333 research outputs found

    Clonal expansion within pneumococcal serotype 6C after use of seven-valent vaccine

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    Streptococcus pneumoniae causes invasive infections, primarily at the extremes of life. A seven-valent conjugate vaccine (PCV7) is used to protect against invasive pneumococcal disease in children. Within three years of PCV7 introduction, we observed a fourfold increase in serotype 6C carriage, predominantly due to a single clone. We determined the whole-genome sequences of nineteen S. pneumoniae serotype 6C isolates, from both carriage (n = 15) and disease (n = 4) states, to investigate the emergence of serotype 6C in our population, focusing on a single multi-locus sequence type (MLST) clonal complex 395 (CC395). A phylogenetic network was constructed to identify different lineages, followed by analysis of variability in gene sets and sequences. Serotype 6C isolates from this single geographical site fell into four broad phylogenetically distinct lineages. Variation was seen in the 6C capsular locus and in sequences of genes encoding surface proteins. The largest clonal complex was characterised by the presence of lantibiotic synthesis locus. In our population, the 6C capsular locus has been introduced into multiple lineages by independent capsular switching events. However, rapid clonal expansion has occurred within a single MLST clonal complex. Worryingly, plasticity exists within current and potential vaccine-associated loci, a consideration for future vaccine use, target selection and design

    EntrezAJAX : direct web browser access to the Entrez Programming Utilities

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    Web applications for biology and medicine often need to integrate data from Entrez services provided by the National Center for Biotechnology Information. However, direct access to Entrez from a web browser is not possible due to 'same-origin' security restrictions. The use of "Asynchronous JavaScript and XML" (AJAX) to create rich, interactive web applications is now commonplace. The ability to access Entrez via AJAX would be advantageous in the creation of integrated biomedical web resources. We describe EntrezAJAX, which provides access to Entrez eUtils and is able to circumvent same-origin browser restrictions. EntrezAJAX is easily implemented by JavaScript developers and provides identical functionality as Entrez eUtils as well as enhanced functionality to ease development. We provide easy-to-understand developer examples written in JavaScript to illustrate potential uses of this service. For the purposes of speed, reliability and scalability, EntrezAJAX has been deployed on Google App Engine, a freely available cloud service. The EntrezAJAX webpage is located at http://entrezajax.appspot.com

    "Il giardino dei Loman"

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    "Il giardino dei Loman" verte sull'analisi del giardino nella pièce di Arthur Miller, "Death of a Salesman". L'autrice ripercorre la storia del teatro del Novecento relativamente alle influenze europeee e al carattere innovativo acquisito oltre-oceano a cominciare dagli esperimenti di Eugene O'Neill. In particolare, si esamina il nascere di una nuova professionalita', quella dello scenografo, assunta con genialita' e passione da Jo Mielziner. Il contributo dello scenografo alla messa in scena di 'Death of a Salesman' è esaminato in riferimento ai materiali, anche inediti, conservati presso il Lincoln Center for Performing Arts di New York, dove e' stata condotta parte della ricerca. Le modalità di traduzione teatrale della metafora creata da Miller si rivelano un prodotto della collaborazione tra autore, regista e scenografo. L’ approccio metodologico è innovativo per l’integrazione raggiunta tra le conclusioni raggiunte tramite le discipline teatrali e quelle letterarie, una sintesi raramente raggiunta dagli studiosi dei due diversi settori disciplinari."The Loman's Garden" focuses on the analysis of Arthur Miller's play, “Death of a Salesman”. The author walks into the steps of 19th century theatre stressing the European influences and their innovative character in the US, starting from E.O'Neill's dramatic experiments. In particular, the new professional figure called scenographer is focused on, and the important passionate role played by Jo Mielziner in establishing it. Mielziner's contribution to the staging of “Death of a Salesman” is examined with reference to the unpublished materials kept at New York Lincoln Center for the Performing Arts, where research for the paper was undertaken. The translation of Miller's metaphor into theatrical terms is carried out in the light of the tight collaboration between playwright, director, and scenic designer (Miller-Kazan-Mielziner). The methodological approach is innovative in that it has been possible to reach conclusions that belong to the theatrical disciplines studies and the literary ones, so much so that a synthesis has been reached on this rare occasion

    Author and Authorship in Arthur Miller’s Death of a Salesman: Willy Loman\u27s Attempts to Author a Nostalgic, Fictitious Past Lead to His Downfall, While Linda Loman’s Miller-Authored Warnings Fall on Willy’s Ever-Deaf Ears

