483 research outputs found
Polyphony and the anxiety of influence in the fiction of Henry James
No full textJames's fiction, especially in the Middle Phase, centres
on the figure of the artist and is characterized by, the two
interrelated aspects which previous criticism has largely
overlooked: the Bakhtinian 'polyphonic' -creation of
'author-thinkers'; and the conflict between ephebes and
precursors, for which Harold-Bloom's concept of 'the-anxiety of
influence' is the most illuminating model. Polyphony is the
narrative mode, and influence is the intra-artistic, theme.
These, as the Introduction to the thesis makes clear, are
rehearsed in James's inaugural novel, Roderick Hudson. Rowland
Mallet is an author-thinker, and his failure is caused by
authorial limitations. His monologism -is impaired by his
mistaking empathy for the authorial sympathy. Likewise,
Hudson's failure does not arise from a mercurial temperament,
but from a polyphonic shortcoming: not possessing the power of
fiction to contain the fiction of power in, his mentor. And the
relationships among the three artists - Gloriani, Hudson and
Singleton - perfectly exemplify the Bloomian-theme. It is these
two concepts, polyphony and influence, which are the major
preoccupation in the Middle Phase; as, the works chosen
demonstrate. These are a novella, a novel, and a number of
short stories all of which have been unjustifiably neglected.
Chapter One, on The Aspern Papers, argues that Tina Bordereau,
far from being, the artless victim seen by many critics,
actually challenges and defeats the narrator by the very form
of her narrative. Her 'realist' discourse undermines his
language of 'romance', and shows up its internal unstability.
Chapter Two is an extensive study of the critical reception of
The Tragic Muse. The most common areas of critical attention
have been its contemporary topicality, its relation to previous
novels on similar themes, and the possible genealogy of Gabriel
Nash. Those have all missed the core of the work. - Chapter Three
demonstrates how polyphony and the anxiety of influence make
the novel what it really is. Influence arises from the
juxtaposition of, and the wrestling between, artistic ephebes
and their precursors (Nick and Nash,, Miriam and Madame Carre).
The dialogic quality defined by Bakhtin is crucial to the
proper, and even-handed, characterization of all, the conflicts
in the novel. And since most of James's tales in the eighties
and nineties -are about 'masters - and acolytes, the anxiety of
influence remains central. Chapter Four is a study of 'The
Author of Beltraffiol' and 'The Lesson of the Master'. Again the
characters' manipulations are a crucial focus in a way that
G6rard Genette's terminology helps to illuminate. The fact that
the ephebe is the author-thinker emphasizes the inextricability
of the Bakhtinian and the Bloomian in James. Just as
polyphony offers a different focus for explicating the poetics
of James's fiction; so the ephebal conflict provides the basis
for a fresh perception of James's own artistic struggle
Analysis of the Quorum Sensing Regulons of Vibrio parahaemolyticus BB22 and Pantoea stewartii subspecies stewartii
No full textQuorum sensing is utilized by many different proteobacteria, including the two studied for this dissertation work, Vibrio parahaemolyticus and Pantoea stewartii subsp. stewartii. V. parahaemolyticus causes acute gastroenteritis in people who eat contaminated raw or undercooked shellfish. It is found in warmer marine waters and in rare cases, causes systemic infections when bacteria enter the body through open wounds. P. stewartii, on the other hand, is a phytopathogen that causes Stewart's wilt in maize. It is found in soil or the mid-gut of the corn flea beetle, its insect vector. Both V. parahaemolyticus and P. stewartii utilize quorum sensing to control their pathogenicity.
Quorum sensing enables coordinate gene expression across a bacterial population. The V. parahaemolyticus quorum-sensing system utilizes the master regulator OpaR, which is homologous to the V. harveyii LuxRVh and the P. stewartii system contains EsaR which is homologous to the V. fischeri LuxRVf regulator. While the two systems differ in the molecular details of their mechanistic control, they are both forms of cell density dependent regulation that are either directly or indirectly controlled by small signaling molecules. Three different signaling molecules are found in V. parahaemolyticus, and only one signal is used in P. stewartii. The focus of this dissertation has been on understanding the downstream targets of OpaR and EsaR in their respective quorum-sensing systems.
Prior to this work, it was known that when OpaR is not present or is nonfunctional V. parahaemolyticus changes from an opaque to a translucent colony morphology phenotype and the cells also become swarm proficient and more pathogenic. The complete genome of the V. parahaemolyticus BB22OP strain was assembled and annotated (Chapter 2). RNA-Seq was then used to analyze the transcriptomes of OpaR-active and OpaR-deficient strains of V. parahaemolyticus and identify genes that were regulated via quorum sensing (Chapter 3).
