8,914 research outputs found
Characterization of Novel Alpha-1-Antitrypsin Coding Variants in a Mammalian Cellular Model
Advances in genetic screening technologies have considerably accelerated the discovery of rare alpha-1-antitrypsin (AAT) variants. Expression in cellular models is an effective approach to evaluate the pathogenic potential of these new AAT variants, whose clinical significance would otherwise remain uncertain. Here we provide a detailed description of established methods for in vitro characterization of AAT coding variants expressed in HEK293T/17 cells. The protocols include determination of secretion efficiency, the tendency to form polymeric chains and the anti-elastase inhibitory activity
Andrea Bacová
Andrea Bacová focuses on research and teaching in the field of residential architecture. Her work includes systematic research on residential buildings and their urban context. She actively participates in promoting Slovak architecture and is the author of several publications and exhibitions
Viewer-, Author-, and Ownership in the Work of Andrea Zittel
Andrea Zittel invites others to collapse the distinctions between artist, viewer, and collaborator by interacting with her usable works. This thesis explores the process of interacting with Zittel\u27s works, and how it affects viewer-, author- and ownership
The Lettere of Andrea Calmo: authorial artifices and historical reality
openNonostante l’edizione di Vittorio Rossi del 1888, la raccolta di "ingegnosi cheribizzi" e di "fantastiche fantasie" di Andrea Calmo è ancora avvolta da un certo mistero. L’autore, dissimulando la propria identità dietro alla “maschera” dell’umile pescatore veneziano, è stato in grado di offrire uno spaccato della cultura e della società nella Venezia cinquecentesca.
In particolare, è il quarto libro delle Lettere ad aver suscitato maggiore interesse tra gli studiosi ed i lettori: pubblicato nel 1566, a diversi anni di distanza dai primi tre, questo libro si distingue per il fatto che tutte le epistole sono indirizzate a delle donne immaginarie o realmente esistite.
In questa sede si propone, in primo luogo, uno studio della biografia del Calmo accompagnata da un’analisi del contesto storico-culturale della Venezia cinquecentesca; in secondo luogo, invece, viene proposto un commento di alcune lettere dell’ultimo libro dell’opera calmiana, che cerchi di far luce principalmente sull’aspetto linguistico e contenutistico del testo.Despite Vittorio Rossi's 1888 edition, Andrea Calmo's collection of "ingegnosi cheribizzi" and "fantastiche fantasie" is still shrouded in a certain mystery. The author, dissimulating his own identity behind the "mask" of the humble Venetian fisherman, was able to offer a cross-section of culture and society in sixteenth-century Venice.
In particular, it is the fourth book of the Letters that has aroused greater interest among scholars and readers: published in 1566, several years after the first three, this book stands out for the fact that all the epistles are addressed to women imaginary or actually existed.
Here we propose, first of all, a study of Calmo's biography accompanied by an analysis of the historical-cultural context of sixteenth-century Venice; secondly, however, a commentary on some letters from the last book of Calmo's work is proposed, which seeks to shed light mainly on the linguistic and content aspect of the text
Trusted Tales: Creating Authenticity in Literary Representations from Ex-Yugoslavia
This research deals with questions of authority and authenticity and how they are expressed, constructed, and appropriated within the Anglophone book market. It considers the body of literature written about ex-Yugoslavia since the 1990s Balkan conflicts by exiled writers from the region which has entered the international literary canon. Books’ routes from original publishers into English translation are discussed through practices of trust, one of the crucial social devices underpinning their exchange. Within these cross-cultural processes, the role of cultural brokers is crucial. Symbolic and cultural resources are specifically mobilised through their powerful author brands.
By exploring authenticity in the context of book publishing, I further look at how ideas and practices of community are employed and negotiated by writers and those who promote their books. My field is multi-sited and fluid, reflecting how different individual and national positions are enacted and performed through strategies ranging from unconscious dispositions to deliberate intentions. This research thus brings together ideas of the author as an authentic, representative voice together with exile as a position that grants them a new lease of relevancy in the post-socialist context.