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    Throughout the 20th century, the American male protagonist’s obsession with and longing for a past that never existed brings about his own downfall. In Death of a Salesman, by Arthur Miller, Willy Loman nostalgically fantasizes about a bygone era, the pre-war days of glory and greatness, but as he attempts to recreate his presumed former prestige in a post-war world, the fantasy unravels, with not only death and destruction in his dream’s widening, illusory wake, but the unraveling also presents itself in the recognition that Willy’s carefully crafted memories are works of fiction. Decades of literary research focus on Willy’s fascination and obsession with memory, nostalgia for a previous age that never measures up to his memory of it. But, there is a wider gap in the research when it comes to the woman’s role. Willy’s female counterpart, Linda Loman, manages to survive because she is rooted in reality. For Linda, time moves on and reality fuels her forward progress, while Willy remains irrevocably tied to a false, self-conceived past. Routinely focusing on Linda as permissive or assisting in prolonging Willy’s fantasies, as merely the long-suffering housewife motif that Willy proposes, only exacerbates the notion that women are superfluous to the stories of men. Linda’s attempts to awaken her fantasy laden husband fall on deaf ears, and they also fall on blind critics. As the author of his fictions, Willy veers further and further from the truth of his situation and his character, while Miller’s moral lessons assert their sway through Linda as the truth teller. Linda is Miller’s voice, reminding the readers that “attention must be paid” to both Willy’s delusions and Linda’s accuracy

    Willy Loman and the American Dream

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    The unavoidable question in Death of a Salesman that lingers is whether Willy Loman is an attack, defense or ploy in the representation of the American dream. Death of a Salesman has created considerable controversy for its theatrical style, production values and its dramatic content. When first exposed to it as an underclassman, I wasn’t affected by the controversy of its theatrical style or production decisions. I accepted it as a modern tragedy and a hybrid of American Realism and German Expressionism without reservation about its theatrical style. But I found it hard to accept and participate in the political debates it seemed to engender; in fact, I was offended by its obvious ambiguity and invitation to argument. I never felt comfortable in either position, considering Death of a Salesman as being a defense of or an attack upon the American Capitalist system or the pursuit of the American dream. These arguments seemed contrived to me, and these issues and the intentional ambiguity of Miller in Death of a Salesman smacked of manipulation and seemed to be career moves designed to enhance the appeal of the play by creating controversy. Miller readily admitted that he had written his previous play, All My Sons, to shock and promote discussion (S. C. Abbotson 1999, 46). So, why can’t Willy be a straw man that was created to bring more and continuing controversy and attention to Miller’s work, which had just caused political commotion with the play All My Sons about war profiteering. Of course, Miller was accused of being a communist when that play appeared in 1947, also (A. Miller, Time bends 1987, 238). It became clear to me that Death of a Salesman could be interpreted as an oblique attack on the American dream or an ambiguous defense of that dream that one could embrace or reject according for personal or partisan reasons. It was a clever manipulation by the author designed to capitalize on his reputation as a leftist and the controversy of All My Sons to give the play more appeal and to enhance its chance at success, blending ideological controversy with the universal themes of family, love and death.Master of Arts (MA)Liberal StudiesUniversity of Michigan-Flinthttps://deepblue.lib.umich.edu/bitstream/2027.42/143408/1/YoungV.pd

    Pre-, pro-, and synbiotic modulation of the intestinal microbiota stimulates enteroendocrine mediated intestinal adaptation in piglets with short-bowel syndrome