Similarly, P. stewartii was also analyzed using RNA-Seq to identify genes controlled by EsaR in the transcriptome that had not been detected through prior proteomic studies. The initial RNA-Seq work confirmed the control of some previously identified direct targets of EsaR and newly identified ten other genes also directly controlled by EsaR (Chapter 4). Two direct targets of EsaR, rcsA and lrhA, became the focus of additional studies to further define the hierarchy of gene control downstream of the quorum-sensing regulator EsaR. RcsA controls capsule production, while LrhA controls motility and adhesion in P. stewartii. The regulons of rcsA and lrhA were defined by RNA-Seq, which also revealed multi-level control of rcsA gene expression (Chapter 5). Tight coordinated and temporal control of virulence factors is important for successful disease progression by pathogens. This dissertation work aims to enable a better understanding of the quorum-sensing hierarchy of genetic control in V. parahaemolyticus and P. stewartii.Ph. D
BMC Genomics
No full textCorrection to Bemmo A, Benovoy D, Kwan T, Gaffney DJ, Jensen RV, Majewski J: Gene expression and isoform variation analysis using Affymetrix Exon Arrays. BMC Genomics 2008, 9: 529.Published versio
Klinicko-patologické, morfologické, imunohistochemické a molekulárně biologické charakteristiky vzácných nádorů slinných žláz
No full textThe actual dissertation is the result of Olena Koshyk's doctoral study at Charles University in Prague, Faculty of Medicine in Pilsen, from 2019 to 2023. The author focused the main part of her research on rare salivary gland tumors but also participated in studies related to sinonasal soft tissue tumors. The studies used a wide range of investigation methods including morphology, immunohistochemistry, and molecular genetic methods in order to provide new insights for accurate tumor diagnosis and to propose novel approaches and refinements in the classification of selected head and neck tumors. The dissertation is divided into two parts. The first part represents four articles that present the latest data on rare salivary gland tumors. The first paper concentrated on the new rare oncocytic variant of mucoepidermoid carcinoma with comprehensive morphological and immunohistochemical descriptions, and molecular alterations. Special attention was paid to the differential diagnosis with oncocytic tumors for accurate diagnosis. The second study covered a clear cell subtype of myoepithelial carcinoma which showed EWSR gene rearrangements. Different fusions in the PLAG1 gene were found in such tumors but fusion transcripts for the EWSR gene were not detected. The study also focusses on a comparison of the...Vlastní disertační práce je výsledkem doktorandského studia Oleny Koshyk na Univerzitě Karlově v Praze, Lékařské fakultě v Plzni, v letech 2019 až 2023. Autorka zaměřila hlavní část svého výzkumu na vzácné nádory slinných žláz, ale podílela se i na studiích souvisejících se sinonazálními nádory měkkých tkání. Práce využívaly širokou škálu vyšetřovacích metod včetně morfologie, imunohistochemie a molekulárně genetických metod za účelem získání nových poznatků pro přesnou diagnostiku nádorů a navrhly nové přístupy a vylepšení v klasifikaci specifických nádorů. Dizertační práce je rozdělena do dvou částí. První část představuje čtyři články, které prezentují nejnovější údaje o vzácných nádorech slinných žláz. První práce se soustředila na novou vzácnou onkocytární variantu mukoepidermoidního karcinomu s komplexním morfologickým a imunohistochemickým popisem a molekulárními změnami. Zvláštní pozornost byla věnována diferenciální diagnostice s onkocytárními nádory. Druhá studie se věnovala světlobuněčnému myoepiteliálnímu karcinomu, který vykazoval rearanži genu EWSR. V takových nádorech byly nalezeny různé fúze v genu PLAG1, ale fúzní transkripty pro gen EWSR nebyly nalezeny. Studie také pojednává o srovnání biologie myoepiteliálních nádorů slinné žlázy s myoepiteliálními nádorry měkkých tkání a kůže....Šiklův ústav patologieFaculty of Medicine in PilsenLékařská fakulta v Plzn
The utility of liver function tests for mortality prediction within one year in primary care using the algorithm for liver function investigations (ALFI)
No full textBACKGROUND: Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease.METHODS: In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices.RESULTS: From the derivation cohort (n?=?95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n?=?11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity?=?52.8%, specificity?=?94.0%, PPV?=?21.0%, NPV?=?98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%.CONCLUSIONS: The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV
Molecular Investigations of Protein Assemblies Involved in Prokaryotic Virulence
No full textProtein complexes mediate a diverse range of behavior in prokaryotic cells, yet the exact molecular mechanisms explaining how many of these complexes assemble and function remain unknown. This work focuses on understanding the molecular mechanisms of two different protein assemblies responsible for regulating virulence in the opportunistic pathogen Pseudomonas aeruginosa. P. aeruginosa utilizes type IV pili (T4P) to adhere to, and move along, surfaces. Assembly of T4P is powered by a dedicated cytoplasmic ATPase, PilB. The structural study of PilB from a related system (chapter 2) resulted in the formulation of the first model describing the mechanism of force generation resulting from ATP hydrolysis, which explains how T4P are assembled. Chapter 3 focuses on the RetS/GacS interaction, which is responsible for globally regulating virulence in P. aeruginosa. A comprehensive structural study reveals a dynamics of a novel regulatory interaction and the discovery of a potentially universal transmembrane signaling mechanism.Doctor of PhilosophyBacteria have threatened human health since the beginning of recorded history. With the development of antibiotics in the early twentieth century, the threat posed by bacterial infection was greatly lessened. However, decades of antibiotic mismanagement has led to the evolution of bacteria which are no longer vulnerable to these antibiotics. In order to combat this rising threat of resistant bacteria, we require a deeper understanding of how bacteria function and cause disease. Proteins play a crucial role in the diseases caused by bacteria, either by directly damaging host cells or regulating the expression of these damaging factors. By increasing our knowledge of the roles played by protein during bacterial infections, it will be possible to create new antibiotics while minimizing the risk of resistance. The work presented here grants a deeper understanding into how proteins work together to allow bacteria to survive inside the human body
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