. Ceci a comme consĂ©quence d augmenter la rĂ©sistance aux peptides antimicrobiens cationiques (PAC). Deux gĂšnes paralogues putatifs (mprF1 et mprF2) ont Ă©tĂ© identifiĂ©s chez E. faecalis par recherche BLAST en utilisant le gĂšne dĂ©crit chez S. aureus. Une caractĂ©risation de ces deux gĂšnes d E. faecalis ainsi que des mĂ©canismes conduisant Ă  une rĂ©sistance aux PAC, pourrait aider Ă  dĂ©velopper des nouvelles stratĂ©gies thĂ©rapeutiques contre ce pathogĂšne. Deux mutants de dĂ©lĂ©tion et un double mutant ont Ă©tĂ© construits par recombinaison homologue chez E. faecalis. L analyse des phospholipides des membranes cytoplasmiques des deux mutants mprF1 et mprF2 par chromatographie sur couche mince a montrĂ© que seule l inactivation de mprF2 inhibe la synthĂšse de trois amino-phosphatidlyglycĂ©rol distincts (comme la Lysine-PG, l Alanine-PG et l Arginine-PG). De plus, le mutant mprF2 est Ă©galement plus sensible aux PAC que la souche sauvage. La capacitĂ© de formation d un biofilm est gĂ©nĂ©ralement considĂ©rĂ©e comme un facteur important de virulence, ce qui est Ă©galement le cas pour les entĂ©rocoques. Le mutant mprF2 montre une capacitĂ© accrue dans ce phĂ©nomĂšne. Ceci semble ĂȘtre du Ă  une augmentation de la concentration d ADN extracellulaire dans le biofilm formĂ© par ce mutant. Curieusement, cette augmentation est indĂ©pendante d une autolyse. Le mutant mprF2 est Ă©galement plus rĂ©sistant Ă  l opsonophagocytose. Cependant, le gĂšne mprF2 ne joue aucun rĂŽle dans les bactĂ©riĂ©mies de souris et les endocardites de rats.En revanche, aucun phĂ©notype n a Ă©tĂ© trouvĂ© pour un mutant mprF1 jusqu Ă  prĂ©sent. Cette mutation ne modifie ni la synthĂšse de l aminoacyl-PG en condition de laboratoire ni la rĂ©sistance aux PAC et Ă  l opsonophagocytose. Par consĂ©quent, il semble que mprF2 soit le seul gĂšne mprF fonctionnel chez E. faecalis. NĂ©anmoins, contrairement Ă  d autres bactĂ©ries, mprF2 ne semble pas ĂȘtre un facteur de virulence majeur pour cette espĂšce.Enterococcus faecalis is regarded nowadays as one of the most important nosocomial pathogens. Due to its innate and acquired resistance to antibiotics, identification of new targets for antimicrobial treatment of E. faecalis is a high priority. The multiple peptides resistance factor (MprF), which was first described in Staphylococcus aureus, modifies phosphatidylglycerol with lysine and reduces the negative charge of the membrane, thus increasing resistance to cationic antimicrobial peptides (CAMPs). Two putative mprF paralogs (mprF1 and mprF2) were identified in E. faecalis by Blast search using the well-described S. aureus gene as a lead. A better understanding of these two genes and mechanisms leads to enterococcal resistance to CAMPs might help designing therapeutic strategies against this bacteria. Two single deletion mutants and double mutant in E. faecalis were created by homologues recombination. Analysis of cell membrane phospholipids from both mutants by thin-layer chromatography showed that inactivation of mprF2 abolished the synthesis of three distinct amino-phosphatidylglycerol (mostly likely Lysin-PG, Alanine-PG and Argine-PG). The CAMPs testing assay demonstrated that the deletion mutant of mprF2 was more susceptible to CAMPs than the wild type. Biofilm formation is usually regarded as a virulence factor which provides an important way for enterococci to cause infections. Inactivation of mprF2 led to increase the biofilm formation which we showed that it was due to the accumulation of eDNA in the biofilm, but the release of eDNA is independent from autolysis. The mprF2 mutant was resistance to killing by opsonophagocytosis more than wild type. However, the mprF2 gene plays no role in bacteremia in mice and rat endocarditis. Our results showed that non polar effect mprF1 mutant does not affect in the synthesis of aminoacyl-PG in the laboratory condition. It also has no effect on susceptible to CAMPs, opsonic killing and autolysis. Therefore, it seems that mprF2 is the only functional mprF gene in E. faecalis in the laboratory condition. Unlike mprF found in other bacteria, mprF does not seem to be a major virulence factor in enterococci.CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

    Tick-borne lymphadenopathy (TIBOLA) acquired in Southwestern Germany

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    <p>Abstract</p> <p>Background</p> <p>Tick-borne lymphadenopathy (TIBOLA) was first described in 1997 in a patient in France. The causative agent, <it>Rickettsia slovaca</it>, is transmitted by <it>Dermacentor </it>ticks.</p> <p>Case presentation</p> <p>In southwestern Germany we encountered a patient with a tick bite at the dorsal scalp that resulted in an eschar and nuchal lymphadenopathy. Additionally, fever, malaise as well as elevated inflammatory markers and transaminases occurred. The characteristic clinical picture along with positive antibody testing for rickettsiae of the tick-borne spotted fever group strongly suggest the diagnosis TIBOLA.</p> <p>Conclusion</p> <p>Human rickettsioses are emerging infections. Clinicians should be aware of TIBOLA as a newly described rickettsial disease. As in our case, TIBOLA may be encountered in regions/countries where <it>R. slovaca </it>and <it>Dermacentor </it>ticks are prevalent but autochthonous acquisition was not described before.</p
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