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    Short-bowel syndrome (SBS) is a costly condition primarily affecting very low birth weight, premature infants with long-term detriment to nutritional adequacy and quality of life. Necrotizing enterocolitis (NEC) -the primary cause of surgical resection leading to pediatric SBS- has an ill-defined etiology that is associated with intestinal microbial dysbiosis, defined by altered intestinal microbiota, decreased bacterial diversity, and antibiotic use. SBS is associated with an enteroendocrine cascade beginning with intestinal secretion of glucagon-like peptide-2 (GLP-2), an intestinotrophic hormone, stimulating innate intestinal adaptation. Treatments such as prebiotics and probiotics that increase luminal production of short-chain fatty acids (SCFA), especially butyrate, could further enhance this process through stimulating higher secretion of GLP-2 from enteroendocrine L-cells. Hence, manipulation of the intestinal microbiota is a logical target for the treatment of NEC and SBS, given its ability to produce butyrate and other SCFA through microbial syntrophy. In this series of studies, we: 1) Identified key existing information related to the etiology, treatment, and physiology related to SBS and the intestinal microbiota (literature review) 2) Investigated potential interactions between abundances of ileal and colonic butyrate and lactate-producing bacterial populations and their modulation of intestinal nutrient transport 3) Determined the associations between changes in the intestinal microbiota, intestinal epithelium, and enteroendocrine system related to intestinal adaptation in the distal ileum and proximal colon 4) Identified key traits that differentiated our four treatment groups utilizing linear discriminant analysis, and developed statistical models that could identify which variables accounted for changes in specific structural and functional adaptations using multiple linear regression. Studies 2-4 were conducted within the same group of piglets receiving an 80% ileojejunal resection, receiving 80% of their nutritional needs via parenteral nutrition and 20% of their needs via enteral nutrition, supplemented with: [1] nothing, control (CON); [2] 10g/L short-chain fructooligosaccharide (scFOS), prebiotic (PRE); [3] 109 colony forming units Lactobacillus rhamnosus GG (LGG), probiotic (PRO); OR [4] scFOS + LGG. Treatments with scFOS were associated with increased chao1 alpha diversity (P = 0.0427) and increased butyrate-producing bacteria in the ileal digesta (P = 0.04) (as measured by 16s, V3-V5 DNA sequencing), which was associated with increased electrogenic glucose absorption as measured ex vivo in modified Ussing chambers (R2 = 0.477, P = 0.0529). The probiotic, LGG, primarily colonized the ileal digesta where it increased total Lactobacillus (all P = 0.04). Specifically, PRO increased D-lactate producing Lactobacillus (P = 0.0712) with negative effects on ileal peptide absorption (R2 = -0.485, P = 0.0567). L-cell density, as assessed by immunofluorescence, did not differ between treatments in the ileum (P = 0.602) or the colon (P = 0.4319), but L-cell density was higher in the ileum vs the colon (P = 0.0003). mRNA expression of primary GLP-2 signaling elements was enhanced by PRE in the ileum. Most notably, PRE decreased expression of Dipeptidyl-peptidase 4 (P = 0.0027). mRNA expression of secondary GLP-2 signaling elements was diminished by PRO in the colon. Treatments with scFOS (PRE and SYN) decreased abundance of bacterial species detrimental to GLP-2 signaling, including Enterococcus faecalis (P = 0.04) and Escherichia coli E851/71 (P = 0.01). Three linear models were generated to predict ileal villus height (R2 adjusted = 0.890, 0.793, and 0.753; all P < 0.001) two linear models were generated to predict colonic electrogenic glutamine transport (R2 adjusted = 0.815 and 0.655; both P < 0.001), and one LDA was conducted to differentiate between treatment groups for each the ileum and the colon (all groups completely differentiated with 100% confidence and P < 0.0001). Overall, this data demonstrates that overabundance of Lactobacillus, especially those that produce D-lactate, contraindicates the use of LGG with scFOS as a synbiotic combination. The increase in total butyrate-producers and glucose absorption associated with scFOS reinforces its potential usefulness in the treatment of SBS. Furthermore, the associated increase in butyrate may enhance primary GLP-2 signaling through altered gene expression and decreasing abundance of detrimental bacterial species, highly contributing to predictions of enhanced structural and functional adaptation in the ileum and colon.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2019-05-01The student, Brett Loman, accepted the attached license on 2017-04-21 at 10:05.The student, Brett Loman, submitted this Dissertation for approval on 2017-04-21 at 10:18.This Dissertation was approved for publication on 2017-04-21 at 12:24.DSpace SAF Submission Ingestion Package generated from Vireo submission #10959 on 2017-08-10 at 14:32:24Made available in DSpace on 2017-08-10T19:52:19Z (GMT). No. of bitstreams: 3 LOMAN-DISSERTATION-2017.pdf: 13207925 bytes, checksum: 20445181e494072ee1fc9bd48edf6b9c (MD5) LICENSE.txt: 4208 bytes, checksum: 7db721c97741248d4b8d65e00efad171 (MD5) PROQUEST_LICENSE.txt: 4554 bytes, checksum: 748254b418b7fccdb1830fff014f104a (MD5) Previous issue date: 2017-04-21Embargo set by: Colleen Fallaw for item 102670 Lift date: 2019-08-10T21:25:30Z Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemLimited Restriction Lifted for Item 102670 on 2019-08-11T09:15:35Z

    Hydrogen-Bonded Clusters: A Study of the Elusive Anisole-Ammonia and Anisole-Water 1:1 Complexes

