1,611 research outputs found
The role of the Swain-Langley and McCoy polymorphisms in complement receptor 1 in cerebral malaria
No full textMalaria has been a major driving force in the evolution of the human genome. In
sub-Saharan African populations, two neighbouring polymorphisms in the
Complement Receptor 1 (CR1) gene, named Swain-Langley (Sl2) and McCoy (McCb),
occur at high frequencies, consistent with selection by malaria. This thesis
investigates the association between these two polymorphisms and severe malaria.
Previous studies into this area have produced conflicting findings.
Using a large case-control study of severe malaria in Kenyan children and statistical
models adjusted for confounders, I found that the Sl2 polymorphism was associated
with markedly reduced odds of cerebral malaria and death, while the McCb
polymorphism was associated with increased odds of cerebral malaria. I also
identified an interaction between Sl2 and α+thalassaemia, with the protective
association of Sl2 greatest in children with normal α-globin.
Following these epidemiological findings, I explored potential biological hypotheses
which might explain them. The first approach examined whether the Sl2 and McCb
polymorphisms affected how CR1 forms clusters on erythrocyte membranes, a
process which is key in the binding and transfer of immune complexes from
erythrocytes to macrophages. Using erythrocytes from Kenyan children, I
performed immunofluorescence assays (IFAs) with confocal microscopy to quantify
CR1 cluster number and volume. I found no association between the Sl2 and McCb
polymorphisms and either the number or volume of CR1 clusters formed.
The second approach investigated whether the cerebral malaria-specific
associations seen with Sl2 and McCb might be due to expression of CR1 by human
brain endothelial cells (HBEC). The immortalised cell line HBEC-5i was investigated
for expression of CR1 using IFA, flow cytometry, western blotting, functional C3b
degradation assays, mass spectrometry, immunoprecipitation and siRNA
knockdown experiments. A pool of α-CR1 monoclonal antibodies recognised an
intracellular antigen in permeabilised HBEC-5i cells which was a similar molecular
weight to CR1 on western blotting. However, when the α-CR1 monoclonal
antibodies were tested individually, only E11 recognised an HBEC-5i antigen.
Further investigative approaches did not support the presence of CR1 on HBEC-5i
cells, instead suggesting that E11 was not specific for CR1 and was instead
recognising a protein in the Golgi apparatus.
The final approach was to examine whether the Sl2 and McCb polymorphisms might
influence the binding of the complement components mannose binding lectin, C1q
and L-ficolin to the LHR-D region of CR1. I aimed to generate recombinant proteins
of the LHR-D region which included the polymorphisms. Site-directed mutagenesis
of the region was successful and subcloning and expression of the mutant
amplicons will be performed at a later date.
In summary, I have identified opposing associations between the Sl2 and McCb
polymorphisms and cerebral malaria, which do not appear to be due to differences
in CR1 clustering or expression of CR1 by human brain endothelial cells. My
investigation into whether the polymorphisms might influence complement
component binding is ongoing
L. T. Meade\u27s Avaricious Anomaly: Â Madame Sara, British Imperialism, and Greedy Wolves in The Sorceress of the Strand
No full textL. T. Meade\u27s Avaricious Anomaly: Madame Sara, British Imperialism, and Greedy Wolves in The Sorceress of the Strand. Laurie Langlois Denning, Department of English, BYU Master of Arts. Critics interested in the prolific late Victorian author L.T. Meade have primarily focused on her work as an author of girls\u27 stories and novels for young people, which enjoyed fantastic commercial success in her lifetime but fell into obscurity after her death. Recent scholarship on her detective fiction shows Meade\u27s significant contributions to the genre as well as her engagement with social and political discourse. Scholars have noted ways that Meade\u27s popular series, The Sorceress of the Strand, contributes to the New Woman debate and expresses anxiety over the British imperial project. This project examines Meade\u27s villain in the series as a social anomaly that functions to interrogate the greed at the heart of imperialism. Examining the series\u27 conclusion and the unusual nature of its ending sheds new light on Meade\u27s contribution to debate over empire at the fin de siécle. Meade\u27s fascinating villain, Madame Sara, is doggedly pursued by two detective figures--one is considered the top forensic specialist in the British police force and the other is the head of a business fraud agency--but the detectives are never able to bring Madam Sara to justice. Instead, it is a wolf that finally defeats the brilliant criminal mastermind. Why a wolf? Madam Sara\u27s unusual demise serves as a deus ex machina that invites the reader to consider the Dante symbolism embedded in the text. Other critics see Meade\u27s ending as reinforcing the empire; however, given the Dante imagery that has Madam Sara symbolizing a greedy imperial force, Meade\u27s series indicts imperial greed and warns British citizens about failure to apprehend the evil in empire