Although ex-Yugoslav books occupy a ‘high end’ niche of the UK market, constrained by commercial as well as political, cultural, and institutional forces, in public discourse ideas of the ‘free market’ and ‘free speech’ are mobilised to produce various types of modernisation narratives. The (post)socialist production of literature is perceived as having to ‘evolve’ into a capitalist model: this would allow not only healthy competition and consumer choice but guarantee an individual writer ‘free speech’ as a basic human right. Therefore, the most general question this research raises is what kind of foreign literature gets translated into English, under what socio-cultural conditions and which politics of representation it serves within the project of world literature
Pentosan polysulfate to control hepcidin expression in vitro and in vivo
Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin dysregulation causes different human disorders ranging from iron overload (e.g. hemochromatosis) to iron deficiency (e.g. anemia). Hepcidin excess is common in the Anemia of Chronic Diseases or Anemia of Inflammation and in the genetic form of anemia named IRIDA; the pharmacological downregulation of hepcidin in these disorders could improve the anemia. Commercial heparins were shown to be strong inhibitors of hepcidin expression, by interfering with BMP6/SMAD pathway. The non-anticoagulant heparins, modified to abolish the anti-thrombin binding site, were equally potent and could be used to improve iron status. To perform its anti-hepcidin activity heparin needs 2O- and 6O-sulfation and an average molecular weight (MW) up to 4000-8000 Dalton, depending on the sulfation level. The pentosane polysulfate (PPS), which shares with heparin a high degree of sulfation, is a compound with low anti-coagulant activity that is already in use for pharmaceutical treatment. In the present work we analyzed the anti-hepcidin activity of PPS in vitro and in vivo. We found that it acts as a strong inhibitor of hepcidin expression in HepG2 cells with an effect already visible after 2-3 h of treatment. It also suppressed hepcidin in mice in a dose dependent manner after 3 h and with a significant redistribution of systemic iron without evident side effects. PPS is also able to abolish the LPS dependent hepcidin upregulation similarly to that showed for heparin derivatives. These results suggest PPS as an interesting compound to control hepcidin in vivo
Ms. Courtney Chartier, RWWL AUC, August 2011
This video is a conversation with Ms. Courtney Chartier. Ms. Chartier talks about her work on the "New Georgia Encyclopedia" and "Online Voter Education Project." Andrea Jackson, AUC Woodruff Library, is the interviewer
Functional characterization of amino acid variants of the reactive-center-loop of alpha-1-antitrypsin
Alpha-1-antitrypsin (AAT) is an abundant glycoprotein in the plasma, is synthetized in the liver and acts as an inhibitor of serine proteases like neutrophil elastase (HNE). Mutations in the AAT gene generally lead to reduced AAT levels in the plasma (AAT deficiency, AATD), thus diagnostic protocols are based primarily on AAT plasma quantification. The unbalance between AAT and the target proteases in the lungs predisposes to emphysema.
AAT specifically binds HNE via its flexible and solvent exposed reactive center loop (RCL) and, upon cleavage, undergoes a conformational change that traps the protease in a covalent irreversible complex.
Our aim was to identify amino acid variants in the RCL domain that impair anti-elastase activity. We considered AAT variants arising from all possible amino acid changes due to single nucleotide variations, excluding residues with high similarity. Interestingly, a subset of these variants is reported in the gnomAD database.
The selected variants were expressed in HEK293T cells along with wild-type AAT, the common polymerogenic mutant Z (E342K) and the previously characterized dysfunctional Iners (G349R). We quantified AAT in conditioned media by ELISA and by non-denaturing PAGE analysis. In contrast with the Z AAT mutant, which is conformationally altered and preferentially accumulates in the endoplasmic reticulum as polymeric chains, all the selected RCL variants were secreted normally in the native monomeric conformation. Then anti-elastase activity of RCL variants was investigated by three independent assays: (1) analysis of HNE-AAT complexes by SDS-PAGE analysis; (2) binding to elastase adsorbed on multi-well plates, (3) inhibition of HNE activity on chromogenic substrates. Our results identified five fully dysfunctional AAT variants and four ones with diminished anti-elastase activity. Notably, due to their normal secretion, such variants would not be identified by AATD diagnostic protocols
Tribute to Andrea Infuso
This special issue of Eurosurveillance is dedicated to the memory of Andrea Infuso, a dear and respected colleague and friend, who died suddenly on 20 September 2005 at the age of 44.
Andrea was actively involved in the preparation of this special issue on vaccination and tuberculosis. As EuroTB coordinator since 2000, his knowledge of and contacts with all European experts involved in tuberculosis surveillance in Europe were very valuable in conceiving this thematic issue. The Euroroundup published in this issue, European survey of BCG vaccination policies and surveillance in children, 2005, written by Andrea as first author, is a posthumous publication.</jats:p
Search-based multi-vulnerability testing of XML injections in web applications (vol 24, pg 3696, 2019): Search-based multi-vulnerability testing of XML injections in web applications (Empirical Software Engineering, (2019), 10.1007/s10664-019-09707-8)
The article Search-based multi-vulnerability testing of XML injections in web applications, written by Sadeeq Jan, Annibale Panichella, Andrea Arcuri, and Lionel Briand, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on May 2019 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on June 2019 toSoftware Engineerin
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