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    The hydrogen bond is one of the most important and versatile interactions found in most subsets of chemistry and biology. This interaction is responsible for reactions and characteristic properties of the systems in thereof. This interaction is just one of several available non-covalent interactions that can occur and over the past several decades of molecular spectroscopy studies, the definition of the hydrogen bond has become broader compared to the “classic” definition. To accurately study the hydrogen-bonding in these systems can be quite challenging due to the size and complexity of the molecules involved, as well as the other interactions that may play a role. In order to study these interactions, model systems containing the isolated conditions for hydrogen bonding similar to their real-world counterparts have been of great use. By studying the strength, geometric orientation, and spectral features of these systems, these types of interactions are better understood. Of the model systems involved, those containing ammonia and water have been widely studied due to the critical role of the two solvents across all of chemistry, especially biochemistry. In the past few decades, the anisole-ammonia and anisole-water 1:1 complexes, two potential candidates for hydrogen bonding, have been studied. However, these studies have been mostly comprised of initial experimental investigations and low-level theoretical calculations. This leaves some ambiguity as to the exact strength and binding motifs of these complexes. The focus of this thesis is to identify the shortcomings of the recent literature and answer some of the remaining questions. The ground-state experimental binding energy for the anisole-ammonia complex is reported for the first time via 2-color-resonant 2-photon ionization (2CR2PI) spectroscopy. Through several high-level DFT calculations, the ground-state structure and binding energy are reported and compared to previous literature. Also, the same plethora of theoretical methods were used to explore the complex in the cation-radical state for the first time. Similarly, the same theoretical investigations were employed to study the ground-state and cation radical structure and binding energy were studied for the anisole-water 1:1 complex. The results obtained were then compared to the previous studies

    Are diagnostic and public health bacteriology ready to become branches of genomic medicine?

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    Diagnostic medical bacteriology is a conservative discipline. When busy house officers scribble 'M, C & S' on a form, they are requesting two techniques - microscopy and culture of microorganisms - that date back to the late 17th and late 19th century, respectively. The third technique - antibiotic susceptibility testing - has changed little in a half a century. Relatively few front-line diagnostic bacteriology laboratories have embraced molecular methods; on my own campus, the hospital's medical microbiology department does not even possess a thermal cycler! And yet in the research arena, genome sequencing has transformed almost every corner of the biomedical sciences, including the study of bacterial pathogens Furthermore, over the past 5 years, high-throughput (or 'next-generation') sequencing technologies have delivered a step change in our ability to sequence microbial genomes [1]. Since arriving in the market place, these technologies have experienced sustained technical improvement, which, twinned with lively competition between alternative platforms, has placed sequencing in a state of 'permanent revolution'. At last, it seems that genomics has come up with a game-changer, a killer app, a disruptive technology that even those long wedded to the Gram stain and the agar plate can no longer ignore. Does this mean we are on the brink of a revolution in diagnostic and public health microbiology, in which high-throughput sequencing usurps the traditional 'M, C & S', or will the discipline's innate conservatism stand firm for decades to come

    Tombolovorming achter offshore golfbreker

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    In het afstudeerontwerp is de aandacht gericht op stromingen als gevolg van gediffrakteerde golven. Een stringente scheiding van diffraktie en refraktie is in een kustgebied nauwelijks mogelijk, aangezien in het diffraktiegebied de zandbodem in het algemeen niet vlak en horizontaal is, waardoor tevens refraktie optreedt. In schaduwgebieden van offshore obstakels ontstaan nabij de kustlijn cirkulatiestromingen als gevolg van een sterke variatie in de golfhoogte door diffraktie. De afname van de golfhoogte in het schaduwgebied reduceert de golfopzet ten opzichte van het ongestoorde gebied, afhankelijk van een aantal procesparameters. In de natuur resulteert dit in een sedimentbeweging,met als gevolg de vorming van een landtong in de richting van het obstakel. Afhankelijk van de vorm en grootte van het obstakel kunnen zelfs langsstromingen leiden tot spitvorming in het schaduwgebied. Het uiteindelijke resuJtaat is veelal een smalle verbinding met het "vasteland". Het onderhavige onderzoek is specifiek gericht op de responsie van een offshore golfbreker op een oorspronkelijk recht zandkustprofiel . Het beoogt een bijdrage te leveren tot het onderzoek naar deze zogenaamde tombolovorming en naar de mogelijk stabiliserende invloed ervan op de algehele kustlijn.Hydraulic EngineeringCivil Engineering and Geoscience
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