The Kepler-454 system : A small, not-rocky inner planet, a Jovian world, and a distant companion
No full textKepler-454 (KOI-273) is a relatively bright (V = 11.69 mag), Sun-like starthat hosts a transiting planet candidate in a 10.6 d orbit. From spectroscopy, we estimate the stellar temperature to be 5687 +/- 50 K, its metallicity to be [m/H] = 0.32 +/- 0.08, and the projected rotational velocity to be v sin i 10 years and mass >12.1M_J . The twelve exoplanets with radii <2.7 R_Earth and precise mass measurements appear to fall into two populations, with those <1.6 R_Earth following an Earth-like composition curve and larger planets requiring a significant fraction of volatiles. With a density of 2.76 +/- 0.73 g cm-3, Kepler-454b lies near the mass transition between these two populations and requires the presence of volatiles and/or H/He gas.Peer reviewe
Site Effects from the Building Scale to the Seismic Microzonation Scale: Examples from the Experience of L’Aquila
No full textAbstractThis paper illustrates the site characterization for evaluating local ground motion amplifications at two sites in the urban area of L’Aquila, performed for the reconstruction of buildings damaged by the April 6, 2009 earthquake. The paper is focused on the comparison between results obtained from site investigations carried out at the building scale and from information contained in the seismic microzonation study. Local amplifications inferred from microzonation may be considerably different from those provided by ground response analyses based on punctual soil data, due to the complex geological setting and the marked variability in geotechnical properties of the foundation soils. The practice of using seismic microzonation data for deriving the seismic action on buildings, not infrequent in structural engineering design, should be avoided or considered with caution
Vittorio Alfieri e l’‘antipanegirico’. Studio comparativo con l’orazione pliniana
No full textThe paper aims to investigate the relation between Vittorio Alfieri's Panegirico di Plinio a Trajano, written by the author in Pisa in 1785, and its Latin model, the speech read by Plinio il Giovane to Traiano in the Senate in the year 100 AD. The study of Alfieri's work has proven interesting from several points of view, primarily because of the author's overturning of the oratorio genre: the work, in fact, has been called by scholars an «antipanegirico», a «panegirico capovolto». Alfieri replaces the original glorification of the optimus princeps with a political proposal, dispensing with the encomiastic aspect that characterizes Plinio’s panegyric in order to emphasize his authorial voice. Indeed, the praises of Traiano in the text are reduced and relegated to a marginal role, while Plinio-Alfieri’s speech assumes an exhortatory and moral function.Il contributo intende indagare il rapporto tra il Panegirico di Plinio a Trajano di Vittorio Alfieri, ideato e steso dall’autore a Pisa nel 1785, e il suo modello latino, il discorso letto da Plinio il Giovane a Traiano in Senato nell’anno 100 d.C. Lo studio dell’opera di Alfieri si rivela interessante da diversi punti di vista, in primis per il rovesciamento che l’autore attua del genere oratorio: l’opera, infatti, è stata definita dagli studiosi un ‘antipanegirico’, un ‘panegirico capovolto’. L’Astigiano sostituisce all’originaria esaltazione dell’optimus princeps una proposta politica, eliminando l’aspetto encomiastico che contraddistingue il panegirico pliniano per mettere in rilievo la sua voce di autore. Le lodi di Traiano, nel testo, sono infatti ridotte e relegate a un ruolo marginale, mentre il discorso del Plinio-Alfieri assume una funzione esortativa e morale
Revisionismo omerico e caratterizzazione degli eroi nel ‘Romanzo di Troia’. La trasformazione di Aiace nell’Ephemeris greca e latina
No full textThis paper discusses how variation and (re-)use of ancient sources, along with own invention of the author, is deployed in the alleged chronicle of the Trojan War composed by Dictys of Crete and in its Latin adaptation, the Ephemeris belli Troiani by L. Septimius, in order to ‘correct’ Homer and allow insertion of adventure and ‘romance’. More specifically, it focuses on such narrative strategy of combining Homeric revisionism with revisitation of earlier traditions in the characterization of Telamon Ajax and its role in Dictys’ narrative
Semantic Web Technologies for Digital Libraries: From Libraries to Social Semantic Digital Libraries (SSDL), Over Semantic Digital Libraries (SDL)
No full textDigital libraries have been an important source of information throughout the history of mankind. It has been present in our societies in different forms. Notably, traditional libraries have found their on the desktops of internet users. They have taken the shape of semantic digital libraries, which are accessible at any time, and accordingly provide a more meaningful search. This paper further discusses social semantic digital libraries that also incorporate the social and collaborative aspect
Sara y Simón o la reconstrucción del pasado: el problema de la verdad en la escritura de la historia del tiempo presente. Cuicuilco Revista de la Escuela Nacional de Antropología e Historia: Las disciplinas históricas y antropológicas: vertientes y estudios de caso. Num. 30 (2004) Vol. 11 enero-abril
No full textEste artículo aborda la historia de una mujer en búsqueda de su hijo, quien fue secuestrado en el marco del Plan Condor en Uruguay. Este relato nos sirve como base para preguntarnos qué es laverdad en la historia del tiempo presente, y cuál es su relación con la escritura de la historia, siempre teniendo en mente que las visiones que se tienen del pasado (historia o memoria), resultan clave paraentender el presente y el futuro.This article is about the story of a woman searching her son, who was kidnapped during the Condor Plan in Uruguay. This story is useful to question ourselves about truth in contemporary history, and the relation between truth and history’s writing, always bearing in mind that visions of the past (from history or memory), are fundamental to understand the present and the future.Actes de la journée d´études de l´Institut d´Histoire du Temps Présent, 14 de mayo, 1992.Aguilar, C. et al.
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Recensione a: Sara J. Newman, Aristotle and Style, Lewingston-Queenston-Lampeter: The Edwin Mellen Press, 2005
No full textWell fitting into the recent Aristotelian bibliography, as Alan G. Gross rightly points out in his preface to the book, Sara Newman’s work offers a very engaged commentary to the relationship between Aristotle’s theory and practice of metaphor and contemporary under-standings of it. As in a roundtrip, the author comes back at the end of her analysis to her open-ing question ‘Why Aristotle and Style?’ (p. 1) which she can now answer saying that “In spite of its limitations, Aristotle notion of style is more than ornamental and substitutive; it operates consistently in his texts to enhance, to facilitate, and to systematically guide certain concep-tual inquiries” (p. 263). Indeed the book has not only the merit to stress the role of Aristotle’s metaphor within the clarifying function of style and consequently its link with the logical process of persuasion, but it is also an important contribution to vindicate Aristotle’s rights in the development of the modern conceptual theory of metaphor
The mass of Kepler-93b and the composition of terrestrial planets
No full textKepler-93b is a 1.478 ± 0.019 R ⊕ planet with a 4.7 day period around a bright (V = 10.2), astroseismically characterized host star with a mass of 0.911 ± 0.033 M ☉ and a radius of 0.919 ± 0.011 R ☉. Based on 86 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 32 archival Keck/HIRES observations, we present a precise mass estimate of 4.02 ± 0.68 M ⊕. The corresponding high density of 6.88 ± 1.18 g cm–3 is consistent with a rocky composition of primarily iron and magnesium silicate. We compare Kepler-93b to other dense planets with well-constrained parameters and find that between 1 and 6 M ⊕, all dense planets including the Earth and Venus are well-described by the same fixed ratio of iron to magnesium silicate. There are as of yet no examples of such planets with masses >6 M ⊕. All known planets in this mass regime have lower densities requiring significant fractions of volatiles or H/He gas. We also constrain the mass and period of the outer companion in the Kepler-93 system from the long-term radial velocity trend and archival adaptive optics images. As the sample of dense planets with well-constrained masses and radii continues to grow, we will be able to test whether the fixed compositional model found for the seven dense planets considered in this paper extends to the full population of 1-6 M ⊕ planets.Peer reviewe
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